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1. Rationale and design of the DAPA-MI trial : Dapagliflozin in patients without diabetes mellitus with acute myocardial infarction

Author: James, Stefan, Erlinge, David, Storey, Robert F., Mcguire, Darren K., de Belder, Mark, Björkgren, Ida, Johansson, Peter A., Langkilde, Anna Maria, Ridderstrale, Wilhelm, Rizi, Ehsan Parvaresh, Deanfield, John, Oldgren, Jonas, James, Stefan, Erlinge, David, Storey, Robert F., Mcguire, Darren K., de Belder, Mark, Björkgren, Ida, Johansson, Peter A., Langkilde, Anna Maria, Ridderstrale, Wilhelm, Rizi, Ehsan Parvaresh, Deanfield, John, and Oldgren, Jonas
Abstract: Background Therapies that could further prevent the development of heart failure (HF) and other cardiovascular and metabolic events in patients with recent myocardial infarction (MI) represent a large and unmet medical need. Methods DAPA-MI is a multicenter, parallel-group, registry-based, randomized, double-blind, placebo-controlled phase 3 trial in patients without known diabetes or established HF, presenting with MI and impaired left ventricular systolic function or Q-wave MI. The trial evaluated the effect of dapagliflozin 10 mg vs placebo, given once daily in addition to standard of care therapy, on death, hospitalization for HF (HHF), and other cardiometabolic outcomes. The primary objective of the trial was to determine, using the win-ratio method, if dapagliflozin is superior to placebo by comparing the hierarchical composite outcome of death, HHF, nonfatal MI, atrial fibrillation/flutter, new onset of type 2 diabetes mellitus, HF symptoms as measured by New York Heart Association Functional Classification at last visit, and body weight decrease >= 5% at last visit. Assuming a true win-ratio of 1.20 between dapagliflozin and placebo, 4,000 patients provide a statistical power of 80% for the test of the primary composite outcome. A registry-based randomized controlled trial framework allowed for recruitment, randomization, blinding, and pragmatic data collection of baseline demographics, medications, and clinical outcomes using existing national clinical registries (in Sweden and the UK) integrated with the trial database. Conclusions The trial explores opportunities to improve further the outcome of patients with impaired LV function after MI. The innovative trial design of DAPA-MI, incorporating national clinical registry data, has facilitated efficient patient recruitment as well as outcome ascertainment.
Published: 2023
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2. Rationale and design of the DAPA-MI trial : Dapagliflozin in patients without diabetes mellitus with acute myocardial infarction

Author: James, Stefan, Erlinge, David, Storey, Robert F., Mcguire, Darren K., de Belder, Mark, Björkgren, Ida, Johansson, Peter A., Langkilde, Anna Maria, Ridderstrale, Wilhelm, Rizi, Ehsan Parvaresh, Deanfield, John, Oldgren, Jonas, James, Stefan, Erlinge, David, Storey, Robert F., Mcguire, Darren K., de Belder, Mark, Björkgren, Ida, Johansson, Peter A., Langkilde, Anna Maria, Ridderstrale, Wilhelm, Rizi, Ehsan Parvaresh, Deanfield, John, and Oldgren, Jonas
Abstract: Background Therapies that could further prevent the development of heart failure (HF) and other cardiovascular and metabolic events in patients with recent myocardial infarction (MI) represent a large and unmet medical need. Methods DAPA-MI is a multicenter, parallel-group, registry-based, randomized, double-blind, placebo-controlled phase 3 trial in patients without known diabetes or established HF, presenting with MI and impaired left ventricular systolic function or Q-wave MI. The trial evaluated the effect of dapagliflozin 10 mg vs placebo, given once daily in addition to standard of care therapy, on death, hospitalization for HF (HHF), and other cardiometabolic outcomes. The primary objective of the trial was to determine, using the win-ratio method, if dapagliflozin is superior to placebo by comparing the hierarchical composite outcome of death, HHF, nonfatal MI, atrial fibrillation/flutter, new onset of type 2 diabetes mellitus, HF symptoms as measured by New York Heart Association Functional Classification at last visit, and body weight decrease >= 5% at last visit. Assuming a true win-ratio of 1.20 between dapagliflozin and placebo, 4,000 patients provide a statistical power of 80% for the test of the primary composite outcome. A registry-based randomized controlled trial framework allowed for recruitment, randomization, blinding, and pragmatic data collection of baseline demographics, medications, and clinical outcomes using existing national clinical registries (in Sweden and the UK) integrated with the trial database. Conclusions The trial explores opportunities to improve further the outcome of patients with impaired LV function after MI. The innovative trial design of DAPA-MI, incorporating national clinical registry data, has facilitated efficient patient recruitment as well as outcome ascertainment.
Published: 2023
Full Text: View/download PDF

3. Rationale and design of the DAPA-MI trial : Dapagliflozin in patients without diabetes mellitus with acute myocardial infarction

Author: James, Stefan, Erlinge, David, Storey, Robert F., Mcguire, Darren K., de Belder, Mark, Björkgren, Ida, Johansson, Peter A., Langkilde, Anna Maria, Ridderstrale, Wilhelm, Rizi, Ehsan Parvaresh, Deanfield, John, Oldgren, Jonas, James, Stefan, Erlinge, David, Storey, Robert F., Mcguire, Darren K., de Belder, Mark, Björkgren, Ida, Johansson, Peter A., Langkilde, Anna Maria, Ridderstrale, Wilhelm, Rizi, Ehsan Parvaresh, Deanfield, John, and Oldgren, Jonas
Abstract: Background Therapies that could further prevent the development of heart failure (HF) and other cardiovascular and metabolic events in patients with recent myocardial infarction (MI) represent a large and unmet medical need. Methods DAPA-MI is a multicenter, parallel-group, registry-based, randomized, double-blind, placebo-controlled phase 3 trial in patients without known diabetes or established HF, presenting with MI and impaired left ventricular systolic function or Q-wave MI. The trial evaluated the effect of dapagliflozin 10 mg vs placebo, given once daily in addition to standard of care therapy, on death, hospitalization for HF (HHF), and other cardiometabolic outcomes. The primary objective of the trial was to determine, using the win-ratio method, if dapagliflozin is superior to placebo by comparing the hierarchical composite outcome of death, HHF, nonfatal MI, atrial fibrillation/flutter, new onset of type 2 diabetes mellitus, HF symptoms as measured by New York Heart Association Functional Classification at last visit, and body weight decrease >= 5% at last visit. Assuming a true win-ratio of 1.20 between dapagliflozin and placebo, 4,000 patients provide a statistical power of 80% for the test of the primary composite outcome. A registry-based randomized controlled trial framework allowed for recruitment, randomization, blinding, and pragmatic data collection of baseline demographics, medications, and clinical outcomes using existing national clinical registries (in Sweden and the UK) integrated with the trial database. Conclusions The trial explores opportunities to improve further the outcome of patients with impaired LV function after MI. The innovative trial design of DAPA-MI, incorporating national clinical registry data, has facilitated efficient patient recruitment as well as outcome ascertainment.
Published: 2023
Full Text: View/download PDF

4. Rationale and design of the DAPA-MI trial : Dapagliflozin in patients without diabetes mellitus with acute myocardial infarction

Author: James, Stefan, Erlinge, David, Storey, Robert F., Mcguire, Darren K., de Belder, Mark, Björkgren, Ida, Johansson, Peter A., Langkilde, Anna Maria, Ridderstrale, Wilhelm, Rizi, Ehsan Parvaresh, Deanfield, John, Oldgren, Jonas, James, Stefan, Erlinge, David, Storey, Robert F., Mcguire, Darren K., de Belder, Mark, Björkgren, Ida, Johansson, Peter A., Langkilde, Anna Maria, Ridderstrale, Wilhelm, Rizi, Ehsan Parvaresh, Deanfield, John, and Oldgren, Jonas
Abstract: Background Therapies that could further prevent the development of heart failure (HF) and other cardiovascular and metabolic events in patients with recent myocardial infarction (MI) represent a large and unmet medical need. Methods DAPA-MI is a multicenter, parallel-group, registry-based, randomized, double-blind, placebo-controlled phase 3 trial in patients without known diabetes or established HF, presenting with MI and impaired left ventricular systolic function or Q-wave MI. The trial evaluated the effect of dapagliflozin 10 mg vs placebo, given once daily in addition to standard of care therapy, on death, hospitalization for HF (HHF), and other cardiometabolic outcomes. The primary objective of the trial was to determine, using the win-ratio method, if dapagliflozin is superior to placebo by comparing the hierarchical composite outcome of death, HHF, nonfatal MI, atrial fibrillation/flutter, new onset of type 2 diabetes mellitus, HF symptoms as measured by New York Heart Association Functional Classification at last visit, and body weight decrease >= 5% at last visit. Assuming a true win-ratio of 1.20 between dapagliflozin and placebo, 4,000 patients provide a statistical power of 80% for the test of the primary composite outcome. A registry-based randomized controlled trial framework allowed for recruitment, randomization, blinding, and pragmatic data collection of baseline demographics, medications, and clinical outcomes using existing national clinical registries (in Sweden and the UK) integrated with the trial database. Conclusions The trial explores opportunities to improve further the outcome of patients with impaired LV function after MI. The innovative trial design of DAPA-MI, incorporating national clinical registry data, has facilitated efficient patient recruitment as well as outcome ascertainment.
Published: 2023
Full Text: View/download PDF

5. Rationale and design of the DAPA-MI trial : Dapagliflozin in patients without diabetes mellitus with acute myocardial infarction

Author: James, Stefan, Erlinge, David, Storey, Robert F., Mcguire, Darren K., de Belder, Mark, Björkgren, Ida, Johansson, Peter A., Langkilde, Anna Maria, Ridderstrale, Wilhelm, Rizi, Ehsan Parvaresh, Deanfield, John, Oldgren, Jonas, James, Stefan, Erlinge, David, Storey, Robert F., Mcguire, Darren K., de Belder, Mark, Björkgren, Ida, Johansson, Peter A., Langkilde, Anna Maria, Ridderstrale, Wilhelm, Rizi, Ehsan Parvaresh, Deanfield, John, and Oldgren, Jonas
Abstract: Background Therapies that could further prevent the development of heart failure (HF) and other cardiovascular and metabolic events in patients with recent myocardial infarction (MI) represent a large and unmet medical need. Methods DAPA-MI is a multicenter, parallel-group, registry-based, randomized, double-blind, placebo-controlled phase 3 trial in patients without known diabetes or established HF, presenting with MI and impaired left ventricular systolic function or Q-wave MI. The trial evaluated the effect of dapagliflozin 10 mg vs placebo, given once daily in addition to standard of care therapy, on death, hospitalization for HF (HHF), and other cardiometabolic outcomes. The primary objective of the trial was to determine, using the win-ratio method, if dapagliflozin is superior to placebo by comparing the hierarchical composite outcome of death, HHF, nonfatal MI, atrial fibrillation/flutter, new onset of type 2 diabetes mellitus, HF symptoms as measured by New York Heart Association Functional Classification at last visit, and body weight decrease >= 5% at last visit. Assuming a true win-ratio of 1.20 between dapagliflozin and placebo, 4,000 patients provide a statistical power of 80% for the test of the primary composite outcome. A registry-based randomized controlled trial framework allowed for recruitment, randomization, blinding, and pragmatic data collection of baseline demographics, medications, and clinical outcomes using existing national clinical registries (in Sweden and the UK) integrated with the trial database. Conclusions The trial explores opportunities to improve further the outcome of patients with impaired LV function after MI. The innovative trial design of DAPA-MI, incorporating national clinical registry data, has facilitated efficient patient recruitment as well as outcome ascertainment.
Published: 2023
Full Text: View/download PDF

6. Is the ESC blowing its own trumpet or should it have a deserved fanfare? The impact and power of registry data

Author: de Belder, Mark A, Deanfield, John, James, Stefan, Oldgren, Jonas, de Belder, Mark A, Deanfield, John, James, Stefan, and Oldgren, Jonas
Published: 2022
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7. Metabolomic profiles predict individual multidisease outcomes

Author: Buergel, Thore, Steinfeldt, Jakob, Ruyoga, Greg, Pietzner, Maik, Bizzarri, Daniele, Vojinovic, Dina, zu Belzen, Julius Upmeier, Loock, Lukas, Kittner, Paul, Christmann, Lara, Hollmann, Noah, Strangalies, Henrik, Braunger, Jana M., Wild, Benjamin, Chiesa, Scott T., Spranger, Joachim, Klostermann, Fabian, van den Akker, Erik B., Trompet, Stella, Mooijaart, Simon P., Sattar, Naveed, Jukema, J. Wouter, Lavrijssen, Birgit, Kavousi, Maryam, Ghanbari, Mohsen, Ikram, Mohammad A., Slagboom, Eline, Kivimaki, Mika, Langenberg, Claudia, Deanfield, John, Eils, Roland, Landmesser, Ulf, Buergel, Thore, Steinfeldt, Jakob, Ruyoga, Greg, Pietzner, Maik, Bizzarri, Daniele, Vojinovic, Dina, zu Belzen, Julius Upmeier, Loock, Lukas, Kittner, Paul, Christmann, Lara, Hollmann, Noah, Strangalies, Henrik, Braunger, Jana M., Wild, Benjamin, Chiesa, Scott T., Spranger, Joachim, Klostermann, Fabian, van den Akker, Erik B., Trompet, Stella, Mooijaart, Simon P., Sattar, Naveed, Jukema, J. Wouter, Lavrijssen, Birgit, Kavousi, Maryam, Ghanbari, Mohsen, Ikram, Mohammad A., Slagboom, Eline, Kivimaki, Mika, Langenberg, Claudia, Deanfield, John, Eils, Roland, and Landmesser, Ulf
Abstract: Risk stratification is critical for the early identification of high-risk individuals and disease prevention. Here we explored the potential of nuclear magnetic resonance (NMR) spectroscopy-derived metabolomic profiles to inform on multidisease risk beyond conventional clinical predictors for the onset of 24 common conditions, including metabolic, vascular, respiratory, musculoskeletal and neurological diseases and cancers. Specifically, we trained a neural network to learn disease-specific metabolomic states from 168 circulating metabolic markers measured in 117,981 participants with -1.4 million person-years of follow-up from the UK Biobank and validated the model in four independent cohorts. We found metabolomic states to be associated with incident event rates in all the investigated conditions, except breast cancer. For 10-year outcome prediction for 15 endpoints, with and without established metabolic contribution, a combination of age and sex and the metabolomic state equaled or outperformed established predictors. Moreover, metabolomic state added predictive information over comprehensive clinical variables for eight common diseases, including type 2 diabetes, dementia and heart failure. Decision curve analyses showed that predictive improvements translated into clinical utility for a wide range of potential decision thresholds. Taken together, our study demonstrates both the potential and limitations of NMR-derived metabolomic profiles as a multidisease assay to inform on the risk of many common diseases simultaneously.
Published: 2022

8. Sex-specific evaluation and redevelopment of the GRACE score in non-ST-segment elevation acute coronary syndromes in populations from the UK and Switzerland: a multinational analysis with external cohort validation

Author: Wenzl, Florian A, Kraler, Simon, Ambler, Gareth, Weston, Clive, Herzog, Sereina A, Räber, Lorenz, Muller, Olivier, Camici, Giovanni G, Roffi, Marco, Rickli, Hans, Fox, Keith A A, de Belder, Mark, Radovanovic, Dragana, Deanfield, John, Lüscher, Thomas F, Wenzl, Florian A, Kraler, Simon, Ambler, Gareth, Weston, Clive, Herzog, Sereina A, Räber, Lorenz, Muller, Olivier, Camici, Giovanni G, Roffi, Marco, Rickli, Hans, Fox, Keith A A, de Belder, Mark, Radovanovic, Dragana, Deanfield, John, and Lüscher, Thomas F
Abstract: BACKGROUND The Global Registry of Acute Coronary Events (GRACE) 2.0 score was developed and validated in predominantly male patient populations. We aimed to assess its sex-specific performance in non-ST-segment elevation acute coronary syndromes (NSTE-ACS) and to develop an improved score (GRACE 3.0) that accounts for sex differences in disease characteristics. METHODS We evaluated the GRACE 2.0 score in 420 781 consecutive patients with NSTE-ACS in contemporary nationwide cohorts from the UK and Switzerland. Machine learning models to predict in-hospital mortality were informed by the GRACE variables and developed in sex-disaggregated data from 386 591 patients from England, Wales, and Northern Ireland (split into a training cohort of 309 083 [80·0%] patients and a validation cohort of 77 508 [20·0%] patients). External validation of the GRACE 3.0 score was done in 20 727 patients from Switzerland. FINDINGS Between Jan 1, 2005, and Aug 27, 2020, 400 054 patients with NSTE-ACS in the UK and 20 727 patients with NSTE-ACS in Switzerland were included in the study. Discrimination of in-hospital death by the GRACE 2.0 score was good in male patients (area under the receiver operating characteristic curve [AUC] 0·86, 95% CI 0·86-0·86) and notably lower in female patients (0·82, 95% CI 0·81-0·82; p<0·0001). The GRACE 2.0 score underestimated in-hospital mortality risk in female patients, favouring their incorrect stratification to the low-to-intermediate risk group, for which the score does not indicate early invasive treatment. Accounting for sex differences, GRACE 3.0 showed superior discrimination and good calibration with an AUC of 0·91 (95% CI 0·89-0·92) in male patients and 0·87 (95% CI 0·84-0·89) in female patients in an external cohort validation. GRACE 3·0 led to a clinically relevant reclassification of female patients to the high-risk group. INTERPRETATION The GRACE 2.0 score has limited discriminatory performance and underestimates in-hospital mortality in fem
Published: 2022

9. Association of factor v leiden with subsequent atherothrombotic events: A GENIUS-CHD study of individual participant data

Author: Mahmoodi, Bakhtawar K., Tragante, Vinicius, Kleber, Marcus E., Holmes, Michael V., Schmidt, Amand F., McCubrey, Raymond O., Howe, Laurence J., Direk, Kenan, Allayee, Hooman, Baranova, Ekaterina V., Braund, Peter S., Delgado, Graciela E., Eriksson, Niclas, Gijsberts, Crystel M., Gong, Yan, Hartiala, Jaana, Heydarpour, Mahyar, Pasterkamp, Gerard, Kotti, Salma, Kuukasjärvi, Pekka, Lenzini, Petra A., Levin, Daniel, Lyytikäinen, Leo Pekka, Muehlschlegel, Jochen D., Nelson, Christopher P., Nikus, Kjell, Pilbrow, Anna P., Wilson Tang, W. H., Van Der Laan, Sander W., Van Setten, Jessica, Vilmundarson, Ragnar O., Deanfield, John, Deloukas, Panos, Dudbridge, Frank, James, Stefan, Mordi, Ify R., Teren, Andrej, Bergmeijer, Thomas O., Body, Simon C., Bots, Michiel, Burkhardt, Ralph, Cooper-Dehoff, Rhonda M., Cresci, Sharon, Danchin, Nicolas, Doughty, Robert N., Grobbee, Diederick E., Hagström, Emil, Hazen, Stanley L., Held, Claes, Hoefer, Imo E., Hovingh, G. Kees, Johnson, Julie A., Kaczor, Marcin P., Kähönen, Mika, Klungel, Olaf H., Laurikka, Jari O., Lehtimäki, Terho, Maitland-Van Der Zee, Anke H., McPherson, Ruth, Palmer, Colin N., Kraaijeveld, Adriaan O., Pepine, Carl J., Sanak, Marek, Sattar, Naveed, Scholz, Markus, Simon, Tabassome, Spertus, John A., Stewart, Alexandre F.R., Szczeklik, Wojciech, Thiery, Joachim, Visseren, Frank L.J., Waltenberger, Johannes, Richards, A. Mark, Lang, Chim C., Cameron, Vicky A., Åkerblom, Axel, Pare, Guillaume, März, Winfried, Samani, Nilesh J., Hingorani, Aroon D., Ten Berg, Jurriën M., Wallentin, Lars, Asselbergs, Folkert W., Patel, Riyaz S., Mahmoodi, Bakhtawar K., Tragante, Vinicius, Kleber, Marcus E., Holmes, Michael V., Schmidt, Amand F., McCubrey, Raymond O., Howe, Laurence J., Direk, Kenan, Allayee, Hooman, Baranova, Ekaterina V., Braund, Peter S., Delgado, Graciela E., Eriksson, Niclas, Gijsberts, Crystel M., Gong, Yan, Hartiala, Jaana, Heydarpour, Mahyar, Pasterkamp, Gerard, Kotti, Salma, Kuukasjärvi, Pekka, Lenzini, Petra A., Levin, Daniel, Lyytikäinen, Leo Pekka, Muehlschlegel, Jochen D., Nelson, Christopher P., Nikus, Kjell, Pilbrow, Anna P., Wilson Tang, W. H., Van Der Laan, Sander W., Van Setten, Jessica, Vilmundarson, Ragnar O., Deanfield, John, Deloukas, Panos, Dudbridge, Frank, James, Stefan, Mordi, Ify R., Teren, Andrej, Bergmeijer, Thomas O., Body, Simon C., Bots, Michiel, Burkhardt, Ralph, Cooper-Dehoff, Rhonda M., Cresci, Sharon, Danchin, Nicolas, Doughty, Robert N., Grobbee, Diederick E., Hagström, Emil, Hazen, Stanley L., Held, Claes, Hoefer, Imo E., Hovingh, G. Kees, Johnson, Julie A., Kaczor, Marcin P., Kähönen, Mika, Klungel, Olaf H., Laurikka, Jari O., Lehtimäki, Terho, Maitland-Van Der Zee, Anke H., McPherson, Ruth, Palmer, Colin N., Kraaijeveld, Adriaan O., Pepine, Carl J., Sanak, Marek, Sattar, Naveed, Scholz, Markus, Simon, Tabassome, Spertus, John A., Stewart, Alexandre F.R., Szczeklik, Wojciech, Thiery, Joachim, Visseren, Frank L.J., Waltenberger, Johannes, Richards, A. Mark, Lang, Chim C., Cameron, Vicky A., Åkerblom, Axel, Pare, Guillaume, März, Winfried, Samani, Nilesh J., Hingorani, Aroon D., Ten Berg, Jurriën M., Wallentin, Lars, Asselbergs, Folkert W., and Patel, Riyaz S.
Abstract: Background: Studies examining the role of factor V Leiden among patients at higher risk of atherothrombotic events, such as those with established coronary heart disease (CHD), are lacking. Given that coagulation is involved in the thrombus formation stage on atherosclerotic plaque rupture, we hypothesized that factor V Leiden may be a stronger risk factor for atherothrombotic events in patients with established CHD. Methods: We performed an individual-level meta-analysis including 25 prospective studies (18 cohorts, 3 case-cohorts, 4 randomized trials) from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) consortium involving patients with established CHD at baseline. Participating studies genotyped factor V Leiden status and shared risk estimates for the outcomes of interest using a centrally developed statistical code with harmonized definitions across studies. Cox proportional hazards regression models were used to obtain age- and sex-adjusted estimates. The obtained estimates were pooled using fixed-effect meta-analysis. The primary outcome was composite of myocardial infarction and CHD death. Secondary outcomes included any stroke, ischemic stroke, coronary revascularization, cardiovascular mortality, and all-cause mortality. Results: The studies included 69 681 individuals of whom 3190 (4.6%) were either heterozygous or homozygous (n=47) carriers of factor V Leiden. Median follow-up per study ranged from 1.0 to 10.6 years. A total of 20 studies with 61 147 participants and 6849 events contributed to analyses of the primary outcome. Factor V Leiden was not associated with the combined outcome of myocardial infarction and CHD death (hazard ratio, 1.03 [95% CI, 0.92-1.16]; I2=28%; P-heterogeneity=0.12). Subgroup analysis according to baseline characteristics or strata of traditional cardiovascular risk factors did not show relevant differences. Similarly, risk estimates for the secondary outcomes including stroke, coronary revasculari
Published: 2020

10. Association of Factor V Leiden With Subsequent Atherothrombotic Events A GENIUS-CHD Study of Individual Participant Data

Author: Mahmoodi, Bakhtawar K., Tragante, Vinicius, Kleber, Marcus E., Holmes, Michael V., Schmidt, Amand F., McCubrey, Raymond O., Howe, Laurence J., Direk, Kenan, Allayee, Hooman, Baranova, Ekaterina V., Braund, Peter S., Delgado, Graciela E., Eriksson, Niclas, Gijsberts, Crystel M., Gong, Yan, Hartiala, Jaana, Heydarpour, Mahyar, Pasterkamp, Gerard, Kotti, Salma, Kuukasjarvi, Pekka, Lenzini, Petra A., Levin, Daniel, Lyytikainen, Leo-Pekka, Muehlschlegel, Jochen D., Nelson, Christopher P., Nikus, Kjell, Pilbrow, Anna P., Wilson Tang, W. H., van der Laan, Sander W., van Setten, Jessica, Vilmundarson, Ragnar O., Deanfield, John, Deloukas, Panos, Dudbridge, Frank, James, Stefan, Mordi, Ify R., Teren, Andrej, Bergmeijer, Thomas O., Body, Simon C., Bots, Michiel, Burkhardt, Ralph, Cooper-DeHoff, Rhonda M., Cresci, Sharon, Danchin, Nicolas, Doughty, Robert N., Grobbee, Diederick E., Hagström, Emil, Hazen, Stanley L., Held, Claes, Hoefer, Imo E., Hovingh, G. Kees, Johnson, Julie A., Kaczor, Marcin P., Kahonen, Mika, Klungel, Olaf H., Laurikka, Jari O., Lehtimaki, Terho, van der Zee, Anke H., McPherson, Ruth, Palmer, Colin N., Kraaijeveld, Adriaan O., Pepine, Carl J., Sanak, Marek, Sattar, Naveed, Scholz, Markus, Simon, Tabassome, Spertus, John A., Stewart, Alexandre F. R., Szczeklik, Wojciech, Thiery, Joachim, Visseren, Frank L. J., Waltenberger, Johannes, Richards, A. Mark, Lang, Chim C., Cameron, Vicky A., Åkerblom, Axel, Pare, Guillaume, Maerz, Winfried, Samani, Nilesh J., Hingorani, Aroon D., ten Berg, Jurrien M., Wallentin, Lars, Asselbergs, Folkert W., Patel, Riyaz S., Mahmoodi, Bakhtawar K., Tragante, Vinicius, Kleber, Marcus E., Holmes, Michael V., Schmidt, Amand F., McCubrey, Raymond O., Howe, Laurence J., Direk, Kenan, Allayee, Hooman, Baranova, Ekaterina V., Braund, Peter S., Delgado, Graciela E., Eriksson, Niclas, Gijsberts, Crystel M., Gong, Yan, Hartiala, Jaana, Heydarpour, Mahyar, Pasterkamp, Gerard, Kotti, Salma, Kuukasjarvi, Pekka, Lenzini, Petra A., Levin, Daniel, Lyytikainen, Leo-Pekka, Muehlschlegel, Jochen D., Nelson, Christopher P., Nikus, Kjell, Pilbrow, Anna P., Wilson Tang, W. H., van der Laan, Sander W., van Setten, Jessica, Vilmundarson, Ragnar O., Deanfield, John, Deloukas, Panos, Dudbridge, Frank, James, Stefan, Mordi, Ify R., Teren, Andrej, Bergmeijer, Thomas O., Body, Simon C., Bots, Michiel, Burkhardt, Ralph, Cooper-DeHoff, Rhonda M., Cresci, Sharon, Danchin, Nicolas, Doughty, Robert N., Grobbee, Diederick E., Hagström, Emil, Hazen, Stanley L., Held, Claes, Hoefer, Imo E., Hovingh, G. Kees, Johnson, Julie A., Kaczor, Marcin P., Kahonen, Mika, Klungel, Olaf H., Laurikka, Jari O., Lehtimaki, Terho, van der Zee, Anke H., McPherson, Ruth, Palmer, Colin N., Kraaijeveld, Adriaan O., Pepine, Carl J., Sanak, Marek, Sattar, Naveed, Scholz, Markus, Simon, Tabassome, Spertus, John A., Stewart, Alexandre F. R., Szczeklik, Wojciech, Thiery, Joachim, Visseren, Frank L. J., Waltenberger, Johannes, Richards, A. Mark, Lang, Chim C., Cameron, Vicky A., Åkerblom, Axel, Pare, Guillaume, Maerz, Winfried, Samani, Nilesh J., Hingorani, Aroon D., ten Berg, Jurrien M., Wallentin, Lars, Asselbergs, Folkert W., and Patel, Riyaz S.
Abstract: Background: Studies examining the role of factor V Leiden among patients at higher risk of atherothrombotic events, such as those with established coronary heart disease (CHD), are lacking. Given that coagulation is involved in the thrombus formation stage on atherosclerotic plaque rupture, we hypothesized that factor V Leiden may be a stronger risk factor for atherothrombotic events in patients with established CHD. Methods: We performed an individual-level meta-analysis including 25 prospective studies (18 cohorts, 3 case-cohorts, 4 randomized trials) from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) consortium involving patients with established CHD at baseline. Participating studies genotyped factor V Leiden status and shared risk estimates for the outcomes of interest using a centrally developed statistical code with harmonized definitions across studies. Cox proportional hazards regression models were used to obtain age- and sex-adjusted estimates. The obtained estimates were pooled using fixed-effect meta-analysis. The primary outcome was composite of myocardial infarction and CHD death. Secondary outcomes included any stroke, ischemic stroke, coronary revascularization, cardiovascular mortality, and all-cause mortality. Results: The studies included 69 681 individuals of whom 3190 (4.6%) were either heterozygous or homozygous (n=47) carriers of factor V Leiden. Median follow-up per study ranged from 1.0 to 10.6 years. A total of 20 studies with 61 147 participants and 6849 events contributed to analyses of the primary outcome. Factor V Leiden was not associated with the combined outcome of myocardial infarction and CHD death (hazard ratio, 1.03 [95% CI, 0.92-1.16];I-2=28%;P-heterogeneity=0.12). Subgroup analysis according to baseline characteristics or strata of traditional cardiovascular risk factors did not show relevant differences. Similarly, risk estimates for the secondary outcomes including stroke, coronary revascularization, cardiov
Published: 2020
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11. Systems Analysis Implicates WAVE2 Complex in the Pathogenesis of Developmental Left-Sided Obstructive Heart Defects.

Author: Edwards, Jonathan J, Edwards, Jonathan J, Rouillard, Andrew D, Fernandez, Nicolas F, Wang, Zichen, Lachmann, Alexander, Shankaran, Sunita S, Bisgrove, Brent W, Demarest, Bradley, Turan, Nahid, Srivastava, Deepak, Bernstein, Daniel, Deanfield, John, Giardini, Alessandro, Porter, George, Kim, Richard, Roberts, Amy E, Newburger, Jane W, Goldmuntz, Elizabeth, Brueckner, Martina, Lifton, Richard P, Seidman, Christine E, Chung, Wendy K, Tristani-Firouzi, Martin, Yost, H Joseph, Ma'ayan, Avi, Gelb, Bruce D, Edwards, Jonathan J, Edwards, Jonathan J, Rouillard, Andrew D, Fernandez, Nicolas F, Wang, Zichen, Lachmann, Alexander, Shankaran, Sunita S, Bisgrove, Brent W, Demarest, Bradley, Turan, Nahid, Srivastava, Deepak, Bernstein, Daniel, Deanfield, John, Giardini, Alessandro, Porter, George, Kim, Richard, Roberts, Amy E, Newburger, Jane W, Goldmuntz, Elizabeth, Brueckner, Martina, Lifton, Richard P, Seidman, Christine E, Chung, Wendy K, Tristani-Firouzi, Martin, Yost, H Joseph, Ma'ayan, Avi, and Gelb, Bruce D
Abstract: Genetic variants are the primary driver of congenital heart disease (CHD) pathogenesis. However, our ability to identify causative variants is limited. To identify causal CHD genes that are associated with specific molecular functions, the study used prior knowledge to filter de novo variants from 2,881 probands with sporadic severe CHD. This approach enabled the authors to identify an association between left ventricular outflow tract obstruction lesions and genes associated with the WAVE2 complex and regulation of small GTPase-mediated signal transduction. Using CRISPR zebrafish knockdowns, the study confirmed that WAVE2 complex proteins brk1, nckap1, and wasf2 and the regulators of small GTPase signaling cul3a and racgap1 are critical to cardiac development.
Published: 2020

12. Association of factor v leiden with subsequent atherothrombotic events: A GENIUS-CHD study of individual participant data

Author: Afd Pharmacoepi & Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology, Mahmoodi, Bakhtawar K., Tragante, Vinicius, Kleber, Marcus E., Holmes, Michael V., Schmidt, Amand F., McCubrey, Raymond O., Howe, Laurence J., Direk, Kenan, Allayee, Hooman, Baranova, Ekaterina V., Braund, Peter S., Delgado, Graciela E., Eriksson, Niclas, Gijsberts, Crystel M., Gong, Yan, Hartiala, Jaana, Heydarpour, Mahyar, Pasterkamp, Gerard, Kotti, Salma, Kuukasjärvi, Pekka, Lenzini, Petra A., Levin, Daniel, Lyytikäinen, Leo Pekka, Muehlschlegel, Jochen D., Nelson, Christopher P., Nikus, Kjell, Pilbrow, Anna P., Wilson Tang, W. H., Van Der Laan, Sander W., Van Setten, Jessica, Vilmundarson, Ragnar O., Deanfield, John, Deloukas, Panos, Dudbridge, Frank, James, Stefan, Mordi, Ify R., Teren, Andrej, Bergmeijer, Thomas O., Body, Simon C., Bots, Michiel, Burkhardt, Ralph, Cooper-Dehoff, Rhonda M., Cresci, Sharon, Danchin, Nicolas, Doughty, Robert N., Grobbee, Diederick E., Hagström, Emil, Hazen, Stanley L., Held, Claes, Hoefer, Imo E., Hovingh, G. Kees, Johnson, Julie A., Kaczor, Marcin P., Kähönen, Mika, Klungel, Olaf H., Laurikka, Jari O., Lehtimäki, Terho, Maitland-Van Der Zee, Anke H., McPherson, Ruth, Palmer, Colin N., Kraaijeveld, Adriaan O., Pepine, Carl J., Sanak, Marek, Sattar, Naveed, Scholz, Markus, Simon, Tabassome, Spertus, John A., Stewart, Alexandre F.R., Szczeklik, Wojciech, Thiery, Joachim, Visseren, Frank L.J., Waltenberger, Johannes, Richards, A. Mark, Lang, Chim C., Cameron, Vicky A., Åkerblom, Axel, Pare, Guillaume, März, Winfried, Samani, Nilesh J., Hingorani, Aroon D., Ten Berg, Jurriën M., Wallentin, Lars, Asselbergs, Folkert W., Patel, Riyaz S., Afd Pharmacoepi & Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology, Mahmoodi, Bakhtawar K., Tragante, Vinicius, Kleber, Marcus E., Holmes, Michael V., Schmidt, Amand F., McCubrey, Raymond O., Howe, Laurence J., Direk, Kenan, Allayee, Hooman, Baranova, Ekaterina V., Braund, Peter S., Delgado, Graciela E., Eriksson, Niclas, Gijsberts, Crystel M., Gong, Yan, Hartiala, Jaana, Heydarpour, Mahyar, Pasterkamp, Gerard, Kotti, Salma, Kuukasjärvi, Pekka, Lenzini, Petra A., Levin, Daniel, Lyytikäinen, Leo Pekka, Muehlschlegel, Jochen D., Nelson, Christopher P., Nikus, Kjell, Pilbrow, Anna P., Wilson Tang, W. H., Van Der Laan, Sander W., Van Setten, Jessica, Vilmundarson, Ragnar O., Deanfield, John, Deloukas, Panos, Dudbridge, Frank, James, Stefan, Mordi, Ify R., Teren, Andrej, Bergmeijer, Thomas O., Body, Simon C., Bots, Michiel, Burkhardt, Ralph, Cooper-Dehoff, Rhonda M., Cresci, Sharon, Danchin, Nicolas, Doughty, Robert N., Grobbee, Diederick E., Hagström, Emil, Hazen, Stanley L., Held, Claes, Hoefer, Imo E., Hovingh, G. Kees, Johnson, Julie A., Kaczor, Marcin P., Kähönen, Mika, Klungel, Olaf H., Laurikka, Jari O., Lehtimäki, Terho, Maitland-Van Der Zee, Anke H., McPherson, Ruth, Palmer, Colin N., Kraaijeveld, Adriaan O., Pepine, Carl J., Sanak, Marek, Sattar, Naveed, Scholz, Markus, Simon, Tabassome, Spertus, John A., Stewart, Alexandre F.R., Szczeklik, Wojciech, Thiery, Joachim, Visseren, Frank L.J., Waltenberger, Johannes, Richards, A. Mark, Lang, Chim C., Cameron, Vicky A., Åkerblom, Axel, Pare, Guillaume, März, Winfried, Samani, Nilesh J., Hingorani, Aroon D., Ten Berg, Jurriën M., Wallentin, Lars, Asselbergs, Folkert W., and Patel, Riyaz S.
Published: 2020

13. Association of factor v leiden with subsequent atherothrombotic events: A GENIUS-CHD study of individual participant data

