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Prognostic importance of emerging cardiac, inflammatory, and renal biomarkers in chronic heart failure patients with reduced ejection fraction and anaemia: RED‐HF study
Author(s) -
Welsh Paul,
Kou Lei,
Yu Changhong,
Anand Inder,
van Veldhuisen Dirk J.,
Maggioni Aldo P.,
Desai Akshay S.,
Solomon Scott D.,
Pfeffer Marc A.,
Cheng Sunfa,
Gullestad Lars,
Aukrust Pål,
Ueland Thor,
Swedberg Karl,
Young James B.,
Kattan Michael W.,
Sattar Naveed,
McMurray John J.V.
Publication year - 2018
Publication title -
european journal of heart failure
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.149
H-Index - 133
eISSN - 1879-0844
pISSN - 1388-9842
DOI - 10.1002/ejhf.988
Subject(s) - medicine , copeptin , heart failure , cardiology , hazard ratio , natriuretic peptide , ejection fraction , cystatin c , biomarker , proportional hazards model , clinical endpoint , confidence interval , creatinine , randomized controlled trial , biochemistry , chemistry , vasopressin
Aims To test the prognostic value of emerging biomarkers in the Reduction of Events by Darbepoetin Alfa in Heart Failure (RED‐HF) trial. Methods and results Circulating cardiac [N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP), and high‐sensitivity troponin T (hsTnT)], neurohumoral [mid‐regional pro‐adrenomedullin (MR‐proADM) and copeptin], renal (cystatin C), and inflammatory [high‐sensitivity C‐reactive protein (hsCRP)] biomarkers were measured at randomization in 1853 participants with complete data. The relationship between these biomarkers and the primary composite endpoint of heart failure hospitalization or cardiovascular death over 28 months of follow‐up ( n = 834) was evaluated using Cox proportional hazards regression, the c‐statistic and the net reclassification index (NRI). After adjustment, the hazard ratio (HR) for the composite outcome in the top tertile of the distribution compared to the lowest tertile for each biomarker was: NT‐proBNP 3.96 (95% CI 3.16–4.98), hsTnT 3.09 (95% CI 2.47–3.88), MR‐proADM 2.28 (95% CI 1.83–2.84), copeptin 1.66 (95% CI 1.35–2.04), cystatin C 1.92 (95% CI 1.55–2.37), and hsCRP 1.51 (95% CI 1.27–1.80). A basic clinical prediction model was improved on addition of each biomarker individually, most strongly by NT‐proBNP (NRI +62.3%, P < 0.001), but thereafter was only improved marginally by addition of hsTnT (NRI +33.1%, P = 0.004). Further addition of biomarkers did not improve discrimination further. Findings were similar for all‐cause mortality. Conclusion Once NT‐proBNP is included, only hsTnT moderately further improved risk stratification in this group of chronic heart failure with reduced ejection fraction patients with moderate anaemia. NT‐proBNP and hsTnT far outperform other emerging biomarkers in prediction of adverse outcome.