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

Nissinen, M.J.; Miettinen, T.E.; Gylling, H.; Miettinen, T.A.

doi:10.1016/j.numecd.2009.04.014

« Previous Next »Nutrition, Metabolism & Cardiovascular Diseases
Volume 20, Issue 5 , Pages 308-316, June 2010

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

M.J. Nissinen
- Department of Medicine, Division of Gastroenterology, University of Helsinki, Helsinki, Finland
- Corresponding author. Department of Medicine, Division of Gastroenterology, Biomedicum Helsinki, Room C422, University of Helsinki, P.O. Box 700, FI-00029 Helsinki, Finland. Tel.: +358 50 5268538; fax: +358 9 4717 1851.
- These authors equally contributed to this work.
T.E. Miettinen
- Department of Medicine, Division of Internal Medicine, University of Helsinki, Helsinki, Finland
- These authors equally contributed to this work.
H. Gylling
- Department of Clinical Nutrition, University of Kuopio, Finland
- Department of Medicine, Kuopio University Hospital, Kuopio, Finland
T.A. Miettinen
- Department of Medicine, Division of Internal Medicine, University of Helsinki, Helsinki, Finland

Received 28 December 2008; received in revised form 18 March 2009; accepted 23 April 2009. published online 20 August 2009.

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.

Keywords: Cholesterol metabolism, Cholesterol precursors, Good and poor responders, Plant sterols, Statins