| Neuregulin-1 beta is associated with disease severity and adverse outcomes in chronic heart failure. | |
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MedLine Citation:
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PMID: 19597049 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Neuregulin-1 (NRG-1) is a paracrine factor released by microvascular endothelial cells that has cardioprotective effects in animal models of heart failure. However, circulating NRG-1 has not been studied in human heart disease. We used a novel immunoassay to test whether circulating NRG-1beta is associated with disease severity and clinical outcomes in chronic heart failure. METHODS AND RESULTS: Serum NRG-1beta was quantified in 899 outpatients in the Penn Heart Failure Study, a referral cohort representing a broad spectrum of systolic heart failure. Circulating NRG-1beta was significantly elevated in patients with worse disease severity (median, 6.2 ng/mL for New York Heart Association class IV versus 4.4 ng/mL for class I; P=0.002). In adjusted models, NRG-1beta was independently associated with an increased risk of death or cardiac transplantation over a median follow-up of 2.4 years (adjusted hazard ratio, 1.58; 95% confidence interval, 1.04 to 2.39; P=0.03 comparing fourth versus first NRG-1beta quartile). Associations with outcome differed by heart failure cause and symptom severity, with the strongest associations observed in patients with ischemic cardiomyopathy (interaction P=0.008) and New York Heart Association class III/IV symptoms (interaction P=0.01). These findings were all independent of brain natriuretic peptide, and assessment of NRG-1beta and brain natriuretic peptide jointly provided better risk stratification than each biomarker individually in patients with ischemic or New York Heart Association class III/IV heart failure. CONCLUSIONS: Circulating NRG-1beta is independently associated with heart failure severity and risk of death or cardiac transplantation. These findings support a role for NRG-1/ErbB signaling in human heart failure and identify serum NRG-1beta as a novel biomarker that may have clinical applications. |
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Authors:
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Bonnie Ky; Stephen E Kimmel; Radwan N Safa; Mary E Putt; Nancy K Sweitzer; James C Fang; Douglas B Sawyer; Thomas P Cappola |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2009-07-13 |
Journal Detail:
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Title: Circulation Volume: 120 ISSN: 1524-4539 ISO Abbreviation: Circulation Publication Date: 2009 Jul |
Date Detail:
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Created Date: 2009-07-28 Completed Date: 2009-08-13 Revised Date: 2011-09-26 |
Medline Journal Info:
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Nlm Unique ID: 0147763 Medline TA: Circulation Country: United States |
Other Details:
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Languages: eng Pagination: 310-7 Citation Subset: AIM; IM |
Affiliation:
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Penn Cardiovascular Institute, University of Pennsylvania School of Medicine, Philadelphia, PA, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aged Biological Markers / blood Chronic Disease Cohort Studies Female Follow-Up Studies Heart Failure / diagnosis*, mortality, therapy* Heart Transplantation Humans Male Middle Aged Neuregulin-1 / blood* Prospective Studies Severity of Illness Index* Survival Rate / trends Treatment Outcome |
| Grant Support | |
ID/Acronym/Agency:
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HL068144/HL/NHLBI NIH HHS; HL088577/HL/NHLBI NIH HHS; R01 HL068144-08/HL/NHLBI NIH HHS; R01 HL088577-02/HL/NHLBI NIH HHS; T32 HL00789-09/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Biological Markers; 0/Neuregulin-1 |
| Comments/Corrections | |
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