Neuregulin-1 beta is associated with disease severity and adverse outcomes in chronic heart failure.

Ky B, Kimmel SE, Safa RN, Putt ME, Sweitzer NK, Fang JC, Sawyer DB, Cappola TP
Circulation. 2009 120 (4): 310-7

PMID: 19597049 · PMCID: PMC2741393 · DOI:10.1161/CIRCULATIONAHA.109.856310

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.

MeSH Terms (17)

Adult Aged Biomarkers Chronic Disease Cohort Studies Female Follow-Up Studies Heart Failure Heart Transplantation Humans Male Middle Aged Neuregulin-1 Prospective Studies Severity of Illness Index Survival Rate Treatment Outcome

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