Impaired resolution of inflammation in human chronic heart failure

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. Materials and methods Lipoxin A(4) (LXA(4)), 15-epi-lipoxin A(4) (15-epi-LXA(4)) 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 LXA(4) (0.262 +/- 0.034 vs. 0.362 +/- 0.039ng/mL, P<0.05) and decreased urinary 15-epi-LXA(4) levels (2.28 +/- 0.44 vs. 4.88 +/- 1.03 mu g/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 mu mol/min/mg protein, P<0.05). Plasma LXA(4) was inversely correlated with BNP, troponin, myoglobin, CRP, UA and MPO activity. ASA treatment was associated with higher urinary excretion of 15-epi-LXA(4) (7.70 +/- 1.48 vs. 2.06 +/- 0.30g/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 LXA(4) appears to be a valuable marker for risk stratification in CHF. Furthermore, the ASA-related increase in urinary 15-epi-LXA(4) suggests enhanced renal synthesis of this eicosanoid and may represent a disregarded benefit of ASA.