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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:799.)
© 2002 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Intensive Lipid Lowering by Statin Therapy Does Not Improve Vasoreactivity in Patients With Type 2 Diabetes

Ronald W. van Etten; Eelco J.P. de Koning; Marina L. Honing; Erik S. Stroes; Carlo A. Gaillard; Ton J. Rabelink

From the Department of Vascular Medicine and Diabetes (R.W.v.E., E.J.P.d.K., M.L.H., E.S.S., C.A.G., T.J.R.), University Medical Center, Utrecht, the Netherlands, and the Department of Internal Medicine (R.W.v.E., C.A.G.), Eemland Hospital, Amersfoort, the Netherlands.

Correspondence to Prof Dr T.J. Rabelink, Department of Vascular Medicine and Diabetes, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, Netherlands. E-mail t.rabelink{at}azu.nl

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 2 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.

Key Words: plethysmography • nitric oxide • type 2 diabetes • dyslipidemia • atorvastatin

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