Intensive lipid lowering by statin therapy does not improve vasoreactivity in patients with Type 2 diabetes

Abstract—Cardiovascular disease is the most important cause of morbidity and mortality in patients with type 2 diabetes. Endothelial dysfunction predicts cardiovascular outcome. Type 2 diabetes is characterized by endothelial dysfunction, which may be caused by dyslipidemia. Statin therapy restores endothelial function in hyperlipidemic patients. Therefore, we hypothesize a beneficial effect of atorvastatin on NO-dependent vasodilation in patients with type 2 diabetes and mild dyslipidemia (low density lipoproteins 4.0 mmol/L and/or triglycerides 1.8 mmol/L). We evaluated the effect of intensive lipid lowering (4 weeks of 80 mg atorvastatin once daily) on vasoreactivity in 23 patients with type 2 diabetes by using venous occlusion plethysmography. Twenty-one control subjects were matched for age, sex, body mass index, blood pressure, and smoking habits. The ratio of blood flows in the infused (measurement [M]) and noninfused (control [C]) arm was calculated for each recording (M/C ratio), and M/C % indicates the percentage change from the baseline M/C ratio. Serotonin-induced NO-dependent vasodilation was significantly blunted (5230 versus 10266 M/C%, P0.005), and nitroprusside-induced endothelium-independent vasodilation was modestly reduced (275146 versus 391203 M/C%, P0.05) in patients with type 2 diabetes compared with control subjects. Despite significant reduction of total cholesterol, low density lipoproteins, and triglycerides (5.81.0 to 3.20.6 [P0.0001], 4.11.1 to 1.80.7 [P0.0001], and 2.21.3 to 1.40.5 [P0.05] mmol/L, respectively), no effect on NO-dependent (5944 M/C%) and endothelium-independent (292202 M/C%) vasodilation was demonstrated. These data sugges