J. Lipid Res. Neurobiology of Lipids (ISSN1683-5506)
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A more recent version of this article appeared on April 1, 2003

Papers In Press, published online ahead of print February 1, 2003
J. Lipid Res., doi:10.1194/jlr.M200439-JLR200
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Submitted on November 13, 2002
Revised on January 15, 2003
Accepted on January 23, 2003

Impact of simvastatin and niacin with and without antioxidants on plasma cholesterol absorption and synthesis markers in coronary artery disease patients with low HDL

Nirupa R. Matthan, 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

Corresponding Author: nirupa.matthan{at}tufts.edu

The HDL Atherosclerosis Treatment Study demonstrated clinical benefit in coronary artery disease patients with low HDL cholesterol levels treated with simvastatin and niacin (S-N), or S-N plus antioxidants (S-N+A), compared to antioxidants alone or placebo. Angiographically documented stenosis regressed in the S-N group but progressed in all other groups. To assess mechanism(s) responsible for these observations, surrogate markers of cholesterol absorption and synthesis were measured. Treatment with S-N reduced desmosterol and lathosterol levels (cholesterol synthesis indicators) 46% and 36% (p<0.05), and elevated campesterol and ß-sitosterol levels (cholesterol absorption indicators) 70% and 59% (p<0.05), 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. Percent change in stenosis was not associated with total and LDL cholesterol levels, but was positively associated with lathosterol (r=0.26, p<0.05), and negatively associated with ß-sitosterol (r=-0.21, p<0.01). These data suggest that changes in stenosis were attributable in part, to changes in cholesterol metabolism. Measurement of cholesterol absorption and synthesis markers may help better predict changes in stenosis than plasma cholesterol levels alone.


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