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1. Co-circulation of genetically distinct highly pathogenic avian influenza A clade 2.3.4.4 (H5N6) viruses in wild waterfowl and poultry in Europe and East Asia, 2017-18

Author

Poen, M.J. (Marjolein), Venkatesh, D., Bestebroer, T.M. (Theo), Vuong, O. (Oanh), Scheuer, R.D. (Rachel), Munnink, BBO, Meulder, D. (Dennis) de, Richard, M., Kuiken, T. (Thijs), Koopmans D.V.M., M.P.G. (Marion), Kelder, L., Kim, Y-J. (Yong-Jin), Lee, YJ, Steensels, M., Lambrecht, B.N.M. (Bart), Dan, A., Pohlmann, A., Beer, M. (Martin), Savic, V., Brown, I.H. (Ian), Fouchier, R.A.M. (Ron), Lewis, NS, Poen, M.J. (Marjolein), Venkatesh, D., Bestebroer, T.M. (Theo), Vuong, O. (Oanh), Scheuer, R.D. (Rachel), Munnink, BBO, Meulder, D. (Dennis) de, Richard, M., Kuiken, T. (Thijs), Koopmans D.V.M., M.P.G. (Marion), Kelder, L., Kim, Y-J. (Yong-Jin), Lee, YJ, Steensels, M., Lambrecht, B.N.M. (Bart), Dan, A., Pohlmann, A., Beer, M. (Martin), Savic, V., Brown, I.H. (Ian), Fouchier, R.A.M. (Ron), and Lewis, NS

Abstract

Highly pathogenic avian influenza (HPAI) H5 clade 2.3.4.4 viruses were first introduced into Europe in late 2014 and reintroduced in late 2016, following detections in Asia and Russia. In contrast to the 2014–15 H5N8 wave, there was substantial local virus amplification in wild birds in Europe in 2016–17 and associated wild bird mortality, with evidence for occasional gene exchange with low pathogenic avian influenza (LPAI) viruses. Since December 20

Published
2019
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2. Incremental prognostic value of coronary computed tomography angiography over coronary calcium scoring for major adverse cardiac events in elderly asymptomatic individuals

Author

Han, D. (Donghee), Hartaigh, B.T. (Bríain ó), Gransar, H. (Heidi), Lee, J.H. (Ji Hyun), Rizvi, A. (Asim), Baskaran, L. (Lohendran), Schulman-Marcus, J. (Joshua), Dunning, A.M. (Alison), Achenbach, S. (Stephan), Al-Mallah, M. (Mouaz), Berman, D.S. (Daniel), Budoff, M.J. (Matthew), Cademartiri, F. (Filippo), Maffei, E. (Erica), Callister, T.Q. (Tracy), Chinnaiyan, K. (Kavitha), Chow, B.J.W. (Benjamin), Delago, A. (Augustin), Hadamitzky, M. (Martin), Hausleiter, J. (Jörg), Kaufmann, P.A. (Philipp), Raff, G.L. (Gilbert), Shaw, L.J. (Leslee), Villines, T.C. (Todd), Kim, Y.-J. (Yong-Jin), Leipsic, J. (Jonathon), Feuchtner, G.M. (Gudrun), Cury, R.C. (Ricardo), Pontone, G. (Gianluca), Andreini, D. (Daniele), Marques, H. (Hugo), Rubinshtein, R. (Ronen), Hindoyan, N. (Niree), Jones, E.C. (Erica C), Gomez, M. (Millie), Lin, F.Y. (Fay), Chang, H.-J. (Hyuk-Jae), Min, J.K. (James K), Han, D. (Donghee), Hartaigh, B.T. (Bríain ó), Gransar, H. (Heidi), Lee, J.H. (Ji Hyun), Rizvi, A. (Asim), Baskaran, L. (Lohendran), Schulman-Marcus, J. (Joshua), Dunning, A.M. (Alison), Achenbach, S. (Stephan), Al-Mallah, M. (Mouaz), Berman, D.S. (Daniel), Budoff, M.J. (Matthew), Cademartiri, F. (Filippo), Maffei, E. (Erica), Callister, T.Q. (Tracy), Chinnaiyan, K. (Kavitha), Chow, B.J.W. (Benjamin), Delago, A. (Augustin), Hadamitzky, M. (Martin), Hausleiter, J. (Jörg), Kaufmann, P.A. (Philipp), Raff, G.L. (Gilbert), Shaw, L.J. (Leslee), Villines, T.C. (Todd), Kim, Y.-J. (Yong-Jin), Leipsic, J. (Jonathon), Feuchtner, G.M. (Gudrun), Cury, R.C. (Ricardo), Pontone, G. (Gianluca), Andreini, D. (Daniele), Marques, H. (Hugo), Rubinshtein, R. (Ronen), Hindoyan, N. (Niree), Jones, E.C. (Erica C), Gomez, M. (Millie), Lin, F.Y. (Fay), Chang, H.-J. (Hyuk-Jae), and Min, J.K. (James K)

Abstract

Aims Coronary computed tomography angiography (CCTA) and coronary artery calcium score (CACS) have prognostic value for coronary artery disease (CAD) events beyond traditional risk assessment. Age is a risk factor with very high weight and little is known regarding the incremental value of CCTA over CAC for predicting cardiac events in older adults. Methods and results Of 27 125 individuals undergoing CCTA, a total of 3145 asymptomatic adults were identified. This study sample was categorized according to tertiles of age (cut-off points: 52 and 62 years). CAD severity was classified as 0, 1-49, and ≥50% maximal stenosis in CCTA, and further categorized according to number of vessels ≥50% stenosis. The Framingham 10-year risk score (FRS) and CACS were employed as major covariates. Major adverse cardiovascular events (MACE) were defined as a composite of all-cause death or non-fatal MI. During a median follow-up of 26 months (interquartile range: 18-41 months), 59 (1.9%) MACE occurred. For patients in the top age tertile, CCTA improved discrimination beyond a model included FRS and CACS (C-statistic: 0.75 vs. 0.70, P-value = 0.015). Likewise, the addition of CCTA improved category-free net reclassification (cNRI) of MACE in patients within the highest age tertile (e.g. cNRI = 0.75; proportion of events/non-events reclassified were 50 and 25%, respectively; P-value <0.05, all). CCTA displayed no incremental benefit beyond FRS and CACS for prediction of MACE in the lower age tertiles. Conclusion CCTA provides added prognostic value beyond cardiac risk factors and CACS for the prediction of MACE in asymptomatic older adults.

Published
2018
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3. Machine learning for prediction of all-cause mortality in patients with suspected coronary artery disease

Author

Motwani, M. (Manish), Dey, D. (Damini), Berman, D.S. (Daniel), Germano, G. (Guido), Achenbach, S. (Stephan), Al-Mallah, M. (Mouaz), Andreini, D. (Daniele), Budoff, M.J. (Matthew), Cademartiri, F. (Filippo), Callister, T.Q. (Tracy), Chang, H.-J. (Hyuk-Jae), Chinnaiyan, K. (Kavitha), Chow, B.J.W. (Benjamin), Cury, R.C. (Ricardo), Delago, A. (Augustin), Gomez, M. (Millie), Gransar, H. (Heidi), Hadamitzky, M. (Martin), Hausleiter, J. (Jörg), Hindoyan, N. (Niree), Feuchtner, G.M. (Gudrun), Kaufmann, P.A. (Philipp), Kim, Y.-J. (Yong-Jin), Leipsic, J. (Jonathon), Lin, F.Y. (Fay), Maffei, E. (Erica), Marques, H. (Hugo), Pontone, G. (Gianluca), Raff, G.L. (Gilbert), Rubinshtein, R. (Ronen), Shaw, L.J. (Leslee), Stehli, J. (Julia), Villines, T.C. (Todd), Dunning, A.M. (Alison), Min, J.K. (James), Slomka, P.J. (Piotr J.), Motwani, M. (Manish), Dey, D. (Damini), Berman, D.S. (Daniel), Germano, G. (Guido), Achenbach, S. (Stephan), Al-Mallah, M. (Mouaz), Andreini, D. (Daniele), Budoff, M.J. (Matthew), Cademartiri, F. (Filippo), Callister, T.Q. (Tracy), Chang, H.-J. (Hyuk-Jae), Chinnaiyan, K. (Kavitha), Chow, B.J.W. (Benjamin), Cury, R.C. (Ricardo), Delago, A. (Augustin), Gomez, M. (Millie), Gransar, H. (Heidi), Hadamitzky, M. (Martin), Hausleiter, J. (Jörg), Hindoyan, N. (Niree), Feuchtner, G.M. (Gudrun), Kaufmann, P.A. (Philipp), Kim, Y.-J. (Yong-Jin), Leipsic, J. (Jonathon), Lin, F.Y. (Fay), Maffei, E. (Erica), Marques, H. (Hugo), Pontone, G. (Gianluca), Raff, G.L. (Gilbert), Rubinshtein, R. (Ronen), Shaw, L.J. (Leslee), Stehli, J. (Julia), Villines, T.C. (Todd), Dunning, A.M. (Alison), Min, J.K. (James), and Slomka, P.J. (Piotr J.)

Abstract

__Aims__ Traditional prognostic risk assessment in patients undergoing non-invasive imaging is based upon a limited selection of clinical and imaging findings. Machine learning (ML) can consider a greater number and complexity of variables. Therefore, we investigated the feasibility and accuracy of ML to predict 5-year all-cause mortality (ACM) in patients undergoing coronary computed tomographic angiography (CCTA), and compared the performance to existing clinical or CCTA metrics. __Methods and results__ The analysis included 10 030 patients with suspected coronary artery disease and 5-year follow-up from the COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter registry. All patients underwent CCTA as their standard of care. Twenty-five clinical and 44 CCTA parameters were evaluated, including segment stenosis score (SSS), segment involvement score (SIS), modified Duke index (DI), number of segments with non-calcified, mixed or calcified plaques, age, sex, gender, standard cardiovascular risk factors, and Framingham risk score (FRS). Machine learning involved automated feature selection by information gain ranking, model building with a boosted ensemble algorithm, and 10-fold stratified cross-validation. Seven hundred and forty-five patients died during 5-year follow-up. Machine learning exhibited a higher area-under-curve compared with the FRS or CCTA severity scores alone (SSS, SIS, DI) for predicting all-cause mortality (ML: 0.79 vs. FRS: 0.61, SSS: 0.64, SIS: 0.64, DI: 0.62; P , 0.001). __Conclusions__ Machine learning combining clinical and CCTA data was found to predict 5-year ACM significantly better than existing clinical or CCTA metrics alone.

