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Associations between macrophage colony-stimulating factor and monocyte chemotactic protein 1 in plasma and first-time coronary events : A Nested case-control Study

Schiopu, Alexandru LU orcid ; Bengtsson, Eva LU orcid ; Goncalves, Isabel LU orcid ; Nilsson, Jan LU ; Fredrikson, Gunilla Nordin LU and Björkbacka, Harry LU orcid (2016) In Journal of the American Heart Association 5(9).
Abstract

Myeloid cells play a central role in atherosclerosis. We investigated the associations between the plasma levels of growth factors and chemokines that regulate myeloid cell homeostasis and function and the risk of first-time acute coronary events in middle-aged persons. Methods and Results-We measured baseline plasma levels of macrophage colony-stimulating factor monocyte chemotactic protein 1; C-C motif chemokine ligands 3, 4, and 20; C-X-C motif chemokine ligands 1, 6, and 16; and C-X3-C motif chemokine ligand 1 in 292 participants who had a coronary event during follow-up and 366 controls matched for age, sex, and time of inclusion who remained event free. Study participants were recruited from the Malmö Diet and Cancer Study... (More)

Myeloid cells play a central role in atherosclerosis. We investigated the associations between the plasma levels of growth factors and chemokines that regulate myeloid cell homeostasis and function and the risk of first-time acute coronary events in middle-aged persons. Methods and Results-We measured baseline plasma levels of macrophage colony-stimulating factor monocyte chemotactic protein 1; C-C motif chemokine ligands 3, 4, and 20; C-X-C motif chemokine ligands 1, 6, and 16; and C-X3-C motif chemokine ligand 1 in 292 participants who had a coronary event during follow-up and 366 controls matched for age, sex, and time of inclusion who remained event free. Study participants were recruited from the Malmö Diet and Cancer Study population cohort and had no previous history of coronary artery disease. We found a strong independent negative association between macrophage colony-stimulating factor and incident coronary events in a forward stepwise Cox proportional hazards model including all biomarkers alongside the classic Framingham risk factors (age, sex, smoking, total cholesterol, high-density lipoprotein cholesterol, systolic blood pressure), diabetes mellitus, and medication. Conversely, monocyte chemotactic protein 1 had the strongest independent positive association with the outcome. The addition of macrophage colony-stimulating factor and monocyte chemotactic protein 1 significantly improved the predictive ability of a model including traditional risk factors alone (C statistic 0.81 [95% CI 0.78-0.84] versus 0.67 [95% CI 0.63-0.71]; net reclassification index 0.52 [0.42-0.62]; P<0.001). The combined model led to a 54% net downclassification of participants who did not have a coronary event during follow-up and was particularly effective in the intermediate-risk group. Conclusions-High levels of macrophage colony-stimulating factor and low levels of monocyte chemotactic protein 1 in plasma characterize middle-aged persons at low risk to develop clinically manifested coronary artery disease.

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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Coronary artery disease, Inflammation, Innate immunity, Leukocytes, Macrophage colony-stimulating factor, Monocyte chemotactic protein 1
in
Journal of the American Heart Association
volume
5
issue
9
article number
e002851
publisher
Wiley-Blackwell
external identifiers
  • scopus:85019144976
  • pmid:27625345
  • wos:000386716900005
ISSN
2047-9980
DOI
10.1161/JAHA.115.002851
language
English
LU publication?
yes
id
03c1e596-376f-4df9-8a2e-e063565a273e
date added to LUP
2017-06-07 11:49:46
date last changed
2025-02-17 17:55:55
@article{03c1e596-376f-4df9-8a2e-e063565a273e,
  abstract     = {{<p>Myeloid cells play a central role in atherosclerosis. We investigated the associations between the plasma levels of growth factors and chemokines that regulate myeloid cell homeostasis and function and the risk of first-time acute coronary events in middle-aged persons. Methods and Results-We measured baseline plasma levels of macrophage colony-stimulating factor monocyte chemotactic protein 1; C-C motif chemokine ligands 3, 4, and 20; C-X-C motif chemokine ligands 1, 6, and 16; and C-X3-C motif chemokine ligand 1 in 292 participants who had a coronary event during follow-up and 366 controls matched for age, sex, and time of inclusion who remained event free. Study participants were recruited from the Malmö Diet and Cancer Study population cohort and had no previous history of coronary artery disease. We found a strong independent negative association between macrophage colony-stimulating factor and incident coronary events in a forward stepwise Cox proportional hazards model including all biomarkers alongside the classic Framingham risk factors (age, sex, smoking, total cholesterol, high-density lipoprotein cholesterol, systolic blood pressure), diabetes mellitus, and medication. Conversely, monocyte chemotactic protein 1 had the strongest independent positive association with the outcome. The addition of macrophage colony-stimulating factor and monocyte chemotactic protein 1 significantly improved the predictive ability of a model including traditional risk factors alone (C statistic 0.81 [95% CI 0.78-0.84] versus 0.67 [95% CI 0.63-0.71]; net reclassification index 0.52 [0.42-0.62]; P&lt;0.001). The combined model led to a 54% net downclassification of participants who did not have a coronary event during follow-up and was particularly effective in the intermediate-risk group. Conclusions-High levels of macrophage colony-stimulating factor and low levels of monocyte chemotactic protein 1 in plasma characterize middle-aged persons at low risk to develop clinically manifested coronary artery disease.</p>}},
  author       = {{Schiopu, Alexandru and Bengtsson, Eva and Goncalves, Isabel and Nilsson, Jan and Fredrikson, Gunilla Nordin and Björkbacka, Harry}},
  issn         = {{2047-9980}},
  keywords     = {{Coronary artery disease; Inflammation; Innate immunity; Leukocytes; Macrophage colony-stimulating factor; Monocyte chemotactic protein 1}},
  language     = {{eng}},
  number       = {{9}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Journal of the American Heart Association}},
  title        = {{Associations between macrophage colony-stimulating factor and monocyte chemotactic protein 1 in plasma and first-time coronary events : A Nested case-control Study}},
  url          = {{http://dx.doi.org/10.1161/JAHA.115.002851}},
  doi          = {{10.1161/JAHA.115.002851}},
  volume       = {{5}},
  year         = {{2016}},
}