Soluble CD40 levels in plasma are associated with cardiovascular disease and in carotid plaques with a vulnerable phenotype

Annelie Shami (Lead / Corresponding author), Andreas Edsfeldt, Eva Bengtsson, Jan Nilsson, Angela C. Shore, Andrea Natali, Faisel Khan, Esther Lutgens, Isabel Gonçalve

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)
49 Downloads (Pure)


Background and Purpose CD40 and CD40 ligand (CD40L) are costimulatory molecules of the tumor necrosis factor receptor superfamily and well known for their involvement in inflammatory diseases: atherosclerotic mouse models with disrupted CD40 signalling develop lesions of reduced size with a more stable plaque profile. This study investigated the potential of plasma and intraplaque levels of CD40 and CD40L as markers for cardiovascular disease (CVD) in humans and their association with plaque stability. Methods Soluble CD40 and CD40L (sCD40L) were measured in plasma in 1,437 subjects from The SUrrogate markers for Micro-and Macro-vascular hard endpoints for Innovative diabetes Tools (SUMMIT) cohort. Intra-plaque levels of sCD40 and sCD40L were measured in atherosclerotic plaque homogenates from 199 subjects of the Carotid Plaque Imaging Project (CPIP) cohort. Results Both plasma sCD40 and sCD40L levels were elevated in individuals with prevalent stroke, while sCD40 levels also were higher in individuals with a prior acute myocardial infarction. Plasma levels of sCD40 correlated with carotid intima-media thickness and total carotid plaque area and were associated with risk of cardiovascular events over a 3-year follow-up period. Intra-plaque levels of sCD40 and sCD40L were associated with plaque components characteristic for plaque vulnerability and extracellular matrix remodelling. Conclusions Higher plasma sCD40 and sCD40L levels are associated with prevalent CVD. Plasma sCD40 levels also correlate with the severity of carotid atherosclerosis and predict future cardiovascular events, while intra-plaque levels correlate with a vulnerable plaque phenotype. Our findings thus demonstrate that elevated levels of sCD40 and sCD40L are markers of CVD.

Original languageEnglish
Pages (from-to)367-376
Number of pages10
JournalJournal of Stroke
Issue number3
Early online date30 Sept 2021
Publication statusPublished - Sept 2021


  • CD40
  • CD40 Ligand
  • atherosclerosis
  • carotid arteries
  • inflammation
  • CD40 ligand
  • Atherosclerosis
  • Inflammation
  • Carotid arteries

ASJC Scopus subject areas

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine


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