Author: Afd Pharmacoepi & Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology, Mahmoodi, Bakhtawar K., Tragante, Vinicius, Kleber, Marcus E., Holmes, Michael V., Schmidt, Amand F., McCubrey, Raymond O., Howe, Laurence J., Direk, Kenan, Allayee, Hooman, Baranova, Ekaterina V., Braund, Peter S., Delgado, Graciela E., Eriksson, Niclas, Gijsberts, Crystel M., Gong, Yan, Hartiala, Jaana, Heydarpour, Mahyar, Pasterkamp, Gerard, Kotti, Salma, Kuukasjärvi, Pekka, Lenzini, Petra A., Levin, Daniel, Lyytikäinen, Leo Pekka, Muehlschlegel, Jochen D., Nelson, Christopher P., Nikus, Kjell, Pilbrow, Anna P., Wilson Tang, W. H., Van Der Laan, Sander W., Van Setten, Jessica, Vilmundarson, Ragnar O., Deanfield, John, Deloukas, Panos, Dudbridge, Frank, James, Stefan, Mordi, Ify R., Teren, Andrej, Bergmeijer, Thomas O., Body, Simon C., Bots, Michiel, Burkhardt, Ralph, Cooper-Dehoff, Rhonda M., Cresci, Sharon, Danchin, Nicolas, Doughty, Robert N., Grobbee, Diederick E., Hagström, Emil, Hazen, Stanley L., Held, Claes, Hoefer, Imo E., Hovingh, G. Kees, Johnson, Julie A., Kaczor, Marcin P., Kähönen, Mika, Klungel, Olaf H., Laurikka, Jari O., Lehtimäki, Terho, Maitland-Van Der Zee, Anke H., McPherson, Ruth, Palmer, Colin N., Kraaijeveld, Adriaan O., Pepine, Carl J., Sanak, Marek, Sattar, Naveed, Scholz, Markus, Simon, Tabassome, Spertus, John A., Stewart, Alexandre F.R., Szczeklik, Wojciech, Thiery, Joachim, Visseren, Frank L.J., Waltenberger, Johannes, Richards, A. Mark, Lang, Chim C., Cameron, Vicky A., Åkerblom, Axel, Pare, Guillaume, März, Winfried, Samani, Nilesh J., Hingorani, Aroon D., Ten Berg, Jurriën M., Wallentin, Lars, Asselbergs, Folkert W., Patel, Riyaz S., Afd Pharmacoepi & Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology, Mahmoodi, Bakhtawar K., Tragante, Vinicius, Kleber, Marcus E., Holmes, Michael V., Schmidt, Amand F., McCubrey, Raymond O., Howe, Laurence J., Direk, Kenan, Allayee, Hooman, Baranova, Ekaterina V., Braund, Peter S., Delgado, Graciela E., Eriksson, Niclas, Gijsberts, Crystel M., Gong, Yan, Hartiala, Jaana, Heydarpour, Mahyar, Pasterkamp, Gerard, Kotti, Salma, Kuukasjärvi, Pekka, Lenzini, Petra A., Levin, Daniel, Lyytikäinen, Leo Pekka, Muehlschlegel, Jochen D., Nelson, Christopher P., Nikus, Kjell, Pilbrow, Anna P., Wilson Tang, W. H., Van Der Laan, Sander W., Van Setten, Jessica, Vilmundarson, Ragnar O., Deanfield, John, Deloukas, Panos, Dudbridge, Frank, James, Stefan, Mordi, Ify R., Teren, Andrej, Bergmeijer, Thomas O., Body, Simon C., Bots, Michiel, Burkhardt, Ralph, Cooper-Dehoff, Rhonda M., Cresci, Sharon, Danchin, Nicolas, Doughty, Robert N., Grobbee, Diederick E., Hagström, Emil, Hazen, Stanley L., Held, Claes, Hoefer, Imo E., Hovingh, G. Kees, Johnson, Julie A., Kaczor, Marcin P., Kähönen, Mika, Klungel, Olaf H., Laurikka, Jari O., Lehtimäki, Terho, Maitland-Van Der Zee, Anke H., McPherson, Ruth, Palmer, Colin N., Kraaijeveld, Adriaan O., Pepine, Carl J., Sanak, Marek, Sattar, Naveed, Scholz, Markus, Simon, Tabassome, Spertus, John A., Stewart, Alexandre F.R., Szczeklik, Wojciech, Thiery, Joachim, Visseren, Frank L.J., Waltenberger, Johannes, Richards, A. Mark, Lang, Chim C., Cameron, Vicky A., Åkerblom, Axel, Pare, Guillaume, März, Winfried, Samani, Nilesh J., Hingorani, Aroon D., Ten Berg, Jurriën M., Wallentin, Lars, Asselbergs, Folkert W., and Patel, Riyaz S.
Published: 2020

14. Systems Analysis Implicates WAVE2 Complex in the Pathogenesis of Developmental Left-Sided Obstructive Heart Defects.

Author: Edwards, Jonathan J, Edwards, Jonathan J, Rouillard, Andrew D, Fernandez, Nicolas F, Wang, Zichen, Lachmann, Alexander, Shankaran, Sunita S, Bisgrove, Brent W, Demarest, Bradley, Turan, Nahid, Srivastava, Deepak, Bernstein, Daniel, Deanfield, John, Giardini, Alessandro, Porter, George, Kim, Richard, Roberts, Amy E, Newburger, Jane W, Goldmuntz, Elizabeth, Brueckner, Martina, Lifton, Richard P, Seidman, Christine E, Chung, Wendy K, Tristani-Firouzi, Martin, Yost, H Joseph, Ma'ayan, Avi, Gelb, Bruce D, Edwards, Jonathan J, Edwards, Jonathan J, Rouillard, Andrew D, Fernandez, Nicolas F, Wang, Zichen, Lachmann, Alexander, Shankaran, Sunita S, Bisgrove, Brent W, Demarest, Bradley, Turan, Nahid, Srivastava, Deepak, Bernstein, Daniel, Deanfield, John, Giardini, Alessandro, Porter, George, Kim, Richard, Roberts, Amy E, Newburger, Jane W, Goldmuntz, Elizabeth, Brueckner, Martina, Lifton, Richard P, Seidman, Christine E, Chung, Wendy K, Tristani-Firouzi, Martin, Yost, H Joseph, Ma'ayan, Avi, and Gelb, Bruce D
Abstract: Genetic variants are the primary driver of congenital heart disease (CHD) pathogenesis. However, our ability to identify causative variants is limited. To identify causal CHD genes that are associated with specific molecular functions, the study used prior knowledge to filter de novo variants from 2,881 probands with sporadic severe CHD. This approach enabled the authors to identify an association between left ventricular outflow tract obstruction lesions and genes associated with the WAVE2 complex and regulation of small GTPase-mediated signal transduction. Using CRISPR zebrafish knockdowns, the study confirmed that WAVE2 complex proteins brk1, nckap1, and wasf2 and the regulators of small GTPase signaling cul3a and racgap1 are critical to cardiac development.
Published: 2020

15. Association of factor v leiden with subsequent atherothrombotic events: A GENIUS-CHD study of individual participant data

Author: Afd Pharmacoepi & Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology, PECP - Centre for Pharmacoepidemiology, Mahmoodi, Bakhtawar K., Tragante, Vinicius, Kleber, Marcus E., Holmes, Michael V., Schmidt, Amand F., McCubrey, Raymond O., Howe, Laurence J., Direk, Kenan, Allayee, Hooman, Baranova, Ekaterina V., Braund, Peter S., Delgado, Graciela E., Eriksson, Niclas, Gijsberts, Crystel M., Gong, Yan, Hartiala, Jaana, Heydarpour, Mahyar, Pasterkamp, Gerard, Kotti, Salma, Kuukasjärvi, Pekka, Lenzini, Petra A., Levin, Daniel, Lyytikäinen, Leo Pekka, Muehlschlegel, Jochen D., Nelson, Christopher P., Nikus, Kjell, Pilbrow, Anna P., Wilson Tang, W. H., Van Der Laan, Sander W., Van Setten, Jessica, Vilmundarson, Ragnar O., Deanfield, John, Deloukas, Panos, Dudbridge, Frank, James, Stefan, Mordi, Ify R., Teren, Andrej, Bergmeijer, Thomas O., Body, Simon C., Bots, Michiel, Burkhardt, Ralph, Cooper-Dehoff, Rhonda M., Cresci, Sharon, Danchin, Nicolas, Doughty, Robert N., Grobbee, Diederick E., Hagström, Emil, Hazen, Stanley L., Held, Claes, Hoefer, Imo E., Hovingh, G. Kees, Johnson, Julie A., Kaczor, Marcin P., Kähönen, Mika, Klungel, Olaf H., Laurikka, Jari O., Lehtimäki, Terho, Maitland-Van Der Zee, Anke H., McPherson, Ruth, Palmer, Colin N., Kraaijeveld, Adriaan O., Pepine, Carl J., Sanak, Marek, Sattar, Naveed, Scholz, Markus, Simon, Tabassome, Spertus, John A., Stewart, Alexandre F.R., Szczeklik, Wojciech, Thiery, Joachim, Visseren, Frank L.J., Waltenberger, Johannes, Richards, A. Mark, Lang, Chim C., Cameron, Vicky A., Åkerblom, Axel, Pare, Guillaume, März, Winfried, Samani, Nilesh J., Hingorani, Aroon D., Ten Berg, Jurriën M., Wallentin, Lars, Asselbergs, Folkert W., Patel, Riyaz S., Afd Pharmacoepi & Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology, PECP - Centre for Pharmacoepidemiology, Mahmoodi, Bakhtawar K., Tragante, Vinicius, Kleber, Marcus E., Holmes, Michael V., Schmidt, Amand F., McCubrey, Raymond O., Howe, Laurence J., Direk, Kenan, Allayee, Hooman, Baranova, Ekaterina V., Braund, Peter S., Delgado, Graciela E., Eriksson, Niclas, Gijsberts, Crystel M., Gong, Yan, Hartiala, Jaana, Heydarpour, Mahyar, Pasterkamp, Gerard, Kotti, Salma, Kuukasjärvi, Pekka, Lenzini, Petra A., Levin, Daniel, Lyytikäinen, Leo Pekka, Muehlschlegel, Jochen D., Nelson, Christopher P., Nikus, Kjell, Pilbrow, Anna P., Wilson Tang, W. H., Van Der Laan, Sander W., Van Setten, Jessica, Vilmundarson, Ragnar O., Deanfield, John, Deloukas, Panos, Dudbridge, Frank, James, Stefan, Mordi, Ify R., Teren, Andrej, Bergmeijer, Thomas O., Body, Simon C., Bots, Michiel, Burkhardt, Ralph, Cooper-Dehoff, Rhonda M., Cresci, Sharon, Danchin, Nicolas, Doughty, Robert N., Grobbee, Diederick E., Hagström, Emil, Hazen, Stanley L., Held, Claes, Hoefer, Imo E., Hovingh, G. Kees, Johnson, Julie A., Kaczor, Marcin P., Kähönen, Mika, Klungel, Olaf H., Laurikka, Jari O., Lehtimäki, Terho, Maitland-Van Der Zee, Anke H., McPherson, Ruth, Palmer, Colin N., Kraaijeveld, Adriaan O., Pepine, Carl J., Sanak, Marek, Sattar, Naveed, Scholz, Markus, Simon, Tabassome, Spertus, John A., Stewart, Alexandre F.R., Szczeklik, Wojciech, Thiery, Joachim, Visseren, Frank L.J., Waltenberger, Johannes, Richards, A. Mark, Lang, Chim C., Cameron, Vicky A., Åkerblom, Axel, Pare, Guillaume, März, Winfried, Samani, Nilesh J., Hingorani, Aroon D., Ten Berg, Jurriën M., Wallentin, Lars, Asselbergs, Folkert W., and Patel, Riyaz S.
Published: 2020

16. Impact of Coronavirus Disease 2019 Pandemic on the Incidence and Management of Out-of-Hospital Cardiac Arrest in Patients Presenting With Acute Myocardial Infarction in England.

Author: Rashid Hons, Muhammad, Gale Hons, Chris P., Curzen Hons, Nick, Ludman Hons, Peter, De Belder Hons, Mark, Timmis Hons, Adam, Mohamed Hons, Mohamed O, Lüscher Hons, Thomas F, Hains Hons, Julian, Wu, Jianhua, Shoaib, Ahmad, Kontopantelis, Evangelos, Roebuck, Chris, Denwood, Tom, Deanfield, John, Mamas, Mamas A., Rashid Hons, Muhammad, Gale Hons, Chris P., Curzen Hons, Nick, Ludman Hons, Peter, De Belder Hons, Mark, Timmis Hons, Adam, Mohamed Hons, Mohamed O, Lüscher Hons, Thomas F, Hains Hons, Julian, Wu, Jianhua, Shoaib, Ahmad, Kontopantelis, Evangelos, Roebuck, Chris, Denwood, Tom, Deanfield, John, and Mamas, Mamas A.
Abstract: Background Studies have reported significant reduction in acute myocardial infarction-related hospitalizations during the coronavirus disease 2019 (COVID-19) pandemic. However, whether these trends are associated with increased incidence of out-of-hospital cardiac arrest (OHCA) in this population is unknown. Methods and Results Acute myocardial infarction hospitalizations with OHCA during the COVID-19 period (February 1-May 14, 2020) from the Myocardial Ischaemia National Audit Project and British Cardiovascular Intervention Society data sets were analyzed. Temporal trends were assessed using Poisson models with equivalent pre-COVID-19 period (February 1-May 14, 2019) as reference. Acute myocardial infarction hospitalizations during COVID-19 period were reduced by >50% (n=20 310 versus n=9325). OHCA was more prevalent during the COVID-19 period compared with the pre-COVID-19 period (5.6% versus 3.6%), with a 56% increase in the incidence of OHCA (incidence rate ratio, 1.56; 95% CI, 1.39-1.74). Patients experiencing OHCA during COVID-19 period were likely to be older, likely to be women, likely to be of Asian ethnicity, and more likely to present with ST-segment-elevation myocardial infarction. The overall rates of invasive coronary angiography (58.4% versus 71.6%; P
Published: 2020

17. Impact of the COVID-19 Pandemic on Percutaneous Coronary Intervention in England: Insights From the British Cardiovascular Intervention Society PCI Database Cohort

Author: Kwok, Chun Shing, Gale, Chris P, Curzen, Nick, de Belder, Mark A, Ludman, Peter, Lüscher, Thomas F; https://orcid.org/0000-0002-5259-538X, Kontopantelis, Evangelos, Roebuck, Chris, Denwood, Tom, Burton, Tony, Hains, Julian, Deanfield, John E, Mamas, Mamas A, Kwok, Chun Shing, Gale, Chris P, Curzen, Nick, de Belder, Mark A, Ludman, Peter, Lüscher, Thomas F; https://orcid.org/0000-0002-5259-538X, Kontopantelis, Evangelos, Roebuck, Chris, Denwood, Tom, Burton, Tony, Hains, Julian, Deanfield, John E, and Mamas, Mamas A
Abstract: BACKGROUND The objective of the study was to evaluate changes in percutaneous coronary intervention (PCI) practice in England by analyzing procedural numbers, changes in the clinical presentation, and characteristics of patients and their clinical outcomes during the coronavirus disease 2019 (COVID-19) pandemic. METHODS We conducted a retrospective cohort study of all patients who underwent PCI in England between January 2017 and April 2020 in the British Cardiovascular Intervention Society database. RESULTS Forty-four hospitals reported PCI procedures for 126 491 patients. There were ≈700 procedures performed each week before the lockdown. After the March 23, 2020 lockdown (11th/12th week in 2020), there was a 49% fall in the number of PCI procedures after the 12th week in 2020. The decrease was greatest in PCI procedures performed for stable angina (66%), followed by non-ST-segment-elevation myocardial infarction (45%), and ST-segment-elevation myocardial infarction (33%). Patients after the lockdown were younger (64.5 versus 65.5 years, P<0.001) and less likely to have diabetes (20.4% versus 24.6%, P<0.001), hypertension (52.0% versus 56.8%, P=0.001), previous myocardial infarction (23.5% versus 26.7%, P=0.008), previous PCI (24.3% versus 28.3%, P=0.001), or previous coronary artery bypass graft (4.6% versus 7.2%, P<0.001) compared with before the lockdown. CONCLUSIONS The lockdown in England has resulted in a significant decline in PCI procedures. Fewer patients underwent PCI for stable angina. This enabled greater capacity for urgent and emergency cases, and a reduced length of stay was seen for such patients. Significant changes in the characteristics of patients towards a lower risk phenotype were observed, particularly for non-ST-segment-elevation myocardial infarction, reflecting a more conservative approach to this cohort.
Published: 2020

18. Association of Factor V Leiden With Subsequent Atherothrombotic Events: A GENIUS-CHD Study of Individual Participant Data

Author: Onderzoek Precision medicine, Circulatory Health, CDL Onderzoek Pasterkamp, Cardiovasculaire Epidemiologie, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Global Health, CDL Arcadia, JC onderzoeksprogramma Methodologie, Team Medisch, Interne Geneeskunde Vasculaire, Mahmoodi, Bakhtawar K, Tragante, Vinicius, Kleber, Marcus E, Holmes, Michael V, Schmidt, Amand F, McCubrey, Raymond O, Howe, Laurence J, Direk, Kenan, Allayee, Hooman, Baranova, Ekaterina V, Braund, Peter S, Delgado, Graciela E, Eriksson, Niclas, Gijsberts, Crystel M, Gong, Yan, Hartiala, Jaana, Heydarpour, Mahyar, Pasterkamp, Gerard, Kotti, Salma, Kuukasjärvi, Pekka, Lenzini, Petra A, Levin, Daniel, Lyytikäinen, Leo-Pekka, Muehlschlegel, Jochen D, Nelson, Christopher P, Nikus, Kjell, Pilbrow, Anna P, Wilson Tang, W H, van der Laan, Sander W, van Setten, Jessica, Vilmundarson, Ragnar O, Deanfield, John, Deloukas, Panos, Dudbridge, Frank, James, Stefan, Mordi, Ify R, Teren, Andrej, Bergmeijer, Thomas O, Body, Simon C, Bots, Michiel, Burkhardt, Ralph, Cooper-DeHoff, Rhonda M, Cresci, Sharon, Danchin, Nicolas, Doughty, Robert N, Grobbee, Diederick E, Hagström, Emil, Hazen, Stanley L, Held, Claes, Hoefer, Imo E, Hovingh, G Kees, Johnson, Julie A, Kaczor, Marcin P, Kähönen, Mika, Klungel, Olaf H, Laurikka, Jari O, Lehtimäki, Terho, Maitland-van der Zee, Anke H, McPherson, Ruth, Palmer, Colin N, Kraaijeveld, Adriaan O, Pepine, Carl J, Sanak, Marek, Sattar, Naveed, Scholz, Markus, Simon, Tabassome, Spertus, John A, Stewart, Alexandre F R, Szczeklik, Wojciech, Thiery, Joachim, Visseren, Frank L J, Waltenberger, Johannes, Richards, A Mark, Lang, Chim C, Cameron, Vicky A, Åkerblom, Axel, Pare, Guillaume, März, Winfried, Samani, Nilesh J, Hingorani, Aroon D, Ten Berg, Jurriën M, Wallentin, Lars, Asselbergs, Folkert W, Patel, Riyaz S, Onderzoek Precision medicine, Circulatory Health, CDL Onderzoek Pasterkamp, Cardiovasculaire Epidemiologie, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Global Health, CDL Arcadia, JC onderzoeksprogramma Methodologie, Team Medisch, Interne Geneeskunde Vasculaire, Mahmoodi, Bakhtawar K, Tragante, Vinicius, Kleber, Marcus E, Holmes, Michael V, Schmidt, Amand F, McCubrey, Raymond O, Howe, Laurence J, Direk, Kenan, Allayee, Hooman, Baranova, Ekaterina V, Braund, Peter S, Delgado, Graciela E, Eriksson, Niclas, Gijsberts, Crystel M, Gong, Yan, Hartiala, Jaana, Heydarpour, Mahyar, Pasterkamp, Gerard, Kotti, Salma, Kuukasjärvi, Pekka, Lenzini, Petra A, Levin, Daniel, Lyytikäinen, Leo-Pekka, Muehlschlegel, Jochen D, Nelson, Christopher P, Nikus, Kjell, Pilbrow, Anna P, Wilson Tang, W H, van der Laan, Sander W, van Setten, Jessica, Vilmundarson, Ragnar O, Deanfield, John, Deloukas, Panos, Dudbridge, Frank, James, Stefan, Mordi, Ify R, Teren, Andrej, Bergmeijer, Thomas O, Body, Simon C, Bots, Michiel, Burkhardt, Ralph, Cooper-DeHoff, Rhonda M, Cresci, Sharon, Danchin, Nicolas, Doughty, Robert N, Grobbee, Diederick E, Hagström, Emil, Hazen, Stanley L, Held, Claes, Hoefer, Imo E, Hovingh, G Kees, Johnson, Julie A, Kaczor, Marcin P, Kähönen, Mika, Klungel, Olaf H, Laurikka, Jari O, Lehtimäki, Terho, Maitland-van der Zee, Anke H, McPherson, Ruth, Palmer, Colin N, Kraaijeveld, Adriaan O, Pepine, Carl J, Sanak, Marek, Sattar, Naveed, Scholz, Markus, Simon, Tabassome, Spertus, John A, Stewart, Alexandre F R, Szczeklik, Wojciech, Thiery, Joachim, Visseren, Frank L J, Waltenberger, Johannes, Richards, A Mark, Lang, Chim C, Cameron, Vicky A, Åkerblom, Axel, Pare, Guillaume, März, Winfried, Samani, Nilesh J, Hingorani, Aroon D, Ten Berg, Jurriën M, Wallentin, Lars, Asselbergs, Folkert W, and Patel, Riyaz S
Published: 2020

19. Association of Chromosome 9p21 With Subsequent Coronary Heart Disease Events : A GENIUS-CHD Study of Individual Participant Data

Author: Patel, Riyaz S., Schmidt, Amand F., Tragante, Vinicius, McCubrey, Raymond O., Holmes, Michael, V, Howe, Laurence J., Direk, Kenan, Åkerblom, Axel, Leander, Karin, Virani, Salim S., Kaminski, Karol A., Muehlschlegel, Jochen D., Dube, Marie-Pierre, Allayee, Hooman, Almgren, Peter, Alver, Maris, Baranova, Ekaterina, V, Behlouli, Hassan, Boeckx, Bram, Braund, Peter S., Breitling, Lutz P., Delgado, Graciela, Duarte, Nubia E., Dufresne, Line, Eriksson, Niclas, Foco, Luisa, Gijsberts, Crystel M., Gong, Yan, Hartiala, Jaana, Heydarpour, Mahyar, Hubacek, Jaroslav A., Kleber, Marcus, Kofink, Daniel, Kuukasjarvi, Pekka, Lee, Vei-Vei, Leiherer, Andreas, Lenzini, Petra A., Levin, Daniel, Lyytikainen, Leo-Pekka, Martinelli, Nicola, Mons, Ute, Nelson, Christopher P., Nikus, Kjell, Pilbrow, Anna P., Ploski, Rafal, Sun, Yan, V, Tanck, Michael W. T., Tang, W. H. Wilson, Trompet, Stella, van der Laan, Sander W., van Setten, Jessica, Vilmundarson, Ragnar O., Anselmi, Chiara Viviani, Vlachopoulou, Efthymia, Boerwinkle, Eric, Briguori, Carlo, Carlquist, John F., Carruthers, Kathryn F., Casu, Gavino, Deanfield, John, Deloukas, Panos, Dudbridge, Frank, Fitzpatrick, Natalie, Gigante, Bruna, James, Stefan, Lokki, Marja-Liisa, Lotufo, Paulo A., Marziliano, Nicola, Mordi, Ify R., Muhlestein, Joseph B., Cheh, Chris Newton, Pitha, Jan, Saely, Christoph H., Samman-Tahhan, Ayman, Sandesara, Pratik B., Teren, Andrej, Timmis, Adam, Van de Werf, Frans, Wauters, Els, Wilde, Arthur A. M., Ford, Ian, Stott, David J., Algra, Ale, Andreassi, Maria G., Ardissino, Diego, Arsenault, Benoit J., Ballantyne, Christie M., Bergmeijer, Thomas O., Bezzina, Connie R., Body, Simon C., Bogaty, Peter, de Borst, Gert J., Brenner, Hermann, Burkhardt, Ralph, Carpeggiani, Clara, Condorelli, Gianluigi, Cooper-DeHoff, Rhonda M., Cresci, Sharon, de Faire, Ulf, Doughty, Robert N., Drexel, Heinz, Engert, James C., Fox, Keith A. A., Girelli, Domenico, Hagström, Emil, Hazen, Stanley L., Held, Claes, Hemingway, Harry, Hoefer, Imo E., Hovingh, G. Kees, Johnson, Julie A., De Jong, Pim A., Jukema, J. Wouter, Kaczor, Marcin P., Kahonen, Mika, Kettner, Jiri, Kiliszek, Marek, Klungel, Olaf H., Lagerqvist, Bo, Lambrechts, Diether, Laurikka, Jari O., Lehtimaki, Terho, Lindholm, Daniel, Mahmoodi, Bakhtawar K., Maitland-van der Zee, Anke H., McPherson, Ruth, Melander, Olle, Metspalu, Andres, Pepinski, Witold, Olivieri, Oliviero, Opolski, Grzegorz, Palmer, Colin N., Pasterkamp, Gerard, Pepine, Carl J., Pereira, Alexandre C., Note, Louise, Quyyumi, Arshed A., Richards, A. Mark, Sanak, Marek, Scholz, Markus, Siegbahn, Agneta, Sinisalo, Juha, Smith, J. Gustav, Spertus, John A., Stewart, Alexandre F. R., Szczeklik, Wojciech, Szpakowicz, Anna, ten Berg, Jurrien M., Thanassoulis, George, Thieiy, Joachim, van der Graaf, Yolanda, Visseren, Frank L. J., Waltenberger, Johannes, Van der Harst, Pim, Tardif, Jean-Claude, Sattar, Naveed, Lang, Chim C., Pare, Guillaume, Brophy, James M., Anderson, Jeffrey L., Maerz, Winfried, Wallentin, Lars, Cameron, Vicky A., Horne, Benjamin D., Samani, Nilesh J., Hingorani, Aroon D., Asselbergs, Folkert W., Patel, Riyaz S., Schmidt, Amand F., Tragante, Vinicius, McCubrey, Raymond O., Holmes, Michael, V, Howe, Laurence J., Direk, Kenan, Åkerblom, Axel, Leander, Karin, Virani, Salim S., Kaminski, Karol A., Muehlschlegel, Jochen D., Dube, Marie-Pierre, Allayee, Hooman, Almgren, Peter, Alver, Maris, Baranova, Ekaterina, V, Behlouli, Hassan, Boeckx, Bram, Braund, Peter S., Breitling, Lutz P., Delgado, Graciela, Duarte, Nubia E., Dufresne, Line, Eriksson, Niclas, Foco, Luisa, Gijsberts, Crystel M., Gong, Yan, Hartiala, Jaana, Heydarpour, Mahyar, Hubacek, Jaroslav A., Kleber, Marcus, Kofink, Daniel, Kuukasjarvi, Pekka, Lee, Vei-Vei, Leiherer, Andreas, Lenzini, Petra A., Levin, Daniel, Lyytikainen, Leo-Pekka, Martinelli, Nicola, Mons, Ute, Nelson, Christopher P., Nikus, Kjell, Pilbrow, Anna P., Ploski, Rafal, Sun, Yan, V, Tanck, Michael W. T., Tang, W. H. Wilson, Trompet, Stella, van der Laan, Sander W., van Setten, Jessica, Vilmundarson, Ragnar O., Anselmi, Chiara Viviani, Vlachopoulou, Efthymia, Boerwinkle, Eric, Briguori, Carlo, Carlquist, John F., Carruthers, Kathryn F., Casu, Gavino, Deanfield, John, Deloukas, Panos, Dudbridge, Frank, Fitzpatrick, Natalie, Gigante, Bruna, James, Stefan, Lokki, Marja-Liisa, Lotufo, Paulo A., Marziliano, Nicola, Mordi, Ify R., Muhlestein, Joseph B., Cheh, Chris Newton, Pitha, Jan, Saely, Christoph H., Samman-Tahhan, Ayman, Sandesara, Pratik B., Teren, Andrej, Timmis, Adam, Van de Werf, Frans, Wauters, Els, Wilde, Arthur A. M., Ford, Ian, Stott, David J., Algra, Ale, Andreassi, Maria G., Ardissino, Diego, Arsenault, Benoit J., Ballantyne, Christie M., Bergmeijer, Thomas O., Bezzina, Connie R., Body, Simon C., Bogaty, Peter, de Borst, Gert J., Brenner, Hermann, Burkhardt, Ralph, Carpeggiani, Clara, Condorelli, Gianluigi, Cooper-DeHoff, Rhonda M., Cresci, Sharon, de Faire, Ulf, Doughty, Robert N., Drexel, Heinz, Engert, James C., Fox, Keith A. A., Girelli, Domenico, Hagström, Emil, Hazen, Stanley L., Held, Claes, Hemingway, Harry, Hoefer, Imo E., Hovingh, G. Kees, Johnson, Julie A., De Jong, Pim A., Jukema, J. Wouter, Kaczor, Marcin P., Kahonen, Mika, Kettner, Jiri, Kiliszek, Marek, Klungel, Olaf H., Lagerqvist, Bo, Lambrechts, Diether, Laurikka, Jari O., Lehtimaki, Terho, Lindholm, Daniel, Mahmoodi, Bakhtawar K., Maitland-van der Zee, Anke H., McPherson, Ruth, Melander, Olle, Metspalu, Andres, Pepinski, Witold, Olivieri, Oliviero, Opolski, Grzegorz, Palmer, Colin N., Pasterkamp, Gerard, Pepine, Carl J., Pereira, Alexandre C., Note, Louise, Quyyumi, Arshed A., Richards, A. Mark, Sanak, Marek, Scholz, Markus, Siegbahn, Agneta, Sinisalo, Juha, Smith, J. Gustav, Spertus, John A., Stewart, Alexandre F. R., Szczeklik, Wojciech, Szpakowicz, Anna, ten Berg, Jurrien M., Thanassoulis, George, Thieiy, Joachim, van der Graaf, Yolanda, Visseren, Frank L. J., Waltenberger, Johannes, Van der Harst, Pim, Tardif, Jean-Claude, Sattar, Naveed, Lang, Chim C., Pare, Guillaume, Brophy, James M., Anderson, Jeffrey L., Maerz, Winfried, Wallentin, Lars, Cameron, Vicky A., Horne, Benjamin D., Samani, Nilesh J., Hingorani, Aroon D., and Asselbergs, Folkert W.
Abstract: BACKGROUND: Genetic variation at chromosome 9p21 is a recognized risk factor for coronary heart disease (CHD). However, its effect on disease progression and subsequent events is unclear, raising questions about its value for stratification of residual risk. METHODS: A variant at chromosome 9p21 (rs1333049) was tested for association with subsequent events during follow-up in 103 357 Europeans with established CHD at baseline from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) Consortium (73.1% male, mean age 62.9 years). The primary outcome, subsequent CHD death or myocardial infarction (CHD death/myocardial infarction), occurred in 13 040 of the 93 115 participants with available outcome data. Effect estimates were compared with case/control risk obtained from the CARDIoGRAMplusC4D consortium (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics) including 47 222 CHD cases and 122 264 controls free of CHD. RESULTS: Meta-analyses revealed no significant association between chromosome 9p21 and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline (GENIUSCHD odds ratio, 1.02; 95% CI, 0.99-1.05). This contrasted with a strong association in CARDIoGRAMPlusC4D odds ratio 1.20; 95% CI, 1.18-1.22; P for interaction < 0.001 compared with the GENIUS-CHD estimate. Similarly, no clear associations were identified for additional subsequent outcomes, including all-cause death, although we found a modest positive association between chromosome 9p21 and subsequent revascularization (odds ratio, 1.07; 95% CI, 1.04-1.09). CONCLUSIONS: In contrast to studies comparing individuals with CHD to disease-free controls, we found no clear association between genetic variation at chromosome 9p21 and risk of subsequent acute CHD events when all individuals had CHD at baseline. However, the association with subsequent revascularization may support the post
Published: 2019
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20. Subsequent Event Risk in Individuals With Established Coronary Heart Disease : Design and Rationale of the GENIUS-CHD Consortium

Author: Patel, Riyaz S., Tragante, Vinicius, Schmidt, Amand F., McCubrey, Raymond O., Holmes, Michael, V, Howe, Laurence J., Direk, Kenan, Åkerblom, Axel, Leander, Karin, Virani, Salim S., Kaminski, Karol A., Muehlschlegel, Jochen D., Allayee, Hooman, Almgren, Peter, Alver, Maris, Baranova, Ekaterina, V, Behloui, Hassan, Boeckx, Bram, Braund, Peter S., Breitling, Lutz P., Delgado, Gradela, Duarte, Nubia E., Dube, Marie-Pierre, Dufresne, Line, Eriksson, Niclas, Foco, Luisa, Scholz, Markus, Gijsberts, Crystel M., Glinge, Charlotte, Gong, Yan, Hartiala, Jaana, Heydarpour, Mahyar, Hubacek, Jaroslav A., Kleber, Marcus, Kofink, Daniel, Kotti, Salma, Kuukasjarvi, Pekka, Lee, Vei-Vei, Leiherer, Andreas, Lenzini, Petra A., Levin, Daniel, Lyytikainen, Leo-Pekka, Martinelli, Nicola, Mons, Ute, Nelson, Christopher P., Nikus, Kjell, Pilbrow, Anna P., Ploski, Rafal, Sun, Yan, V, Tanck, Michael W. T., Tang, W. H. Wilson, Trompet, Stella, van der Laan, Sander W., Van Setten, Jessica, Vilmundarson, Ragnar O., Anselmi, Chiara Viviani, Vlachopoulou, Efthymia, Al Ali, Lawien, Boerwinkle, Eric, Briguori, Carlo, Carlquist, John F., Carruthers, Kathryn F., Casu, Gavino, Deanfield, John, Deloukas, Panos, Dudbridge, Frank, Engstrom, Thomas, Fitzpatrick, Natalie, Fox, Kim, Gigante, Bruna, James, Stefan, Lokki, Marja-Liisa, Lotufo, Paulo A., Marziliano, Nicola, Mordi, Ify R., Muhlestein, Joseph B., Newton-Cheh, Christopher, Pitha, Jan, Saely, Christoph H., Samman-Tahhan, Ayman, Sandesara, Pratik B., Teren, Andrej, Timmis, Adam, Van de Werf, Frans, Wauters, Els, Wilde, Arthur A. M., Ford, Ian, Stott, David J., Algra, Ale, Andreassi, Maria G., Ardissino, Diego, Arsenault, Benoit J., Ballantyne, Christie M., Bergmeijer, Thomas O., Bezzina, Connie R., Body, Simon C., Boersma, Eric H., Bogaty, Peter, Bots, Michiel L., Brenner, Hermann, Brugts, Jasper J., Burkhardt, Ralph, Carpeggiani, Clara, Condorelli, Gianluigi, Cooper-DeHoff, Rhonda M., Cresci, Sharon, Danchin, Nicolas, de Faire, Ulf, Doughty, Robert N., Drexel, Heinz, Engert, James C., Fox, Keith A. A., Girelli, Domenico, Grobbee, Diederick E., Hagström, Emil, Hazen, Stanley L., Held, Claes, Hemingway, Harry, Hoefer, Imo E., Hovingh, G. Kees, Jabbari, Reza, Johnson, Julie A., Jukema, J. Wouter, Kaczor, Marcin P., Kahonen, Mika, Kettner, Jiri, Kiliszek, Marek, Klungel, Olaf H., Lagerqvist, Bo, Lambrechts, Diether, Laurikka, Jari O., Lehtimaki, Terho, Lindholm, Daniel, Mahmoodi, B. K., Maitland-van der Zee, Anke H., McPherson, Ruth, Melander, Olle, Metspalu, Andres, Niemcunowicz-Janica, Anna, Olivieri, Oliviero, Opolski, Grzegorz, Palmer, Colin N., Pasterkamp, Gerard, Pepine, Carl J., Pereira, Alexandre C., Pilote, Louise, Quyyumi, Arshed A., Richards, A. Mark, Sanak, Marek, Siegbahn, Agneta, Simon, Tabassome, Sinisalo, Juha, Smith, J. Gustav, Spertus, John A., Stender, Steen, Stewart, Alexandre F. R., Szczeklik, Wojciech, Szpakowicz, Anna, Tardif, Jean-Claude, ten Berg, Jurrien M., Tfelt-Hansen, Jacob, Thanassoulis, George, Thiery, Joachim, Torp-Pedersen, Christian, van der Graaf, Yolanda, Visseren, Frank L. J., Waltenberger, Johannes, Weeke, Peter E., Van der Harst, Pim, Lang, Chim C., Sattar, Naveed, Cameron, Vicky A., Anderson, Jeffrey L., Brophy, James M., Pare, Guillaume, Horne, Benjamin D., Marz, Winfried, Wallentin, Lars, Samani, Nilesh J., Hingorani, Aroon D., Asselbergs, Folkert W., Patel, Riyaz S., Tragante, Vinicius, Schmidt, Amand F., McCubrey, Raymond O., Holmes, Michael, V, Howe, Laurence J., Direk, Kenan, Åkerblom, Axel, Leander, Karin, Virani, Salim S., Kaminski, Karol A., Muehlschlegel, Jochen D., Allayee, Hooman, Almgren, Peter, Alver, Maris, Baranova, Ekaterina, V, Behloui, Hassan, Boeckx, Bram, Braund, Peter S., Breitling, Lutz P., Delgado, Gradela, Duarte, Nubia E., Dube, Marie-Pierre, Dufresne, Line, Eriksson, Niclas, Foco, Luisa, Scholz, Markus, Gijsberts, Crystel M., Glinge, Charlotte, Gong, Yan, Hartiala, Jaana, Heydarpour, Mahyar, Hubacek, Jaroslav A., Kleber, Marcus, Kofink, Daniel, Kotti, Salma, Kuukasjarvi, Pekka, Lee, Vei-Vei, Leiherer, Andreas, Lenzini, Petra A., Levin, Daniel, Lyytikainen, Leo-Pekka, Martinelli, Nicola, Mons, Ute, Nelson, Christopher P., Nikus, Kjell, Pilbrow, Anna P., Ploski, Rafal, Sun, Yan, V, Tanck, Michael W. T., Tang, W. H. Wilson, Trompet, Stella, van der Laan, Sander W., Van Setten, Jessica, Vilmundarson, Ragnar O., Anselmi, Chiara Viviani, Vlachopoulou, Efthymia, Al Ali, Lawien, Boerwinkle, Eric, Briguori, Carlo, Carlquist, John F., Carruthers, Kathryn F., Casu, Gavino, Deanfield, John, Deloukas, Panos, Dudbridge, Frank, Engstrom, Thomas, Fitzpatrick, Natalie, Fox, Kim, Gigante, Bruna, James, Stefan, Lokki, Marja-Liisa, Lotufo, Paulo A., Marziliano, Nicola, Mordi, Ify R., Muhlestein, Joseph B., Newton-Cheh, Christopher, Pitha, Jan, Saely, Christoph H., Samman-Tahhan, Ayman, Sandesara, Pratik B., Teren, Andrej, Timmis, Adam, Van de Werf, Frans, Wauters, Els, Wilde, Arthur A. M., Ford, Ian, Stott, David J., Algra, Ale, Andreassi, Maria G., Ardissino, Diego, Arsenault, Benoit J., Ballantyne, Christie M., Bergmeijer, Thomas O., Bezzina, Connie R., Body, Simon C., Boersma, Eric H., Bogaty, Peter, Bots, Michiel L., Brenner, Hermann, Brugts, Jasper J., Burkhardt, Ralph, Carpeggiani, Clara, Condorelli, Gianluigi, Cooper-DeHoff, Rhonda M., Cresci, Sharon, Danchin, Nicolas, de Faire, Ulf, Doughty, Robert N., Drexel, Heinz, Engert, James C., Fox, Keith A. A., Girelli, Domenico, Grobbee, Diederick E., Hagström, Emil, Hazen, Stanley L., Held, Claes, Hemingway, Harry, Hoefer, Imo E., Hovingh, G. Kees, Jabbari, Reza, Johnson, Julie A., Jukema, J. Wouter, Kaczor, Marcin P., Kahonen, Mika, Kettner, Jiri, Kiliszek, Marek, Klungel, Olaf H., Lagerqvist, Bo, Lambrechts, Diether, Laurikka, Jari O., Lehtimaki, Terho, Lindholm, Daniel, Mahmoodi, B. K., Maitland-van der Zee, Anke H., McPherson, Ruth, Melander, Olle, Metspalu, Andres, Niemcunowicz-Janica, Anna, Olivieri, Oliviero, Opolski, Grzegorz, Palmer, Colin N., Pasterkamp, Gerard, Pepine, Carl J., Pereira, Alexandre C., Pilote, Louise, Quyyumi, Arshed A., Richards, A. Mark, Sanak, Marek, Siegbahn, Agneta, Simon, Tabassome, Sinisalo, Juha, Smith, J. Gustav, Spertus, John A., Stender, Steen, Stewart, Alexandre F. R., Szczeklik, Wojciech, Szpakowicz, Anna, Tardif, Jean-Claude, ten Berg, Jurrien M., Tfelt-Hansen, Jacob, Thanassoulis, George, Thiery, Joachim, Torp-Pedersen, Christian, van der Graaf, Yolanda, Visseren, Frank L. J., Waltenberger, Johannes, Weeke, Peter E., Van der Harst, Pim, Lang, Chim C., Sattar, Naveed, Cameron, Vicky A., Anderson, Jeffrey L., Brophy, James M., Pare, Guillaume, Horne, Benjamin D., Marz, Winfried, Wallentin, Lars, Samani, Nilesh J., Hingorani, Aroon D., and Asselbergs, Folkert W.
Abstract: BACKGROUND: The Genetics of Subsequent Coronary Heart Disease (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD. METHODS: The consortium currently includes 57 studies from 18 countries, recruiting 185 614 participants with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events. RESULTS: Enrollment into the individual studies took place between 1985 to present day with a duration of follow-up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38%-100%), mostly male (44%-91%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (hazard ratio, 1.15; 95% CI, 1.14-1.16) per 5-year increase, male sex (hazard ratio, 1.17; 95% CI, 1.13-1.21) and smoking (hazard ratio, 1.43; 95% CI, 1.35-1.51) with risk of subsequent CHD death or myocardial infarction and differing associations with other individual and composite cardiovascular endpoints. CONCLUSIONS: GENIUS-CHD is a global collaboration seeking to elucidate genetic and nongenetic determinants of subsequent event risk in individuals with established CHD, to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators.
Published: 2019
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21. Subsequent Event Risk in Individuals With Established Coronary Heart Disease : Design and Rationale of the GENIUS-CHD Consortium

