Lipoprotein (a): a Unique Independent Risk Factor for Coronary Artery Disease

Abstract

The current epidemic affecting Indians is coronary artery disease (CAD), and is currently one of the most common causes of mortality and morbidity in developed and developing countries. The higher rate of CAD in Indians, as compared to people of other ethnic origin, may indicate a possible genetic susceptibility. Hence, Lp(a), an independent genetic risk marker for atherosclerosis and cardiovascular disease assumes great importance. Lp(a), an atherogenic lipoprotein, contains a cholesterol rich LDL particle, one molecule of apolipoprotein B-100 and a unique protein, apolipoprotein (a) which distinguishes it from LDL. Apo(a) is highly polymorphic and an inverse relationship between Lp(a) concentration and apo(a) isoform size has been observed. This is genetically controlled suggesting a functional diversity among the apo(a) isoforms. The LPA gene codes for apo(a) whose genetic heterogeneity is due to variations in its number of kringles. The exact pathogenic mechanism of Lp(a) is still not completely elucidated, but the structural homology of Lp(a) with LDL and plasmin is possibly responsible for its acting as a link between atherosclerosis and thrombosis. Upper limits of normal Lp(a) levels have not been defined for the Indian population. A cut off limit of 20 mg/dL has been suggested while for the Caucasian population it is 30 mg/dL. Though a variety of assays are available for its measurement, standardization of the analytical method is highly complicated as a majority of the methods are affected by the heterogeneity in apo(a) size. No therapeutic drug selectively targets Lp(a) but recently, new modifiers of apo(a) synthesis are being considered.

Keywords: Apolipoprotein (a); Coronary artery disease; Genetics; Lipoprotein (a); Risk factor.

Fig. 1

Structure of Lp(a)

Fig. 2

Schematic diagram representing different modes of action of Lp(a) in the vessel wall