title: 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.
authors.affiliation: Cardiovascular Nutrition Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, USA. nirupa.matthan@tufts.edu
authors.forename: Nirupa R
authors.initials: NR
authors.lastname: Matthan
authors.forename: Ann
authors.initials: A
authors.lastname: Giovanni
authors.forename: Ernst J
authors.initials: EJ
authors.lastname: Schaefer
authors.forename: B Greg
authors.initials: BG
authors.lastname: Brown
authors.forename: Alice H
authors.initials: AH
authors.lastname: Lichtenstein
mesh_terms: D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D002784:Cholesterol / Q000097:blood / Q000378:metabolism*; D003251:Constriction, Pathologic / Q000097:blood / Q000188:drug therapy; D003324:Coronary Artery Disease / Q000097:blood / Q000188:drug therapy*; D003897:Desmosterol / Q000097:blood; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D008075:Lipoproteins, HDL / Q000097:blood* / Q000172:deficiency; D008297:Male; D008875:Middle Aged; D009525:Niacin / Q000008:administration & dosage / Q000494:pharmacology; D019821:Simvastatin / Q000008:administration & dosage / Q000494:pharmacology; D012855:Sitosterols / Q000097:blood
chemical_list: D000975:Antioxidants; D000960:Hypolipidemic Agents; D008075:Lipoproteins, HDL; D012855:Sitosterols; D009525:Niacin; D003897:Desmosterol; C025473:gamma-sitosterol; C001521:lathosterol; D002784:Cholesterol; D019821:Simvastatin