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CLINICAL STUDIES

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

Michael Shechter, MD, MA, FACC^* , C. Noel Bairey Merz, MD, FACC^* , Maura J. Paul-Labrador, MPH^* and Sanjay Kaul, MD^*

^* Preventive and Rehabilitative Cardiac Center, Cedars-Sinai Burns and Allen Research Institute, Division of Cardiology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA
Atherosclerosis Research Center, Cedars-Sinai Burns and Allen Research Institute, Division of Cardiology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA
UCLA School of Medicine, Los Angeles, California, USA

Manuscript received July 27, 1998; revised manuscript received August 16, 1999, accepted October 18, 1999.

Reprint requests and correspondence: Dr. Sanjay Kaul, Division of Cardiology, Room 5314, Cedars-Sinai Medical Center, 8700, Beverly Boulevard, Los Angeles, California 90048
kaul{at}cshs.org

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 µm²/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.

Abbreviations and Acronyms   ADP = adenosine diphosphate   ANOVA = analysis of variance   BMI = body mass index   CAD = coronary artery disease   CHD = coronary heart disease   FBG = fasting blood glucose   HDL-C = high-density lipoprotein cholesterol   LDL-C = low-density lipoprotein cholesterol   NYHA = New York Heart Association   PDT = platelet-dependent thrombosis

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