Published
2017
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4. Long-term prognostic impact of CT-Leaman score in patients with non-obstructive CAD: Results from the COronary CT Angiography EvaluatioN For Clinical Outcomes InteRnational Multicenter (CONFIRM) study

Author

Andreini, D. (Daniele), Pontone, G. (Gianluca), Mushtaq, S. (Saima), Gransar, H. (Heidi), Conte, E. (Edoardo), Bartorelli, A. (Antonio), Pepi, M. (Mauro), Opolski, M.P. (Maksymilian P.), Ó Hartaigh, B. (Bríain), Berman, D.S. (Daniel), Budoff, M.J. (Matthew), Achenbach, S. (Stephan), Al-Mallah, M. (Mouaz), Cademartiri, F. (Filippo), Callister, T.Q. (Tracy), Chang, H.-J. (Hyuk-Jae), Chinnaiyan, K. (Kavitha), Chow, B.J.W. (Benjamin), Cury, R.C. (Ricardo), Delago, A. (Augustin), Hadamitzky, M. (Martin), Hausleiter, J. (Jörg), Feuchtner, G.M. (Gudrun), Kim, Y.-J. (Yong-Jin), Kaufmann, P.A. (Philipp), Leipsic, J. (Jonathon), Lin, F.Y. (Fay), Maffei, E. (Erica), Raff, G.L. (Gilbert), Shaw, L.J. (Leslee), Villines, T.C. (Todd), Dunning, A.M. (Alison), Marques, H. (Hugo), Rubinshtein, R. (Ronen), Hindoyan, N. (Niree), Gomez, M. (Millie), Min, J.K. (James), Andreini, D. (Daniele), Pontone, G. (Gianluca), Mushtaq, S. (Saima), Gransar, H. (Heidi), Conte, E. (Edoardo), Bartorelli, A. (Antonio), Pepi, M. (Mauro), Opolski, M.P. (Maksymilian P.), Ó Hartaigh, B. (Bríain), Berman, D.S. (Daniel), Budoff, M.J. (Matthew), Achenbach, S. (Stephan), Al-Mallah, M. (Mouaz), Cademartiri, F. (Filippo), Callister, T.Q. (Tracy), Chang, H.-J. (Hyuk-Jae), Chinnaiyan, K. (Kavitha), Chow, B.J.W. (Benjamin), Cury, R.C. (Ricardo), Delago, A. (Augustin), Hadamitzky, M. (Martin), Hausleiter, J. (Jörg), Feuchtner, G.M. (Gudrun), Kim, Y.-J. (Yong-Jin), Kaufmann, P.A. (Philipp), Leipsic, J. (Jonathon), Lin, F.Y. (Fay), Maffei, E. (Erica), Raff, G.L. (Gilbert), Shaw, L.J. (Leslee), Villines, T.C. (Todd), Dunning, A.M. (Alison), Marques, H. (Hugo), Rubinshtein, R. (Ronen), Hindoyan, N. (Niree), Gomez, M. (Millie), and Min, J.K. (James)

Abstract

__Background:__ Non-obstructive coronary artery disease (CAD) identified by coronary computed tomography angiography (CCTA) demonstrated prognostic value. CT-adapted Leaman score (CT-LeSc) showed to improve the prognostic stratification. Aim of the study was to evaluate the capability of CT-LeSc to assess long-term prognosis of patients with non-obstructive (CAD). __Methods:__ From 17 centers, we enrolled 2402 patients without prior CAD history who underwent CCTA that showed non-obstructive CAD and provided complete information on plaque composition. Patients were divided into a group without CAD and a group with non-obstructive CAD (<. 50% stenosis). Segment-involvement score (SIS) and CT-LeSc were calculated. Outcomes were non-fatal myocardial infarction (MI) and the combined end-point of MI and all-cause mortality. __Results:__ Patient mean age was 56. ±. 12. years. At follow-up (mean 59.8. ±. 13.9. months), 183 events occurred (53 MI, 99 all-cause deaths and 31 late revascularizations). CT-LeSc was the only multivariate predictor of MI (HRs 2.84 and 2.98 in two models with Framingham and risk factors, respectively) and of MI plus all-cause mortality (HR 2.48 and 1.94 in two models with Framingham and risk factors, respectively). This was confirmed by a net reclassification analysis confirming that the CT-LeSc was able to correctly reclassify a significant proportion of patients (cNRI 0.28 and 0.23 for MI and MI plus all-cause mortality, respectively) vs. baseline model, whereas SIS did not. __Conclusion:__ CT-LeSc is an independent predictor of major acute cardiac events, improving prognostic stratification of patients with non-obstructive CAD.

Published
2017
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5. Prognostic implications of coronary artery calcium in the absence of coronary artery luminal narrowing

Author

Cho, I. (Iksung), Ó Hartaigh, B. (Bríain), Gransar, H. (Heidi), Valenti, V. (Valentina), Lin, F.Y. (Fay), Achenbach, S. (Stephan), Berman, D.S. (Daniel), Budoff, M.J. (Matthew), Callister, T.Q. (Tracy), Al-Mallah, M. (Mouaz), Cademartiri, F. (Filippo), Chinnaiyan, K. (Kavitha), Chow, B.J.W. (Benjamin), Dunning, A.M. (Alison), Delago, A. (Augustin), Villines, T.C. (Todd), Hadamitzky, M. (Martin), Hausleiter, J. (Jörg), Leipsic, J. (Jonathon), Shaw, L.J. (Leslee), Kaufmann, P.A. (Philipp), Cury, R.C. (Ricardo), Feuchtner, G.M. (Gudrun), Kim, Y.-J. (Yong-Jin), Maffei, E. (Erica), Raff, G.L. (Gilbert), Pontone, G. (Gianluca), Andreini, D. (Daniele), Chang, H.-J. (Hyuk-Jae), Min, J.K. (James), Cho, I. (Iksung), Ó Hartaigh, B. (Bríain), Gransar, H. (Heidi), Valenti, V. (Valentina), Lin, F.Y. (Fay), Achenbach, S. (Stephan), Berman, D.S. (Daniel), Budoff, M.J. (Matthew), Callister, T.Q. (Tracy), Al-Mallah, M. (Mouaz), Cademartiri, F. (Filippo), Chinnaiyan, K. (Kavitha), Chow, B.J.W. (Benjamin), Dunning, A.M. (Alison), Delago, A. (Augustin), Villines, T.C. (Todd), Hadamitzky, M. (Martin), Hausleiter, J. (Jörg), Leipsic, J. (Jonathon), Shaw, L.J. (Leslee), Kaufmann, P.A. (Philipp), Cury, R.C. (Ricardo), Feuchtner, G.M. (Gudrun), Kim, Y.-J. (Yong-Jin), Maffei, E. (Erica), Raff, G.L. (Gilbert), Pontone, G. (Gianluca), Andreini, D. (Daniele), Chang, H.-J. (Hyuk-Jae), and Min, J.K. (James)

Abstract

Background and aims: Coronary artery calcium (CAC) scoring is a predictor of future adverse clinical events, and a surrogate measure of overall coronary artery plaque burden. Coronary computed tomographic angiography (CCTA) is a contrast-enhanced method that allows for visualization of plaque as well as whether that plaque causes luminal narrowing. To date, the prognosis of individuals with CAC but without stenosis has not been reported. We explored the prevalence of CAC>0 and its prognostic utility for future mortality for patients without luminal narrowing by CCTA. Methods: From 17 sites in 9 countries, we identified patients without known coronary artery disease, who underwent CAC scoring and CCTA, and were followed for >3 years. CCTA was graded for % stenosis according to a modified American Heart Association 16-segment model. We calculated hazard ratios (HR) with 95% confidence intervals (95% CI) for incident mortality and compared risk of death for patients as a function of presence or absence of CAC and presence or absence of luminal narrowing by CCTA. Results: Among 6656 patients who underwent CCTA and CAC scoring, 399 patients (6.0%) had no coronary luminal narrowing but CAC>0. During a median follow-up of 5.1 years (IQR: 3.9-5.9 years), 456 deaths occurred. Compared to individuals without luminal narrowing or CAC, individuals without luminal narrowing but CAC>0 were older, more likely to be male and had higher rates of diabetes, hypertension, and dyslipidemia. Individuals without luminal narrowing but CAC experienced a 2-fold increased risk of mortality, with increasing risk of mortality with higher CAC score. Following adjustment, incident death persisted (HR, 1.8; 95% CI, 1.1-2.9, p = 0.02) among patients without luminal narrowing but with CAC>0 compared with patients whose CACS = 0. Individuals without luminal narrowing but CAC ≥100 had mortality risks similar to individuals with non-obstructive CAD (0 < stenosis<50%) by CCTA [HR 2.5 (95% CI 1.3-4.9) an

Published
2017
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6. Impact of age and sex on left ventricular function determined by coronary computed tomographic angiography

Author

Gebhard, C. (Catherine), Buechel, R.R. (Ronny R.), Stähli, B.E. (Barbara E.), Gransar, H. (Heidi), Achenbach, S. (Stephan), Berman, D.S. (Daniel), Budoff, M.J. (Matthew), Callister, T.Q. (Tracy), Chow, B.J.W. (Benjamin), Dunning, A.M. (Alison), Al-Mallah, M. (Mouaz), Cademartiri, F. (Filippo), Chinnaiyan, K. (Kavitha), Rubinshtein, R. (Ronen), Marques, H. (Hugo), Delago, A. (Augustin), Villines, T.C. (Todd), Hadamitzky, M. (Martin), Hausleiter, J. (Jörg), Shaw, L.J. (Leslee), Cury, R.C. (Ricardo), Feuchtner, G.M. (Gudrun), Kim, Y.-J. (Yong-Jin), Maffei, E. (Erica), Raff, G.L. (Gilbert), Pontone, G. (Gianluca), Andreini, D. (Daniele), Chang, H.-J. (Hyuk-Jae), Leipsic, J. (Jonathon), Min, J.K. (James K.), Kaufmann, P.A. (Philipp), Gebhard, C. (Catherine), Buechel, R.R. (Ronny R.), Stähli, B.E. (Barbara E.), Gransar, H. (Heidi), Achenbach, S. (Stephan), Berman, D.S. (Daniel), Budoff, M.J. (Matthew), Callister, T.Q. (Tracy), Chow, B.J.W. (Benjamin), Dunning, A.M. (Alison), Al-Mallah, M. (Mouaz), Cademartiri, F. (Filippo), Chinnaiyan, K. (Kavitha), Rubinshtein, R. (Ronen), Marques, H. (Hugo), Delago, A. (Augustin), Villines, T.C. (Todd), Hadamitzky, M. (Martin), Hausleiter, J. (Jörg), Shaw, L.J. (Leslee), Cury, R.C. (Ricardo), Feuchtner, G.M. (Gudrun), Kim, Y.-J. (Yong-Jin), Maffei, E. (Erica), Raff, G.L. (Gilbert), Pontone, G. (Gianluca), Andreini, D. (Daniele), Chang, H.-J. (Hyuk-Jae), Leipsic, J. (Jonathon), Min, J.K. (James K.), and Kaufmann, P.A. (Philipp)

Abstract

__Background__ Left ventricular (LV) volumetric and functional parameters measured with cardiac computed tomography (cardiac CT) augment risk prediction and discrimination for future mortality. Gender- and age-specific standard values for LV dimensions and systolic function obtained by 64-slice cardiac CT are lacking __Methods and results __ 1155 patients from the Coronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenterregistry (54.5% males, mean age 53.1 + 12.4 years, range: 18 – 92 years) without known coronary artery disease (CAD), structural heart disease, diabetes, or hypertension who underwent cardiac CT for various indications were categorized according to age and sex. A cardiac CT data acquisition protocol was used that allowed volumetric measuring of LV function. Image interpretation was performed at each site. Patients with significant CAD (.50% stenosis) on cardiac CT were excluded from the analysis. Overall, mean left ventricular ejection fraction (LVEF) was higher in women when compared with men (66.6 + 7.7% vs. 64.6 + 8.1%, P, 0.001). This gender-difference in overall LVEF was caused by a significantly higher LVEF in women ≥70 years when compared with men ≥70 years (69.95 + 8.89% vs. 65.50 + 9.42%, P ¼ 0.004). Accordingly, a significant increase in LVEF was observed with age (P ¼ 0.005 for males and P, 0.001 for females), which was more pronounced in females (5.21%) than in males (2.6%). LV end-diastolic volume decreased in females from 122.48+27.87 (,40 years) to 95.56+23.17 (.70 years; P, 0.001) and in males from 155.22+35.07 (,40 years) to 130.26+27.18 (.70 years; P, 0.001). __Conclusion__ Our findings indicate that the LV undergoes a lifelong remodelling and highlight the need for age and gender adjusted reference values.

