Soluble CD40L in patients with morbid obesity: significant reduction after bariatric surgery.

Background: Morbid obesity is associated with increased cardiovascular morbidity and mortality. Recent studies suggest that soluble CD40 Ligand (sCD40L) may play a pathogenetic role in atherothrombotic complications in cardiovascular disease as well as in inflammation and thrombosis. As morbid obesity is closely associated with chronic inflammation and insulin resistance (IR), it was of interest to study sCD40L in patients with morbid obesity before and after massive weight loss induced by bariatric surgery.
Patients and Methods: A total of 34 patients (mean age 40 +/- 12 years) with morbid obesity were studied before and 27.2 months after bariatric surgery. High sensitivity assays were used to measure concentrations of fasting sCD40L, monocyte-chemoattractant-protein-1 (MCP-1) and high-sensitive C-reactive protein (hsCRP). To investigate the associations of concentration changes of the parameters studied, differences between pre- and post-operative data were assessed and tested by univariate and multivariate linear regression analysis.
Results: After a mean weight loss of 33.1 +/- 18.4 kg, circulating sCD40L decreased significantly from (3.7 +/- 1.5) ng mL(-1) to (2.2 +/- 0.7) ng mL(-1), (P < 0.001). The decline in sCD40L after weight loss correlated significantly with the decrease in fasting insulin, 2-h insulin, HOMA insulin resistance (HOMA-IR), triglycerides, and the inflammatory biomarkers MCP-1 and hsCRP.
Conclusions: We have shown a marked decrease in circulating sCD40L in association with an improvement of both insulin resistance and chronic inflammation in morbidly obese patients after bariatric surgery. As high sCD40L was shown to predict cardiovascular death and myocardial infarction in several prospective studies, the observed marked lowering of sCD40L might be of clinical relevance in morbidly obese patients.