Soluble CD40L, platelet surface CD40L and total platelet CD40L in congestive heart failure: relationship to platelet volume, mass and granularity

Abstract

Many complications associated with congestive heart failure (CHF) have a thrombosis-related aetiology, which may involve platelets. The immune modulator pair CD40-CD40L has been proposed to be an important link between inflammation and thrombosis and may be important in the pathophysiology of CHF. To study soluble CD40L (sCD40L), platelet surface CD40L (%GCD40L) and total platelet CD40L (pCD40L) levels in CHF patients, their relationships to other platelet indices (platelet volume, mass and component) and to assess their prognostic value. We measured sCD40L (by ELISA); pCD40L (by a platelet lysate assay); platelet surface CD40L (%GCD40L) expression by flow cytometry; mean platelet volume (MPV), mean platelet mass (MPM) and mean platelet component (MPC); in 108 patients with stable CHF. Levels were compared with 37 'healthy controls' and 63 'disease controls'. After a median follow-up period of 490 days, clinical endpoints were determined. pCD40L was significantly higher in CHF than disease controls, but not sCD40L or %GCD40L levels. CHF patients and disease controls had higher MPV (one-way anova, P < 0.0001), whilst MPC was significantly lower in CHF patients (P < 0.0001), compared to healthy controls. All indices related to CD40L (i.e. sCD40L, pCD40L and %GCD40L) were neither related to disease severity or left ventricular ejection function, nor to clinical endpoints at follow-ups. Patients with stable CHF patients did not exhibit enhanced levels of CD40L and the latter did not predict clinical events at follow-up. The lack of difference in CD40L levels between CHF and disease controls suggests that CD40L may not have a major role in CHF per se, but in the comorbidities associated with CHF.