Background: Shear stress generated in stenosed arteries promotes platelet thrombi formation at the stenosed sites by accelerating the binding of von Willebrand factor (vWF) to platelets. Shear-induced platelet aggregation (SIPA) has been studied in acute coronary syndromes, but not in chronic coronary disease. Hypothesis: We investigated the effect of both the site and severity of coronary stenosis on SIPA in patients with chronic coronary artery disease. Methods: Shear-induced platelet aggregation was measured using platelet-rich plasma in 49 patients (41 men and 8 women; mean age 61 ± 10 years) with coronary artery disease to evaluate the association between the extent of SIPA and coronary angiographic findings. Stenoses > 75% were considered severe. In all, 62 healthy individuals (54 men and 18 women; mean age 45 ± 7 years) served as controls. The correlation between SIPA and the site and severity of the coronary lesion, and parameters of coagulation and fibrinolysis were evaluated. Results: Shear-induced platelet aggregation was increased in the stenosis group (69.0 ± 10.6%) compared with the controls (57.7 ± 10.3%, p<0.0001). Patients with severe stenosis in the proximal segments had significantly increased SIPA (p < 0.0001) and vWF larger multimer concentration (p < 0.0001) compared with the control group. A significant correlation existed between SIPA and the vWF larger multimer concentration in all subjects studied (r = 0.422, p < 0.0001). Conclusions: Shear-induced platelet aggregation is increased in patients with severe stenosis of the proximal coronary arteries and correlates with plasma concentrations of vWF larger multimers, suggesting that severe stenosis in the proximal segments is not only associated with an increased risk of significant myocardial ischemia, but may also generate high shear stress in the stenosed artery and increase plasma vWF larger multimers, thereby promoting the formation of platelet thrombi.
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