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.

Aim:The aim of this study was to evaluate the significance of endothelial cell-derived microparticles (EDMP), angiopoietin-2 (Ang-2) and adiponectin in hyperlipidemic patients with and without type 2 diabetes mellitus, and to compare the two for the effects of eicosapentaenoic acid (EPA) on these markers. Methods: One hundred and twenty-six hyperlipidemic patients with and without type 2 diabetes mellitus received EPA 1,800 mg daily, and 50 of the patients were non-diabetic. Results: EDMP and Ang-2 levels prior to treatment were higher in diabetic patients than in non-diabetic patients, whereas adiponectin levels were lower in diabetics. When diabetic patients were classified into two groups on the basis of Ang-2 levels, the levels of all markers remained unchanged in those without a high Ang-2 level after EPA treatment. In contrast, all markers except for adiponectin were decreased significantly in diabetic patients with high Ang-2 levels after 6 months of EPA treatment. These diabetic patients with high Ang-2 levels displayed a more significant increase in adiponectin levels after EPA treatment than those who did not. Conclusion: These results suggest that EPA possesses an adiponectin-dependent anti-atherosclerotic effect and may be beneficial for the prevention of vascular complications in diabetic patients with high Ang-2 levels. J Atheroscler

Nifedipine, a dihydropyridine calcium antagonist, improves endothelial function in patients with hypercholesterolaemia by enhancing nitric oxide (NO) activity, and increases endothelial NO bioavailability by antioxidant mechanisms. We administered a long-acting nifedipine formulation (controlled release (CR) nifedipine: 20 mg/day) to hypertensive patients for 6 months. There were no other changes of drug treatment during therapy with CR nifedipine. Clinical and biochemical data obtained before and after CR nifedipine administration were compared. All markers were measured by enzyme-linked immunosorbant assay. The levels of soluble markers (soluble CD40 ligand, soluble P-selectin, and soluble E-selectin), microparticles (MP) (platelet-derived MP, monocyte-derived MP, and endothelial cell-derived MP), and adiponectin differed between the control group and the hypertension group. The levels of these markers were also different in hypertensive patients with and without type 2 diabetes compared with the control group. In the hypertensive patients with type 2 diabetes, all markers except adiponectin decreased significantly after 3 months of CR nifedipine treatment. In contrast, markers were unchanged in the hypertensive patients without type 2 diabetes. Adiponectin was increased after 6 months of CR nifedipine treatment in hypertensive patients with type 2 diabetes. The effects of CR nifedipine on platelet/monocyte activation and adiponectin levels demonstrated in the present study indicate the potential effectiveness of calcium antagonist therapy for hypertensive patients with type 2 diabetes.

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Aim:The aim of this study was to clarify the relationship between platelet-derived microparticles (PDMPs) and the Framingham 10-yr coronary heart disease (CHD) risk score. Methods: A cross-sectional study of healthy volunteers free of medication, and cardiovascular or cerebrovascular disease was conducted. The subjects were 190 Japanese men (median age 41). An ELISA kit and monoclonal antibodies against CD42b and CD42a (glycoprotein Ib and IX) were used. Results: PDMPs are correlated with platelet count, high sensitivity C-reactive protein (hsCRP), and diastolic blood pressure by multivariate analysis (R 2 0.316, p 0.001). Quartile range of PDMPs is significantly associated with the 10-yr CHD risk score after adjusting for age, platelet count, hsCRP, and hypertension (p 0.033) and for age, platelet count, hsCRP, and presence of metabolic syndrome (MS) (p 0.020). In individuals with a predicted 10-yr risk for CHD 8% (corresponding with the highest quartile), compared to those with a predicted 10-yr risk 8%, the odds ratio (OR), adjusted for age, platelet count, hsCRP, and hypertension, was 3.3 (1.2 8.9) and adjusted for age, platelet count, hsCRP, and MS, was 4.5 (1.6 11.8). The age-, platelet count-, hsCRP-and hypertensionadjusted OR for a 10-yr CHD risk score 8% was 0.8 (0.5 1.3) for hsCRP and 3.9 (1.6 9.4) for hypertension. The age-, platelet count-, hsCRP-and MS -adjusted OR for a 10-yr CHD risk score 8% was 0.7 (0.4 1.2) for hsCRP and 7.9 (2.6 24.5) for MS. Conclusion: Elevated PDMPs are associated with the 10-yr CHD risk score in healthy men. J Atheroscler Thromb, 2010; 17:342-349.