Bezafibrate therapy in patients with isolated low high-density lipoprotein cholesterol levels may have a beneficial effect in prevention of atherosclerosis

Abstract

Although a low plasma high-density lipoprotein cholesterol (HDL-C) level is a well-accepted risk factor for coronary artery disease (CAD), it 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 levels is the efficiency of postprandial lipoprotein catabolism. The purpose of the present study was to evaluate the efficacy of bezafibrate therapy in increasing HDL-C levels in these patients and to examine its effect on postprandial lipoprotein levels. Fasting and postprandial lipid and lipoprotein levels were studied in 23 patients with isolated low HDL-C levels before and during 3 and 6 months of bezafibrate treatment. Postprandial lipoprotein levels were evaluated using the vitamin A—fat loading test, in which these intestinally derived lipoproteins are specifically labeled with retinyl palmitate (RP). Patients with isolated low HDL had 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 μg/L · h, respectively ( P < .005). No differences were found in chylomicron remnant levels between the groups. Bezafibrate therapy reduced the chylomicron RP area by 27%, from 17,773 ± 6,821 to 12,895 ± 2,576, and the nonchylomicron 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 < .001). A highly significant inverse correlation ( r = .8885, P < .001) was found between fasting HDL-C and postprandial chylomicron RP levels. The patients did not respond to therapy as a homogenous group. That is, eight patients did not respond to bezafibrate either by reducing postprandial lipoprotein levels or by increasing HDL-C levels, bezafibrate in these patients did significantly reduce low-density lipoprotein cholesterol (LDL-C) levels from 138 ± 4.8 to 125 ± 5.9 mg/dL ( P < .0001) while the patients were on a strict low-fat, low-cholesterol diet. In conclusion, most patients with isolated low HDL-C levels also have a defect in postprandial lipoprotein metabolism. Bezafibrate therapy has a dual effect: it reduces the level of these possibly atherogenic lipoproteins and increases HDL-C levels. These findings support the use of bezafibrate therapy in high-risk patients with isolated low HDL-C levels.