Abstract 2837: The Impact of Proinflammatory Cytokines And Risk Factors on sCD40L Levels In Stable Coronary Artery Disease And Acute Myocardial Infarction
Background: Evidence suggests that soluble CD40-ligand is elevated in coronary artery disease and is released in large amounts from activated platelets during the acute phase of myocardial infarction. Although sCD40L is considered to be part of the physiological immune response, the mechanisms regulating its release in different disease states remain unknown.
Methods: This study enrolled 596 subjects: 201 patients with stable coronary artery disease (CAD), 109 patients with acute myocardial infarction (AMI, recruited by their admission to the hospital) and 286 healthy controls. Circulating sCD40L, interleukin 6 (IL-6), vascular cells adhesion molecules (sVCAM-1) and intercellular adhesion molecules (sICAM-1) were determined by ELISA.
Results: Patients with AMI had significantly higher levels of sCD40L (18.8±1.2 ng/ml) and IL-6 (9.1±0.5pg/ml) compared to both CAD (7.0±0.5 ng/ml and 5.0±0.4pg/ml p<0.01 for both) and controls (4.6±0.2ng/ml and 2.1±2.3pg/ml p<0.01 for both vs CAD or AMI). Similarly, SICAM-1 and sVCAM-1 levels were significantly higher in CAD (316±8 and 753±39 ng/ml) and AMI (360±18 and 806±52 ng/ml) compared to controls (287±6.5 and 631±270 ng/ml, p<0.05 for both vs CAD and AMI). IL-6 was the only independent predictor of sCD40L in healthy individuals (β(SE):0.491(0.096), p=0.0001). However, in CAD or AMI, only diabetes mellitus (β (SE):2.689(1.082), p=0.044 and β(SE):10.406(3.215), p=0.002 respectively) and smoking (β(SE):3.470(1.111), p=0.002 and β (SE):9.694(2.478), p=0.0001 respectively) (but not IL-6), were independently associated with sCD40L.
Conclusions: Both CAD and AMI were accompanied by increased levels of sCD40L in parallel with an elevation of proinflammatory cytokine IL-6 and adhesion molecules sVCAM-1 and sICAM-1. Diabetes mellitus and smoking (but not IL-6 or adhesion molecules) were the only independent predictors of sCD40L levels in CAD and AMI patients. These findings suggest that the complex interaction between proinflammatory cytokines and sCD40L release is largely dependent on the underlying disease state.