Author: Patel, Riyaz S., Tragante, Vinicius, Schmidt, Amand F., McCubrey, Raymond O., Holmes, Michael, V, Howe, Laurence J., Direk, Kenan, Åkerblom, Axel, Leander, Karin, Virani, Salim S., Kaminski, Karol A., Muehlschlegel, Jochen D., Allayee, Hooman, Almgren, Peter, Alver, Maris, Baranova, Ekaterina, V, Behloui, Hassan, Boeckx, Bram, Braund, Peter S., Breitling, Lutz P., Delgado, Gradela, Duarte, Nubia E., Dube, Marie-Pierre, Dufresne, Line, Eriksson, Niclas, Foco, Luisa, Scholz, Markus, Gijsberts, Crystel M., Glinge, Charlotte, Gong, Yan, Hartiala, Jaana, Heydarpour, Mahyar, Hubacek, Jaroslav A., Kleber, Marcus, Kofink, Daniel, Kotti, Salma, Kuukasjarvi, Pekka, Lee, Vei-Vei, Leiherer, Andreas, Lenzini, Petra A., Levin, Daniel, Lyytikainen, Leo-Pekka, Martinelli, Nicola, Mons, Ute, Nelson, Christopher P., Nikus, Kjell, Pilbrow, Anna P., Ploski, Rafal, Sun, Yan, V, Tanck, Michael W. T., Tang, W. H. Wilson, Trompet, Stella, van der Laan, Sander W., Van Setten, Jessica, Vilmundarson, Ragnar O., Anselmi, Chiara Viviani, Vlachopoulou, Efthymia, Al Ali, Lawien, Boerwinkle, Eric, Briguori, Carlo, Carlquist, John F., Carruthers, Kathryn F., Casu, Gavino, Deanfield, John, Deloukas, Panos, Dudbridge, Frank, Engstrom, Thomas, Fitzpatrick, Natalie, Fox, Kim, Gigante, Bruna, James, Stefan, Lokki, Marja-Liisa, Lotufo, Paulo A., Marziliano, Nicola, Mordi, Ify R., Muhlestein, Joseph B., Newton-Cheh, Christopher, Pitha, Jan, Saely, Christoph H., Samman-Tahhan, Ayman, Sandesara, Pratik B., Teren, Andrej, Timmis, Adam, Van de Werf, Frans, Wauters, Els, Wilde, Arthur A. M., Ford, Ian, Stott, David J., Algra, Ale, Andreassi, Maria G., Ardissino, Diego, Arsenault, Benoit J., Ballantyne, Christie M., Bergmeijer, Thomas O., Bezzina, Connie R., Body, Simon C., Boersma, Eric H., Bogaty, Peter, Bots, Michiel L., Brenner, Hermann, Brugts, Jasper J., Burkhardt, Ralph, Carpeggiani, Clara, Condorelli, Gianluigi, Cooper-DeHoff, Rhonda M., Cresci, Sharon, Danchin, Nicolas, de Faire, Ulf, Doughty, Robert N., Drexel, Heinz, Engert, James C., Fox, Keith A. A., Girelli, Domenico, Grobbee, Diederick E., Hagström, Emil, Hazen, Stanley L., Held, Claes, Hemingway, Harry, Hoefer, Imo E., Hovingh, G. Kees, Jabbari, Reza, Johnson, Julie A., Jukema, J. Wouter, Kaczor, Marcin P., Kahonen, Mika, Kettner, Jiri, Kiliszek, Marek, Klungel, Olaf H., Lagerqvist, Bo, Lambrechts, Diether, Laurikka, Jari O., Lehtimaki, Terho, Lindholm, Daniel, Mahmoodi, B. K., Maitland-van der Zee, Anke H., McPherson, Ruth, Melander, Olle, Metspalu, Andres, Niemcunowicz-Janica, Anna, Olivieri, Oliviero, Opolski, Grzegorz, Palmer, Colin N., Pasterkamp, Gerard, Pepine, Carl J., Pereira, Alexandre C., Pilote, Louise, Quyyumi, Arshed A., Richards, A. Mark, Sanak, Marek, Siegbahn, Agneta, Simon, Tabassome, Sinisalo, Juha, Smith, J. Gustav, Spertus, John A., Stender, Steen, Stewart, Alexandre F. R., Szczeklik, Wojciech, Szpakowicz, Anna, Tardif, Jean-Claude, ten Berg, Jurrien M., Tfelt-Hansen, Jacob, Thanassoulis, George, Thiery, Joachim, Torp-Pedersen, Christian, van der Graaf, Yolanda, Visseren, Frank L. J., Waltenberger, Johannes, Weeke, Peter E., Van der Harst, Pim, Lang, Chim C., Sattar, Naveed, Cameron, Vicky A., Anderson, Jeffrey L., Brophy, James M., Pare, Guillaume, Horne, Benjamin D., Marz, Winfried, Wallentin, Lars, Samani, Nilesh J., Hingorani, Aroon D., Asselbergs, Folkert W., Patel, Riyaz S., Tragante, Vinicius, Schmidt, Amand F., McCubrey, Raymond O., Holmes, Michael, V, Howe, Laurence J., Direk, Kenan, Åkerblom, Axel, Leander, Karin, Virani, Salim S., Kaminski, Karol A., Muehlschlegel, Jochen D., Allayee, Hooman, Almgren, Peter, Alver, Maris, Baranova, Ekaterina, V, Behloui, Hassan, Boeckx, Bram, Braund, Peter S., Breitling, Lutz P., Delgado, Gradela, Duarte, Nubia E., Dube, Marie-Pierre, Dufresne, Line, Eriksson, Niclas, Foco, Luisa, Scholz, Markus, Gijsberts, Crystel M., Glinge, Charlotte, Gong, Yan, Hartiala, Jaana, Heydarpour, Mahyar, Hubacek, Jaroslav A., Kleber, Marcus, Kofink, Daniel, Kotti, Salma, Kuukasjarvi, Pekka, Lee, Vei-Vei, Leiherer, Andreas, Lenzini, Petra A., Levin, Daniel, Lyytikainen, Leo-Pekka, Martinelli, Nicola, Mons, Ute, Nelson, Christopher P., Nikus, Kjell, Pilbrow, Anna P., Ploski, Rafal, Sun, Yan, V, Tanck, Michael W. T., Tang, W. H. Wilson, Trompet, Stella, van der Laan, Sander W., Van Setten, Jessica, Vilmundarson, Ragnar O., Anselmi, Chiara Viviani, Vlachopoulou, Efthymia, Al Ali, Lawien, Boerwinkle, Eric, Briguori, Carlo, Carlquist, John F., Carruthers, Kathryn F., Casu, Gavino, Deanfield, John, Deloukas, Panos, Dudbridge, Frank, Engstrom, Thomas, Fitzpatrick, Natalie, Fox, Kim, Gigante, Bruna, James, Stefan, Lokki, Marja-Liisa, Lotufo, Paulo A., Marziliano, Nicola, Mordi, Ify R., Muhlestein, Joseph B., Newton-Cheh, Christopher, Pitha, Jan, Saely, Christoph H., Samman-Tahhan, Ayman, Sandesara, Pratik B., Teren, Andrej, Timmis, Adam, Van de Werf, Frans, Wauters, Els, Wilde, Arthur A. M., Ford, Ian, Stott, David J., Algra, Ale, Andreassi, Maria G., Ardissino, Diego, Arsenault, Benoit J., Ballantyne, Christie M., Bergmeijer, Thomas O., Bezzina, Connie R., Body, Simon C., Boersma, Eric H., Bogaty, Peter, Bots, Michiel L., Brenner, Hermann, Brugts, Jasper J., Burkhardt, Ralph, Carpeggiani, Clara, Condorelli, Gianluigi, Cooper-DeHoff, Rhonda M., Cresci, Sharon, Danchin, Nicolas, de Faire, Ulf, Doughty, Robert N., Drexel, Heinz, Engert, James C., Fox, Keith A. A., Girelli, Domenico, Grobbee, Diederick E., Hagström, Emil, Hazen, Stanley L., Held, Claes, Hemingway, Harry, Hoefer, Imo E., Hovingh, G. Kees, Jabbari, Reza, Johnson, Julie A., Jukema, J. Wouter, Kaczor, Marcin P., Kahonen, Mika, Kettner, Jiri, Kiliszek, Marek, Klungel, Olaf H., Lagerqvist, Bo, Lambrechts, Diether, Laurikka, Jari O., Lehtimaki, Terho, Lindholm, Daniel, Mahmoodi, B. K., Maitland-van der Zee, Anke H., McPherson, Ruth, Melander, Olle, Metspalu, Andres, Niemcunowicz-Janica, Anna, Olivieri, Oliviero, Opolski, Grzegorz, Palmer, Colin N., Pasterkamp, Gerard, Pepine, Carl J., Pereira, Alexandre C., Pilote, Louise, Quyyumi, Arshed A., Richards, A. Mark, Sanak, Marek, Siegbahn, Agneta, Simon, Tabassome, Sinisalo, Juha, Smith, J. Gustav, Spertus, John A., Stender, Steen, Stewart, Alexandre F. R., Szczeklik, Wojciech, Szpakowicz, Anna, Tardif, Jean-Claude, ten Berg, Jurrien M., Tfelt-Hansen, Jacob, Thanassoulis, George, Thiery, Joachim, Torp-Pedersen, Christian, van der Graaf, Yolanda, Visseren, Frank L. J., Waltenberger, Johannes, Weeke, Peter E., Van der Harst, Pim, Lang, Chim C., Sattar, Naveed, Cameron, Vicky A., Anderson, Jeffrey L., Brophy, James M., Pare, Guillaume, Horne, Benjamin D., Marz, Winfried, Wallentin, Lars, Samani, Nilesh J., Hingorani, Aroon D., and Asselbergs, Folkert W.
Abstract: BACKGROUND: The Genetics of Subsequent Coronary Heart Disease (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD. METHODS: The consortium currently includes 57 studies from 18 countries, recruiting 185 614 participants with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events. RESULTS: Enrollment into the individual studies took place between 1985 to present day with a duration of follow-up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38%-100%), mostly male (44%-91%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (hazard ratio, 1.15; 95% CI, 1.14-1.16) per 5-year increase, male sex (hazard ratio, 1.17; 95% CI, 1.13-1.21) and smoking (hazard ratio, 1.43; 95% CI, 1.35-1.51) with risk of subsequent CHD death or myocardial infarction and differing associations with other individual and composite cardiovascular endpoints. CONCLUSIONS: GENIUS-CHD is a global collaboration seeking to elucidate genetic and nongenetic determinants of subsequent event risk in individuals with established CHD, to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators.
Published: 2019
Full Text: View/download PDF

22. Association of Chromosome 9p21 With Subsequent Coronary Heart Disease Events : A GENIUS-CHD Study of Individual Participant Data

Author: Patel, Riyaz S., Schmidt, Amand F., Tragante, Vinicius, McCubrey, Raymond O., Holmes, Michael, V, Howe, Laurence J., Direk, Kenan, Åkerblom, Axel, Leander, Karin, Virani, Salim S., Kaminski, Karol A., Muehlschlegel, Jochen D., Dube, Marie-Pierre, Allayee, Hooman, Almgren, Peter, Alver, Maris, Baranova, Ekaterina, V, Behlouli, Hassan, Boeckx, Bram, Braund, Peter S., Breitling, Lutz P., Delgado, Graciela, Duarte, Nubia E., Dufresne, Line, Eriksson, Niclas, Foco, Luisa, Gijsberts, Crystel M., Gong, Yan, Hartiala, Jaana, Heydarpour, Mahyar, Hubacek, Jaroslav A., Kleber, Marcus, Kofink, Daniel, Kuukasjarvi, Pekka, Lee, Vei-Vei, Leiherer, Andreas, Lenzini, Petra A., Levin, Daniel, Lyytikainen, Leo-Pekka, Martinelli, Nicola, Mons, Ute, Nelson, Christopher P., Nikus, Kjell, Pilbrow, Anna P., Ploski, Rafal, Sun, Yan, V, Tanck, Michael W. T., Tang, W. H. Wilson, Trompet, Stella, van der Laan, Sander W., van Setten, Jessica, Vilmundarson, Ragnar O., Anselmi, Chiara Viviani, Vlachopoulou, Efthymia, Boerwinkle, Eric, Briguori, Carlo, Carlquist, John F., Carruthers, Kathryn F., Casu, Gavino, Deanfield, John, Deloukas, Panos, Dudbridge, Frank, Fitzpatrick, Natalie, Gigante, Bruna, James, Stefan, Lokki, Marja-Liisa, Lotufo, Paulo A., Marziliano, Nicola, Mordi, Ify R., Muhlestein, Joseph B., Cheh, Chris Newton, Pitha, Jan, Saely, Christoph H., Samman-Tahhan, Ayman, Sandesara, Pratik B., Teren, Andrej, Timmis, Adam, Van de Werf, Frans, Wauters, Els, Wilde, Arthur A. M., Ford, Ian, Stott, David J., Algra, Ale, Andreassi, Maria G., Ardissino, Diego, Arsenault, Benoit J., Ballantyne, Christie M., Bergmeijer, Thomas O., Bezzina, Connie R., Body, Simon C., Bogaty, Peter, de Borst, Gert J., Brenner, Hermann, Burkhardt, Ralph, Carpeggiani, Clara, Condorelli, Gianluigi, Cooper-DeHoff, Rhonda M., Cresci, Sharon, de Faire, Ulf, Doughty, Robert N., Drexel, Heinz, Engert, James C., Fox, Keith A. A., Girelli, Domenico, Hagström, Emil, Hazen, Stanley L., Held, Claes, Hemingway, Harry, Hoefer, Imo E., Hovingh, G. Kees, Johnson, Julie A., De Jong, Pim A., Jukema, J. Wouter, Kaczor, Marcin P., Kahonen, Mika, Kettner, Jiri, Kiliszek, Marek, Klungel, Olaf H., Lagerqvist, Bo, Lambrechts, Diether, Laurikka, Jari O., Lehtimaki, Terho, Lindholm, Daniel, Mahmoodi, Bakhtawar K., Maitland-van der Zee, Anke H., McPherson, Ruth, Melander, Olle, Metspalu, Andres, Pepinski, Witold, Olivieri, Oliviero, Opolski, Grzegorz, Palmer, Colin N., Pasterkamp, Gerard, Pepine, Carl J., Pereira, Alexandre C., Note, Louise, Quyyumi, Arshed A., Richards, A. Mark, Sanak, Marek, Scholz, Markus, Siegbahn, Agneta, Sinisalo, Juha, Smith, J. Gustav, Spertus, John A., Stewart, Alexandre F. R., Szczeklik, Wojciech, Szpakowicz, Anna, ten Berg, Jurrien M., Thanassoulis, George, Thieiy, Joachim, van der Graaf, Yolanda, Visseren, Frank L. J., Waltenberger, Johannes, Van der Harst, Pim, Tardif, Jean-Claude, Sattar, Naveed, Lang, Chim C., Pare, Guillaume, Brophy, James M., Anderson, Jeffrey L., Maerz, Winfried, Wallentin, Lars, Cameron, Vicky A., Horne, Benjamin D., Samani, Nilesh J., Hingorani, Aroon D., Asselbergs, Folkert W., Patel, Riyaz S., Schmidt, Amand F., Tragante, Vinicius, McCubrey, Raymond O., Holmes, Michael, V, Howe, Laurence J., Direk, Kenan, Åkerblom, Axel, Leander, Karin, Virani, Salim S., Kaminski, Karol A., Muehlschlegel, Jochen D., Dube, Marie-Pierre, Allayee, Hooman, Almgren, Peter, Alver, Maris, Baranova, Ekaterina, V, Behlouli, Hassan, Boeckx, Bram, Braund, Peter S., Breitling, Lutz P., Delgado, Graciela, Duarte, Nubia E., Dufresne, Line, Eriksson, Niclas, Foco, Luisa, Gijsberts, Crystel M., Gong, Yan, Hartiala, Jaana, Heydarpour, Mahyar, Hubacek, Jaroslav A., Kleber, Marcus, Kofink, Daniel, Kuukasjarvi, Pekka, Lee, Vei-Vei, Leiherer, Andreas, Lenzini, Petra A., Levin, Daniel, Lyytikainen, Leo-Pekka, Martinelli, Nicola, Mons, Ute, Nelson, Christopher P., Nikus, Kjell, Pilbrow, Anna P., Ploski, Rafal, Sun, Yan, V, Tanck, Michael W. T., Tang, W. H. Wilson, Trompet, Stella, van der Laan, Sander W., van Setten, Jessica, Vilmundarson, Ragnar O., Anselmi, Chiara Viviani, Vlachopoulou, Efthymia, Boerwinkle, Eric, Briguori, Carlo, Carlquist, John F., Carruthers, Kathryn F., Casu, Gavino, Deanfield, John, Deloukas, Panos, Dudbridge, Frank, Fitzpatrick, Natalie, Gigante, Bruna, James, Stefan, Lokki, Marja-Liisa, Lotufo, Paulo A., Marziliano, Nicola, Mordi, Ify R., Muhlestein, Joseph B., Cheh, Chris Newton, Pitha, Jan, Saely, Christoph H., Samman-Tahhan, Ayman, Sandesara, Pratik B., Teren, Andrej, Timmis, Adam, Van de Werf, Frans, Wauters, Els, Wilde, Arthur A. M., Ford, Ian, Stott, David J., Algra, Ale, Andreassi, Maria G., Ardissino, Diego, Arsenault, Benoit J., Ballantyne, Christie M., Bergmeijer, Thomas O., Bezzina, Connie R., Body, Simon C., Bogaty, Peter, de Borst, Gert J., Brenner, Hermann, Burkhardt, Ralph, Carpeggiani, Clara, Condorelli, Gianluigi, Cooper-DeHoff, Rhonda M., Cresci, Sharon, de Faire, Ulf, Doughty, Robert N., Drexel, Heinz, Engert, James C., Fox, Keith A. A., Girelli, Domenico, Hagström, Emil, Hazen, Stanley L., Held, Claes, Hemingway, Harry, Hoefer, Imo E., Hovingh, G. Kees, Johnson, Julie A., De Jong, Pim A., Jukema, J. Wouter, Kaczor, Marcin P., Kahonen, Mika, Kettner, Jiri, Kiliszek, Marek, Klungel, Olaf H., Lagerqvist, Bo, Lambrechts, Diether, Laurikka, Jari O., Lehtimaki, Terho, Lindholm, Daniel, Mahmoodi, Bakhtawar K., Maitland-van der Zee, Anke H., McPherson, Ruth, Melander, Olle, Metspalu, Andres, Pepinski, Witold, Olivieri, Oliviero, Opolski, Grzegorz, Palmer, Colin N., Pasterkamp, Gerard, Pepine, Carl J., Pereira, Alexandre C., Note, Louise, Quyyumi, Arshed A., Richards, A. Mark, Sanak, Marek, Scholz, Markus, Siegbahn, Agneta, Sinisalo, Juha, Smith, J. Gustav, Spertus, John A., Stewart, Alexandre F. R., Szczeklik, Wojciech, Szpakowicz, Anna, ten Berg, Jurrien M., Thanassoulis, George, Thieiy, Joachim, van der Graaf, Yolanda, Visseren, Frank L. J., Waltenberger, Johannes, Van der Harst, Pim, Tardif, Jean-Claude, Sattar, Naveed, Lang, Chim C., Pare, Guillaume, Brophy, James M., Anderson, Jeffrey L., Maerz, Winfried, Wallentin, Lars, Cameron, Vicky A., Horne, Benjamin D., Samani, Nilesh J., Hingorani, Aroon D., and Asselbergs, Folkert W.
Abstract: BACKGROUND: Genetic variation at chromosome 9p21 is a recognized risk factor for coronary heart disease (CHD). However, its effect on disease progression and subsequent events is unclear, raising questions about its value for stratification of residual risk. METHODS: A variant at chromosome 9p21 (rs1333049) was tested for association with subsequent events during follow-up in 103 357 Europeans with established CHD at baseline from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) Consortium (73.1% male, mean age 62.9 years). The primary outcome, subsequent CHD death or myocardial infarction (CHD death/myocardial infarction), occurred in 13 040 of the 93 115 participants with available outcome data. Effect estimates were compared with case/control risk obtained from the CARDIoGRAMplusC4D consortium (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics) including 47 222 CHD cases and 122 264 controls free of CHD. RESULTS: Meta-analyses revealed no significant association between chromosome 9p21 and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline (GENIUSCHD odds ratio, 1.02; 95% CI, 0.99-1.05). This contrasted with a strong association in CARDIoGRAMPlusC4D odds ratio 1.20; 95% CI, 1.18-1.22; P for interaction < 0.001 compared with the GENIUS-CHD estimate. Similarly, no clear associations were identified for additional subsequent outcomes, including all-cause death, although we found a modest positive association between chromosome 9p21 and subsequent revascularization (odds ratio, 1.07; 95% CI, 1.04-1.09). CONCLUSIONS: In contrast to studies comparing individuals with CHD to disease-free controls, we found no clear association between genetic variation at chromosome 9p21 and risk of subsequent acute CHD events when all individuals had CHD at baseline. However, the association with subsequent revascularization may support the post
Published: 2019
Full Text: View/download PDF

23. Subsequent Event Risk in Individuals With Established Coronary Heart Disease : Design and Rationale of the GENIUS-CHD Consortium

Author: Patel, Riyaz S., Tragante, Vinicius, Schmidt, Amand F., McCubrey, Raymond O., Holmes, Michael, V, Howe, Laurence J., Direk, Kenan, Åkerblom, Axel, Leander, Karin, Virani, Salim S., Kaminski, Karol A., Muehlschlegel, Jochen D., Allayee, Hooman, Almgren, Peter, Alver, Maris, Baranova, Ekaterina, V, Behloui, Hassan, Boeckx, Bram, Braund, Peter S., Breitling, Lutz P., Delgado, Gradela, Duarte, Nubia E., Dube, Marie-Pierre, Dufresne, Line, Eriksson, Niclas, Foco, Luisa, Scholz, Markus, Gijsberts, Crystel M., Glinge, Charlotte, Gong, Yan, Hartiala, Jaana, Heydarpour, Mahyar, Hubacek, Jaroslav A., Kleber, Marcus, Kofink, Daniel, Kotti, Salma, Kuukasjarvi, Pekka, Lee, Vei-Vei, Leiherer, Andreas, Lenzini, Petra A., Levin, Daniel, Lyytikainen, Leo-Pekka, Martinelli, Nicola, Mons, Ute, Nelson, Christopher P., Nikus, Kjell, Pilbrow, Anna P., Ploski, Rafal, Sun, Yan, V, Tanck, Michael W. T., Tang, W. H. Wilson, Trompet, Stella, van der Laan, Sander W., Van Setten, Jessica, Vilmundarson, Ragnar O., Anselmi, Chiara Viviani, Vlachopoulou, Efthymia, Al Ali, Lawien, Boerwinkle, Eric, Briguori, Carlo, Carlquist, John F., Carruthers, Kathryn F., Casu, Gavino, Deanfield, John, Deloukas, Panos, Dudbridge, Frank, Engstrom, Thomas, Fitzpatrick, Natalie, Fox, Kim, Gigante, Bruna, James, Stefan, Lokki, Marja-Liisa, Lotufo, Paulo A., Marziliano, Nicola, Mordi, Ify R., Muhlestein, Joseph B., Newton-Cheh, Christopher, Pitha, Jan, Saely, Christoph H., Samman-Tahhan, Ayman, Sandesara, Pratik B., Teren, Andrej, Timmis, Adam, Van de Werf, Frans, Wauters, Els, Wilde, Arthur A. M., Ford, Ian, Stott, David J., Algra, Ale, Andreassi, Maria G., Ardissino, Diego, Arsenault, Benoit J., Ballantyne, Christie M., Bergmeijer, Thomas O., Bezzina, Connie R., Body, Simon C., Boersma, Eric H., Bogaty, Peter, Bots, Michiel L., Brenner, Hermann, Brugts, Jasper J., Burkhardt, Ralph, Carpeggiani, Clara, Condorelli, Gianluigi, Cooper-DeHoff, Rhonda M., Cresci, Sharon, Danchin, Nicolas, de Faire, Ulf, Doughty, Robert N., Drexel, Heinz, Engert, James C., Fox, Keith A. A., Girelli, Domenico, Grobbee, Diederick E., Hagström, Emil, Hazen, Stanley L., Held, Claes, Hemingway, Harry, Hoefer, Imo E., Hovingh, G. Kees, Jabbari, Reza, Johnson, Julie A., Jukema, J. Wouter, Kaczor, Marcin P., Kahonen, Mika, Kettner, Jiri, Kiliszek, Marek, Klungel, Olaf H., Lagerqvist, Bo, Lambrechts, Diether, Laurikka, Jari O., Lehtimaki, Terho, Lindholm, Daniel, Mahmoodi, B. K., Maitland-van der Zee, Anke H., McPherson, Ruth, Melander, Olle, Metspalu, Andres, Niemcunowicz-Janica, Anna, Olivieri, Oliviero, Opolski, Grzegorz, Palmer, Colin N., Pasterkamp, Gerard, Pepine, Carl J., Pereira, Alexandre C., Pilote, Louise, Quyyumi, Arshed A., Richards, A. Mark, Sanak, Marek, Siegbahn, Agneta, Simon, Tabassome, Sinisalo, Juha, Smith, J. Gustav, Spertus, John A., Stender, Steen, Stewart, Alexandre F. R., Szczeklik, Wojciech, Szpakowicz, Anna, Tardif, Jean-Claude, ten Berg, Jurrien M., Tfelt-Hansen, Jacob, Thanassoulis, George, Thiery, Joachim, Torp-Pedersen, Christian, van der Graaf, Yolanda, Visseren, Frank L. J., Waltenberger, Johannes, Weeke, Peter E., Van der Harst, Pim, Lang, Chim C., Sattar, Naveed, Cameron, Vicky A., Anderson, Jeffrey L., Brophy, James M., Pare, Guillaume, Horne, Benjamin D., Marz, Winfried, Wallentin, Lars, Samani, Nilesh J., Hingorani, Aroon D., Asselbergs, Folkert W., Patel, Riyaz S., Tragante, Vinicius, Schmidt, Amand F., McCubrey, Raymond O., Holmes, Michael, V, Howe, Laurence J., Direk, Kenan, Åkerblom, Axel, Leander, Karin, Virani, Salim S., Kaminski, Karol A., Muehlschlegel, Jochen D., Allayee, Hooman, Almgren, Peter, Alver, Maris, Baranova, Ekaterina, V, Behloui, Hassan, Boeckx, Bram, Braund, Peter S., Breitling, Lutz P., Delgado, Gradela, Duarte, Nubia E., Dube, Marie-Pierre, Dufresne, Line, Eriksson, Niclas, Foco, Luisa, Scholz, Markus, Gijsberts, Crystel M., Glinge, Charlotte, Gong, Yan, Hartiala, Jaana, Heydarpour, Mahyar, Hubacek, Jaroslav A., Kleber, Marcus, Kofink, Daniel, Kotti, Salma, Kuukasjarvi, Pekka, Lee, Vei-Vei, Leiherer, Andreas, Lenzini, Petra A., Levin, Daniel, Lyytikainen, Leo-Pekka, Martinelli, Nicola, Mons, Ute, Nelson, Christopher P., Nikus, Kjell, Pilbrow, Anna P., Ploski, Rafal, Sun, Yan, V, Tanck, Michael W. T., Tang, W. H. Wilson, Trompet, Stella, van der Laan, Sander W., Van Setten, Jessica, Vilmundarson, Ragnar O., Anselmi, Chiara Viviani, Vlachopoulou, Efthymia, Al Ali, Lawien, Boerwinkle, Eric, Briguori, Carlo, Carlquist, John F., Carruthers, Kathryn F., Casu, Gavino, Deanfield, John, Deloukas, Panos, Dudbridge, Frank, Engstrom, Thomas, Fitzpatrick, Natalie, Fox, Kim, Gigante, Bruna, James, Stefan, Lokki, Marja-Liisa, Lotufo, Paulo A., Marziliano, Nicola, Mordi, Ify R., Muhlestein, Joseph B., Newton-Cheh, Christopher, Pitha, Jan, Saely, Christoph H., Samman-Tahhan, Ayman, Sandesara, Pratik B., Teren, Andrej, Timmis, Adam, Van de Werf, Frans, Wauters, Els, Wilde, Arthur A. M., Ford, Ian, Stott, David J., Algra, Ale, Andreassi, Maria G., Ardissino, Diego, Arsenault, Benoit J., Ballantyne, Christie M., Bergmeijer, Thomas O., Bezzina, Connie R., Body, Simon C., Boersma, Eric H., Bogaty, Peter, Bots, Michiel L., Brenner, Hermann, Brugts, Jasper J., Burkhardt, Ralph, Carpeggiani, Clara, Condorelli, Gianluigi, Cooper-DeHoff, Rhonda M., Cresci, Sharon, Danchin, Nicolas, de Faire, Ulf, Doughty, Robert N., Drexel, Heinz, Engert, James C., Fox, Keith A. A., Girelli, Domenico, Grobbee, Diederick E., Hagström, Emil, Hazen, Stanley L., Held, Claes, Hemingway, Harry, Hoefer, Imo E., Hovingh, G. Kees, Jabbari, Reza, Johnson, Julie A., Jukema, J. Wouter, Kaczor, Marcin P., Kahonen, Mika, Kettner, Jiri, Kiliszek, Marek, Klungel, Olaf H., Lagerqvist, Bo, Lambrechts, Diether, Laurikka, Jari O., Lehtimaki, Terho, Lindholm, Daniel, Mahmoodi, B. K., Maitland-van der Zee, Anke H., McPherson, Ruth, Melander, Olle, Metspalu, Andres, Niemcunowicz-Janica, Anna, Olivieri, Oliviero, Opolski, Grzegorz, Palmer, Colin N., Pasterkamp, Gerard, Pepine, Carl J., Pereira, Alexandre C., Pilote, Louise, Quyyumi, Arshed A., Richards, A. Mark, Sanak, Marek, Siegbahn, Agneta, Simon, Tabassome, Sinisalo, Juha, Smith, J. Gustav, Spertus, John A., Stender, Steen, Stewart, Alexandre F. R., Szczeklik, Wojciech, Szpakowicz, Anna, Tardif, Jean-Claude, ten Berg, Jurrien M., Tfelt-Hansen, Jacob, Thanassoulis, George, Thiery, Joachim, Torp-Pedersen, Christian, van der Graaf, Yolanda, Visseren, Frank L. J., Waltenberger, Johannes, Weeke, Peter E., Van der Harst, Pim, Lang, Chim C., Sattar, Naveed, Cameron, Vicky A., Anderson, Jeffrey L., Brophy, James M., Pare, Guillaume, Horne, Benjamin D., Marz, Winfried, Wallentin, Lars, Samani, Nilesh J., Hingorani, Aroon D., and Asselbergs, Folkert W.
Abstract: BACKGROUND: The Genetics of Subsequent Coronary Heart Disease (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD. METHODS: The consortium currently includes 57 studies from 18 countries, recruiting 185 614 participants with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events. RESULTS: Enrollment into the individual studies took place between 1985 to present day with a duration of follow-up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38%-100%), mostly male (44%-91%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (hazard ratio, 1.15; 95% CI, 1.14-1.16) per 5-year increase, male sex (hazard ratio, 1.17; 95% CI, 1.13-1.21) and smoking (hazard ratio, 1.43; 95% CI, 1.35-1.51) with risk of subsequent CHD death or myocardial infarction and differing associations with other individual and composite cardiovascular endpoints. CONCLUSIONS: GENIUS-CHD is a global collaboration seeking to elucidate genetic and nongenetic determinants of subsequent event risk in individuals with established CHD, to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators.
Published: 2019
Full Text: View/download PDF

24. Association of Chromosome 9p21 With Subsequent Coronary Heart Disease Events : A GENIUS-CHD Study of Individual Participant Data

