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Low Levels of CD4+CD28null T Cells at Baseline Are Associated With First-Time Coronary Events in a Prospective Population-Based Case-Control Cohort

Tomas, Lukas LU ; Bengtsson, Eva LU orcid ; Andersson, Linda LU ; Badn, Wiaam LU ; Tengryd, Christoffer LU ; Persson, Ana LU ; Edsfeldt, Andreas LU ; Nilsson, Peter M LU ; Schiopu, Alexandru LU and Nilsson, Jan LU , et al. (2020) In Arteriosclerosis, Thrombosis, and Vascular Biology 40(2). p.426-436
Abstract

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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
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
in
Arteriosclerosis, Thrombosis, and Vascular Biology
volume
40
issue
2
pages
426 - 436
publisher
Lippincott Williams & Wilkins
external identifiers
  • scopus:85078549211
  • pmid:31801374
ISSN
1524-4636
DOI
10.1161/ATVBAHA.119.313032
language
English
LU publication?
yes
id
7b23d003-74d0-410a-9387-dd7f792cf014
date added to LUP
2020-08-17 09:11:02
date last changed
2024-03-20 14:03:45
@article{7b23d003-74d0-410a-9387-dd7f792cf014,
  abstract     = {{<p>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 &gt;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.</p><p>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.</p>}},
  author       = {{Tomas, Lukas and Bengtsson, Eva and Andersson, Linda and Badn, Wiaam and Tengryd, Christoffer and Persson, Ana and Edsfeldt, Andreas and Nilsson, Peter M and Schiopu, Alexandru and Nilsson, Jan and Gonçalves, Isabel and Björkbacka, Harry}},
  issn         = {{1524-4636}},
  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}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{426--436}},
  publisher    = {{Lippincott Williams & Wilkins}},
  series       = {{Arteriosclerosis, Thrombosis, and Vascular Biology}},
  title        = {{Low Levels of CD4+CD28null T Cells at Baseline Are Associated With First-Time Coronary Events in a Prospective Population-Based Case-Control Cohort}},
  url          = {{http://dx.doi.org/10.1161/ATVBAHA.119.313032}},
  doi          = {{10.1161/ATVBAHA.119.313032}},
  volume       = {{40}},
  year         = {{2020}},
}