The effect of statin therapy on endothelial function in type 2 diabetes without manifest cardiovascular disease.
OBJECTIVE
Cardiovascular disease (CVD) is the most important cause of mortality in patients with type 2 diabetes and is preceded by endothelial dysfunction. Flow-mediated dilation (FMD) is a noninvasive technique for measuring endothelial dysfunction. We aimed to determine the effect of long-term statin therapy versus placebo on FMD in patients with type 2 diabetes without manifest CVD.


METHODS
A randomized, placebo-controlled, double-blind trial was performed with 250 type 2 diabetic patients. Patients were given 0.4 mg cerivastatin or placebo daily. In August 2001, when cerivastatin was withdrawn from the market, the 0.4 mg cerivastatin was replaced by 20 mg simvastatin, without deblinding the study. The primary end point was the change in FMD, measured by B-mode ultrasound, after 2 years.


RESULTS
Determinants of baseline FMD were diabetes duration, common carotid intima-media thickness, and brachial artery diameter. FMD at baseline was 1.51% in the placebo group and 1.66% in the statin group and did not change significantly after 2 years.


CONCLUSIONS
The 2-year statin therapy had no effect on FMD in type 2 diabetes. Statin-induced improvement of cardiovascular risk in patients with type 2 diabetes may be mediated through mechanisms other than increased nitric oxide availability.
Department of General Internal Medicine, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, Netherlands. e.d.beishuizen@lumc.nl
Edith D
ED
Beishuizen
Jouke T
JT
Tamsma
J Wouter
JW
Jukema
Marcel A
MA
van de Ree
J Carel M
JC
van der Vijver
A Edo
AE
Meinders
Menno V
MV
Huisman
D001783:Blood Flow Velocity / Q000187:drug effects*; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000517:prevention & control; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011725:Pyridines / Q000494:pharmacology*; D019821:Simvastatin / Q000494:pharmacology; D014463:Ultrasonography
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010919:Placebos; D011725:Pyridines; D019821:Simvastatin; C086276:cerivastatin