Background-Recent genetic animal models reveal important roles of platelet P-selectin on progression of atherosclerosis.In the present study, we examine the relation between platelet P-selectin expression and atherosclerotic parameters in 517 subjects. Methods and Results-Unrelated subjects (nϭ517; 235 male and 282 female), including 187 with type 2 diabetes, 184with hypertension, and 366 with hyperlipidemia, were enrolled in the study. P-selectin expression was determined by whole-blood flow cytometry. Arterial stiffness (stiffness index ␤) and arterial wall thickness (intima-media thickness [IMT]) were determined by carotid ultrasound. P-selectin expression was significantly and positively correlated with carotid IMT and stiffness index ␤. Multiple regression analyses showed that the association of the percentage of P-selectin-positive platelets with carotid IMT was independent of other clinical factors. Moreover, the percentage of P-selectin-positive platelets was higher in subjects with carotid plaque and was an independent factor associated with occurrence of carotid plaque analyzed by multiple logistic regression analysis. Finally, the percentage of P-selectinpositive platelets was positively associated with age, body mass index, systolic and diastolic blood pressure, and HbA1c and inversely associated with HDL cholesterol. Conclusions-Platelet P-selectin is independently associated with atherosclerotic arterial wall changes in human subjects.(Circulation. 2003;108:524-529.)

Objective: A statin, a potent lipid-lowering drug, improves pain-free walking distance in patients with peripheral arterial disease (PAD) without increasing the ankle-brachial pressure index (ABI). Arterial stiffness affects the blood flow of peripheral arteries. The purpose of this study was to evaluate the effect of cholesterol-lowering with atorvastatin on regional arterial stiffness in patients with type 2 diabetes mellitus. Methods: The subjects were 22 type 2 diabetic patients with hypercholesterolemia, who received atorvastatin at a daily dose of 10 mg for 6 months. Before and after the treatment with atorvastatin, we measured pulse wave velocity (PWV) in the heartbrachial, heart-carotid, heart-femoral and femoral-ankle segments. Results: Following treatment with atorvastatin, femoral-ankle PWV showed a significant reduction. The PWV of other arterial segments tended to decrease, although the changes were not statistically significant. We found no significant changes in blood pressure, heart rate, ABI, or plasma concentrations of glucose, L-arginine and asymmetric dimethylarginine (

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