Polygenic Risk Scores and Extreme Coronary Artery Calcium Phenotypes (CAC=0 and CAC≥1000) in Adults ≥75 Years Old: The ARIC Study

作者：Omar Dzaye, Alexander C. Razavi, Zeina Dardari, Frances Wang, Yasuyuki Honda, Khurram Nasir, Josef Coresh, Candace M. Howard, Jin Jin, Bing Yu, Paul S. de Vries, Lynne E. Wagenknecht, Aaron R. Folsom, Ron Blankstein, Tanika N. Kelly, Seamus P. Whelton, Martin Bødtker Mortensen, Ziqiao Wang, Nilanjan Chatterjee, Kunihiro Matsushita, Michael J. Blaha · 发表于：Circulation Cardiovascular Imaging · 年份：2024 · DOI：10.1161/circimaging.123.016377 · 被引用次数：6 · 研究领域：Genetic Associations and Epidemiology、Cardiac Imaging and Diagnostics、BRCA gene mutations in cancer

BACKGROUND: Coronary artery calcium (CAC) is heterogeneous in older age and is incompletely explained by traditional atherosclerotic cardiovascular disease risk factors. The extremes of subclinical atherosclerosis burden are strongly associated with either a low or high 10-year risk of incident atherosclerotic cardiovascular disease, respectively. However, the genetic underpinnings of differences in arterial aging remain unclear. We sought to determine the independent association of 2 polygenic scores for coronary heart disease (CHD) with CAC in adults ≥75 years of age. METHODS: There were 1865 ARIC (Atherosclerosis Risk in Communities) participants who underwent genetic testing at visit 1 (1987-1989) and CAC scans at visit 7 (2018-2019). In the primary analysis, an externally derived multi-ancestry polygenic CHD risk score was calculated for both White and Black participants. Results were confirmed using a separate ARIC-derived polygenic CHD risk score, including ≥6 million variants computed for White participants. We used multivariable logistic regression models to assess the association of polygenic CHD risk with CAC, after adjusting for baseline, time-averaged lifestyle, traditional risk factors, and local ancestry principal components. RESULTS: In the primary analysis, the average age was 80.6 years old, 61.6% were women, and the median CAC score was 246 (189 participants with CAC=0, 364 participants with CAC≥1000). Compared with persons below the 20th percentile of poly...