Postprandial lipoprotein metabolism in familial hypercholesterolemia: thinking outside the box

Familial hypercholesterolemia (FH) is a dominantly inherited disorder principally due to mutations in the low-density lipoprotein (LDL) receptor that classically cause markedly elevated plasma LDL cholesterol concentrations and premature coronary heart disease (CHD). However, elevated plasma LDL cholesterol alone does not fully account for the increase or variation in risk of CHD. We propose a hypothetical model for the role of postprandial dyslipoproteinemia based on the overproduction and decreased catabolism of triglyceride-rich lipoproteins, which may be a consequence of LDL receptor deficiency. Expression of postprandial dyslipoproteinemia in FH may also depend on the type of pathogenic gene variants and on coexistent conditions, particularly obesity and insulin resistance. Further research is required to investigate our model proposed and to test whether treating postprandial dyslipoproteinemia decreases CHD risk in FH incremental to standard therapy. (C) 2012 Elsevier Inc. All rights reserved.