Midregional pro-atrial natriuretic peptide (MR-proANP) is a powerful predictor of adverse outcome after acute myocardial infarction (AMI), and gives complementary information when combined with measurement of the prohormone of B-type NP (proBNP), say researchers.

Measuring biomarkers of both natriuretic peptide neurohormonal systems combined in this way allows more accurate risk stratification than measurement of existing clinical characteristics, report Sohail Khan (University of Leicester, UK) and team.

The researchers explain that measuring MR-proANP involves detecting midregional epitopes of the prohormone of ANP, which may be less vulnerable to degradation than the epitopes in the amino or carboxy terminal of proANP targeted in assays in the past.

The team studied 983 consecutive AMI patients admitted to their coronary care unit.

They measured patients' plasma MR-proANP and amino-terminal (NT)-proBNP levels in a single blood sample drawn 3-5 days after the onset of chest pain.

Median plasma MR-proANP level was significantly higher in patients who died during the 1-year follow-up than in survivors, at 310 versus 108 pmol/l (p<0.0001).

Both MR-proANP, with a hazard ratio (HR) of 3.87, and NT-proBNP, with a HR of 3.25, were significant independent predictors of death in Cox proportional hazards analysis, along with use of beta blockers, ACE inhibitors, and angiotensin receptor blockers, and age.

MR-proANP and NT-proBNP showed comparable accuracy for predicting death, with an area under the receiver-operating characteristic (ROC) curve of 0.83 for both factors.

These values were higher than those obtained with markers of structural myocardial damage, namely troponin and peak creatine kinase.

Kaplan-Meier analysis showed that MR-proANP levels distinguished differing risk for mortality irrespective of NT-proBNP levels.

Patients in the top quartile of MR-proANP levels (above 331 pmol/l) had significantly higher mortality than those with lower levels (p<0.0001). And in patients stratified by NT-proBNP in the highest quartile (median 5934 pmol/l), MR-proANP in the highest quartile was still associated with worse outcome compared with lower levels.

Khan and co-authors say the two biomarkers most likely provide complementary information owing to their distinct secretion profiles. MR-proANP peaks on Day 1 after AMI, while NT-proBNP peaks on Day 2, they report.

"A multimarker approach with MR-proANP and NT-proBNP targeting both the A- and B-type natriuretic neurohormonal pathways is more informative than either marker alone and may be useful for risk stratification in AMI patients," the authors conclude.

J Am Coll Cardiol 2008; 51: 1857-1864