BEZAFIBRATE THERAPY IN PATIENTS WITH ISOLATED LOW HIGH-DENSITY-LIPOPROTEIN CHOLESTEROL LEVELS MAY HAVE A BENEFICIAL EFFECT IN PREVENTION OFATHEROSCLEROSIS

Although a low plasma high-density lipoprotein cholesterol (HDL-C) lev el is a well-accepted risk factor for coronary artery disease (CAD), i t is unclear whether pharmacologic agents can effectively increase HDL -C levels and/or reduce the incidence of CAD in patients with isolated low HDL-C levels. An important determinant of HDL revels is the effic iency of postprandial lipoprotein catabolism. The purpose of the prese nt study was to evaluate the efficacy of bezafibrate therapy in increa sing HDL-C levels in these patients and to examine its effect on postp randial lipoprotein levels. Easting and postprandial lipid and lipopro tein levels were studied in 23 patients with isolated low HDL-C levels before and during 3 and 6 months of bezafibrate treatment. Postprandi al lipoprotein levels were evaluated using the vitamin A-fat loading t est, in which these intestinally derived lipoproteins are specifically labeled with retinyl palmitate (RP). Patients with isolated low HDL h ad significantly higher levels of chylomicron RP than a control group of 19 normolipidemic subjects. The area below the chylomicron RP curve was 17,773 +/- 6.821 versus 13,936 +/- 6,217 mu g/L . k, respectively (P <.005). No differences were found in chylomicron remnant levels be tween the groups. Bezafibrate therapy reduced the chylomicron RP area by 27%, from 17,773 +/- 6,821 to 12.895 +/- 2,576, and the nonchylomic ron RP area by 25%, from 6.059 +/- 3.310 to 4.430 +/- 1,963 (P <.0001) . It increased fasting HDL-C levels from 35 +/- 3 to 38 +/- 1.4 mg/dL after 3 months (P <.001) and to 40 +/- 2.2 mg/dL after 6 months (P <.0 01). A highly significant inverse correlation (r =.8885, P <.001) was found between fasting HDL-C and postprandial chylomicron RP levels. Th e patients did not respond to therapy as a homogenous group. That is, eight patients did not respond to bezafibrate either by reducing postp randial lipoprotein levels or by increasing HDL-C levels. bezafibrate in these patients did significantly reduce low-density lipoprotein cho lesterol (LDL-C) levels from 138 +/- 4.8 to 125 +/- 5.9 mg/dL (P <.000 1) while the patients were on a strict low-fat, low-cholesterol diet. In conclusion, most patients with isolated low HDL-C revels also have a defect in postprandial lipoprotein metabolism. Bezafibrate therapy h as a dual effect: it reduces the level of these possibly atherogenic l ipoproteins and increases HDL-C levels. These findings support the use of bezafibrate therapy in high-risk patients with isolated low HDL-C levels. Copyright (C) 1995 by W.B. Saunders Company