Cardiovascular disease is the leading contributor to years lost due to disability or premature death among adults. Current efforts focus on risk prediction and risk factor mitigation‚ which have been recognized for the past half-century. However, despite advances, risk prediction remains imprecise with persistently high rates of incident cardiovascular disease. Genetic characterization has been proposed as an approach to enable earlier and potentially tailored prevention. Rare mendelian pathogenic variants predisposing to cardiometabolic conditions have long been known to contribute to disease risk in some families. However, twin and familial aggregation studies imply that diverse cardiovascular conditions are heritable in the general population. Significant technological and methodological advances since the Human Genome Project are facilitating population-based comprehensive genetic profiling at decreasing costs. Genome-wide association studies from such endeavors continue to elucidate causal mechanisms for cardiovascular diseases. Systematic cataloging for cardiovascular risk alleles also enabled the development of polygenic risk scores. Genetic profiling is becoming widespread in large-scale research, including in health care–associated biobanks, randomized controlled trials, and direct-to-consumer profiling in tens of millions of people. Thus, individuals and their physicians are increasingly presented with polygenic risk scores for cardiovascular conditions in clinical encounters. In this scientific statement, we review the contemporary science, clinical considerations, and future challenges for polygenic risk scores for cardiovascular diseases. We selected 5 cardiometabolic diseases (coronary artery disease, hypercholesterolemia, type 2 diabetes, atrial fibrillation, and venous thromboembolic disease) and response to drug therapy and offer provisional guidance to health care professionals, researchers, policymakers, and patients.

中文翻译：

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心血管疾病的多基因风险评分：美国心脏协会的科学声明

心血管疾病是成年人因残疾或过早死亡而损失寿命的主要原因。当前的工作重点是风险预测和风险因素缓解，这在过去的半个世纪中已得到认可。然而，尽管取得了进展，但由于心血管疾病的发病率持续居高不下，风险预测仍然不准确。遗传表征已被提议作为一种能够实现更早且可能量身定制的预防的方法。人们早就知道，罕见的孟德尔致病变异会导致心脏代谢疾病，从而增加一些家庭的疾病风险。然而，双胞胎和家族聚集研究表明，不同的心血管疾病在普通人群中是可遗传的。自人类基因组计划以来，技术和方法上的重大进步正在以不断降低的成本促进基于人群的全面基因分析。这些努力的全基因组关联研究继续阐明心血管疾病的因果机制。心血管风险等位基因的系统编目也促进了多基因风险评分的发展。基因分析在大规模研究中变得越来越普遍，包括医疗保健相关的生物库、随机对照试验以及针对数千万人的直接面向消费者的分析。因此，在临床中，个人及其医生越来越多地看到心血管疾病的多基因风险评分。在这份科学声明中，我们回顾了心血管疾病多基因风险评分的当代科学、临床考虑和未来挑战。我们选择了 5 种心脏代谢疾病（冠状动脉疾病、高胆固醇血症、2 型糖尿病、心房颤动和静脉血栓栓塞性疾病）以及对药物治疗的反应，为医疗保健专业人员、研究人员、政策制定者和患者提供临时指导。