Lipids and AtherosclerosisElevated plasma lipids have been reported in one third to one half of patients with peripheral vascular disease (PVD). 17 Low levels of high-density lipoprotein (HDL) cholesterol are associated with PVD. There are several apoprotein levels and apoprotein ratios which are predictive of PVD: A-I and A-II levels, and A-I:B and A-I:C-III ratios.
Lipoprotein (a) [Lp(a)], a cholesterol ester, is a low-density lipoprotein–like particle associated with an increased risk of cardiovascular disease. Elevated Lp(a) may represent the most prevalent inherited risk factor for atherosclerosis. Lp(a) levels are insensitive to dietary and drug manipulations. 18
Elevated LDL and very low-density lipoprotein (VLDL) levels have long been associated with increased risk of atherosclerosis. Cells contain a specific receptor for LDL, and there is a correlation between LDL binding and control of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase—the rate-limiting step for cholesterol synthesis. It is proposed that the number of receptors expressed by the cell varies, protecting the cell against excess cholesterol. However, as the number of expressed LDL receptors decreases, the rate of cholesterol clearance decreases and plasma levels rise. It is postulated that hypercholesterolemia may induce a subtle form of injury. Changes in the cholesterol:phospholipid cell membrane ratios may result in altered endothelial malleability.
Another possible mechanism of endothelial injury in hypercholesterolemia is via oxidization of LDLs. If LDLs are oxidized by macrophages, then toxic products may result in endothelial injury and explain the progression of fatty streaks to fibrous plaques.
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