Polygenic risk, aspirin and primary prevention of coronary artery disease.

IF 5.3 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS
Chenglong Yu, Pradeep Natarajan, Aniruddh P Patel, Harpreet S Bhatia, Amit V Khera, Johannes T Neumann, Sotirios Tsimikas, Rory Wolfe, Stephen J Nicholls, Christopher M Reid, Sophia Zoungas, Andrew M Tonkin, John J McNeil, Paul Lacaze
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引用次数: 0

Abstract

Aims: Recent aspirin primary prevention trials failed to identify a net benefit of aspirin for preventing cardiovascular disease versus the harms of bleeding. This study aimed to investigate whether a high-risk subgroup, individuals with elevated genetic predisposition to coronary artery disease (CAD), might derive more benefit than harm with aspirin, compared to those with lower genetic risk.

Methods and results: We performed genetic risk stratification of the Aspirin in Reducing Events in the Elderly (ASPREE) randomized controlled trial using a CAD polygenic risk score (GPSMult). For 12,031 genotyped participants (5,974 aspirin, 6,057 placebo) overall, we stratified them by GPSMult quintiles (q1-5), then examined risk of CAD (composite of myocardial infarction and coronary heart disease death) and bleeding events using Cox models. During a median 4.6 years of follow-up with randomization to 100 mg/day aspirin versus placebo, 234 (1.9%) participants had CAD and 373 (3.1%) had bleeding events. In the overall cohort, aspirin resulted in higher bleeding risk (adjusted Hazard Ratio [aHR]=1.30 [1.06-1.61], P=0.01) but no significant CAD reduction (aHR=0.84 [0.64-1.09], P=0.19). However, among the highest quintile of polygenic risk (q5, top 20% of the GPSMult distribution), there was a 47% reduction in risk of CAD events with aspirin (aHR=0.53 [0.31-0.90], P=0.02) without increased bleeding risk (aHR=1.05 [0.60-1.82], P=0.88). Interaction between the GPSMult and aspirin was significant for CAD (q5 versus q1, P=0.02) but not bleeding (P=0.80).

Conclusion: The balance between net benefit and harm on aspirin in the primary prevention setting shifts favourably in individuals with an elevated genetic predisposition.

多基因风险、阿司匹林和冠心病一级预防。
目的:最近的阿司匹林一级预防试验未能确定阿司匹林对预防心血管疾病的净益处与出血的危害。本研究旨在探讨与遗传风险较低的人群相比,冠状动脉疾病(CAD)遗传易感性较高的高风险亚群服用阿司匹林是否利大于弊:我们使用 CAD 多基因风险评分(GPSMult)对阿司匹林减少老年人冠心病事件(ASPREE)随机对照试验进行了基因风险分层。对于 12,031 名基因分型参与者(5,974 人服用阿司匹林,6,057 人服用安慰剂),我们按 GPSMult 五分位数(q1-5)对他们进行了分层,然后使用 Cox 模型检测了 CAD(心肌梗死和冠心病死亡的复合)和出血事件的风险。在随机给予 100 毫克/天阿司匹林与安慰剂的中位 4.6 年随访期间,有 234 人(1.9%)患有心血管并发症,373 人(3.1%)发生了出血事件。在整个队列中,阿司匹林会导致更高的出血风险(调整后危险比 [aHR]=1.30 [1.06-1.61],P=0.01),但不会显著降低 CAD 风险(aHR=0.84 [0.64-1.09],P=0.19)。然而,在多基因风险最高的五分之一人群中(q5,GPSMult 分布的前 20%),服用阿司匹林可使 CAD 事件风险降低 47%(aHR=0.53 [0.31-0.90],P=0.02),但出血风险并未增加(aHR=1.05 [0.60-1.82],P=0.88)。GPSMult与阿司匹林之间的相互作用对CAD有显著影响(q5对q1,P=0.02),但对出血无显著影响(P=0.80):结论:在一级预防中,阿司匹林的净收益与危害之间的平衡在遗传易感性增高的个体中发生了有利的变化。
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来源期刊
European Heart Journal - Cardiovascular Pharmacotherapy
European Heart Journal - Cardiovascular Pharmacotherapy Medicine-Cardiology and Cardiovascular Medicine
CiteScore
10.10
自引率
14.10%
发文量
65
期刊介绍: The European Heart Journal - Cardiovascular Pharmacotherapy (EHJ-CVP) is an international, peer-reviewed journal published in English, specifically dedicated to clinical cardiovascular pharmacology. EHJ-CVP publishes original articles focusing on clinical research involving both new and established drugs and methods, along with meta-analyses and topical reviews. The journal's primary aim is to enhance the pharmacological treatment of patients with cardiovascular disease by interpreting and integrating new scientific developments in this field. While the emphasis is on clinical topics, EHJ-CVP also considers basic research articles from fields such as physiology and molecular biology that contribute to the understanding of cardiovascular drug therapy. These may include articles related to new drug development and evaluation, the physiological and pharmacological basis of drug action, metabolism, drug interactions, and side effects.
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