Genetic Variation In Pcsk9 And Protection From Peripheral Artery Disease

Introduction: In the recently published FOURIER trial, an inhibitor of PCSK9 reduced LDL cholesterol levels by 56 mg/dl, and also reduced the risk of the primary outcome (a composite of cardiovascular death, stroke, myocardial infarction, hospitalization for unstable angina or revascularization) by 15%. Whereas symptomatic peripheral artery disease (PAD) was an inclusion criteria for this trial, PAD outcomes were not reported, and questions about the role of PCSK9 in PAD remain unanswered. Hypothesis: DNA sequence variants leading to loss of PCSK9 function are associated with reduced risk of PAD. Methods: We analyzed the electronic health records from 230,080 white and 60,386 black U.S. veterans with available genetic data from the VA Million Veteran Program (MVP). We studied three DNA sequence variants in PCSK9 that lead to loss of PCSK9 function and as such, represent a model of pharmacologic inhibition. We performed logistic regression adjusting for age, sex, and 10 principal components of ancestry, to...