Effect of simvastatin on apoprotein B—containing lipoproteins in patients with diabetic nephropathy

Abstract

Background: Diabetic patients with nephropathy usually have a more atherogenic lipoprotein profile than those without nephropathy, which may be associated with the substantially higher incidence of coronary heart disease (CHD) in this population. Simvastatin has been shown to significantly reduce the incidence of CHD events in diabetic patients. Objective: The purpose of this study was to evaluate the effect of simvastatin (10 mg/d) on atherogenic apoprotein (apo) B—containing lipoproteins in type 2 diabetic patients with nephropathy. Methods: Diabetic patients with nephropathy and a group of healthy control subjects matched for age, sex, and body weight were enrolled. Diabetic patients were administered simvastatin 10 mg/d for 6 months. Apo B—containing lipoproteins were sequentially separated by ultracentrifugation to yield very low-density lipoprotein (VLDL) (density <1.006 g/mL), intermediate-density lipoprotein (IDL) (1.006–1.019 g/mL), light low-density lipoprotein (LDL) (1.019–1.044 g/mL), and dense LDL (1.044–1.063 g/mL) fractions. Apo B in lipoproteins was measured by a sensitive enzyme-linked immunosorbent assay at baseline and after 6 months of simvastatin treatment. Results: A total of 18 patients with diabetic nephropathy and 36 matched controls were enrolled. The diabetic patients had significantly higher levels ( P < 0.01) of total cholesterol, LDL cholesterol, triglycerides, and apo B compared with age- and weight-matched control subjects at baseline. The diabetic patients also had significantly higher levels ( P < 0.05) of cholesterol and apo B in the VLDL, light LDL, and dense LDL fractions. Treatment with simvastatin for 6 months significantly reduced plasma total cholesterol by 21%, LDL cholesterol by 30%, and apo B by 25% ( P < 0.001), but did not affect urinary albumin excretion. Simvastatin significantly decreased both triglyceride and cholesterol levels in VLDL by 18% ( P < 0.05), and cholesterol and apo B in IDL by 22% ( P < 0.05) and 26% ( P < 0.01). Simvastatin decreased both the light and dense LDL subfractions to a similar extent, reducing cholesterol and apo B in light LDL by 27% ( P < 0.001) and in dense LDL by 28% ( P < 0.01) and 18% ( P < 0.05), respectively. The light LDL/dense LDL ratio for apo B and for cholesterol were not altered by simvastatin therapy. Conclusions: The results of this study suggest that simvastatin may reduce levels of atherogenic apo B—containing lipoproteins and small dense LDL in diabetic patients with nephropathy.