Proenkephalin for early post–MI risk stratification: comparative prognostic performance versus NT‑proBNP and GRACE

Ashutosh Mathur; Sumit K. Jha; Saurabh Singhal; Dhruv Jain; Harsha Shahi

doi:10.18203/2320-6012.ijrms20260241

Authors

Ashutosh Mathur Department of Internal Medicine, Subharti Medical College, Swami Vivekanand Subharti University, Meerut, Uttar Pradesh, India
Sumit K. Jha Department of Internal Medicine, Subharti Medical College, Swami Vivekanand Subharti University, Meerut, Uttar Pradesh, India
Saurabh Singhal Department of Internal Medicine, Subharti Medical College, Swami Vivekanand Subharti University, Meerut, Uttar Pradesh, India
Dhruv Jain Department of Internal Medicine, Subharti Medical College, Swami Vivekanand Subharti University, Meerut, Uttar Pradesh, India
Harsha Shahi Department of Internal Medicine, Subharti Medical College, Swami Vivekanand Subharti University, Meerut, Uttar Pradesh, India

DOI:

https://doi.org/10.18203/2320-6012.ijrms20260241

Keywords:

Cardiorenal syndrome, NT-proBNP, Proenkaphlin, Grace score, Myocardial infarction

Abstract

Background: Accurate post–myocardial infarction (MI) risk stratification is essential, yet clinical scores and natriuretic peptides incompletely capture early cardiorenal stress. Proenkephalin (PENK), a stable endogenous opioid precursor, reflects early glomerular dysfunction and neurohormonal activation. This study evaluated PENK for mortality prediction after MI compared with NT-proBNP and the GRACE risk score and identified optimal cutoffs.

Methods: In this prospective observational cohort, 50 consecutive MI patients enrolled between December 2024 and July 2025 at a tertiary center were studied. Clinical variables, lifestyle factors, comorbidities, hemodynamics, Killip class, MI type and biomarkers (Troponin-I, serum creatinine, NT-proBNP and Proenkephalin) were measured at presentation and Day 28. GRACE scores were calculated at baseline. The primary outcome was all-cause mortality. Cox proportional hazards models assessed independent prognostic value and ROC analysis compared discrimination and derived cutoffs.

Results: Mean age was 62.25±15.19 years; 68% were male, 66% smokers, 46% diabetics and 48% hypertensive. STEMI constituted 62%. Killip class I–IV: 42%, 28%, 8% and 22%. Troponin-I declined from 5,925±11,262 to 784±1,431 pg/ml (p=0.005). NT-proBNP remained elevated (4,019±4,096 to 3,880±3,695 pg/ml, p=0.001). PENK decreased from 138±35 to 89.7±28.5 pg/ml (p=0.003). Mean GRACE score was 133.6±38.1, mortality was 6%. PENK (HR 1.004, p=0.011), NT-proBNP (HR 1.001, p=0.048) and GRACE (HR 1.015, p=0.002) independently predicted mortality. ROC AUCs were 0.78 (PENK), 0.74 (NT-proBNP) and 0.69 (GRACE).

Conclusions: Proenkephalin provided the strongest mortality discrimination after MI with high negative predictive value, complementing NT-proBNP and GRACE for refined post-MI risk stratification.

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