Short-term atorvastatin treatment improves endothelial function in hypercholesterolemic women

Endothelial dysfunction represents the earliest stage of atherosclerosis an d is usually present in hypercholesterolemia. Treatment with statins has be en shown to normalize endothelial function in middle-aged men with hypercho lesterolemia. We evaluated the effect over time of atorvastatin on the endo thelial reactivity in postmenopausal hypercholesterolemic women (mean age. 58 +/- 6 years), receiving atorvastatin, 10 mg daily (n = 20) or American H eart Association step 1 diet (n = 10) for 8 weeks. Lipid profile and brachi al artery flow-mediated vasodilation (FMV) were determined at baseline and after 1, 2, 4, and 8 weeks. FMV increased progressively in subjects treated with atorvastatin, and the difference was significant (p < 0.05 vs. baseli ne) after the second week (baseline 3.8 +/- 3%; first week, 4.8 +/- 3%; sec ond week, 9.2 +/- 3%; fourth week, 11.0 +/- 3%; eighth week, 11.7 +/- 3%). No significant changes were observed in subjects receiving diet (baseline, 3.1 +/- 4%; first week, 2.4 +/- 2%; second week, 2.9 +/- 2%; fourth week 3. 1 +/- 2%; eighth week, 3.3 +/- 2%; p = NS). In the atorvastatin group, low- density lipoprotein (LDL) cholesterol showed a significant decrease since t he first week (baseline, 228 +/- 37 mg/dl; first week, 171 +/- 32; second w eek, 147 +/- 27; fourth week, 139 +/- 29; eighth week, 135 +/- 27; all p < 0.05). In the control group, LDL cholesterol showed a smaller but significa nt (p < 0.05) reduction after the second week (baseline, 226 +/- 17 mg/dl; first week, 225 +/- 16; second week, 220 +/- 17; fourth week, 203 +/- 27; e ighth week, 198 +/- 27). In conclusion, hypercholesterolemic women treated with atorvastatin show a significant improvement in endothelial reactivity after as early as 2 weeks of therapy. The extent to which these beneficial effects are attributable to cholesterol reduction or to a direct effect of the drug remains to be established.