Screening and management of familial hypercholesterolemia

Purpose of review To discuss recent findings related to epidemiology, diagnosis, natural history, atherosclerotic cardiovascular disease (ASCVD) risk heterogeneity and stratification, and treatment of familial hypercholesterolemia. Recent findings Familial hypercholesterolemia persists subdiagnosed, inadequately treated and social disparities aggravate this scenario. Molecular diagnosis is recommended but still not widely available and reimbursed, also recent reclassification of genetic variants associated with familial hypercholesterolemia limits its routine use. New familial hypercholesterolemia clinical diagnostic criteria like FAMCAT are being tested and are apparently more accurate than the classical ones. Genetic traits for familial hypercholesterolemia and high lipoprotein(a) concentrations apparently co-exist and are associated with a higher ASVCD risk than each alone. Indeed, ASCVD risk is heterogenous in heterozygous familial hypercholesterolemia and prospective studies show that it is influenced not only by high LDL-C but also by other risk features like smoking, hypertension, or diabetes. Coronary artery calcification might indicate a higher risk familial hypercholesterolemia population that could benefit from further LDL-C lowering with PCSK9 inhibitors. The latter medications may reduce ASCVD risk in familial hypercholesterolemia individuals similarly to their impact on the general population as shown in a randomized prospective development program (SPIRE). Knowledge about familial hypercholesterolemia has improved but there are still many challenges for its optimal management.