“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,” said 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.

The research team identified 35 single nucleotide polymorphisms — single “letter” genetic changes — that were connected to EC function and CAD, to create a risk score that they then used to make predictions while following participants in three separate study populations. They found that individuals with high EC risk benefited greatly from LDL-C lowering therapies, and that the score could be used to predict CAD risk.

One of the main limitations of the risk score that the team developed is that it does not directly measure endothelial cell function. In the future, the researchers would like to assess phenotypes and serum biomarkers, as well as analyze environmental factors like smoking that can adversely affect endothelial cells.