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 sterols to cholesterol (indicating low cholesterol absorption) but not those with high ratios (high absorption) experienced reduced recurrences of coronary events during simvastatin treatment in the Scandinavian Simvastatin Survival 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 period of placebo treatment (n=433) and simvastatin treatment (n=434) in patients from a subgroup of the Scandinavian Simvastatin Survival Study to determine whether changes in cholesterol synthesis and serum levels were related to cholesterol absorption. Serum cholesterol level was unchanged, the ratios of cholesterol precursor sterols to cholesterol were decreased, and the ratios of plant sterols to cholesterol were increased in relation to increasing baseline ratios of cholestanol quartiles. The latter predicted 5-year ratios and simvastatin-induced reductions of the precursor sterols, with the lowering of the ratios (cholesterol synthesis reduction) being almost twice higher in the lowest versus the highest quartile. The ratios of plant sterols, especially campesterol, to cholesterol were markedly increased during simvastatin treatment, mostly in subjects with the highest baseline cholestanol quartiles. Simvastatin reduced serum cholesterol more (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 metabolism, measured by serum noncholesterol sterols, predicts the effectiveness of simvastatin in reducing cholesterol synthesis and serum levels of cholesterol. The drug suppresses the synthesis of cholesterol markedly more effectively 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 prevent an increase in the levels of plant sterols.