The incremental prognostic and clinical value of multiple novel biomarkers in heart failure.
In recent years there has been an increase in the number of biomarkers in heart failure (HF). The clinical role for these novel biomarkers in combination is not clear.



The following novel biomarkers were measured from 628 patients recently hospitalized with decompensated HF; mid-regional pro-adrenomedullin (MR-proADM), mid-regional pro-atrial natriuretic peptide (MR-proANP), copeptin, high-sensitivity cardiac troponin T (hs-cTnT), ST2, galectin-3, cystatin C, combined free light chains (cFLC) and high sensitivity C-reactive protein (hsCRP). The incremental prognostic value of these novel biomarkers was evaluated within an extensive model containing established predictors of mortality. During a mean (SD) follow-up of 3.2 (1.5) years, 290 (46%) patients died. Elevated concentrations of all novel biomarkers were associated with an increased unadjusted risk of mortality but only two-thirds were independent predictors following multivariable analysis. Using dichotomized cut-points from receiver operating characteristic analysis, MR-proADM, hs-cTnT, cFLC, hsCRP, and ST2 remained independent predictors of mortality. Further dichotomization into low (0-2 elevated biomarkers) or high (at least three of the five biomarkers elevated) risk groups provided greatest incremental prognostic value (hazard ratio 2.20, 95% confidence interval 1.37-3.54; P = 0.001) and improved the performance of the model (C-statistic 0.730 from 0.721, net reclassification index 32.5%).



The novel biomarkers included in this study added little, if any, incremental prognostic value on their own to a model containing established predictors of mortality. However, following dichotomization, five of the novel biomarkers provided incremental prognostic value. There was a clear gradient in the risk of death with increasing numbers of elevated novel biomarkers, with the presence of at least three identifying patients at greatest risk of mortality.
British Heart Foundation Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow, G12 8TA, UK.
Colette E
CE
Jackson
Robertson Centre for Biostatistics, University of Glasgow, Glasgow, UK.
Caroline
C
Haig
British Heart Foundation Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow, G12 8TA, UK.
Paul
P
Welsh
British Heart Foundation Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow, G12 8TA, UK.
Jonathan R
JR
Dalzell
British Heart Foundation Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow, G12 8TA, UK.
Ioannis K
IK
Tsorlalis
Robertson Centre for Biostatistics, University of Glasgow, Glasgow, UK.
Alex
A
McConnachie
British Heart Foundation Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow, G12 8TA, UK.
David
D
Preiss
Innovative Clinical Trials, Department of Cardiology and Pneumology, University Medical Centre Göttingen, Germany.
Stefan D
SD
Anker
British Heart Foundation Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow, G12 8TA, UK.
Naveed
N
Sattar
Scottish National Advanced Heart Failure Service, Golden Jubilee National Hospital, Glasgow, UK.
Mark C
MC
Petrie
Scottish National Advanced Heart Failure Service, Golden Jubilee National Hospital, Glasgow, UK.
Roy S
RS
Gardner
British Heart Foundation Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow, G12 8TA, UK.
John J V
JJ
McMurray
D053607:Adrenomedullin / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism*; D002097:C-Reactive Protein / Q000378:metabolism; D055316:Cystatin C / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D037502:Galectin 3 / Q000378:metabolism; D006020:Glycopeptides / Q000378:metabolism; D006333:Heart Failure / Q000378:metabolism*; D006801:Humans; D000072179:Interleukin-1 Receptor-Like 1 Protein / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009026:Mortality; D015999:Multivariate Analysis; D010446:Peptide Fragments / Q000378:metabolism; D011379:Prognosis; D016016:Proportional Hazards Models; D011498:Protein Precursors / Q000378:metabolism; D012372:ROC Curve; D013318:Stroke Volume; D020107:Troponin T / Q000378:metabolism
D015415:Biomarkers; D055316:Cystatin C; D037502:Galectin 3; D006020:Glycopeptides; C079241:IL1RL1 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D010446:Peptide Fragments; D011498:Protein Precursors; D020107:Troponin T; C048197:copeptins; C574167:mid-regional pro-adrenomedullin, human; D053607:Adrenomedullin; D009320:Atrial Natriuretic Factor; D002097:C-Reactive Protein
Heart failure; Novel biomarkers; Prognosis; Risk stratification