OBJECTIVE: CD4+CD28null T cells have been shown to be associated with recurrent coronary events and suggested as potential biomarker and therapeutic target. It is unknown whether CD4+CD28null T cells associate with first-time cardiovascular events. We examined CD4+CD28null T cells in a prospective population-based cohort and in patients with advanced atherosclerosis. Approach and Results: CD4+CD28null T cells were quantified in 272 individuals experiencing a first-time coronary event during up to 17 years of follow-up and 272 age- and sex-matched controls in a case-control study, nested within the population-based Malmö Diet and Cancer study. The highest tertile of CD4+CD28null T cells was associated with a lower incidence of first-time coronary events compared with the lowest tertile (odds ratio, 0.48 [95% CI, 0.29-0.79], P=0.004) when adjusting for Framingham risk factors. This association remained significant for events recorded after >9 years of follow-up, when most coronary events occurred, but not during the first 9 years of follow-up, despite similar odds ratio. Additionally, we analyzed CD4+CD28null T cells in 201 patients with advanced atherosclerosis undergoing carotid endarterectomy. The adjusted hazard ratio for cardiovascular events in patients with advanced atherosclerosis was 2.11 (95% CI, 1.10-4.05, P=0.024), comparing the highest with the lowest CD4+CD28null T-cell tertile.

CONCLUSIONS: Our findings reveal complex associations between CD4+CD28null T cells and cardiovascular disease. Although we confirm the reported positive associations with an adverse prognosis in patients with already established disease, the opposite associations with first-time coronary events in the population-based cohort may limit the clinical use of CD4+CD28null T cells.

Original languageEnglish
Pages (from-to)426-436
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Issue number2
Publication statusPublished - 2020 Feb

Subject classification (UKÄ)

  • Cardiac and Cardiovascular Systems

Free keywords

  • Atherosclerosis/blood
  • CD28 Antigens/immunology
  • CD4-Positive T-Lymphocytes/immunology
  • Case-Control Studies
  • Coronary Artery Disease/blood
  • Coronary Vessels/diagnostic imaging
  • Female
  • Flow Cytometry
  • Follow-Up Studies
  • Forecasting
  • Humans
  • Incidence
  • Lymphocyte Count
  • Male
  • Middle Aged
  • Population Surveillance
  • Prospective Studies
  • Sweden/epidemiology
  • T-Lymphocytes/immunology


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