title: The impact of CD4+CD28nullT-lymphocytes on atrial fibrillation and mortality in patients with chronic heart failure.
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+CD28nullcells 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+CD28nullcells proved to be predictive on outcome in CHF-patients presenting with AF. Our results might indicate a potential role of CD4+CD28nullcells in the pathogenesis of AF which needs to be confirmed in future studies.
authors.forename: Patrick
authors.initials: P
authors.lastname: Sulzgruber
authors.forename: Lorenz
authors.initials: L
authors.lastname: Koller
authors.forename: Max-Paul
authors.initials: MP
authors.lastname: Winter
authors.forename: Bernhard
authors.initials: B
authors.lastname: Richter
authors.forename: Steffen
authors.initials: S
authors.lastname: Blum
authors.forename: Magdalena
authors.initials: M
authors.lastname: Korpak
authors.forename: Martin
authors.initials: M
authors.lastname: Hülsmann
authors.forename: Georg
authors.initials: G
authors.lastname: Goliasch
authors.forename: Johann
authors.initials: J
authors.lastname: Wojta
authors.affiliation: Alexander Niessner, MD, MSc in Epidemiology, Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria, Tel.: +431404004614, Fax: +431404004216, E-mail: alexander.niessner@meduniwien.ac.at.
authors.forename: Alexander
authors.initials: A
authors.lastname: Niessner
mesh_terms: D000368:Aged; D001281:Atrial Fibrillation / Q000097:blood / Q000175:diagnosis / Q000276:immunology* / Q000401:mortality; D015415:Biomarkers / Q000097:blood; D018106:CD28 Antigens / Q000097:blood*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002469:Cell Separation / Q000379:methods; D002908:Chronic Disease; D005260:Female; D005434:Flow Cytometry; D006333:Heart Failure / Q000097:blood / Q000175:diagnosis / Q000276:immunology* / Q000401:mortality; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D013997:Time Factors
chemical_list: D015415:Biomarkers; D018106:CD28 Antigens
keywords: CD4+CD28null cells; atrial fibrillation; heart failure; mortality