Abstract
AimsTo test the prognostic value of emerging biomarkers in the Reduction of Events by Darbepoetin Alfa in Heart Failure (RED‐HF) trial.Methods and resultsCirculating 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.ConclusionOnce 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.
Highlights
B-type natriuretic peptide, produced by the myocardium primarily in response to volume overload and increase in wall stress, and its inactive metabolite N-terminal pro-B-type natriuretic peptide (NT-proBNP), are established prognostic markers in patients with heart failure and reduced ejection fraction (HFrEF).[1]
Results], neurohumoral [mid-regional pro-adrenomedullin (MR-proADM) and copeptin], renal, and inflammatory [high-sensitivity C-reactive protein] biomarkers were measured at randomization in 1853 participants with complete data
The main questions about emerging biomarkers in HF prognostication are: (i) how do they perform as prognostic markers compared to B-type natriuretic peptides, troponin or both, or (ii) do they individually or collectively add further meaningful prognostic information to the routinely collected variables including a B-type natriuretic peptide and a troponin? Few studies have addressed these questions for the emerging biomarkers used either alone or in a multiple biomarker panel
Summary
B-type natriuretic peptide, produced by the myocardium primarily in response to volume overload and increase in wall stress, and its inactive metabolite N-terminal pro-B-type natriuretic peptide (NT-proBNP), are established prognostic markers in patients with heart failure and reduced ejection fraction (HFrEF).[1] elevated levels of cardiac troponins reflecting cardiomyocyte necrosis, consistently relate to worse clinical outcomes in both acute[2,3] and chronic[4,5,6,7,8] HFrEF patients Both these biomarkers may provide additive prognostic information to routinely collected demographic, clinical and laboratory data in patients with chronic heart failure (HF).[5,6,7]. In acute and chronic HF, cystatin C has been reported to be a better predictor of adverse outcomes than creatinine-based eGFR, and to add incremental prognostic information to both NT-proBNP and hsTnT.[19,20,21,22,23] whereas inflammation has been implicated in the pathogenesisis of HF, the relative value of high-sensitivity C-reactive protein (hsCRP), a reliable and stable marker of systemic inflammation, as a prognostic marker in patients with HFrEF is uncertain.[7,24,25,26] The main questions about emerging biomarkers in HF prognostication are: (i) how do they perform as prognostic markers compared to B-type natriuretic peptides, troponin or both (i.e. could we find a better replacement for one or both of these effective prognostic markers?), or (ii) do they individually or collectively add further meaningful prognostic information to the routinely collected variables including a B-type natriuretic peptide and a troponin? Few studies have addressed these questions for the emerging biomarkers used either alone or in a multiple biomarker panel
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