Familial Hypercholesterolemia: Update and Review

Abstract

Knowledge of epidemiology, genetic etiopathogenesis, diagnostic criteria, and management of familial hypercholesterolemia have increased in the last two decades. Several population studies have shown that familial hypercholesterolemia is more frequent than previously thought, making this entity the most common metabolic disease with monogenic inheritance in the world. Identification of causal heterozygous pathogenic variants in LDLR, APOB, and PCSK9 genes has increased diagnostic accuracy of classical criteria (extreme hypercholesterolemia, personal / family history of premature coronary artery disease or other cardiovascular diseases). Genetic screening has been recently introduced in many European countries to detect patients with familial hypercholesterolemia, mainly affected pediatric subjects, asymptomatic or those at the beggining of their disease, to increase surveillance and avoid complications such as cardiovascular diseases. Cholesterol- lowering drugs should be started as soon as the diagnosis is made. Various combinations between drugs can be used when the goal is not achieved. New therapies, including small interference ribonucleic acids (siRNA) are being tested in different clinical trials.

Keywords: Dyslipidemia; LDLR; NGS; acute myocardial infarction; familial hypercholesterolemia; mutation; xanthomas.