Novel Genetic Risk Score for Individuals at Higher Risk of Coronary Artery Disease

Researchers have developed a polygenic risk score to analyze the link between dysfunctional endothelial cells (EC) function and individuals at higher risk of coronary artery disease (CAD). The findings were published in Nature Medicine.

The investigators assessed 35 single nucleotide polymorphisms linked to EC function and subsequently developed a risk score that could predict CAD risk in three separate study populations. The findings showed that low-density lipoprotein cholesterol (LDL-C) lowering therapies significantly benefited individuals with high EC risk. Moreover, they observed that the score could be used to predict CAD risk.

While the findings were promising, the study was limited by the fact that the risk score that the team developed does not directly measure endothelial cell function. Moving forward, the researchers noted that they aim to assess phenotypes and serum biomarkers and analyze environmental factors that affect endothelial cells, such as smoking.

Lead author Nicholas Marston, MD, MPH, from the Division of Cardiovascular Medicine at Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system, said of the findings: “We have been trying to understand why two patients with similarly high cholesterol can have very different degrees of CAD. Our work suggests that intact endothelial function may provide protection in some, while in other patients, EC dysfunction may increase their sensitivity to LDL-C concentrations and amplify their risk of cardiovascular events. As a result, patients who are LDL-C sensitive have a much greater benefit from aggressive cholesterol-lowering therapies, creating an opportunity for personalized prevention plans.”

Source:

New genetic risk score identifies individuals at risk for heart disease who may benefit most from cholesterol-lowering therapies. News release. Mass General Brigham. February 26, 2025. Accessed February 26, 2025. https://www.eurekalert.org/news-releases/1074994