CD4+ CD28(null) cells are an independent predictor of mortality in patients with heart failure.

ABSTRACT

AIMS: Immune activation and subsequent release of proinflammatory cytokines plays a central role in the pathophysiology of chronic heart failure (CHF). Cytotoxic CD4(+)CD28(null) cells are generated under inflammatory conditions and implicated in a variety of pathological processes like atherosclerosis and autoimmune diseases. The study aim was to assess the impact of CD4(+)CD28(null) cells on survival in CHF patients. METHODS AND RESULTS: Circulating lymphocytes from 107 CHF patients were analyzed for the distribution of CD4 subsets by flow cytometry. During a median follow-up of 23 months, 22 (20%) persons died. CD4(+)CD28(null) 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. Further, we found a significant association with NT-proBNP (r = 0.23). CONCLUSION: Circulating CD4(+)CD28(null) cells are associated with CHF severity and are a strong and independent predictor of mortality in CHF fostering the implication of the immune system in CHF pathophysiology.