Author: Patel, Riyaz S., Schmidt, Amand F., Tragante, Vinicius, McCubrey, Raymond O., Holmes, Michael, V, Howe, Laurence J., Direk, Kenan, Åkerblom, Axel, Leander, Karin, Virani, Salim S., Kaminski, Karol A., Muehlschlegel, Jochen D., Dube, Marie-Pierre, Allayee, Hooman, Almgren, Peter, Alver, Maris, Baranova, Ekaterina, V, Behlouli, Hassan, Boeckx, Bram, Braund, Peter S., Breitling, Lutz P., Delgado, Graciela, Duarte, Nubia E., Dufresne, Line, Eriksson, Niclas, Foco, Luisa, Gijsberts, Crystel M., Gong, Yan, Hartiala, Jaana, Heydarpour, Mahyar, Hubacek, Jaroslav A., Kleber, Marcus, Kofink, Daniel, Kuukasjarvi, Pekka, Lee, Vei-Vei, Leiherer, Andreas, Lenzini, Petra A., Levin, Daniel, Lyytikainen, Leo-Pekka, Martinelli, Nicola, Mons, Ute, Nelson, Christopher P., Nikus, Kjell, Pilbrow, Anna P., Ploski, Rafal, Sun, Yan, V, Tanck, Michael W. T., Tang, W. H. Wilson, Trompet, Stella, van der Laan, Sander W., van Setten, Jessica, Vilmundarson, Ragnar O., Anselmi, Chiara Viviani, Vlachopoulou, Efthymia, Boerwinkle, Eric, Briguori, Carlo, Carlquist, John F., Carruthers, Kathryn F., Casu, Gavino, Deanfield, John, Deloukas, Panos, Dudbridge, Frank, Fitzpatrick, Natalie, Gigante, Bruna, James, Stefan, Lokki, Marja-Liisa, Lotufo, Paulo A., Marziliano, Nicola, Mordi, Ify R., Muhlestein, Joseph B., Cheh, Chris Newton, Pitha, Jan, Saely, Christoph H., Samman-Tahhan, Ayman, Sandesara, Pratik B., Teren, Andrej, Timmis, Adam, Van de Werf, Frans, Wauters, Els, Wilde, Arthur A. M., Ford, Ian, Stott, David J., Algra, Ale, Andreassi, Maria G., Ardissino, Diego, Arsenault, Benoit J., Ballantyne, Christie M., Bergmeijer, Thomas O., Bezzina, Connie R., Body, Simon C., Bogaty, Peter, de Borst, Gert J., Brenner, Hermann, Burkhardt, Ralph, Carpeggiani, Clara, Condorelli, Gianluigi, Cooper-DeHoff, Rhonda M., Cresci, Sharon, de Faire, Ulf, Doughty, Robert N., Drexel, Heinz, Engert, James C., Fox, Keith A. A., Girelli, Domenico, Hagström, Emil, Hazen, Stanley L., Held, Claes, Hemingway, Harry, Hoefer, Imo E., Hovingh, G. Kees, Johnson, Julie A., De Jong, Pim A., Jukema, J. Wouter, Kaczor, Marcin P., Kahonen, Mika, Kettner, Jiri, Kiliszek, Marek, Klungel, Olaf H., Lagerqvist, Bo, Lambrechts, Diether, Laurikka, Jari O., Lehtimaki, Terho, Lindholm, Daniel, Mahmoodi, Bakhtawar K., Maitland-van der Zee, Anke H., McPherson, Ruth, Melander, Olle, Metspalu, Andres, Pepinski, Witold, Olivieri, Oliviero, Opolski, Grzegorz, Palmer, Colin N., Pasterkamp, Gerard, Pepine, Carl J., Pereira, Alexandre C., Note, Louise, Quyyumi, Arshed A., Richards, A. Mark, Sanak, Marek, Scholz, Markus, Siegbahn, Agneta, Sinisalo, Juha, Smith, J. Gustav, Spertus, John A., Stewart, Alexandre F. R., Szczeklik, Wojciech, Szpakowicz, Anna, ten Berg, Jurrien M., Thanassoulis, George, Thieiy, Joachim, van der Graaf, Yolanda, Visseren, Frank L. J., Waltenberger, Johannes, Van der Harst, Pim, Tardif, Jean-Claude, Sattar, Naveed, Lang, Chim C., Pare, Guillaume, Brophy, James M., Anderson, Jeffrey L., Maerz, Winfried, Wallentin, Lars, Cameron, Vicky A., Horne, Benjamin D., Samani, Nilesh J., Hingorani, Aroon D., Asselbergs, Folkert W., Patel, Riyaz S., Schmidt, Amand F., Tragante, Vinicius, McCubrey, Raymond O., Holmes, Michael, V, Howe, Laurence J., Direk, Kenan, Åkerblom, Axel, Leander, Karin, Virani, Salim S., Kaminski, Karol A., Muehlschlegel, Jochen D., Dube, Marie-Pierre, Allayee, Hooman, Almgren, Peter, Alver, Maris, Baranova, Ekaterina, V, Behlouli, Hassan, Boeckx, Bram, Braund, Peter S., Breitling, Lutz P., Delgado, Graciela, Duarte, Nubia E., Dufresne, Line, Eriksson, Niclas, Foco, Luisa, Gijsberts, Crystel M., Gong, Yan, Hartiala, Jaana, Heydarpour, Mahyar, Hubacek, Jaroslav A., Kleber, Marcus, Kofink, Daniel, Kuukasjarvi, Pekka, Lee, Vei-Vei, Leiherer, Andreas, Lenzini, Petra A., Levin, Daniel, Lyytikainen, Leo-Pekka, Martinelli, Nicola, Mons, Ute, Nelson, Christopher P., Nikus, Kjell, Pilbrow, Anna P., Ploski, Rafal, Sun, Yan, V, Tanck, Michael W. T., Tang, W. H. Wilson, Trompet, Stella, van der Laan, Sander W., van Setten, Jessica, Vilmundarson, Ragnar O., Anselmi, Chiara Viviani, Vlachopoulou, Efthymia, Boerwinkle, Eric, Briguori, Carlo, Carlquist, John F., Carruthers, Kathryn F., Casu, Gavino, Deanfield, John, Deloukas, Panos, Dudbridge, Frank, Fitzpatrick, Natalie, Gigante, Bruna, James, Stefan, Lokki, Marja-Liisa, Lotufo, Paulo A., Marziliano, Nicola, Mordi, Ify R., Muhlestein, Joseph B., Cheh, Chris Newton, Pitha, Jan, Saely, Christoph H., Samman-Tahhan, Ayman, Sandesara, Pratik B., Teren, Andrej, Timmis, Adam, Van de Werf, Frans, Wauters, Els, Wilde, Arthur A. M., Ford, Ian, Stott, David J., Algra, Ale, Andreassi, Maria G., Ardissino, Diego, Arsenault, Benoit J., Ballantyne, Christie M., Bergmeijer, Thomas O., Bezzina, Connie R., Body, Simon C., Bogaty, Peter, de Borst, Gert J., Brenner, Hermann, Burkhardt, Ralph, Carpeggiani, Clara, Condorelli, Gianluigi, Cooper-DeHoff, Rhonda M., Cresci, Sharon, de Faire, Ulf, Doughty, Robert N., Drexel, Heinz, Engert, James C., Fox, Keith A. A., Girelli, Domenico, Hagström, Emil, Hazen, Stanley L., Held, Claes, Hemingway, Harry, Hoefer, Imo E., Hovingh, G. Kees, Johnson, Julie A., De Jong, Pim A., Jukema, J. Wouter, Kaczor, Marcin P., Kahonen, Mika, Kettner, Jiri, Kiliszek, Marek, Klungel, Olaf H., Lagerqvist, Bo, Lambrechts, Diether, Laurikka, Jari O., Lehtimaki, Terho, Lindholm, Daniel, Mahmoodi, Bakhtawar K., Maitland-van der Zee, Anke H., McPherson, Ruth, Melander, Olle, Metspalu, Andres, Pepinski, Witold, Olivieri, Oliviero, Opolski, Grzegorz, Palmer, Colin N., Pasterkamp, Gerard, Pepine, Carl J., Pereira, Alexandre C., Note, Louise, Quyyumi, Arshed A., Richards, A. Mark, Sanak, Marek, Scholz, Markus, Siegbahn, Agneta, Sinisalo, Juha, Smith, J. Gustav, Spertus, John A., Stewart, Alexandre F. R., Szczeklik, Wojciech, Szpakowicz, Anna, ten Berg, Jurrien M., Thanassoulis, George, Thieiy, Joachim, van der Graaf, Yolanda, Visseren, Frank L. J., Waltenberger, Johannes, Van der Harst, Pim, Tardif, Jean-Claude, Sattar, Naveed, Lang, Chim C., Pare, Guillaume, Brophy, James M., Anderson, Jeffrey L., Maerz, Winfried, Wallentin, Lars, Cameron, Vicky A., Horne, Benjamin D., Samani, Nilesh J., Hingorani, Aroon D., and Asselbergs, Folkert W.
Abstract: BACKGROUND: Genetic variation at chromosome 9p21 is a recognized risk factor for coronary heart disease (CHD). However, its effect on disease progression and subsequent events is unclear, raising questions about its value for stratification of residual risk. METHODS: A variant at chromosome 9p21 (rs1333049) was tested for association with subsequent events during follow-up in 103 357 Europeans with established CHD at baseline from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) Consortium (73.1% male, mean age 62.9 years). The primary outcome, subsequent CHD death or myocardial infarction (CHD death/myocardial infarction), occurred in 13 040 of the 93 115 participants with available outcome data. Effect estimates were compared with case/control risk obtained from the CARDIoGRAMplusC4D consortium (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics) including 47 222 CHD cases and 122 264 controls free of CHD. RESULTS: Meta-analyses revealed no significant association between chromosome 9p21 and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline (GENIUSCHD odds ratio, 1.02; 95% CI, 0.99-1.05). This contrasted with a strong association in CARDIoGRAMPlusC4D odds ratio 1.20; 95% CI, 1.18-1.22; P for interaction < 0.001 compared with the GENIUS-CHD estimate. Similarly, no clear associations were identified for additional subsequent outcomes, including all-cause death, although we found a modest positive association between chromosome 9p21 and subsequent revascularization (odds ratio, 1.07; 95% CI, 1.04-1.09). CONCLUSIONS: In contrast to studies comparing individuals with CHD to disease-free controls, we found no clear association between genetic variation at chromosome 9p21 and risk of subsequent acute CHD events when all individuals had CHD at baseline. However, the association with subsequent revascularization may support the post
Published: 2019
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25. Subsequent Event Risk in Individuals with Established Coronary Heart Disease : Design and Rationale of the GENIUS-CHD Consortium

Author: Patel, Riyaz S., Tragante, Vinicius, Schmidt, Amand F., McCubrey, Raymond O., Holmes, Michael V., Howe, Laurence J., Direk, Kenan, Åkerblom, Axel, Leander, Karin, Virani, Salim S., Kaminski, Karol A., Muehlschlegel, Jochen D., Allayee, Hooman, Almgren, Peter, Alver, Maris, Baranova, Ekaterina V., Behloui, Hassan, Boeckx, Bram, Braund, Peter S., Breitling, Lutz P., Delgado, Graciela, Duarte, Nubia E., Dubé, Marie Pierre, Dufresne, Line, Eriksson, Niclas, Foco, Luisa, Scholz, Markus, Gijsberts, Crystel M., Glinge, Charlotte, Gong, Yan, Hartiala, Jaana, Heydarpour, Mahyar, Hubacek, Jaroslav A., Kleber, Marcus, Kofink, Daniel, Kotti, Salma, Kuukasjärvi, Pekka, Lee, Vei Vei, Leiherer, Andreas, Lenzini, Petra A., Levin, Daniel, Lyytikäinen, Leo Pekka, Martinelli, Nicola, Mons, Ute, Nelson, Christopher P., Nikus, Kjell, Pilbrow, Anna P., Ploski, Rafal, Sun, Yan V., Tanck, Michael W.T., Tang, W. H.Wilson, Trompet, Stella, van der Laan, Sander W., Van Setten, Jessica, Vilmundarson, Ragnar O., Viviani Anselmi, Chiara, Vlachopoulou, Efthymia, Al Ali, Lawien, Boerwinkle, Eric, Briguori, Carlo, Carlquist, John F., Carruthers, Kathryn F., Casu, Gavino, Deanfield, John, Deloukas, Panos, Dudbridge, Frank, Engstrøm, Thomas, Fitzpatrick, Natalie, Fox, Kim, Gigante, Bruna, James, Stefan, Lokki, Marja Liisa, Lotufo, Paulo A., Marziliano, Nicola, Mordi, Ify R., Muhlestein, Joseph B., Newton-Cheh, Christopher, Pitha, Jan, Saely, Christoph H., Samman-Tahhan, Ayman, Sandesara, Pratik B., Teren, Andrej, Timmis, Adam, Van de Werf, Frans, Wauters, Els, Wilde, Arthur A.M., Ford, Ian, Stott, David J., Algra, Ale, Andreassi, Maria G., Ardissino, Diego, Arsenault, Benoit J., Ballantyne, Christie M., Bergmeijer, Thomas O., Bezzina, Connie R., Body, Simon C., Boersma, Eric H., Bogaty, Peter, Bots, Michiel L., Brenner, Hermann, Brugts, Jasper J., Burkhardt, Ralph, Carpeggiani, Clara, Condorelli, Gianluigi, Cooper-DeHoff, Rhonda M., Cresci, Sharon, Danchin, Nicolas, de Faire, Ulf, Doughty, Robert N., Drexel, Heinz, Engert, James C., Fox, Keith A.A., Girelli, Domenico, Grobbee, Diederick E., Hagström, Emil, Hazen, Stanley L., Held, Claes, Hemingway, Harry, Hoefer, Imo E., Hovingh, G. Kees, Jabbari, Reza, Johnson, Julie A., Jukema, J. Wouter, Kaczor, Marcin P., Kähönen, Mika, Kettner, Jiri, Kiliszek, Marek, Klungel, Olaf H., Lagerqvist, Bo, Lambrechts, Diether, Laurikka, Jari O., Lehtimäki, Terho, Lindholm, Daniel, Mahmoodi, B. K., Maitland-van der Zee, Anke H., McPherson, Ruth, Melander, Olle, Metspalu, Andres, Niemcunowicz-Janica, Anna, Olivieri, Oliviero, Opolski, Grzegorz, Palmer, Colin N., Pasterkamp, Gerard, Pepine, Carl J., Pereira, Alexandre C., Pilote, Louise, Quyyumi, Arshed A., Richards, A. Mark, Sanak, Marek, Siegbahn, Agneta, Simon, Tabassome, Sinisalo, Juha, Smith, J. Gustav, Spertus, John A., Stender, Steen, Stewart, Alexandre F.R., Szczeklik, Wojciech, Szpakowicz, Anna, Tardif, Jean Claude, Ten Berg, Jurriën M., Tfelt-Hansen, Jacob, Thanassoulis, George, Thiery, Joachim, Torp-Pedersen, Christian, van der Graaf, Yolanda, Visseren, Frank L.J., Waltenberger, Johannes, Weeke, Peter E., Van der Harst, Pim, Lang, Chim C., Sattar, Naveed, Cameron, Vicky A., Anderson, Jeffrey L., Brophy, James M., Pare, Guillaume, Horne, Benjamin D., März, Winfried, Wallentin, Lars, Samani, Nilesh J., Hingorani, Aroon D., Asselbergs, Folkert W., Patel, Riyaz S., Tragante, Vinicius, Schmidt, Amand F., McCubrey, Raymond O., Holmes, Michael V., Howe, Laurence J., Direk, Kenan, Åkerblom, Axel, Leander, Karin, Virani, Salim S., Kaminski, Karol A., Muehlschlegel, Jochen D., Allayee, Hooman, Almgren, Peter, Alver, Maris, Baranova, Ekaterina V., Behloui, Hassan, Boeckx, Bram, Braund, Peter S., Breitling, Lutz P., Delgado, Graciela, Duarte, Nubia E., Dubé, Marie Pierre, Dufresne, Line, Eriksson, Niclas, Foco, Luisa, Scholz, Markus, Gijsberts, Crystel M., Glinge, Charlotte, Gong, Yan, Hartiala, Jaana, Heydarpour, Mahyar, Hubacek, Jaroslav A., Kleber, Marcus, Kofink, Daniel, Kotti, Salma, Kuukasjärvi, Pekka, Lee, Vei Vei, Leiherer, Andreas, Lenzini, Petra A., Levin, Daniel, Lyytikäinen, Leo Pekka, Martinelli, Nicola, Mons, Ute, Nelson, Christopher P., Nikus, Kjell, Pilbrow, Anna P., Ploski, Rafal, Sun, Yan V., Tanck, Michael W.T., Tang, W. H.Wilson, Trompet, Stella, van der Laan, Sander W., Van Setten, Jessica, Vilmundarson, Ragnar O., Viviani Anselmi, Chiara, Vlachopoulou, Efthymia, Al Ali, Lawien, Boerwinkle, Eric, Briguori, Carlo, Carlquist, John F., Carruthers, Kathryn F., Casu, Gavino, Deanfield, John, Deloukas, Panos, Dudbridge, Frank, Engstrøm, Thomas, Fitzpatrick, Natalie, Fox, Kim, Gigante, Bruna, James, Stefan, Lokki, Marja Liisa, Lotufo, Paulo A., Marziliano, Nicola, Mordi, Ify R., Muhlestein, Joseph B., Newton-Cheh, Christopher, Pitha, Jan, Saely, Christoph H., Samman-Tahhan, Ayman, Sandesara, Pratik B., Teren, Andrej, Timmis, Adam, Van de Werf, Frans, Wauters, Els, Wilde, Arthur A.M., Ford, Ian, Stott, David J., Algra, Ale, Andreassi, Maria G., Ardissino, Diego, Arsenault, Benoit J., Ballantyne, Christie M., Bergmeijer, Thomas O., Bezzina, Connie R., Body, Simon C., Boersma, Eric H., Bogaty, Peter, Bots, Michiel L., Brenner, Hermann, Brugts, Jasper J., Burkhardt, Ralph, Carpeggiani, Clara, Condorelli, Gianluigi, Cooper-DeHoff, Rhonda M., Cresci, Sharon, Danchin, Nicolas, de Faire, Ulf, Doughty, Robert N., Drexel, Heinz, Engert, James C., Fox, Keith A.A., Girelli, Domenico, Grobbee, Diederick E., Hagström, Emil, Hazen, Stanley L., Held, Claes, Hemingway, Harry, Hoefer, Imo E., Hovingh, G. Kees, Jabbari, Reza, Johnson, Julie A., Jukema, J. Wouter, Kaczor, Marcin P., Kähönen, Mika, Kettner, Jiri, Kiliszek, Marek, Klungel, Olaf H., Lagerqvist, Bo, Lambrechts, Diether, Laurikka, Jari O., Lehtimäki, Terho, Lindholm, Daniel, Mahmoodi, B. K., Maitland-van der Zee, Anke H., McPherson, Ruth, Melander, Olle, Metspalu, Andres, Niemcunowicz-Janica, Anna, Olivieri, Oliviero, Opolski, Grzegorz, Palmer, Colin N., Pasterkamp, Gerard, Pepine, Carl J., Pereira, Alexandre C., Pilote, Louise, Quyyumi, Arshed A., Richards, A. Mark, Sanak, Marek, Siegbahn, Agneta, Simon, Tabassome, Sinisalo, Juha, Smith, J. Gustav, Spertus, John A., Stender, Steen, Stewart, Alexandre F.R., Szczeklik, Wojciech, Szpakowicz, Anna, Tardif, Jean Claude, Ten Berg, Jurriën M., Tfelt-Hansen, Jacob, Thanassoulis, George, Thiery, Joachim, Torp-Pedersen, Christian, van der Graaf, Yolanda, Visseren, Frank L.J., Waltenberger, Johannes, Weeke, Peter E., Van der Harst, Pim, Lang, Chim C., Sattar, Naveed, Cameron, Vicky A., Anderson, Jeffrey L., Brophy, James M., Pare, Guillaume, Horne, Benjamin D., März, Winfried, Wallentin, Lars, Samani, Nilesh J., Hingorani, Aroon D., and Asselbergs, Folkert W.
Published: 2019

26. Association between fat mass through adolescence and arterial stiffness : a population-based study from The Avon Longitudinal Study of Parents and Children

Author: Dangardt, Frida, Charakida, Marietta, Georgiopoulos, Georgios, Chiesa, Scott T., Rapala, Alicja, Wade, Kaitlin H., Hughes, Alun D., Timpson, Nicholas J., Pateras, Konstantinos, Finer, Nick, Sattar, Naveed, Davey Smith, George, Lawlor, Debbie A., Deanfield, John E., Dangardt, Frida, Charakida, Marietta, Georgiopoulos, Georgios, Chiesa, Scott T., Rapala, Alicja, Wade, Kaitlin H., Hughes, Alun D., Timpson, Nicholas J., Pateras, Konstantinos, Finer, Nick, Sattar, Naveed, Davey Smith, George, Lawlor, Debbie A., and Deanfield, John E.
Published: 2019

27. Association between fat mass through adolescence and arterial stiffness : a population-based study from The Avon Longitudinal Study of Parents and Children

Author: Dangardt, Frida, Charakida, Marietta, Georgiopoulos, Georgios, Chiesa, Scott T., Rapala, Alicja, Wade, Kaitlin H., Hughes, Alun D., Timpson, Nicholas J., Pateras, Konstantinos, Finer, Nick, Sattar, Naveed, Davey Smith, George, Lawlor, Debbie A., Deanfield, John E., Dangardt, Frida, Charakida, Marietta, Georgiopoulos, Georgios, Chiesa, Scott T., Rapala, Alicja, Wade, Kaitlin H., Hughes, Alun D., Timpson, Nicholas J., Pateras, Konstantinos, Finer, Nick, Sattar, Naveed, Davey Smith, George, Lawlor, Debbie A., and Deanfield, John E.
Published: 2019

28. Subsequent Event Risk in Individuals with Established Coronary Heart Disease : Design and Rationale of the GENIUS-CHD Consortium

Author: Patel, Riyaz S., Tragante, Vinicius, Schmidt, Amand F., McCubrey, Raymond O., Holmes, Michael V., Howe, Laurence J., Direk, Kenan, Åkerblom, Axel, Leander, Karin, Virani, Salim S., Kaminski, Karol A., Muehlschlegel, Jochen D., Allayee, Hooman, Almgren, Peter, Alver, Maris, Baranova, Ekaterina V., Behloui, Hassan, Boeckx, Bram, Braund, Peter S., Breitling, Lutz P., Delgado, Graciela, Duarte, Nubia E., Dubé, Marie Pierre, Dufresne, Line, Eriksson, Niclas, Foco, Luisa, Scholz, Markus, Gijsberts, Crystel M., Glinge, Charlotte, Gong, Yan, Hartiala, Jaana, Heydarpour, Mahyar, Hubacek, Jaroslav A., Kleber, Marcus, Kofink, Daniel, Kotti, Salma, Kuukasjärvi, Pekka, Lee, Vei Vei, Leiherer, Andreas, Lenzini, Petra A., Levin, Daniel, Lyytikäinen, Leo Pekka, Martinelli, Nicola, Mons, Ute, Nelson, Christopher P., Nikus, Kjell, Pilbrow, Anna P., Ploski, Rafal, Sun, Yan V., Tanck, Michael W.T., Tang, W. H.Wilson, Trompet, Stella, van der Laan, Sander W., Van Setten, Jessica, Vilmundarson, Ragnar O., Viviani Anselmi, Chiara, Vlachopoulou, Efthymia, Al Ali, Lawien, Boerwinkle, Eric, Briguori, Carlo, Carlquist, John F., Carruthers, Kathryn F., Casu, Gavino, Deanfield, John, Deloukas, Panos, Dudbridge, Frank, Engstrøm, Thomas, Fitzpatrick, Natalie, Fox, Kim, Gigante, Bruna, James, Stefan, Lokki, Marja Liisa, Lotufo, Paulo A., Marziliano, Nicola, Mordi, Ify R., Muhlestein, Joseph B., Newton-Cheh, Christopher, Pitha, Jan, Saely, Christoph H., Samman-Tahhan, Ayman, Sandesara, Pratik B., Teren, Andrej, Timmis, Adam, Van de Werf, Frans, Wauters, Els, Wilde, Arthur A.M., Ford, Ian, Stott, David J., Algra, Ale, Andreassi, Maria G., Ardissino, Diego, Arsenault, Benoit J., Ballantyne, Christie M., Bergmeijer, Thomas O., Bezzina, Connie R., Body, Simon C., Boersma, Eric H., Bogaty, Peter, Bots, Michiel L., Brenner, Hermann, Brugts, Jasper J., Burkhardt, Ralph, Carpeggiani, Clara, Condorelli, Gianluigi, Cooper-DeHoff, Rhonda M., Cresci, Sharon, Danchin, Nicolas, de Faire, Ulf, Doughty, Robert N., Drexel, Heinz, Engert, James C., Fox, Keith A.A., Girelli, Domenico, Grobbee, Diederick E., Hagström, Emil, Hazen, Stanley L., Held, Claes, Hemingway, Harry, Hoefer, Imo E., Hovingh, G. Kees, Jabbari, Reza, Johnson, Julie A., Jukema, J. Wouter, Kaczor, Marcin P., Kähönen, Mika, Kettner, Jiri, Kiliszek, Marek, Klungel, Olaf H., Lagerqvist, Bo, Lambrechts, Diether, Laurikka, Jari O., Lehtimäki, Terho, Lindholm, Daniel, Mahmoodi, B. K., Maitland-van der Zee, Anke H., McPherson, Ruth, Melander, Olle, Metspalu, Andres, Niemcunowicz-Janica, Anna, Olivieri, Oliviero, Opolski, Grzegorz, Palmer, Colin N., Pasterkamp, Gerard, Pepine, Carl J., Pereira, Alexandre C., Pilote, Louise, Quyyumi, Arshed A., Richards, A. Mark, Sanak, Marek, Siegbahn, Agneta, Simon, Tabassome, Sinisalo, Juha, Smith, J. Gustav, Spertus, John A., Stender, Steen, Stewart, Alexandre F.R., Szczeklik, Wojciech, Szpakowicz, Anna, Tardif, Jean Claude, Ten Berg, Jurriën M., Tfelt-Hansen, Jacob, Thanassoulis, George, Thiery, Joachim, Torp-Pedersen, Christian, van der Graaf, Yolanda, Visseren, Frank L.J., Waltenberger, Johannes, Weeke, Peter E., Van der Harst, Pim, Lang, Chim C., Sattar, Naveed, Cameron, Vicky A., Anderson, Jeffrey L., Brophy, James M., Pare, Guillaume, Horne, Benjamin D., März, Winfried, Wallentin, Lars, Samani, Nilesh J., Hingorani, Aroon D., Asselbergs, Folkert W., Patel, Riyaz S., Tragante, Vinicius, Schmidt, Amand F., McCubrey, Raymond O., Holmes, Michael V., Howe, Laurence J., Direk, Kenan, Åkerblom, Axel, Leander, Karin, Virani, Salim S., Kaminski, Karol A., Muehlschlegel, Jochen D., Allayee, Hooman, Almgren, Peter, Alver, Maris, Baranova, Ekaterina V., Behloui, Hassan, Boeckx, Bram, Braund, Peter S., Breitling, Lutz P., Delgado, Graciela, Duarte, Nubia E., Dubé, Marie Pierre, Dufresne, Line, Eriksson, Niclas, Foco, Luisa, Scholz, Markus, Gijsberts, Crystel M., Glinge, Charlotte, Gong, Yan, Hartiala, Jaana, Heydarpour, Mahyar, Hubacek, Jaroslav A., Kleber, Marcus, Kofink, Daniel, Kotti, Salma, Kuukasjärvi, Pekka, Lee, Vei Vei, Leiherer, Andreas, Lenzini, Petra A., Levin, Daniel, Lyytikäinen, Leo Pekka, Martinelli, Nicola, Mons, Ute, Nelson, Christopher P., Nikus, Kjell, Pilbrow, Anna P., Ploski, Rafal, Sun, Yan V., Tanck, Michael W.T., Tang, W. H.Wilson, Trompet, Stella, van der Laan, Sander W., Van Setten, Jessica, Vilmundarson, Ragnar O., Viviani Anselmi, Chiara, Vlachopoulou, Efthymia, Al Ali, Lawien, Boerwinkle, Eric, Briguori, Carlo, Carlquist, John F., Carruthers, Kathryn F., Casu, Gavino, Deanfield, John, Deloukas, Panos, Dudbridge, Frank, Engstrøm, Thomas, Fitzpatrick, Natalie, Fox, Kim, Gigante, Bruna, James, Stefan, Lokki, Marja Liisa, Lotufo, Paulo A., Marziliano, Nicola, Mordi, Ify R., Muhlestein, Joseph B., Newton-Cheh, Christopher, Pitha, Jan, Saely, Christoph H., Samman-Tahhan, Ayman, Sandesara, Pratik B., Teren, Andrej, Timmis, Adam, Van de Werf, Frans, Wauters, Els, Wilde, Arthur A.M., Ford, Ian, Stott, David J., Algra, Ale, Andreassi, Maria G., Ardissino, Diego, Arsenault, Benoit J., Ballantyne, Christie M., Bergmeijer, Thomas O., Bezzina, Connie R., Body, Simon C., Boersma, Eric H., Bogaty, Peter, Bots, Michiel L., Brenner, Hermann, Brugts, Jasper J., Burkhardt, Ralph, Carpeggiani, Clara, Condorelli, Gianluigi, Cooper-DeHoff, Rhonda M., Cresci, Sharon, Danchin, Nicolas, de Faire, Ulf, Doughty, Robert N., Drexel, Heinz, Engert, James C., Fox, Keith A.A., Girelli, Domenico, Grobbee, Diederick E., Hagström, Emil, Hazen, Stanley L., Held, Claes, Hemingway, Harry, Hoefer, Imo E., Hovingh, G. Kees, Jabbari, Reza, Johnson, Julie A., Jukema, J. Wouter, Kaczor, Marcin P., Kähönen, Mika, Kettner, Jiri, Kiliszek, Marek, Klungel, Olaf H., Lagerqvist, Bo, Lambrechts, Diether, Laurikka, Jari O., Lehtimäki, Terho, Lindholm, Daniel, Mahmoodi, B. K., Maitland-van der Zee, Anke H., McPherson, Ruth, Melander, Olle, Metspalu, Andres, Niemcunowicz-Janica, Anna, Olivieri, Oliviero, Opolski, Grzegorz, Palmer, Colin N., Pasterkamp, Gerard, Pepine, Carl J., Pereira, Alexandre C., Pilote, Louise, Quyyumi, Arshed A., Richards, A. Mark, Sanak, Marek, Siegbahn, Agneta, Simon, Tabassome, Sinisalo, Juha, Smith, J. Gustav, Spertus, John A., Stender, Steen, Stewart, Alexandre F.R., Szczeklik, Wojciech, Szpakowicz, Anna, Tardif, Jean Claude, Ten Berg, Jurriën M., Tfelt-Hansen, Jacob, Thanassoulis, George, Thiery, Joachim, Torp-Pedersen, Christian, van der Graaf, Yolanda, Visseren, Frank L.J., Waltenberger, Johannes, Weeke, Peter E., Van der Harst, Pim, Lang, Chim C., Sattar, Naveed, Cameron, Vicky A., Anderson, Jeffrey L., Brophy, James M., Pare, Guillaume, Horne, Benjamin D., März, Winfried, Wallentin, Lars, Samani, Nilesh J., Hingorani, Aroon D., and Asselbergs, Folkert W.
Published: 2019

29. Effects of Hemodiafiltration versus Conventional Hemodialysis in Children with ESKD: The HDF, Heart and Height Study

Author: Shroff, Rukshana, Smith, Colette, Ranchin, Bruno, Bayazit, Aysun K., Stefanidis, Constantinos J., Askiti, Varvara, Azukaitis, Karolis, Canpolat, Nur, Agbas, Ayse, Aitkenhead, Helen, Anarat, Ali, Aoun, Bilal, Aofolaju, Daley, Bakkaloglu, Sevcan Azime, Bhowruth, Devina, Borzych-Duzalka, Dagmara, Bulut, Ipek Kaplan, Buescher, Rainer, Deanfield, John, Dempster, Claire, Duzova, Ali, Habbig, Sandra, Hayes, Wesley, Hegde, Shivram, Krid, Saoussen, Licht, Christoph, Litwin, Mieczyslaw, Mayes, Mark, Mir, Sevgi, Nemec, Rose, Obrycki, Lukasz, Paglialonga, Fabio, Picca, Stefano, Samaille, Charlotte, Shenoy, Mohan, Sinha, Manish D., Spasojevic, Brankica, Stronach, Lynsey, Vidal, Enrico, Vondrak, Karel, Yilmaz, Alev, Zaloszyc, Ariane, Fischbach, Michel, Schmitt, Claus Peter, Schaefer, Franz, Shroff, Rukshana, Smith, Colette, Ranchin, Bruno, Bayazit, Aysun K., Stefanidis, Constantinos J., Askiti, Varvara, Azukaitis, Karolis, Canpolat, Nur, Agbas, Ayse, Aitkenhead, Helen, Anarat, Ali, Aoun, Bilal, Aofolaju, Daley, Bakkaloglu, Sevcan Azime, Bhowruth, Devina, Borzych-Duzalka, Dagmara, Bulut, Ipek Kaplan, Buescher, Rainer, Deanfield, John, Dempster, Claire, Duzova, Ali, Habbig, Sandra, Hayes, Wesley, Hegde, Shivram, Krid, Saoussen, Licht, Christoph, Litwin, Mieczyslaw, Mayes, Mark, Mir, Sevgi, Nemec, Rose, Obrycki, Lukasz, Paglialonga, Fabio, Picca, Stefano, Samaille, Charlotte, Shenoy, Mohan, Sinha, Manish D., Spasojevic, Brankica, Stronach, Lynsey, Vidal, Enrico, Vondrak, Karel, Yilmaz, Alev, Zaloszyc, Ariane, Fischbach, Michel, Schmitt, Claus Peter, and Schaefer, Franz
Abstract: Background Hypertension and cardiovascular disease are common in children undergoing dialysis. Studies suggest that hemodiafiltration (HDF) may reduce cardiovascular mortality in adults, but data for children are scarce. Methods The HDF, Heart and Height study is a nonrandomized observational study comparing outcomes on conventional hemodialysis (HD) versus postdilution online HDF in children. Primary outcome measures were annualized changes in carotid intima-media thickness (cIMT) SD score and height SD score. Results We enrolled 190 children from 28 centers; 78 on HD and 55 on HDF completed 1-year follow-up. The groups were comparable for age, dialysis vintage, access type, dialysis frequency, blood flow, and residual renal function. At 1 year, cIMT SD score increased significantly in children on HD but remained static in the HDF cohort. On propensity score analysis, HD was associated with a +0.47 higher annualized cIMT SD score compared with HDF. Height SD score increased in HDF but remained static in HD. Mean arterial pressure SD score increased with HD only. Factors associated with higher cIMT and mean arterial pressure SD-scores were HD group, higher ultrafiltration rate, and higher 2-microglobulin. The HDF cohort had lower 2-microglobulin, parathyroid hormone, and high-sensitivity C-reactive protein at 1 year; fewer headaches, dizziness, or cramps; and shorter postdialysis recovery time. Conclusions HDF is associated with a lack of progression in vascular measures versus progression with HD, as well as an increase in height not seen in the HD cohort. Patient-related outcomes improved among children on HDF correlating with improved BP control and clearances. Confirmation through randomized trials is required.
Published: 2019

30. Association of Chromosome 9p21 With Subsequent Coronary Heart Disease Events : A GENIUS-CHD Study of Individual Participant Data

