BACKGROUND: Platelets play a key role in atherogenesis and thromboembolic complications in patients with type 2 diabetes. METHODS AND RESULTS: We prospectively examined the relationship between systemic platelet activation and progression of carotid wall thickness within 1 year in 105 patients with type 2 diabetes. The intima-media thickness (IMT) of the common carotid artery was measured bilaterally at study entry and after 1 year. Platelet activation was assessed with the use of immunologic markers of platelet activation (CD62P, CD63, and CD40L) and flow cytometry. The prevalence for progression of atherosclerotic carotid disease in this population was 55.2%. We found that platelet degranulation (CD63 and CD40L) correlated with progression of IMT within 1 year (CD63: r=0.231, P=0.022; CD40L: r=0.230, P=0.029). Diabetic patients with progression of IMT had a significantly increased expression of CD63 compared with patients with stable carotid disease (mean intensity of immunofluorescence; median, interquartile range: 17.1 [12.4, 25.8] versus 11.9 [7.7, 19.8]; P=0.004). Multivariate logistic regression analysis revealed that degranulation of platelet CD63 is a predictor for progression of IMT independently of classical cardiovascular risk factors and hemoglobin A1c in diabetic patients (P=0.017). CONCLUSIONS: Enhanced systemic platelet degranulation is associated with progression of carotid artery disease in type 2 diabetes.
BACKGROUND: Platelets play a key role in atherogenesis and thromboembolic complications in patients with type 2 diabetes. METHODS AND RESULTS: We prospectively examined the relationship between systemic platelet activation and progression of carotid wall thickness within 1 year in 105 patients with type 2 diabetes. The intima-media thickness (IMT) of the common carotid artery was measured bilaterally at study entry and after 1 year. Platelet activation was assessed with the use of immunologic markers of platelet activation (CD62P, CD63, and CD40L) and flow cytometry. The prevalence for progression of atherosclerotic carotid disease in this population was 55.2%. We found that platelet degranulation (CD63 and CD40L) correlated with progression of IMT within 1 year (CD63: r=0.231, P=0.022; CD40L: r=0.230, P=0.029). Diabeticpatients with progression of IMT had a significantly increased expression of CD63 compared with patients with stable carotid disease (mean intensity of immunofluorescence; median, interquartile range: 17.1 [12.4, 25.8] versus 11.9 [7.7, 19.8]; P=0.004). Multivariate logistic regression analysis revealed that degranulation of platelet CD63 is a predictor for progression of IMT independently of classical cardiovascular risk factors and hemoglobin A1c in diabeticpatients (P=0.017). CONCLUSIONS: Enhanced systemic platelet degranulation is associated with progression of carotid artery disease in type 2 diabetes.
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Authors: Nathalie Cloutier; Isabelle Allaeys; Genevieve Marcoux; Kellie R Machlus; Benoit Mailhot; Anne Zufferey; Tania Levesque; Yann Becker; Nicolas Tessandier; Imene Melki; Huiying Zhi; Guy Poirier; Matthew T Rondina; Joseph E Italiano; Louis Flamand; Steven E McKenzie; Francine Cote; Bernhard Nieswandt; Waliul I Khan; Matthew J Flick; Peter J Newman; Steve Lacroix; Paul R Fortin; Eric Boilard Journal: Proc Natl Acad Sci U S A Date: 2018-01-31 Impact factor: 11.205