Effect of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor on sterol absorption in hypercholesterolemic subjects

To investigate the potential effects of high-dose 3-hydroxy-3-methylglutary l-coenzyme A (HMG-CoA) reductase inhibitor on plasma phytosterol, total cho lesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density li poprotein cholesterol (HDL-C), and triglyceride (TG), hypercholesterolemic subjects received 40 or 80 mg/d simvastatin in a 24-week prospective clinic al trial. Plasma lipid levels were analyzed enzymatically, and plasma phyto sterol concentrations were determined using gas-liquid chromatography. The change in the plasma phytosterol-campesterol level was used as an indicator of cholesterol absorption in humans. Simvastatin treatment reduced plasma campesterol (-24%, P=.017) but did not affect circulating stigmasterol and sitosterol levels. A dose of 80 mg/d simvastatin produced a larger decrease (P =.050) in plasma campesterol (0.1680 mmol/L) than 40 mg/d (0.0237 mmol/ L) versus baseline. There was a positive correlation between plasma campest erol and TC both before (r =.54, P =.027) and after (r =.63, P =.009) treat ment. Plasma To and TG levels did not differ between groups receiving 40 or 80 mg/d simvastatin. Simvastatin treatment reduced circulating TC, LDL-C, and TG by 40%, 50%, and 33% (P <.007), respectively. There was no significa nt effect of simvastatin on plasma HDL-C, but the HDL-C/LDL-C ratio increas ed 1.3-fold (P <.0001). In conclusion, this HMG-CoA reductase inhibitor red uces the plasma campesterol level, a marker of cholesterol absorption, whic h may contribute to the mechanism by which simvastatin decreases circulatin g cholesterol levels. Copyright (C) 1999 by W.B. Saunders Company.