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1. Low-Density Lipoprotein Cholesterol Target Attainment in Patients With Established Cardiovascular Disease: Analysis of Routine Care Data

Author

Groenhof, T Katrien J, Kofink, Daniel, Bots, Michiel L, Nathoe, Hendrik M, Hoefer, Imo E, Van Solinge, Wouter W, Lely, A Titia, Asselbergs, Folkert W, and Haitjema, Saskia

Subjects
Computer applications to medicine. Medical informatics, R858-859.7
Abstract

BackgroundDirect feedback on quality of care is one of the key features of a learning health care system (LHS), enabling health care professionals to improve upon the routine clinical care of their patients during practice. ObjectiveThis study aimed to evaluate the potential of routine care data extracted from electronic health records (EHRs) in order to obtain reliable information on low-density lipoprotein cholesterol (LDL-c) management in cardiovascular disease (CVD) patients referred to a tertiary care center. MethodsWe extracted all LDL-c measurements from the EHRs of patients with a history of CVD referred to the University Medical Center Utrecht. We assessed LDL-c target attainment at the time of referral and per year. In patients with multiple measurements, we analyzed LDL-c trajectories, truncated at 6 follow-up measurements. Lastly, we performed a logistic regression analysis to investigate factors associated with improvement of LDL-c at the next measurement. ResultsBetween February 2003 and December 2017, 250,749 LDL-c measurements were taken from 95,795 patients, of whom 23,932 had a history of CVD. At the time of referral, 51% of patients had not reached their LDL-c target. A large proportion of patients (55%) had no follow-up LDL-c measurements. Most of the patients with repeated measurements showed no change in LDL-c levels over time: the transition probability to remain in the same category was up to 0.84. Sequence clustering analysis showed more women (odds ratio 1.18, 95% CI 1.07-1.10) in the cluster with both most measurements off target and the most LDL-c measurements furthest from the target. Timing of drug prescription was difficult to determine from our data, limiting the interpretation of results regarding medication management. ConclusionsRoutine care data can be used to provide feedback on quality of care, such as LDL-c target attainment. These routine care data show high off-target prevalence and little change in LDL-c over time. Registrations of diagnosis; follow-up trajectory, including primary and secondary care; and medication use need to be improved in order to enhance usability of the EHR system for adequate feedback.

Published
2020
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2. Preclinical Aortic Atherosclerosis in Adolescents With Chronic Disease

Author

Ververs, Francesca A., primary, Eikendal, Anouk L. M., additional, Kofink, Daniel, additional, Nuboer, Roos, additional, Westenberg, Jos J. M., additional, Hovenkamp, Gijs T., additional, Kemps, Jitske J.A., additional, Coenen, Iris C. J., additional, Daems, Joëlle J. N., additional, Claus, Laura R., additional, Ju, Yillie, additional, Wulffraat, Nico M., additional, van der Ent, Cornelis K., additional, Monaco, Claudia, additional, Boes, Marianne, additional, Leiner, Tim, additional, Grotenhuis, Heynric B., additional, and Schipper, Henk S., additional

Published
2022
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3. Preclinical Aortic Atherosclerosis in Adolescents With Chronic Disease

Author

CTI Boes, Onderzoek Vrouw Hart & Vaatziekten, Circulatory Health, Experimentele Afd. Cardiologie 1, Genetica Oper.Mang. Clinical Genetics, Cancer, Cluster B, Immuno/reuma ERN, Child Health, Infection & Immunity, Regenerative Medicine and Stem Cells, Longziekten patientenzorg, Speerpunt Child Health, Onderzoek, MS Radiologie, Cardiologie patientenzorg, Ververs, Francesca A, Eikendal, Anouk L M, Kofink, Daniel, Nuboer, Roos, Westenberg, Jos J M, Hovenkamp, Gijs T, Kemps, Jitske J A, Coenen, Iris C J, Daems, Joëlle J N, Claus, Laura R, Ju, Yillie, Wulffraat, Nico M, van der Ent, Cornelis K, Monaco, Claudia, Boes, Marianne, Leiner, Tim, Grotenhuis, Heynric B, Schipper, Henk S, CTI Boes, Onderzoek Vrouw Hart & Vaatziekten, Circulatory Health, Experimentele Afd. Cardiologie 1, Genetica Oper.Mang. Clinical Genetics, Cancer, Cluster B, Immuno/reuma ERN, Child Health, Infection & Immunity, Regenerative Medicine and Stem Cells, Longziekten patientenzorg, Speerpunt Child Health, Onderzoek, MS Radiologie, Cardiologie patientenzorg, Ververs, Francesca A, Eikendal, Anouk L M, Kofink, Daniel, Nuboer, Roos, Westenberg, Jos J M, Hovenkamp, Gijs T, Kemps, Jitske J A, Coenen, Iris C J, Daems, Joëlle J N, Claus, Laura R, Ju, Yillie, Wulffraat, Nico M, van der Ent, Cornelis K, Monaco, Claudia, Boes, Marianne, Leiner, Tim, Grotenhuis, Heynric B, and Schipper, Henk S

Published
2022

4. Model selection for metabolomics: predicting diagnosis of coronary artery disease using automated machine learning

Author

Experimentele Afd. Cardiologie 1, Team Medisch, Circulatory Health, Orlenko, Alena, Kofink, Daniel, Lyytikäinen, Leo-Pekka, Nikus, Kjell, Mishra, Pashupati, Kuukasjärvi, Pekka, Karhunen, Pekka J, Kähönen, Mika, Laurikka, Jari O, Lehtimäki, Terho, Asselbergs, Folkert W, Moore, Jason H, Experimentele Afd. Cardiologie 1, Team Medisch, Circulatory Health, Orlenko, Alena, Kofink, Daniel, Lyytikäinen, Leo-Pekka, Nikus, Kjell, Mishra, Pashupati, Kuukasjärvi, Pekka, Karhunen, Pekka J, Kähönen, Mika, Laurikka, Jari O, Lehtimäki, Terho, Asselbergs, Folkert W, and Moore, Jason H

Published
2020

5. Low-Density Lipoprotein Cholesterol Target Attainment in Patients With Established Cardiovascular Disease: Analysis of Routine Care Data

Author

Cardiovasculaire Epi Team 5, Circulatory Health, Cardiovasculaire Epidemiologie, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Team Medisch, CDL Arcadia, Centraal Diagnostisch Laboratorium, MS Verloskunde, Child Health, Groenhof, T Katrien J, Kofink, Daniel, Bots, Michiel L, Nathoe, Hendrik M, Hoefer, Imo E, Van Solinge, Wouter W, Lely, A Titia, Asselbergs, Folkert W, Haitjema, Saskia, Cardiovasculaire Epi Team 5, Circulatory Health, Cardiovasculaire Epidemiologie, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Team Medisch, CDL Arcadia, Centraal Diagnostisch Laboratorium, MS Verloskunde, Child Health, Groenhof, T Katrien J, Kofink, Daniel, Bots, Michiel L, Nathoe, Hendrik M, Hoefer, Imo E, Van Solinge, Wouter W, Lely, A Titia, Asselbergs, Folkert W, and Haitjema, Saskia

Published
2020

6. Model selection for metabolomics: predicting diagnosis of coronary artery disease using automated machine learning

Author

Orlenko, Alena, primary, Kofink, Daniel, additional, Lyytikäinen, Leo-Pekka, additional, Nikus, Kjell, additional, Mishra, Pashupati, additional, Kuukasjärvi, Pekka, additional, Karhunen, Pekka J, additional, Kähönen, Mika, additional, Laurikka, Jari O, additional, Lehtimäki, Terho, additional, Asselbergs, Folkert W, additional, and Moore, Jason H, additional

Published
2019
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7. 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., and Asselbergs, Folkert W.

