Current clinical guidelines for the prevention of cardiovascular disease were not found to fully take into account to the polygenicity underlying coronary artery disease (CAD) susceptibility, according to a study published in the Journal of the American College of Cardiology.

In this study, a genome-wide polygenic risk score (PRS) was applied to 47,108 individuals (mean age, 59.6 years) across the Partners Healthcare Biobank, the Penn Medicine Biobank, and the Mount Sinai BioMe Biobank. Genomic and clinical data as well as linked data from electronic health records (EHR) from hospitals affiliated with the Partners Healthcare System, the University of Pennsylvania Health System, and the Mount Sinai Health System were included in the analysis. A genome-wide PRS for CAD which included 6,630,150 common (minor allele frequency >1%) genetic variants based on genetic data from a genome-wide association study of CAD and a computational algorithm, was used.

A total of 11,020 individuals (23.4%) in the cohort had CAD. In this cohort, there was an association between the CAD PRS and CAD (odds ratio [OR], 1.42 per 1 standard deviation increase in PRS; 95% CI, 1.38-1.46; P <.0001). The odds of CAD were 1.9- and 2.3-fold higher for individuals in the top 20% and 5% of the PRS, respectively vs the remaining population (95% CI, 1.8-2.0; P <.0001 and 95% CI, 2.0-2.5, respectively).

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A high polygenic risk in patients consulting for primary cardiovascular prevention (n=33,251) was not associated with increased recommendations for statin therapy, as formulated by the American College of Cardiology and American Heart Association (46.2% for high PRS vs 46.8% for others; P =.54) or by the US Preventive Services Task Force (43.7% for high PRS vs 43.7% for others; P =.99), or with higher rates of statin prescriptions (25.0% vs 23.8%, respectively; P =.04).

Limitations of the analysis include the determination of disease phenotypes based on EHR data as well as limited data on certain risk enhancers.

“Given the increasing availability of a CAD PRS to health care–associated biobank researchers and consumers of direct-to-consumer genetic testing, prior and present observations may support focused incorporation of CAD PRS into guideline-based primary prevention algorithms,” noted the study authors.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Aragam KG, Dobbyn A, Judy R, et al. Limitations of contemporary guidelines for managing patients at high genetic risk of coronary artery disease. J Am Coll Cardiol. 2020;75(22):2769‐2780.