PRODUCTION OF SMALL HIGH-DENSITY-LIPOPROTEIN PARTICLES AFTER STIMULATION OF IN-VIVO LIPOLYSIS IN HYPERTRIGLYCERIDEMIC INDIVIDUAL - STUDIES BEFORE AND AFTER TRIGLYCERIDE-LOWERING THERAPY

In hypertriglyceridemic states, triglyceride enrichment of high-densit y lipoprotein (HDL) may play an important role in decreasing the HDL c holesterol and apolipoprotein (apo) A-1 plasma concentration. We have shown previously that HDL particles are transformed into small HDLs wh en lipolysis is stimulated in vivo or in vitro, and this process is mo re marked if the HDL is triglyceride-rich. The present study was condu cted to determine whether the susceptibility of HDL to transformation can be altered by triglyceride-lowering therapy in humans, Seventeen m oderately hypertriglyceridemic individuals (nine with type II diabetes mellitus and eight moderately hypertriglyceridemic nondiabetic subjec ts) were studied before and after 3 months of triglyceride-lowering th erapy with gemfibrozil. Since no significant differences in postprandi al and postheparin HDL metabolism were detected between type II diabet ic and nondiabetic subjects, results ape reported for the two groups c ombined (N = 17), Fasting HDL was triglyceride-rich with a preponderan ce of HDL3, and became more enriched with triglycerides postprandially . Heparin administration resulted in a rapid decrease in plasma and HD L triglycerides and an increase in plasma and HDL free fatty acids (FF As). Postheparin, there was a reduction in HDL size and an increase in the proportion of small (HDL3c) HDL particles (HDL3c constituted 7.1% +/- 1.8% of total HDL preheparin and 26.6% +/- 3.8% postheparin, P < .001). Triglyceride-lowering treatment resulted in a decrease in fasti ng triglycerides (-54%, P < .001) and HDL triglyceride content (-36%, P = .002), an increase in fasting HDL cholesterol (19%, P = .004), and proportionately fewer (13.2% +/- 2.1%, P < .001) HDL3c particles form ed postheparin. Postheparin HDL size correlated inversely with the fas ting triglyceride level (r = -.55, P < .001) and HDL triglyceride conc entration (r = -.34, P = .02). These results shaw that the postprandia l increase in triglyceride levels in hypertriglyceridemic subjects is associated with increased production of small HDL particles when lipol ysis is stimulated, and that lipid-lowering therapy can contribute to favorably reduce this postprandial production of small HDL particles. Further studies are needed to clarify how these abnormalities ultimate ly lead to a decrease of plasma HDL cholesterol and apo A-1 in hypertr iglyceridemic states. Copyright (C) 1998 by W.B. Saunders Company.