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Objective To assess the cardiovascular prognostic value of mid-regional pro-adrenomedullin (MR-proADM) and compare this with B-type natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-proBNP), on death or a composite end point in patients who developed heart failure after an acute myocardial infarction (AMI).
Methods From a subset of 214 patients from the OPTIMAAL study, blood samples were obtained at a median of 3 days after AMI when patients had developed signs and/or symptoms of heart failure (HF) or a left ventricular ejection fraction <0.35%. End points were all-cause mortality and a composite end point, including death, myocardial reinfarction, stroke and/or resuscitated cardiac arrest.
Results Mean age of the patients was 68±10 years and mean follow-up was 918±311 days. During follow-up 31 patients died and 61 reached the composite end point. In multivariable Cox proportional hazard models adjusted for BNP, NT-proBNP and other covariates, a doubling of MR-proADM showed a 3.02 (95% CI 1.66 to 5.49) times increased risk of mortality (p<0.001) and a 1.77 (95% CI 1.13 to 2.78) times increased risk of reaching the composite end point (p=0.013). Receiver operating characteristic curves indicated that MR-proADM (area under the curve (AUC)=0.81) was a stronger predictor of mortality than BNP (AUC=0.66; p=0.0034 vs MR-proADM) and NT-proBNP (AUC=0.67; p<0.001 vs MR-proADM). Furthermore, MR-proADM enhanced significantly risk classification and integrated discrimination improvement in comparison with BNP and NT-proBNP. Finally, changes in MR-proADM over time significantly added prognostic information to the baseline value.
Conclusion MR-proADM is a promising biomarker and has strong prognostic value for mortality and morbidity in patients with HF after an AMI. In this study, MR-proADM had stronger predictive value than BNP and NT-proBNP.
Funding This study was supported by an unrestricted grant form Merck Research Laboratories, Bluebell, Pennsylvania and by research grants from the Brandenburg Ministry of Economics, Germany and the European Regional Development Fund (EFRE/ERDF). DJvV and AAV are clinical established investigators of the Netherlands Heart Foundation (D97-017 and 2006T37).
Competing interests Disclosures and potential conflicts of interest: 1. AAV received a research grant from B.R.A.H.M.S., a biotech company that developed the mid-regional pro-adrenomedullin (MR-proADM) assay. 2. JS is employed by B.R.A.H.M.S. 3. B.R.A.H.M.S holds patent applications with JS as co-inventor on the use of mid-regional pro-adrenomedullin for diagnostics. 4. SDA has received consultant honoraria from B.R.A.H.M.S.
Patient consent Obtained.
Ethics approval This study was conducted with the approval of the local ethics committees and done in accordance with the Declaration of Helsinki.
Provenance and peer review Not commissioned; externally peer reviewed.
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