Abstract 17545: CD4+CD28null Cells Are an Independent Predictor of Mortality in Patients With Heart Failure
Purpose: Immune activation and subsequent release of proinflammatory cytokines plays a central role in the pathophysiology of chronic heart failure (CHF). Cytotoxic CD4+CD28null cells are rarely found in healthy persons but expand dramatically under inflammatory conditions and therefore are implicated in a variety of pathological processes like atherosclerosis and autoimmune diseases. The study aim was to assess the impact of CD4+CD28null cells on survival in CHF patients.
Methods: Circulating lymphocytes from 107 CHF patients were analyzed for the distribution of CD4 subsets by flow cytometry. The presence of CHF was defined by NYHA functional class ≥ II and either left ventricular ejection fraction (LVEF) or pro-BNP >500 pg/ml. Cox regression models were used to assess the influence of CD4+CD28null T cells on survival. The multivariable model was adjusted for age, gender, CHF etiology, NYHA functional class, diabetes, NT-proBNP and estimated glomerular filtration rate (eGFR).
Results: During a median follow-up of 23 months, 22 (20%) persons died including 17 deaths due to cardiovascular causes. CD4+CD28null cells independently predicted all-cause mortality with an adjusted hazard ratio (HR) of 1.88 per 1-standard deviation increase (95% confidence interval (CI): 1.26-2.79, p=0.002) and with a HR of 1.83 for cardiovascular mortality (95%CI: 1.18-2.86, p=0.008), respectively. The 2-year survival rate was 68% in patients with CD4+CD28null cells >10% compared to 86% in the remaining patients (p=0.046). The effect of CD4+CD28null cells on mortality was not affected by CHF etiology (for interaction, p=0.87). Further, we found significant associations with NT-proBNP (r=0.23, p=0.016), chronic obstructive pulmonary disease (p=0.041) and diabetes (p=0.024) as well as an inverse correlation with eGFR (r=-0.26, P=0.007).
Conclusion: Circulating CD4+CD28null cells are associated with CHF severity and represent a strong and independent predictor of mortality in CHF fostering the implication of the immune system in CHF pathophysiology. The predictive value of CD4+CD28null cells in CHF patients points towards chronic antigenic stimulation with adverse functional consequences for cardiac tissue.
- © 2013 by American Heart Association, Inc.