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Blood glucose and platelet-dependent thrombosis in patients with coronary artery disease
M Shechter1, C N Merz, M J Paul-Labrador
1Preventive and Rehabilitative Cardiac Center, Cedars-Sinai Burns and Allen Research Institute, Los Angeles, California, USA.
Insights
High blood glucose independently predicts platelet-dependent thrombosis (PDT) in stable coronary artery disease (CAD) patients. This risk is continuous, even at normal glucose levels, suggesting a link between elevated glucose and increased thrombogenesis.
Area of Science:
- Cardiovascular Medicine
- Hematology
- Metabolic Disorders
Background:
- Elevated blood glucose is a known cardiovascular risk factor, independent of diabetes.
- The specific impact of blood glucose on platelet-dependent thrombosis (PDT) remains largely uncharacterized.
- Understanding this relationship is crucial for managing cardiovascular risk.
Purpose of the Study:
- To investigate the direct influence of blood glucose levels on platelet-dependent thrombosis (PDT).
- To determine if blood glucose is an independent predictor of PDT in patients with stable coronary artery disease (CAD).
Main Methods:
- An ex vivo extracorporeal perfusion protocol using the Badimon chamber was employed.
- Platelet-dependent thrombosis (PDT) was quantified using computerized morphometry.
- Platelet aggregation and P-selectin expression were assessed via whole blood impedance aggregometry and flow cytometry.
Main Results:
- Blood glucose emerged as the strongest independent predictor of PDT (R2 = 0.19, p < 0.008).
- PDT was significantly higher in patients with blood glucose above the median (4.9 mmol/l) compared to those below (p < 0.01).
- No significant differences in platelet aggregation or P-selectin expression were observed between groups, but an interaction between insulin and glucose modulated PDT.
Conclusions:
- Blood glucose is an independent predictor of PDT in stable CAD patients.
- The association between blood glucose and thrombosis risk appears continuous and graded, evident even within normal glucose ranges.
- Enhanced platelet-mediated thrombogenesis may partially explain the increased cardiovascular risk linked to elevated blood glucose.
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.