Published
2016
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7. Coronary dominance and prognosis in patients undergoing coronary computed tomographic angiography: Results from the CONFIRM (COronary CTAngiography EvaluatioN for Clinical Outcomes: An InteRnational Multicenter) registry

Author

Gebhard, C. (Catherine), Fuchs, T.A. (Tobias A.), Stehli, J. (Julia), Gransar, H. (Heidi), Berman, D.S. (Daniel S.), Budoff, M.J. (Matthew), Achenbach, S. (Stephan), Al-Mallah, M. (Mouaz), Andreini, D. (Daniele), Cademartiri, F. (Filippo), Callister, T.Q. (Tracy), Chang, H.-J. (Hyuk-Jae), Chinnaiyan, K. (Kavitha), Chow, B.J.W. (Benjamin), Cury, R.C. (Ricardo), Delago, A. (Augustin), Gomez, M. (Millie), Hadamitzky, M. (Martin), Hausleiter, J. (Jörg), Hindoyan, N. (Niree), Feuchtner, G. (Gudrun), Kim, Y.-J. (Yong-Jin), Leipsic, J. (Jonathon), Lin, F.Y. (Fay), Maffei, E. (Erica), Pontone, G. (Gianluca), Raff, G.L. (Gilbert), Shaw, L.J. (Leslee), Villines, T.C. (Todd), Dunning, A.M. (Allison M.), Min, J.K. (James), Kaufmann, P.A. (Philipp), Gebhard, C. (Catherine), Fuchs, T.A. (Tobias A.), Stehli, J. (Julia), Gransar, H. (Heidi), Berman, D.S. (Daniel S.), Budoff, M.J. (Matthew), Achenbach, S. (Stephan), Al-Mallah, M. (Mouaz), Andreini, D. (Daniele), Cademartiri, F. (Filippo), Callister, T.Q. (Tracy), Chang, H.-J. (Hyuk-Jae), Chinnaiyan, K. (Kavitha), Chow, B.J.W. (Benjamin), Cury, R.C. (Ricardo), Delago, A. (Augustin), Gomez, M. (Millie), Hadamitzky, M. (Martin), Hausleiter, J. (Jörg), Hindoyan, N. (Niree), Feuchtner, G. (Gudrun), Kim, Y.-J. (Yong-Jin), Leipsic, J. (Jonathon), Lin, F.Y. (Fay), Maffei, E. (Erica), Pontone, G. (Gianluca), Raff, G.L. (Gilbert), Shaw, L.J. (Leslee), Villines, T.C. (Todd), Dunning, A.M. (Allison M.), Min, J.K. (James), and Kaufmann, P.A. (Philipp)

Abstract

Aims: Coronary computed tomographic angiography (CCTA) has become an important tool for non-invasive diagnosis of coronary artery disease (CAD). Coronary dominance can be assessed by CCTA; however, the predictive value of coronary dominance is controversially discussed. The aim of this study was to evaluate the prevalence and prognosis of coronary dominance in a large prospective, international multicentre cohort of patients undergoing CCTA. Methods and results: The study population consisted of 6382 patients with or without CAD (47% females, 53% males, mean age 56.9±12.3 years) who underwent CCTA and were followed over a period of 60 months. Right or left coronary dominance was determined. Right dominance was present in 91% (n = 5817) and left in 9% (n = 565) of the study population. At the end of follow-up, outcome in patients with obstructive CAD (>50% luminal stenosis) and right dominance was similar compared with patients with left dominance [hazard ratio (HR) 0.46, 95% CI 0.16-1.32, P = 0.15]. Furthermore, no differences were observed for the type of coronary dominance in patients with non-obstructive CAD(HR 0.95, 95% CI 0.41-2.21, P = 0.8962) or normal coronary arteries (HR 1.04, 95% CI 0.68-1.59, P = 0.9). Subgroup analysis in patients with left main disease revealed an elevated hazard of the combined endpoint for left dominance (HR 6.45, 95% CI 1.66-25.0, P = 0.007), but not for right dominance. Conclusion: In our study population, survival after 5 years of follow-up did not differ significantly between patientswith left or right coronary dominance. Thus, assessment of coronary vessel dominance by CCTA may not enhance risk stratification in patients with normal coronary arteries or obstructive CAD, but may add prognostic information for specific subpopulations.

Published
2015
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8. Prognostic and therapeutic implications of statin and aspirin therapy in individuals with nonobstructive coronary artery disease: Results from the confirm (coronary CT angiography evaluation for clinical outcomes: An international multicenter registry) registry

Author

Chow, B.J.W. (Benjamin), Small, G.R. (Gary), Yam, Y. (Yeung), Chen, L. (Li), McPherson, R. (Ruth), Achenbach, S. (Stephan), Al-Mallah, M. (Mouaz), Berman, D.S. (Daniel), Budoff, M.J. (Matthew J.), Cademartiri, F. (Filippo), Callister, T.Q. (Tracy), Chang, H.-J. (Hyuk-Jae), Cheng, V.Y. (Victor Y.), Chinnaiyan, K. (Kavitha), Cury, R.C. (Ricardo), Delago, A. (Augustin), Dunning, A. (Allison), Feuchtner, G. (Gundrun), Hadamitzky, M. (Martin), Hausleiter, J. (Jörg), Karlsberg, R.P. (Ronald), Kaufmann, P.A. (Philipp A.), Kim, Y.-J. (Yong-Jin), Leipsic, J. (Jonathon), LaBounty, T.M. (Troy), Lin, F.Y. (Fay), Maffei, E. (Erica), Raff, G.L. (Gilbert), Shaw, L.J. (Leslee J.), Villines, T.C. (Todd), Min, J.K. (James), Chow, B.J.W. (Benjamin), Small, G.R. (Gary), Yam, Y. (Yeung), Chen, L. (Li), McPherson, R. (Ruth), Achenbach, S. (Stephan), Al-Mallah, M. (Mouaz), Berman, D.S. (Daniel), Budoff, M.J. (Matthew J.), Cademartiri, F. (Filippo), Callister, T.Q. (Tracy), Chang, H.-J. (Hyuk-Jae), Cheng, V.Y. (Victor Y.), Chinnaiyan, K. (Kavitha), Cury, R.C. (Ricardo), Delago, A. (Augustin), Dunning, A. (Allison), Feuchtner, G. (Gundrun), Hadamitzky, M. (Martin), Hausleiter, J. (Jörg), Karlsberg, R.P. (Ronald), Kaufmann, P.A. (Philipp A.), Kim, Y.-J. (Yong-Jin), Leipsic, J. (Jonathon), LaBounty, T.M. (Troy), Lin, F.Y. (Fay), Maffei, E. (Erica), Raff, G.L. (Gilbert), Shaw, L.J. (Leslee J.), Villines, T.C. (Todd), and Min, J.K. (James)

Abstract

Objective - We sought to examine the risk of mortality associated with nonobstructive coronary artery disease (CAD) and to determine the impact of baseline statin and aspirin use on mortality. Approach and Results - Coronary computed tomographic angiography permits direct visualization of nonobstructive CAD. To date, the prognostic implications of nonobstructive CAD and the potential benefit of directing therapy based on nonobstructive CAD have not been carefully examined. A total of 27 125 consecutive patients who underwent computed tomographic angiography (12 enrolling centers and 6 countries) were prospectively entered into the COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter (CONFIRM) registry. Patients, without history of previous CAD or obstructive CAD, for whom baseline statin and aspirin use was available were analyzed. Each coronary segment was classified as normal or nonobstructive CAD (1%-49% stenosis). Patients were followed up for a median of 27.2 months for all-cause mortality. The study comprised 10 418 patients (5712 normal and 4706 with nonobstructive CAD). In multivariable analyses, patients with nonobstructive CAD had a 6% (95% confidence interval, 1%-12%) higher risk of mortality for each additional segment with nonobstructive plaque (P=0.021). Baseline statin use was associated with a reduced risk of mortality (hazard ratio, 0.44; 95% confidence interval, 0.28-0.68; P=0.0003), a benefit that was present for individuals with nonobstructive CAD (hazard ratio, 0.32; 95% confidence interval, 0.19-0.55; P<0.001) but not for those without plaque (hazard ratio, 0.66; 95% confidence interval, 0.30-1.43; P=0.287). When stratified by National Cholesterol Education Program/Adult Treatment Program III, no mortality benefit was observed in individuals without plaque. Aspirin use was not associated with mortality benefit, irrespective of the status of plaque. Conclusions - The presence and extent of nonobstructive CAD pre

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2015
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9. Incremental prognostic utility of coronary CT angiography for asymptomatic patients based upon extent and severity of coronary artery calcium: Results from the COronary CT Angiography EvaluatioN For Clinical Outcomes InteRnational Multicenter (CONFIRM) Study

Author

Cho, I. (Iksung), Chang, H.-J. (Hyuk-Jae), Hartaigh, B.T. (Bríain ó), Shin, S. (Sanghoon), Sung, J.M. (Ji Min), Lin, F.Y. (Fay), Achenbach, S. (Stephan), Heo, R. (Ran), Berman, D.S. (Daniel), Budoff, M.J. (Matthew J.), Callister, T.Q. (Tracy), Al-Mallah, M. (Mouaz), Cademartiri, F. (Filippo), Chinnaiyan, K. (Kavitha), Chow, B.J.W. (Benjamin), Dunning, A.M. (Allison M.), Delago, A. (Augustin), Villines, T.C. (Todd), Hadamitzky, M. (Martin), Hausleiter, J. (Jörg), Leipsic, J. (Jonathon), Shaw, L.J. (Leslee), Kaufmann, P.A. (Philipp A.), Cury, R.C. (Ricardo), Feuchtner, G.M. (Gudrun), Kim, Y.-J. (Yong-Jin), Maffei, E. (Erica), Raff, G.L. (Gilbert), Pontone, G. (Gianluca), Andreini, D. (Daniele), Min, J.K. (James K.), Cho, I. (Iksung), Chang, H.-J. (Hyuk-Jae), Hartaigh, B.T. (Bríain ó), Shin, S. (Sanghoon), Sung, J.M. (Ji Min), Lin, F.Y. (Fay), Achenbach, S. (Stephan), Heo, R. (Ran), Berman, D.S. (Daniel), Budoff, M.J. (Matthew J.), Callister, T.Q. (Tracy), Al-Mallah, M. (Mouaz), Cademartiri, F. (Filippo), Chinnaiyan, K. (Kavitha), Chow, B.J.W. (Benjamin), Dunning, A.M. (Allison M.), Delago, A. (Augustin), Villines, T.C. (Todd), Hadamitzky, M. (Martin), Hausleiter, J. (Jörg), Leipsic, J. (Jonathon), Shaw, L.J. (Leslee), Kaufmann, P.A. (Philipp A.), Cury, R.C. (Ricardo), Feuchtner, G.M. (Gudrun), Kim, Y.-J. (Yong-Jin), Maffei, E. (Erica), Raff, G.L. (Gilbert), Pontone, G. (Gianluca), Andreini, D. (Daniele), and Min, J.K. (James K.)

Abstract

Aim Prior evidence observed no predictive utility of coronary CT angiography (CCTA) over the coronary artery calcium score (CACS) and the Framingham risk score (FRS), among asymptomatic individuals. Whether the prognostic value of CCTA differs for asymptomatic patients, when stratified by CACS severity, remains unknown. Methods and results From a 12-centre, 6-country observational registry, 3217 asymptomatic individuals without known coronary artery disease (CA

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2015
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10. Medical History for Prognostic Risk Assessment and Diagnosis of Stable Patients with Suspected Coronary Artery Disease

Author

Min, J.K. (James), Dunning, A. (Allison), Gransar, H. (Heidi), Achenbach, S. (Stephan), Lin, F.Y. (Fay), Al-Mallah, M. (Mouaz), Budoff, M.J. (Matthew J.), Callister, T.Q. (Tracy), Chang, H.-J. (Hyuk-Jae), Cademartiri, F. (Filippo), Maffei, E. (Erica), Chinnaiyan, K. (Kavitha), Chow, B.J.W. (Benjamin), D'Agostino, R.B. (Ralph), Delago, A. (Augustin), Friedman, J. (John), Hadamitzky, M. (Martin), Hausleiter, J. (Jörg), Hayes, S.W. (Sean W.), Kaufmann, P.A. (Philipp A.), Raff, G.L. (Gilbert), Shaw, L.J. (Leslee J.), Thomson, L.E.J. (Louise), Villines, T.C. (Todd), Cury, R.C. (Ricardo), Feuchtner, G.M. (Gudrun), Kim, Y.-J. (Yong-Jin), Leipsic, J. (Jonathon), Marques, H. (Hugo), Berman, D.S. (Daniel S.), Pencina, M. (Michael), Min, J.K. (James), Dunning, A. (Allison), Gransar, H. (Heidi), Achenbach, S. (Stephan), Lin, F.Y. (Fay), Al-Mallah, M. (Mouaz), Budoff, M.J. (Matthew J.), Callister, T.Q. (Tracy), Chang, H.-J. (Hyuk-Jae), Cademartiri, F. (Filippo), Maffei, E. (Erica), Chinnaiyan, K. (Kavitha), Chow, B.J.W. (Benjamin), D'Agostino, R.B. (Ralph), Delago, A. (Augustin), Friedman, J. (John), Hadamitzky, M. (Martin), Hausleiter, J. (Jörg), Hayes, S.W. (Sean W.), Kaufmann, P.A. (Philipp A.), Raff, G.L. (Gilbert), Shaw, L.J. (Leslee J.), Thomson, L.E.J. (Louise), Villines, T.C. (Todd), Cury, R.C. (Ricardo), Feuchtner, G.M. (Gudrun), Kim, Y.-J. (Yong-Jin), Leipsic, J. (Jonathon), Marques, H. (Hugo), Berman, D.S. (Daniel S.), and Pencina, M. (Michael)

