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Elevated CD14++CD16- Monocytes Predict Cardiovascular Events.

Berg, Katarina LU ; Ljungcrantz, Irena LU ; Andersson, Linda LU ; Bryngelsson, Carl LU ; Hedblad, Bo LU ; Nordin Fredrikson, Gunilla LU ; Nilsson, Jan LU and Björkbacka, Harry LU (2012) In Circulation: Cardiovascular Genetics 5(1). p.122-131
Abstract
BACKGROUND: -Although monocytes in peripheral blood are no longer considered to be a homogeneous population, associations between distinct monocyte subsets and cardiovascular disease have not been highlighted in large epidemiological studies. METHODS AND RESULTS: -The study included 700 randomly selected subjects from the cardiovascular arm of the Malmö Diet and Cancer study. Among these, 123 subjects suffered ischemic cardiovascular events during the follow-up until December 2008. Mononuclear leukocytes frozen at the baseline investigation in 1991-94 were thawed and analyzed with flow cytometry to enumerate monocyte subsets based on CD14 and CD16 expression. The percentage and number of classical CD14(++)CD16(-) monocytes were increased... (More)
BACKGROUND: -Although monocytes in peripheral blood are no longer considered to be a homogeneous population, associations between distinct monocyte subsets and cardiovascular disease have not been highlighted in large epidemiological studies. METHODS AND RESULTS: -The study included 700 randomly selected subjects from the cardiovascular arm of the Malmö Diet and Cancer study. Among these, 123 subjects suffered ischemic cardiovascular events during the follow-up until December 2008. Mononuclear leukocytes frozen at the baseline investigation in 1991-94 were thawed and analyzed with flow cytometry to enumerate monocyte subsets based on CD14 and CD16 expression. The percentage and number of classical CD14(++)CD16(-) monocytes were increased in the cardiovascular-event group compared to the event-free subjects (median 69% (inter-quartile range 62-76)% vs. 67 (59-72)%, p=0.017; 344 (251-419) cells/μL vs. 297 (212-384) cells/μL, p=0.003). The hazard ratio was 1.66 for suffering a cardiovascular event in the highest tertile of the number of CD14(++)CD16(-) monocytes compared to the lowest tertile even after adjustment for common risk factors (HR 1.66, 95%CI: 1.02-2.72). CD14(++)CD16(-) monocytes did not, however, associate with the extent of atherosclerosis at baseline. In contrast, the percentage of monocytes expressing CD16 was negatively associated to the extent of carotid atherosclerosis measured as intima-media thickness (IMT) at baseline. The chemokine receptors CCR2, CX3CR1 and CCR5 were not differentially expressed between cases and controls on any of the monocyte subsets, but CCR5 expression on CD14(+)CD16(++) monocytes was negatively associated to carotid IMT. CONCLUSIONS: -This study shows that classical CD14(++)CD16(-) monocytes can predict future cardiovascular risk independently of other risk factors in a randomly selected population. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
ischemic stroke, myocardial infarction, cardiovascular disease, monocytes, leukocytes
in
Circulation: Cardiovascular Genetics
volume
5
issue
1
pages
122 - 131
publisher
American Heart Association
external identifiers
  • wos:000309884100019
  • pmid:22238190
  • scopus:84860842552
ISSN
1942-325X
DOI
10.1161/CIRCGENETICS.111.960385
language
English
LU publication?
yes
id
11aadd42-1c51-452c-b816-52b623c44a60 (old id 2336498)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22238190?dopt=Abstract
date added to LUP
2012-02-01 20:42:33
date last changed
2017-11-12 03:13:01
@article{11aadd42-1c51-452c-b816-52b623c44a60,
  abstract     = {BACKGROUND: -Although monocytes in peripheral blood are no longer considered to be a homogeneous population, associations between distinct monocyte subsets and cardiovascular disease have not been highlighted in large epidemiological studies. METHODS AND RESULTS: -The study included 700 randomly selected subjects from the cardiovascular arm of the Malmö Diet and Cancer study. Among these, 123 subjects suffered ischemic cardiovascular events during the follow-up until December 2008. Mononuclear leukocytes frozen at the baseline investigation in 1991-94 were thawed and analyzed with flow cytometry to enumerate monocyte subsets based on CD14 and CD16 expression. The percentage and number of classical CD14(++)CD16(-) monocytes were increased in the cardiovascular-event group compared to the event-free subjects (median 69% (inter-quartile range 62-76)% vs. 67 (59-72)%, p=0.017; 344 (251-419) cells/μL vs. 297 (212-384) cells/μL, p=0.003). The hazard ratio was 1.66 for suffering a cardiovascular event in the highest tertile of the number of CD14(++)CD16(-) monocytes compared to the lowest tertile even after adjustment for common risk factors (HR 1.66, 95%CI: 1.02-2.72). CD14(++)CD16(-) monocytes did not, however, associate with the extent of atherosclerosis at baseline. In contrast, the percentage of monocytes expressing CD16 was negatively associated to the extent of carotid atherosclerosis measured as intima-media thickness (IMT) at baseline. The chemokine receptors CCR2, CX3CR1 and CCR5 were not differentially expressed between cases and controls on any of the monocyte subsets, but CCR5 expression on CD14(+)CD16(++) monocytes was negatively associated to carotid IMT. CONCLUSIONS: -This study shows that classical CD14(++)CD16(-) monocytes can predict future cardiovascular risk independently of other risk factors in a randomly selected population.},
  author       = {Berg, Katarina and Ljungcrantz, Irena and Andersson, Linda and Bryngelsson, Carl and Hedblad, Bo and Nordin Fredrikson, Gunilla and Nilsson, Jan and Björkbacka, Harry},
  issn         = {1942-325X},
  keyword      = {ischemic stroke,myocardial infarction,cardiovascular disease,monocytes,leukocytes},
  language     = {eng},
  number       = {1},
  pages        = {122--131},
  publisher    = {American Heart Association},
  series       = {Circulation: Cardiovascular Genetics},
  title        = {Elevated CD14++CD16- Monocytes Predict Cardiovascular Events.},
  url          = {http://dx.doi.org/10.1161/CIRCGENETICS.111.960385},
  volume       = {5},
  year         = {2012},
}