Pro-adrenomedullin levels predictive of death, HF

Issue: August 2010

Levels of mid-regional pro-adrenomedullin were prognostic of early mortality and HF, and helped to improve risk stratification, study findings indicated.

The study included 745 patients with non-STEMI who had their plasma pro-adrenomedullin measured on admission and discharge. The primary endpoints over a mean follow-up of 760 days were a composite of death, HF, hospitalization and recurrent acute MI, whereas the events assessed individually were secondary endpoints.

During follow-up, there were 65 (8.7%) HF hospitalizations, 77 (10.3%) recurrent acute MIs and 120 (16.1%) deaths. Compared with established normal ranges, levels of admission (median: 0.81 nmol/L; range 0.06-5.75 nmol/L) and discharge (median: 0.76 nmol/L; range 0.25-6.95 nmol/L) were increased. Multivariate adjusted Cox regression models indicated that levels of admission and discharge were associated with the primary endpoint (HR=9.75 on admission, 7.54 on discharge; both P<.001). Admission pro-adrenomedullin in particular correlated with early mortality (P<.001) and, when compared with N-terminal pro-B-type natriuretic peptide (NT-proBNP) and Global Registry of Acute Coronary Events (GRACE) score, was the only independent predictor of this endpoint.

According to researchers, this study represents the first report confirming activation of the adrenomedullin system in a cohort of patients with non-STEMI. “[Mid-regional pro-adrenomedullin] … represents a powerful new biomarker of risk of adverse events, death or HR rehospitalization beyond established clinical, biochemical or echocardiographic markers, NT-proBNP and GRACE score,” they wrote. “Admission [mid-regional pro-adrenomedullin] level is a particularly strong predictor of early mortality and, when >1.11 nmol/L, complemented the GRACE score to improve risk stratification.” – by Brian Ellis

Dhillon O. J Am Coll Cardiol. 2010;56:125-133.

The manuscript by Dhillon and colleagues builds on the theme that biomarkers are important prognostically in acute coronary syndromes. This group has shown previously that mid-regional pro-adrenomedullin levels were important prognostically in STEMIs. In the current manuscript, they extend their observations by showing that mid-regional pro-adrenomedullin are important in non-STEMIs in terms of predicting GRACE score. The data suggest that measurement of mid-regional pro-adrenomedullin levels on admission, which is a relatively new biomarker, is better than NT-proBNP, a biomarker for which there are a lot of data, for predicting GRACE scores. Because of the overall sample size of the study and the single-center population nature of the study, I don’t think you can use this study to say unequivocally that mid-regional pro-adrenomedullin is better than NT-proBNP. However, I think these findings are suggestive and provocative.

One part of the study that is interesting, but which I am not sure they have sufficient data for at present, is the suggestion that patients who have the highest tertile of mid-regional pro-adrenomedullin who underwent revascularization had better outcomes than the patients who were not revascularized. Although these data are interesting and potentially important, it may be that the patients who were not operated on were simply sicker (than the patients who were operated on) and therefore had worse outcomes. The authors did not perform any risk adjustment modeling for the two cohorts of patients, which would have strengthened the argument that levels of mid-regional pro-adrenomedullin could be used to identify patients who would fare better if they underwent revascularization. Nonetheless, the data are fascinating and warrant additional investigation.

The important question this study raises is whether it is time to conduct a prospective multimarker-driven strategy to see whether the combination of markers is better at guiding therapy in ACS than a single-marker driven approach (eg, troponin alone). The concept that a multibiomarker-driven strategy could guide clinicians to be more or less aggressive with revascularization strategies would be something that would advance the field and that many of us would find exciting.

– Douglas Mann, MD
Cardiology Today Board Member

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