Limitations of Contemporary Guidelines for Managing Patients at High Genetic Risk of Coronary Artery Disease
Limitations of Contemporary Guidelines for Managing Patients at High Genetic Risk of Coronary Artery Disease
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DOI：
10.1016/j.jacc.2020.04.027
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发表时间：
2020-06-09
影响因子：
24
通讯作者：
Natarajan, Pradeep
中科院分区：
文献类型：
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作者：
Aragam, Krishna G.;Dobbyn, Amanda;Natarajan, Pradeep
背景：冠状动脉疾病（CAD）的多基因风险评分（PRS）识别高危人群更有可能从一级预防他汀类药物治疗中获益。临床心血管风险评估的传统模式是否捕获了多基因CAD风险仍不清楚。目的：本研究旨在探讨冠心病一级预防的多基因风险与基于指南的建议和管理模式之间的关系。方法全基因组CAD PRS应用于美国3个医疗保健系统的47,108个人。然后，作者评估了高多基因风险的一级预防患者是否可以根据更大的指南推荐的他汀类药物资格和更高的他汀类药物治疗率来区分。在47108名研究参与者中，平均年龄为60岁，11020人（23.4%）患有CAD。CAD PRS与流行CAD密切相关（优势比：每SD增加1.4个PRS； p < 0.0001）。高多基因风险（PRS前20%）导致发生CAD的几率为1.9倍（p < 0.0001）。然而，在一级预防患者（n = 33,251）中，根据美国心脏病学会/美国心脏协会（高PRS患者为46.2%，其他患者为46.8%,p = 0.54）或美国预防服务工作组（43.7%对43.7%,p = 0.99）或更高的他汀类药物处方率（25.0%对23.8%,p = 0.04），高多基因风险并不符合他汀类药物治疗建议的增加（p = 0.54）。如果高CAD PRS被认为是一个基于指南的风险增强因素，那么额外的4.1%的一级预防患者可能会被推荐他汀类药物治疗。结论：目前的心血管一级预防模式没有完全捕捉到冠心病的多基因易感性。通过整合遗传和临床风险，可能存在改善CAD预防工作的机会。
BackgroundPolygenic risk scores (PRS) for coronary artery disease (CAD) identify high-risk individuals more likely to benefit from primary prevention statin therapy. Whether polygenic CAD risk is captured by conventional paradigms for assessing clinical cardiovascular risk remains unclear.ObjectivesThis study sought to intersect polygenic risk with guideline-based recommendations and management patterns for CAD primary prevention.MethodsA genome-wide CAD PRS was applied to 47,108 individuals across 3 U.S. health care systems. The authors then assessed whether primary prevention patients at high polygenic risk might be distinguished on the basis of greater guideline-recommended statin eligibility and higher rates of statin therapy.ResultsOf 47,108 study participants, the mean age was 60 years, and 11,020 (23.4%) had CAD. The CAD PRS strongly associated with prevalent CAD (odds ratio: 1.4 per SD increase in PRS; p < 0.0001). High polygenic risk (top 20% of PRS) conferred 1.9-fold odds of developing CAD (p < 0.0001). However, among primary prevention patients (n = 33,251), high polygenic risk did not correspond with increased recommendations for statin therapy per the American College of Cardiology/American Heart Association (46.2% for those with high PRS vs. 46.8% for all others, p = 0.54) or U.S. Preventive Services Task Force (43.7% vs. 43.7%, p = 0.99) or higher rates of statin prescriptions (25.0% vs. 23.8%, p = 0.04). An additional 4.1% of primary prevention patients may be recommended for statin therapy if high CAD PRS were considered a guideline-based risk-enhancing factor.ConclusionsCurrent paradigms for primary cardiovascular prevention incompletely capture a polygenic susceptibility to CAD. An opportunity may exist to improve CAD prevention efforts by integrating both genetic and clinical risk.