Soluble CD40 receptor is a biomarker of the burden of carotid artery atherosclerosis in subjects at high cardiovascular risk
Atherosclerosis — Leonetti S, Tricò D, Nesti L, et al. | January 19, 2022
In a high cardiovascular (CV) risk cohort, CD40 receptor (CD40R) emerged as the most powerful predictor of carotid atherosclerosis burden among an extended set of plausible atherosclerosis-linked biomarkers.
The SUMMIT study cohort (n = 1,500) comprised patients with type 2 diabetes (66%) and established CV disease (50%), who had ultrasound evaluation of carotid atherosclerosis with total plaque area quantification.
In participants, circulating proteins implicated in inflammation, plaque remodeling, smooth muscle cell migration, apoptosis and endothelial activity were measured.
In 1,174 patients, carotid artery atherosclerosis was evident; seven biomarkers in these patients were discovered to be more closely linked with atherosclerosis extension.
Relative to a multivariable model incorporating major conventional CV risk factors, the % gain of explained variability in total plaque area was shown to be the greatest (33%) post inclusion of CD40R ligand, followed by PDGF (30%), CD40R (26%), EGF (22%), CXCL1 (15%), HBEGF and MMP-17 (both 11%).
A hyperbolic association of total plaque area with CD40R, PDGF was identified.
CD40R was found to be the strongest predictor of the presence and extension of carotid atherosclerosis in the entire population including those without carotid plaques.
A more than two-fold greater atherosclerotic burden was seen in those in the third CD40R tertile, vs lower CD40R tertiles, despite an only marginally higher load of CV risk factors.