Subjects
Genetics & Heredity, RISK, Kardiologi, Science & Technology, Cardiac & Cardiovascular Systems, VARIANTS, RECURRENT MYOCARDIAL-INFARCTION, myocardial infarction, risk factor, BIAS, Cardiovascular System & Cardiology, LOCUS, Cardiac and Cardiovascular Systems, cardiovascular diseases, chromosome, genetic, variation, Medical Genetics, Life Sciences & Biomedicine, secondary prevention, Medicinsk genetik
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 (GENIUS-CHD 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

Published
2019

8. Subsequent Event Risk in Individuals With Established Coronary Heart Disease

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, Klungel, Olaf H, Maitland-van der Zee, Anke H, Afd Pharmacoepi & Clinical Pharmacology, and Pharmacoepidemiology and Clinical Pharmacology

Subjects
myocardial infarction, genetics, prognosis, coronary artery disease, sedundary preventation
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

9. Association of Chromosome 9p21 With Subsequent Coronary Heart Disease Events

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, Dubé, 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, 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 WT, Tang, WH Wilson, Trompet, Stella, van der Laan, Sander W, van Setten, Jessica, Vilmundarson, Ragnar O, Viviani Anselmi, Chiara, 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, Newton Cheh, Chris, Pitha, Jan, Saely, Christoph H, Samman-Tahhan, Ayman, Sandesara, Pratik B, Teren, Andrej, Timmis, Adam, Van de Werf, Frans, Wauters, Els, Wilde, Arthur AM, 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 AA, 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, Kähönen, Mika, Kettner, Jiri, Kiliszek, Marek, Klungel, Olaf H, Lagerqvist, Bo, Lambrechts, Diether, Laurikka, Jari O, Lehtimäki, 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, Pilote, Louise, Quyyumi, Arshed A, Richards, A Mark, Sanak, Marek, Scholz, Markus, Siegbahn, Agneta, Sinisalo, Juha, Smith, J Gustav, Spertus, John A, Stewart, Alexandre FR, Szczeklik, Wojciech, Szpakowicz, Anna, Ten Berg, Jurriën M, Thanassoulis, George, Thiery, Joachim, van der Graaf, Yolanda, Visseren, Frank LJ, Waltenberger, Johannes, CARDIoGRAMPlusC4D Consortium, Van der Harst, Pim, Tardif, Jean-Claude, Sattar, Naveed, Lang, Chim C, Pare, Guillaume, Brophy, James M, Anderson, Jeffrey L, März, Winfried, Wallentin, Lars, Cameron, Vicky A, Horne, Benjamin D, Samani, Nilesh J, Hingorani, Aroon D, and Asselbergs, Folkert W

Subjects
cardiovascular diseases
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 (GENIUS-CHD 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

Published
2019

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

Subjects
myocardial infarction, genetics, prognosis, coronary artery disease, secondary prevention
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

11. Model selection for metabolomics : predicting diagnosis of coronary artery disease using automated machine learning (AutoML)

Author

Orlenko, Alena, Kofink, Daniel, Lyytikäinen, Leo-Pekka, Nikus, Kjell, Mishra, Pashupati, Kuukasjärvi, Pekka, Karhunen, Pekka, Kähönen, Mika, Laurikka, Jari, Lehtimäki, Terho, Asselberg, Folkert, Moore, Jason, Lääketieteen ja terveysteknologian tiedekunta - Faculty of Medicine and Health Technology, and Tampere University

Subjects
Sisätaudit - Internal medicine, Kirurgia, anestesiologia, tehohoito, radiologia - Surgery, anesthesiology, intensive care, radiology
Published
2019

12. 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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13. Association of the coronary artery disease risk gene GUCY1A3 with ischaemic events after coronary intervention

Author

Kessler, Thorsten, Wolf, Bernhard, Eriksson, Niclas, Kofink, Daniel, Mahmoodi, Bakhtawar K., Rai, Himanshu, Tragante, Vinicius, Åkerblom, Axel, Becker, Richard C., Bernlochner, Isabell, Bopp, Roman, James, Stefan, Katus, Hugo A., Mayer, Katharina, Munz, Matthias, Nordio, Francesco, O'Donoghue, Michelle L., Sager, Hendrik B., Sibbing, Dirk, Solakov, Linda, Storey, Robert F., Wobst, Jana, Asselbergs, Folkert W., Byrne, Robert A., Erdmann, Jeanette, Koenig, Wolfgang, Laugwitz, Karl-Ludwig, ten Berg, Jurrien M., Wallentin, Lars, Kastrati, Adnan, Schunkert, Heribert, Kessler, Thorsten, Wolf, Bernhard, Eriksson, Niclas, Kofink, Daniel, Mahmoodi, Bakhtawar K., Rai, Himanshu, Tragante, Vinicius, Åkerblom, Axel, Becker, Richard C., Bernlochner, Isabell, Bopp, Roman, James, Stefan, Katus, Hugo A., Mayer, Katharina, Munz, Matthias, Nordio, Francesco, O'Donoghue, Michelle L., Sager, Hendrik B., Sibbing, Dirk, Solakov, Linda, Storey, Robert F., Wobst, Jana, Asselbergs, Folkert W., Byrne, Robert A., Erdmann, Jeanette, Koenig, Wolfgang, Laugwitz, Karl-Ludwig, ten Berg, Jurrien M., Wallentin, Lars, Kastrati, Adnan, and Schunkert, Heribert

Abstract

Aim A common genetic variant at the GUCY1A3 coronary artery disease locus has been shown to influence platelet aggregation. The risk of ischaemic events including stent thrombosis varies with the efficacy of aspirin to inhibit platelet reactivity. This study sought to investigate whether homozygous GUCY1A3 (rs7692387) risk allele carriers display higher on-aspirin platelet reactivity and risk of ischaemic events early after coronary intervention. Methods and results The association of GUCY1A3 genotype and on-aspirin platelet reactivity was analysed in the genetics substudy of the ISAR-ASPI registry (n = 1678) using impedance aggregometry. The clinical outcome cardiovascular death or stent thrombosis within 30 days after stenting was investigated in a meta-analysis of substudies of the ISAR-ASPI registry, the PLATO trial (n = 3236), and the Utrecht Coronary Biobank (n = 1003) comprising a total 5917 patients. Homozygous GUCY1A3 risk allele carriers (GG) displayed increased on-aspirin platelet reactivity compared with non-risk allele (AA/AG) carriers [150 (interquartile range 91-209) vs. 134 (85-194) AU.min, P < 0.01]. More homozygous risk allele carriers, compared with non-risk allele carriers, were assigned to the high-risk group for ischaemic events (>203AU.min; 29.5 vs. 24.2%, P = 0.02). Homozygous risk allele carriers were also at higher risk for cardiovascular death or stent thrombosis (hazard ratio 1.70, 95% confidence interval 1.08-2.68; P = 0.02). Bleeding risk was not altered. Conclusion We conclude that homozygous GUCY1A3 risk allele carriers are at increased risk of cardiovascular death or stent thrombosis within 30 days after coronary stenting, likely due to higher on-aspirin platelet reactivity. Whether GUCY1A3 genotype helps to tailor antiplatelet treatment remains to be investigated.

