Lipoprotein(a): a genetically determined risk factor for Cardiovascular disease

Abstract

Lipoprotein(a) is a complex lipoprotein with unique characteristics distinguishing it from all the other apolipoprotein B-containing lipoprotein particles. Its lipid composition and the presence of a single molecule of apolipoprotein B per particle, render lipoprotein(a) similar to low-density lipoproteins. However, the presence of a unique, carbohydrate-rich protein termed apolipoprotein(a), linked by a covalent bond to apolipoprotein B imparts unique characteristics to lipoprotein(a) distinguishing it from all the other lipoproteins. Apolipoprotein(a) is highly polymorphic in size ranging in molecular weight from <300 KDa to >800 kDa. Both the size polymorphism and the concentration of lipoprotein(a) in plasma are genetically determined and unlike other lipoproteins, plasma concentration is minimally impacted by lifestyle modifications or lipid-lowering drugs. Many studies involving hundreds of thousands of individuals have provided strong evidence that elevated lipoprotein(a) is genetically determined and a causal risk factor for atherosclerotic cardiovascular disease. The concentration attained in adulthood is already present in children at around 5 years of age and therefore, those with elevated lipoprotein(a) are prematurely exposed to a high risk of cardiovascular disease. Despite the large number of guidelines and consensus statements on the management of lipoprotein(a) in atherosclerotic cardiovascular disease published in the last decade, lipoprotein(a) is still seldom measured in clinical settings. In this review, we provide an overview of the most important features that characterize lipoprotein(a), its role in cardiovascular disease, and the importance of adding the measurement of lipoprotein(a) for screening adults and youths to identify those at increased risk of atherosclerotic cardiovascular disease due to their elevated plasma concentration of lipoprotein(a).