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Abstract: Background: The presence of effort induced angina, positive exercise stress test responses and angiographically normal coronary arteries defines cardiac syndrome X (CSX). Its pathogenesis, although mostly attributed to endothelial dysfunction and coronary microcirculation abnormalities, is incompletely understood. The soluble CD40 ligand (sCD40L) has multiple autocrine, paracrine and endocrine actions that may lead to endothelial dysfunction and atherothrombosis. We sought to investigate the relationship among sCD40L levels and ischemic burden in patients with CSX and whether sCD40L levels are increased in patients with CSX compared to control subjects. Methods: We assessed 30 prospectively enrolled patients with CSX and 28 apparently healthy subjects matched for coronary risk factors. All CSX patients and control subjects underwent myocardial perfusion scintigraphy. The summed difference score is taken to be an index of ischemic burden. This was classified as mildly, moderately and severely abnormal. White blood cells, sCD40L and C-reactive protein (CRP) concentrations were measured at peak exercise. Results: At peak exercise, sCD40L levels were significantly greater in CSX patients than in the control group (P =0.008). Similarly, white blood cell count and CRP levels were higher in patients with CSX than in normal controls (P =0.02). After multivariable adjustment, sCD40L (P =0.03) was the only independent predictor of severe ischemic burden in CSX patients. Conclusions: The present study showed for the first time that sCD40L is associated with ischemic burden in patients with CSX. The potential role of this inflammatory molecule in the pathogenesis of CSX deserves investigation in future studies. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: CD40 ligand has been suggested to play a pathogenic role in atherogenesis and coronary artery disease progression. Clinical studies suggest that intravenous (IV) abciximab administration attenuates the acute inflammatory response associated with percutaneous coronary intervention (PCI). The anti-inflammatory effects of intracoronary (IC) versus IV administration of abciximab have not been systematically investigated. We assessed changes in soluble CD40 ligand (sCD40L) concentrations in response to IC versus IV abciximab in patients with ST-elevation myocardial infarction (STEMI) undergoing thrombus-aspirating device during primary PCI. Methods: Patients were randomized to receive IC (n =25) or IV (n =25) bolus abciximab followed in every case by a 12-h IV abciximab infusion. sCD40L was measured immediately before the administration of abciximab (baseline) and 60min post bolus administration. Results: Clinical baseline and angiographic characteristics were similar in both patient groups. Similarly, there were no significant differences in baseline serum sCD40L levels in the IC group compared to IV group (116.6±42.13pg/mL vs 124.9±43.04pg/mL, P =0.49). At 60min post PCI, however, sCD40L levels decreased by 23% (P <0.001) in the IC group and by 11% (P <0.001) in the IV group. sCD40L levels 60min post PCI were significantly reduced, particularly in the IC group compared to the IV group (73.04±12.21pg/mL vs 99.92±25.89pg/mL, P <0.001). Conclusion: In STEMI patients undergoing primary PCI, IC bolus administration of abciximab was associated with a larger reduction in sCD40L levels compared to standard IV bolus. Whether this more powerful anti-inflammatory effect of IC abciximab translates into improved clinical outcomes deserves investigation. [Copyright &y& Elsevier]