Abstract 17645: Predictive Power ff the Fractalkine Receptor CX3CR1 on CD4 T Cells in Patients With Chronic Heart Failure
Objective: Increasing evidence identified activation of the immune system characterized by enhanced release of pro-inflammatory cytokines and activation of immune cells as important mediator in the complex pathophysiology of chronic heart failure (CHF). Chemokines thereby mediate leukocyte trafficking to the site of affected tissue. In this respect, the fractalkine (FKN)/CX3CR1-axis has been shown to be crucially involved in the pathophysiology of several cardiovascular diseases. However, no data exist about the role of CX3CR1-expression on CD4 T cells in CHF. We therefore aimed to assess the prognostic impact of CD4+CX3CR1+ cells on mortality in patients with CHF.
Approach and Results: Circulating lymphocytes from 105 CHF patients were analyzed for the distribution of CD4 subsets and expression of CX3CR1 by flow cytometry. Cox regression models were used to assess the influence of T cells cells on survival.. During a median follow-up of 23 months 19% of patients (n=20) died. CD4+CX3CR1+ cells independently predicted all-cause mortality with an adjusted hazard ratio (HR) of 2.28 (95% confidence interval [CI]: 1.48-3.52, P<0.001) and cardiovascular mortality with an adj. HR of 2.15 (95% CI: 1.35-3.42, P=0.001), respectively . No difference in their predictive value was found between patients with ischemic and non-ischemic etiology of CHF (for interaction, P=0.418). In contrast, increased frequencies of the entire CD4 T cell population revealed protective effects on survival with a HR of 0.58 (95% CI: 0.39-0.88, P=0.01) in univariate analysis, but lost significance after multivariable adjustment.
Conclusion: The strong impact of circulating CD4+CX3CR1+ cells on mortality indicates a potential role of these CD4 effector cells in the progression of CHF. Activation of the fractalkine(FKN)/CX3CR1-axis under the condition of the failing heart may direct these cytotoxic immune cells to the myocardium with potentially detrimental impact on myocardial integrity. [[Unable to Display Character: ]]
- © 2013 by American Heart Association, Inc.