Published
2019
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14. Subsequent Event Risk in Individuals With Established Coronary Heart Disease

Author

Afd Pharmacoepi & Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology, 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, Klungel, Olaf H, Maitland-van der Zee, Anke H, Afd Pharmacoepi & Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology, 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, Klungel, Olaf H, and Maitland-van der Zee, Anke H

Published
2019

15. 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

16. 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

17. Association of the coronary artery disease risk gene GUCY1A3 with ischaemic events after coronary intervention

Author

Kessler, Thorsten, primary, Wolf, Bernhard, additional, Eriksson, Niclas, additional, Kofink, Daniel, additional, Mahmoodi, Bakhtawar K, additional, Rai, Himanshu, additional, Tragante, Vinicius, additional, Åkerblom, Axel, additional, Becker, Richard C, additional, Bernlochner, Isabell, additional, Bopp, Roman, additional, James, Stefan, additional, Katus, Hugo A, additional, Mayer, Katharina, additional, Munz, Matthias, additional, Nordio, Francesco, additional, O’Donoghue, Michelle L, additional, Sager, Hendrik B, additional, Sibbing, Dirk, additional, Solakov, Linda, additional, Storey, Robert F, additional, Wobst, Jana, additional, Asselbergs, Folkert W, additional, Byrne, Robert A, additional, Erdmann, Jeanette, additional, Koenig, Wolfgang, additional, Laugwitz, Karl-Ludwig, additional, ten Berg, Jurrien M, additional, Wallentin, Lars, additional, Kastrati, Adnan, additional, and Schunkert, Heribert, additional

Published
2019
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18. Monocyte gene expression in childhood obesity is associated with obesity and complexity of atherosclerosis in adults

Author

Keustermans, G C, Kofink, Daniel, Eikendal, A.L., de Jager, W., Meerding, J., Nuboer, R., Waltenberger, J., Kraaijeveld, A.O., Jukema, J Wouter, Sels, J.W., Garssen, J, Prakken, Berent J., Asselbergs, Folkert W, Kalkhoven, E., Hoefer, Imo E., Pasterkamp, G., Schipper, Henk S, Afd Pharmacology, Pharmacology, Cardiology, Gastroenterology and Hepatology, Graduate School, General Internal Medicine, Afd Pharmacology, Pharmacology, RS: CARIM - R3 - Vascular biology, Cardiologie, Intensive Care, MUMC+: MA Med Staf Spec Cardiologie (9), and MUMC+: MA Medische Staf IC (9)

Subjects
0301 basic medicine, Male, Pediatric Obesity, PREDICTION, SUBSETS, lcsh:Medicine, Coronary Artery Disease, 030204 cardiovascular system & hematology, Coronary Angiography, Severity of Illness Index, Monocytes, Body Mass Index, Coronary artery disease, Cohort Studies, 0302 clinical medicine, IMP Dehydrogenase, Child, lcsh:Science, Foam cells, RISK, SYNTAX SCORE, Multidisciplinary, Middle Aged, medicine.anatomical_structure, METABOLIC DISEASE, Female, Adult, Adolescent, CD14, Down-Regulation, Childhood obesity, Article, 03 medical and health sciences, Monocytosis, INFLAMMATION, medicine, Humans, General, Coronary atherosclerosis, business.industry, Monocyte, lcsh:R, Case-control study, Membrane Proteins, IMMUNOMETABOLISM, medicine.disease, Atherosclerosis, Obesity, 030104 developmental biology, Case-Control Studies, Immunology, lcsh:Q, business, Transcriptome
Abstract

Childhood obesity coincides with increased numbers of circulating classical CD14++CD16- and intermediate CD14++CD16+ monocytes. Monocytes are key players in the development and exacerbation of atherosclerosis, which prompts the question as to whether the monocytosis in childhood obesity contributes to atherogenesis over the years. Here, we dissected the monocyte gene expression profile in childhood obesity using an Illumina microarray platform on sorted monocytes of 35 obese children and 16 lean controls. Obese children displayed a distinctive monocyte gene expression profile compared to lean controls. Upon validation with quantitative PCR, we studied the association of the top 5 differentially regulated monocyte genes in childhood obesity with obesity and complexity of coronary atherosclerosis (SYNTAX score) in a cohort of 351 adults at risk for ischemic cardiovascular disease. The downregulation of monocyte IMPDH2 and TMEM134 in childhood obesity was also observed in obese adults. Moreover, downregulation of monocyte TMEM134 was associated with a higher SYNTAX atherosclerosis score in adults. In conclusion, childhood obesity entails monocyte gene expression alterations associated with obesity and enhanced complexity of coronary atherosclerosis in adults.

Published
2017

19. Use of novel biomarkers to explore cardiovascular risk and drug effects

Author

Kofink, Daniel, Asselbergs, Folkert, van der Harst, P., Patel, R.S., and University Utrecht

Subjects
risk prediction, cardiovascular disease, drug effects, biomarkers, secondary prevention
Abstract

Cardiovascular disease causes immense health care costs and production losses, underscoring the need to identify individuals at risk requiring preventive treatment. This thesis aims to identify novel cardiovascular biomarkers and to advance understanding of the pathophysiological mechanisms underlying cardiovascular disease progression. Moreover, we used high-throughput metabolic profiling to study molecular drug effects. Chapter 2 relates altered monocyte gene expression in childhood obesity to atherosclerotic disease complexity in adult patients. Chapter 3 investigates the association of loss of chromosome Y with atherosclerotic plaque characteristics and clinical outcome after endarterectomy. Chapter 4 explores the ability of routinely measured hematological parameters to improve prediction of recurrent vascular events in vascular patients. The remaining chapters report results from metabolic profiling studies. Chapter 5 presents findings from a prospective study of two angiographic cohorts, in which we identified biomarkers that improve prediction of subsequent cardiovascular events. In Chapter 6, we use clinical trial data to explore the effect of metformin on metabolic profiles and to study biomarkers of infarct size and left ventricular ejection fraction after myocardial infarction. In Chapter 7, we investigate the longitudinal effect of pravastatin treatment on metabolic profiles, using data from a randomized clinical trial.

Published
2017

20. Routinely measured hematological parameters and prediction of recurrent vascular events in patients with clinically manifest vascular disease

Author

Kofink, Daniel, Muller, Steven A., Patel, Riyaz S., Dorresteijn, Jannick A.N., Berkelmans, Gijs F.N., De Groot, Mark C.H., Van Solinge, Wouter W., Haitjema, Saskia, Leiner, Tim, Visseren, Frank L.J., Hoefer, Imo E., Asselbergs, Folkert W., on behalf of the SMART Study Group, Kofink, Daniel, Muller, Steven A., Patel, Riyaz S., Dorresteijn, Jannick A.N., Berkelmans, Gijs F.N., De Groot, Mark C.H., Van Solinge, Wouter W., Haitjema, Saskia, Leiner, Tim, Visseren, Frank L.J., Hoefer, Imo E., Asselbergs, Folkert W., and on behalf of the SMART Study Group

Published
2018

21. Routinely measured hematological parameters and prediction of recurrent vascular events in patients with clinically manifest vascular disease

