title: Inflammatory cytokines in chronic heart failure: interleukin-8 is associated with adverse outcome. Results from CORONA.
abstract: OBJECTIVE
  We investigated the ability of prototypical inflammatory cytokines to predict clinical outcomes in a large population of patients with chronic systolic heart failure (HF).
  
  
  RESULTS
  Serum levels of tumour necrosis factor-α (TNF-α), soluble TNF receptors type I and II (sTNF-RI and sTNF-RII), and the chemokines monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) were analysed in 1464 patients with chronic ischaemic systolic HF in the CORONA study, aged ≥ 60 years, in NYHA class II-IV, and related to the primary endpoint (n = 320), as well as any coronary event (n = 255), all-cause mortality (n = 329), cardiovascular (CV) mortality (n = 268), and the composite endpoint hospitalization from worsening heart failure (WHF) or CV mortality (n = 547). TNF-α, sTNF-RI, sTNF-RII, and IL-8, but not MCP-1, were independent predictors of all endpoints except the coronary endpoint in multivariable models including conventional clinical variables. After further adjustment for estimated glomerular filtration rate, the ApoB/ApoA-1 ratio, NT-proBNP, and high-sensitivity C-reactive protein, only IL-8 remained a significant predictor of all endpoints (except the coronary endpoint), while sTNF- RI remained independently associated with CV mortality. Adding IL-8 to the full model led to a significant improvement in net reclassification for all-cause mortality and CV hospitalization, but only a borderline significant improvement for the primary endpoint, CV mortality, and the composite endpoint WHF hospitalization or CV mortality.
  
  
  CONCLUSIONS
  Our study supports a relationship between IL-8 and outcomes in patients with chronic HF. However, the clinical usefulness of IL-8 as a biomarker in an unselected HF population is at present unclear.
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Center for Heart Failure Research, University of Oslo, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Ståle H
authors.initials: SH
authors.lastname: Nymo
authors.forename: Johannes
authors.initials: J
authors.lastname: Hulthe
authors.forename: Thor
authors.initials: T
authors.lastname: Ueland
authors.forename: John
authors.initials: J
authors.lastname: McMurray
authors.forename: John
authors.initials: J
authors.lastname: Wikstrand
authors.forename: Erik T
authors.initials: ET
authors.lastname: Askevold
authors.forename: Arne
authors.initials: A
authors.lastname: Yndestad
authors.forename: Lars
authors.initials: L
authors.lastname: Gullestad
authors.forename: Pål
authors.initials: P
authors.lastname: Aukrust
mesh_terms: D015415:Biomarkers; D016207:Cytokines / Q000097:blood*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000097:blood* / Q000150:complications; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000150:complications; D016209:Interleukin-8 / Q000097:blood; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies
chemical_list: D015415:Biomarkers; D016207:Cytokines; D016209:Interleukin-8
keywords: Heart failure; Inflammation; Interleukins; Prognosis; Survival