Associations Between Soluble CD40 Ligand, Atherosclerosis Risk Factors, and Subclinical Atherosclerosis

Abstract

Objectives-The purpose of this study was to evaluate the associations between plasma levels of soluble CD40 ligand (sCD40L), atherosclerosis risk factors, and evidence of subclinical atherosclerosis. Methods and Results-Plasma levels of sCD40L were measured in 2811 subjects from the Dallas Heart Study, a multiethnic population-based cross-sectional study. Electron Beam Computed Tomography measurements of coronary artery calcium (CAC) and MRI measurements of aortic plaque were performed in 2198 and 1965 subjects, respectively. No association was observed between quartiles of sCD40L and age, sex, race, body mass index, diabetes, smoking, creatinine clearance, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or C-reactive protein.In contrast, weak but statistically significant associations were observed between sCD40L and total cholesterol and triglycerides. The prevalence of detectable CAC (CAC score Ն10) and aortic plaque did not differ across sCD40L quartiles, and individuals with CAC scores Ͻ10, Ն10 to 100, Ͼ100 to 400, and Ͼ400 had similar sCD40L levels. Conclusions-In a large and representative multiethnic population-based sample, sCD40L was not associated with most atherosclerotic risk factors or with subclinical atherosclerosis. These findings suggest that sCD40L will not be useful as a tool to screen for the presence of subclinical atherosclerosis in the population.

Relation of smoking status to a panel of inflammatory markers: The Framingham offspring

“…We also found a statistically significant inverse relation between smoking status and plasma CD40L, unlike others. 21 Potential explanations for the contrast between our findings with respect to serum and plasma CD40L compared with others may be due to differences in biomarker collection techniques, study sample, covariate adjustment, and smoking status definitions. We are uncertain why plasma CD40L concentrations were higher in never smokers, and smokers with the fewest pack-years exposure, in contrast to the lack of a trend with serum CD40L.…”

“…15,19 MCP-1, a chemokine found in atherosclerotic plaque, attracts monocytes to developing plaque. 21,22 MPO, a leukocyte enzyme, is elevated in culprit lesions of patients with acute coronary syndrome. 20 Urinary isoprostanes indexed to urinary creatinine (isoprostanes) are measures of oxidative stress.…”

Coronary artery disease progression is associated with C-reactive protein and conventional risk factors but not soluble CD40 ligand

“…One prospective study (21) showed that apparently healthy women with elevation of baseline sCD40L will have higher future cardiovascular event rate. However, de Lemos et al (22) reported sCD40L was not associated with subclinical atherosclerosis, as evaluated by the coronary calcium score of the electron beam computed tomography examination in a population-based study. Moreover, Verma et al (23) reported poor correlation between sCD40L and the calculated Framingham CAD risk score in a healthy, middle-aged male cohort.…”

Stratification of ST-elevation myocardial infarction patients based on soluble CD40L longitudinal changes

“…† Significantly different from the low-sCD40L group, P , 0.05. mentioned by us, 5 none of these studies exclusively assessed STEMI patients or variations of sCD40L over time as in the current work. Furthermore, more recent studies not only fail to demonstrate an association of high level of sCD40L with increased risk of cardiovascular events, [21][22][23][24] but in fact, indicate an inverse relation of sCD40L levels with risk of recurrent ischemia. 23 The CD40/CD40L system represents a major costimulator system triggering different signaling pathways mainly attending as amplification of immune and inflammatory responses, 25 including in endothelial cells.…”