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Soluble CD40 receptor is a biomarker of the burden of carotid artery atherosclerosis in subjects at high cardiovascular risk

AtherosclerosisLeonetti 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.