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

Abstract:

: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 beta-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 beta-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 beta-sitosterol (r = -0.21, P < 0.01). These data suggest that changes in stenosis were attributable, in part, to changes in cholesterol metabolism.

journal_name

J Lipid Res

authors

Matthan NR,Giovanni A,Schaefer EJ,Brown BG,Lichtenstein AH

doi

10.1194/jlr.M200439-JLR200

keywords:

subject

Has Abstract

pub_date

2003-04-01 00:00:00

pages

800-6

issue

4

eissn

0022-2275

issn

1539-7262

pii

M200439-JLR200

journal_volume

44

pub_type

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