Genetic Risk Score Enables a Vaccine for Early Primary Prevention of CAD.

Abstract

Early primary prevention of coronary artery disease (CAD) is limited by lack of biomarkers to detect CAD risk among young asymptomatic individuals. Although early prevention is more effective than secondary interventions, conventional risk factors such as hypertension usually do not appear until the fifth or sixth decade of life. Conversely, genetic risk, which accounts for 50% of all CAD risk, is randomly distributed at conception and does not change with age; therefore, it can be determined any time after birth using a genetic polygenic risk score (PRS). Genetic risk is markedly modified by lifestyle changes and, specifically, lowering levels of low-density lipoproteins (LDL). CAD risk depends on the concentration and duration of exposure to plasma LDL, which is estimated by the product of age times LDL (mg-years). The minimum threshold for a myocardial infarction (MI) in someone with a plasma LDL of 125 at age 40 is 5,000 mg-years. The goal of primary prevention is to delay reaching the minimal clinical threshold as long as possible. This review makes the case for a long-acting, lipid-lowering drug, administered annually starting at age 30, that could delay the threshold for MI until age 100.