Clinical correlates, heritability, and genetic linkage of circulating CD40 ligand in the Framingham Offspring Study

Background The CD40 receptor and its ligand (CD40L) are known to modulate both inflammation and thrombosis—2 processes important for the development and clinical expression of atherosclerosis. Circulating soluble CD40L (sCD40L) concentration predicts cardiovascular risk in selected patient samples. The purpose of this study was to determine the predictors of sCD40L in a large, community-based sample. Methods We determined both serum and plasma sCD40L concentration in 3,259 participants (54% women) from the Framingham Offspring Study. Results In multivariable models, advancing age was the only consistent (inverse) correlate of both serum and plasma sCD40L concentration. Overall, the variability explained by clinical covariates was very low for both measurements of sCD40L; with values of only 1.4% and 2.7% for serum and plasma, respectively. We observed that genetic factors accounted for a modest (12% serum; 14% plasma) amount of the adjusted variability in sCD40L. Conclusions Circulating sCD40L concentration was poorly associated with known cardiovascular disease (CVD) risk factors and was modestly heritable. Determining if either serum or plasma sCD40L are predictive of CVD risk in the community will require longitudinal follow-up.