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CLINICAL RESEARCH: MYOCARDIAL INFARCTION

Plasma N-Terminal B-Type Natriuretic Peptide as an Indicator of Long-Term Survival After Acute Myocardial Infarction: Comparison With Plasma Midregional Pro-Atrial Natriuretic Peptide

The LAMP (Leicester Acute Myocardial Infarction Peptide) Study

Sohail Q. Khan, MB^_*,_*, Onkar Dhillon, MB^_*, Dominic Kelly, MB^_*, Iain B. Squire, MD^_*, Joachim Struck, PhD, Paulene Quinn, MPhil^_*, Nils G. Morgenthaler, MD, Andreas Bergmann, PhD, Joan E. Davies, PhD^_* and Leong L. Ng, MD^_*

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

Manuscript received September 17, 2007; revised manuscript received January 15, 2008, accepted January 21, 2008.

^_* 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: Our aim was to assess the prognostic value of midregional proatrial natriuretic peptide (MR-proANP) in patients after acute myocardial infarction (AMI).

Background: Multimarker strategies may assist risk stratification after AMI. Midregional proatrial natriuretic peptide is a newly described stable fragment of N-terminal proatrial natriuretic peptide. We compared the prognostic value of MR-proANP and an established marker, N-terminal pro-B-type natriuretic peptide (NT-proBNP), after AMI.

Methods: We recruited 983 consecutive post-AMI patients (720 men, median age 65 [range 24 to 95] years) in a prospective study with follow-up over 343 (range 0 to 764) days.

Results: Plasma MR-proANP was raised in patients who died (n = 101) compared with that seen in survivors (median 310 [range 48 to 1,150] pmol/l vs. 108 [range 4.9 to 1,210] pmol/l, p < 0.0001). Using Cox modeling, log₁₀MR-proANP (hazard ratio 3.87) and log₁₀NT-proBNP (hazard ratio 3.25) were significant independent predictors of death. In patients stratified by NT-proBNP in the highest quartile (>5,900 pmol/l), MR-proANP in the top quartile (330 pmol/l) was associated with poorer outcome (p < 0.0001). Findings were similar for heart failure as an individual end point. However, neither marker predicted recurrent AMI.

Conclusions: The A- and B-type natriuretic systems are activated after AMI. Midregional proatrial natriuretic peptide is a powerful predictor of adverse outcome, especially in those with an elevated NT-proBNP. Midregional proatrial natriuretic peptide may represent a clinically useful marker of prognosis after an AMI as part of a multimarker strategy targeting the natriuretic neurohormonal pathway.

Abbreviations and Acronyms   AMI = acute myocardial infarction   ANP = atrial natriuretic peptide   AUC = area under the curve(s)   BNP = B-type natriuretic peptide   CI = confidence interval   CV = coefficient of variation   eGFR = estimated glomerular filtration rate   HF = heart failure   HR = hazard ratio   MI = myocardial infarction   MR-proANP = midregional proatrial natriuretic peptide   NSTEMI = non–ST-segment elevation myocardial infarction   NT-proBNP = N-terminal pro-B-type natriuretic peptide   STEMI = ST-segment elevation myocardial infarction

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