title: Impaired resolution of inflammation in human chronic heart failure.
abstract: BACKGROUND
  Lipoxins (LXs) are proresolving and anti-inflammatory eicosanoids whose role in chronic heart failure (CHF) pathogenesis has never been investigated. This study evaluated levels of LXs in CHF patients, its relationship with disease severity and correlation with established CHF biomarkers. The effect of low-dose aspirin [acetylsalicylic acid (ASA)] on the levels of LXs was also studied.
  
  
  METHODS
  Lipoxin A4 (LXA4 ), 15-epi-lipoxin A4 (15-epi-LXA4 ) and myeloperoxidase (MPO) concentration and activity were evaluated by immunoenzymatic and spectrophotometric assays in 34 CHF patients [New York Heart Association (NYHA) functional class I to IV]. B-type natriuretic peptide (BNP), troponin, myoglobin, C-reactive protein (CRP) and uric acid (UA) were also analyzed.
  
  
  RESULTS
  Patients were stratified into mild-to-moderate CHF (NYHA, classes I and II) and severe CHF (NYHA classes III and IV). Severe patients had lower plasma LXA4 (0·262 ± 0·034 vs. 0·362 ± 0·039 ng/mL, P < 0·05) and decreased urinary 15-epi-LXA4 levels (2·28 ± 0·44 vs. 4·88 ± 1·03 μg/day, P < 0·05) besides exhibiting increased plasma BNP (1464 ± 442 vs. 555 ± 162 pg/mL, P < 0·05) and MPO activity (45·15 ± 11·56 vs. 15·90 ± 2·80 μmol/min/mg protein, P < 0·05). Plasma LXA4 was inversely correlated with BNP, troponin, myoglobin, CRP, UA and MPO activity. ASA treatment was associated with higher urinary excretion of 15-epi-LXA4 (7·70 ± 1·48 vs. 2·06 ± 0·30 μg/day, P < 0·05) in mild-to-moderate CHF patients and lower BNP levels in both groups.
  
  
  CONCLUSIONS
  Higher severity of CHF is associated with reduced levels of LXs. Plasma LXA4 appears to be a valuable marker for risk stratification in CHF. Furthermore, the ASA-related increase in urinary 15-epi-LXA4 suggests enhanced renal synthesis of this eicosanoid and may represent a disregarded benefit of ASA.
authors.affiliation: Departamento de Farmacologia e Terapêutica, Faculdade de Medicina da Universidade do Porto, Porto, Portugal; MedInUP - Centro de Investigação Farmacológica e Inovação Medicamentosa, Universidade do Porto, Porto, Portugal; Departamento de Medicina Interna, Centro Hospitalar São João, Porto, Portugal.
authors.forename: Marta
authors.initials: M
authors.lastname: Reina-Couto
authors.forename: Jorge
authors.initials: J
authors.lastname: Carvalho
authors.forename: Maria João
authors.initials: MJ
authors.lastname: Valente
authors.forename: Luís
authors.initials: L
authors.lastname: Vale
authors.forename: Joana
authors.initials: J
authors.lastname: Afonso
authors.forename: Félix
authors.initials: F
authors.lastname: Carvalho
authors.forename: Paulo
authors.initials: P
authors.lastname: Bettencourt
authors.forename: Teresa
authors.initials: T
authors.lastname: Sousa
authors.forename: António
authors.initials: A
authors.lastname: Albino-Teixeira
mesh_terms: D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology; D015415:Biomarkers / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000209:etiology; D002908:Chronic Disease; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology; D006333:Heart Failure / Q000209:etiology*; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D007958:Leukocyte Count; D044045:Lipoxins / Q000378:metabolism*; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D012307:Risk Factors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D044045:Lipoxins; C040527:lipoxin A4; D009195:Peroxidase; D001241:Aspirin
keywords: Aspirin; biomarkers; chronic heart failure; lipoxins; resolution of inflammation