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Proenkephalin improves cardio-renal risk prediction in acute coronary syndromes: the KID-ACS score
FA. Wenzl, P. Wang, M. Arrigo, J. Parenica, DJL. Jones, F. Bruno, D. Tarnowski, O. Hartmann, L. Boucek, F. Lang, S. Obeid, A. Schober, S. Kraler, A. Akhmedov, F. Kahles, A. Schober, KW. Ow, S. Ministrini, GG. Camici, A. Bergmann, L. Liberale, J....
Language English Country England, Great Britain
Document type Journal Article, Multicenter Study
Grant support
SPUM 33CM30-124112
Swiss National Science Foundation - Switzerland
Swiss Heart Foundation
Medtronic
Merck Sharpe and Dohme
sanofi-aventis
St Jude Medical AG
Theodor und Ida Herzog-Egli Stiftung
Foundation for Cardiovascular Research-Zurich Heart House
the Lindenhof Foundation
Fonds zur Förderung des akademischen Nachwuchses of the University of Zurich
British Heart Foundation - United Kingdom
SphingoTec GmbH GmbH
65269705
Ministry of Health of the Czech Republic
- 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
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.
Center for Molecular Cardiology University of Zurich Wagistrasse 12 8952 Schlieren Switzerland
Department of Cardiology Cardiovascular Center University Hospital Bern Bern Switzerland
Department of Cardiology Geneva University Hospital Geneva Switzerland
Department of Cardiology University Hospital Zurich Zurich Switzerland
Department of Cardiovascular Sciences Glenfield Hospital University of Leicester Leicester UK
Department of Cardiovascular Sciences University of Leicester Leicester UK
Department of Clinical Sciences Karolinska Institutet Stockholm Sweden
Department of Internal Medicine 1 University Hospital Aachen Pauwelsstraße 30 52074 Aachen Germany
Department of Internal Medicine Stadtspital Zurich Zurich Switzerland
Department of Research and Education University Hospital Zurich Zurich Switzerland
Division of Cardiology Department of Medicine Basel Cantonal Hospital Basel Switzerland
Faculty of Medicine Institute of Biostatistics and Analysis Masaryk University Brno Czechia
Institute of Health Information and Statistics of the Czech Republic Prague Czechia
Leicester van Geest Multi OMICS Facility University of Leicester Leicester UK
National Disease Registration and Analysis Service NHS London UK
National Heart and Lung Institute Imperial College London UK
National Institute for Health and Care Research Leicester UK
Royal Brompton and Harefield Hospitals Sydney Street London SW3 6NP UK
School of Cardiovascular Medicine and Sciences Kings College London London UK
Service of Cardiology Lausanne University Hospital Lausanne Switzerland
References provided by Crossref.org
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- $a Wenzl, Florian A $u Center for Molecular Cardiology, University of Zurich, Wagistrasse 12, 8952 Schlieren, Switzerland $u National Disease Registration and Analysis Service, NHS, London, UK $u Department of Cardiovascular Sciences, University of Leicester, Leicester, UK $u Department of Clinical Sciences, Karolinska Institutet, Stockholm, Sweden $1 https://orcid.org/0000000166549918
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