title: Cystatin C, NT-proBNP, and inflammatory markers in acute heart failure: insights into the cardiorenal syndrome.
abstract: BACKGROUND
  Inflammation is thought to be a mediator in the pathophysiology of the cardiorenal syndrome. We evaluated the interactions between kidney function, cardiac stress, and various inflammatory cytokines in patients with acute heart failure (AHF). The effect on 1-year mortality was also assessed.
  
  
  RESULTS
  Plasma levels of cystatin C, NT-proBNP, and inflammatory cytokines (interleukin [IL]-6, tumor necrosis factor-α [TNF-α], IL-10) were measured in consecutive patients (n = 465) hospitalized for AHF. After adjustment for demographic characteristics and comorbidities, TNF-α had the strongest relation with renal function (β = 0.39, P < 0.0001). Elevated TNF-α levels were seen in patients with high cystatin C, irrespective of NT-proBNP. Levels of IL-6 (β = 0.26, P < 0.0001) and IL-10 (β = 0.15, P < 0.01), but not TNF-α, were associated with NT-proBNP. Moreover, the most elevated levels of IL-6 were seen in patients with combined high NT-proBNP and high cystatin C. Cox regression analysis found IL-6 above median to be independently predictive of mortality (hazard ratio 1.9; 95% CI 1.2-2.9, P = 0.003). TNF-α was not significantly associated with prognosis in the overall population after adjustment for multiple covariates, but improved risk stratification in the subgroup with low cystatin C and NT-proBNP.
  
  
  CONCLUSIONS
  Levels of TNF-α in AHF are related to kidney function, but not to NT-proBNP. IL-6 seems to be more associated with cardiac stress. Patients with severe dual organ dysfunction have the highest levels of IL-6 and TNF-α. Different relations of inflammatory cytokines to renal function and cardiac stress need to be considered when evaluating heart--kidney interactions.
authors.affiliation: Department of Medicine, Division of Cardiology, Helsinki University Central Hospital, Helsinki, Finland. Johan.Lassus@fimnet.fi
authors.forename: J P E
authors.initials: JP
authors.lastname: Lassus
authors.forename: V-P
authors.initials: VP
authors.lastname: Harjola
authors.forename: K
authors.initials: K
authors.lastname: Peuhkurinen
authors.forename: R
authors.initials: R
authors.lastname: Sund
authors.forename: A
authors.initials: A
authors.lastname: Mebazaa
authors.forename: K
authors.initials: K
authors.lastname: Siirilä-Waris
authors.forename: K
authors.initials: K
authors.lastname: Miettinen
authors.forename: K R
authors.initials: KR
authors.lastname: Punnonen
authors.forename: J
authors.initials: J
authors.lastname: Melin
authors.forename: K
authors.initials: K
authors.lastname: Pulkki
authors.forename: M S
authors.initials: MS
authors.lastname: Nieminen
mesh_terms: D015415:Biomarkers / Q000097:blood; D055316:Cystatin C / Q000097:blood*; D006333:Heart Failure / Q000150:complications / Q000473:pathology*; D006801:Humans; D007249:Inflammation / Q000175:diagnosis*; D015850:Interleukin-6; D007674:Kidney Diseases / Q000150:complications*; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D013577:Syndrome; D014409:Tumor Necrosis Factor-alpha
chemical_list: D015415:Biomarkers; D055316:Cystatin C; D015850:Interleukin-6; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain