Proenkephalin and Prognosis After Acute Myocardial Infarction

• Published in: Journal of the American College of Cardiology Vol. 63; no. 3; pp. 280 - 289
• Main Authors: Ng, Leong L., Sandhu, Jatinderpal K., Narayan, Hafid, Quinn, Paulene A., Squire, Iain B., Davies, Joan E., Bergmann, Andreas, Maisel, Alan, Jones, Donald J.L.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 28.01.2014; Elsevier; Elsevier Limited
• Subjects: Acute coronary syndromes; Aged; Amino acids; Apoptosis; B-type natriuretic peptide; Biological and medical sciences; Biomarkers; Cardiology; Cardiology. Vascular system; Cardiovascular; Confidence intervals; Coronary heart disease; Deoxyribonucleic acid; DNA; Electrocardiography; Enkephalins - blood; Female; Follow-Up Studies; GRACE score; Heart; Heart attacks; Heart failure; Humans; Immunoassay; Incidence; Male; Medical sciences; Middle Aged; Mortality; myocardial infarction; Myocardial Infarction - blood; Myocardial Infarction - epidemiology; Myocardial Infarction - physiopathology; Myocarditis. Cardiomyopathies; opioids; Peptides; proenkephalin; Prognosis; Proportional Hazards Models; Protein Precursors - blood; Registries; Regression analysis; Retrospective Studies; Risk Assessment - methods; Survival Rate - trends; United Kingdom - epidemiology; eGFR; NSTEMI; NRI; GRACE score; myocardial infarction; proenkephalin; OPR; B-type natriuretic peptide; NT-proBNP; re; MACE; PENK; LVSD; MI; AMI; HF; opioids; estimated glomerular filtration rate; recurrent; non–ST-segment elevation myocardial infarction; heart failure; net reclassification improvement; major adverse cardiac event(s); left ventricular systolic dysfunction; opioid receptor; N-terminal pro–B-type natriuretic peptide; acute myocardial infarction; Myocardial infarction; Prognosis; Acute; Cardiovascular disease; Circulatory system; Cardiology; Coronary heart disease; Myocardial disease
• ISSN: 0735-1097; 1558-3597; 1558-3597
• DOI: 10.1016/j.jacc.2013.09.037

The goal of this research was to assess the prognostic value of proenkephalin (PENK) levels in acute myocardial infarction (AMI) by using N-terminal pro–B-type natriuretic peptide and Global Registry of Acute Coronary Events (GRACE) scores as comparators and to identify levels that might be valuable in clinical decision making. PENK is a stable analyte of labile enkephalins. Few biomarkers predict recurrent AMI. We measured PENK in 1,141 patients (820 male subjects; mean age 66.2 ± 12.8 years) with AMI. Endpoints were major adverse events (composite of death, myocardial infarction [MI], and heart failure [HF] hospitalization) and recurrent MI at 2 years. GRACE scoring was used for comparisons with PENK for the death and/or MI endpoint at 6 months. During follow-up, 139 patients died, and there were 112 HF hospitalizations and 149 recurrent AMIs. PENK levels were highest on admission and were related to estimated glomerular filtration rate, left ventricular wall motion index, sex, blood pressure, and age. Multivariable Cox regression models found that the PENK level was a predictor of major adverse events (hazard ratio [HR]: 1.52 [95% confidence interval (CI): 1.19 to 1.94]), death and/or AMI (HR: 1.76 [95% CI: 1.34 to 2.30]), and death and/or HF (HR: 1.67 [95% CI: 1.24 to 2.25]) (all comparisons p < 0.001), as well as recurrent AMI (HR: 1.43 [95% CI: 1.07 to 1.91]; p < 0.01). PENK levels were independent predictors of 6-month death and/or MI compared with GRACE scores. PENK-adjusted GRACE scores reclassified patients significantly (overall category-free net reclassification improvement [>0] of 21.9 [95% CI: 4.5 to 39.4]; p < 0.014). PENK levels <48.3 pmol/l and >91 pmol/l detected low- and high-risk patients, respectively. PENK levels reflect cardiorenal status post-AMI and are prognostic for death, recurrent AMI, or HF. Cutoff values define low- and high-risk groups and improve risk prediction of GRACE scores.