Abstract 1948: Monocyte Chemoattractant Protein 1 And Macrophage Colony Stimulating Factor Are Markers Of Adverse Outcome In Heart Failure Patients.
Introduction: Recruitment and differentiation of progenitor cells may play an important role in the repair of injured myocardium. Granulocyte colony stimulating factor (G-CSF) is an important mobilization factor for hematopoietic progenitor cells, whereas monocyte chemoattractant protein 1 (MCP-1) and macrophage colony stimulating factor (M-CSF) are essential cytokines for recruitment and survival of monocytic progenitor cells and macrophages.
Methods: G-CSF, MCP-1 and M-CSF protein was determined in baseline plasma of 360 patients (mean age 72±13 years) with advanced heart failure with a mean BNP 678.98 ± 760.45 pg/ml and LVEF of 28.8 ± 10% by specific ELISAs. 35% of the patients were females. During a median follow up period of 16 month (confidence interval (CI): 15–17) 92 patients died (26%), death was used as endpoint.
Results: While plasma levels of G-CSF were not significantly different in the event group (25.55±21.37 vs. 27.95±20.25 pg/ml; P=0.064) MCP-1 (103.54 ± 76.81 vs. 87.46 ± 64.18 pg/ml; P=0.036) and M-CSF (659.5±413.13 vs. 434.25±343.88 pg/ml; P<0.001) were significantly higher in the event group compared to the event-free group. Univariate Cox regression analysis showed a trend for a protective effect of G-CSF with a crude proportional hazard ratio (HR) of 0.70 (95% CI: 0.42–1.15, P=0.161) and a significant harmful effect of MCP-1 with a HR of 1.78 (95% CI: 1.04–3.04, P=0.035) for death comparing third to first tertile. Furthermore, we found a significant gradual increase of risk for death with concentrations of M-CSF with a HR of 2.31 (95% CI: 1.31– 4.06, P=0.004) between the second and the first tertile and a HR of 2.64 (95% CI: 1.51– 4.62, P=0.001) between the third and the first tertile. Applying multivariable analysis (including clinical variables and BNP) the HR was 1.84 for MCP-1 (95% CI: 1.05–3.23, P=0.033) and 1.89 for M-CSF (95% CI: 1.05–3.4, P=0.033) comparing third to first tertile.
Conclusion: Our results indicate that higher plasma levels of MCP-1 and M-CSF are associated with a higher rate of mortality in heart failure and could serve as independent markers besides BNP. Therefore we speculate that a prolonged activation of monocytes and macrophages could have detrimental effects on the injured myocardium.