Abstract

Objective To develop a clinical cardiac risk algorithm for stable patients with suspected coronary artery disease based upon angina typicality and coronary artery disease risk factors. Methods Between 2004 and 2011, 14,004 adults with suspected coronary artery disease referred for cardiac imaging were followed: 1) 9093 patients for coronary computed tomography angiography (CCTA) followed for 2.0 years (CCTA-1); 2) 2132 patients for CCTA followed for 1.6 years (CCTA-2); and 3) 2779 patients for exercise myocardial perfusion scintigraphy (MPS) followed for 5.0 years. A best-fit model from CCTA-1 for prediction of death or myocardial infarction was developed, with integer values proportional to regression coefficients. Discrimination was assessed using C-statistic. The validated model was tested for estimation of the likelihood of obstructive coronary artery disease, defined as ≥50% stenosis, as compared with the method of Diamond and Forrester. Primary outcomes included all-cause mortality and nonfatal myocardial infarction. Secondary outcomes included prevalent angiographically obstructive coronary artery disease. Results In CCTA-1, best-fit model discriminated individuals at risk of death or myocardial infarction (C-statistic 0.76). The integer model ranged from 3 to 13, corresponding to 3-year death risk or myocardial infarction of 0.25% to 53.8%. When applied to CCTA-2 and MPS cohorts, the model demonstrated C-statistics of 0.71 and 0.77, respectively. Both best-fit (C = 0.76; 95% confidence interval [CI], 0.746-0.771) and integer models (C = 0.71; 95% CI, 0.693-0.719) performed better than Diamond and Forrester (C = 0.64; 95% CI, 0.628-0.659) for estimating obstructive coronary artery disease. Conclusions For stable symptomatic patients with suspected coronary artery disease, we developed a history-based method for prediction of death and obstructive coronary artery disease.

Published
2015
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11. Is metabolic syndrome predictive of prevalence, extent, and risk of coronary artery disease beyond its components? results from the multinational coronary ct angiography evaluation for clinical outcome: An international multicenter registry (confirm)

Author

Ahmadi, A. (Amir), Leipsic, J. (Jonathon), Feuchtner, G.M. (Gudrun), Gransar, H. (Heidi), Kalra, D. (Dan), Heo, R. (Ran), Achenbach, S. (Stephan), Andreini, D. (Daniele), Al-Mallah, M. (Mouaz), Berman, D.S. (Daniel S.), Budoff, M.J. (Matthew), Cademartiri, F. (Filippo), Callister, T.Q. (Tracy), Chang, H.-J. (Hyuk-Jae), Chinnaiyan, K. (Kavitha), Chow, B.J.W. (Benjamin), Cury, R.C. (Ricardo), Delago, A. (Augustin), Gomez, M. (Millie), Hadamitzky, M. (Martin), Hausleiter, J. (Jörg), Hindoyan, N. (Niree), Kaufmann, P.A. (Philipp), Kim, Y.-J. (Yong-Jin), Lin, F.Y. (Fay), Maffei, E. (Erica), Pontone, G. (Gianluca), Raff, G.L. (Gilbert), Shaw, L.J. (Leslee), Villines, T.C. (Todd), Dunning, A.M. (Allison M.), Min, J.K. (James), Ahmadi, A. (Amir), Leipsic, J. (Jonathon), Feuchtner, G.M. (Gudrun), Gransar, H. (Heidi), Kalra, D. (Dan), Heo, R. (Ran), Achenbach, S. (Stephan), Andreini, D. (Daniele), Al-Mallah, M. (Mouaz), Berman, D.S. (Daniel S.), Budoff, M.J. (Matthew), Cademartiri, F. (Filippo), Callister, T.Q. (Tracy), Chang, H.-J. (Hyuk-Jae), Chinnaiyan, K. (Kavitha), Chow, B.J.W. (Benjamin), Cury, R.C. (Ricardo), Delago, A. (Augustin), Gomez, M. (Millie), Hadamitzky, M. (Martin), Hausleiter, J. (Jörg), Hindoyan, N. (Niree), Kaufmann, P.A. (Philipp), Kim, Y.-J. (Yong-Jin), Lin, F.Y. (Fay), Maffei, E. (Erica), Pontone, G. (Gianluca), Raff, G.L. (Gilbert), Shaw, L.J. (Leslee), Villines, T.C. (Todd), Dunning, A.M. (Allison M.), and Min, J.K. (James)

Abstract

Although metabolic syndrome is associated with increased risk of cardiovascular disease and events, its added prognostic value beyond its components remains unknown. This study compared the prevalence, severity of coronary artery disease (CAD), and prognosis of patients with metabolic syndrome to those with individual metabolic syndrome components. The study cohort consisted of 27125 consecutive individuals who underwent ≥64-detector row coronary CT angiography (CCTA) at 12 centers from 2003 to 2009. Metabolic syndrome was defined as per NCEP/ATP III criteria. Metabolic syndrome patients (n=690) were matched 1:1:1 to those with 1 component (n=690) and 2 components (n=690) of metabolic syndrome for age, sex, smoking status, and family history of premature CAD using propensity scoring. Major adverse cardiac events (MACE) were defined by a composite of myocardial infarction (MI), acute coronary syndrome, mortality and late target vessel revascularization. Patients with 1 component of metabolic syndrome manifested lower rates of obstructive 1-, 2-, and 3-vessel/left main disease compared to metabolic syndrome patients (9.4% vs 13.8%, 2.6% vs 4.5%, and 1.0% vs 2.3%, respectively; p<0.05), while those with 2 components did not (10.5% vs 13.8%, 2.8% vs 4.5% and 1.3% vs 2.3%, respectively; p>0.05). At 2.5 years, metabolic syndrome patients experienced a higher rate of MACE compared to patients with 1 component (4.4% vs 1.6%; p=0.002), while no difference observed compared to individuals with 2 components (4.4% vs 3.2% p=0.25) of metabolic syndrome. In conclusion, Metabolic syndrome patients have significantly greater prevalence, severity, and prognosis of CAD compared to patients with 1 but not 2 components of metabolic syndrome.

Published
2015
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12. Current trends in patients with chronic total occlusions undergoing coronary CT angiography

Author

Opolski, M.P. (Maksymilian P.), Hartaigh, B.T. (Bríain ó), Berman, D.S. (Daniel S.), Budoff, M.J. (Matthew J.), Achenbach, S. (Stephan), Al-Mallah, M. (Mouaz), Andreini, D. (Daniele), Cademartiri, F. (Filippo), Chang, H.-J. (Hyuk-Jae), Chinnaiyan, K. (Kavitha), Chow, B.J.W. (Benjamin), Hadamitzky, M. (Martin), Hausleiter, J. (Jörg), Feuchtner, G. (Gudrun), Kim, Y.-J. (Yong-Jin), Kaufmann, P.A. (Philipp A.), Leipsic, J. (Jonathon), Maffei, E. (Erica), Pontone, G. (Gianluca), Raff, G.L. (Gilbert), Shaw, L.J. (Leslee), Villines, T.C. (Todd), Min, J.K. (James), Opolski, M.P. (Maksymilian P.), Hartaigh, B.T. (Bríain ó), Berman, D.S. (Daniel S.), Budoff, M.J. (Matthew J.), Achenbach, S. (Stephan), Al-Mallah, M. (Mouaz), Andreini, D. (Daniele), Cademartiri, F. (Filippo), Chang, H.-J. (Hyuk-Jae), Chinnaiyan, K. (Kavitha), Chow, B.J.W. (Benjamin), Hadamitzky, M. (Martin), Hausleiter, J. (Jörg), Feuchtner, G. (Gudrun), Kim, Y.-J. (Yong-Jin), Kaufmann, P.A. (Philipp A.), Leipsic, J. (Jonathon), Maffei, E. (Erica), Pontone, G. (Gianluca), Raff, G.L. (Gilbert), Shaw, L.J. (Leslee), Villines, T.C. (Todd), and Min, J.K. (James)

Abstract

Objective: Data describing the prevalence, characteristics and management of coronary chronic total occlusions (CTOs) in patients undergoing coronary CT angiography (CCTA) have not been reported. The purpose of this study was to determine the prevalence, characteristics and treatment strategies of CTO identified by CCTA. Methods: We identified 23 745 patients who underwent CCTA for suspected coronary artery disease (CAD) from the prospective international CCTA registry. Baseline clinical data were collected, and allocation to early coronary revascularisation performed within 90 days of CCTA was determined. Multivariable hierarchical mixed-effects logistic regression reporting OR with 95% CI was performed. Results: The prevalence of CTO was 1.4% (342/23 745) in all patients and 6.2% in patients with obstructive CAD (≥50% stenosis). The presence of CTO was independently associated with male sex (OR 3.12, 95% CI 2.39 to 4.08, p<0.001), smoking (OR 2.02, 95% CI 1.55 to 2.64, p<0.001), diabetes (OR 1.60, 95% CI 1.22 to 2.11, p=0.001), typical angina (OR 1.51, 95% CI 1.12 to 2.06, p=0.008), hypertension (OR 1.47, 95% CI 1.14 to 1.88, p=0.003), family history of CAD (OR 1.30, 95% CI 1.01 to 1.67, p=0.04) and age (OR 1.06, 95% CI 1.05 to 1.07, p<0.001). Most patients with CTO (61%) were treated medically, while 39% underwent coronary revascularisation. In patients with severe CAD (.70% stenosis), CTO independently predicted revascularisation by coronary artery bypass grafting (OR 3.41, 95% CI 2.06 to 5.66, p<0.001), but not by percutaneous coronary intervention (p=0.83). Conclusions: CTOs are not uncommon in a contemporary CCTA population, and are associated with age, gender, angina status and CAD risk factors. Most individuals with CTO undergoing CCTA are managed medically with higher rates of surgical revascularisation in patients with versus without CTO. Trial registration number: ClinicalTrials.gov identifier NCT01443637.

