The impact of CD4+CD28null T-lymphocytes on atrial fibrillation and mortality in patients with chronic heart failure

Thromb Haemost. 2017 Jan 26;117(2):349-356. doi: 10.1160/TH16-07-0531. Epub 2016 Dec 1.

Abstract

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.

Keywords: CD4+CD28null cells; atrial fibrillation; heart failure; mortality.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Atrial Fibrillation / blood
  • Atrial Fibrillation / diagnosis
  • Atrial Fibrillation / immunology*
  • Atrial Fibrillation / mortality
  • Biomarkers / blood
  • CD28 Antigens / blood*
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Separation / methods
  • Chronic Disease
  • Female
  • Flow Cytometry
  • Heart Failure / blood
  • Heart Failure / diagnosis
  • Heart Failure / immunology*
  • Heart Failure / mortality
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Phenotype
  • Predictive Value of Tests
  • Prognosis
  • Proportional Hazards Models
  • Prospective Studies
  • Risk Factors
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism
  • Time Factors

Substances

  • Biomarkers
  • CD28 Antigens