BILE SEQUESTRANT THERAPY ALTERS THE COMPOSITIONS OF LOW-DENSITY AND HIGH-DENSITY LIPOPROTEINS

Bile sequestrant resins are used to lower the levels of low-density lipoprotein cholesterol in plasma because this may ameliorate atherosclerosis. Yet the levels and compositions of all the lipoproteins may affect atherogenesis. We have previously shown alterations in very-low-density lipoprotein (VLDL) metabolism in response to one of these agents, colestipol HCl. Here we report the effects of colestipol on the composition of low-density and high-density lipoproteins (HDL). Eighteen subjects with type II hyperlipoproteinemia were studied during baseline, diet, and drug periods lasting 2-3 mo. Lipoprotein lipids and apolipoproteins A-I, A-II, and B were measured, and indices of lipoprotein composition were calculated. Colestipol produced significant changes in all lipoproteins. VLDL-triglyceride rose transiently, the magnitude and duration both correlated with pretreatment values (r = 0.84 and 0.76, respectively, both p < 0.001). Low-density (density 1.006-1.063) lipoprotein cholesterol fell below the dietary mean by 28%, but low-density triglyceride fell by only 13% and apolipoprotein B by 17%. Thus, low-density lipoprotein cholesterol/apolipoprotein B ratios decreased (1.9 versus 1.6, p < 0.005). Low-density and very-low-density cholesterol/apoprotein B ratios also decreased significantly. Thus, all the apolipoprotein-B-containing lipoproteins had less cholesterol relative to apolipoprotein B. High-density lipoprotein cholesterol remained unchanged, although transient increases in high-density lipoprotein triglyceride occurred. Apolipoprotein A-I levels remained constant (∼105 mg/dl), but A-II levels fell (from 55 to 45 mg/dl); therefore, A-I A-II ratios rose (2.0 versus 2.5, p < 0.001). Thus, alterations in the composition of both high-density and low-density lipoproteins occurred. Colestipol produced changes in lipoprotein composition that may have effects on atherogenesis independent of its effects on lowering plasma cholesterol. Further studies will be needed to determine whether or not these changes are beneficial. © 1979.