Author: Patel, Riyaz S., Schmidt, Amand F., Tragante, Vinicius, McCubrey, Raymond O., Holmes, Michael, V, Howe, Laurence J., Direk, Kenan, Åkerblom, Axel, Leander, Karin, Virani, Salim S., Kaminski, Karol A., Muehlschlegel, Jochen D., Dube, Marie-Pierre, Allayee, Hooman, Almgren, Peter, Alver, Maris, Baranova, Ekaterina, V, Behlouli, Hassan, Boeckx, Bram, Braund, Peter S., Breitling, Lutz P., Delgado, Graciela, Duarte, Nubia E., Dufresne, Line, Eriksson, Niclas, Foco, Luisa, Gijsberts, Crystel M., Gong, Yan, Hartiala, Jaana, Heydarpour, Mahyar, Hubacek, Jaroslav A., Kleber, Marcus, Kofink, Daniel, Kuukasjarvi, Pekka, Lee, Vei-Vei, Leiherer, Andreas, Lenzini, Petra A., Levin, Daniel, Lyytikainen, Leo-Pekka, Martinelli, Nicola, Mons, Ute, Nelson, Christopher P., Nikus, Kjell, Pilbrow, Anna P., Ploski, Rafal, Sun, Yan, V, Tanck, Michael W. T., Tang, W. H. Wilson, Trompet, Stella, van der Laan, Sander W., van Setten, Jessica, Vilmundarson, Ragnar O., Anselmi, Chiara Viviani, Vlachopoulou, Efthymia, Boerwinkle, Eric, Briguori, Carlo, Carlquist, John F., Carruthers, Kathryn F., Casu, Gavino, Deanfield, John, Deloukas, Panos, Dudbridge, Frank, Fitzpatrick, Natalie, Gigante, Bruna, James, Stefan, Lokki, Marja-Liisa, Lotufo, Paulo A., Marziliano, Nicola, Mordi, Ify R., Muhlestein, Joseph B., Cheh, Chris Newton, Pitha, Jan, Saely, Christoph H., Samman-Tahhan, Ayman, Sandesara, Pratik B., Teren, Andrej, Timmis, Adam, Van de Werf, Frans, Wauters, Els, Wilde, Arthur A. M., Ford, Ian, Stott, David J., Algra, Ale, Andreassi, Maria G., Ardissino, Diego, Arsenault, Benoit J., Ballantyne, Christie M., Bergmeijer, Thomas O., Bezzina, Connie R., Body, Simon C., Bogaty, Peter, de Borst, Gert J., Brenner, Hermann, Burkhardt, Ralph, Carpeggiani, Clara, Condorelli, Gianluigi, Cooper-DeHoff, Rhonda M., Cresci, Sharon, de Faire, Ulf, Doughty, Robert N., Drexel, Heinz, Engert, James C., Fox, Keith A. A., Girelli, Domenico, Hagström, Emil, Hazen, Stanley L., Held, Claes, Hemingway, Harry, Hoefer, Imo E., Hovingh, G. Kees, Johnson, Julie A., De Jong, Pim A., Jukema, J. Wouter, Kaczor, Marcin P., Kahonen, Mika, Kettner, Jiri, Kiliszek, Marek, Klungel, Olaf H., Lagerqvist, Bo, Lambrechts, Diether, Laurikka, Jari O., Lehtimaki, Terho, Lindholm, Daniel, Mahmoodi, Bakhtawar K., Maitland-van der Zee, Anke H., McPherson, Ruth, Melander, Olle, Metspalu, Andres, Pepinski, Witold, Olivieri, Oliviero, Opolski, Grzegorz, Palmer, Colin N., Pasterkamp, Gerard, Pepine, Carl J., Pereira, Alexandre C., Note, Louise, Quyyumi, Arshed A., Richards, A. Mark, Sanak, Marek, Scholz, Markus, Siegbahn, Agneta, Sinisalo, Juha, Smith, J. Gustav, Spertus, John A., Stewart, Alexandre F. R., Szczeklik, Wojciech, Szpakowicz, Anna, ten Berg, Jurrien M., Thanassoulis, George, Thieiy, Joachim, van der Graaf, Yolanda, Visseren, Frank L. J., Waltenberger, Johannes, Van der Harst, Pim, Tardif, Jean-Claude, Sattar, Naveed, Lang, Chim C., Pare, Guillaume, Brophy, James M., Anderson, Jeffrey L., Maerz, Winfried, Wallentin, Lars, Cameron, Vicky A., Horne, Benjamin D., Samani, Nilesh J., Hingorani, Aroon D., Asselbergs, Folkert W., Patel, Riyaz S., Schmidt, Amand F., Tragante, Vinicius, McCubrey, Raymond O., Holmes, Michael, V, Howe, Laurence J., Direk, Kenan, Åkerblom, Axel, Leander, Karin, Virani, Salim S., Kaminski, Karol A., Muehlschlegel, Jochen D., Dube, Marie-Pierre, Allayee, Hooman, Almgren, Peter, Alver, Maris, Baranova, Ekaterina, V, Behlouli, Hassan, Boeckx, Bram, Braund, Peter S., Breitling, Lutz P., Delgado, Graciela, Duarte, Nubia E., Dufresne, Line, Eriksson, Niclas, Foco, Luisa, Gijsberts, Crystel M., Gong, Yan, Hartiala, Jaana, Heydarpour, Mahyar, Hubacek, Jaroslav A., Kleber, Marcus, Kofink, Daniel, Kuukasjarvi, Pekka, Lee, Vei-Vei, Leiherer, Andreas, Lenzini, Petra A., Levin, Daniel, Lyytikainen, Leo-Pekka, Martinelli, Nicola, Mons, Ute, Nelson, Christopher P., Nikus, Kjell, Pilbrow, Anna P., Ploski, Rafal, Sun, Yan, V, Tanck, Michael W. T., Tang, W. H. Wilson, Trompet, Stella, van der Laan, Sander W., van Setten, Jessica, Vilmundarson, Ragnar O., Anselmi, Chiara Viviani, Vlachopoulou, Efthymia, Boerwinkle, Eric, Briguori, Carlo, Carlquist, John F., Carruthers, Kathryn F., Casu, Gavino, Deanfield, John, Deloukas, Panos, Dudbridge, Frank, Fitzpatrick, Natalie, Gigante, Bruna, James, Stefan, Lokki, Marja-Liisa, Lotufo, Paulo A., Marziliano, Nicola, Mordi, Ify R., Muhlestein, Joseph B., Cheh, Chris Newton, Pitha, Jan, Saely, Christoph H., Samman-Tahhan, Ayman, Sandesara, Pratik B., Teren, Andrej, Timmis, Adam, Van de Werf, Frans, Wauters, Els, Wilde, Arthur A. M., Ford, Ian, Stott, David J., Algra, Ale, Andreassi, Maria G., Ardissino, Diego, Arsenault, Benoit J., Ballantyne, Christie M., Bergmeijer, Thomas O., Bezzina, Connie R., Body, Simon C., Bogaty, Peter, de Borst, Gert J., Brenner, Hermann, Burkhardt, Ralph, Carpeggiani, Clara, Condorelli, Gianluigi, Cooper-DeHoff, Rhonda M., Cresci, Sharon, de Faire, Ulf, Doughty, Robert N., Drexel, Heinz, Engert, James C., Fox, Keith A. A., Girelli, Domenico, Hagström, Emil, Hazen, Stanley L., Held, Claes, Hemingway, Harry, Hoefer, Imo E., Hovingh, G. Kees, Johnson, Julie A., De Jong, Pim A., Jukema, J. Wouter, Kaczor, Marcin P., Kahonen, Mika, Kettner, Jiri, Kiliszek, Marek, Klungel, Olaf H., Lagerqvist, Bo, Lambrechts, Diether, Laurikka, Jari O., Lehtimaki, Terho, Lindholm, Daniel, Mahmoodi, Bakhtawar K., Maitland-van der Zee, Anke H., McPherson, Ruth, Melander, Olle, Metspalu, Andres, Pepinski, Witold, Olivieri, Oliviero, Opolski, Grzegorz, Palmer, Colin N., Pasterkamp, Gerard, Pepine, Carl J., Pereira, Alexandre C., Note, Louise, Quyyumi, Arshed A., Richards, A. Mark, Sanak, Marek, Scholz, Markus, Siegbahn, Agneta, Sinisalo, Juha, Smith, J. Gustav, Spertus, John A., Stewart, Alexandre F. R., Szczeklik, Wojciech, Szpakowicz, Anna, ten Berg, Jurrien M., Thanassoulis, George, Thieiy, Joachim, van der Graaf, Yolanda, Visseren, Frank L. J., Waltenberger, Johannes, Van der Harst, Pim, Tardif, Jean-Claude, Sattar, Naveed, Lang, Chim C., Pare, Guillaume, Brophy, James M., Anderson, Jeffrey L., Maerz, Winfried, Wallentin, Lars, Cameron, Vicky A., Horne, Benjamin D., Samani, Nilesh J., Hingorani, Aroon D., and Asselbergs, Folkert W.
Abstract: BACKGROUND: Genetic variation at chromosome 9p21 is a recognized risk factor for coronary heart disease (CHD). However, its effect on disease progression and subsequent events is unclear, raising questions about its value for stratification of residual risk. METHODS: A variant at chromosome 9p21 (rs1333049) was tested for association with subsequent events during follow-up in 103 357 Europeans with established CHD at baseline from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) Consortium (73.1% male, mean age 62.9 years). The primary outcome, subsequent CHD death or myocardial infarction (CHD death/myocardial infarction), occurred in 13 040 of the 93 115 participants with available outcome data. Effect estimates were compared with case/control risk obtained from the CARDIoGRAMplusC4D consortium (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics) including 47 222 CHD cases and 122 264 controls free of CHD. RESULTS: Meta-analyses revealed no significant association between chromosome 9p21 and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline (GENIUSCHD odds ratio, 1.02; 95% CI, 0.99-1.05). This contrasted with a strong association in CARDIoGRAMPlusC4D odds ratio 1.20; 95% CI, 1.18-1.22; P for interaction < 0.001 compared with the GENIUS-CHD estimate. Similarly, no clear associations were identified for additional subsequent outcomes, including all-cause death, although we found a modest positive association between chromosome 9p21 and subsequent revascularization (odds ratio, 1.07; 95% CI, 1.04-1.09). CONCLUSIONS: In contrast to studies comparing individuals with CHD to disease-free controls, we found no clear association between genetic variation at chromosome 9p21 and risk of subsequent acute CHD events when all individuals had CHD at baseline. However, the association with subsequent revascularization may support the post
Published: 2019
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31. Subsequent Event Risk in Individuals With Established Coronary Heart Disease : Design and Rationale of the GENIUS-CHD Consortium

Author: Patel, Riyaz S., Tragante, Vinicius, Schmidt, Amand F., McCubrey, Raymond O., Holmes, Michael, V, Howe, Laurence J., Direk, Kenan, Åkerblom, Axel, Leander, Karin, Virani, Salim S., Kaminski, Karol A., Muehlschlegel, Jochen D., Allayee, Hooman, Almgren, Peter, Alver, Maris, Baranova, Ekaterina, V, Behloui, Hassan, Boeckx, Bram, Braund, Peter S., Breitling, Lutz P., Delgado, Gradela, Duarte, Nubia E., Dube, Marie-Pierre, Dufresne, Line, Eriksson, Niclas, Foco, Luisa, Scholz, Markus, Gijsberts, Crystel M., Glinge, Charlotte, Gong, Yan, Hartiala, Jaana, Heydarpour, Mahyar, Hubacek, Jaroslav A., Kleber, Marcus, Kofink, Daniel, Kotti, Salma, Kuukasjarvi, Pekka, Lee, Vei-Vei, Leiherer, Andreas, Lenzini, Petra A., Levin, Daniel, Lyytikainen, Leo-Pekka, Martinelli, Nicola, Mons, Ute, Nelson, Christopher P., Nikus, Kjell, Pilbrow, Anna P., Ploski, Rafal, Sun, Yan, V, Tanck, Michael W. T., Tang, W. H. Wilson, Trompet, Stella, van der Laan, Sander W., Van Setten, Jessica, Vilmundarson, Ragnar O., Anselmi, Chiara Viviani, Vlachopoulou, Efthymia, Al Ali, Lawien, Boerwinkle, Eric, Briguori, Carlo, Carlquist, John F., Carruthers, Kathryn F., Casu, Gavino, Deanfield, John, Deloukas, Panos, Dudbridge, Frank, Engstrom, Thomas, Fitzpatrick, Natalie, Fox, Kim, Gigante, Bruna, James, Stefan, Lokki, Marja-Liisa, Lotufo, Paulo A., Marziliano, Nicola, Mordi, Ify R., Muhlestein, Joseph B., Newton-Cheh, Christopher, Pitha, Jan, Saely, Christoph H., Samman-Tahhan, Ayman, Sandesara, Pratik B., Teren, Andrej, Timmis, Adam, Van de Werf, Frans, Wauters, Els, Wilde, Arthur A. M., Ford, Ian, Stott, David J., Algra, Ale, Andreassi, Maria G., Ardissino, Diego, Arsenault, Benoit J., Ballantyne, Christie M., Bergmeijer, Thomas O., Bezzina, Connie R., Body, Simon C., Boersma, Eric H., Bogaty, Peter, Bots, Michiel L., Brenner, Hermann, Brugts, Jasper J., Burkhardt, Ralph, Carpeggiani, Clara, Condorelli, Gianluigi, Cooper-DeHoff, Rhonda M., Cresci, Sharon, Danchin, Nicolas, de Faire, Ulf, Doughty, Robert N., Drexel, Heinz, Engert, James C., Fox, Keith A. A., Girelli, Domenico, Grobbee, Diederick E., Hagström, Emil, Hazen, Stanley L., Held, Claes, Hemingway, Harry, Hoefer, Imo E., Hovingh, G. Kees, Jabbari, Reza, Johnson, Julie A., Jukema, J. Wouter, Kaczor, Marcin P., Kahonen, Mika, Kettner, Jiri, Kiliszek, Marek, Klungel, Olaf H., Lagerqvist, Bo, Lambrechts, Diether, Laurikka, Jari O., Lehtimaki, Terho, Lindholm, Daniel, Mahmoodi, B. K., Maitland-van der Zee, Anke H., McPherson, Ruth, Melander, Olle, Metspalu, Andres, Niemcunowicz-Janica, Anna, Olivieri, Oliviero, Opolski, Grzegorz, Palmer, Colin N., Pasterkamp, Gerard, Pepine, Carl J., Pereira, Alexandre C., Pilote, Louise, Quyyumi, Arshed A., Richards, A. Mark, Sanak, Marek, Siegbahn, Agneta, Simon, Tabassome, Sinisalo, Juha, Smith, J. Gustav, Spertus, John A., Stender, Steen, Stewart, Alexandre F. R., Szczeklik, Wojciech, Szpakowicz, Anna, Tardif, Jean-Claude, ten Berg, Jurrien M., Tfelt-Hansen, Jacob, Thanassoulis, George, Thiery, Joachim, Torp-Pedersen, Christian, van der Graaf, Yolanda, Visseren, Frank L. J., Waltenberger, Johannes, Weeke, Peter E., Van der Harst, Pim, Lang, Chim C., Sattar, Naveed, Cameron, Vicky A., Anderson, Jeffrey L., Brophy, James M., Pare, Guillaume, Horne, Benjamin D., Marz, Winfried, Wallentin, Lars, Samani, Nilesh J., Hingorani, Aroon D., Asselbergs, Folkert W., Patel, Riyaz S., Tragante, Vinicius, Schmidt, Amand F., McCubrey, Raymond O., Holmes, Michael, V, Howe, Laurence J., Direk, Kenan, Åkerblom, Axel, Leander, Karin, Virani, Salim S., Kaminski, Karol A., Muehlschlegel, Jochen D., Allayee, Hooman, Almgren, Peter, Alver, Maris, Baranova, Ekaterina, V, Behloui, Hassan, Boeckx, Bram, Braund, Peter S., Breitling, Lutz P., Delgado, Gradela, Duarte, Nubia E., Dube, Marie-Pierre, Dufresne, Line, Eriksson, Niclas, Foco, Luisa, Scholz, Markus, Gijsberts, Crystel M., Glinge, Charlotte, Gong, Yan, Hartiala, Jaana, Heydarpour, Mahyar, Hubacek, Jaroslav A., Kleber, Marcus, Kofink, Daniel, Kotti, Salma, Kuukasjarvi, Pekka, Lee, Vei-Vei, Leiherer, Andreas, Lenzini, Petra A., Levin, Daniel, Lyytikainen, Leo-Pekka, Martinelli, Nicola, Mons, Ute, Nelson, Christopher P., Nikus, Kjell, Pilbrow, Anna P., Ploski, Rafal, Sun, Yan, V, Tanck, Michael W. T., Tang, W. H. Wilson, Trompet, Stella, van der Laan, Sander W., Van Setten, Jessica, Vilmundarson, Ragnar O., Anselmi, Chiara Viviani, Vlachopoulou, Efthymia, Al Ali, Lawien, Boerwinkle, Eric, Briguori, Carlo, Carlquist, John F., Carruthers, Kathryn F., Casu, Gavino, Deanfield, John, Deloukas, Panos, Dudbridge, Frank, Engstrom, Thomas, Fitzpatrick, Natalie, Fox, Kim, Gigante, Bruna, James, Stefan, Lokki, Marja-Liisa, Lotufo, Paulo A., Marziliano, Nicola, Mordi, Ify R., Muhlestein, Joseph B., Newton-Cheh, Christopher, Pitha, Jan, Saely, Christoph H., Samman-Tahhan, Ayman, Sandesara, Pratik B., Teren, Andrej, Timmis, Adam, Van de Werf, Frans, Wauters, Els, Wilde, Arthur A. M., Ford, Ian, Stott, David J., Algra, Ale, Andreassi, Maria G., Ardissino, Diego, Arsenault, Benoit J., Ballantyne, Christie M., Bergmeijer, Thomas O., Bezzina, Connie R., Body, Simon C., Boersma, Eric H., Bogaty, Peter, Bots, Michiel L., Brenner, Hermann, Brugts, Jasper J., Burkhardt, Ralph, Carpeggiani, Clara, Condorelli, Gianluigi, Cooper-DeHoff, Rhonda M., Cresci, Sharon, Danchin, Nicolas, de Faire, Ulf, Doughty, Robert N., Drexel, Heinz, Engert, James C., Fox, Keith A. A., Girelli, Domenico, Grobbee, Diederick E., Hagström, Emil, Hazen, Stanley L., Held, Claes, Hemingway, Harry, Hoefer, Imo E., Hovingh, G. Kees, Jabbari, Reza, Johnson, Julie A., Jukema, J. Wouter, Kaczor, Marcin P., Kahonen, Mika, Kettner, Jiri, Kiliszek, Marek, Klungel, Olaf H., Lagerqvist, Bo, Lambrechts, Diether, Laurikka, Jari O., Lehtimaki, Terho, Lindholm, Daniel, Mahmoodi, B. K., Maitland-van der Zee, Anke H., McPherson, Ruth, Melander, Olle, Metspalu, Andres, Niemcunowicz-Janica, Anna, Olivieri, Oliviero, Opolski, Grzegorz, Palmer, Colin N., Pasterkamp, Gerard, Pepine, Carl J., Pereira, Alexandre C., Pilote, Louise, Quyyumi, Arshed A., Richards, A. Mark, Sanak, Marek, Siegbahn, Agneta, Simon, Tabassome, Sinisalo, Juha, Smith, J. Gustav, Spertus, John A., Stender, Steen, Stewart, Alexandre F. R., Szczeklik, Wojciech, Szpakowicz, Anna, Tardif, Jean-Claude, ten Berg, Jurrien M., Tfelt-Hansen, Jacob, Thanassoulis, George, Thiery, Joachim, Torp-Pedersen, Christian, van der Graaf, Yolanda, Visseren, Frank L. J., Waltenberger, Johannes, Weeke, Peter E., Van der Harst, Pim, Lang, Chim C., Sattar, Naveed, Cameron, Vicky A., Anderson, Jeffrey L., Brophy, James M., Pare, Guillaume, Horne, Benjamin D., Marz, Winfried, Wallentin, Lars, Samani, Nilesh J., Hingorani, Aroon D., and Asselbergs, Folkert W.
Abstract: BACKGROUND: The Genetics of Subsequent Coronary Heart Disease (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD. METHODS: The consortium currently includes 57 studies from 18 countries, recruiting 185 614 participants with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events. RESULTS: Enrollment into the individual studies took place between 1985 to present day with a duration of follow-up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38%-100%), mostly male (44%-91%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (hazard ratio, 1.15; 95% CI, 1.14-1.16) per 5-year increase, male sex (hazard ratio, 1.17; 95% CI, 1.13-1.21) and smoking (hazard ratio, 1.43; 95% CI, 1.35-1.51) with risk of subsequent CHD death or myocardial infarction and differing associations with other individual and composite cardiovascular endpoints. CONCLUSIONS: GENIUS-CHD is a global collaboration seeking to elucidate genetic and nongenetic determinants of subsequent event risk in individuals with established CHD, to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators.
Published: 2019
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32. Association between fat mass through adolescence and arterial stiffness : a population-based study from The Avon Longitudinal Study of Parents and Children

Author: Dangardt, Frida, Charakida, Marietta, Georgiopoulos, Georgios, Chiesa, Scott T., Rapala, Alicja, Wade, Kaitlin H., Hughes, Alun D., Timpson, Nicholas J., Pateras, Konstantinos, Finer, Nick, Sattar, Naveed, Davey Smith, George, Lawlor, Debbie A., Deanfield, John E., Dangardt, Frida, Charakida, Marietta, Georgiopoulos, Georgios, Chiesa, Scott T., Rapala, Alicja, Wade, Kaitlin H., Hughes, Alun D., Timpson, Nicholas J., Pateras, Konstantinos, Finer, Nick, Sattar, Naveed, Davey Smith, George, Lawlor, Debbie A., and Deanfield, John E.
Published: 2019

33. Subsequent Event Risk in Individuals with Established Coronary Heart Disease : Design and Rationale of the GENIUS-CHD Consortium

Author: Patel, Riyaz S., Tragante, Vinicius, Schmidt, Amand F., McCubrey, Raymond O., Holmes, Michael V., Howe, Laurence J., Direk, Kenan, Åkerblom, Axel, Leander, Karin, Virani, Salim S., Kaminski, Karol A., Muehlschlegel, Jochen D., Allayee, Hooman, Almgren, Peter, Alver, Maris, Baranova, Ekaterina V., Behloui, Hassan, Boeckx, Bram, Braund, Peter S., Breitling, Lutz P., Delgado, Graciela, Duarte, Nubia E., Dubé, Marie Pierre, Dufresne, Line, Eriksson, Niclas, Foco, Luisa, Scholz, Markus, Gijsberts, Crystel M., Glinge, Charlotte, Gong, Yan, Hartiala, Jaana, Heydarpour, Mahyar, Hubacek, Jaroslav A., Kleber, Marcus, Kofink, Daniel, Kotti, Salma, Kuukasjärvi, Pekka, Lee, Vei Vei, Leiherer, Andreas, Lenzini, Petra A., Levin, Daniel, Lyytikäinen, Leo Pekka, Martinelli, Nicola, Mons, Ute, Nelson, Christopher P., Nikus, Kjell, Pilbrow, Anna P., Ploski, Rafal, Sun, Yan V., Tanck, Michael W.T., Tang, W. H.Wilson, Trompet, Stella, van der Laan, Sander W., Van Setten, Jessica, Vilmundarson, Ragnar O., Viviani Anselmi, Chiara, Vlachopoulou, Efthymia, Al Ali, Lawien, Boerwinkle, Eric, Briguori, Carlo, Carlquist, John F., Carruthers, Kathryn F., Casu, Gavino, Deanfield, John, Deloukas, Panos, Dudbridge, Frank, Engstrøm, Thomas, Fitzpatrick, Natalie, Fox, Kim, Gigante, Bruna, James, Stefan, Lokki, Marja Liisa, Lotufo, Paulo A., Marziliano, Nicola, Mordi, Ify R., Muhlestein, Joseph B., Newton-Cheh, Christopher, Pitha, Jan, Saely, Christoph H., Samman-Tahhan, Ayman, Sandesara, Pratik B., Teren, Andrej, Timmis, Adam, Van de Werf, Frans, Wauters, Els, Wilde, Arthur A.M., Ford, Ian, Stott, David J., Algra, Ale, Andreassi, Maria G., Ardissino, Diego, Arsenault, Benoit J., Ballantyne, Christie M., Bergmeijer, Thomas O., Bezzina, Connie R., Body, Simon C., Boersma, Eric H., Bogaty, Peter, Bots, Michiel L., Brenner, Hermann, Brugts, Jasper J., Burkhardt, Ralph, Carpeggiani, Clara, Condorelli, Gianluigi, Cooper-DeHoff, Rhonda M., Cresci, Sharon, Danchin, Nicolas, de Faire, Ulf, Doughty, Robert N., Drexel, Heinz, Engert, James C., Fox, Keith A.A., Girelli, Domenico, Grobbee, Diederick E., Hagström, Emil, Hazen, Stanley L., Held, Claes, Hemingway, Harry, Hoefer, Imo E., Hovingh, G. Kees, Jabbari, Reza, Johnson, Julie A., Jukema, J. Wouter, Kaczor, Marcin P., Kähönen, Mika, Kettner, Jiri, Kiliszek, Marek, Klungel, Olaf H., Lagerqvist, Bo, Lambrechts, Diether, Laurikka, Jari O., Lehtimäki, Terho, Lindholm, Daniel, Mahmoodi, B. K., Maitland-van der Zee, Anke H., McPherson, Ruth, Melander, Olle, Metspalu, Andres, Niemcunowicz-Janica, Anna, Olivieri, Oliviero, Opolski, Grzegorz, Palmer, Colin N., Pasterkamp, Gerard, Pepine, Carl J., Pereira, Alexandre C., Pilote, Louise, Quyyumi, Arshed A., Richards, A. Mark, Sanak, Marek, Siegbahn, Agneta, Simon, Tabassome, Sinisalo, Juha, Smith, J. Gustav, Spertus, John A., Stender, Steen, Stewart, Alexandre F.R., Szczeklik, Wojciech, Szpakowicz, Anna, Tardif, Jean Claude, Ten Berg, Jurriën M., Tfelt-Hansen, Jacob, Thanassoulis, George, Thiery, Joachim, Torp-Pedersen, Christian, van der Graaf, Yolanda, Visseren, Frank L.J., Waltenberger, Johannes, Weeke, Peter E., Van der Harst, Pim, Lang, Chim C., Sattar, Naveed, Cameron, Vicky A., Anderson, Jeffrey L., Brophy, James M., Pare, Guillaume, Horne, Benjamin D., März, Winfried, Wallentin, Lars, Samani, Nilesh J., Hingorani, Aroon D., Asselbergs, Folkert W., Patel, Riyaz S., Tragante, Vinicius, Schmidt, Amand F., McCubrey, Raymond O., Holmes, Michael V., Howe, Laurence J., Direk, Kenan, Åkerblom, Axel, Leander, Karin, Virani, Salim S., Kaminski, Karol A., Muehlschlegel, Jochen D., Allayee, Hooman, Almgren, Peter, Alver, Maris, Baranova, Ekaterina V., Behloui, Hassan, Boeckx, Bram, Braund, Peter S., Breitling, Lutz P., Delgado, Graciela, Duarte, Nubia E., Dubé, Marie Pierre, Dufresne, Line, Eriksson, Niclas, Foco, Luisa, Scholz, Markus, Gijsberts, Crystel M., Glinge, Charlotte, Gong, Yan, Hartiala, Jaana, Heydarpour, Mahyar, Hubacek, Jaroslav A., Kleber, Marcus, Kofink, Daniel, Kotti, Salma, Kuukasjärvi, Pekka, Lee, Vei Vei, Leiherer, Andreas, Lenzini, Petra A., Levin, Daniel, Lyytikäinen, Leo Pekka, Martinelli, Nicola, Mons, Ute, Nelson, Christopher P., Nikus, Kjell, Pilbrow, Anna P., Ploski, Rafal, Sun, Yan V., Tanck, Michael W.T., Tang, W. H.Wilson, Trompet, Stella, van der Laan, Sander W., Van Setten, Jessica, Vilmundarson, Ragnar O., Viviani Anselmi, Chiara, Vlachopoulou, Efthymia, Al Ali, Lawien, Boerwinkle, Eric, Briguori, Carlo, Carlquist, John F., Carruthers, Kathryn F., Casu, Gavino, Deanfield, John, Deloukas, Panos, Dudbridge, Frank, Engstrøm, Thomas, Fitzpatrick, Natalie, Fox, Kim, Gigante, Bruna, James, Stefan, Lokki, Marja Liisa, Lotufo, Paulo A., Marziliano, Nicola, Mordi, Ify R., Muhlestein, Joseph B., Newton-Cheh, Christopher, Pitha, Jan, Saely, Christoph H., Samman-Tahhan, Ayman, Sandesara, Pratik B., Teren, Andrej, Timmis, Adam, Van de Werf, Frans, Wauters, Els, Wilde, Arthur A.M., Ford, Ian, Stott, David J., Algra, Ale, Andreassi, Maria G., Ardissino, Diego, Arsenault, Benoit J., Ballantyne, Christie M., Bergmeijer, Thomas O., Bezzina, Connie R., Body, Simon C., Boersma, Eric H., Bogaty, Peter, Bots, Michiel L., Brenner, Hermann, Brugts, Jasper J., Burkhardt, Ralph, Carpeggiani, Clara, Condorelli, Gianluigi, Cooper-DeHoff, Rhonda M., Cresci, Sharon, Danchin, Nicolas, de Faire, Ulf, Doughty, Robert N., Drexel, Heinz, Engert, James C., Fox, Keith A.A., Girelli, Domenico, Grobbee, Diederick E., Hagström, Emil, Hazen, Stanley L., Held, Claes, Hemingway, Harry, Hoefer, Imo E., Hovingh, G. Kees, Jabbari, Reza, Johnson, Julie A., Jukema, J. Wouter, Kaczor, Marcin P., Kähönen, Mika, Kettner, Jiri, Kiliszek, Marek, Klungel, Olaf H., Lagerqvist, Bo, Lambrechts, Diether, Laurikka, Jari O., Lehtimäki, Terho, Lindholm, Daniel, Mahmoodi, B. K., Maitland-van der Zee, Anke H., McPherson, Ruth, Melander, Olle, Metspalu, Andres, Niemcunowicz-Janica, Anna, Olivieri, Oliviero, Opolski, Grzegorz, Palmer, Colin N., Pasterkamp, Gerard, Pepine, Carl J., Pereira, Alexandre C., Pilote, Louise, Quyyumi, Arshed A., Richards, A. Mark, Sanak, Marek, Siegbahn, Agneta, Simon, Tabassome, Sinisalo, Juha, Smith, J. Gustav, Spertus, John A., Stender, Steen, Stewart, Alexandre F.R., Szczeklik, Wojciech, Szpakowicz, Anna, Tardif, Jean Claude, Ten Berg, Jurriën M., Tfelt-Hansen, Jacob, Thanassoulis, George, Thiery, Joachim, Torp-Pedersen, Christian, van der Graaf, Yolanda, Visseren, Frank L.J., Waltenberger, Johannes, Weeke, Peter E., Van der Harst, Pim, Lang, Chim C., Sattar, Naveed, Cameron, Vicky A., Anderson, Jeffrey L., Brophy, James M., Pare, Guillaume, Horne, Benjamin D., März, Winfried, Wallentin, Lars, Samani, Nilesh J., Hingorani, Aroon D., and Asselbergs, Folkert W.
Published: 2019

34. Association of Chromosome 9p21 With Subsequent Coronary Heart Disease Events : A GENIUS-CHD Study of Individual Participant Data

Author: Patel, Riyaz S., Schmidt, Amand F., Tragante, Vinicius, McCubrey, Raymond O., Holmes, Michael, V, Howe, Laurence J., Direk, Kenan, Åkerblom, Axel, Leander, Karin, Virani, Salim S., Kaminski, Karol A., Muehlschlegel, Jochen D., Dube, Marie-Pierre, Allayee, Hooman, Almgren, Peter, Alver, Maris, Baranova, Ekaterina, V, Behlouli, Hassan, Boeckx, Bram, Braund, Peter S., Breitling, Lutz P., Delgado, Graciela, Duarte, Nubia E., Dufresne, Line, Eriksson, Niclas, Foco, Luisa, Gijsberts, Crystel M., Gong, Yan, Hartiala, Jaana, Heydarpour, Mahyar, Hubacek, Jaroslav A., Kleber, Marcus, Kofink, Daniel, Kuukasjarvi, Pekka, Lee, Vei-Vei, Leiherer, Andreas, Lenzini, Petra A., Levin, Daniel, Lyytikainen, Leo-Pekka, Martinelli, Nicola, Mons, Ute, Nelson, Christopher P., Nikus, Kjell, Pilbrow, Anna P., Ploski, Rafal, Sun, Yan, V, Tanck, Michael W. T., Tang, W. H. Wilson, Trompet, Stella, van der Laan, Sander W., van Setten, Jessica, Vilmundarson, Ragnar O., Anselmi, Chiara Viviani, Vlachopoulou, Efthymia, Boerwinkle, Eric, Briguori, Carlo, Carlquist, John F., Carruthers, Kathryn F., Casu, Gavino, Deanfield, John, Deloukas, Panos, Dudbridge, Frank, Fitzpatrick, Natalie, Gigante, Bruna, James, Stefan, Lokki, Marja-Liisa, Lotufo, Paulo A., Marziliano, Nicola, Mordi, Ify R., Muhlestein, Joseph B., Cheh, Chris Newton, Pitha, Jan, Saely, Christoph H., Samman-Tahhan, Ayman, Sandesara, Pratik B., Teren, Andrej, Timmis, Adam, Van de Werf, Frans, Wauters, Els, Wilde, Arthur A. M., Ford, Ian, Stott, David J., Algra, Ale, Andreassi, Maria G., Ardissino, Diego, Arsenault, Benoit J., Ballantyne, Christie M., Bergmeijer, Thomas O., Bezzina, Connie R., Body, Simon C., Bogaty, Peter, de Borst, Gert J., Brenner, Hermann, Burkhardt, Ralph, Carpeggiani, Clara, Condorelli, Gianluigi, Cooper-DeHoff, Rhonda M., Cresci, Sharon, de Faire, Ulf, Doughty, Robert N., Drexel, Heinz, Engert, James C., Fox, Keith A. A., Girelli, Domenico, Hagström, Emil, Hazen, Stanley L., Held, Claes, Hemingway, Harry, Hoefer, Imo E., Hovingh, G. Kees, Johnson, Julie A., De Jong, Pim A., Jukema, J. Wouter, Kaczor, Marcin P., Kahonen, Mika, Kettner, Jiri, Kiliszek, Marek, Klungel, Olaf H., Lagerqvist, Bo, Lambrechts, Diether, Laurikka, Jari O., Lehtimaki, Terho, Lindholm, Daniel, Mahmoodi, Bakhtawar K., Maitland-van der Zee, Anke H., McPherson, Ruth, Melander, Olle, Metspalu, Andres, Pepinski, Witold, Olivieri, Oliviero, Opolski, Grzegorz, Palmer, Colin N., Pasterkamp, Gerard, Pepine, Carl J., Pereira, Alexandre C., Note, Louise, Quyyumi, Arshed A., Richards, A. Mark, Sanak, Marek, Scholz, Markus, Siegbahn, Agneta, Sinisalo, Juha, Smith, J. Gustav, Spertus, John A., Stewart, Alexandre F. R., Szczeklik, Wojciech, Szpakowicz, Anna, ten Berg, Jurrien M., Thanassoulis, George, Thieiy, Joachim, van der Graaf, Yolanda, Visseren, Frank L. J., Waltenberger, Johannes, Van der Harst, Pim, Tardif, Jean-Claude, Sattar, Naveed, Lang, Chim C., Pare, Guillaume, Brophy, James M., Anderson, Jeffrey L., Maerz, Winfried, Wallentin, Lars, Cameron, Vicky A., Horne, Benjamin D., Samani, Nilesh J., Hingorani, Aroon D., Asselbergs, Folkert W., Patel, Riyaz S., Schmidt, Amand F., Tragante, Vinicius, McCubrey, Raymond O., Holmes, Michael, V, Howe, Laurence J., Direk, Kenan, Åkerblom, Axel, Leander, Karin, Virani, Salim S., Kaminski, Karol A., Muehlschlegel, Jochen D., Dube, Marie-Pierre, Allayee, Hooman, Almgren, Peter, Alver, Maris, Baranova, Ekaterina, V, Behlouli, Hassan, Boeckx, Bram, Braund, Peter S., Breitling, Lutz P., Delgado, Graciela, Duarte, Nubia E., Dufresne, Line, Eriksson, Niclas, Foco, Luisa, Gijsberts, Crystel M., Gong, Yan, Hartiala, Jaana, Heydarpour, Mahyar, Hubacek, Jaroslav A., Kleber, Marcus, Kofink, Daniel, Kuukasjarvi, Pekka, Lee, Vei-Vei, Leiherer, Andreas, Lenzini, Petra A., Levin, Daniel, Lyytikainen, Leo-Pekka, Martinelli, Nicola, Mons, Ute, Nelson, Christopher P., Nikus, Kjell, Pilbrow, Anna P., Ploski, Rafal, Sun, Yan, V, Tanck, Michael W. T., Tang, W. H. Wilson, Trompet, Stella, van der Laan, Sander W., van Setten, Jessica, Vilmundarson, Ragnar O., Anselmi, Chiara Viviani, Vlachopoulou, Efthymia, Boerwinkle, Eric, Briguori, Carlo, Carlquist, John F., Carruthers, Kathryn F., Casu, Gavino, Deanfield, John, Deloukas, Panos, Dudbridge, Frank, Fitzpatrick, Natalie, Gigante, Bruna, James, Stefan, Lokki, Marja-Liisa, Lotufo, Paulo A., Marziliano, Nicola, Mordi, Ify R., Muhlestein, Joseph B., Cheh, Chris Newton, Pitha, Jan, Saely, Christoph H., Samman-Tahhan, Ayman, Sandesara, Pratik B., Teren, Andrej, Timmis, Adam, Van de Werf, Frans, Wauters, Els, Wilde, Arthur A. M., Ford, Ian, Stott, David J., Algra, Ale, Andreassi, Maria G., Ardissino, Diego, Arsenault, Benoit J., Ballantyne, Christie M., Bergmeijer, Thomas O., Bezzina, Connie R., Body, Simon C., Bogaty, Peter, de Borst, Gert J., Brenner, Hermann, Burkhardt, Ralph, Carpeggiani, Clara, Condorelli, Gianluigi, Cooper-DeHoff, Rhonda M., Cresci, Sharon, de Faire, Ulf, Doughty, Robert N., Drexel, Heinz, Engert, James C., Fox, Keith A. A., Girelli, Domenico, Hagström, Emil, Hazen, Stanley L., Held, Claes, Hemingway, Harry, Hoefer, Imo E., Hovingh, G. Kees, Johnson, Julie A., De Jong, Pim A., Jukema, J. Wouter, Kaczor, Marcin P., Kahonen, Mika, Kettner, Jiri, Kiliszek, Marek, Klungel, Olaf H., Lagerqvist, Bo, Lambrechts, Diether, Laurikka, Jari O., Lehtimaki, Terho, Lindholm, Daniel, Mahmoodi, Bakhtawar K., Maitland-van der Zee, Anke H., McPherson, Ruth, Melander, Olle, Metspalu, Andres, Pepinski, Witold, Olivieri, Oliviero, Opolski, Grzegorz, Palmer, Colin N., Pasterkamp, Gerard, Pepine, Carl J., Pereira, Alexandre C., Note, Louise, Quyyumi, Arshed A., Richards, A. Mark, Sanak, Marek, Scholz, Markus, Siegbahn, Agneta, Sinisalo, Juha, Smith, J. Gustav, Spertus, John A., Stewart, Alexandre F. R., Szczeklik, Wojciech, Szpakowicz, Anna, ten Berg, Jurrien M., Thanassoulis, George, Thieiy, Joachim, van der Graaf, Yolanda, Visseren, Frank L. J., Waltenberger, Johannes, Van der Harst, Pim, Tardif, Jean-Claude, Sattar, Naveed, Lang, Chim C., Pare, Guillaume, Brophy, James M., Anderson, Jeffrey L., Maerz, Winfried, Wallentin, Lars, Cameron, Vicky A., Horne, Benjamin D., Samani, Nilesh J., Hingorani, Aroon D., and Asselbergs, Folkert W.
Abstract: BACKGROUND: Genetic variation at chromosome 9p21 is a recognized risk factor for coronary heart disease (CHD). However, its effect on disease progression and subsequent events is unclear, raising questions about its value for stratification of residual risk. METHODS: A variant at chromosome 9p21 (rs1333049) was tested for association with subsequent events during follow-up in 103 357 Europeans with established CHD at baseline from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) Consortium (73.1% male, mean age 62.9 years). The primary outcome, subsequent CHD death or myocardial infarction (CHD death/myocardial infarction), occurred in 13 040 of the 93 115 participants with available outcome data. Effect estimates were compared with case/control risk obtained from the CARDIoGRAMplusC4D consortium (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics) including 47 222 CHD cases and 122 264 controls free of CHD. RESULTS: Meta-analyses revealed no significant association between chromosome 9p21 and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline (GENIUSCHD odds ratio, 1.02; 95% CI, 0.99-1.05). This contrasted with a strong association in CARDIoGRAMPlusC4D odds ratio 1.20; 95% CI, 1.18-1.22; P for interaction < 0.001 compared with the GENIUS-CHD estimate. Similarly, no clear associations were identified for additional subsequent outcomes, including all-cause death, although we found a modest positive association between chromosome 9p21 and subsequent revascularization (odds ratio, 1.07; 95% CI, 1.04-1.09). CONCLUSIONS: In contrast to studies comparing individuals with CHD to disease-free controls, we found no clear association between genetic variation at chromosome 9p21 and risk of subsequent acute CHD events when all individuals had CHD at baseline. However, the association with subsequent revascularization may support the post
Published: 2019
Full Text: View/download PDF

