Genetic Risk Assessment for Atherosclerotic Cardiovascular Disease: A Guide for the General Cardiologist

Genetic testing for cardiovascular (CV) disease has had a profound impact on the diagnosis and evaluation of monogenic causes of CV disease, such as hypertrophic and familial cardiomyopathies, long QT syndrome, and familial hypercholesterolemia. The success in genetic testing for monogenic diseases has prompted special interest in utilizing genetic information in the risk assessment of more common diseases such as atherosclerotic cardiovascular disease (ASCVD). Polygenic risk scores (PRS) have been developed to assess the risk of coronary artery disease, which now include millions of single-nucleotide polymorphisms that have been identified through genomewide association studies. Although these PRS have demonstrated a strong association with coronary artery disease in large cross-sectional population studies, there remains intense debate regarding the added value that PRS contributes to existing clinical risk prediction models such as the pooled cohort equations. In this review, we provide a brief background of genetic testing for monogenic drivers of CV disease and then focus on the recent developments in genetic risk assessment of ASCVD, including the use of PRS. We outline the genetic testing that is currently available to all cardiologists in the clinic and discuss the evolving sphere of specialized cardiovascular genetics programs that integrate the expertise of cardiologists, geneticists, and genetic counselors. Finally, we review the possible implications that PRS and pharmacogenomic data may soon have on clinical practice in the care for patients with or at risk of developing ASCVD.

Automated summary

Genetic testing for cardiovascular disease has greatly impacted the diagnosis and evaluation of monogenic causes of the disease. There has been increasing interest in using genetic information for risk assessment of more common diseases, such as atherosclerotic cardiovascular disease (ASCVD). Polygenic risk scores (PRS) have been developed to assess the risk of coronary artery disease and have shown a strong association in population studies. However, the added value of PRS to existing clinical risk prediction models remains a topic of debate.