Limitations of Contemporary Guidelines for Managing Patients at High Genetic Risk of Coronary Artery Disease

Polygenic 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. This study sought t...

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Bibliographic Details
Published in:Journal of the American College of Cardiology 2020-06, Vol.75 (22), p.2769-2780
Main Authors: Aragam, Krishna G., Dobbyn, Amanda, Judy, Renae, Chaffin, Mark, Chaudhary, Kumardeep, Hindy, George, Cagan, Andrew, Finneran, Phoebe, Weng, Lu-Chen, Loos, Ruth J.F., Nadkarni, Girish, Cho, Judy H., Kember, Rachel L., Baras, Aris, Reid, Jeffrey, Overton, John, Philippakis, Anthony, Ellinor, Patrick T., Weiss, Scott T., Rader, Daniel J., Lubitz, Steven A., Smoller, Jordan W., Karlson, Elizabeth W., Khera, Amit V., Kathiresan, Sekar, Do, Ron, Damrauer, Scott M., Natarajan, Pradeep
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
coronary artery disease
Coronary Artery Disease - epidemiology
Coronary Artery Disease - genetics
Coronary Artery Disease - therapy
Databases, Factual - standards
Delivery of Health Care - methods
Delivery of Health Care - standards
Disease Management
Electronic Health Records - standards
Female
Genetic Predisposition to Disease - epidemiology
Genetic Predisposition to Disease - genetics
genetic risk
Humans
Male
Middle Aged
Multifactorial Inheritance - genetics
Practice Guidelines as Topic - standards
primary prevention
Risk Factors
statin
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Summary:Polygenic 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. This study sought to intersect polygenic risk with guideline-based recommendations and management patterns for CAD primary prevention. A 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. Of 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 
ISSN:0735-1097
1558-3597
1558-3597
DOI:10.1016/j.jacc.2020.04.027