Blood glucose and platelet-dependent thrombosis in patients with coronary artery disease

OBJECTIVES To investigate the influence of blood glucose on platelet-depend ent thrombosis (PDT). BACKGROUND Elevated blood glucose is a predictor of adverse cardiovascular risk independent of a diagnosis of diabetes, possibly due to adverse effect s promoting thrombosis. The effects of blood glucose on PDT have not been c haracterized. METHODS An ex vivo extracorporeal perfusion protocol was used to measure PD T in 42 patients with stable coronary artery disease (CAD). The Badimon cha mber was perfused with unanticoagulated venous blood and PDT evaluated usin g computerized morphometry. Whole blood impedance aggregometry and flow cyt ometry evaluated platelet aggregation and P-selectin expression, respective ly. RESULTS Using a multivariate stepwise regression model, blood glucose was t he best independent predictor of PDT (R-2 = 0.19, p < 0.008), followed by a polipoprotein B (R-2 = 0.18, p = 0.002) and intracellular magnesium levels (R-2 = 0.12, p = 0.02). Platelet-dependent thrombosis was significantly gre ater in patients with blood glucose >, compared with less than or equal to, the median value of 4.9 mmol/l (159 +/- 141 vs. 67 +/- 69 mu m(2)/mm, p < 0.01), Neither platelet aggregation nor P-selectin expression was significa ntly different between the two groups. Insulin levels correlated with blood glucose (r = 0.56, p = 0.0003), but were not independently associated with either PDT, platelet aggregation or P-selectin expression. A two-way analy sis of variance demonstrated an interaction between insulin (>126 pmol/l) a nd blood glucose (>4.9 mmol/l) in modulating PDT (F [1,38] = 8.5, p < 0.006 ). CONCLUSIONS Blood glucose is an independent predictor of PDT in stable CAD patients. The relationship is evident even in the range of blood glucose le vels considered normal, indicating that the risk associated with blood gluc ose may be continuous and graded. These findings suggest that the increased CAD risk associated with elevated blood glucose may be, in part, related t o enhanced platelet-mediated thrombogenesis. (J Am Coll Cardiol 2000;35:300 -7) (C) 2000 by the American College of Cardiology.