Low Levels of CD4+CD28null T Cells at Baseline Are Associated With First-Time Coronary Events in a Prospective Population-Based Case-Control Cohort
(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.
(Less)
- author
- organization
-
- Cardiovascular Research - Cellular Metabolism and Inflammation (research group)
- Cardiovascular Research - Immunity and Atherosclerosis (research group)
- EXODIAB: Excellence of Diabetes Research in Sweden
- Cardiovascular Research - Matrix and Inflammation in Atherosclerosis (research group)
- Cardiovascular Research - Translational Studies (research group)
- Internal Medicine - Epidemiology (research group)
- EpiHealth: Epidemiology for Health
- Hepato-Pancreato-Biliary Surgery (research group)
- Surgery (Lund)
- publishing date
- 2020-02
- 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 >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}}, }