Published
2015
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13. A Clinical model to identify patients with high-risk coronary artery disease

Author

Yang, Y. (Yelin), Chen, L. (Li), Yam, Y. (Yeung), Achenbach, S. (Stephan), Al-Mallah, M. (Mouaz), Berman, D.S. (Daniel), Budoff, M.J. (Matthew), Cademartiri, F. (Filippo), Callister, T.Q. (Tracy), Chang, H.-J. (Hyuk-Jae), Cheng, V.Y. (Victor), Chinnaiyan, K. (Kavitha), Cury, R.C. (Ricardo), Delago, A. (Augustin), Dunning, A. (Allison), Feuchtner, G.M. (Gudrun), Hadamitzky, M. (Martin), Hausleiter, J. (Jörg), Karlsberg, R.P. (Ronald), Kaufmann, P.A. (Philipp), Kim, Y.-J. (Yong-Jin), Leipsic, J. (Jonathon), LaBounty, T.M. (Troy), Lin, F.Y. (Fay), Maffei, E. (Erica), Raff, G.L. (Gilbert), Shaw, L.J. (Leslee), Villines, T.C. (Todd), Min, J.K. (James K.), Chow, B.J.W. (Benjamin), Yang, Y. (Yelin), Chen, L. (Li), Yam, Y. (Yeung), Achenbach, S. (Stephan), Al-Mallah, M. (Mouaz), Berman, D.S. (Daniel), Budoff, M.J. (Matthew), Cademartiri, F. (Filippo), Callister, T.Q. (Tracy), Chang, H.-J. (Hyuk-Jae), Cheng, V.Y. (Victor), Chinnaiyan, K. (Kavitha), Cury, R.C. (Ricardo), Delago, A. (Augustin), Dunning, A. (Allison), Feuchtner, G.M. (Gudrun), Hadamitzky, M. (Martin), Hausleiter, J. (Jörg), Karlsberg, R.P. (Ronald), Kaufmann, P.A. (Philipp), Kim, Y.-J. (Yong-Jin), Leipsic, J. (Jonathon), LaBounty, T.M. (Troy), Lin, F.Y. (Fay), Maffei, E. (Erica), Raff, G.L. (Gilbert), Shaw, L.J. (Leslee), Villines, T.C. (Todd), Min, J.K. (James K.), and Chow, B.J.W. (Benjamin)

Abstract

Objectives This study sought to develop a clinical model that identifies patients with and without high-risk coronary artery disease (CAD). Background Although current clinical models help to estimate a patient's pre-test probability of obstructive CAD, they do not accurately identify those patients with and without high-risk coronary anatomy. Methods Retrospective analysis of a prospectively collected multinational coronary computed tomographic angiography (CTA) co

Published
2015
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14. Gender differences in the prevalence, severity, and composition of coronary artery disease in the young: A study of 1635 individuals undergoing coronary CT angiography fromthe prospective, multinational confirm registry

Author

Otaki, Y. (Yuka), Gransar, H. (Heidi), Cheng, V.Y. (Victor), Dey, S. (Subhasish), LaBounty, T.M. (Troy), Lin, F.Y. (Fay), Achenbach, S. (Stephan), Al-Mallah, M. (Mouaz), Budoff, M.J. (Matthew), Cademartiri, F. (Filippo), Callister, T.Q. (Tracy), Chang, H.-J. (Hyuk-Jae), Chinnaiyan, K. (Kavitha), Chow, B.J.W. (Benjamin), Delago, A. (Augustin), Hadamitzky, M. (Martin), Hausleiter, J. (Jörg), Kaufmann, P.A. (Philipp A.), Maffei, E. (Erica), Raff, G.L. (Gilbert), Shaw, L.J. (Leslee), Villines, T.C. (Todd), Dunning, A. (Allison), Cury, R.C. (Ricardo), Feuchtner, G. (Gudrun), Kim, Y.-J. (Yong-Jin), Leipsic, J. (Jonathon), Berman, D.S. (Daniel S.), Min, J.K. (James), Otaki, Y. (Yuka), Gransar, H. (Heidi), Cheng, V.Y. (Victor), Dey, S. (Subhasish), LaBounty, T.M. (Troy), Lin, F.Y. (Fay), Achenbach, S. (Stephan), Al-Mallah, M. (Mouaz), Budoff, M.J. (Matthew), Cademartiri, F. (Filippo), Callister, T.Q. (Tracy), Chang, H.-J. (Hyuk-Jae), Chinnaiyan, K. (Kavitha), Chow, B.J.W. (Benjamin), Delago, A. (Augustin), Hadamitzky, M. (Martin), Hausleiter, J. (Jörg), Kaufmann, P.A. (Philipp A.), Maffei, E. (Erica), Raff, G.L. (Gilbert), Shaw, L.J. (Leslee), Villines, T.C. (Todd), Dunning, A. (Allison), Cury, R.C. (Ricardo), Feuchtner, G. (Gudrun), Kim, Y.-J. (Yong-Jin), Leipsic, J. (Jonathon), Berman, D.S. (Daniel S.), and Min, J.K. (James)

Abstract

Objective: Prior studies examining coronary atherosclerosis in the young have been limited by retrospective analyses in small cohorts. We examined the relationship between cardiovascular risk factors (RFs) and prevalence and severity of coronary atherosclerosis in a large, prospective, multinational registry of consecutive young individuals undergoing coronary computerized tomographic angiography (CCTA). Method and results: Of 27 125 patients undergoing CCTA, 1635 young (<45 years) individuals without known coronary artery disease (CAD) or coronary anomalies were identified. Coronary plaque was assessed for any CAD, obstructive CAD (≥50% stenosis), and presence of calcified plaque (CP) and non-calcified plaque (NCP). Among 1635 subjects (70% men, age 38±6 years), any CAD, obstructive CAD, CP, and NCP were observed in 19, 4, 5, and 8%, respectively. Compared with women, men demonstrated higher rates of any CAD (21 vs. 12%, P < 0.001), CP (6 vs. 3%, P = 0.01), and NCP (9 vs. 5%, P = 0.008), although no difference was observed for rates of obstructive CAD (5 vs. 4%, P = 0.46). Any CAD, obstructive CAD, and NCP were higher for young individuals with diabetes, hypertension, dyslipidaemia, current smoking, or family history of CAD; while only diabetes and dyslipidaemia were associated with CP. Increasing cardiovascular RFs was associated with a greater prevalence and extent and severity of CAD, with individuals with 0, 1, 2, ≥3 RFs manifesting a dose-response increase in any CAD (P < 0.001, for trend), obstructive CAD (P < 0.001, for trend), NCP (P < 0.001, for trend), and CP (P < 0.001, for trend). In multivariable analysis adjusting for sex and cardiovascular RFs, male sexwas the strongest predictor for anyCAD(odds ratio [OR] = 1.95, 95% confidence interval [CI] = 1.43-2.66, P < 0.001), CP (OR = 1.46, 95% CI = 1.08-1.98, P = 0.01), and NCP (OR = 1.33, 95% CI = 1.06-1.67, P = 0.01); family history of CAD was the strongest predictor for obstructive CAD (OR = 2.71, 95% CI

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2015
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15. Current but not past smoking increases the risk of cardiac events: Insights from coronary computed tomographic angiography

Author

Nakanishi, R. (Rine), Berman, D.S. (Daniel), Budoff, M.J. (Matthew J.), Gransar, H. (Heidi), Achenbach, S. (Stephan), Al-Mallah, M. (Mouaz), Andreini, D. (Daniele), Cademartiri, F. (Filippo), Callister, T.Q. (Tracy), Chang, H.-J. (Hyuk-Jae), Cheng, V.Y. (Victor Y.), Chinnaiyan, K. (Kavitha), Chow, B.J.W. (Benjamin), Cury, R.C. (Ricardo), Delago, A. (Augustin), Hadamitzky, M. (Martin), Hausleiter, J. (Jörg), Feuchtner, G.M. (Gudrun), Kim, Y.-J. (Yong-Jin), Kaufmann, P.A. (Philipp A.), Leipsic, J. (Jonathon), Lin, F.Y. (Fay), Maffei, E. (Erica), Pontone, G. (Gianluca), Raff, G.L. (Gilbert), Shaw, L.J. (Leslee J.), Villines, T.C. (Todd), Dunning, A. (Allison), Min, J.K. (James), Nakanishi, R. (Rine), Berman, D.S. (Daniel), Budoff, M.J. (Matthew J.), Gransar, H. (Heidi), Achenbach, S. (Stephan), Al-Mallah, M. (Mouaz), Andreini, D. (Daniele), Cademartiri, F. (Filippo), Callister, T.Q. (Tracy), Chang, H.-J. (Hyuk-Jae), Cheng, V.Y. (Victor Y.), Chinnaiyan, K. (Kavitha), Chow, B.J.W. (Benjamin), Cury, R.C. (Ricardo), Delago, A. (Augustin), Hadamitzky, M. (Martin), Hausleiter, J. (Jörg), Feuchtner, G.M. (Gudrun), Kim, Y.-J. (Yong-Jin), Kaufmann, P.A. (Philipp A.), Leipsic, J. (Jonathon), Lin, F.Y. (Fay), Maffei, E. (Erica), Pontone, G. (Gianluca), Raff, G.L. (Gilbert), Shaw, L.J. (Leslee J.), Villines, T.C. (Todd), Dunning, A. (Allison), and Min, J.K. (James)

Abstract

Aims We evaluated coronary artery disease (CAD) extent, severity, and major adverse cardiac events (MACEs) in never, past, and current smokers undergoing coronary CT angiography (CCTA). Methods and results We evaluated 9456 patients (57.1 ± 12.3 years, 55.5% male) without known CAD (1588 current smokers; 2183 past smokers who quit ≥ 3 months before CCTA; and 5685 never smokers). By risk-adjusted Cox proportional-hazards models, we related smoking status to MACE (all-cause death or non-fatal myocardial infarction). We further performed 1:1:1 propensity matching for 1000 in each group evaluate event risk among individuals with similar age, gender, CAD risk factors, and symptom presentation. During a mean follow-up of 2.8 ± 1.9 years, 297 MACE occurred. Compared with never smokers, current and past smokers had greater atherosclerotic burden including extent of plaque defined as segments with any plaque (2.1 ± 2.8 vs. 2.6 ± 3.2 vs. 3.1 ± 3.3, P < 0.0001) and prevalence of obstructive CAD [1-vessel disease (VD): 10.6% vs. 14.9% vs. 15.2%, P < 0.001; 2-VD: 4.4% vs. 6.1% vs. 6.2%, P = 0.001; 3-VD: 3.1% vs. 5.2% vs. 4.3%, P < 0.001]. Compared with never smokers, current smokers experienced higher MACE risk [hazard ratio (HR) 1.9, 95% confidence interval (CI) 1.4-2.6, P < 0.001], while past smokers did not (HR 1.2, 95% CI 0.8-1.6, P = 0.35). Among matched individuals, current smokers had higher MACE risk (HR 2.6, 95% CI 1.6-4.2, P < 0.001), while past smokers did not (HR 1.3, 95% CI 0.7-2.4, P = 0.39). Similar findings were observed for risk of all-cause death. Conclusion Among patients without known CAD undergoing CCTA, current and past smokers had increased burden of atherosclerosis compared with never smokers; however, risk of MACE was heightened only in current smokers.

Published
2015
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16. Incremental prognostic value of coronary computed tomographic angiography over coronary artery calcium score for risk prediction of major adverse cardiac events in asymptomatic diabetic individuals

Author

Min, J.K. (James), LaBounty, T.M. (Troy), Gomez, M. (Millie), Achenbach, S. (Stephan), Al-Mallah, M. (Mouaz), Budoff, M.J. (Matthew), Cademartiri, F. (Filippo), Callister, T.Q. (Tracy), Chang, H.-J. (Hyuk-Jae), Cheng, V.Y. (Victor), Chinnaiyan, K. (Kavitha), Chow, B.J.W. (Benjamin), Cury, R.C. (Ricardo), Delago, A. (Augustin), Dunning, A.M. (Allison), Feuchtner, G.M. (Gudrun), Hadamitzky, M. (Martin), Hausleiter, J. (Jörg), Kaufmann, P.A. (Philipp), Kim, Y-J. (Yong-Jin), Leipsic, J. (Jonathon), Lin, F.Y. (Fay), Maffei, E. (Erica), Raff, G.L. (Gilbert), Shaw, L.J. (Leslee), Villines, T.C. (Todd), Berman, D.S. (Daniel), Min, J.K. (James), LaBounty, T.M. (Troy), Gomez, M. (Millie), Achenbach, S. (Stephan), Al-Mallah, M. (Mouaz), Budoff, M.J. (Matthew), Cademartiri, F. (Filippo), Callister, T.Q. (Tracy), Chang, H.-J. (Hyuk-Jae), Cheng, V.Y. (Victor), Chinnaiyan, K. (Kavitha), Chow, B.J.W. (Benjamin), Cury, R.C. (Ricardo), Delago, A. (Augustin), Dunning, A.M. (Allison), Feuchtner, G.M. (Gudrun), Hadamitzky, M. (Martin), Hausleiter, J. (Jörg), Kaufmann, P.A. (Philipp), Kim, Y-J. (Yong-Jin), Leipsic, J. (Jonathon), Lin, F.Y. (Fay), Maffei, E. (Erica), Raff, G.L. (Gilbert), Shaw, L.J. (Leslee), Villines, T.C. (Todd), and Berman, D.S. (Daniel)

Abstract

Background: Coronary artery disease (CAD) diagnosis by coronary computed tomographic angiography (CCTA) is useful for identification of symptomatic diabetic individuals at heightened risk for death. Whether CCTA-detected CAD enables improved risk assessment of asymptomatic diabetic individuals beyond clinical risk factors and coronary artery calcium scoring (CACS) remains unexplored. Methods: From a prospective 12-center international registry of 27,125 individuals undergoing CCTA, we identified 400 asymptomatic diabetic individuals without known CAD. Coronary stenosis by CCTA was graded as 0%, 1-49%, 50-69%, and ≥70%. CAD was judged on a per-patient, per-vessel and per-segment basis as maximal stenosis severity, number of vessels with ≥50% stenosis, and coronary segments weighted for stenosis severity (segment stenosis score), respectively. We assessed major adverse cardiovascular events (MACE) - inclusive of mortality, nonfatal myocardial infarction (MI), and late target vessel revascularization ≥90 days (REV)- and evaluated the incremental utility of CCTA for risk prediction, discrimination and reclassification.

