desmosterol and Coronary-Artery-Disease

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.

Topics: Antioxidants; Cholesterol; Constriction, Pathologic; Coronary Artery Disease; Desmosterol; Drug Therapy, Combination; Female; Humans; Hypolipidemic Agents; Lipoproteins, HDL; Male; Middle Aged; Niacin; Simvastatin; Sitosterols

It has been suggested that plant sterol absorption is increased in type 1 diabetes mellitus (T1DM) and that this may relate to the increased cardiovascular risk seen in T1DM. The cardiovascular benefit of lowering low-density lipoprotein-cholesterol with statin medication has also been shown to be influenced by plant sterol absorption.. The relationship between sterol concentrations, coronary artery disease (CAD), and the use of statin medications in T1DM was compared between participants with CAD (Minnesota codes 1.1, 1.2, 1.3, 4.1-4.3, 5.1-5.3, and 7.1; n = 82), from the Pittsburgh Epidemiology of Diabetes Complications (EDC) study, and those without (n = 213). Serum sterol concentrations reflecting cholesterol absorption (β-sitosterol and campesterol) and synthesis (desmosterol and lathosterol) were assayed and analyzed by gas chromatography and were expressed as a ratio of total cholesterol (×10(3)).. No differences were observed in markers of cholesterol absorption between individuals with and without CAD. In patients with CAD, significantly lower levels were observed for both sterol markers reflecting cholesterol synthesis compared with individuals without CAD [desmosterol: 0.34 vs 0.42, respectively (P = 0.003); lathosterol 0.47 vs 0.54, respectively (P = 0.019)]. Further stratification by statin medication use revealed significantly lower levels of synthesis-reflecting sterols in individuals taking statin medication, particularly those with CAD.. Although previous reports suggest that higher levels of cholesterol absorption in T1DM potentially increase cardiovascular risk in this population, the present data suggest no differences in cholesterol absorption between T1DM individuals with and without CAD.

Topics: Adult; Cholesterol; Cholesterol, LDL; Coronary Artery Disease; Desmosterol; Diabetes Mellitus, Type 1; Female; Humans; Male; Middle Aged; Phytosterols; Sitosterols