@article {1170, title = {Common variants in KCNN3 are associated with lone atrial fibrillation.}, journal = {Nat Genet}, volume = {42}, year = {2010}, month = {2010 Mar}, pages = {240-4}, abstract = {

Atrial fibrillation (AF) is the most common sustained arrhythmia. Previous studies have identified several genetic loci associated with typical AF. We sought to identify common genetic variants underlying lone AF. This condition affects a subset of individuals without overt heart disease and with an increased heritability of AF. We report a meta-analysis of genome-wide association studies conducted using 1,335 individuals with lone AF (cases) and 12,844 unaffected individuals (referents). Cases were obtained from the German AF Network, Heart and Vascular Health Study, the Atherosclerosis Risk in Communities Study, the Cleveland Clinic and Massachusetts General Hospital. We identified an association on chromosome 1q21 to lone AF (rs13376333, adjusted odds ratio = 1.56; P = 6.3 x 10(-12)), and we replicated this association in two independent cohorts with lone AF (overall combined odds ratio = 1.52, 95\% CI 1.40-1.64; P = 1.83 x 10(-21)). rs13376333 is intronic to KCNN3, which encodes a potassium channel protein involved in atrial repolarization.

}, keywords = {Adolescent, Adult, Aged, Atrial Fibrillation, Case-Control Studies, Cohort Studies, Female, Genome-Wide Association Study, Humans, Introns, Male, Meta-Analysis as Topic, Middle Aged, Polymorphism, Single Nucleotide, Small-Conductance Calcium-Activated Potassium Channels, Young Adult}, issn = {1546-1718}, doi = {10.1038/ng.537}, author = {Ellinor, Patrick T and Lunetta, Kathryn L and Glazer, Nicole L and Pfeufer, Arne and Alonso, Alvaro and Chung, Mina K and Sinner, Moritz F and de Bakker, Paul I W and Mueller, Martina and Lubitz, Steven A and Fox, Ervin and Darbar, Dawood and Smith, Nicholas L and Smith, Jonathan D and Schnabel, Renate B and Soliman, Elsayed Z and Rice, Kenneth M and Van Wagoner, David R and Beckmann, Britt-M and van Noord, Charlotte and Wang, Ke and Ehret, Georg B and Rotter, Jerome I and Hazen, Stanley L and Steinbeck, Gerhard and Smith, Albert V and Launer, Lenore J and Harris, Tamara B and Makino, Seiko and Nelis, Mari and Milan, David J and Perz, Siegfried and Esko, T{\~o}nu and K{\"o}ttgen, Anna and Moebus, Susanne and Newton-Cheh, Christopher and Li, Man and M{\"o}hlenkamp, Stefan and Wang, Thomas J and Kao, W H Linda and Vasan, Ramachandran S and N{\"o}then, Markus M and MacRae, Calum A and Stricker, Bruno H Ch and Hofman, Albert and Uitterlinden, Andr{\'e} G and Levy, Daniel and Boerwinkle, Eric and Metspalu, Andres and Topol, Eric J and Chakravarti, Aravinda and Gudnason, Vilmundur and Psaty, Bruce M and Roden, Dan M and Meitinger, Thomas and Wichmann, H-Erich and Witteman, Jacqueline C M and Barnard, John and Arking, Dan E and Benjamin, Emelia J and Heckbert, Susan R and K{\"a}{\"a}b, Stefan} } @article {7442, title = {Association of Coronary Artery Calcium Score vs Age With Cardiovascular Risk in Older Adults: An Analysis of Pooled Population-Based Studies.}, journal = {JAMA Cardiol}, year = {2017}, month = {2017 Jul 26}, abstract = {

Importance: Besides age, other discriminators of atherosclerotic cardiovascular disease (ASCVD) risk are needed in older adults.

Objectives: To examine the predictive ability of coronary artery calcium (CAC) score vs age for incident ASCVD and how risk prediction changes by adding CAC score and removing only age from prediction models.

Design, Setting, and Participants: We conducted an analysis of pooled US population-based studies, including the Framingham Heart Study, the Multi-Ethnic Study of Atherosclerosis, and the Cardiovascular Health Study. Results were compared with 2 European cohorts, the Rotterdam Study and the Heinz Nixdorf Recall Study. Participants underwent CAC scoring between 1998 and 2006 using cardiac computed tomography. The participants included adults older than 60 years without known ASCVD at baseline.

Exposures: Coronary artery calcium scores.

Main Outcomes and Measures: Incident ASCVD events including coronary heart disease (CHD) and stroke.

Results: The study included 4778 participants from 3 US cohorts, with a mean age of 70.1 years; 2582 (54.0\%) were women, and 2431 (50.9\%) were nonwhite. Over 11 years of follow-up (44 152 person-years), 405 CHD and 228 stroke events occurred. Coronary artery calcium score (vs age) had a greater association with incident CHD (C statistic, 0.733 vs 0.690; C statistics difference, 0.043; 95\% CI of difference, 0.009-0.075) and modestly improved prediction of incident stroke (C statistic, 0.695 vs 0.670; C statistics difference, 0.025; 95\% CI of difference, -0.015 to 0.064). Adding CAC score to models including traditional cardiovascular risk factors, with only age being removed, provided improved discrimination for incident CHD (C statistic, 0.735 vs 0.703; C statistics difference, 0.032; 95\% CI of difference, 0.002-0.062) but not for stroke. Coronary artery calcium score was more likely than age to provide higher category-free net reclassification improvement among participants who experienced an ASCVD event (0.390; 95\% CI, 0.312-0.467 vs 0.08; 95\% CI -0.001 to 0.181) and to result in more accurate reclassification of risk for ASCVD events among these individuals. The findings were similar in the 2 European cohorts (n = 4990).

Conclusions and Relevance: Coronary artery calcium may be an alternative marker besides age to better discriminate between lower and higher CHD risk in older adults. Whether CAC score can assist in guiding the decision to initiate statin treatment for primary prevention in older adults requires further investigation.

}, issn = {2380-6591}, doi = {10.1001/jamacardio.2017.2498}, author = {Yano, Yuichiro and O{\textquoteright}Donnell, Christopher J and Kuller, Lewis and Kavousi, Maryam and Erbel, Raimund and Ning, Hongyan and D{\textquoteright}Agostino, Ralph and Newman, Anne B and Nasir, Khurram and Hofman, Albert and Lehmann, Nils and Dhana, Klodian and Blankstein, Ron and Hoffmann, Udo and M{\"o}hlenkamp, Stefan and Massaro, Joseph M and Mahabadi, Amir-Abbas and Lima, Jo{\~a}o A C and Ikram, M Arfan and J{\"o}ckel, Karl-Heinz and Franco, Oscar H and Liu, Kiang and Lloyd-Jones, Donald and Greenland, Philip} }