| 31. |
- Latini, R., et al.
(författare)
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Pentraxin-3 in chronic heart failure: the CORONA and GISSI-HF trials
- 2012
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Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 14:9, s. 992-999
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Tidskriftsartikel (refereegranskat)abstract
- Pentraxin-3 (PTX3) is a component of the humoral arm of innate immunity which can regulate inflammatory processes. Since the role of inflammation in the progression of chronic heart failure (HF) is debated, we investigated the prognostic value of PTX3 and the effect of a statin in two large populations of patients with HF. Plasma levels of PTX3 were measured at randomization and after 3 months in 1457 patients enrolled in the Controlled Rosuvastatin Multinational Trial in HF (CORONA) and 1233 patients enrolled in the GISSI-Heart Failure trial (GISSI-HF). The relationships between baseline PTX3 levels or their changes over time and mortality were evaluated with multivariable Cox proportional hazard models including clinical factors, high sensitivity C-reactive protein (hsCRP), and N-terminal pro brain natriuretic peptide (NT-proBNP). PTX3 concentration [median (Q1Q3) 5.34 (3.557.64) ng/mL, n 2690] was higher in females, in older patients, and those with lower body mass index. Baseline elevated PTX3 was associated with a higher risk of all-cause mortality [759 events, hazard ratio (HR) for 1 SD increase 1.20, 95 confidence interval (CI) 1.121.30, P 0.0001], cardiovascular mortality (587 events, HR 1.27, 95 CI 1.171.38, P 0.0001), or hospitalization for worsening HF (720 events, HR 1.21, 95 CI 1.121.30, P 0.0001), and marginally improved discrimination. Three-month changes in PTX3 were associated with fatal events after adjustment for hsCRP or NT-proBNP. Rosuvastatin lowered hsCRP levels but significantly raised PTX3. In two independent clinical trials that enrolled patients with chronic HF, PTX3 was consistently associated with outcomes. The opposite effects of a statin on hsCRP and PTX3 call for further investigation. NCT00336336 (GISSI-HF), NCT00206310 (CORONA).
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| 37. |
- Nymo, S. H., et al.
(författare)
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Inflammatory cytokines in chronic heart failure: interleukin-8 is associated with adverse outcome. Results from CORONA
- 2014
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Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842. ; 16:1, s. 68-75
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Tidskriftsartikel (refereegranskat)abstract
- Aim We investigated the ability of prototypical inflammatory cytokines to predict clinical outcomes in a large population of patients with chronic systolic heart failure (HF). Methods and results Serum levels of tumour necrosis factor-alpha (TNF-alpha), 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-alpha, 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. Conclusion 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.
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| 38. |
- Nymo, S. H., et al.
(författare)
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The association between neutrophil gelatinase-associated lipocalin and clinical outcome in chronic heart failure: Results from CORONA
- 2012
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 271, s. 436-443
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To study the prognostic value of neutrophil gelatinase-associated lipocalin (NGAL) in chronic heart failure (HF) of ischaemic aetiology. Background. Neutrophil gelatinase-associated lipocalin is a marker of kidney injury as well as matrix degradation and inflammation and has previously been shown to be increased in HF. We investigated whether serum NGAL levels could provide prognostic information in chronic HF. Methods. We assessed NGAL as a predictor of primary outcomes (cardiovascular death, nonfatal stroke and nonfatal myocardial infarction, n=307) and all-cause mortality (n=321), cardiovascular mortality (n=259) and hospitalization (n=647) as well as the number of hospitalizations during follow-up for all (n=1934) and CV causes (n=1204) in 1415 patients with chronic HF (≥60years, New York Heart Association class II-IV, ischaemic systolic HF) in the CORONA population, randomly assigned to 10mg rosuvastatin or placebo. Results. Multivariate analysis revealed that NGAL added significant information when adjusting for clinical variables, but was no longer significant when further adjusting for apolipoprotein A-1 (ApoA-1), glomerular filtration rate (GFR), C-reactive protein (CRP) and N-terminal pro-brain natriuretic peptide (NT-proBNP). However, belonging to the highest NGAL tertile was associated with more frequent hospitalization, even after adjusting for clinical variables, GFR and ApoA-1, but not after adjusting for CRP and NT-proBNP. There was no interaction between rosuvastatin treatment and NGAL. Conclusion. Neutrophil gelatinase-associated lipocalin added no significant information to NT-proBNP and GFR in a multivariate model for primary and secondary end-points. © 2012 The Association for the Publication of the Journal of Internal Medicine.
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| 40. |
- Nymo, St., et al.
(författare)
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Serum neutrophil gelatinase-associated lipocalin (NGAL) concentration is independently associated with mortality in patients with acute coronary syndrome.
- 2018
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Ingår i: International journal of cardiology. - : Elsevier BV. - 1874-1754 .- 0167-5273. ; 262, s. 79-84
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Tidskriftsartikel (refereegranskat)abstract
- Circulating neutrophil gelatinase-associated lipocalin (NGAL) concentration increases in cardiovascular disease, but the long-term prognostic value of NGAL concentration has not been evaluated in acute coronary syndrome (ACS). We examined the association between NGAL concentration and prognosis in patients with ACS after non-ST-elevation myocardial infarction (NSTEMI) or STEMI.NGAL concentration was measured in blood from 1121 consecutive ACS patients (30% women, mean age 65years) on the first morning after admission. After adjustment for 14 variables, NGAL concentration predicted long-term (median 167months) mortality (hazard ratio [HR] 1.33, 95% confidence interval [CI] 1.10-1.61, P=0.003) for quartile (q) 4 of NGAL concentration. NGAL concentrations also predicted long-term mortality (HR=1.63, 95% CI 1.31-2.03, P<0.001, N=741) when adjusting for Global Registry of Acute Coronary Events (GRACE) score, left ventricular ejection fraction (LVEF), and pro-B-type natriuretic peptide (proBNP) and C-reactive protein (CRP) concentrations. With these adjustments, NGAL concentration predicted long-term mortality in NSTEMI patients (HR=2.02, 95% CI 1.50-2.72, P<0.001) but not in STEMI patients (HR=1.32, 95% CI 0.95-1.83, P=0.100). In all patients, the combination of NGAL concentration and GRACE score yielded an HR of 5.56 (95% CI 4.37-7.06, P<0.001) for q4/q4 for both variables.NGAL concentration in ACS is associated with long-term prognosis after adjustment for clinical confounders. Measuring circulating NGAL concentration may help to identify patients-particularly those with NSTEMI-needing closer follow-up after ACS.
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