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

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.