Author

Researchbureau DHL, Onderzoek Precision medicine, Circulatory Health, Interne Geneeskunde Vasculaire, Unit Opleiding Aios, CDL Arcadia, Other research (not in main researchprogram), Centraal Diagnostisch Laboratorium, Infection & Immunity, Experimentele Afd. Cardiologie 1, Researchgr. Cardiovasculaire Radiologie, Kofink, Daniel, Muller, Steven A., Patel, Riyaz S., Dorresteijn, Jannick A.N., Berkelmans, Gijs F.N., De Groot, Mark C.H., Van Solinge, Wouter W., Haitjema, Saskia, Leiner, Tim, Visseren, Frank L.J., Hoefer, Imo E., Asselbergs, Folkert W., On behalf of the SMART Study Group, Researchbureau DHL, Onderzoek Precision medicine, Circulatory Health, Interne Geneeskunde Vasculaire, Unit Opleiding Aios, CDL Arcadia, Other research (not in main researchprogram), Centraal Diagnostisch Laboratorium, Infection & Immunity, Experimentele Afd. Cardiologie 1, Researchgr. Cardiovasculaire Radiologie, Kofink, Daniel, Muller, Steven A., Patel, Riyaz S., Dorresteijn, Jannick A.N., Berkelmans, Gijs F.N., De Groot, Mark C.H., Van Solinge, Wouter W., Haitjema, Saskia, Leiner, Tim, Visseren, Frank L.J., Hoefer, Imo E., Asselbergs, Folkert W., and On behalf of the SMART Study Group

Published
2018

22. Model selection for metabolomics: predicting diagnosis of coronary artery disease using automated machine learning.

Author

Orlenko, Alena, Kofink, Daniel, Lyytikäinen, Leo-Pekka, Nikus, Kjell, Mishra, Pashupati, Kuukasjärvi, Pekka, Karhunen, Pekka J, Kähönen, Mika, Laurikka, Jari O, Lehtimäki, Terho, Asselbergs, Folkert W, and Moore, Jason H

Subjects
*INTERNET servers, *CORONARY disease, *MACHINE learning
Abstract

Motivation Selecting the optimal machine learning (ML) model for a given dataset is often challenging. Automated ML (AutoML) has emerged as a powerful tool for enabling the automatic selection of ML methods and parameter settings for the prediction of biomedical endpoints. Here, we apply the tree-based pipeline optimization tool (TPOT) to predict angiographic diagnoses of coronary artery disease (CAD). With TPOT, ML models are represented as expression trees and optimal pipelines discovered using a stochastic search method called genetic programing. We provide some guidelines for TPOT-based ML pipeline selection and optimization-based on various clinical phenotypes and high-throughput metabolic profiles in the Angiography and Genes Study (ANGES). Results We analyzed nuclear magnetic resonance-derived lipoprotein and metabolite profiles in the ANGES cohort with a goal to identify the role of non-obstructive CAD patients in CAD diagnostics. We performed a comparative analysis of TPOT-generated ML pipelines with selected ML classifiers, optimized with a grid search approach, applied to two phenotypic CAD profiles. As a result, TPOT-generated ML pipelines that outperformed grid search optimized models across multiple performance metrics including balanced accuracy and area under the precision-recall curve. With the selected models, we demonstrated that the phenotypic profile that distinguishes non-obstructive CAD patients from no CAD patients is associated with higher precision, suggesting a discrepancy in the underlying processes between these phenotypes. Availability and implementation TPOT is freely available via http://epistasislab.github.io/tpot/. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Published
2020
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23. Relations between lipoprotein(a) concentrations, LPA genetic variants, and the risk of mortality in patients with established coronary heart disease : a molecular and genetic association study

Author

Zewinger, Stephen, Kleber, Marcus E., Tragante, Vinicius, McCubrey, Raymond O., Schmidt, Amand F., Direk, Kenan, Laufs, Ulrich, Werner, Christian, Koenig, Wolfgang, Rothenbacher, Dietrich, Mons, Ute, Breitling, Lutz P., Brenner, Herrmann, Jennings, Richard T., Petrakis, Ioannis, Triem, Sarah, Klug, Mira, Filips, Alexandra, Blankenberg, Stefan, Waldeyer, Christoph, Sinning, Christoph, Schnabel, Renate B., Lackner, Karl J., Vlachopoulou, Efthymia, Nygard, Ottar, Svingen, Gard Frodahl Tveitevag, Pedersen, Eva Ringdal, Tell, Grethe S., Sinisalo, Juha, Nieminen, Markku S., Laaksonen, Reijo, Trompet, Stella, Smit, Roelof A. J., Sattar, Naveed, Jukema, J. Wouter, Groesdonk, Heinrich V., Delgado, Graciela, Stojakovic, Tatjana, Pilbrow, Anna P., Cameron, Vicky A., Richards, A. Mark, Doughty, Robert N., Gong, Yan, Cooper-DeHoff, Rhonda, Johnson, Julie, Scholz, Markus, Beutner, Frank, Thiery, Joachim, Smith, J. Gustav, Vilmundarson, Ragnar O., McPherson, Ruth, Stewart, Alexandre F. R., Cresci, Sharon, Lenzini, Petra A., Spertus, John A., Olivieri, Oliviero, Girelli, Domenico, Martinelli, Nicola I., Leiherer, Andreas, Saely, Christoph H., Drexel, Heinz, Muendlein, Axel, Braund, Peter S., Nelson, Christopher P., Samani, Nilesh J., Kofink, Daniel, Hoefer, Imo E., Pasterkamp, Gerard, Quyyumi, Arshed A., Ko, Yi-An, Hartiala, Jaana A., Allayee, Hooman, Tang, W. H. Wilson, Hazen, Stanley L., Eriksson, Niclas, Held, Claes, Hagström, Emil, Wallentin, Lars, Åkerblom, Axel, Siegbahn, A, Karp, Igor, Labos, Christopher, Pilote, Louise, Engert, James C., Brophy, James M., Thanassoulis, George, Bogaty, Peter, Szczeklik, Wojciech, Kaczor, Marcin, Sanak, Marek, Virani, Salim S., Ballantyne, Christie M., Lee, Vei-Vei, Boerwinkle, Eric, Holmes, Michael V., Horne, Benjamin D., Hingorani, Aroon, Asselbergs, Folkert W., Patel, Riyaz S., Kraemer, Bernhard K., Scharnagl, Hubert, Fliser, Danilo, Maerz, Winfried, Speer, Thimoteus, Zewinger, Stephen, Kleber, Marcus E., Tragante, Vinicius, McCubrey, Raymond O., Schmidt, Amand F., Direk, Kenan, Laufs, Ulrich, Werner, Christian, Koenig, Wolfgang, Rothenbacher, Dietrich, Mons, Ute, Breitling, Lutz P., Brenner, Herrmann, Jennings, Richard T., Petrakis, Ioannis, Triem, Sarah, Klug, Mira, Filips, Alexandra, Blankenberg, Stefan, Waldeyer, Christoph, Sinning, Christoph, Schnabel, Renate B., Lackner, Karl J., Vlachopoulou, Efthymia, Nygard, Ottar, Svingen, Gard Frodahl Tveitevag, Pedersen, Eva Ringdal, Tell, Grethe S., Sinisalo, Juha, Nieminen, Markku S., Laaksonen, Reijo, Trompet, Stella, Smit, Roelof A. J., Sattar, Naveed, Jukema, J. Wouter, Groesdonk, Heinrich V., Delgado, Graciela, Stojakovic, Tatjana, Pilbrow, Anna P., Cameron, Vicky A., Richards, A. Mark, Doughty, Robert N., Gong, Yan, Cooper-DeHoff, Rhonda, Johnson, Julie, Scholz, Markus, Beutner, Frank, Thiery, Joachim, Smith, J. Gustav, Vilmundarson, Ragnar O., McPherson, Ruth, Stewart, Alexandre F. R., Cresci, Sharon, Lenzini, Petra A., Spertus, John A., Olivieri, Oliviero, Girelli, Domenico, Martinelli, Nicola I., Leiherer, Andreas, Saely, Christoph H., Drexel, Heinz, Muendlein, Axel, Braund, Peter S., Nelson, Christopher P., Samani, Nilesh J., Kofink, Daniel, Hoefer, Imo E., Pasterkamp, Gerard, Quyyumi, Arshed A., Ko, Yi-An, Hartiala, Jaana A., Allayee, Hooman, Tang, W. H. Wilson, Hazen, Stanley L., Eriksson, Niclas, Held, Claes, Hagström, Emil, Wallentin, Lars, Åkerblom, Axel, Siegbahn, A, Karp, Igor, Labos, Christopher, Pilote, Louise, Engert, James C., Brophy, James M., Thanassoulis, George, Bogaty, Peter, Szczeklik, Wojciech, Kaczor, Marcin, Sanak, Marek, Virani, Salim S., Ballantyne, Christie M., Lee, Vei-Vei, Boerwinkle, Eric, Holmes, Michael V., Horne, Benjamin D., Hingorani, Aroon, Asselbergs, Folkert W., Patel, Riyaz S., Kraemer, Bernhard K., Scharnagl, Hubert, Fliser, Danilo, Maerz, Winfried, and Speer, Thimoteus

