Association of polygenic risk scores with incident atherosclerotic cardiovascular disease events among individuals with coronary artery calcium score of zero: The multi-ethnic study of atherosclerosis

被引：11

作者：

Al Rifai, Mahmoud ^{[1
]}

Yao, Jie ^{[2
]}

Guo, Xiuqing ^{[2
]}

Post, Wendy S. ^{[3
]}

Malik, Shaista ^{[4
]}

Blumenthal, Roger S. ^{[3
]}

Ballantyne, Christie M. ^{[1
]}

Budoff, Matthew ^{[5
]}

Taylor, Kent D. ^{[2
]}

Linb, Henry J. ^{[2
]}

Rich, Stephen S. ^{[6
]}

Hajek, Catherine ^{[7
]}

Greenland, Philip ^{[8
,9
]}

Rotter, Jerome I. ^{[2
]}

Virani, Salim S. ^{[1
,10
]}

机构：

[1] Baylor Coll Med, Sect Cardiol, Houston, TX USA

[2] UCLA Med Ctr, Lundquist Inst Biomed Innovat Harbor, Dept Pediat, Inst Translat Genom & Populat Sci, Torrance, CA USA

[3] Johns Hopkins Univ, Ciccarone Ctr Prevent Cardiovasc Dis, Baltimore, MD USA

[4] Univ Calif Irvine, Sch Med, Div Cardiol, Irvine, CA USA

[5] UCLA Med Ctr, Lundquist Inst Biomed Innovat Harbor, Torrance, CA USA

[6] Univ Virginia, Ctr Publ Hlth Gen, Charlottesville, VA USA

[7] Sanford Hlth, Dept Internal Med & Med Genet, Sioux Falls, SD USA

[8] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL USA

[9] Northwestern Univ, Feinberg Sch Med, Div Cardiol, Chicago, IL USA

[10] Michael E DeBakey VA Med Ctr, Sect Cardiol, Houston, TX USA

来源：

PROGRESS IN CARDIOVASCULAR DISEASES | 2022年 / 74卷

关键词：

Polygenic risk score; Coronary artery calcium; Atherosclerotic cardiovascular disease; Coronary heart disease; AMERICAN-COLLEGE; HEART-DISEASE; CHOLESTEROL; MESA; PROGRESSION; MANAGEMENT; ACCURACY; MARKERS; LOCI;

D O I：

10.1016/j.pcad.2022.08.003

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background: Polygenic risk scores (PRS) are associated with atherosclerotic cardiovascular disease (ASCVD) events. We studied incident ASCVD among individualswith absent coronary artery calcium(CAC= 0), to investigate the association of PRS with incident ASCVD among such individuals. Methods: Data was used fromMulti-Ethnic Study of Atherosclerosis (MESA), a prospective cohort study of participants free of clinical CVD at baseline. PRS were developed based on a literature-derived list of single-nucleotide polymorphisms (SNPs) weighted by effect size. The coronary heart disease (CHD) PRS contained 180 SNPs, and the stroke PRS had 32 SNPs. These SNPs were combined to compute an ASCVD PRS. The PRS were calculated among 3132 participants with CAC = 0. Multivariable-adjusted Cox proportional hazards models evaluated the association between each PRS (top 20% vs bottom 50%) and ASCVD. Results: The study population included 3132 individualswith CAC= 0 [mean (SD) age 58 (9) years; 63% female, 33% White, 31% Black, 12% Chinese-American, 24% Hispanic]. Over a median follow-up of 16 years, there were 108 incident CHD events and 93 stroke events. ASCVD event rates were generally <7.5 per 1000-person years for all ASCVD events regardless of PRS risk stratum. The ASCVD PRS was significantly associated with incident ASCVD: (HR; 95% CI) (1.63; 1.11, 2.39). The CHD PRS was not associated with any ASCVD outcome, whereas the stroke PRS was significantly associated with ASCVD (1.84; 1.27, 2.68), CHD (1.79; 1.05, 3.06), and stroke (1.96; 1.19, 3.23). The stroke PRS results were significant among women and non-Whites. Conclusions: Among individuals with CAC = 0, the ASCVD PRS was associated with incident ASCVD events. This appears to be driven by genetic variants related to stroke but not CHD, and particularly among women and non-Whites. ASCVD event rates remained below the threshold recommended for consideration for initiation of statin therapy even in the high PRS groups. Published by Elsevier Inc.

引用

页码：19 / 27

页数：9

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