BACKGROUND AND AIMS: Circulating proenkephalin (PENK) is a stable endogenous polypeptide with fast response to glomerular dysfunction and tubular damage. This study examined the predictive value of PENK for renal outcomes and mortality in patients with acute coronary syndrome (ACS). METHODS: Proenkephalin was measured in plasma in a prospective multicentre ACS cohort from Switzerland (n = 4787) and in validation cohorts from the UK (n = 1141), Czechia (n = 927), and Germany (n = 220). A biomarker-enhanced risk score (KID-ACS score) for simultaneous prediction of in-hospital acute kidney injury (AKI) and 30-day mortality was derived and externally validated. RESULTS: On multivariable adjustment for established risk factors, circulating PENK remained associated with in-hospital AKI [per log2 increase: adjusted odds ratio 1.53, 95% confidence interval (CI) 1.13-2.09, P = .007] and 30-day mortality (adjusted hazard ratio 2.73, 95% CI 1.85-4.02, P < .001). The KID-ACS score integrates PENK and showed an area under the receiver operating characteristic curve (AUC) of .72 (95% CI .68-.76) for in-hospital AKI and .91 (95% CI .87-.95) for 30-day mortality in the derivation cohort. Upon external validation, KID-ACS achieved similarly high performance for in-hospital AKI (Zurich: AUC .73, 95% CI .70-.77; Czechia: AUC .75, 95% CI .68-.81; Germany: AUC .71, 95% CI .55-.87) and 30-day mortality (UK: AUC .87, 95% CI .83-.91; Czechia: AUC .91, 95% CI .87-.94; Germany: AUC .96, 95% CI .92-1.00), outperforming the contrast-associated AKI score and the Global Registry of Acute Coronary Events 2.0 score, respectively. CONCLUSIONS: Circulating PENK offers incremental value for predicting in-hospital AKI and mortality in ACS. The simple six-item KID-ACS risk score integrates PENK and provides a novel tool for simultaneous assessment of renal and mortality risk in patients with ACS.

• Keywords
• Acute coronary syndromes, Acute kidney injury, Mortality risk, Proenkephalin, Risk prediction,
• MeSH
• Acute Coronary Syndrome * mortality   blood   MeSH
• Acute Kidney Injury * MeSH
• Biomarkers * blood   MeSH
• Enkephalins * blood   MeSH
• Risk Assessment methods   MeSH
• Middle Aged MeSH
• Humans MeSH
• Predictive Value of Tests MeSH
• Prospective Studies MeSH
• Protein Precursors * blood   MeSH
• Risk Factors MeSH
• Aged MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Names of Substances
• Biomarkers * MeSH
• Enkephalins * MeSH
• proenkephalin MeSH Browser
• Protein Precursors * MeSH

BACKGROUND: The assessment of acute heart failure (AHF) in patients with acute coronary syndrome (ACS) is challenging. This study tested whether measuring plasma adrenomedullin in patients admitted for ACS provides valuable information regarding the presence of AHF at admission or its occurrence during hospitalization. METHODS AND RESULTS: The study population consisted of 927 prospectively enrolled patients with ACS. Blood samples for the measurement of plasma bio-adrenomedullin (bio-ADM) were collected at admission. Patients with alveolar pulmonary edema and interstitial pulmonary edema on chest radiography at admission had stepwise higher plasma concentrations of bio-ADM compared to patients with no or mild pulmonary congestion: 54.3 ± 10.6 vs. 27.6 ± 2.1 vs. 22.5 ± 0.7 ng/L, overall P < 0.001. Patients with ACS complicated by AHF during the index hospitalization displayed higher plasma bio-ADM concentrations at admission compared to patients without AHF (33.8 ± 2.7 vs. 21.8 ± 0.7, P < 0.001): the higher the severity of AHF, the higher plasma bio-ADM concentrations at admission. Patients with cardiogenic shock displayed the highest values. Accordingly, bio-ADM concentrations at admission were associated with a higher risk of occurrence of AHF during index hospitalization (odds ratio 1.018, 95% confidence interval 1.011-1.026, P < 0.001). CONCLUSIONS: Plasma adrenomedullin is a marker associated with AHF severity in patients with ACS.

• Keywords
• Acute coronary syndrome, Acute heart failure, Bio-adrenomedullin, Pulmonary edema,
• Publication type
• Journal Article MeSH