Published
2014
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17. Cardiovascular risk among stable individuals suspected of having coronary artery disease with no modifiable risk factors

Author

Leipsic, J. (Jonathon), C.M. Taylor (Carolyn), Grunau, G. (Gilat), Heilbron, J. (Johan), Mancini, G.B.J. (John), Achenbach, S. (Stephan), Al-Mallah, M. (Mouaz), Berman, D.S. (Daniel), Budoff, M.J. (Matthew), Cademartiri, F. (Filippo), Callister, T.Q. (Tracy), Chang, H.-J. (Hyuk-Jae), Cheng, V.Y. (Victor), Chinnaiyan, K. (Kavitha), Chow, B.J.W. (Benjamin), Delago, A. (Augustin), Hadamitzky, M. (Martin), Cury, R.C. (Ricardo), Feuchtner, G.M. (Gudrun), Kim, Y-J. (Yong-Jin), Kaufmann, P.A. (Philipp), Lin, F.Y. (Fay), Maffei, E. (Erica), Raff, G.L. (Gilbert), Shaw, L.J. (Leslee), Villines, T.C. (Todd), Min, J.K. (James), Leipsic, J. (Jonathon), C.M. Taylor (Carolyn), Grunau, G. (Gilat), Heilbron, J. (Johan), Mancini, G.B.J. (John), Achenbach, S. (Stephan), Al-Mallah, M. (Mouaz), Berman, D.S. (Daniel), Budoff, M.J. (Matthew), Cademartiri, F. (Filippo), Callister, T.Q. (Tracy), Chang, H.-J. (Hyuk-Jae), Cheng, V.Y. (Victor), Chinnaiyan, K. (Kavitha), Chow, B.J.W. (Benjamin), Delago, A. (Augustin), Hadamitzky, M. (Martin), Cury, R.C. (Ricardo), Feuchtner, G.M. (Gudrun), Kim, Y-J. (Yong-Jin), Kaufmann, P.A. (Philipp), Lin, F.Y. (Fay), Maffei, E. (Erica), Raff, G.L. (Gilbert), Shaw, L.J. (Leslee), Villines, T.C. (Todd), and Min, J.K. (James)

Abstract

__Purpose:__ To assess the prevalence, extent, severity, and risk of coronary artery disease (CAD) in patients suspected of having CAD but with no medically modifiable risk factors. __Materials and Methods:__ Institutional review board approval or waiver of consent was obtained at each center. This study was HIPAA compliant. From an international multicenter cohort study of 27 125 subjects undergoing coronary computed tomographic (CT) angiography from 12 centers, 5262 patients without known CAD and without modifiable risk factors were identified. CAD severity was defined as none (0%), mild (1%-49%), or obstructive (≥50%) on a per-patient, per-vessel, and per-segment basis. CAD presence, extent, and severity were related to incidence of major adverse cardiovascular event (MACE) by using Cox proportional hazards models. __Results:__ At a mean follow-up of 2.3 years ± 1.2 (standard deviation), MACE occurred in 106 patients. CAD was common for nonobstructive (n = 1452, 27%) and obstructive (n = 629, 12%) CAD. In risk-adjusted analysis, per-patient obstructive CAD (hazard ratio [HR], 6.64; 95% confidence interval [CI]: 3.68, 12.00; P ≤ .001) was related to MACE. MACE was associated with a dose-response relationship to the number of vessels exhibiting obstructive CAD, increasing risk for obstructive one-vessel (HR, 6.11; 95% CI: 3.22, 11.6; P ≤ .001), two-vessel (HR, 5.86; 95% CI: 2.75, 12.5; P ≤ .0001), or three-vessel or left main (HR, 11.69; 95% CI: 5.38, 25.4; P ≤ .001) CAD. The increased hazard for MACE of obstructive disease holds true for symptomatic (HR, 11.9; 95% CI: 4.81, 29.6; P ≤ .001) and asymptomatic (HR, 6.3; 95% CI: 2.4, 16.7; P ≤ .001) patients. No CAD at coronary CT angiography was associated with a low annualized MACE rate: 0.31% versus 2.06% with obstructive disease. __Conclusion:__ Among individuals suspected of having CAD but without modifiable risk factors, CAD is common, with significantly increased hazards for MACE and mortality.

Published
2013
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18. Common variants in mendelian kidney disease genes and their association with renal function

Author

Parsa, A. (Afshin), Fuchsberger, C. (Christian), Köttgen, A. (Anna), O'Seaghdha, C.M. (Conall), Pattaro, C. (Cristian), Andrade, M. (Mariza) de, Chasman, D.I. (Daniel), Teumer, A. (Alexander), Endlich, K. (Karlhans), Olden, M. (Matthias), Chen, M-H. (Ming-Huei), Tin, A. (Adrienne), Kim, Y-J. (Yong-Jin), Taliun, D. (Daniel), Li, M. (Man), Feitosa, M.F. (Mary Furlan), Gorski, M. (Mathias), Yang, Q. (Qiong), Hundertmark, C. (Claudia), Foster, M.C. (Michael), Glazer, N. (Nicole), Isaacs, A.J. (Aaron), Rao, M. (Madhumathi), Smith, A.V. (Davey), O´Connell, J.R., Struchalin, M.V. (Maksim), Tanaka, T. (Toshiko), Li, G. (Guo), Hwang, S.J., Atkinson, E.J. (Elizabeth), Lohman, K. (Kurt), Cornelis, M. (Marilyn), Johansson, A. (Åsa), Tönjes, A. (Anke), Dehghan, A. (Abbas), Couraki, V. (Vincent), Holliday, E.G. (Elizabeth), Sorice, R., Kutalik, Z. (Zoltán), Lehtimäki, T. (Terho), Esko, T. (Tõnu), Deshmukh, H. (Harshal), Ulivi, S. (Shelia), Chu, A.Y. (Audrey), Murgia, D. (Daniela), Trompet, S. (Stella), Imboden, M. (Medea), Kollerits, B. (Barbara), Pistis, G. (Giorgio), Harris, T.B. (Tamara), Launer, L.J. (Lenore), Aspelund, T. (Thor), Eiriksdottir, G. (Gudny), Mitchell, B.D. (Braxton), Boerwinkle, E.A. (Eric), Schmidt, H. (Helena), Hofer, E. (Edith), Hu, F.B. (Frank), Demirkan, A. (Ayşe), Oostra, B.A. (Ben), Turner, S.T. (Stephen), Ding, J. (Jingzhong), Andrews, J.S. (Jeanette), Freedman, B.I. (Barry), Giulianini, F. (Franco), Koenig, W. (Wolfgang), Illig, T. (Thomas), Döring, A. (Angela), Wichmann, H.E. (Heinz Erich), Zgaga, L. (Lina), Zemunik, T. (Tatijana), Boban, M. (Mladen), Minelli, C. (Cosetta), Wheeler, H.E. (Heather), Igl, W. (Wilmar), Zaboli, G. (Ghazal), Wild, S.H. (Sarah), Wright, A.F. (Alan), Campbell, H. (Harry), Ellinghaus, D. (David), Nöthlings, U. (Ute), Jacobs, G. (Gunnar), Biffar, R. (Reiner), Ernst, F.D.J. (Florian), Homuth, G. (Georg), Kroemer, H.K. (Heyo), Nauck, M. (Matthias), Stracke, S. (Sylvia), Vol̈ker, U. (Uwe), Völzke, H. (Henry), Kovacs, P. (Peter), Stumvoll, M. (Michael), Mägi, R. (Reedik), Hofman, A. (Albert), Uitterlinden, A.G. (André), Rivadeneira Ramirez, F. (Fernando), Aulchenko, Y.S. (Yurii), Polasek, O. (Ozren), Hastie, N. (Nick), Vitart, V. (Veronique), Helmer, C. (Catherine), Wang, J.J. (Jie Jin), Stengel, B. (Bernd), Ruggiero, D., Bergmann, S.M. (Sven), Kähönen, M. (Mika), Viikari, J. (Jorma), Nikopensius, T. (Tiit), Province, M.A. (Mike), Colhoun, H.M. (H.), Doney, A.S.F. (Alex), Robino, A. (Antonietta), Krämer, B.K. (Bernhard), Portas, L. (Laura), Ford, I. (Ian), Buckley, B.M. (Brendan M.), Adam, M. (Martin), Thun, G.-A. (Gian-Andri), Paulweber, B. (Bernhard), Haun, M. (Margot), Sala, C. (Cinzia), Mitchell, P. (Paul), Ciullo, M., Vollenweider, P. (Peter), Raitakari, O. (Olli), Metspalu, A. (Andres), Palmer, C.N.A. (Colin), Gasparini, P. (Paolo), Pirastu, M. (Mario), Jukema, J.W. (Jan Wouter), Probst-Hensch, N.M. (Nicole M.), Kronenberg, F. (Florian), Toniolo, D. (Daniela), Gudnason, V. (Vilmundur), Shuldiner, A.R. (Alan), Coresh, J. (Josef), Schmidt, R. (Reinhold), Ferrucci, L. (Luigi), Duijn, C.M. (Cornelia) van, Borecki, I.B. (Ingrid), Kardia, S.L.R. (Sharon), Liu, Y. (YongMei), Curhan, G.C. (Gary), Rudan, I. (Igor), Gyllensten, U. (Ulf), Wilson, J.F. (James), Franke, A. (Andre), Pramstaller, P.P. (Peter Paul), Rettig, R. (Rainer), Prokopenko, I. (Inga), Witteman, J.C.M. (Jacqueline), Hayward, C. (Caroline), Ridker, P.M. (Paul), Bochud, M. (Murielle), Heid, I.M. (Iris), Siscovick, D.S. (David), Fox, C.S. (Caroline), Kao, W.H.L. (Wen), Böger, C.A. (Carsten), Parsa, A. (Afshin), Fuchsberger, C. (Christian), Köttgen, A. (Anna), O'Seaghdha, C.M. (Conall), Pattaro, C. (Cristian), Andrade, M. (Mariza) de, Chasman, D.I. (Daniel), Teumer, A. (Alexander), Endlich, K. (Karlhans), Olden, M. (Matthias), Chen, M-H. (Ming-Huei), Tin, A. (Adrienne), Kim, Y-J. (Yong-Jin), Taliun, D. (Daniel), Li, M. (Man), Feitosa, M.F. (Mary Furlan), Gorski, M. (Mathias), Yang, Q. (Qiong), Hundertmark, C. (Claudia), Foster, M.C. (Michael), Glazer, N. (Nicole), Isaacs, A.J. (Aaron), Rao, M. (Madhumathi), Smith, A.V. (Davey), O´Connell, J.R., Struchalin, M.V. (Maksim), Tanaka, T. (Toshiko), Li, G. (Guo), Hwang, S.J., Atkinson, E.J. (Elizabeth), Lohman, K. (Kurt), Cornelis, M. (Marilyn), Johansson, A. (Åsa), Tönjes, A. (Anke), Dehghan, A. (Abbas), Couraki, V. (Vincent), Holliday, E.G. (Elizabeth), Sorice, R., Kutalik, Z. (Zoltán), Lehtimäki, T. (Terho), Esko, T. (Tõnu), Deshmukh, H. (Harshal), Ulivi, S. (Shelia), Chu, A.Y. (Audrey), Murgia, D. (Daniela), Trompet, S. (Stella), Imboden, M. (Medea), Kollerits, B. (Barbara), Pistis, G. (Giorgio), Harris, T.B. (Tamara), Launer, L.J. (Lenore), Aspelund, T. (Thor), Eiriksdottir, G. (Gudny), Mitchell, B.D. (Braxton), Boerwinkle, E.A. (Eric), Schmidt, H. (Helena), Hofer, E. (Edith), Hu, F.B. (Frank), Demirkan, A. (Ayşe), Oostra, B.A. (Ben), Turner, S.T. (Stephen), Ding, J. (Jingzhong), Andrews, J.S. (Jeanette), Freedman, B.I. (Barry), Giulianini, F. (Franco), Koenig, W. (Wolfgang), Illig, T. (Thomas), Döring, A. (Angela), Wichmann, H.E. (Heinz Erich), Zgaga, L. (Lina), Zemunik, T. (Tatijana), Boban, M. (Mladen), Minelli, C. (Cosetta), Wheeler, H.E. (Heather), Igl, W. (Wilmar), Zaboli, G. (Ghazal), Wild, S.H. (Sarah), Wright, A.F. (Alan), Campbell, H. (Harry), Ellinghaus, D. (David), Nöthlings, U. (Ute), Jacobs, G. (Gunnar), Biffar, R. (Reiner), Ernst, F.D.J. (Florian), Homuth, G. (Georg), Kroemer, H.K. (Heyo), Nauck, M. (Matthias), Stracke, S. (Sylvia), Vol̈ker, U. (Uwe), Völzke, H. (Henry), Kovacs, P. (Peter), Stumvoll, M. (Michael), Mägi, R. (Reedik), Hofman, A. (Albert), Uitterlinden, A.G. (André), Rivadeneira Ramirez, F. (Fernando), Aulchenko, Y.S. (Yurii), Polasek, O. (Ozren), Hastie, N. (Nick), Vitart, V. (Veronique), Helmer, C. (Catherine), Wang, J.J. (Jie Jin), Stengel, B. (Bernd), Ruggiero, D., Bergmann, S.M. (Sven), Kähönen, M. (Mika), Viikari, J. (Jorma), Nikopensius, T. (Tiit), Province, M.A. (Mike), Colhoun, H.M. (H.), Doney, A.S.F. (Alex), Robino, A. (Antonietta), Krämer, B.K. (Bernhard), Portas, L. (Laura), Ford, I. (Ian), Buckley, B.M. (Brendan M.), Adam, M. (Martin), Thun, G.-A. (Gian-Andri), Paulweber, B. (Bernhard), Haun, M. (Margot), Sala, C. (Cinzia), Mitchell, P. (Paul), Ciullo, M., Vollenweider, P. (Peter), Raitakari, O. (Olli), Metspalu, A. (Andres), Palmer, C.N.A. (Colin), Gasparini, P. (Paolo), Pirastu, M. (Mario), Jukema, J.W. (Jan Wouter), Probst-Hensch, N.M. (Nicole M.), Kronenberg, F. (Florian), Toniolo, D. (Daniela), Gudnason, V. (Vilmundur), Shuldiner, A.R. (Alan), Coresh, J. (Josef), Schmidt, R. (Reinhold), Ferrucci, L. (Luigi), Duijn, C.M. (Cornelia) van, Borecki, I.B. (Ingrid), Kardia, S.L.R. (Sharon), Liu, Y. (YongMei), Curhan, G.C. (Gary), Rudan, I. (Igor), Gyllensten, U. (Ulf), Wilson, J.F. (James), Franke, A. (Andre), Pramstaller, P.P. (Peter Paul), Rettig, R. (Rainer), Prokopenko, I. (Inga), Witteman, J.C.M. (Jacqueline), Hayward, C. (Caroline), Ridker, P.M. (Paul), Bochud, M. (Murielle), Heid, I.M. (Iris), Siscovick, D.S. (David), Fox, C.S. (Caroline), Kao, W.H.L. (Wen), and Böger, C.A. (Carsten)