Abstract

Background: Lipoprotein(a) concentrations in plasma are associated with cardiovascular risk in the general population. Whether lipoprotein(a) concentrations or LPA genetic variants predict long-term mortality in patients with established coronary heart disease remains less clear. Methods: We obtained data from 3313 patients with established coronary heart disease in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. We tested associations of tertiles of lipoprotein(a) concentration in plasma and two LPA single-nucleotide polymorphisms ([SNPs] rs10455872 and rs3798220) with all-cause mortality and cardiovascular mortality by Cox regression analysis and with severity of disease by generalised linear modelling, with and without adjustment for age, sex, diabetes diagnosis, systolic blood pressure, BMI, smoking status, estimated glomerular filtration rate, LDL-cholesterol concentration, and use of lipid-lowering therapy. Results for plasma lipoprotein(a) concentrations were validated in five independent studies involving 10 195 patients with established coronary heart disease. Results for genetic associations were replicated through large-scale collaborative analysis in the GENIUS-CHD consortium, comprising 106 353 patients with established coronary heart disease and 19 332 deaths in 22 studies or cohorts. Findings: The median follow-up was 9.9 years. Increased severity of coronary heart disease was associated with lipoprotein(a) concentrations in plasma in the highest tertile (adjusted hazard radio [HR] 1.44, 95% CI 1.14-1.83) and the presence of either LPA SNP (1.88, 1.40-2.53). No associations were found in LURIC with all-cause mortality (highest tertile of lipoprotein(a) concentration in plasma 0.95, 0.81-1.11 and either LPA SNP 1.10, 0.92-1.31) or cardiovascular mortality (0.99, 0.81-1.2 and 1.13, 0.90-1.40, respectively) or in the validation studies. Interpretation: In patients with prevalent coronary heart disease, lipoprotein(a) concentrations and gen

Published
2017
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26. Loss of y Chromosome in Blood Is Associated with Major Cardiovascular Events during Follow-Up in Men after Carotid Endarterectomy

Author

Haitjema, Saskia, Kofink, Daniel, Van Setten, Jessica, Van Der Laan, Sander W., Schoneveld, Arjan H., Eales, James, Tomaszewski, Maciej, De Jager, Saskia C.A., Pasterkamp, Gerard, Asselbergs, Folkert W., Den Ruijter, Hester M., Haitjema, Saskia, Kofink, Daniel, Van Setten, Jessica, Van Der Laan, Sander W., Schoneveld, Arjan H., Eales, James, Tomaszewski, Maciej, De Jager, Saskia C.A., Pasterkamp, Gerard, Asselbergs, Folkert W., and Den Ruijter, Hester M.

Published
2017

27. Effect of Metformin on Metabolites and Relation With Myocardial Infarct Size and Left Ventricular Ejection Fraction After Myocardial Infarction

Author

Eppinga, Ruben N, Kofink, Daniel, Dullaart, Robin P F, Dalmeijer, Geertje W, Lipsic, Erik, van Veldhuisen, Dirk J, van der Horst, Iwan C C, Asselbergs, Folkert W, van der Harst, Pim, Eppinga, Ruben N, Kofink, Daniel, Dullaart, Robin P F, Dalmeijer, Geertje W, Lipsic, Erik, van Veldhuisen, Dirk J, van der Horst, Iwan C C, Asselbergs, Folkert W, and van der Harst, Pim

Published
2017

28. Additional Candidate Genes for Human Atherosclerotic Disease Identified Through Annotation Based on Chromatin Organization

Author

Haitjema, Saskia, Meddens, Claartje A., Van Der Laan, Sander W., Kofink, Daniel, Harakalova, Magdalena, Tragante, Vinicius, Foroughi Asl, Hassan, Van Setten, Jessica, Brandt, Maarten M., Bis, Joshua C., O'Donnell, Christopher, Cheng, Caroline, Hoefer, Imo E., Waltenberger, Johannes, Biessen, Erik A L, Jukema, J. Wouter, Doevendans, Pieter A.F.M., Nieuwenhuis, Edward E.S., Erdmann, Jeanette, Björkegren, Johan L M, Pasterkamp, Gerard, Asselbergs, Folkert W., Den Ruijter, Hester M., Mokry, Michal, Haitjema, Saskia, Meddens, Claartje A., Van Der Laan, Sander W., Kofink, Daniel, Harakalova, Magdalena, Tragante, Vinicius, Foroughi Asl, Hassan, Van Setten, Jessica, Brandt, Maarten M., Bis, Joshua C., O'Donnell, Christopher, Cheng, Caroline, Hoefer, Imo E., Waltenberger, Johannes, Biessen, Erik A L, Jukema, J. Wouter, Doevendans, Pieter A.F.M., Nieuwenhuis, Edward E.S., Erdmann, Jeanette, Björkegren, Johan L M, Pasterkamp, Gerard, Asselbergs, Folkert W., Den Ruijter, Hester M., and Mokry, Michal

Published
2017

29. Monocyte gene expression in childhood obesity is associated with obesity and complexity of atherosclerosis in adults

Author

Afd Pharmacology, Pharmacology, Keustermans, G C, Kofink, Daniel, Eikendal, A.L., de Jager, W., Meerding, J., Nuboer, R., Waltenberger, J., Kraaijeveld, A.O., Jukema, J Wouter, Sels, J.W., Garssen, J, Prakken, Berent J., Asselbergs, Folkert W, Kalkhoven, E., Hoefer, Imo E., Pasterkamp, G., Schipper, Henk S, Afd Pharmacology, Pharmacology, Keustermans, G C, Kofink, Daniel, Eikendal, A.L., de Jager, W., Meerding, J., Nuboer, R., Waltenberger, J., Kraaijeveld, A.O., Jukema, J Wouter, Sels, J.W., Garssen, J, Prakken, Berent J., Asselbergs, Folkert W, Kalkhoven, E., Hoefer, Imo E., Pasterkamp, G., and Schipper, Henk S

Published
2017

30. Statin Effects on Metabolic Profiles: Data from the PREVEND IT (Prevention of Renal and Vascular End-stage Disease Intervention Trial)

Author

Onderzoek Vrouw Hart & Vaatziekten, Onderzoek Precision medicine, Circulatory Health, Team Medisch, Kofink, Daniel, Eppinga, Ruben N., Gilst, Wiek H.Van, Bakker, Stephan J.L., Dullaart, Robin P.F., Harst, Pim Van Der, Asselbergs, Folkert W., Onderzoek Vrouw Hart & Vaatziekten, Onderzoek Precision medicine, Circulatory Health, Team Medisch, Kofink, Daniel, Eppinga, Ruben N., Gilst, Wiek H.Van, Bakker, Stephan J.L., Dullaart, Robin P.F., Harst, Pim Van Der, and Asselbergs, Folkert W.

