Noncholesterol sterols and cholesterol lowering by long-term simvastatin treatment in coronary patients - Relation to basal serum cholestanol

Coronary patients with low baseline ratios of serum cholestanol and plant s terols to cholesterol (indicating low cholesterol absorption) but not those with high ratios (high absorption) experienced reduced recurrences of coro nary events during simvastatin treatment in the Scandinavian Simvastatin Su rvival Study. Thus, in the present study, serum cholesterol, its precursor sterols (reflecting cholesterol synthesis), plant sterols (campesterol and sitosterol), and cholestanol were measured before and during a 5-year perio d of placebo treatment (n=433) and simvastatin treatment (n=434) in patient s from a subgroup of the Scandinavian Simvastatin Survival Study to determi ne whether changes in cholesterol synthesis and serum levels were related t o cholesterol absorption. Serum cholesterol level was unchanged, the ratios of cholesterol precursor sterols to cholesterol were decreased, and the ra tios of plant sterols to cholesterol were increased in relation to increasi ng baseline ratios of cholestanol qual-tiles. The latter predicted 5-year r atios and simvastatin-induced reductions of the precursor sterols, with the lowering of the ratios (cholesterol synthesis reduction) being almost twic e higher in the lowest versus the highest quartile. The ratios of plant ste rols, especially campesterol, to cholesterol were markedly increased during simvastatin treatment, mostly in subjects with the highest baseline choles tanol quartiles. Simvastatin reduced serum cholesterol mon (P=0.003) in the lowest versus the highest cholestanol quartile during the 5-year treatment period. The results show for the first time that baseline cholesterol meta bolism, measured by serum noncholesterol sterols, predicts the effectivenes s of simvastatin in reducing cholesterol synthesis and serum levels of chol esterol. The drug suppresses the synthesis of cholesterol markedly more eff ectively in subjects with high than with low baseline synthesis but reduces respective serum cholesterol levels less markedly than synthesis. Subjects with high cholesterol absorption and low synthesis may need a combination therapy to lower more effectively their serum cholesterol levels and preven t an increase in the levels of plant sterols.