Effects of simvastatin on lipoprotein (a) and lipoprotein composition in patients with nephrotic syndrome.

The influence of simvastatin, a competitive inhibitor of 3-hydroxy-3-methyl glutaryl coenzyme A reductase, on quantitative and qualitative changes in lipoprotein metabolism was investigated in 18 patients (group I, 10 with primary kidney disease and group II, 8 with diabetic nephropathy) with nephrotic syndrome. Nephrotic patients exhibited severe hyperlipidemia (serum cholesterol 390 +/- 17 mg/dl and triglyceride 335 +/- 42 mg/dl; mean +/- SEM) and had significantly higher lipoprotein (a) [Lp(a)] levels (54 +/- 12 mg/dl; median 31 mg/dl, p < 0.01) compared with 20 healthy subjects (mean 12 +/- 1.8 mg/dl; median 7 mg/dl). Fifty-six percent of the patients and 15% of the controls had values greater than 30 mg/dl. Treatment with simvastatin in increasing doses over a period of three months (13 patients received 40 mg/day and 5 patients 20 mg/day at the end of the third month) reduced LDL-cholesterol in both groups of patients (35% and 54%) as well as apolipoprotein B (apoB) (31% and 46%) significantly, but Lp(a) levels were not influenced (57 +/- 21 vs 59 +/- 20 and 50 +/- 14 vs 53 +/- 16 mg/dl, respectively). On the other hand a complex change in lipoprotein composition occurred. The ratio of LDL apoB/LDL cholesterol-ester increased significantly (0.75 +/- 0.03 to 0.84 +/- 0.03 and 0.80 +/- 0.03 to 1.02 +/- 0.1, respectively) and cholesterol concentration in VLDL (64 +/- 16 to 39 +/- 7 and 74 +/- 18 to 55 +/- 74 mg/dl, respectively) was reduced.(ABSTRACT TRUNCATED AT 250 WORDS)

Lovastatin versus bezafibrate: efficacy, tolerability, and effect on urinary mevalonate.

Lovastatin and benzafibrate have proved effective in lowering low-density-lipoprotein (LDL) cholesterol and elevating high-density-lipoprotein (HDL) cholesterol. We compared their tolerability, safety, and effects on lipoproteins and urinary mevalonate excretion in a short-term study. Forty patients with primary hypercholesterolemia were enrolled in a single-blind randomized study with a diet/placebo period of 8 weeks and a treatment period of 12 weeks. Twenty patients received lovastatin (final average dose 70.5 mg/day), and 20 patients received bezafibrate 400 mg/day. LDL cholesterol was lowered by 35% (from 323 to 208 mg/dl) with lovastatin and by 8% (from 289 to 264 mg/dl) with benzafibrate. HDL cholesterol increased by 21 and 20% with lovastatin and benzafibrate, respectively. Twenty-four-hour urinary mevalonic acid output decreased by 37% during treatment with lovastatin and by 2% during treatment with bezafibrate. Thus, the lowering of cholesterol by lovastatin, but not by bezafibrate, can be attributed to inhibition of HMG CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase. Both lovastatin and bezafibrate are well tolerated.