Published
2017

32. Relations between lipoprotein(a) concentrations, LPA genetic variants, and the risk of mortality in patients with established coronary heart disease: a molecular and genetic association study

Author

Experimentele Afd. Cardiologie 1, Circulatory Health, Cardiovasculaire Immunologie, UMC Utrecht, Onderzoek Precision medicine, CDL Staf Research, CDL Arcadia, CDL Cluster Onderzoek en Onderwijs, Team Medisch, Zewinger, Stephen, Kleber, Marcus E., Tragante Do O, V, McCubrey, Raymond O., Schmidt, Amand F., Direk, Kenan, Laufs, Ulrich, Werner, Christian, Koenig, Wolfgang, Rothenbacher, Dietrich, Mons, Ute, Breitling, Lutz P, Brenner, Herrmann, Jennings, Richard T., Petrakis, Ioannis, Triem, Sarah, Klug, Mira, Filips, Alexandra, Blankenberg, Stefan, Waldeyer, Christoph, Sinning, Christoph, Schnabel, Renate B., Lackner, Karl J., Vlachopoulou, Efthymia, Nygård, Ottar, Svingen, Gard Frodahl Tveitevåg, Pedersen, Eva Ringdal, Tell, Grethe S., Sinisalo, Juha, Nieminen, Markku S., Laaksonen, Reijo, Trompet, Stella, Smit, Roelof A.J., Sattar, Naveed, Jukema, J. Wouter, Groesdonk, Heinrich V., Delgado, Graciela, Stojakovic, Tatjana, Pilbrow, Anna P., Cameron, Vicky A., Richards, A. Mark, Doughty, Robert N., Gong, Yan, Cooper-Dehoff, Rhonda M, Johnson, Julie A, Scholz, Markus, Kofink, Daniel, Hoefer, Imo E., Pasterkamp, Gerard, Asselbergs, Folkert W., GENIUS-CHD consortium, Experimentele Afd. Cardiologie 1, Circulatory Health, Cardiovasculaire Immunologie, UMC Utrecht, Onderzoek Precision medicine, CDL Staf Research, CDL Arcadia, CDL Cluster Onderzoek en Onderwijs, Team Medisch, Zewinger, Stephen, Kleber, Marcus E., Tragante Do O, V, McCubrey, Raymond O., Schmidt, Amand F., Direk, Kenan, Laufs, Ulrich, Werner, Christian, Koenig, Wolfgang, Rothenbacher, Dietrich, Mons, Ute, Breitling, Lutz P, Brenner, Herrmann, Jennings, Richard T., Petrakis, Ioannis, Triem, Sarah, Klug, Mira, Filips, Alexandra, Blankenberg, Stefan, Waldeyer, Christoph, Sinning, Christoph, Schnabel, Renate B., Lackner, Karl J., Vlachopoulou, Efthymia, Nygård, Ottar, Svingen, Gard Frodahl Tveitevåg, Pedersen, Eva Ringdal, Tell, Grethe S., Sinisalo, Juha, Nieminen, Markku S., Laaksonen, Reijo, Trompet, Stella, Smit, Roelof A.J., Sattar, Naveed, Jukema, J. Wouter, Groesdonk, Heinrich V., Delgado, Graciela, Stojakovic, Tatjana, Pilbrow, Anna P., Cameron, Vicky A., Richards, A. Mark, Doughty, Robert N., Gong, Yan, Cooper-Dehoff, Rhonda M, Johnson, Julie A, Scholz, Markus, Kofink, Daniel, Hoefer, Imo E., Pasterkamp, Gerard, Asselbergs, Folkert W., and GENIUS-CHD consortium

Published
2017

33. Loss of y Chromosome in Blood Is Associated with Major Cardiovascular Events during Follow-Up in Men after Carotid Endarterectomy

Author

Experimentele Afd. Cardiologie 1, Circulatory Health, Onderzoek Precision medicine, Onderzoek Vrouw Hart & Vaatziekten, Analisten, Experimentele Afd. Cardiologie 2, CDL Cluster Onderzoek en Onderwijs, Verpleegkundig Onderzoek, Team Medisch, Haitjema, Saskia, Kofink, Daniel, Van Setten, Jessica, Van Der Laan, Sander W., Schoneveld, Arjan H., Eales, James, Tomaszewski, Maciej, De Jager, Saskia C.A., Pasterkamp, Gerard, Asselbergs, Folkert W., Den Ruijter, Hester M., Experimentele Afd. Cardiologie 1, Circulatory Health, Onderzoek Precision medicine, Onderzoek Vrouw Hart & Vaatziekten, Analisten, Experimentele Afd. Cardiologie 2, CDL Cluster Onderzoek en Onderwijs, Verpleegkundig Onderzoek, Team Medisch, Haitjema, Saskia, Kofink, Daniel, Van Setten, Jessica, Van Der Laan, Sander W., Schoneveld, Arjan H., Eales, James, Tomaszewski, Maciej, De Jager, Saskia C.A., Pasterkamp, Gerard, Asselbergs, Folkert W., and Den Ruijter, Hester M.

Published
2017

34. Effect of Metformin on Metabolites and Relation With Myocardial Infarct Size and Left Ventricular Ejection Fraction After Myocardial Infarction

Author

Circulatory Health, Team Medisch, Eppinga, Ruben N, Kofink, Daniel, Dullaart, Robin P F, Dalmeijer, Geertje W, Lipsic, Erik, van Veldhuisen, Dirk J, van der Horst, Iwan C C, Asselbergs, Folkert W, van der Harst, Pim, Circulatory Health, Team Medisch, Eppinga, Ruben N, Kofink, Daniel, Dullaart, Robin P F, Dalmeijer, Geertje W, Lipsic, Erik, van Veldhuisen, Dirk J, van der Horst, Iwan C C, Asselbergs, Folkert W, and van der Harst, Pim

Published
2017

35. Additional Candidate Genes for Human Atherosclerotic Disease Identified Through Annotation Based on Chromatin Organization

Author

Experimentele Afd. Cardiologie 1, MDL onderzoek 3, Child Health, Circulatory Health, Onderzoek Precision medicine, Planningssecretariaat HCK, Nefro Vasculaire Geneeskunde, Regenerative Medicine and Stem Cells, CDL Staf Research, CDL Arcadia, Team Medisch, Pathologie Groep Brosens, Zorg en O&O, Infection & Immunity, CDL Cluster Onderzoek en Onderwijs, Haitjema, Saskia, Meddens, Claartje A., Van Der Laan, Sander W., Kofink, Daniel, Harakalova, Magdalena, Tragante, Vinicius, Foroughi Asl, Hassan, Van Setten, Jessica, Brandt, Maarten M., Bis, Joshua C., O'Donnell, Christopher, Cheng, Caroline, Hoefer, Imo E., Waltenberger, Johannes, Biessen, Erik A L, Jukema, J. Wouter, Doevendans, Pieter A.F.M., Nieuwenhuis, Edward E.S., Erdmann, Jeanette, Björkegren, Johan L M, Pasterkamp, Gerard, Asselbergs, Folkert W., Den Ruijter, Hester M., Mokry, Michal, Experimentele Afd. Cardiologie 1, MDL onderzoek 3, Child Health, Circulatory Health, Onderzoek Precision medicine, Planningssecretariaat HCK, Nefro Vasculaire Geneeskunde, Regenerative Medicine and Stem Cells, CDL Staf Research, CDL Arcadia, Team Medisch, Pathologie Groep Brosens, Zorg en O&O, Infection & Immunity, CDL Cluster Onderzoek en Onderwijs, Haitjema, Saskia, Meddens, Claartje A., Van Der Laan, Sander W., Kofink, Daniel, Harakalova, Magdalena, Tragante, Vinicius, Foroughi Asl, Hassan, Van Setten, Jessica, Brandt, Maarten M., Bis, Joshua C., O'Donnell, Christopher, Cheng, Caroline, Hoefer, Imo E., Waltenberger, Johannes, Biessen, Erik A L, Jukema, J. Wouter, Doevendans, Pieter A.F.M., Nieuwenhuis, Edward E.S., Erdmann, Jeanette, Björkegren, Johan L M, Pasterkamp, Gerard, Asselbergs, Folkert W., Den Ruijter, Hester M., and Mokry, Michal

Published
2017

38. Stress-Induced Enhancement of Mouse Amygdalar Synaptic Plasticity Depends on Glucocorticoid and β-Adrenergic Activity.

