Associations Between Macrophage Colony-Stimulating Factor and Monocyte Chemotactic Protein 1 in Plasma and First-Time Coronary Events: A Nested Case-Control Study.
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.



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.



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.
Department of Clinical Sciences Malmö, Lund University, Sweden Cardiology Unit, Skane University Hospital, Malmö, Sweden alexandru.schiopu@med.lu.se.
Alexandru
A
Schiopu
Department of Clinical Sciences Malmö, Lund University, Sweden.
Eva
E
Bengtsson
Department of Clinical Sciences Malmö, Lund University, Sweden Cardiology Unit, Skane University Hospital, Malmö, Sweden.
Isabel
I
Gonçalves
Department of Clinical Sciences Malmö, Lund University, Sweden.
Jan
J
Nilsson
Department of Clinical Sciences Malmö, Lund University, Sweden.
Gunilla Nordin
GN
Fredrikson
Department of Clinical Sciences Malmö, Lund University, Sweden.
Harry
H
Björkbacka
D000368:Aged; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000097:blood*; D054418:Chemokine CCL20 / Q000097:blood; D054405:Chemokine CCL3 / Q000097:blood; D054407:Chemokine CCL4 / Q000097:blood; D054428:Chemokine CX3CL1 / Q000097:blood; D054360:Chemokine CXCL1 / Q000097:blood; D000075743:Chemokine CXCL16 / Q000097:blood; D054427:Chemokine CXCL6 / Q000097:blood; D015331:Cohort Studies; D005260:Female; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000453:epidemiology; D017202:Myocardial Ischemia / Q000097:blood* / Q000401:mortality; D016016:Proportional Hazards Models; D013548:Sweden / Q000453:epidemiology
C111835:CCL2 protein, human; C108355:CCL20 protein, human; C515429:CCL3 protein, human; C066507:CCL4 protein, human; C515538:CX3CL1 protein, human; C475829:CXCL1 protein, human; C423727:CXCL16 protein, human; C515503:CXCL6 protein, human; D018932:Chemokine CCL2; D054418:Chemokine CCL20; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D054428:Chemokine CX3CL1; D054360:Chemokine CXCL1; D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6; D016173:Macrophage Colony-Stimulating Factor
coronary artery disease; inflammation; innate immunity; leukocytes; macrophage colony‐stimulating factor; monocyte chemotactic protein 1