Objectives: To investigate the influence of blood glucose on platelet-dependent thrombosis (PDT).
Background: Elevated blood glucose is a predictor of adverse cardiovascular risk independent of a diagnosis of diabetes, possibly due to adverse effects promoting thrombosis. The effects of blood glucose on PDT have not been characterized.
Methods: An ex vivo extracorporeal perfusion protocol was used to measure PDT in 42 patients with stable coronary artery disease (CAD). The Badimon chamber was perfused with unanticoagulated venous blood and PDT evaluated using computerized morphometry. Whole blood impedance aggregometry and flow cytometry evaluated platelet aggregation and P-selectin expression, respectively.
Results: Using a multivariate stepwise regression model, blood glucose was the best independent predictor of PDT (R2 = 0.19, p < 0.008), followed by apolipoprotein B (R2 = 0.18, p = 0.002) and intracellular magnesium levels (R2 = 0.12, p = 0.02). Platelet-dependent thrombosis was significantly greater in patients with blood glucose >, compared with <, the median value of 4.9 mmol/l (159 +/- 141 vs. 67 +/- 69 microm2/mm, p < 0.01). Neither platelet aggregation nor P-selectin expression was significantly 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 analysis of variance demonstrated an interaction between insulin (>126 pmol/l) and 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 levels considered normal, indicating that the risk associated with blood glucose may be continuous and graded. These findings suggest that the increased CAD risk associated with elevated blood glucose may be, in part, related to enhanced platelet-mediated thrombogenesis.