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CLINICAL RESEARCH: MYOCARDIAL INFARCTION

Prognostic Value of Midregional Pro-Adrenomedullin in Patients With Acute Myocardial Infarction

The LAMP (Leicester Acute Myocardial Infarction Peptide) Study

Sohail Q. Khan, BSc (Hons), MBChB, MRCP^_*,1,_*, Russell J. O’Brien, MBChB, MRCP^_*, Joachim Struck, PhD^,3, Paulene Quinn, MPhil^_*, Nils Morgenthaler, PhD^,4, Iain Squire, MD, FRCP^_*, Joan Davies, PhD, FRCP^_*, Andreas Bergmann, PhD^,2 and Leong L. Ng, MD, FRCP^_*

^_* University of Leicester, Department of Cardiovascular Sciences, Leicester Royal Infirmary, Leicester, United Kingdom
Research Department, BRAHMS Aktiengesellschaft, Hennigsdorf, Germany.

Manuscript received August 14, 2006; revised manuscript received November 28, 2006, accepted December 5, 2006.

^_* Reprint requests and correspondence: Dr. Sohail Q. Khan, Department of Cardiovascular Sciences, Clinical Sciences Building, Leicester Royal Infirmary, Leicester LE2 7LX, United Kingdom. (Email: sqk1{at}le.ac.uk).

Objectives: This study sought to assess the prognostic impact of midregional pro-adrenomedullin (MR-proADM) after an acute myocardial infarction (AMI).

Background: Adrenomedullin (ADM) is elevated in heart failure (HF) and after AMI. Another part of its precursor, MR-proADM, is more stable in circulation and ex vivo. We investigated the cardiovascular prognostic value after AMI of MR-proADM and compared it with N-terminal pro-B-type natriuretic peptide (NTproBNP), a marker of death and HF.

Methods: We measured plasma MR-proADM and NTproBNP in 983 consecutive post-AMI patients (721 men, mean age 65.0 ± 12.2 years), 3 to 5 days after chest pain onset.

Results: There were 101 deaths and 49 readmissions with HF during follow-up (median 342, range 0 to 764 days). The MR-proADM was increased in patients with death or HF compared with survivors (median 1.19 nmol/l, range 0.09 to 5.39 nmol/l, vs. 0.71 nmol/l, range 0.25 to 6.66 nmol/l, p < 0.0001). Using a multivariate binary logistic model, log MR-proADM (odds ratio 4.22) and log NTproBNP (odds ratio 3.20) were significant independent predictors of death or HF (with creatinine, age, gender, and history of AMI). The areas under the receiver-operating characteristic curve for MR-proADM, NTproBNP, and the logistic model with both markers were 0.77, 0.79, and 0.84 respectively. Cox models for the predictors of death or HF showed the same variables (including log MR-proADM, hazard ratio 3.63; log NTproBNP, hazard ratio 2.67). The MR-proADM provided further risk stratification in those patients who had NTproBNP levels above the median (p < 0.0001). Findings were similar for death and HF as individual end points.

Conclusions: The ADM system is activated after AMI. The MR-proADM is a powerful predictor of adverse outcome, especially in those with an elevated NTproBNP. The MR-proADM may represent a clinically useful marker of prognosis after AMI.

Abbreviations and Acronyms   ADM = adrenomedullin   AMI = acute myocardial infarction   HF = heart failure   MR-proADM = midregional pro-adrenomedullin   NSTEMI = non–ST-segment elevation myocardial infarction   NTproBNP = N-terminal pro-B-type natriuretic peptide   STEMI = ST-segment elevation myocardial infarction

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