Author

Sarabdjitsingh, Ratna Angela, Kofink, Daniel, Karst, Henk, De Kloet, E. Ron, Joëls, Marian, and Mansvelde, Huibert D.

Subjects
*GLUCOCORTICOIDS, *NORADRENALINE, *RODENTS, *HUMAN beings, *AMYGDALOID body, *EMOTIONS, *MEMORY
Abstract

Background: Glucocorticoid hormones, in interaction with noradrenaline, enable the consolidation of emotionally arousing and stressful experiences in rodents and humans. Such interaction is thought to occur at least partly in the basolateral nucleus of the amygdala (BLA) which is crucially involved in emotional memory formation. Extensive evidence points to long-term synaptic potentiation (LTP) as a mechanism contributing to memory formation. Here we determined in adolescent C57/Bl6 mice the effects of stress on LTP in the LA-BLA pathway and the specific roles of corticosteroid and β-adrenergic receptor activation in this process. Principal Findings: Exposure to 20 min of restraint stress (compared to control treatment) prior to slice preparation enhanced subsequent LTP induction in vitro, without affecting baseline fEPSP responses. The role of glucocorticoid receptors, mineralocorticoid receptors and β2- adrenoceptors in the effects of stress was studied by treating mice with the antagonists mifepristone, spironolactone or propranolol respectively (or the corresponding vehicles) prior to stress or control treatment. In undisturbed controls, mifepristone and propranolol administration in vivo did not influence LTP induced in vitro. By contrast, spironolactone caused a gradually attenuating form of LTP, both in unstressed and stressed mice. Mifepristone treatment prior to stress strongly reduced the ability to induce LTP in vitro. Propranolol normalized the stress-induced enhancement of LTP to control levels during the first 10 min after high frequency stimulation, after which synaptic responses further declined. Conclusions: Acute stress changes BLA electrical properties such that subsequent LTP induction is facilitated. Both β-adrenergic and glucocorticoid receptors are involved in the development of these changes. Mineralocorticoid receptors are important for the maintenance of LTP in the BLA, irrespective of stress-induced changes in the circuit. The prolonged changes in BLA network function after stress may contribute to effective memory formation of emotional and stressful events. [ABSTRACT FROM AUTHOR]

Published
2012
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39. Association of Chromosome 9p21 With Subsequent Coronary Heart Disease Events.

Author

Patel RS, Schmidt AF, Tragante V, McCubrey RO, Holmes MV, Howe LJ, Direk K, Åkerblom A, Leander K, Virani SS, Kaminski KA, Muehlschlegel JD, Dubé MP, Allayee H, Almgren P, Alver M, Baranova EV, Behlouli H, Boeckx B, Braund PS, Breitling LP, Delgado G, Duarte NE, Dufresne L, Eriksson N, Foco L, Gijsberts CM, Gong Y, Hartiala J, Heydarpour M, Hubacek JA, Kleber M, Kofink D, Kuukasjärvi P, Lee VV, Leiherer A, Lenzini PA, Levin D, Lyytikäinen LP, Martinelli N, Mons U, Nelson CP, Nikus K, Pilbrow AP, Ploski R, Sun YV, Tanck MWT, Tang WHW, Trompet S, van der Laan SW, van Setten J, Vilmundarson RO, Viviani Anselmi C, Vlachopoulou E, Boerwinkle E, Briguori C, Carlquist JF, Carruthers KF, Casu G, Deanfield J, Deloukas P, Dudbridge F, Fitzpatrick N, Gigante B, James S, Lokki ML, Lotufo PA, Marziliano N, Mordi IR, Muhlestein JB, Newton Cheh C, Pitha J, Saely CH, Samman-Tahhan A, Sandesara PB, Teren A, Timmis A, Van de Werf F, Wauters E, Wilde AAM, Ford I, Stott DJ, Algra A, Andreassi MG, Ardissino D, Arsenault BJ, Ballantyne CM, Bergmeijer TO, Bezzina CR, Body SC, Bogaty P, de Borst GJ, Brenner H, Burkhardt R, Carpeggiani C, Condorelli G, Cooper-DeHoff RM, Cresci S, de Faire U, Doughty RN, Drexel H, Engert JC, Fox KAA, Girelli D, Hagström E, Hazen SL, Held C, Hemingway H, Hoefer IE, Hovingh GK, Johnson JA, de Jong PA, Jukema JW, Kaczor MP, Kähönen M, Kettner J, Kiliszek M, Klungel OH, Lagerqvist B, Lambrechts D, Laurikka JO, Lehtimäki T, Lindholm D, Mahmoodi BK, Maitland-van der Zee AH, McPherson R, Melander O, Metspalu A, Pepinski W, Olivieri O, Opolski G, Palmer CN, Pasterkamp G, Pepine CJ, Pereira AC, Pilote L, Quyyumi AA, Richards AM, Sanak M, Scholz M, Siegbahn A, Sinisalo J, Smith JG, Spertus JA, Stewart AFR, Szczeklik W, Szpakowicz A, Ten Berg JM, Thanassoulis G, Thiery J, van der Graaf Y, Visseren FLJ, Waltenberger J, Van der Harst P, Tardif JC, Sattar N, Lang CC, Pare G, Brophy JM, Anderson JL, März W, Wallentin L, Cameron VA, Horne BD, Samani NJ, Hingorani AD, and Asselbergs FW

Subjects
Case-Control Studies, Coronary Artery Disease genetics, Female, Gene Frequency, Genetic Predisposition to Disease, Humans, Male, Middle Aged, Myocardial Infarction genetics, Myocardial Infarction pathology, Odds Ratio, Risk Factors, Chromosomes, Human, Pair 9, Coronary Artery Disease pathology
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 (GENIUS-CHD 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 postulated mechanism of chromosome 9p21 for promoting atheroma development.

Published
2019
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40. Subsequent Event Risk in Individuals With Established Coronary Heart Disease.

