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Journal of Lipid Research, Vol. 44, 800-806, April 2003
Copyright © 2003 by Lipid Research, Inc.

Impact of simvastatin, niacin, and/or antioxidants on cholesterol metabolism in CAD patients with low HDL

Nirupa R. Matthan^1,*, Ann Giovanni^*, Ernst J. Schaefer, B. Greg Brown and Alice H. Lichtenstein^*

^* Cardiovascular Nutrition Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111
Lipid Metabolism Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111
Division of Cardiology, University of Washington, Seattle, WA 98195

¹ To whom correspondence should be addressed. e-mail: nirupa.matthan{at}tufts.edu

The HDL Atherosclerosis Treatment Study (HATS) demonstrated a clinical benefit in coronary artery disease patients with low HDL cholesterol (HDL-C) levels treated with simvastatin and niacin (S-N) or S-N plus antioxidants (S-N+A) compared with antioxidants alone or placebo. Angiographically documented stenosis regressed in the S-N group but progressed in all other groups. To assess the mechanism(s) responsible for these observations, surrogate markers of cholesterol absorption and synthesis were measured in a subset of 123 HATS participants at 24 months (on treatment) and at 38 months (off treatment). Treatment with S-N reduced desmosterol and lathosterol levels (cholesterol synthesis indicators) 46% and 36% (P < 0.05), respectively, and elevated campesterol and ß-sitosterol levels (cholesterol absorption indicators) 70% and 59% (P < 0.05), respectively, relative to placebo and antioxidant but not S-N+A. Treatment with antioxidants alone had no significant effect. Combining S-N with antioxidants reduced desmosterol and lathosterol by 37% and 31%, and elevated campesterol and ß-sitosterol levels by 54% and 46%, but differences did not attain significance. Mean change in percent stenosis was positively associated with a percent change in lathosterol (r = 0.26, P < 0.005) and negatively associated with a percent change in ß-sitosterol (r = -0.21, P < 0.01).

These data suggest that changes in stenosis were attributable, in part, to changes in cholesterol metabolism.

Supplementary key words desmosterol • lathosterol • campesterol • ß-sitosterol • cholesterol synthesis • cholesterol absorption • statins • niacin • coronary artery disease

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