Key result
Proenkephalin predicts ~52% higher risk of major events post-AMI and improves prediction over GRACE scores.
Why the study?
Few biomarkers predict recurrent AMI, and the prognostic value of proenkephalin (PENK) levels after AMI compared with established scores was unclear.
Cohort (n=1,141)
Hazard Ratio: 1.52 (95% CI 1.19–1.94)
p-value: p=< 0.001
May enhance AMI risk stratification beyond GRACE; hypothesis-generating pending prospective validation.
OBJECTIVES: 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. BACKGROUND: PENK is a stable analyte of labile enkephalins. Few biomarkers predict recurrent AMI. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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Ng et al. (2013) conducted a cohort in Acute myocardial infarction (n=1,141). Proenkephalin (PENK) levels vs. GRACE scores was evaluated on Major adverse events (composite of death, myocardial infarction, and heart failure hospitalization) (HR 1.52, 95% CI 1.19 to 1.94, p=< 0.001). Proenkephalin levels independently predicted major adverse events after acute myocardial infarction (HR 1.52; 95% CI 1.19-1.94; p<0.001) and improved risk prediction compared with GRACE scores.
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