Abstract

Many common genetic variants identified by genome-wide association studies for complex traitsmap to genes previously linked to rare inherited Mendelian disorders. A systematic analysis of common single-nucleotide polymorphisms (SNPs) in genes responsible for Mendelian diseases with kidney phenotypes has not been performed. We thus developed a comprehensive database of genes for Mendelian kidney conditions and evaluated the association between common genetic variants within these genes and kidney function in the general population. Using the Online Mendelian Inheritance in Man database, we identified 731 unique disease entries related to specific renal search terms and confirmed a kidney phenotype in 218 of these entries, corresponding to mutations in 258 genes. We interrogated common SNPs (minor allele frequency >5%) within these genes for association with the estimated GFR in 74,354 European-ancestry participants from the CKDGen Consortium. However, the top four candidate SNPs (rs6433115 at LRP2, rs1050700 at TSC1, rs249942 at PALB2, and rs9827843 at ROBO2) did not achieve significance in a stage 2meta-analysis performed in 56,246 additional independent individuals, indicating that these common SNPs are not associated with estimated GFR. The effect of less common or rare variants in these genes on kidney function in the general population and disease-specific cohorts requires further research. Copyright

Published
2013
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19. Differences in prevalence, extent, severity, and prognosis of coronary artery disease among patients with and without diabetes undergoing coronary computed tomography angiography: Results from 10,110 individuals from the CONFIRM (COronary CT Angiography EvaluatioN for Clinical Outcomes): An InteRnational Multicenter Registry

Author

Rana, J.S. (Jamal), Dunning, A.M. (Alison), Achenbach, S. (Stephan), Al-Mallah, M. (Mouaz), Budoff, M.J. (Matthew), Cademartiri, F. (Filippo), Callister, T.Q. (Tracy), Chang, H.-J. (Hyuk-Jae), Cheng, V.Y. (Victor), Chinnaiyan, K. (Kavitha), Chow, B.J.W. (Benjamin), Cury, R.C. (Ricardo), Delago, A. (Augustin), Feuchtner, G.M. (Gudrun), Hadamitzky, M. (Martin), Hausleiter, J. (Jörg), Kaufmann, P.A. (Philipp), Karlsberg, R.P. (Ronald), Kim, Y-J. (Yong-Jin), Leipsic, J. (Jonathon), LaBounty, T.M. (Troy), Lin, F.Y. (Fay), Maffei, E. (Erica), Raff, G.L. (Gilbert), Villines, T.C. (Todd), Shaw, L.J. (Leslee), Berman, D.S. (Daniel), Min, J.K. (James), Rana, J.S. (Jamal), Dunning, A.M. (Alison), Achenbach, S. (Stephan), Al-Mallah, M. (Mouaz), Budoff, M.J. (Matthew), Cademartiri, F. (Filippo), Callister, T.Q. (Tracy), Chang, H.-J. (Hyuk-Jae), Cheng, V.Y. (Victor), Chinnaiyan, K. (Kavitha), Chow, B.J.W. (Benjamin), Cury, R.C. (Ricardo), Delago, A. (Augustin), Feuchtner, G.M. (Gudrun), Hadamitzky, M. (Martin), Hausleiter, J. (Jörg), Kaufmann, P.A. (Philipp), Karlsberg, R.P. (Ronald), Kim, Y-J. (Yong-Jin), Leipsic, J. (Jonathon), LaBounty, T.M. (Troy), Lin, F.Y. (Fay), Maffei, E. (Erica), Raff, G.L. (Gilbert), Villines, T.C. (Todd), Shaw, L.J. (Leslee), Berman, D.S. (Daniel), and Min, J.K. (James)

Abstract

OBJECTIVE - We examined the prevalence, extent, severity, and prognosis of coronary artery disease (CAD) in individualswith and without diabetes (DM) who are similar in CAD risk factors. RESEARCH DESIGN ANDMETHODS - We identified 23,643 consecutive individuals without known CAD undergoing coronary computed tomography angiography. A total of 3,370 DM individuals were propensity matched in a 1-to-2 fashion to 6,740 unique non-DM individuals. CAD was defined as none, nonobstructive (1-49% stenosis), or obstructive (≥50% stenosis). All-cause mortality was assessed by risk-adjusted Cox proportional hazards models. RESULTS - At a 2.2-year follow-up, 108 (3.2%) and 115 (1.7%) deaths occurred among DM and non-DM individuals, respectively. Compared with non-DM individuals, DM individuals possessed higher rates of obstructive CAD (37 vs. 27%) and lower rates of having normal arteries (28 vs. 36%) (P < 0.0001). CAD extent was higher for DM versus non-DM individuals for obstructive one-vessel disease (19 vs. 14%), two-vessel disease (9 vs. 7%), and three-vessel disease (9 vs. 5%) (P < 0.0001 for comparison), with higher per-segment stenosis in the proximal and mid-segments of every coronary artery (P < 0.001 for all). Compared with non-DM individuals with no CAD, risk of mortality for DM individuals was higher for those with no CAD (hazard ratio 3.63 [95% CI 1.67-7.91]; P = 0.001), nonobstructive CAD (5.25 [2.56-10.8]; P < 0.001), one-vessel disease (6.39 [2.98-13.7]; P , 0.0001), two-vessel disease (12.33 [5.622-27.1]; P < 0.0001), and three-vessel disease (13.25 [6.15-28.6]; P < 0.0001). CONCLUSIONS - Compared with matched non-DM individuals, DM individuals possess higher prevalence, extent, and severity of CAD. At comparable levels of CAD, DM individuals experience higher risk of mortality compared with non-DM individuals.

Published
2012
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20. Biological, clinical and population relevance of 95 loci for blood lipids