35. Subsequent Event Risk in Individuals With Established Coronary Heart Disease : Design and Rationale of the GENIUS-CHD Consortium

Author: Patel, Riyaz S., Tragante, Vinicius, Schmidt, Amand F., McCubrey, Raymond O., Holmes, Michael, V, Howe, Laurence J., Direk, Kenan, Åkerblom, Axel, Leander, Karin, Virani, Salim S., Kaminski, Karol A., Muehlschlegel, Jochen D., Allayee, Hooman, Almgren, Peter, Alver, Maris, Baranova, Ekaterina, V, Behloui, Hassan, Boeckx, Bram, Braund, Peter S., Breitling, Lutz P., Delgado, Gradela, Duarte, Nubia E., Dube, Marie-Pierre, Dufresne, Line, Eriksson, Niclas, Foco, Luisa, Scholz, Markus, Gijsberts, Crystel M., Glinge, Charlotte, Gong, Yan, Hartiala, Jaana, Heydarpour, Mahyar, Hubacek, Jaroslav A., Kleber, Marcus, Kofink, Daniel, Kotti, Salma, Kuukasjarvi, Pekka, Lee, Vei-Vei, Leiherer, Andreas, Lenzini, Petra A., Levin, Daniel, Lyytikainen, Leo-Pekka, Martinelli, Nicola, Mons, Ute, Nelson, Christopher P., Nikus, Kjell, Pilbrow, Anna P., Ploski, Rafal, Sun, Yan, V, Tanck, Michael W. T., Tang, W. H. Wilson, Trompet, Stella, van der Laan, Sander W., Van Setten, Jessica, Vilmundarson, Ragnar O., Anselmi, Chiara Viviani, Vlachopoulou, Efthymia, Al Ali, Lawien, Boerwinkle, Eric, Briguori, Carlo, Carlquist, John F., Carruthers, Kathryn F., Casu, Gavino, Deanfield, John, Deloukas, Panos, Dudbridge, Frank, Engstrom, Thomas, Fitzpatrick, Natalie, Fox, Kim, Gigante, Bruna, James, Stefan, Lokki, Marja-Liisa, Lotufo, Paulo A., Marziliano, Nicola, Mordi, Ify R., Muhlestein, Joseph B., Newton-Cheh, Christopher, Pitha, Jan, Saely, Christoph H., Samman-Tahhan, Ayman, Sandesara, Pratik B., Teren, Andrej, Timmis, Adam, Van de Werf, Frans, Wauters, Els, Wilde, Arthur A. M., Ford, Ian, Stott, David J., Algra, Ale, Andreassi, Maria G., Ardissino, Diego, Arsenault, Benoit J., Ballantyne, Christie M., Bergmeijer, Thomas O., Bezzina, Connie R., Body, Simon C., Boersma, Eric H., Bogaty, Peter, Bots, Michiel L., Brenner, Hermann, Brugts, Jasper J., Burkhardt, Ralph, Carpeggiani, Clara, Condorelli, Gianluigi, Cooper-DeHoff, Rhonda M., Cresci, Sharon, Danchin, Nicolas, de Faire, Ulf, Doughty, Robert N., Drexel, Heinz, Engert, James C., Fox, Keith A. A., Girelli, Domenico, Grobbee, Diederick E., Hagström, Emil, Hazen, Stanley L., Held, Claes, Hemingway, Harry, Hoefer, Imo E., Hovingh, G. Kees, Jabbari, Reza, Johnson, Julie A., Jukema, J. Wouter, Kaczor, Marcin P., Kahonen, Mika, Kettner, Jiri, Kiliszek, Marek, Klungel, Olaf H., Lagerqvist, Bo, Lambrechts, Diether, Laurikka, Jari O., Lehtimaki, Terho, Lindholm, Daniel, Mahmoodi, B. K., Maitland-van der Zee, Anke H., McPherson, Ruth, Melander, Olle, Metspalu, Andres, Niemcunowicz-Janica, Anna, Olivieri, Oliviero, Opolski, Grzegorz, Palmer, Colin N., Pasterkamp, Gerard, Pepine, Carl J., Pereira, Alexandre C., Pilote, Louise, Quyyumi, Arshed A., Richards, A. Mark, Sanak, Marek, Siegbahn, Agneta, Simon, Tabassome, Sinisalo, Juha, Smith, J. Gustav, Spertus, John A., Stender, Steen, Stewart, Alexandre F. R., Szczeklik, Wojciech, Szpakowicz, Anna, Tardif, Jean-Claude, ten Berg, Jurrien M., Tfelt-Hansen, Jacob, Thanassoulis, George, Thiery, Joachim, Torp-Pedersen, Christian, van der Graaf, Yolanda, Visseren, Frank L. J., Waltenberger, Johannes, Weeke, Peter E., Van der Harst, Pim, Lang, Chim C., Sattar, Naveed, Cameron, Vicky A., Anderson, Jeffrey L., Brophy, James M., Pare, Guillaume, Horne, Benjamin D., Marz, Winfried, Wallentin, Lars, Samani, Nilesh J., Hingorani, Aroon D., Asselbergs, Folkert W., Patel, Riyaz S., Tragante, Vinicius, Schmidt, Amand F., McCubrey, Raymond O., Holmes, Michael, V, Howe, Laurence J., Direk, Kenan, Åkerblom, Axel, Leander, Karin, Virani, Salim S., Kaminski, Karol A., Muehlschlegel, Jochen D., Allayee, Hooman, Almgren, Peter, Alver, Maris, Baranova, Ekaterina, V, Behloui, Hassan, Boeckx, Bram, Braund, Peter S., Breitling, Lutz P., Delgado, Gradela, Duarte, Nubia E., Dube, Marie-Pierre, Dufresne, Line, Eriksson, Niclas, Foco, Luisa, Scholz, Markus, Gijsberts, Crystel M., Glinge, Charlotte, Gong, Yan, Hartiala, Jaana, Heydarpour, Mahyar, Hubacek, Jaroslav A., Kleber, Marcus, Kofink, Daniel, Kotti, Salma, Kuukasjarvi, Pekka, Lee, Vei-Vei, Leiherer, Andreas, Lenzini, Petra A., Levin, Daniel, Lyytikainen, Leo-Pekka, Martinelli, Nicola, Mons, Ute, Nelson, Christopher P., Nikus, Kjell, Pilbrow, Anna P., Ploski, Rafal, Sun, Yan, V, Tanck, Michael W. T., Tang, W. H. Wilson, Trompet, Stella, van der Laan, Sander W., Van Setten, Jessica, Vilmundarson, Ragnar O., Anselmi, Chiara Viviani, Vlachopoulou, Efthymia, Al Ali, Lawien, Boerwinkle, Eric, Briguori, Carlo, Carlquist, John F., Carruthers, Kathryn F., Casu, Gavino, Deanfield, John, Deloukas, Panos, Dudbridge, Frank, Engstrom, Thomas, Fitzpatrick, Natalie, Fox, Kim, Gigante, Bruna, James, Stefan, Lokki, Marja-Liisa, Lotufo, Paulo A., Marziliano, Nicola, Mordi, Ify R., Muhlestein, Joseph B., Newton-Cheh, Christopher, Pitha, Jan, Saely, Christoph H., Samman-Tahhan, Ayman, Sandesara, Pratik B., Teren, Andrej, Timmis, Adam, Van de Werf, Frans, Wauters, Els, Wilde, Arthur A. M., Ford, Ian, Stott, David J., Algra, Ale, Andreassi, Maria G., Ardissino, Diego, Arsenault, Benoit J., Ballantyne, Christie M., Bergmeijer, Thomas O., Bezzina, Connie R., Body, Simon C., Boersma, Eric H., Bogaty, Peter, Bots, Michiel L., Brenner, Hermann, Brugts, Jasper J., Burkhardt, Ralph, Carpeggiani, Clara, Condorelli, Gianluigi, Cooper-DeHoff, Rhonda M., Cresci, Sharon, Danchin, Nicolas, de Faire, Ulf, Doughty, Robert N., Drexel, Heinz, Engert, James C., Fox, Keith A. A., Girelli, Domenico, Grobbee, Diederick E., Hagström, Emil, Hazen, Stanley L., Held, Claes, Hemingway, Harry, Hoefer, Imo E., Hovingh, G. Kees, Jabbari, Reza, Johnson, Julie A., Jukema, J. Wouter, Kaczor, Marcin P., Kahonen, Mika, Kettner, Jiri, Kiliszek, Marek, Klungel, Olaf H., Lagerqvist, Bo, Lambrechts, Diether, Laurikka, Jari O., Lehtimaki, Terho, Lindholm, Daniel, Mahmoodi, B. K., Maitland-van der Zee, Anke H., McPherson, Ruth, Melander, Olle, Metspalu, Andres, Niemcunowicz-Janica, Anna, Olivieri, Oliviero, Opolski, Grzegorz, Palmer, Colin N., Pasterkamp, Gerard, Pepine, Carl J., Pereira, Alexandre C., Pilote, Louise, Quyyumi, Arshed A., Richards, A. Mark, Sanak, Marek, Siegbahn, Agneta, Simon, Tabassome, Sinisalo, Juha, Smith, J. Gustav, Spertus, John A., Stender, Steen, Stewart, Alexandre F. R., Szczeklik, Wojciech, Szpakowicz, Anna, Tardif, Jean-Claude, ten Berg, Jurrien M., Tfelt-Hansen, Jacob, Thanassoulis, George, Thiery, Joachim, Torp-Pedersen, Christian, van der Graaf, Yolanda, Visseren, Frank L. J., Waltenberger, Johannes, Weeke, Peter E., Van der Harst, Pim, Lang, Chim C., Sattar, Naveed, Cameron, Vicky A., Anderson, Jeffrey L., Brophy, James M., Pare, Guillaume, Horne, Benjamin D., Marz, Winfried, Wallentin, Lars, Samani, Nilesh J., Hingorani, Aroon D., and Asselbergs, Folkert W.
Abstract: BACKGROUND: The Genetics of Subsequent Coronary Heart Disease (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD. METHODS: The consortium currently includes 57 studies from 18 countries, recruiting 185 614 participants with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events. RESULTS: Enrollment into the individual studies took place between 1985 to present day with a duration of follow-up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38%-100%), mostly male (44%-91%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (hazard ratio, 1.15; 95% CI, 1.14-1.16) per 5-year increase, male sex (hazard ratio, 1.17; 95% CI, 1.13-1.21) and smoking (hazard ratio, 1.43; 95% CI, 1.35-1.51) with risk of subsequent CHD death or myocardial infarction and differing associations with other individual and composite cardiovascular endpoints. CONCLUSIONS: GENIUS-CHD is a global collaboration seeking to elucidate genetic and nongenetic determinants of subsequent event risk in individuals with established CHD, to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators.
Published: 2019
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36. Association between fat mass through adolescence and arterial stiffness: a population-based study from The Avon Longitudinal Study of Parents and Children

Author: Biostatistiek Onderzoek, Circulatory Health, Dangardt, Frida, Charakida, Marietta, Georgiopoulos, Georgios, Chiesa, Scott T., Rapala, Alicja, Wade, Kaitlin H., Hughes, Alun D., Timpson, Nicholas J., Pateras, Konstantinos, Finer, Nick, Sattar, Naveed, Davey Smith, George, Lawlor, Debbie A., Deanfield, John E., Biostatistiek Onderzoek, Circulatory Health, Dangardt, Frida, Charakida, Marietta, Georgiopoulos, Georgios, Chiesa, Scott T., Rapala, Alicja, Wade, Kaitlin H., Hughes, Alun D., Timpson, Nicholas J., Pateras, Konstantinos, Finer, Nick, Sattar, Naveed, Davey Smith, George, Lawlor, Debbie A., and Deanfield, John E.
Published: 2019

37. Subsequent Event Risk in Individuals with Established Coronary Heart Disease: Design and Rationale of the GENIUS-CHD Consortium

Author: Onderzoek Precision medicine, Circulatory Health, UMC Utrecht, Aios en Stafsecr. Cardiologie, Experimentele Afd. Cardiologie 1, Apotheek Klinische Farmacie Kinderen, CDL Onderzoek Pasterkamp, Cardiovasculaire Epi Team 6, ZL Cerebrovasculaire Ziekten Medisch, Brain, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Cardiovasculaire Epi Team 5, Cardiovasculaire Epi Team 9, CDL Arcadia, Global Health, JC onderzoeksprogramma Methodologie, dLAB Afdelingen, Device, Interne Geneeskunde Vasculaire, Team Medisch, Patel, Riyaz S., Tragante, Vinicius, Schmidt, Amand F., McCubrey, Raymond O., Holmes, Michael V., Howe, Laurence J., Direk, Kenan, Åkerblom, Axel, Leander, Karin, Virani, Salim S., Kaminski, Karol A., Muehlschlegel, Jochen D., Allayee, Hooman, Almgren, Peter, Alver, Maris, Baranova, Ekaterina V., Behloui, Hassan, Boeckx, Bram, Braund, Peter S., Breitling, Lutz P., Delgado, Graciela, Duarte, Nubia E., Dubé, Marie Pierre, Dufresne, Line, Eriksson, Niclas, Foco, Luisa, Scholz, Markus, Gijsberts, Crystel M., Glinge, Charlotte, Gong, Yan, Hartiala, Jaana, Heydarpour, Mahyar, Hubacek, Jaroslav A., Kleber, Marcus, Kofink, Daniel, Kotti, Salma, Kuukasjärvi, Pekka, Lee, Vei Vei, Leiherer, Andreas, Lenzini, Petra A., Levin, Daniel, Lyytikäinen, Leo Pekka, Martinelli, Nicola, Mons, Ute, Nelson, Christopher P., Nikus, Kjell, Pilbrow, Anna P., Ploski, Rafal, Sun, Yan V., Tanck, Michael W.T., Tang, W. H.Wilson, Trompet, Stella, van der Laan, Sander W., Van Setten, Jessica, Vilmundarson, Ragnar O., Viviani Anselmi, Chiara, Vlachopoulou, Efthymia, Al Ali, Lawien, Boerwinkle, Eric, Briguori, Carlo, Carlquist, John F., Carruthers, Kathryn F., Casu, Gavino, Deanfield, John, Deloukas, Panos, Dudbridge, Frank, Engstrøm, Thomas, Fitzpatrick, Natalie, Fox, Kim, Gigante, Bruna, James, Stefan, Lokki, Marja Liisa, Lotufo, Paulo A., Marziliano, Nicola, Mordi, Ify R., Muhlestein, Joseph B., Newton-Cheh, Christopher, Pitha, Jan, Saely, Christoph H., Samman-Tahhan, Ayman, Sandesara, Pratik B., Teren, Andrej, Timmis, Adam, Van de Werf, Frans, Wauters, Els, Wilde, Arthur A.M., Ford, Ian, Stott, David J., Algra, Ale, Andreassi, Maria G., Ardissino, Diego, Arsenault, Benoit J., Ballantyne, Christie M., Bergmeijer, Thomas O., Bezzina, Connie R., Body, Simon C., Boersma, Eric H., Bogaty, Peter, Bots, Michiel L., Brenner, Hermann, Brugts, Jasper J., Burkhardt, Ralph, Carpeggiani, Clara, Condorelli, Gianluigi, Cooper-DeHoff, Rhonda M., Cresci, Sharon, Danchin, Nicolas, de Faire, Ulf, Doughty, Robert N., Drexel, Heinz, Engert, James C., Fox, Keith A.A., Girelli, Domenico, Grobbee, Diederick E., Hagström, Emil, Hazen, Stanley L., Held, Claes, Hemingway, Harry, Hoefer, Imo E., Hovingh, G. Kees, Jabbari, Reza, Johnson, Julie A., Jukema, J. Wouter, Kaczor, Marcin P., Kähönen, Mika, Kettner, Jiri, Kiliszek, Marek, Klungel, Olaf H., Lagerqvist, Bo, Lambrechts, Diether, Laurikka, Jari O., Lehtimäki, Terho, Lindholm, Daniel, Mahmoodi, B. K., Maitland-van der Zee, Anke H., McPherson, Ruth, Melander, Olle, Metspalu, Andres, Niemcunowicz-Janica, Anna, Olivieri, Oliviero, Opolski, Grzegorz, Palmer, Colin N., Pasterkamp, Gerard, Pepine, Carl J., Pereira, Alexandre C., Pilote, Louise, Quyyumi, Arshed A., Richards, A. Mark, Sanak, Marek, Siegbahn, Agneta, Simon, Tabassome, Sinisalo, Juha, Smith, J. Gustav, Spertus, John A., Stender, Steen, Stewart, Alexandre F.R., Szczeklik, Wojciech, Szpakowicz, Anna, Tardif, Jean Claude, Ten Berg, Jurriën M., Tfelt-Hansen, Jacob, Thanassoulis, George, Thiery, Joachim, Torp-Pedersen, Christian, van der Graaf, Yolanda, Visseren, Frank L.J., Waltenberger, Johannes, Weeke, Peter E., Van der Harst, Pim, Lang, Chim C., Sattar, Naveed, Cameron, Vicky A., Anderson, Jeffrey L., Brophy, James M., Pare, Guillaume, Horne, Benjamin D., März, Winfried, Wallentin, Lars, Samani, Nilesh J., Hingorani, Aroon D., Asselbergs, Folkert W., Onderzoek Precision medicine, Circulatory Health, UMC Utrecht, Aios en Stafsecr. Cardiologie, Experimentele Afd. Cardiologie 1, Apotheek Klinische Farmacie Kinderen, CDL Onderzoek Pasterkamp, Cardiovasculaire Epi Team 6, ZL Cerebrovasculaire Ziekten Medisch, Brain, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Cardiovasculaire Epi Team 5, Cardiovasculaire Epi Team 9, CDL Arcadia, Global Health, JC onderzoeksprogramma Methodologie, dLAB Afdelingen, Device, Interne Geneeskunde Vasculaire, Team Medisch, Patel, Riyaz S., Tragante, Vinicius, Schmidt, Amand F., McCubrey, Raymond O., Holmes, Michael V., Howe, Laurence J., Direk, Kenan, Åkerblom, Axel, Leander, Karin, Virani, Salim S., Kaminski, Karol A., Muehlschlegel, Jochen D., Allayee, Hooman, Almgren, Peter, Alver, Maris, Baranova, Ekaterina V., Behloui, Hassan, Boeckx, Bram, Braund, Peter S., Breitling, Lutz P., Delgado, Graciela, Duarte, Nubia E., Dubé, Marie Pierre, Dufresne, Line, Eriksson, Niclas, Foco, Luisa, Scholz, Markus, Gijsberts, Crystel M., Glinge, Charlotte, Gong, Yan, Hartiala, Jaana, Heydarpour, Mahyar, Hubacek, Jaroslav A., Kleber, Marcus, Kofink, Daniel, Kotti, Salma, Kuukasjärvi, Pekka, Lee, Vei Vei, Leiherer, Andreas, Lenzini, Petra A., Levin, Daniel, Lyytikäinen, Leo Pekka, Martinelli, Nicola, Mons, Ute, Nelson, Christopher P., Nikus, Kjell, Pilbrow, Anna P., Ploski, Rafal, Sun, Yan V., Tanck, Michael W.T., Tang, W. H.Wilson, Trompet, Stella, van der Laan, Sander W., Van Setten, Jessica, Vilmundarson, Ragnar O., Viviani Anselmi, Chiara, Vlachopoulou, Efthymia, Al Ali, Lawien, Boerwinkle, Eric, Briguori, Carlo, Carlquist, John F., Carruthers, Kathryn F., Casu, Gavino, Deanfield, John, Deloukas, Panos, Dudbridge, Frank, Engstrøm, Thomas, Fitzpatrick, Natalie, Fox, Kim, Gigante, Bruna, James, Stefan, Lokki, Marja Liisa, Lotufo, Paulo A., Marziliano, Nicola, Mordi, Ify R., Muhlestein, Joseph B., Newton-Cheh, Christopher, Pitha, Jan, Saely, Christoph H., Samman-Tahhan, Ayman, Sandesara, Pratik B., Teren, Andrej, Timmis, Adam, Van de Werf, Frans, Wauters, Els, Wilde, Arthur A.M., Ford, Ian, Stott, David J., Algra, Ale, Andreassi, Maria G., Ardissino, Diego, Arsenault, Benoit J., Ballantyne, Christie M., Bergmeijer, Thomas O., Bezzina, Connie R., Body, Simon C., Boersma, Eric H., Bogaty, Peter, Bots, Michiel L., Brenner, Hermann, Brugts, Jasper J., Burkhardt, Ralph, Carpeggiani, Clara, Condorelli, Gianluigi, Cooper-DeHoff, Rhonda M., Cresci, Sharon, Danchin, Nicolas, de Faire, Ulf, Doughty, Robert N., Drexel, Heinz, Engert, James C., Fox, Keith A.A., Girelli, Domenico, Grobbee, Diederick E., Hagström, Emil, Hazen, Stanley L., Held, Claes, Hemingway, Harry, Hoefer, Imo E., Hovingh, G. Kees, Jabbari, Reza, Johnson, Julie A., Jukema, J. Wouter, Kaczor, Marcin P., Kähönen, Mika, Kettner, Jiri, Kiliszek, Marek, Klungel, Olaf H., Lagerqvist, Bo, Lambrechts, Diether, Laurikka, Jari O., Lehtimäki, Terho, Lindholm, Daniel, Mahmoodi, B. K., Maitland-van der Zee, Anke H., McPherson, Ruth, Melander, Olle, Metspalu, Andres, Niemcunowicz-Janica, Anna, Olivieri, Oliviero, Opolski, Grzegorz, Palmer, Colin N., Pasterkamp, Gerard, Pepine, Carl J., Pereira, Alexandre C., Pilote, Louise, Quyyumi, Arshed A., Richards, A. Mark, Sanak, Marek, Siegbahn, Agneta, Simon, Tabassome, Sinisalo, Juha, Smith, J. Gustav, Spertus, John A., Stender, Steen, Stewart, Alexandre F.R., Szczeklik, Wojciech, Szpakowicz, Anna, Tardif, Jean Claude, Ten Berg, Jurriën M., Tfelt-Hansen, Jacob, Thanassoulis, George, Thiery, Joachim, Torp-Pedersen, Christian, van der Graaf, Yolanda, Visseren, Frank L.J., Waltenberger, Johannes, Weeke, Peter E., Van der Harst, Pim, Lang, Chim C., Sattar, Naveed, Cameron, Vicky A., Anderson, Jeffrey L., Brophy, James M., Pare, Guillaume, Horne, Benjamin D., März, Winfried, Wallentin, Lars, Samani, Nilesh J., Hingorani, Aroon D., and Asselbergs, Folkert W.
Published: 2019

38. Effects of Hemodiafiltration versus Conventional Hemodialysis in Children with ESKD: The HDF, Heart and Height Study

Author: Shroff, Rukshana, Smith, Colette, Ranchin, Bruno, Bayazit, Aysun K., Stefanidis, Constantinos J., Askiti, Varvara, Azukaitis, Karolis, Canpolat, Nur, Agbas, Ayse, Aitkenhead, Helen, Anarat, Ali, Aoun, Bilal, Aofolaju, Daley, Bakkaloglu, Sevcan Azime, Bhowruth, Devina, Borzych-Duzalka, Dagmara, Bulut, Ipek Kaplan, Buescher, Rainer, Deanfield, John, Dempster, Claire, Duzova, Ali, Habbig, Sandra, Hayes, Wesley, Hegde, Shivram, Krid, Saoussen, Licht, Christoph, Litwin, Mieczyslaw, Mayes, Mark, Mir, Sevgi, Nemec, Rose, Obrycki, Lukasz, Paglialonga, Fabio, Picca, Stefano, Samaille, Charlotte, Shenoy, Mohan, Sinha, Manish D., Spasojevic, Brankica, Stronach, Lynsey, Vidal, Enrico, Vondrak, Karel, Yilmaz, Alev, Zaloszyc, Ariane, Fischbach, Michel, Schmitt, Claus Peter, Schaefer, Franz, Shroff, Rukshana, Smith, Colette, Ranchin, Bruno, Bayazit, Aysun K., Stefanidis, Constantinos J., Askiti, Varvara, Azukaitis, Karolis, Canpolat, Nur, Agbas, Ayse, Aitkenhead, Helen, Anarat, Ali, Aoun, Bilal, Aofolaju, Daley, Bakkaloglu, Sevcan Azime, Bhowruth, Devina, Borzych-Duzalka, Dagmara, Bulut, Ipek Kaplan, Buescher, Rainer, Deanfield, John, Dempster, Claire, Duzova, Ali, Habbig, Sandra, Hayes, Wesley, Hegde, Shivram, Krid, Saoussen, Licht, Christoph, Litwin, Mieczyslaw, Mayes, Mark, Mir, Sevgi, Nemec, Rose, Obrycki, Lukasz, Paglialonga, Fabio, Picca, Stefano, Samaille, Charlotte, Shenoy, Mohan, Sinha, Manish D., Spasojevic, Brankica, Stronach, Lynsey, Vidal, Enrico, Vondrak, Karel, Yilmaz, Alev, Zaloszyc, Ariane, Fischbach, Michel, Schmitt, Claus Peter, and Schaefer, Franz
Abstract: Background Hypertension and cardiovascular disease are common in children undergoing dialysis. Studies suggest that hemodiafiltration (HDF) may reduce cardiovascular mortality in adults, but data for children are scarce. Methods The HDF, Heart and Height study is a nonrandomized observational study comparing outcomes on conventional hemodialysis (HD) versus postdilution online HDF in children. Primary outcome measures were annualized changes in carotid intima-media thickness (cIMT) SD score and height SD score. Results We enrolled 190 children from 28 centers; 78 on HD and 55 on HDF completed 1-year follow-up. The groups were comparable for age, dialysis vintage, access type, dialysis frequency, blood flow, and residual renal function. At 1 year, cIMT SD score increased significantly in children on HD but remained static in the HDF cohort. On propensity score analysis, HD was associated with a +0.47 higher annualized cIMT SD score compared with HDF. Height SD score increased in HDF but remained static in HD. Mean arterial pressure SD score increased with HD only. Factors associated with higher cIMT and mean arterial pressure SD-scores were HD group, higher ultrafiltration rate, and higher 2-microglobulin. The HDF cohort had lower 2-microglobulin, parathyroid hormone, and high-sensitivity C-reactive protein at 1 year; fewer headaches, dizziness, or cramps; and shorter postdialysis recovery time. Conclusions HDF is associated with a lack of progression in vascular measures versus progression with HD, as well as an increase in height not seen in the HD cohort. Patient-related outcomes improved among children on HDF correlating with improved BP control and clearances. Confirmation through randomized trials is required.
Published: 2019

39. Subsequent Event Risk in Individuals with Established Coronary Heart Disease:Design and Rationale of the GENIUS-CHD Consortium

Author: Patel, Riyaz, Tragante, Vinicius, Schmidt, Amand F, McCubrey, Raymond O, Holmes, Michael V, Howe, Laurence J, Direk, Kenan, Åkerblom, Axel, Leander, Karin, Virani, Salim S, Kaminski, Karol A, Muehlschlegel, Jochen D, Allayee, Hooman, Almgren, Peter, Alver, Maris, Baranova, Ekaterina V, Behlouli, Hassan, Boeckx, Bram, Braund, Peter S, Breitling, Lutz P, Delgado, Graciela, Duarte, Nubia E, Dubé, Marie-Pierre, Dufresne, Line, Eriksson, Niclas, Foco, Luisa, Scholz, Markus, Gijsberts, Crystel M, Glinge, Charlotte, Gong, Yan, Hartiala, Jaana, Heydarpour, Mahyar, Hubacek, Jaroslav A, Kleber, Marcus, Kofink, Daniel, Kotti, Salma, Kuukasjärvi, Pekka, Lee, Vei-Vei, Leiherer, Andreas, Lenzini, Petra A, Levin, Daniel, Lyytikäinen, Leo-Pekka, Martinelli, Nicola, Mons, Ute, Nelson, Christopher P, Nikus, Kjell, Pilbrow, Anna P, Ploski, Rafal, Sun, Yan V, Tanck, Michael W T, Tang, W H Wilson, Trompet, Stella, van der Laan, Sander W, Van Setten, Jessica, Vilmundarson, Ragnar O, Viviani Anselmi, Chiara, Vlachopoulou, Efthymia, Al Ali, Lawien, Boerwinkle, Eric, Briguori, Carlo, Carlquist, John F, Carruthers, Kathryn F, Casu, Gavino, Deanfield, John, Deloukas, Panos, Dudbridge, Frank, Engström, Thomas, Fitzpatrick, Natalie, Fox, Kim, Gigante, Bruna, James, Stefan, Lokki, Marja-Liisa, Lotufo, Paulo A, Marziliano, Nicola, Mordi, Ify R, Muhlestein, Joseph B, Newton-Cheh, Christopher, Pitha, Jan, Saely, Christoph H, Samman-Tahhan, Ayman, Sandesara, Pratik B, Teren, Andrej, Timmis, Adam, Van de Werf, Frans, Wauters, Els, Wilde, Arthur A M, Ford, Ian, Stott, David J, Algra, Ale, Andreassi, Maria G, Ardissino, Diego, Arsenault, Benoit J, Ballantyne, Christie M, Bergmeijer, Thomas O, Bezzina, Connie R, Body, Simon C, Boersma, Eric H, Bogaty, Peter, Bots, Michiel, Brenner, Hermann, Brugts, Jasper J, Burkhardt, Ralph, Carpeggiani, Clara, Condorelli, Gianluigi, Cooper-DeHoff, Rhonda M, Cresci, Sharon, Danchin, Nicolas, de Faire, Ulf, Doughty, Robert N, Drexel, Heinz, Engert, James C, Fox, Keith A A, Girelli, Domenico, Grobbee, Diederick E, Hagström, Emil, Hazen, Stanley L, Held, Claes, Hemingway, Harry, Hoefer, Imo E, Hovingh, G Kees, Jabbari, Reza, Johnson, Julie A, Jukema, J Wouter, Kaczor, Marcin P, Kähönen, Mika, Kettner, Jiri, Kiliszek, Marek, Klungel, Olaf H, Lagerqvist, Bo, Lambrechts, Diether, Laurikka, Jari O, Lehtimäki, Terho, Lindholm, Daniel, Mahmoodi, B K, Maitland-van der Zee, Anke H, McPherson, Ruth, Melander, Olle, Metspalu, Andres, Niemcunowicz-Janica, Anna, Olivieri, Oliviero, Opolski, Grzegorz, Palmer, Colin N, Pasterkamp, Gerard, Pepine, Carl J, Pereira, Alexandre C, Pilote, Louise, Quyyumi, Arshed A, Richards, A Mark, Sanak, Marek, Siegbahn, Agneta, Simon, Tabassome, Sinisalo, Juha, Smith, J Gustav, Spertus, John A, Stender, Steen, Stewart, Alexandre F R, Szczeklik, Wojciech, Szpakowicz, Anna, Tardif, Jean-Claude, Ten Berg, Jurriën M, Tfelt-Hansen, Jacob, Thanassoulis, George, Thiery, Joachim, Torp-Pedersen, Christian, van der Graaf, Yolanda, Visseren, Frank L J, Waltenberger, Johannes, Weeke, Peter E, Van der Harst, Pim, Lang, Chim C, Sattar, Naveed, Cameron, Vicky A, Anderson, Jeffrey L, Brophy, James M, Paré, Guillaume, Horne, Benjamin D, März, Winfried, Wallentin, Lars, Samani, Nilesh J, Hingorani, Aroon D, Asselbergs, Folkert W, Patel, Riyaz, Tragante, Vinicius, Schmidt, Amand F, McCubrey, Raymond O, Holmes, Michael V, Howe, Laurence J, Direk, Kenan, Åkerblom, Axel, Leander, Karin, Virani, Salim S, Kaminski, Karol A, Muehlschlegel, Jochen D, Allayee, Hooman, Almgren, Peter, Alver, Maris, Baranova, Ekaterina V, Behlouli, Hassan, Boeckx, Bram, Braund, Peter S, Breitling, Lutz P, Delgado, Graciela, Duarte, Nubia E, Dubé, Marie-Pierre, Dufresne, Line, Eriksson, Niclas, Foco, Luisa, Scholz, Markus, Gijsberts, Crystel M, Glinge, Charlotte, Gong, Yan, Hartiala, Jaana, Heydarpour, Mahyar, Hubacek, Jaroslav A, Kleber, Marcus, Kofink, Daniel, Kotti, Salma, Kuukasjärvi, Pekka, Lee, Vei-Vei, Leiherer, Andreas, Lenzini, Petra A, Levin, Daniel, Lyytikäinen, Leo-Pekka, Martinelli, Nicola, Mons, Ute, Nelson, Christopher P, Nikus, Kjell, Pilbrow, Anna P, Ploski, Rafal, Sun, Yan V, Tanck, Michael W T, Tang, W H Wilson, Trompet, Stella, van der Laan, Sander W, Van Setten, Jessica, Vilmundarson, Ragnar O, Viviani Anselmi, Chiara, Vlachopoulou, Efthymia, Al Ali, Lawien, Boerwinkle, Eric, Briguori, Carlo, Carlquist, John F, Carruthers, Kathryn F, Casu, Gavino, Deanfield, John, Deloukas, Panos, Dudbridge, Frank, Engström, Thomas, Fitzpatrick, Natalie, Fox, Kim, Gigante, Bruna, James, Stefan, Lokki, Marja-Liisa, Lotufo, Paulo A, Marziliano, Nicola, Mordi, Ify R, Muhlestein, Joseph B, Newton-Cheh, Christopher, Pitha, Jan, Saely, Christoph H, Samman-Tahhan, Ayman, Sandesara, Pratik B, Teren, Andrej, Timmis, Adam, Van de Werf, Frans, Wauters, Els, Wilde, Arthur A M, Ford, Ian, Stott, David J, Algra, Ale, Andreassi, Maria G, Ardissino, Diego, Arsenault, Benoit J, Ballantyne, Christie M, Bergmeijer, Thomas O, Bezzina, Connie R, Body, Simon C, Boersma, Eric H, Bogaty, Peter, Bots, Michiel, Brenner, Hermann, Brugts, Jasper J, Burkhardt, Ralph, Carpeggiani, Clara, Condorelli, Gianluigi, Cooper-DeHoff, Rhonda M, Cresci, Sharon, Danchin, Nicolas, de Faire, Ulf, Doughty, Robert N, Drexel, Heinz, Engert, James C, Fox, Keith A A, Girelli, Domenico, Grobbee, Diederick E, Hagström, Emil, Hazen, Stanley L, Held, Claes, Hemingway, Harry, Hoefer, Imo E, Hovingh, G Kees, Jabbari, Reza, Johnson, Julie A, Jukema, J Wouter, Kaczor, Marcin P, Kähönen, Mika, Kettner, Jiri, Kiliszek, Marek, Klungel, Olaf H, Lagerqvist, Bo, Lambrechts, Diether, Laurikka, Jari O, Lehtimäki, Terho, Lindholm, Daniel, Mahmoodi, B K, Maitland-van der Zee, Anke H, McPherson, Ruth, Melander, Olle, Metspalu, Andres, Niemcunowicz-Janica, Anna, Olivieri, Oliviero, Opolski, Grzegorz, Palmer, Colin N, Pasterkamp, Gerard, Pepine, Carl J, Pereira, Alexandre C, Pilote, Louise, Quyyumi, Arshed A, Richards, A Mark, Sanak, Marek, Siegbahn, Agneta, Simon, Tabassome, Sinisalo, Juha, Smith, J Gustav, Spertus, John A, Stender, Steen, Stewart, Alexandre F R, Szczeklik, Wojciech, Szpakowicz, Anna, Tardif, Jean-Claude, Ten Berg, Jurriën M, Tfelt-Hansen, Jacob, Thanassoulis, George, Thiery, Joachim, Torp-Pedersen, Christian, van der Graaf, Yolanda, Visseren, Frank L J, Waltenberger, Johannes, Weeke, Peter E, Van der Harst, Pim, Lang, Chim C, Sattar, Naveed, Cameron, Vicky A, Anderson, Jeffrey L, Brophy, James M, Paré, Guillaume, Horne, Benjamin D, März, Winfried, Wallentin, Lars, Samani, Nilesh J, Hingorani, Aroon D, and Asselbergs, Folkert W
Abstract: BACKGROUND: The "GENetIcs of sUbSequent Coronary Heart Disease" (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD.METHODS: The consortium currently includes 57 studies from 18 countries, recruiting 185,614 participants with either acute coronary syndrome, stable CHD or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events.RESULTS: Enrollment into the individual studies took place between 1985 to present day with duration of follow up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38%-100%), mostly male (44%-91%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (HR 1.15 95% CI 1.14-1.16) per 5-year increase, male sex (HR 1.17, 95% CI 1.13-1.21) and smoking (HR 1.43, 95% CI 1.35-1.51) with risk of subsequent CHD death or myocardial infarction, and differing associations with other individual and composite cardiovascular endpoints.CONCLUSIONS: GENIUS-CHD is a global collaboration seeking to elucidate genetic and non-genetic determinants of subsequent event risk in individuals with established CHD, in order to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators.
Published: 2019