Author

Patel RS, Tragante V, Schmidt AF, McCubrey RO, Holmes MV, Howe LJ, Direk K, Åkerblom A, Leander K, Virani SS, Kaminski KA, Muehlschlegel JD, Allayee H, Almgren P, Alver M, Baranova EV, Behloui H, Boeckx B, Braund PS, Breitling LP, Delgado G, Duarte NE, Dubé MP, Dufresne L, Eriksson N, Foco L, Scholz M, Gijsberts CM, Glinge C, Gong Y, Hartiala J, Heydarpour M, Hubacek JA, Kleber M, Kofink D, Kotti S, Kuukasjärvi P, Lee VV, Leiherer A, Lenzini PA, Levin D, Lyytikäinen LP, Martinelli N, Mons U, Nelson CP, Nikus K, Pilbrow AP, Ploski R, Sun YV, Tanck MWT, Tang WHW, Trompet S, van der Laan SW, Van Setten J, Vilmundarson RO, Viviani Anselmi C, Vlachopoulou E, Al Ali L, Boerwinkle E, Briguori C, Carlquist JF, Carruthers KF, Casu G, Deanfield J, Deloukas P, Dudbridge F, Engstrøm T, Fitzpatrick N, Fox K, Gigante B, James S, Lokki ML, Lotufo PA, Marziliano N, Mordi IR, Muhlestein JB, Newton-Cheh C, Pitha J, Saely CH, Samman-Tahhan A, Sandesara PB, Teren A, Timmis A, Van de Werf F, Wauters E, Wilde AAM, Ford I, Stott DJ, Algra A, Andreassi MG, Ardissino D, Arsenault BJ, Ballantyne CM, Bergmeijer TO, Bezzina CR, Body SC, Boersma EH, Bogaty P, Bots ML, Brenner H, Brugts JJ, Burkhardt R, Carpeggiani C, Condorelli G, Cooper-DeHoff RM, Cresci S, Danchin N, de Faire U, Doughty RN, Drexel H, Engert JC, Fox KAA, Girelli D, Grobbee DE, Hagström E, Hazen SL, Held C, Hemingway H, Hoefer IE, Hovingh GK, Jabbari R, Johnson JA, Jukema JW, Kaczor MP, Kähönen M, Kettner J, Kiliszek M, Klungel OH, Lagerqvist B, Lambrechts D, Laurikka JO, Lehtimäki T, Lindholm D, Mahmoodi BK, Maitland-van der Zee AH, McPherson R, Melander O, Metspalu A, Niemcunowicz-Janica A, Olivieri O, Opolski G, Palmer CN, Pasterkamp G, Pepine CJ, Pereira AC, Pilote L, Quyyumi AA, Richards AM, Sanak M, Siegbahn A, Simon T, Sinisalo J, Smith JG, Spertus JA, Stender S, Stewart AFR, Szczeklik W, Szpakowicz A, Tardif JC, Ten Berg JM, Tfelt-Hansen J, Thanassoulis G, Thiery J, Torp-Pedersen C, van der Graaf Y, Visseren FLJ, Waltenberger J, Weeke PE, Van der Harst P, Lang CC, Sattar N, Cameron VA, Anderson JL, Brophy JM, Pare G, Horne BD, März W, Wallentin L, Samani NJ, Hingorani AD, and Asselbergs FW

Subjects
Adult, Age Factors, Aged, Female, Humans, Male, Middle Aged, Prognosis, Proportional Hazards Models, Risk Factors, Sex Factors, Smoking, Coronary Disease pathology
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. Routinely measured hematological parameters and prediction of recurrent vascular events in patients with clinically manifest vascular disease.

Author

Kofink D, Muller SA, Patel RS, Dorresteijn JAN, Berkelmans GFN, de Groot MCH, van Solinge WW, Haitjema S, Leiner T, Visseren FLJ, Hoefer IE, and Asselbergs FW

Subjects
Aged, Female, Humans, Male, Middle Aged, Predictive Value of Tests, Prognosis, Recurrence, Risk Assessment, Vascular Diseases diagnosis, Hematologic Tests, Vascular Diseases blood
Abstract

Background and Aims: The predictive value of traditional risk factors for vascular events in patients with manifest vascular disease is limited, underscoring the need for novel biomarkers to improve risk stratification. Since hematological parameters are routinely assessed in clinical practice, they are readily available candidates., Methods: We used data from 3,922 vascular patients, who participated in the Second Manifestations of ARTerial Disease (SMART) study. We first investigated associations between recurrent vascular events and 22 hematological parameters, obtained from the Utrecht Patient Oriented Database (UPOD), and then assessed whether parameters associated with outcome improved risk prediction., Results: After adjustment for all SMART risk score (SRS) variables, lymphocyte %, neutrophil count, neutrophil % and red cell distribution width (RDW) were significantly associated with vascular events. When individually added to the SRS, lymphocyte % improved prediction of recurrent vascular events with a continuous net reclassification improvement (cNRI) of 17.4% [95% CI: 2.1, 32.1%] and an increase in c-statistic of 0.011 [0.000, 0.022]. The combination of lymphocyte % and neutrophil count resulted in a cNRI of 22.2% [3.2, 33.4%] and improved c-statistic by 0.011 [95% CI: 0.000, 0.022]. Lymphocyte % and RDW yielded a cNRI of 18.7% [3.3, 31.9%] and improved c-statistic by 0.016 [0.004, 0.028]. However, the addition of hematological parameters only modestly increased risk estimates for patients with an event during follow-up., Conclusions: Several hematological parameters were independently associated with recurrent vascular events. Lymphocyte % alone and in combination with other parameters enhanced discrimination and reclassification. However, the incremental value for patients with a recurrent event was limited., Competing Interests: The authors have declared that no competing interests exist.

Published
2018
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42. Generic atorvastatin is as effective as the brand-name drug (LIPITOR ® ) in lowering cholesterol levels: a cross-sectional retrospective cohort study.

Author

Loch A, Bewersdorf JP, Kofink D, Ismail D, Abidin IZ, and Veriah RS

Subjects
Aged, Cross-Sectional Studies, Female, Humans, Male, Middle Aged, Retrospective Studies, Atorvastatin pharmacology, Cholesterol, LDL drug effects, Drugs, Generic, Hydroxymethylglutaryl-CoA Reductase Inhibitors pharmacology, Hypercholesterolemia drug therapy, Triglycerides blood
Abstract

Background: In a world of ever increasing health care costs, generic drugs represent a major opportunity to ensure access to essential medicines for people who otherwise would be unable to afford them. However, some clinicians and patients are still questioning the safety and effectiveness of generic formulations compared to the proprietary drugs necessitating further systematic research analyzing the generic drugs' efficacy. Our objective was to compare the lipid lowering effects of generic and branded atorvastatin., Methods: This cross-sectional, retrospective cohort study was conducted at the University of Malaya Medical Centre from 1 May 2013 until 30 May 2013. We analyzed the lipid profiles (total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides) of 629 patients before and at least 3 months after switching them from proprietary atorvastatin (Lipitor ® ) to generic atorvastatin (atorvastatin calcium from Ranbaxy Laboratories, Inc.). We also investigated if there was any difference in the effectiveness of both atorvastatin formulations in various ethnic groups., Results: 266 patients were included in this study. When comparing the median values we found no statistically significant differences (Wilcoxon signed-rank test; p < 0.05) between proprietary and generic atorvastatin in lowering total cholesterol (4.60 mmol/l pre-transition vs. 4.50 mmol/l post-transition; p = 0.583), LDL-cholesterol (2.42 mmol/l vs. 2.41 mmol/l; p = 0.923) and triglycerides (1.50 mmol/l vs. 1.50 mmol/l; p = 0.513). While there was a statistically significant (p = 0.009) difference in HDL-cholesterol levels favouring proprietary atorvastatin, the extent of this change (1.26 mmol/l vs. 1.25 mmol/l) was deemed not to be clinically relevant. There was no statistically significant difference when analyzing the effects on various ethnic groups., Conclusions: Substituting proprietary atorvastatin for its generic formulation atorvastatin calcium does not result in a less effective management of hyperlipidemia. Our findings lend support to the approach of lowering health care costs by switching patients from branded drugs to their less expensive generic analogues.

Published
2017
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