Author

Teslovich, T.M. (Tanya), Musunuru, K. (Kiran), Smith, A.V. (Albert Vernon), Edmondson, A.C. (Andrew), Stylianou, I.M. (Ioannis), Koseki, M. (Masahiro), Pirruccello, J.P. (James), Ripatti, S. (Samuli), Chasman, D.I. (Daniel), Willer, C.J. (Cristen), Johansen, C.T. (Christopher), Fouchier, S.W. (Sigrid), Isaacs, A.J. (Aaron), Peloso, G.M. (Gina), Barbalic, M. (maja), Ricketts, S.L. (Sally), Bis, J.C. (Joshua), Aulchenko, Y.S. (Yurii), Thorleifsson, G. (Gudmar), Feitosa, M.F. (Mary Furlan), Chambers, J. (John), Orho-Melander, M. (Marju), Melander, O. (Olle), Johnson, T. (Toby), Li, X. (Xiaohui), Guo, X. (Xiuqing), Shin Cho, Y. (Yoon), Jin Go, M. (Min), Jin Kim, Y. (Young), Lee, J.Y. (Jong Young), Park, T. (Taesung), Kim, Y-J. (Yong-Jin), Sim, X. (Xueling), Twee-Hee Ong, R. (Rick), Croteau-Chonka, D.C. (Damien), Lange, L.A. (Leslie), Song, K. (Kijoung), Zhao, J.H. (Jing Hua), Yuan, X. (Xin), Luan, J., Lamina, C. (Claudia), Ziegler, A. (Andreas), Zhang, W. (Weibo), Zee, R.Y.L. (Robert), Wright, A.F. (Alan), Witteman, J.C.M. (Jacqueline), Wilson, J.F. (James), Willemsen, G.A.H.M. (Gonneke), Wichmann, H.E. (Heinz Erich), Whitfield, J. (John), Waterworth, D. (Dawn), Wareham, N.J. (Nick), Waeber, G. (Gérard), Vollenweider, P. (Peter), Voight, B.F. (Benjamin), Vitart, V. (Veronique), Uitterlinden, A.G. (André), Uda, M. (Manuela), Tuomilehto, J. (Jaakko), Thompson, J.R. (John), Tanaka, T. (Toshiko), Surakka, I. (Ida), Stringham, H.M. (Heather), Spector, T.D. (Timothy), Soranzo, N. (Nicole), Smit, J.H. (Johannes), Sinisalo, J. (Juha), Silander, K. (Kaisa), Sijbrands, E.J.G. (Eric), Scuteri, A. (Angelo), Scott, J. (James), Schlessinger, D. (David), Sanna, S. (Serena), Salomaa, V. (Veikko), Saharinen, J. (Juha), Sabatti, C. (Chiara), Ruokonen, A. (Aimo), Rudan, I. (Igor), Rose, L.M. (Lynda), Roberts, R. (Robert), Rieder, M. (Mark), Psaty, B.M. (Bruce), Pramstaller, P.P. (Peter Paul), Pichler, I. (Irene), Perola, M. (Markus), Penninx, B.W.J.H. (Brenda), Pedersen, N.L. (Nancy), Pattaro, C. (Cristian), Parker, A.N. (Alex), Pare, G. (Guillaume), Oostra, B.A. (Ben), Nieminen, M.S. (Markku), Nickerson, D.A. (Deborah), Montgomery, G.W. (Grant), Meitinger, T. (Thomas), McPherson, R. (Ruth), McCarthy, M.I. (Mark), McArdle, W.L. (Wendy), Masson, D. (David), Martin, N.G. (Nicholas), Marroni, F. (Fabio), Mangino, M. (Massimo), Magnusson, P.K. (Patrik), Lucas, G. (Gavin), Luben, R.N. (Robert), Loos, R.J.F. (Ruth), Lokki, M.L., Lettre, G. (Guillaume), Langenberg, C. (Claudia), Launer, L.J. (Lenore), Lakatta, E. (Edward), Laaksonen, R. (Reijo), Kyvik, K.O. (Kirsten Ohm), Kronenberg, F. (Florian), König, I.R. (Inke), Khaw, K-T. (Kay-Tee), Kaprio, J. (Jaakko), Kaplan, R.C. (Robert), Johansson, A. (Åsa), Jarvelin, M.-R. (Marjo-Riitta), Cecile, A. (A.), Ingelsson, E. (Erik), Igl, W. (Wilmar), Hovingh, G.K. (Kees), Hottenga, J.J. (Jouke Jan), Hofman, A. (Albert), Hicks, A.A. (Andrew), Hengstenberg, C. (Christian), Heid, I.M. (Iris), Hayward, C. (Caroline), Havulinna, A.S. (Aki), Hastie, N. (Nick), Harris, T.B. (Tamara), Haritunians, T. (Talin), Hall, A.S. (Alistair), Gyllensten, U. (Ulf), Guiducci, C. (Candace), Groop, L. (Leif), Gonzalez, E. (Elena), Gieger, C. (Christian), Freimer, N.B. (Nelson), Ferrucci, L. (Luigi), Erdmann, J. (Jeanette), Elliott, P. (Paul), Ejebe, K.G. (Kenechi), Döring, A. (Angela), Dominiczak, A. (Anna), Demissie, S. (Serkalem), Deloukas, P. (Panagiotis), Geus, E.J.C. (Eco) de, Faire, U. (Ulf) de, Crawford, G. (Gabe), Collins, F.S. (Francis), Chen, C. (Chao), Caulfield, M. (Mark), Campbell, H. (Harry), Burtt, N.P. (Noël), Bonnycastle, L.L. (Lori), Boomsma, D.I. (Dorret), Boekholdt, S.M. (Matthijs), Bergman, R.N. (Richard), Barroso, I.E. (Inês), Bandinelli, S. (Stefania), Ballantyne, C. (Christie), Assimes, T.L. (Themistocles), Quertermous, T. (Thomas), Altshuler, D. (David), Seielstad, M. (Mark), Wong, T.Y. (Tien Yin), Tai, E.S. (Shyong), Feranil, A.B. (Alan), Kuzawa, C.W. (Christopher), Adair, L.S. (Linda), Taylor, H.A. (Herman), Borecki, I.B. (Ingrid), Gabriel, S.B. (Stacey), Holm, H. (Hilma), Thorsteinsdottir, U. (Unnur), Gudnason, V. (Vilmundur), Krauss, R.M. (Ronald), Mohlke, K.L. (Karen), Ordovas, J.M. (Jose), Munroe, P. (Patricia), Kooner, J.S. (Jaspal), Tall, A.R. (Alan), Hegele, R.A. (Robert), Kastelein, J.J.P. (John), Schadt, E.E. (Eric), Rotter, J.I. (Jerome), Boerwinkle, E.A. (Eric), Strachan, D.P. (David), Mooser, V. (Vincent), Zwart, J-A. (John-Anker), Reilly, M.P. (Muredach), Samani, N.J. (Nilesh), Schunkert, H. (Heribert), Cupples, L.A. (Adrienne), Sandhu, M.S. (Manjinder), Ridker, P.M. (Paul), Rader, D.J. (Daniel), Tikka-Kleemola, P. (Päivi), Peltonen, L. (Leena Johanna), Abecasis, G.R. (Gonçalo), Boehnke, M. (Michael), Kathiresan, S. (Sekar), O'Donnell, C.J. (Christopher), Teslovich, T.M. (Tanya), Musunuru, K. (Kiran), Smith, A.V. (Albert Vernon), Edmondson, A.C. (Andrew), Stylianou, I.M. (Ioannis), Koseki, M. (Masahiro), Pirruccello, J.P. (James), Ripatti, S. (Samuli), Chasman, D.I. (Daniel), Willer, C.J. (Cristen), Johansen, C.T. (Christopher), Fouchier, S.W. (Sigrid), Isaacs, A.J. (Aaron), Peloso, G.M. (Gina), Barbalic, M. (maja), Ricketts, S.L. (Sally), Bis, J.C. (Joshua), Aulchenko, Y.S. (Yurii), Thorleifsson, G. (Gudmar), Feitosa, M.F. (Mary Furlan), Chambers, J. (John), Orho-Melander, M. (Marju), Melander, O. (Olle), Johnson, T. (Toby), Li, X. (Xiaohui), Guo, X. (Xiuqing), Shin Cho, Y. (Yoon), Jin Go, M. (Min), Jin Kim, Y. (Young), Lee, J.Y. (Jong Young), Park, T. (Taesung), Kim, Y-J. (Yong-Jin), Sim, X. (Xueling), Twee-Hee Ong, R. (Rick), Croteau-Chonka, D.C. (Damien), Lange, L.A. (Leslie), Song, K. (Kijoung), Zhao, J.H. (Jing Hua), Yuan, X. (Xin), Luan, J., Lamina, C. (Claudia), Ziegler, A. (Andreas), Zhang, W. (Weibo), Zee, R.Y.L. (Robert), Wright, A.F. (Alan), Witteman, J.C.M. (Jacqueline), Wilson, J.F. (James), Willemsen, G.A.H.M. (Gonneke), Wichmann, H.E. (Heinz Erich), Whitfield, J. (John), Waterworth, D. (Dawn), Wareham, N.J. (Nick), Waeber, G. (Gérard), Vollenweider, P. (Peter), Voight, B.F. (Benjamin), Vitart, V. (Veronique), Uitterlinden, A.G. (André), Uda, M. (Manuela), Tuomilehto, J. (Jaakko), Thompson, J.R. (John), Tanaka, T. (Toshiko), Surakka, I. (Ida), Stringham, H.M. (Heather), Spector, T.D. (Timothy), Soranzo, N. (Nicole), Smit, J.H. (Johannes), Sinisalo, J. (Juha), Silander, K. (Kaisa), Sijbrands, E.J.G. (Eric), Scuteri, A. (Angelo), Scott, J. (James), Schlessinger, D. (David), Sanna, S. (Serena), Salomaa, V. (Veikko), Saharinen, J. (Juha), Sabatti, C. (Chiara), Ruokonen, A. (Aimo), Rudan, I. (Igor), Rose, L.M. (Lynda), Roberts, R. (Robert), Rieder, M. (Mark), Psaty, B.M. (Bruce), Pramstaller, P.P. (Peter Paul), Pichler, I. (Irene), Perola, M. (Markus), Penninx, B.W.J.H. (Brenda), Pedersen, N.L. (Nancy), Pattaro, C. (Cristian), Parker, A.N. (Alex), Pare, G. (Guillaume), Oostra, B.A. (Ben), Nieminen, M.S. (Markku), Nickerson, D.A. (Deborah), Montgomery, G.W. (Grant), Meitinger, T. (Thomas), McPherson, R. (Ruth), McCarthy, M.I. (Mark), McArdle, W.L. (Wendy), Masson, D. (David), Martin, N.G. (Nicholas), Marroni, F. (Fabio), Mangino, M. (Massimo), Magnusson, P.K. (Patrik), Lucas, G. (Gavin), Luben, R.N. (Robert), Loos, R.J.F. (Ruth), Lokki, M.L., Lettre, G. (Guillaume), Langenberg, C. (Claudia), Launer, L.J. (Lenore), Lakatta, E. (Edward), Laaksonen, R. (Reijo), Kyvik, K.O. (Kirsten Ohm), Kronenberg, F. (Florian), König, I.R. (Inke), Khaw, K-T. (Kay-Tee), Kaprio, J. (Jaakko), Kaplan, R.C. (Robert), Johansson, A. (Åsa), Jarvelin, M.-R. (Marjo-Riitta), Cecile, A. (A.), Ingelsson, E. (Erik), Igl, W. (Wilmar), Hovingh, G.K. (Kees), Hottenga, J.J. (Jouke Jan), Hofman, A. (Albert), Hicks, A.A. (Andrew), Hengstenberg, C. (Christian), Heid, I.M. (Iris), Hayward, C. (Caroline), Havulinna, A.S. (Aki), Hastie, N. (Nick), Harris, T.B. (Tamara), Haritunians, T. (Talin), Hall, A.S. (Alistair), Gyllensten, U. (Ulf), Guiducci, C. (Candace), Groop, L. (Leif), Gonzalez, E. (Elena), Gieger, C. (Christian), Freimer, N.B. (Nelson), Ferrucci, L. (Luigi), Erdmann, J. (Jeanette), Elliott, P. (Paul), Ejebe, K.G. (Kenechi), Döring, A. (Angela), Dominiczak, A. (Anna), Demissie, S. (Serkalem), Deloukas, P. (Panagiotis), Geus, E.J.C. (Eco) de, Faire, U. (Ulf) de, Crawford, G. (Gabe), Collins, F.S. (Francis), Chen, C. (Chao), Caulfield, M. (Mark), Campbell, H. (Harry), Burtt, N.P. (Noël), Bonnycastle, L.L. (Lori), Boomsma, D.I. (Dorret), Boekholdt, S.M. (Matthijs), Bergman, R.N. (Richard), Barroso, I.E. (Inês), Bandinelli, S. (Stefania), Ballantyne, C. (Christie), Assimes, T.L. (Themistocles), Quertermous, T. (Thomas), Altshuler, D. (David), Seielstad, M. (Mark), Wong, T.Y. (Tien Yin), Tai, E.S. (Shyong), Feranil, A.B. (Alan), Kuzawa, C.W. (Christopher), Adair, L.S. (Linda), Taylor, H.A. (Herman), Borecki, I.B. (Ingrid), Gabriel, S.B. (Stacey), Holm, H. (Hilma), Thorsteinsdottir, U. (Unnur), Gudnason, V. (Vilmundur), Krauss, R.M. (Ronald), Mohlke, K.L. (Karen), Ordovas, J.M. (Jose), Munroe, P. (Patricia), Kooner, J.S. (Jaspal), Tall, A.R. (Alan), Hegele, R.A. (Robert), Kastelein, J.J.P. (John), Schadt, E.E. (Eric), Rotter, J.I. (Jerome), Boerwinkle, E.A. (Eric), Strachan, D.P. (David), Mooser, V. (Vincent), Zwart, J-A. (John-Anker), Reilly, M.P. (Muredach), Samani, N.J. (Nilesh), Schunkert, H. (Heribert), Cupples, L.A. (Adrienne), Sandhu, M.S. (Manjinder), Ridker, P.M. (Paul), Rader, D.J. (Daniel), Tikka-Kleemola, P. (Päivi), Peltonen, L. (Leena Johanna), Abecasis, G.R. (Gonçalo), Boehnke, M. (Michael), Kathiresan, S. (Sekar), and O'Donnell, C.J. (Christopher)

Abstract

Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with plasma lipids in >100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P<-10-8), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (for example, CYP7A1, NPC1L1 and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and have an impact on lipid traits in three non-European populations (East Asians, South Asians and African Americans). Our results identify several novel loci associated with plasma lipids that are also associated with CAD. Finally, we validated three of the novel genes-GALNT2, PPP1R3B and TTC39B-with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD.

Published
2010
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