Abstract 22: Monocyte Chemotactic Protein-1 and Macrophage Colony-Stimulating Factor Are Strong Predictors of First-Time Myocardial Infarction in the General Population
Objective: Monocytes/macrophages and neutrophils play important roles in the pathogenesis of cardiovascular disease. We hypothesized that mediators governing myeloid cell homeostasis might help predict the incidence of first-time acute myocardial infarction (AMI).
Methods: We included 385 individuals who suffered an AMI during a median follow-up of 15.2 years, and 401 age and sex-matched controls that remained event free, recruited from the Malmö Diet and Cancer Study cohort. The participants had no documented coronary artery disease previous to inclusion. We performed parallel measurements of monocyte chemotactic protein-1 (MCP-1), macrophage colony-stimulating factor (M-CSF), CCL3, CCL4, CCL20, CXCL1, CXCL16, and CX3CL1 in plasma samples collected at baseline, by using a Proximity Ligation Assay.
Results: MCP-1 presented a strong positive correlation (HR (95% CI): 2.07 (1.77-2.43), p<0.001), whereas M-CSF had a strong negative correlation with incident AMI (HR (95% CI): 0.49 (0.41-0.58), p<0.001). These relationships were independent of the classic Framingham risk factors (age, ex, smoking, total cholesterol, HDL, systolic blood pressure), diabetes, CRP, and of the other considered myeloid biomarkers. Addition of MCP-1 and M-CSF significantly improved the predictive ability of a model including the Framingham risk factors alone (c-statistic 0.82 [95% CI 0.78-0.85] with MCP-1 and M-CSF vs. 0.66 [95% CI 0.62-0.70], P<0.05). Addition of MCP-1 and M-CSF to the risk model led to a net reclassification improvement (NRI) of 0.51 (95% CI 0.42-0.60), and an integrated discrimination improvement (IDI) of 0.19 (95% CI 0.16-0.21). The model including MCP-1 and M-CSF was particularly effective in controls, leading to a 65% net re-classification into lower risk categories, and in subjects within the intermediate risk group (10-20%), where 70% of individuals were correctly up or down re-classified.
Conclusion: MCP-1 and M-CSF have opposite relationships with the risk for AMI in the general population. Addition of MCP-1 and M-CSF significantly improves the predictive power of the Framingham risk model, leading to correct re-classification of a high percentage of individuals, particularly in the intermediate risk group.
Author Disclosures: A. Schiopu: None. E. Bengtsson: None. I. Goncalves: None. J. Nilsson: None. G. Nordin Fredrikson: None. H. Björkbacka: None.
- © 2015 by American Heart Association, Inc.