Elevated circulating soluble form of CD40 ligand in patients with cardiac syndrome X

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.