Platelet-derived microparticles (
PDMP) play an important role in the pathogenesis of diabetic vasculopathy, and
statins or
eicosapentaenoic acid (EPA) have been shown to have a beneficial effect on
atherosclerosis in hyperlipidemic patients. However, the influence of EPA and
statins on
PDMP and
adiponectin in
atherosclerosis is poorly understood. We investigated the effect of
pitavastatin and EPA on circulating levels of
PDMP and
adiponectin in hyperlipidemic patients with type II diabetes. A total of 191 hyperlipidemic patients with type II diabetes were divided into three groups: group A received
pitavastatin 2 mg once daily (n = 64), group B received EPA 1800 mg daily (n = 55) and group C received both drugs (n = 72).
PDMP and
adiponectin were measured by ELISA at baseline and after 3 and 6 months of
drug treatment. Thirty normolipidemic patients were recruited as healthy controls.
PDMP levels prior to treatment in hyperlipidemic patients with diabetes were higher than levels in healthy controls (10.4 +/- 1.9 vs. 3.1 +/- 0.4 U/ml, p < 0.0001), and
adiponectin levels were lower than controls (3.20 +/- 0.49 vs. 5.98 +/- 0.42 microg/ml, p < 0.0001).
PDMP decreased significantly in group B (before vs. 6M, 10.6 +/- 2.0 vs. 8.0 +/- 1.7 U/ml, p < 0.01), but not in group A (before vs. 6M, 9.4 +/- 1.9 vs. 9.6 +/- 1.7 U/ml, not significant). In contrast, group A exhibited a significant increase in
adiponectin levels
after treatment (before vs. 6M, 3.29 +/- 0.51 vs. 4.16 +/- 0.60 microg/ml, p < 0.001). Furthermore, group C exhibited significant improvement in both
PDMP and
adiponectin levels
after treatment (
PDMP, before vs. 6M, 11.2 +/- 2.0 vs. 4.5 +/- 2.7 U/ml, p < 0.001;
adiponectin, before vs. 6M, 3.24 +/- 0.41 vs. 4.02 +/- 0.70 microg/ml, p < 0.001). Reductions of
PDMP in combined
therapy were significantly greater than those observed with EPA alone (p < 0.05 by ANOVA). In addition, soluble
CD40 ligand exhibited almost the same change as
PDMP in all
therapy groups. These results suggest that
pitavastatin possesses an
adiponectin-dependent antiatherosclerotic effect, and this
drug is able to enhance the anti-platelet effect of EPA. The combination
therapy of
pitavastatin and EPA may be beneficial for the prevention of vascular complication in hyperlipidemic patients with type II diabetes.