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

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 (52+/-30 versus 102+/-66 M/C%, P<0.005), and nitroprusside-induced endothelium-independent vasodilation was modestly reduced (275+/-146 versus 391+/-203 M/C%, P<0.05) in patients with type 21 diabetes compared with control subjects. Despite significant reduction of total cholesterol, low density lipoproteins, and triglycerides (5.8+/-1.0 to 3.2+/-0.6 [P<0.0001], 4.1+/-1.1 to 1.8+/-0.7 [P<0.0001], and 2.2+/-1.3 to 1.4+/-0.5 [P<0.05] mmol/L, respectively), no effect on NO-dependent (59+/-44 M/C%) and endothelium-independent (292 202 M/C%) vasodilation was demonstrated. These data suggest that intensive lipid lowering by atorvastatin has no effect on NO availability in forearm resistance arteries in type 2 diabetic patients. Other factors, such as hyperglycemia, may be a more important contributing factor regarding impaired vasoreactivity in this patient group.