RESUMO
Atrial fibrillation (AF) represents the most common cardiac arrhythmia. Especially in patients with chronic heart failure (CHF) the development of AF represents a severe complication resulting in haemodynamic deterioration. While pro-inflammatory cytokines proved to have a pivotal role in the development and progression of both AF and CHF, less attention has been paid to the cellular immunity. Therefore we prospectively enrolled 112 patients with CHF and performed fluorescein-activated cell sorting (FACS). Patients were stratified in two subgroups according to patients presenting with AF (n=56) and patients free of AF (n=56). Comparing AF to non-AF patients we found a significantly lower fraction of regulatory T cells (p<0.001) in patients presenting with AF. However there was a higher fraction of CD4+ cells (p=0.007) and more specifically a significantly higher number of cytotoxic T cells characterised by the loss of CD28 within CD4 T cells (CD4+CD28null; p=0.035) in individuals with AF. After a mean follow-up time of 4.5 years 32 (28.6 %) patients died due to cardiovascular causes. CD4+CD28null cells were significantly associated with cardiovascular mortality in patients presenting with AF, with an adjusted HR per one standard deviation (1-SD) of 1.59 (95 % CI 1.13-2.24; p=0.008), but not in patients free of AF with an adjusted HR per 1-SD of 1.27 (95 % CI 0.86-1.87; p=0.216). We found that the fraction of CD4+CD28null cells proved to be predictive on outcome in CHF-patients presenting with AF. Our results might indicate a potential role of CD4+CD28null cells in the pathogenesis of AF which needs to be confirmed in future studies.
Assuntos
Fibrilação Atrial/imunologia , Antígenos CD28/sangue , Linfócitos T CD4-Positivos/imunologia , Insuficiência Cardíaca/imunologia , Idoso , Fibrilação Atrial/sangue , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/mortalidade , Biomarcadores/sangue , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos/metabolismo , Separação Celular/métodos , Doença Crônica , Feminino , Citometria de Fluxo , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/mortalidade , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Fenótipo , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Fatores de TempoAssuntos
Linfócitos T CD4-Positivos/metabolismo , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/diagnóstico , Receptores de Quimiocinas/sangue , Idoso , Biomarcadores/sangue , Receptor 1 de Quimiocina CX3C , Doença Crônica , Feminino , Seguimentos , Insuficiência Cardíaca/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos TestesRESUMO
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.