40. Subsequent Event Risk in Individuals With Established Coronary Heart Disease : Design and Rationale of the GENIUS-CHD Consortium

Author: Patel, Riyaz S., Tragante, Vinicius, Schmidt, Amand F., McCubrey, Raymond O., Holmes, Michael, V, Howe, Laurence J., Direk, Kenan, Åkerblom, Axel, Leander, Karin, Virani, Salim S., Kaminski, Karol A., Muehlschlegel, Jochen D., Allayee, Hooman, Almgren, Peter, Alver, Maris, Baranova, Ekaterina, V, Behloui, Hassan, Boeckx, Bram, Braund, Peter S., Breitling, Lutz P., Delgado, Gradela, Duarte, Nubia E., Dube, Marie-Pierre, Dufresne, Line, Eriksson, Niclas, Foco, Luisa, Scholz, Markus, Gijsberts, Crystel M., Glinge, Charlotte, Gong, Yan, Hartiala, Jaana, Heydarpour, Mahyar, Hubacek, Jaroslav A., Kleber, Marcus, Kofink, Daniel, Kotti, Salma, Kuukasjarvi, Pekka, Lee, Vei-Vei, Leiherer, Andreas, Lenzini, Petra A., Levin, Daniel, Lyytikainen, Leo-Pekka, Martinelli, Nicola, Mons, Ute, Nelson, Christopher P., Nikus, Kjell, Pilbrow, Anna P., Ploski, Rafal, Sun, Yan, V, Tanck, Michael W. T., Tang, W. H. Wilson, Trompet, Stella, van der Laan, Sander W., Van Setten, Jessica, Vilmundarson, Ragnar O., Anselmi, Chiara Viviani, Vlachopoulou, Efthymia, Al Ali, Lawien, Boerwinkle, Eric, Briguori, Carlo, Carlquist, John F., Carruthers, Kathryn F., Casu, Gavino, Deanfield, John, Deloukas, Panos, Dudbridge, Frank, Engstrom, Thomas, Fitzpatrick, Natalie, Fox, Kim, Gigante, Bruna, James, Stefan, Lokki, Marja-Liisa, Lotufo, Paulo A., Marziliano, Nicola, Mordi, Ify R., Muhlestein, Joseph B., Newton-Cheh, Christopher, Pitha, Jan, Saely, Christoph H., Samman-Tahhan, Ayman, Sandesara, Pratik B., Teren, Andrej, Timmis, Adam, Van de Werf, Frans, Wauters, Els, Wilde, Arthur A. M., Ford, Ian, Stott, David J., Algra, Ale, Andreassi, Maria G., Ardissino, Diego, Arsenault, Benoit J., Ballantyne, Christie M., Bergmeijer, Thomas O., Bezzina, Connie R., Body, Simon C., Boersma, Eric H., Bogaty, Peter, Bots, Michiel L., Brenner, Hermann, Brugts, Jasper J., Burkhardt, Ralph, Carpeggiani, Clara, Condorelli, Gianluigi, Cooper-DeHoff, Rhonda M., Cresci, Sharon, Danchin, Nicolas, de Faire, Ulf, Doughty, Robert N., Drexel, Heinz, Engert, James C., Fox, Keith A. A., Girelli, Domenico, Grobbee, Diederick E., Hagström, Emil, Hazen, Stanley L., Held, Claes, Hemingway, Harry, Hoefer, Imo E., Hovingh, G. Kees, Jabbari, Reza, Johnson, Julie A., Jukema, J. Wouter, Kaczor, Marcin P., Kahonen, Mika, Kettner, Jiri, Kiliszek, Marek, Klungel, Olaf H., Lagerqvist, Bo, Lambrechts, Diether, Laurikka, Jari O., Lehtimaki, Terho, Lindholm, Daniel, Mahmoodi, B. K., Maitland-van der Zee, Anke H., McPherson, Ruth, Melander, Olle, Metspalu, Andres, Niemcunowicz-Janica, Anna, Olivieri, Oliviero, Opolski, Grzegorz, Palmer, Colin N., Pasterkamp, Gerard, Pepine, Carl J., Pereira, Alexandre C., Pilote, Louise, Quyyumi, Arshed A., Richards, A. Mark, Sanak, Marek, Siegbahn, Agneta, Simon, Tabassome, Sinisalo, Juha, Smith, J. Gustav, Spertus, John A., Stender, Steen, Stewart, Alexandre F. R., Szczeklik, Wojciech, Szpakowicz, Anna, Tardif, Jean-Claude, ten Berg, Jurrien M., Tfelt-Hansen, Jacob, Thanassoulis, George, Thiery, Joachim, Torp-Pedersen, Christian, van der Graaf, Yolanda, Visseren, Frank L. J., Waltenberger, Johannes, Weeke, Peter E., Van der Harst, Pim, Lang, Chim C., Sattar, Naveed, Cameron, Vicky A., Anderson, Jeffrey L., Brophy, James M., Pare, Guillaume, Horne, Benjamin D., Marz, Winfried, Wallentin, Lars, Samani, Nilesh J., Hingorani, Aroon D., Asselbergs, Folkert W., Patel, Riyaz S., Tragante, Vinicius, Schmidt, Amand F., McCubrey, Raymond O., Holmes, Michael, V, Howe, Laurence J., Direk, Kenan, Åkerblom, Axel, Leander, Karin, Virani, Salim S., Kaminski, Karol A., Muehlschlegel, Jochen D., Allayee, Hooman, Almgren, Peter, Alver, Maris, Baranova, Ekaterina, V, Behloui, Hassan, Boeckx, Bram, Braund, Peter S., Breitling, Lutz P., Delgado, Gradela, Duarte, Nubia E., Dube, Marie-Pierre, Dufresne, Line, Eriksson, Niclas, Foco, Luisa, Scholz, Markus, Gijsberts, Crystel M., Glinge, Charlotte, Gong, Yan, Hartiala, Jaana, Heydarpour, Mahyar, Hubacek, Jaroslav A., Kleber, Marcus, Kofink, Daniel, Kotti, Salma, Kuukasjarvi, Pekka, Lee, Vei-Vei, Leiherer, Andreas, Lenzini, Petra A., Levin, Daniel, Lyytikainen, Leo-Pekka, Martinelli, Nicola, Mons, Ute, Nelson, Christopher P., Nikus, Kjell, Pilbrow, Anna P., Ploski, Rafal, Sun, Yan, V, Tanck, Michael W. T., Tang, W. H. Wilson, Trompet, Stella, van der Laan, Sander W., Van Setten, Jessica, Vilmundarson, Ragnar O., Anselmi, Chiara Viviani, Vlachopoulou, Efthymia, Al Ali, Lawien, Boerwinkle, Eric, Briguori, Carlo, Carlquist, John F., Carruthers, Kathryn F., Casu, Gavino, Deanfield, John, Deloukas, Panos, Dudbridge, Frank, Engstrom, Thomas, Fitzpatrick, Natalie, Fox, Kim, Gigante, Bruna, James, Stefan, Lokki, Marja-Liisa, Lotufo, Paulo A., Marziliano, Nicola, Mordi, Ify R., Muhlestein, Joseph B., Newton-Cheh, Christopher, Pitha, Jan, Saely, Christoph H., Samman-Tahhan, Ayman, Sandesara, Pratik B., Teren, Andrej, Timmis, Adam, Van de Werf, Frans, Wauters, Els, Wilde, Arthur A. M., Ford, Ian, Stott, David J., Algra, Ale, Andreassi, Maria G., Ardissino, Diego, Arsenault, Benoit J., Ballantyne, Christie M., Bergmeijer, Thomas O., Bezzina, Connie R., Body, Simon C., Boersma, Eric H., Bogaty, Peter, Bots, Michiel L., Brenner, Hermann, Brugts, Jasper J., Burkhardt, Ralph, Carpeggiani, Clara, Condorelli, Gianluigi, Cooper-DeHoff, Rhonda M., Cresci, Sharon, Danchin, Nicolas, de Faire, Ulf, Doughty, Robert N., Drexel, Heinz, Engert, James C., Fox, Keith A. A., Girelli, Domenico, Grobbee, Diederick E., Hagström, Emil, Hazen, Stanley L., Held, Claes, Hemingway, Harry, Hoefer, Imo E., Hovingh, G. Kees, Jabbari, Reza, Johnson, Julie A., Jukema, J. Wouter, Kaczor, Marcin P., Kahonen, Mika, Kettner, Jiri, Kiliszek, Marek, Klungel, Olaf H., Lagerqvist, Bo, Lambrechts, Diether, Laurikka, Jari O., Lehtimaki, Terho, Lindholm, Daniel, Mahmoodi, B. K., Maitland-van der Zee, Anke H., McPherson, Ruth, Melander, Olle, Metspalu, Andres, Niemcunowicz-Janica, Anna, Olivieri, Oliviero, Opolski, Grzegorz, Palmer, Colin N., Pasterkamp, Gerard, Pepine, Carl J., Pereira, Alexandre C., Pilote, Louise, Quyyumi, Arshed A., Richards, A. Mark, Sanak, Marek, Siegbahn, Agneta, Simon, Tabassome, Sinisalo, Juha, Smith, J. Gustav, Spertus, John A., Stender, Steen, Stewart, Alexandre F. R., Szczeklik, Wojciech, Szpakowicz, Anna, Tardif, Jean-Claude, ten Berg, Jurrien M., Tfelt-Hansen, Jacob, Thanassoulis, George, Thiery, Joachim, Torp-Pedersen, Christian, van der Graaf, Yolanda, Visseren, Frank L. J., Waltenberger, Johannes, Weeke, Peter E., Van der Harst, Pim, Lang, Chim C., Sattar, Naveed, Cameron, Vicky A., Anderson, Jeffrey L., Brophy, James M., Pare, Guillaume, Horne, Benjamin D., Marz, Winfried, Wallentin, Lars, Samani, Nilesh J., Hingorani, Aroon D., and Asselbergs, Folkert W.
Abstract: BACKGROUND: The Genetics of Subsequent Coronary Heart Disease (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD. METHODS: The consortium currently includes 57 studies from 18 countries, recruiting 185 614 participants with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events. RESULTS: Enrollment into the individual studies took place between 1985 to present day with a duration of follow-up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38%-100%), mostly male (44%-91%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (hazard ratio, 1.15; 95% CI, 1.14-1.16) per 5-year increase, male sex (hazard ratio, 1.17; 95% CI, 1.13-1.21) and smoking (hazard ratio, 1.43; 95% CI, 1.35-1.51) with risk of subsequent CHD death or myocardial infarction and differing associations with other individual and composite cardiovascular endpoints. CONCLUSIONS: GENIUS-CHD is a global collaboration seeking to elucidate genetic and nongenetic determinants of subsequent event risk in individuals with established CHD, to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators.
Published: 2019
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41. Association of Chromosome 9p21 With Subsequent Coronary Heart Disease Events : A GENIUS-CHD Study of Individual Participant Data

Author: Patel, Riyaz S., Schmidt, Amand F., Tragante, Vinicius, McCubrey, Raymond O., Holmes, Michael, V, Howe, Laurence J., Direk, Kenan, Åkerblom, Axel, Leander, Karin, Virani, Salim S., Kaminski, Karol A., Muehlschlegel, Jochen D., Dube, Marie-Pierre, Allayee, Hooman, Almgren, Peter, Alver, Maris, Baranova, Ekaterina, V, Behlouli, Hassan, Boeckx, Bram, Braund, Peter S., Breitling, Lutz P., Delgado, Graciela, Duarte, Nubia E., Dufresne, Line, Eriksson, Niclas, Foco, Luisa, Gijsberts, Crystel M., Gong, Yan, Hartiala, Jaana, Heydarpour, Mahyar, Hubacek, Jaroslav A., Kleber, Marcus, Kofink, Daniel, Kuukasjarvi, Pekka, Lee, Vei-Vei, Leiherer, Andreas, Lenzini, Petra A., Levin, Daniel, Lyytikainen, Leo-Pekka, Martinelli, Nicola, Mons, Ute, Nelson, Christopher P., Nikus, Kjell, Pilbrow, Anna P., Ploski, Rafal, Sun, Yan, V, Tanck, Michael W. T., Tang, W. H. Wilson, Trompet, Stella, van der Laan, Sander W., van Setten, Jessica, Vilmundarson, Ragnar O., Anselmi, Chiara Viviani, Vlachopoulou, Efthymia, Boerwinkle, Eric, Briguori, Carlo, Carlquist, John F., Carruthers, Kathryn F., Casu, Gavino, Deanfield, John, Deloukas, Panos, Dudbridge, Frank, Fitzpatrick, Natalie, Gigante, Bruna, James, Stefan, Lokki, Marja-Liisa, Lotufo, Paulo A., Marziliano, Nicola, Mordi, Ify R., Muhlestein, Joseph B., Cheh, Chris Newton, Pitha, Jan, Saely, Christoph H., Samman-Tahhan, Ayman, Sandesara, Pratik B., Teren, Andrej, Timmis, Adam, Van de Werf, Frans, Wauters, Els, Wilde, Arthur A. M., Ford, Ian, Stott, David J., Algra, Ale, Andreassi, Maria G., Ardissino, Diego, Arsenault, Benoit J., Ballantyne, Christie M., Bergmeijer, Thomas O., Bezzina, Connie R., Body, Simon C., Bogaty, Peter, de Borst, Gert J., Brenner, Hermann, Burkhardt, Ralph, Carpeggiani, Clara, Condorelli, Gianluigi, Cooper-DeHoff, Rhonda M., Cresci, Sharon, de Faire, Ulf, Doughty, Robert N., Drexel, Heinz, Engert, James C., Fox, Keith A. A., Girelli, Domenico, Hagström, Emil, Hazen, Stanley L., Held, Claes, Hemingway, Harry, Hoefer, Imo E., Hovingh, G. Kees, Johnson, Julie A., De Jong, Pim A., Jukema, J. Wouter, Kaczor, Marcin P., Kahonen, Mika, Kettner, Jiri, Kiliszek, Marek, Klungel, Olaf H., Lagerqvist, Bo, Lambrechts, Diether, Laurikka, Jari O., Lehtimaki, Terho, Lindholm, Daniel, Mahmoodi, Bakhtawar K., Maitland-van der Zee, Anke H., McPherson, Ruth, Melander, Olle, Metspalu, Andres, Pepinski, Witold, Olivieri, Oliviero, Opolski, Grzegorz, Palmer, Colin N., Pasterkamp, Gerard, Pepine, Carl J., Pereira, Alexandre C., Note, Louise, Quyyumi, Arshed A., Richards, A. Mark, Sanak, Marek, Scholz, Markus, Siegbahn, Agneta, Sinisalo, Juha, Smith, J. Gustav, Spertus, John A., Stewart, Alexandre F. R., Szczeklik, Wojciech, Szpakowicz, Anna, ten Berg, Jurrien M., Thanassoulis, George, Thieiy, Joachim, van der Graaf, Yolanda, Visseren, Frank L. J., Waltenberger, Johannes, Van der Harst, Pim, Tardif, Jean-Claude, Sattar, Naveed, Lang, Chim C., Pare, Guillaume, Brophy, James M., Anderson, Jeffrey L., Maerz, Winfried, Wallentin, Lars, Cameron, Vicky A., Horne, Benjamin D., Samani, Nilesh J., Hingorani, Aroon D., Asselbergs, Folkert W., Patel, Riyaz S., Schmidt, Amand F., Tragante, Vinicius, McCubrey, Raymond O., Holmes, Michael, V, Howe, Laurence J., Direk, Kenan, Åkerblom, Axel, Leander, Karin, Virani, Salim S., Kaminski, Karol A., Muehlschlegel, Jochen D., Dube, Marie-Pierre, Allayee, Hooman, Almgren, Peter, Alver, Maris, Baranova, Ekaterina, V, Behlouli, Hassan, Boeckx, Bram, Braund, Peter S., Breitling, Lutz P., Delgado, Graciela, Duarte, Nubia E., Dufresne, Line, Eriksson, Niclas, Foco, Luisa, Gijsberts, Crystel M., Gong, Yan, Hartiala, Jaana, Heydarpour, Mahyar, Hubacek, Jaroslav A., Kleber, Marcus, Kofink, Daniel, Kuukasjarvi, Pekka, Lee, Vei-Vei, Leiherer, Andreas, Lenzini, Petra A., Levin, Daniel, Lyytikainen, Leo-Pekka, Martinelli, Nicola, Mons, Ute, Nelson, Christopher P., Nikus, Kjell, Pilbrow, Anna P., Ploski, Rafal, Sun, Yan, V, Tanck, Michael W. T., Tang, W. H. Wilson, Trompet, Stella, van der Laan, Sander W., van Setten, Jessica, Vilmundarson, Ragnar O., Anselmi, Chiara Viviani, Vlachopoulou, Efthymia, Boerwinkle, Eric, Briguori, Carlo, Carlquist, John F., Carruthers, Kathryn F., Casu, Gavino, Deanfield, John, Deloukas, Panos, Dudbridge, Frank, Fitzpatrick, Natalie, Gigante, Bruna, James, Stefan, Lokki, Marja-Liisa, Lotufo, Paulo A., Marziliano, Nicola, Mordi, Ify R., Muhlestein, Joseph B., Cheh, Chris Newton, Pitha, Jan, Saely, Christoph H., Samman-Tahhan, Ayman, Sandesara, Pratik B., Teren, Andrej, Timmis, Adam, Van de Werf, Frans, Wauters, Els, Wilde, Arthur A. M., Ford, Ian, Stott, David J., Algra, Ale, Andreassi, Maria G., Ardissino, Diego, Arsenault, Benoit J., Ballantyne, Christie M., Bergmeijer, Thomas O., Bezzina, Connie R., Body, Simon C., Bogaty, Peter, de Borst, Gert J., Brenner, Hermann, Burkhardt, Ralph, Carpeggiani, Clara, Condorelli, Gianluigi, Cooper-DeHoff, Rhonda M., Cresci, Sharon, de Faire, Ulf, Doughty, Robert N., Drexel, Heinz, Engert, James C., Fox, Keith A. A., Girelli, Domenico, Hagström, Emil, Hazen, Stanley L., Held, Claes, Hemingway, Harry, Hoefer, Imo E., Hovingh, G. Kees, Johnson, Julie A., De Jong, Pim A., Jukema, J. Wouter, Kaczor, Marcin P., Kahonen, Mika, Kettner, Jiri, Kiliszek, Marek, Klungel, Olaf H., Lagerqvist, Bo, Lambrechts, Diether, Laurikka, Jari O., Lehtimaki, Terho, Lindholm, Daniel, Mahmoodi, Bakhtawar K., Maitland-van der Zee, Anke H., McPherson, Ruth, Melander, Olle, Metspalu, Andres, Pepinski, Witold, Olivieri, Oliviero, Opolski, Grzegorz, Palmer, Colin N., Pasterkamp, Gerard, Pepine, Carl J., Pereira, Alexandre C., Note, Louise, Quyyumi, Arshed A., Richards, A. Mark, Sanak, Marek, Scholz, Markus, Siegbahn, Agneta, Sinisalo, Juha, Smith, J. Gustav, Spertus, John A., Stewart, Alexandre F. R., Szczeklik, Wojciech, Szpakowicz, Anna, ten Berg, Jurrien M., Thanassoulis, George, Thieiy, Joachim, van der Graaf, Yolanda, Visseren, Frank L. J., Waltenberger, Johannes, Van der Harst, Pim, Tardif, Jean-Claude, Sattar, Naveed, Lang, Chim C., Pare, Guillaume, Brophy, James M., Anderson, Jeffrey L., Maerz, Winfried, Wallentin, Lars, Cameron, Vicky A., Horne, Benjamin D., Samani, Nilesh J., Hingorani, Aroon D., and Asselbergs, Folkert W.
Abstract: BACKGROUND: Genetic variation at chromosome 9p21 is a recognized risk factor for coronary heart disease (CHD). However, its effect on disease progression and subsequent events is unclear, raising questions about its value for stratification of residual risk. METHODS: A variant at chromosome 9p21 (rs1333049) was tested for association with subsequent events during follow-up in 103 357 Europeans with established CHD at baseline from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) Consortium (73.1% male, mean age 62.9 years). The primary outcome, subsequent CHD death or myocardial infarction (CHD death/myocardial infarction), occurred in 13 040 of the 93 115 participants with available outcome data. Effect estimates were compared with case/control risk obtained from the CARDIoGRAMplusC4D consortium (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics) including 47 222 CHD cases and 122 264 controls free of CHD. RESULTS: Meta-analyses revealed no significant association between chromosome 9p21 and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline (GENIUSCHD odds ratio, 1.02; 95% CI, 0.99-1.05). This contrasted with a strong association in CARDIoGRAMPlusC4D odds ratio 1.20; 95% CI, 1.18-1.22; P for interaction < 0.001 compared with the GENIUS-CHD estimate. Similarly, no clear associations were identified for additional subsequent outcomes, including all-cause death, although we found a modest positive association between chromosome 9p21 and subsequent revascularization (odds ratio, 1.07; 95% CI, 1.04-1.09). CONCLUSIONS: In contrast to studies comparing individuals with CHD to disease-free controls, we found no clear association between genetic variation at chromosome 9p21 and risk of subsequent acute CHD events when all individuals had CHD at baseline. However, the association with subsequent revascularization may support the post
Published: 2019
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42. Subsequent Event Risk in Individuals with Established Coronary Heart Disease:Design and Rationale of the GENIUS-CHD Consortium

Author: Patel, Riyaz, Tragante, Vinicius, Schmidt, Amand F, McCubrey, Raymond O, Holmes, Michael V, Howe, Laurence J, Direk, Kenan, Åkerblom, Axel, Leander, Karin, Virani, Salim S, Kaminski, Karol A, Muehlschlegel, Jochen D, Allayee, Hooman, Almgren, Peter, Alver, Maris, Baranova, Ekaterina V, Behlouli, Hassan, Boeckx, Bram, Braund, Peter S, Breitling, Lutz P, Delgado, Graciela, Duarte, Nubia E, Dubé, Marie-Pierre, Dufresne, Line, Eriksson, Niclas, Foco, Luisa, Scholz, Markus, Gijsberts, Crystel M, Glinge, Charlotte, Gong, Yan, Hartiala, Jaana, Heydarpour, Mahyar, Hubacek, Jaroslav A, Kleber, Marcus, Kofink, Daniel, Kotti, Salma, Kuukasjärvi, Pekka, Lee, Vei-Vei, Leiherer, Andreas, Lenzini, Petra A, Levin, Daniel, Lyytikäinen, Leo-Pekka, Martinelli, Nicola, Mons, Ute, Nelson, Christopher P, Nikus, Kjell, Pilbrow, Anna P, Ploski, Rafal, Sun, Yan V, Tanck, Michael W T, Tang, W H Wilson, Trompet, Stella, van der Laan, Sander W, Van Setten, Jessica, Vilmundarson, Ragnar O, Viviani Anselmi, Chiara, Vlachopoulou, Efthymia, Al Ali, Lawien, Boerwinkle, Eric, Briguori, Carlo, Carlquist, John F, Carruthers, Kathryn F, Casu, Gavino, Deanfield, John, Deloukas, Panos, Dudbridge, Frank, Engström, Thomas, Fitzpatrick, Natalie, Fox, Kim, Gigante, Bruna, James, Stefan, Lokki, Marja-Liisa, Lotufo, Paulo A, Marziliano, Nicola, Mordi, Ify R, Muhlestein, Joseph B, Newton-Cheh, Christopher, Pitha, Jan, Saely, Christoph H, Samman-Tahhan, Ayman, Sandesara, Pratik B, Teren, Andrej, Timmis, Adam, Van de Werf, Frans, Wauters, Els, Wilde, Arthur A M, Ford, Ian, Stott, David J, Algra, Ale, Andreassi, Maria G, Ardissino, Diego, Arsenault, Benoit J, Ballantyne, Christie M, Bergmeijer, Thomas O, Bezzina, Connie R, Body, Simon C, Boersma, Eric H, Bogaty, Peter, Bots, Michiel, Brenner, Hermann, Brugts, Jasper J, Burkhardt, Ralph, Carpeggiani, Clara, Condorelli, Gianluigi, Cooper-DeHoff, Rhonda M, Cresci, Sharon, Danchin, Nicolas, de Faire, Ulf, Doughty, Robert N, Drexel, Heinz, Engert, James C, Fox, Keith A A, Girelli, Domenico, Grobbee, Diederick E, Hagström, Emil, Hazen, Stanley L, Held, Claes, Hemingway, Harry, Hoefer, Imo E, Hovingh, G Kees, Jabbari, Reza, Johnson, Julie A, Jukema, J Wouter, Kaczor, Marcin P, Kähönen, Mika, Kettner, Jiri, Kiliszek, Marek, Klungel, Olaf H, Lagerqvist, Bo, Lambrechts, Diether, Laurikka, Jari O, Lehtimäki, Terho, Lindholm, Daniel, Mahmoodi, B K, Maitland-van der Zee, Anke H, McPherson, Ruth, Melander, Olle, Metspalu, Andres, Niemcunowicz-Janica, Anna, Olivieri, Oliviero, Opolski, Grzegorz, Palmer, Colin N, Pasterkamp, Gerard, Pepine, Carl J, Pereira, Alexandre C, Pilote, Louise, Quyyumi, Arshed A, Richards, A Mark, Sanak, Marek, Siegbahn, Agneta, Simon, Tabassome, Sinisalo, Juha, Smith, J Gustav, Spertus, John A, Stender, Steen, Stewart, Alexandre F R, Szczeklik, Wojciech, Szpakowicz, Anna, Tardif, Jean-Claude, Ten Berg, Jurriën M, Tfelt-Hansen, Jacob, Thanassoulis, George, Thiery, Joachim, Torp-Pedersen, Christian, van der Graaf, Yolanda, Visseren, Frank L J, Waltenberger, Johannes, Weeke, Peter E, Van der Harst, Pim, Lang, Chim C, Sattar, Naveed, Cameron, Vicky A, Anderson, Jeffrey L, Brophy, James M, Paré, Guillaume, Horne, Benjamin D, März, Winfried, Wallentin, Lars, Samani, Nilesh J, Hingorani, Aroon D, Asselbergs, Folkert W, Patel, Riyaz, Tragante, Vinicius, Schmidt, Amand F, McCubrey, Raymond O, Holmes, Michael V, Howe, Laurence J, Direk, Kenan, Åkerblom, Axel, Leander, Karin, Virani, Salim S, Kaminski, Karol A, Muehlschlegel, Jochen D, Allayee, Hooman, Almgren, Peter, Alver, Maris, Baranova, Ekaterina V, Behlouli, Hassan, Boeckx, Bram, Braund, Peter S, Breitling, Lutz P, Delgado, Graciela, Duarte, Nubia E, Dubé, Marie-Pierre, Dufresne, Line, Eriksson, Niclas, Foco, Luisa, Scholz, Markus, Gijsberts, Crystel M, Glinge, Charlotte, Gong, Yan, Hartiala, Jaana, Heydarpour, Mahyar, Hubacek, Jaroslav A, Kleber, Marcus, Kofink, Daniel, Kotti, Salma, Kuukasjärvi, Pekka, Lee, Vei-Vei, Leiherer, Andreas, Lenzini, Petra A, Levin, Daniel, Lyytikäinen, Leo-Pekka, Martinelli, Nicola, Mons, Ute, Nelson, Christopher P, Nikus, Kjell, Pilbrow, Anna P, Ploski, Rafal, Sun, Yan V, Tanck, Michael W T, Tang, W H Wilson, Trompet, Stella, van der Laan, Sander W, Van Setten, Jessica, Vilmundarson, Ragnar O, Viviani Anselmi, Chiara, Vlachopoulou, Efthymia, Al Ali, Lawien, Boerwinkle, Eric, Briguori, Carlo, Carlquist, John F, Carruthers, Kathryn F, Casu, Gavino, Deanfield, John, Deloukas, Panos, Dudbridge, Frank, Engström, Thomas, Fitzpatrick, Natalie, Fox, Kim, Gigante, Bruna, James, Stefan, Lokki, Marja-Liisa, Lotufo, Paulo A, Marziliano, Nicola, Mordi, Ify R, Muhlestein, Joseph B, Newton-Cheh, Christopher, Pitha, Jan, Saely, Christoph H, Samman-Tahhan, Ayman, Sandesara, Pratik B, Teren, Andrej, Timmis, Adam, Van de Werf, Frans, Wauters, Els, Wilde, Arthur A M, Ford, Ian, Stott, David J, Algra, Ale, Andreassi, Maria G, Ardissino, Diego, Arsenault, Benoit J, Ballantyne, Christie M, Bergmeijer, Thomas O, Bezzina, Connie R, Body, Simon C, Boersma, Eric H, Bogaty, Peter, Bots, Michiel, Brenner, Hermann, Brugts, Jasper J, Burkhardt, Ralph, Carpeggiani, Clara, Condorelli, Gianluigi, Cooper-DeHoff, Rhonda M, Cresci, Sharon, Danchin, Nicolas, de Faire, Ulf, Doughty, Robert N, Drexel, Heinz, Engert, James C, Fox, Keith A A, Girelli, Domenico, Grobbee, Diederick E, Hagström, Emil, Hazen, Stanley L, Held, Claes, Hemingway, Harry, Hoefer, Imo E, Hovingh, G Kees, Jabbari, Reza, Johnson, Julie A, Jukema, J Wouter, Kaczor, Marcin P, Kähönen, Mika, Kettner, Jiri, Kiliszek, Marek, Klungel, Olaf H, Lagerqvist, Bo, Lambrechts, Diether, Laurikka, Jari O, Lehtimäki, Terho, Lindholm, Daniel, Mahmoodi, B K, Maitland-van der Zee, Anke H, McPherson, Ruth, Melander, Olle, Metspalu, Andres, Niemcunowicz-Janica, Anna, Olivieri, Oliviero, Opolski, Grzegorz, Palmer, Colin N, Pasterkamp, Gerard, Pepine, Carl J, Pereira, Alexandre C, Pilote, Louise, Quyyumi, Arshed A, Richards, A Mark, Sanak, Marek, Siegbahn, Agneta, Simon, Tabassome, Sinisalo, Juha, Smith, J Gustav, Spertus, John A, Stender, Steen, Stewart, Alexandre F R, Szczeklik, Wojciech, Szpakowicz, Anna, Tardif, Jean-Claude, Ten Berg, Jurriën M, Tfelt-Hansen, Jacob, Thanassoulis, George, Thiery, Joachim, Torp-Pedersen, Christian, van der Graaf, Yolanda, Visseren, Frank L J, Waltenberger, Johannes, Weeke, Peter E, Van der Harst, Pim, Lang, Chim C, Sattar, Naveed, Cameron, Vicky A, Anderson, Jeffrey L, Brophy, James M, Paré, Guillaume, Horne, Benjamin D, März, Winfried, Wallentin, Lars, Samani, Nilesh J, Hingorani, Aroon D, and Asselbergs, Folkert W
Abstract: BACKGROUND: The "GENetIcs of sUbSequent Coronary Heart Disease" (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD.METHODS: The consortium currently includes 57 studies from 18 countries, recruiting 185,614 participants with either acute coronary syndrome, stable CHD or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events.RESULTS: Enrollment into the individual studies took place between 1985 to present day with duration of follow up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38%-100%), mostly male (44%-91%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (HR 1.15 95% CI 1.14-1.16) per 5-year increase, male sex (HR 1.17, 95% CI 1.13-1.21) and smoking (HR 1.43, 95% CI 1.35-1.51) with risk of subsequent CHD death or myocardial infarction, and differing associations with other individual and composite cardiovascular endpoints.CONCLUSIONS: GENIUS-CHD is a global collaboration seeking to elucidate genetic and non-genetic determinants of subsequent event risk in individuals with established CHD, in order to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators.
Published: 2019

43. GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes

Author: Franceschini, Nora, Giambartolomei, Claudia, de Vries, Paul S., Finan, Chris, Bis, Joshua C., Huntley, Rachael P., Lovering, Ruth C., Tajuddin, Salman M., Winkler, Thomas W., Graff, Misa, Kavousi, Maryam, Dale, Caroline, Smith, Albert V., Hofer, Edith, van Leeuwen, Elisabeth M., Nolte, Ilja M., Lu, Lingyi, Scholz, Markus, Sargurupremraj, Muralidharan, Pitkanen, Niina, Franzen, Oscar, Joshi, Peter K., Noordam, Raymond, Marioni, Riccardo E., Hwang, Shih-Jen, Musani, Solomon K., Schminke, Ulf, Palmas, Walter, Isaacs, Aaron, Correa, Adolfo, Zonderman, Alan B., Hofman, Albert, Teumer, Alexander, Cox, Amanda J., Uitterlinden, Andre G., Wong, Andrew, Smit, Andries J., Newman, Anne B., Britton, Annie, Ruusalepp, Arno, Sennblad, Bengt, Hedblad, Bo, Pasaniuc, Bogdan, Penninx, Brenda W., Langefeld, Carl D., Wassel, Christina L., Tzourio, Christophe, Fava, Cristiano, Baldassarre, Damiano, O'Leary, Daniel H., Teupser, Daniel, Kuh, Diana, Tremoli, Elena, Mannarino, Elmo, Grossi, Enzo, Boerwinkle, Eric, Schadt, Eric E., Ingelsson, Erik, Veglia, Fabrizio, Rivadeneira, Fernando, Beutner, Frank, Chauhan, Ganesh, Heiss, Gerardo, Snieder, Harold, Campbell, Harry, Voelzke, Henry, Markus, Hugh S., Deary, Ian J., Jukema, J. Wouter, de Graaf, Jacqueline, Price, Jacqueline, Pott, Janne, Hopewell, Jemma C., Liang, Jingjing, Thiery, Joachim, Engmann, Jorgen, Gertow, Karl, Rice, Kenneth, Taylor, Kent D., Dhana, Klodian, Kiemeney, Lambertus A. L. M., Lind, Lars, Raffield, Laura M., Launer, Lenore J., Holdt, Lesca M., Doer, Marcus, Dichgans, Martin, Traylor, Matthew, Sitzer, Matthias, Kumari, Meena, Kivimaki, Mika, Nalls, Mike A., Melander, Olle, Raitakari, Olli, Franco, Oscar H., Rueda-Ochoa, Oscar L., Roussos, Panos, Whincup, Peter H., Amouyel, Philippe, Giral, Philippe, Anugu, Pramod, Wong, Quenna, Malik, Rainer, Rauramaa, Rainer, Burkhardt, Ralph, Hardy, Rebecca, Schmidt, Reinhold, de Mutsert, Renee, Morris, Richard W., Strawbridge, Rona J., Wannamethee, S. Goya, Hagg, Sara, Shah, Sonia, McLachlan, Stela, Trompet, Stella, Seshadri, Sudha, Kurl, Sudhir, Heckbert, Susan R., Ring, Susan, Harris, Tamara B., Lehtimaki, Terho, Galesloot, Tessel E., Shah, Tina, de Faire, Ulf, Plagnol, Vincent, Rosamond, Wayne D., Post, Wendy, Zhu, Xiaofeng, Zhang, Xiaoling, Guo, Xiuqing, Saba, Yasaman, Dehghan, Abbas, Seldenrijk, Adrie, Morrison, Alanna C., Hamsten, Anders, Psaty, Bruce M., van Duijn, Cornelia M., Lawlor, Deborah A., Mook-Kanamori, Dennis O., Bowden, Donald W., Schmidt, Helena, Wilson, James F., Wilson, James G., Rotter, Jerome I., Wardlaw, Joanna M., Deanfield, John, Halcox, Julian, Lyytikainen, Leo-Pekka, Loeffler, Markus, Evans, Michele K., Debette, Stephanie, Humphries, Steve E., Voelker, Uwe, Gudnason, Vilmundur, Hingorani, Aroon D., Bjorkegren, Johan L. M., Casas, Juan P., O'Donnell, Christopher J., Franceschini, Nora, Giambartolomei, Claudia, de Vries, Paul S., Finan, Chris, Bis, Joshua C., Huntley, Rachael P., Lovering, Ruth C., Tajuddin, Salman M., Winkler, Thomas W., Graff, Misa, Kavousi, Maryam, Dale, Caroline, Smith, Albert V., Hofer, Edith, van Leeuwen, Elisabeth M., Nolte, Ilja M., Lu, Lingyi, Scholz, Markus, Sargurupremraj, Muralidharan, Pitkanen, Niina, Franzen, Oscar, Joshi, Peter K., Noordam, Raymond, Marioni, Riccardo E., Hwang, Shih-Jen, Musani, Solomon K., Schminke, Ulf, Palmas, Walter, Isaacs, Aaron, Correa, Adolfo, Zonderman, Alan B., Hofman, Albert, Teumer, Alexander, Cox, Amanda J., Uitterlinden, Andre G., Wong, Andrew, Smit, Andries J., Newman, Anne B., Britton, Annie, Ruusalepp, Arno, Sennblad, Bengt, Hedblad, Bo, Pasaniuc, Bogdan, Penninx, Brenda W., Langefeld, Carl D., Wassel, Christina L., Tzourio, Christophe, Fava, Cristiano, Baldassarre, Damiano, O'Leary, Daniel H., Teupser, Daniel, Kuh, Diana, Tremoli, Elena, Mannarino, Elmo, Grossi, Enzo, Boerwinkle, Eric, Schadt, Eric E., Ingelsson, Erik, Veglia, Fabrizio, Rivadeneira, Fernando, Beutner, Frank, Chauhan, Ganesh, Heiss, Gerardo, Snieder, Harold, Campbell, Harry, Voelzke, Henry, Markus, Hugh S., Deary, Ian J., Jukema, J. Wouter, de Graaf, Jacqueline, Price, Jacqueline, Pott, Janne, Hopewell, Jemma C., Liang, Jingjing, Thiery, Joachim, Engmann, Jorgen, Gertow, Karl, Rice, Kenneth, Taylor, Kent D., Dhana, Klodian, Kiemeney, Lambertus A. L. M., Lind, Lars, Raffield, Laura M., Launer, Lenore J., Holdt, Lesca M., Doer, Marcus, Dichgans, Martin, Traylor, Matthew, Sitzer, Matthias, Kumari, Meena, Kivimaki, Mika, Nalls, Mike A., Melander, Olle, Raitakari, Olli, Franco, Oscar H., Rueda-Ochoa, Oscar L., Roussos, Panos, Whincup, Peter H., Amouyel, Philippe, Giral, Philippe, Anugu, Pramod, Wong, Quenna, Malik, Rainer, Rauramaa, Rainer, Burkhardt, Ralph, Hardy, Rebecca, Schmidt, Reinhold, de Mutsert, Renee, Morris, Richard W., Strawbridge, Rona J., Wannamethee, S. Goya, Hagg, Sara, Shah, Sonia, McLachlan, Stela, Trompet, Stella, Seshadri, Sudha, Kurl, Sudhir, Heckbert, Susan R., Ring, Susan, Harris, Tamara B., Lehtimaki, Terho, Galesloot, Tessel E., Shah, Tina, de Faire, Ulf, Plagnol, Vincent, Rosamond, Wayne D., Post, Wendy, Zhu, Xiaofeng, Zhang, Xiaoling, Guo, Xiuqing, Saba, Yasaman, Dehghan, Abbas, Seldenrijk, Adrie, Morrison, Alanna C., Hamsten, Anders, Psaty, Bruce M., van Duijn, Cornelia M., Lawlor, Deborah A., Mook-Kanamori, Dennis O., Bowden, Donald W., Schmidt, Helena, Wilson, James F., Wilson, James G., Rotter, Jerome I., Wardlaw, Joanna M., Deanfield, John, Halcox, Julian, Lyytikainen, Leo-Pekka, Loeffler, Markus, Evans, Michele K., Debette, Stephanie, Humphries, Steve E., Voelker, Uwe, Gudnason, Vilmundur, Hingorani, Aroon D., Bjorkegren, Johan L. M., Casas, Juan P., and O'Donnell, Christopher J.
Abstract: Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans.
Published: 2018
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44. Work stress and risk of death in men and women with and without cardiometabolic disease : a multicohort study

Author: Kivimäki, Mika, Pentti, Jaana, Ferrie, Jane E., Batty, G. David, Nyberg, Solja T., Jokela, Markus, Virtanen, Marianna, Alfredsson, Lars, Dragano, Nico, Fransson, Eleonor I., Goldberg, Marcel, Knutsson, Anders, Koskenvuo, Markku, Koskinen, Aki, Kouvonen, Anne, Luukkonen, Ritva, Oksanen, Tuula, Rugulies, Reiner, Siegrist, Johannes, Singh-Manoux, Archana, Suominen, Sakari, Theorell, Töres, Väänänen, Ari, Vahtera, Jussi, Westerholm, Peter, Westerlund, Hugo, Zins, Marie, Strandberg, Timo, Steptoe, Andrew, Deanfield, John, Kivimäki, Mika, Pentti, Jaana, Ferrie, Jane E., Batty, G. David, Nyberg, Solja T., Jokela, Markus, Virtanen, Marianna, Alfredsson, Lars, Dragano, Nico, Fransson, Eleonor I., Goldberg, Marcel, Knutsson, Anders, Koskenvuo, Markku, Koskinen, Aki, Kouvonen, Anne, Luukkonen, Ritva, Oksanen, Tuula, Rugulies, Reiner, Siegrist, Johannes, Singh-Manoux, Archana, Suominen, Sakari, Theorell, Töres, Väänänen, Ari, Vahtera, Jussi, Westerholm, Peter, Westerlund, Hugo, Zins, Marie, Strandberg, Timo, Steptoe, Andrew, and Deanfield, John
Abstract: Background: Although some cardiovascular disease prevention guidelines suggest a need to manage work stress in patients with established cardiometabolic disease, the evidence base for this recommendation is weak. We sought to clarify the status of stress as a risk factor in cardiometabolic disease by investigating the associations between work stress and mortality in men and women with and without pre-existing cardiometabolic disease. Methods: In this multicohort study, we used data from seven cohort studies in the IPD-Work consortium, initiated between 1985 and 2002 in Finland, France, Sweden, and the UK, to examine the association between work stress and mortality. Work stress was denoted as job strain or effort-reward imbalance at work. We extracted individual-level data on prevalent cardiometabolic diseases (coronary heart disease, stroke, or diabetes [without differentiation by diabetes type]) at baseline. Work stressors, socioeconomic status, and conventional and lifestyle risk factors (systolic and diastolic blood pressure, total cholesterol, smoking status, BMI, physical activity, and alcohol consumption) were also assessed at baseline. Mortality data, including date and cause of death, were obtained from national death registries. We used Cox proportional hazards regression to study the associations of work stressors with mortality in men and women with and without cardiometabolic disease. Results: We identified 102 633 individuals with 1 423 753 person-years at risk (mean follow-up 13.9 years [SD 3.9]), of whom 3441 had prevalent cardiometabolic disease at baseline and 3841 died during follow-up. In men with cardiometabolic disease, age-standardised mortality rates were substantially higher in people with job strain (149.8 per 10 000 person-years) than in those without (97.7 per 10 000 person-years; mortality difference 52.1 per 10 000 person-years; multivariable-adjusted hazard ratio [HR] 1.68, 95% CI 1.19-2.35). This mortality difference for job strain w
Published: 2018
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45. Work stress and risk of death in men and women with and without cardiometabolic disease : a multicohort study

Author: Kivimäki, Mika, Pentti, Jaana, Ferrie, Jane E., Batty, G David., Nyberg, Solja T., Jokela, Markus, Virtanen, Marianna, Alfredsson, Lars, Dragano, Nico, Fransson, Eleonor I., Goldberg, Marcel, Knutsson, Anders, Koskenvuo, Markku, Koskinen, Aki, Kouvonen, Anne, Luukkonen, Ritva, Oksanen, Tuula, Rugulies, Reiner, Siegrist, Johannes, Singh-Manoux, Archana, Suominen, Sakari, Theorell, Töres, Väänänen, Ari, Vahtera, Jussi, Westerholm, Peter J. M., Westerlund, Hugo, Zins, Marie, Strandberg, Timo, Steptoe, Andrew, Deanfield, John, Kivimäki, Mika, Pentti, Jaana, Ferrie, Jane E., Batty, G David., Nyberg, Solja T., Jokela, Markus, Virtanen, Marianna, Alfredsson, Lars, Dragano, Nico, Fransson, Eleonor I., Goldberg, Marcel, Knutsson, Anders, Koskenvuo, Markku, Koskinen, Aki, Kouvonen, Anne, Luukkonen, Ritva, Oksanen, Tuula, Rugulies, Reiner, Siegrist, Johannes, Singh-Manoux, Archana, Suominen, Sakari, Theorell, Töres, Väänänen, Ari, Vahtera, Jussi, Westerholm, Peter J. M., Westerlund, Hugo, Zins, Marie, Strandberg, Timo, Steptoe, Andrew, and Deanfield, John
Abstract: BACKGROUND: Although some cardiovascular disease prevention guidelines suggest a need to manage work stress in patients with established cardiometabolic disease, the evidence base for this recommendation is weak. We sought to clarify the status of stress as a risk factor in cardiometabolic disease by investigating the associations between work stress and mortality in men and women with and without pre-existing cardiometabolic disease. METHODS: In this multicohort study, we used data from seven cohort studies in the IPD-Work consortium, initiated between 1985 and 2002 in Finland, France, Sweden, and the UK, to examine the association between work stress and mortality. Work stress was denoted as job strain or effort-reward imbalance at work. We extracted individual-level data on prevalent cardiometabolic diseases (coronary heart disease, stroke, or diabetes [without differentiation by diabetes type]) at baseline. Work stressors, socioeconomic status, and conventional and lifestyle risk factors (systolic and diastolic blood pressure, total cholesterol, smoking status, BMI, physical activity, and alcohol consumption) were also assessed at baseline. Mortality data, including date and cause of death, were obtained from national death registries. We used Cox proportional hazards regression to study the associations of work stressors with mortality in men and women with and without cardiometabolic disease. RESULTS: We identified 102 633 individuals with 1 423 753 person-years at risk (mean follow-up 13·9 years [SD 3·9]), of whom 3441 had prevalent cardiometabolic disease at baseline and 3841 died during follow-up. In men with cardiometabolic disease, age-standardised mortality rates were substantially higher in people with job strain (149·8 per 10 000 person-years) than in those without (97·7 per 10 000 person-years; mortality difference 52·1 per 10 000 person-years; multivariable-adjusted hazard ratio [HR] 1·68, 95% CI 1·19-2·35). This mortality difference for job strain w, CC BY 4.0
Published: 2018
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46. Work stress and risk of death in men and women with and without cardiometabolic disease : a multicohort study

Author: Kivimäki, Mika, Pentti, Jaana, Ferrie, Jane E., Batty, G David., Nyberg, Solja T., Jokela, Markus, Virtanen, Marianna, Alfredsson, Lars, Dragano, Nico, Fransson, Eleonor I., Goldberg, Marcel, Knutsson, Anders, Koskenvuo, Markku, Koskinen, Aki, Kouvonen, Anne, Luukkonen, Ritva, Oksanen, Tuula, Rugulies, Reiner, Siegrist, Johannes, Singh-Manoux, Archana, Suominen, Sakari, Theorell, Töres, Väänänen, Ari, Vahtera, Jussi, Westerholm, Peter J. M., Westerlund, Hugo, Zins, Marie, Strandberg, Timo, Steptoe, Andrew, Deanfield, John, Kivimäki, Mika, Pentti, Jaana, Ferrie, Jane E., Batty, G David., Nyberg, Solja T., Jokela, Markus, Virtanen, Marianna, Alfredsson, Lars, Dragano, Nico, Fransson, Eleonor I., Goldberg, Marcel, Knutsson, Anders, Koskenvuo, Markku, Koskinen, Aki, Kouvonen, Anne, Luukkonen, Ritva, Oksanen, Tuula, Rugulies, Reiner, Siegrist, Johannes, Singh-Manoux, Archana, Suominen, Sakari, Theorell, Töres, Väänänen, Ari, Vahtera, Jussi, Westerholm, Peter J. M., Westerlund, Hugo, Zins, Marie, Strandberg, Timo, Steptoe, Andrew, and Deanfield, John
Abstract: BACKGROUND: Although some cardiovascular disease prevention guidelines suggest a need to manage work stress in patients with established cardiometabolic disease, the evidence base for this recommendation is weak. We sought to clarify the status of stress as a risk factor in cardiometabolic disease by investigating the associations between work stress and mortality in men and women with and without pre-existing cardiometabolic disease. METHODS: In this multicohort study, we used data from seven cohort studies in the IPD-Work consortium, initiated between 1985 and 2002 in Finland, France, Sweden, and the UK, to examine the association between work stress and mortality. Work stress was denoted as job strain or effort-reward imbalance at work. We extracted individual-level data on prevalent cardiometabolic diseases (coronary heart disease, stroke, or diabetes [without differentiation by diabetes type]) at baseline. Work stressors, socioeconomic status, and conventional and lifestyle risk factors (systolic and diastolic blood pressure, total cholesterol, smoking status, BMI, physical activity, and alcohol consumption) were also assessed at baseline. Mortality data, including date and cause of death, were obtained from national death registries. We used Cox proportional hazards regression to study the associations of work stressors with mortality in men and women with and without cardiometabolic disease. RESULTS: We identified 102 633 individuals with 1 423 753 person-years at risk (mean follow-up 13·9 years [SD 3·9]), of whom 3441 had prevalent cardiometabolic disease at baseline and 3841 died during follow-up. In men with cardiometabolic disease, age-standardised mortality rates were substantially higher in people with job strain (149·8 per 10 000 person-years) than in those without (97·7 per 10 000 person-years; mortality difference 52·1 per 10 000 person-years; multivariable-adjusted hazard ratio [HR] 1·68, 95% CI 1·19-2·35). This mortality difference for job strain w, CC BY 4.0
Published: 2018
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47. Work stress and risk of death in men and women with and without cardiometabolic disease : a multicohort study

Author: Kivimäki, Mika, Pentti, Jaana, Ferrie, Jane E., Batty, G. David, Nyberg, Solja T., Jokela, Markus, Virtanen, Marianna, Alfredsson, Lars, Dragano, Nico, Fransson, Eleonor I., Goldberg, Marcel, Knutsson, Anders, Koskenvuo, Markku, Koskinen, Aki, Kouvonen, Anne, Luukkonen, Ritva, Oksanen, Tuula, Rugulies, Reiner, Siegrist, Johannes, Singh-Manoux, Archana, Suominen, Sakari, Theorell, Tores, Vaananen, Ari, Vahtera, Jussi, Westerholm, Peter J. M., Westerlund, Hugo, Zins, Marie, Strandberg, Timo, Steptoe, Andrew, Deanfield, John, Kivimäki, Mika, Pentti, Jaana, Ferrie, Jane E., Batty, G. David, Nyberg, Solja T., Jokela, Markus, Virtanen, Marianna, Alfredsson, Lars, Dragano, Nico, Fransson, Eleonor I., Goldberg, Marcel, Knutsson, Anders, Koskenvuo, Markku, Koskinen, Aki, Kouvonen, Anne, Luukkonen, Ritva, Oksanen, Tuula, Rugulies, Reiner, Siegrist, Johannes, Singh-Manoux, Archana, Suominen, Sakari, Theorell, Tores, Vaananen, Ari, Vahtera, Jussi, Westerholm, Peter J. M., Westerlund, Hugo, Zins, Marie, Strandberg, Timo, Steptoe, Andrew, and Deanfield, John
Abstract: Background Although some cardiovascular disease prevention guidelines suggest a need to manage work stress in patients with established cardiometabolic disease, the evidence base for this recommendation is weak. We sought to clarify the status of stress as a risk factor in cardiometabolic disease by investigating the associations between work stress and mortality in men and women with and without pre-existing cardiometabolic disease. Methods In this multicohort study, we used data from seven cohort studies in the IPD-Work consortium, initiated between 1985 and 2002 in Finland, France, Sweden, and the UK, to examine the association between work stress and mortality. Work stress was denoted as job strain or effort-reward imbalance at work. We extracted individual-level data on prevalent cardiometabolic diseases (coronary heart disease, stroke, or diabetes [without differentiation by diabetes type]) at baseline. Work stressors, socioeconomic status, and conventional and lifestyle risk factors (systolic and diastolic blood pressure, total cholesterol, smoking status, BMI, physical activity, and alcohol consumption) were also assessed at baseline. Mortality data, including date and cause of death, were obtained from national death registries. We used Cox proportional hazards regression to study the associations of work stressors with mortality in men and women with and without cardiometabolic disease. Results We identified 102 633 individuals with 1 423 753 person-years at risk (mean follow-up 13.9 years [SD 3.9]), of whom 3441 had prevalent cardiometabolic disease at baseline and 3841 died during follow-up. In men with cardiometabolic disease, age-standardised mortality rates were substantially higher in people with job strain (149.8 per 10 000 person-years) than in those without (97.7 per 10 000 person-years; mortality difference 52.1 per 10 000 person-years; multivariable-adjusted hazard ratio [HR] 1.68, 95% CI 1.19-2.35). This mortality difference for job strain was
Published: 2018
Full Text: View/download PDF

48. Work stress and risk of death in men and women with and without cardiometabolic disease : a multicohort study

Author: Kivimäki, Mika, Pentti, Jaana, Ferrie, Jane E., Batty, G. David, Nyberg, Solja T., Jokela, Markus, Virtanen, Marianna, Alfredsson, Lars, Dragano, Nico, Fransson, Eleonor I., Goldberg, Marcel, Knutsson, Anders, Koskenvuo, Markku, Koskinen, Aki, Kouvonen, Anne, Luukkonen, Ritva, Oksanen, Tuula, Rugulies, Reiner, Siegrist, Johannes, Singh-Manoux, Archana, Suominen, Sakari, Theorell, Tores, Vaananen, Ari, Vahtera, Jussi, Westerholm, Peter J. M., Westerlund, Hugo, Zins, Marie, Strandberg, Timo, Steptoe, Andrew, Deanfield, John, Kivimäki, Mika, Pentti, Jaana, Ferrie, Jane E., Batty, G. David, Nyberg, Solja T., Jokela, Markus, Virtanen, Marianna, Alfredsson, Lars, Dragano, Nico, Fransson, Eleonor I., Goldberg, Marcel, Knutsson, Anders, Koskenvuo, Markku, Koskinen, Aki, Kouvonen, Anne, Luukkonen, Ritva, Oksanen, Tuula, Rugulies, Reiner, Siegrist, Johannes, Singh-Manoux, Archana, Suominen, Sakari, Theorell, Tores, Vaananen, Ari, Vahtera, Jussi, Westerholm, Peter J. M., Westerlund, Hugo, Zins, Marie, Strandberg, Timo, Steptoe, Andrew, and Deanfield, John
Abstract: Background Although some cardiovascular disease prevention guidelines suggest a need to manage work stress in patients with established cardiometabolic disease, the evidence base for this recommendation is weak. We sought to clarify the status of stress as a risk factor in cardiometabolic disease by investigating the associations between work stress and mortality in men and women with and without pre-existing cardiometabolic disease. Methods In this multicohort study, we used data from seven cohort studies in the IPD-Work consortium, initiated between 1985 and 2002 in Finland, France, Sweden, and the UK, to examine the association between work stress and mortality. Work stress was denoted as job strain or effort-reward imbalance at work. We extracted individual-level data on prevalent cardiometabolic diseases (coronary heart disease, stroke, or diabetes [without differentiation by diabetes type]) at baseline. Work stressors, socioeconomic status, and conventional and lifestyle risk factors (systolic and diastolic blood pressure, total cholesterol, smoking status, BMI, physical activity, and alcohol consumption) were also assessed at baseline. Mortality data, including date and cause of death, were obtained from national death registries. We used Cox proportional hazards regression to study the associations of work stressors with mortality in men and women with and without cardiometabolic disease. Results We identified 102 633 individuals with 1 423 753 person-years at risk (mean follow-up 13.9 years [SD 3.9]), of whom 3441 had prevalent cardiometabolic disease at baseline and 3841 died during follow-up. In men with cardiometabolic disease, age-standardised mortality rates were substantially higher in people with job strain (149.8 per 10 000 person-years) than in those without (97.7 per 10 000 person-years; mortality difference 52.1 per 10 000 person-years; multivariable-adjusted hazard ratio [HR] 1.68, 95% CI 1.19-2.35). This mortality difference for job strain was
Published: 2018
Full Text: View/download PDF

49. GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes

Author: Franceschini, Nora, Giambartolomei, Claudia, de Vries, Paul S., Finan, Chris, Bis, Joshua C., Huntley, Rachael P., Lovering, Ruth C., Tajuddin, Salman M., Winkler, Thomas W., Graff, Misa, Kavousi, Maryam, Dale, Caroline, Smith, Albert V., Hofer, Edith, van Leeuwen, Elisabeth M., Nolte, Ilja M., Lu, Lingyi, Scholz, Markus, Sargurupremraj, Muralidharan, Pitkanen, Niina, Franzen, Oscar, Joshi, Peter K., Noordam, Raymond, Marioni, Riccardo E., Hwang, Shih-Jen, Musani, Solomon K., Schminke, Ulf, Palmas, Walter, Isaacs, Aaron, Correa, Adolfo, Zonderman, Alan B., Hofman, Albert, Teumer, Alexander, Cox, Amanda J., Uitterlinden, Andre G., Wong, Andrew, Smit, Andries J., Newman, Anne B., Britton, Annie, Ruusalepp, Arno, Sennblad, Bengt, Hedblad, Bo, Pasaniuc, Bogdan, Penninx, Brenda W., Langefeld, Carl D., Wassel, Christina L., Tzourio, Christophe, Fava, Cristiano, Baldassarre, Damiano, O'Leary, Daniel H., Teupser, Daniel, Kuh, Diana, Tremoli, Elena, Mannarino, Elmo, Grossi, Enzo, Boerwinkle, Eric, Schadt, Eric E., Ingelsson, Erik, Veglia, Fabrizio, Rivadeneira, Fernando, Beutner, Frank, Chauhan, Ganesh, Heiss, Gerardo, Snieder, Harold, Campbell, Harry, Voelzke, Henry, Markus, Hugh S., Deary, Ian J., Jukema, J. Wouter, de Graaf, Jacqueline, Price, Jacqueline, Pott, Janne, Hopewell, Jemma C., Liang, Jingjing, Thiery, Joachim, Engmann, Jorgen, Gertow, Karl, Rice, Kenneth, Taylor, Kent D., Dhana, Klodian, Kiemeney, Lambertus A. L. M., Lind, Lars, Raffield, Laura M., Launer, Lenore J., Holdt, Lesca M., Doer, Marcus, Dichgans, Martin, Traylor, Matthew, Sitzer, Matthias, Kumari, Meena, Kivimaki, Mika, Nalls, Mike A., Melander, Olle, Raitakari, Olli, Franco, Oscar H., Rueda-Ochoa, Oscar L., Roussos, Panos, Whincup, Peter H., Amouyel, Philippe, Giral, Philippe, Anugu, Pramod, Wong, Quenna, Malik, Rainer, Rauramaa, Rainer, Burkhardt, Ralph, Hardy, Rebecca, Schmidt, Reinhold, de Mutsert, Renee, Morris, Richard W., Strawbridge, Rona J., Wannamethee, S. Goya, Hagg, Sara, Shah, Sonia, McLachlan, Stela, Trompet, Stella, Seshadri, Sudha, Kurl, Sudhir, Heckbert, Susan R., Ring, Susan, Harris, Tamara B., Lehtimaki, Terho, Galesloot, Tessel E., Shah, Tina, de Faire, Ulf, Plagnol, Vincent, Rosamond, Wayne D., Post, Wendy, Zhu, Xiaofeng, Zhang, Xiaoling, Guo, Xiuqing, Saba, Yasaman, Dehghan, Abbas, Seldenrijk, Adrie, Morrison, Alanna C., Hamsten, Anders, Psaty, Bruce M., van Duijn, Cornelia M., Lawlor, Deborah A., Mook-Kanamori, Dennis O., Bowden, Donald W., Schmidt, Helena, Wilson, James F., Wilson, James G., Rotter, Jerome I., Wardlaw, Joanna M., Deanfield, John, Halcox, Julian, Lyytikainen, Leo-Pekka, Loeffler, Markus, Evans, Michele K., Debette, Stephanie, Humphries, Steve E., Voelker, Uwe, Gudnason, Vilmundur, Hingorani, Aroon D., Bjorkegren, Johan L. M., Casas, Juan P., O'Donnell, Christopher J., Franceschini, Nora, Giambartolomei, Claudia, de Vries, Paul S., Finan, Chris, Bis, Joshua C., Huntley, Rachael P., Lovering, Ruth C., Tajuddin, Salman M., Winkler, Thomas W., Graff, Misa, Kavousi, Maryam, Dale, Caroline, Smith, Albert V., Hofer, Edith, van Leeuwen, Elisabeth M., Nolte, Ilja M., Lu, Lingyi, Scholz, Markus, Sargurupremraj, Muralidharan, Pitkanen, Niina, Franzen, Oscar, Joshi, Peter K., Noordam, Raymond, Marioni, Riccardo E., Hwang, Shih-Jen, Musani, Solomon K., Schminke, Ulf, Palmas, Walter, Isaacs, Aaron, Correa, Adolfo, Zonderman, Alan B., Hofman, Albert, Teumer, Alexander, Cox, Amanda J., Uitterlinden, Andre G., Wong, Andrew, Smit, Andries J., Newman, Anne B., Britton, Annie, Ruusalepp, Arno, Sennblad, Bengt, Hedblad, Bo, Pasaniuc, Bogdan, Penninx, Brenda W., Langefeld, Carl D., Wassel, Christina L., Tzourio, Christophe, Fava, Cristiano, Baldassarre, Damiano, O'Leary, Daniel H., Teupser, Daniel, Kuh, Diana, Tremoli, Elena, Mannarino, Elmo, Grossi, Enzo, Boerwinkle, Eric, Schadt, Eric E., Ingelsson, Erik, Veglia, Fabrizio, Rivadeneira, Fernando, Beutner, Frank, Chauhan, Ganesh, Heiss, Gerardo, Snieder, Harold, Campbell, Harry, Voelzke, Henry, Markus, Hugh S., Deary, Ian J., Jukema, J. Wouter, de Graaf, Jacqueline, Price, Jacqueline, Pott, Janne, Hopewell, Jemma C., Liang, Jingjing, Thiery, Joachim, Engmann, Jorgen, Gertow, Karl, Rice, Kenneth, Taylor, Kent D., Dhana, Klodian, Kiemeney, Lambertus A. L. M., Lind, Lars, Raffield, Laura M., Launer, Lenore J., Holdt, Lesca M., Doer, Marcus, Dichgans, Martin, Traylor, Matthew, Sitzer, Matthias, Kumari, Meena, Kivimaki, Mika, Nalls, Mike A., Melander, Olle, Raitakari, Olli, Franco, Oscar H., Rueda-Ochoa, Oscar L., Roussos, Panos, Whincup, Peter H., Amouyel, Philippe, Giral, Philippe, Anugu, Pramod, Wong, Quenna, Malik, Rainer, Rauramaa, Rainer, Burkhardt, Ralph, Hardy, Rebecca, Schmidt, Reinhold, de Mutsert, Renee, Morris, Richard W., Strawbridge, Rona J., Wannamethee, S. Goya, Hagg, Sara, Shah, Sonia, McLachlan, Stela, Trompet, Stella, Seshadri, Sudha, Kurl, Sudhir, Heckbert, Susan R., Ring, Susan, Harris, Tamara B., Lehtimaki, Terho, Galesloot, Tessel E., Shah, Tina, de Faire, Ulf, Plagnol, Vincent, Rosamond, Wayne D., Post, Wendy, Zhu, Xiaofeng, Zhang, Xiaoling, Guo, Xiuqing, Saba, Yasaman, Dehghan, Abbas, Seldenrijk, Adrie, Morrison, Alanna C., Hamsten, Anders, Psaty, Bruce M., van Duijn, Cornelia M., Lawlor, Deborah A., Mook-Kanamori, Dennis O., Bowden, Donald W., Schmidt, Helena, Wilson, James F., Wilson, James G., Rotter, Jerome I., Wardlaw, Joanna M., Deanfield, John, Halcox, Julian, Lyytikainen, Leo-Pekka, Loeffler, Markus, Evans, Michele K., Debette, Stephanie, Humphries, Steve E., Voelker, Uwe, Gudnason, Vilmundur, Hingorani, Aroon D., Bjorkegren, Johan L. M., Casas, Juan P., and O'Donnell, Christopher J.
Abstract: Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans.
Published: 2018
Full Text: View/download PDF

50. GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes

Author: Franceschini, Nora, Giambartolomei, Claudia, de Vries, Paul S., Finan, Chris, Bis, Joshua C., Huntley, Rachael P., Lovering, Ruth C., Tajuddin, Salman M., Winkler, Thomas W., Graff, Misa, Kavousi, Maryam, Dale, Caroline, Smith, Albert V., Hofer, Edith, van Leeuwen, Elisabeth M., Nolte, Ilja M., Lu, Lingyi, Scholz, Markus, Sargurupremraj, Muralidharan, Pitkanen, Niina, Franzen, Oscar, Joshi, Peter K., Noordam, Raymond, Marioni, Riccardo E., Hwang, Shih-Jen, Musani, Solomon K., Schminke, Ulf, Palmas, Walter, Isaacs, Aaron, Correa, Adolfo, Zonderman, Alan B., Hofman, Albert, Teumer, Alexander, Cox, Amanda J., Uitterlinden, Andre G., Wong, Andrew, Smit, Andries J., Newman, Anne B., Britton, Annie, Ruusalepp, Arno, Sennblad, Bengt, Hedblad, Bo, Pasaniuc, Bogdan, Penninx, Brenda W., Langefeld, Carl D., Wassel, Christina L., Tzourio, Christophe, Fava, Cristiano, Baldassarre, Damiano, O'Leary, Daniel H., Teupser, Daniel, Kuh, Diana, Tremoli, Elena, Mannarino, Elmo, Grossi, Enzo, Boerwinkle, Eric, Schadt, Eric E., Ingelsson, Erik, Veglia, Fabrizio, Rivadeneira, Fernando, Beutner, Frank, Chauhan, Ganesh, Heiss, Gerardo, Snieder, Harold, Campbell, Harry, Voelzke, Henry, Markus, Hugh S., Deary, Ian J., Jukema, J. Wouter, de Graaf, Jacqueline, Price, Jacqueline, Pott, Janne, Hopewell, Jemma C., Liang, Jingjing, Thiery, Joachim, Engmann, Jorgen, Gertow, Karl, Rice, Kenneth, Taylor, Kent D., Dhana, Klodian, Kiemeney, Lambertus A. L. M., Lind, Lars, Raffield, Laura M., Launer, Lenore J., Holdt, Lesca M., Doer, Marcus, Dichgans, Martin, Traylor, Matthew, Sitzer, Matthias, Kumari, Meena, Kivimaki, Mika, Nalls, Mike A., Melander, Olle, Raitakari, Olli, Franco, Oscar H., Rueda-Ochoa, Oscar L., Roussos, Panos, Whincup, Peter H., Amouyel, Philippe, Giral, Philippe, Anugu, Pramod, Wong, Quenna, Malik, Rainer, Rauramaa, Rainer, Burkhardt, Ralph, Hardy, Rebecca, Schmidt, Reinhold, de Mutsert, Renee, Morris, Richard W., Strawbridge, Rona J., Wannamethee, S. Goya, Hagg, Sara, Shah, Sonia, McLachlan, Stela, Trompet, Stella, Seshadri, Sudha, Kurl, Sudhir, Heckbert, Susan R., Ring, Susan, Harris, Tamara B., Lehtimaki, Terho, Galesloot, Tessel E., Shah, Tina, de Faire, Ulf, Plagnol, Vincent, Rosamond, Wayne D., Post, Wendy, Zhu, Xiaofeng, Zhang, Xiaoling, Guo, Xiuqing, Saba, Yasaman, Dehghan, Abbas, Seldenrijk, Adrie, Morrison, Alanna C., Hamsten, Anders, Psaty, Bruce M., van Duijn, Cornelia M., Lawlor, Deborah A., Mook-Kanamori, Dennis O., Bowden, Donald W., Schmidt, Helena, Wilson, James F., Wilson, James G., Rotter, Jerome I., Wardlaw, Joanna M., Deanfield, John, Halcox, Julian, Lyytikainen, Leo-Pekka, Loeffler, Markus, Evans, Michele K., Debette, Stephanie, Humphries, Steve E., Voelker, Uwe, Gudnason, Vilmundur, Hingorani, Aroon D., Bjorkegren, Johan L. M., Casas, Juan P., O'Donnell, Christopher J., Franceschini, Nora, Giambartolomei, Claudia, de Vries, Paul S., Finan, Chris, Bis, Joshua C., Huntley, Rachael P., Lovering, Ruth C., Tajuddin, Salman M., Winkler, Thomas W., Graff, Misa, Kavousi, Maryam, Dale, Caroline, Smith, Albert V., Hofer, Edith, van Leeuwen, Elisabeth M., Nolte, Ilja M., Lu, Lingyi, Scholz, Markus, Sargurupremraj, Muralidharan, Pitkanen, Niina, Franzen, Oscar, Joshi, Peter K., Noordam, Raymond, Marioni, Riccardo E., Hwang, Shih-Jen, Musani, Solomon K., Schminke, Ulf, Palmas, Walter, Isaacs, Aaron, Correa, Adolfo, Zonderman, Alan B., Hofman, Albert, Teumer, Alexander, Cox, Amanda J., Uitterlinden, Andre G., Wong, Andrew, Smit, Andries J., Newman, Anne B., Britton, Annie, Ruusalepp, Arno, Sennblad, Bengt, Hedblad, Bo, Pasaniuc, Bogdan, Penninx, Brenda W., Langefeld, Carl D., Wassel, Christina L., Tzourio, Christophe, Fava, Cristiano, Baldassarre, Damiano, O'Leary, Daniel H., Teupser, Daniel, Kuh, Diana, Tremoli, Elena, Mannarino, Elmo, Grossi, Enzo, Boerwinkle, Eric, Schadt, Eric E., Ingelsson, Erik, Veglia, Fabrizio, Rivadeneira, Fernando, Beutner, Frank, Chauhan, Ganesh, Heiss, Gerardo, Snieder, Harold, Campbell, Harry, Voelzke, Henry, Markus, Hugh S., Deary, Ian J., Jukema, J. Wouter, de Graaf, Jacqueline, Price, Jacqueline, Pott, Janne, Hopewell, Jemma C., Liang, Jingjing, Thiery, Joachim, Engmann, Jorgen, Gertow, Karl, Rice, Kenneth, Taylor, Kent D., Dhana, Klodian, Kiemeney, Lambertus A. L. M., Lind, Lars, Raffield, Laura M., Launer, Lenore J., Holdt, Lesca M., Doer, Marcus, Dichgans, Martin, Traylor, Matthew, Sitzer, Matthias, Kumari, Meena, Kivimaki, Mika, Nalls, Mike A., Melander, Olle, Raitakari, Olli, Franco, Oscar H., Rueda-Ochoa, Oscar L., Roussos, Panos, Whincup, Peter H., Amouyel, Philippe, Giral, Philippe, Anugu, Pramod, Wong, Quenna, Malik, Rainer, Rauramaa, Rainer, Burkhardt, Ralph, Hardy, Rebecca, Schmidt, Reinhold, de Mutsert, Renee, Morris, Richard W., Strawbridge, Rona J., Wannamethee, S. Goya, Hagg, Sara, Shah, Sonia, McLachlan, Stela, Trompet, Stella, Seshadri, Sudha, Kurl, Sudhir, Heckbert, Susan R., Ring, Susan, Harris, Tamara B., Lehtimaki, Terho, Galesloot, Tessel E., Shah, Tina, de Faire, Ulf, Plagnol, Vincent, Rosamond, Wayne D., Post, Wendy, Zhu, Xiaofeng, Zhang, Xiaoling, Guo, Xiuqing, Saba, Yasaman, Dehghan, Abbas, Seldenrijk, Adrie, Morrison, Alanna C., Hamsten, Anders, Psaty, Bruce M., van Duijn, Cornelia M., Lawlor, Deborah A., Mook-Kanamori, Dennis O., Bowden, Donald W., Schmidt, Helena, Wilson, James F., Wilson, James G., Rotter, Jerome I., Wardlaw, Joanna M., Deanfield, John, Halcox, Julian, Lyytikainen, Leo-Pekka, Loeffler, Markus, Evans, Michele K., Debette, Stephanie, Humphries, Steve E., Voelker, Uwe, Gudnason, Vilmundur, Hingorani, Aroon D., Bjorkegren, Johan L. M., Casas, Juan P., and O'Donnell, Christopher J.
Abstract: Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans.
Published: 2018
Full Text: View/download PDF

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