The association between neutrophil gelatinase-associated lipocalin and clinical outcome in chronic heart failure: results from CORONA

Authors

  • S. H. Nymo,

    1. From the Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet
    2. Centre for Heart Failure Research
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  • T. Ueland,

    1. From the Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet
    2. Faculty of Medicine, University of Oslo
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  • E. T. Askevold,

    1. From the Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet
    2. Centre for Heart Failure Research
    3. Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo
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  • T. H. Flo,

    1. Department of Cancer Research and Molecular Medicine, Norwegian University of Technology and Science, Trondheim, Norway
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  • J. Kjekshus,

    1. Centre for Heart Failure Research
    2. Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo
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  • J. Hulthe,

    1. Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska Academy, Gothenburg University, Gothenburg
    2. AstraZeneca, Mölndal, Sweden
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  • J. Wikstrand,

    1. Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska Academy, Gothenburg University, Gothenburg
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  • J. McMurray,

    1. BHF Glasgow Cardiovascular Research Centre, University of Glasgow, UK
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  • D. J. Van Veldhuisen,

    1. Department of Cardiology, Thoraxcenter, University Medical Center Groningen, University of Groningen, The Netherlands
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  • L. Gullestad,

    1. Centre for Heart Failure Research
    2. Faculty of Medicine, University of Oslo
    3. Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo
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  • P. Aukrust,

    1. From the Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet
    2. Faculty of Medicine, University of Oslo
    3. Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway
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  • A. Yndestad

    1. From the Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet
    2. Centre for Heart Failure Research
    3. Faculty of Medicine, University of Oslo
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  • AstraZeneca, Mölndal, Sweden sponsored the CORONA trial.

Ståle H. Nymo, BSc, Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, 0424 Oslo, Norway.
(fax: +47-23073630; e-mail: snymo@rr-research.no).

Abstract

Abstract.  Nymo SH, Ueland T, Askevold ET, Flo TH, Kjekshus J, Hulthe J, Wikstrand J, McMurray J, Van Veldhuisen DJ, Gullestad L, Aukrust P, Yndestad A (Oslo University Hospital Rikshospitalet; University of Oslo; Oslo; Norwegian University of Technology and Science, Trondheim, Norway; Gothenburg University, Gothenburg; AstraZeneca, Mölndal, Sweden; University of Glasgow, UK; and University Medical Center Groningen, University of Groningen, The Netherlands). The association between neutrophil gelatinase-associated lipocalin and clinical outcome in chronic heart failure: results from CORONA. J Intern Med 2012; 271: 436–443.

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, = 307) and all-cause mortality (= 321), cardiovascular mortality (= 259) and hospitalization (= 647) as well as the number of hospitalizations during follow-up for all (= 1934) and CV causes (= 1204) in 1415 patients with chronic HF (≥60 years, New York Heart Association class II–IV, ischaemic systolic HF) in the CORONA population, randomly assigned to 10 mg 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.

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