Recent data have shown that
peroxisome proliferator-activated receptor-gamma agonists may exert protective effects on the vascular endothelium by amelioration of
insulin resistance and through direct anti-inflammatory effects. In this study we assessed the effect of
rosiglitazone on biochemical and biophysical indexes of endothelial function in male, nondiabetic patients with
coronary artery disease. Consecutive male subjects (n = 71) with clinically stable, angiographically documented
coronary artery disease and without
diabetes mellitus were investigated. Patients were randomized in a double-blind manner to placebo or
rosiglitazone for a total of 24 weeks. Flow-mediated dilation (FMD) of the brachial artery,
C-reactive protein,
von Willebrand factor,
intercellular adhesion molecule-1 and
vascular cell adhesion molecule-1 levels, and parameters of
glucose and lipid metabolism were measured at baseline and after 12 and 24 weeks of treatment.
Rosiglitazone treatment significantly reduced
C-reactive protein (median 0.56 mg/L [interquartile range 0.33 to 1.02] to 0.33 mg/L [interquartile range 0.26 to 0.40], p <0.01),
von Willebrand factor (139 +/- 47 to 132 +/- 44 IU/dl, p = 0.02),
insulin resistance index (p = 0.05), and mean
low-density lipoprotein (
LDL) density (p <0.001) compared with placebo. However, no significant differences were seen between the
rosiglitazone and placebo groups with regard to brachial artery FMD,
intercellular adhesion molecule-1, or
vascular cell adhesion molecule-1 levels.
Rosiglitazone treatment significantly increased
LDL (2.62 +/- 0.72 to 2.95 +/- 0.84 mmol/L, p = 0.03) and
triglyceride (1.23 +/- 0.63 to 1.56 +/- 0.98 mmol/L, p = 0.04) levels. Thus,
rosiglitazone reduced markers of
inflammation and endothelial activation, but this did not translate into an improvement in FMD. Increased
LDL and
triglyceride levels may have played a role.