Prognostic value of different biomarkers for cardiovascular death in unselected older patients in the emergency department.
BACKGROUND
Risk stratification of elderly patients presenting with heart failure (HF) to an emergency department (ED) is an unmet challenge. We prospectively investigated the prognostic performance of different biomarkers in unselected older patients in the ED.


METHODS
We consecutively enrolled 302 non-surgical patients ⩾70 years presenting to the ED with a wide range of cardiovascular and non-cardiovascular comorbid conditions. N-terminal pro-B-type natriuretic peptide (NT-proBNP), mid-regional pro-adrenomedullin (MR-proADM), mid-regional pro-atrial natriuretic peptide (MR-proANP), C-terminal pro-endothelin-1 (CT-proET-1), ultrasensitive C-terminal pro-arginine-vasopressin (Copeptin-us) and high-sensitivity cardiac troponin T (hs-cTnT) were measured at admission. Two cardiologists independently adjudicated the final diagnosis of HF after reviewing all available baseline data using circulating NT-proBNP levels. A final diagnosis of HF was found in 120 (40%) of the 302 patients. All patients were followed up for cardiovascular death within the following 12 months. In order to test the prognostic performance of the investigated biomarkers we used boosting models with age and sex as mandatory covariates. Boosting is a statistical learning technique with built-in variable selection developed to obtain sparse and interpretable prediction models.


RESULTS
Follow-up was 100% complete. During a median follow-up time of 225 days (interquartile range (IQR) 156-319 days), 30 (9.9%) of 302 patients (aged 81±6 years) had cardiovascular deaths. Of these 30 patients, 21 had HF and nine had no HF diagnosed prior to admission. The boosting model selected MR-proADM and hs-cTNT as predictors of cardiovascular deaths. The median values of MR-proADM and hs-cTnT at presentation were significantly higher in patients with cardiovascular deaths compared to surviving patients during follow-up (2.56 nmol/L (IQR 1.62-4.48) vs. 1.11 nmol/L (IQR 0.83-1.80), P<0.001 and 81 ng/L (IQR 38-340) vs. 17 ng/L (IQR 0.9-38), P=0.004). One unit increase in the log-transformed MR-proADM levels was associated with a 1.99-fold risk of death (95% confidence interval (CI) 1.61-2.45, P<0.001). The second marker, hs-cTnT, showed an increased predicted risk but was not significantly correlated to event-free survival (hazard ratio 3.22, 95% CI 0.97-10.68, P=0.056).


CONCLUSIONS
Within different biomarkers, MR-proADM was the only predictor of cardiovascular deaths in unselected older patients presenting to the ED.
Institute for Biomedicine of Aging, Friedrich-Alexander-University, Nuernberg, Germany philipp.bahrmann@fau.de.
Philipp
P
Bahrmann
Department of Emergency and Critical Care Medicine, Paracelsus Medical University, Klinikum Nuernberg, Germany.
Michael
M
Christ
Department of Medical Informatics, Biometry and Epidemiology, Friedrich-Alexander-University, Erlangen, Germany.
Benjamin
B
Hofner
Department of Cardiology, University Hospital of Heidelberg, Germany.
Anke
A
Bahrmann
Department of Cardiology, Friedrich-Alexander-University, Erlangen, Germany.
Stefan
S
Achenbach
Institute for Biomedicine of Aging, Friedrich-Alexander-University, Nuernberg, Germany.
Cornel Christian
CC
Sieber
Institute for Clinical Chemistry, Laboratory Medicine and Transfusion Medicine, Paracelsus Medical University, Klinikum Nuernberg, Germany.
Thomas
T
Bertsch
D053607:Adrenomedullin / Q000378:metabolism*; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D004636:Emergency Service, Hospital; D005260:Female; D006333:Heart Failure / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality*; D006801:Humans; D008297:Male; D015233:Models, Statistical; D010446:Peptide Fragments / Q000378:metabolism*; D011379:Prognosis; D011498:Protein Precursors / Q000378:metabolism*; D018570:Risk Assessment
D015415:Biomarkers; D010446:Peptide Fragments; D011498:Protein Precursors; C574167:mid-regional pro-adrenomedullin, human; D053607:Adrenomedullin
Heart failure; adrenomedullin; aged; copeptin; endothelin; natriuretic peptides; prognosis