Applicability of non-cholesterol sterols in predicting response in cholesterol metabolism to simvastatin and fluvastatin treatment among hypercholesterolemic men.

ABSTRACT

BACKGROUND AND AIMS: We hypothesized that (I) certain features in cholesterol metabolism at baseline could predict a response to statins, (II) good and poor responders to statins have a differential profile of serum and fecal sterols and (III) serum non-cholesterol sterols reflect cholesterol metabolism on statins. METHODS AND RESULTS: We examined serum lipids, serum and fecal cholesterol, cholesterol precursors, cholestanol and phytosterols and cholesterol metabolism among 20 hypercholesterolemic men at baseline and on 16-wk simvastatin/fluvastatin treatment. At baseline, the mean of serum cholestanol/cholesterol was 11% lower but those of lathosterol/cholesterol, lathosterol/cholestanol, desmosterol/cholesterol, desmosterol/cholestanol were 36-65% higher among good than poor responders (p<0.05 for each). On statins, reductions in ratios of serum precursor sterols and increases of absorption sterols were 1.8-2.9 times higher among good than poor responders (p<0.05 for each). In the whole study group, changes from baseline values of lathosterol/cholestanol were related to those of cholesterol and LDL-C in serum (r=+0.513 and +0.451, p=0.021 and 0.046, respectively). Serum lathosterol ratios to cholesterol, cholestanol and sitosterol consistently reflected a ratio of cholesterol synthesis (mg/d/kg)/fractional cholesterol absorption (%) (r-range +0.456 to +0.727, p<0.05 for each). CONCLUSIONS: Low serum baseline ratios to cholesterol of lathosterol, cholestenol and desmosterol, but a high ratio of cholestanol predicted a poor response to statins. Good responders were characterized by more profound reductions of serum and fecal (lathosterol) precursor sterols and increases of serum absorption marker sterol ratios on statins. Serum surrogate sterol markers of cholesterol metabolism were applicable in evaluating cholesterol absorption and synthesis also on statins.