PATIENTS WITH COMBINED HYPERLIPIDEMIA

Abstract

Combined Hyperlipidaemia or Familial hypercholesterolemia (FH) is a frequent genetic disorder viz., an autosomal codominant disorder, characterized by elevated low-density lipoprotein (LDL)-cholesterol (LDL-C) levels and early onset of atherosclerotic cardiovascular disease1. The expression of the genetic potential for these lipid disorders is a complex process which only occurs when genetically inherited predisposing factors interact with other metabolic factors that exacerbate hyperlipidaemia2. Adipose tissue secretes several adipocytokines (i.e. adiponectin, leptin, and others) that regulate appetite, immunity, inflammation, and glucose/lipid metabolism3. Basically, hepatocytes and steroid hormone-producing cells have LDL receptors. Normally, these cell surface receptor for LDL removes cholesterol-carrying LDL from the plasma by a process of receptor-mediated endocytosis. However, mutations in the LDL receptor gene results in FH4. FH is caused by mutations in genes that regulate LDL catabolism, mainly the LDL receptor (LDLR), apolipoprotein B (apo B), and gain of function of proprotein convertase subtilisin kexin type 9 (PCSK9). However, the phenotype may be encountered in individuals not carrying the latter monogenic defects, in approximately 20% of these effects of polygenes predominate, and in many individuals, no molecular defects are encountered at all. These so-called FH phenocopy individuals have an elevated atherosclerotic cardiovascular disease (CVD; ASCVD) risk in comparison with normolipidemic individuals but this risk is lower than in those with monogenic disease 1.