Hypocholesterolemia, hypolipoproteinemia, and risk of death.

Abstract

Although it is well established that high levels of cholesterol and certain lipoproteins are strongly associated with increased risk for coronary artery disease, cerebrovascular disease, and death from myocardial infarction and stroke, the association of low levels of cholesterol and certain lipoproteins with increased prevalence of other diseases and risk of death from these diseases has been equally well established. The earliest reports of association of low cholesterol levels with disease, particularly malnutrition and cancer, are from the 1930s (G. L. Muller, 1930). Reports from the 1940s describe the association between low cholesterol levels and acute febrile illnesses (Nishita, 1941).Since these early studies on low blood lipid levels in chronic and acute disease, there have been significant changes in both our understanding of the biochemistry of lipids and lipoproteins and the methodology used to measure blood lipids and lipoproteins. Initially, blood lipid levels measured included only total cholesterol, triglyceride, and phospholipid. In the 1 9 5 0 ~~ lipoproteins were discovered to be the carriers of these lipids, and measurements of specific lipoproteins, primarily chylomicrons, very low density lipoproteins (VLDLs), low density lipoproteins (LDLs), and high density lipoproteins (HDLs), became necessary to understand the characteristics of dyslipoproteinemias. More recently, the proteins associated with lipoproteins, apolipoproteins, have been exhaustively studied. Each lipoprotein species has specific apolipoproteins that are important structural elements and help regulate the metabolism of the lipids that are carried.Careful metabolic studies of synthesis and turnover rates of apolipoproteins have shown that to a great extent, levels of cholesterol and other lipids and of specific lipoproteins are regulated by synthesis and turnover rates of associated apolipoproteins and levels of certain enzymes, including lipoprotein lipase (LPL), hepatic triglyceride lipase (WGL), lecithin cho-This work was supported in part by National Institute on Aging Grant SERCA KOl-AGO0414 and the Arizona Center on Aging,