Key result
Higher M-CSF levels are linked to a ~51% lower risk of first-time acute coronary events.
Why the study?
The associations between plasma levels of growth factors and chemokines regulating myeloid cell homeostasis and the risk of first-time acute coronary events in middle-aged persons were unclear.
Are plasma levels of macrophage colony-stimulating factor and monocyte chemotactic protein 1 associated with the risk of first-time acute coronary events in middle-aged persons?
Case-Control (n=658)
No
Are plasma levels of macrophage colony-stimulating factor and monocyte chemotactic protein 1 associated with the risk of first-time acute coronary events in middle-aged persons?
Hazard Ratio: 0.49 (95% CI 0.41–0.6)
p-value: p=3.5x10^-13
High levels of macrophage colony-stimulating factor and low levels of monocyte chemotactic protein 1 in plasma are associated with a lower risk of developing clinically manifested coronary artery disease and improve risk prediction beyond traditional risk factors.
BACKGROUND: 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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Șchiopu et al. (2016) conducted a case-control in First-time acute coronary events (n=658). Macrophage colony-stimulating factor (M-CSF) and monocyte chemotactic protein 1 (MCP-1) vs. Lower levels of M-CSF and MCP-1 was evaluated on Incident first-time acute coronary events (HR 0.49, 95% CI 0.41-0.60, p=3.5x10^-13). Higher plasma levels of macrophage colony-stimulating factor (HR 0.49) and lower levels of monocyte chemotactic protein 1 (HR 2.06) were independently associated with a reduced risk of first-time acute coronary events.
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