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Then, C.* ; Sujana, C. ; Herder, C.* ; Then, H.* ; Heier, M. ; Meisinger, C. ; Peters, A. ; Koenig, W.* ; Rathmann, W.* ; Maalmi, H.* ; Ritzel, K.* ; Roden, M.* ; Stumvoll, M.* ; Thorand, B. ; Seissler, J.*

Association of C-terminal pro-endothelin-1 with mortality in the population-based KORA F4 study.

Vasc. Health Risk Manag. 18, 335-346 (2022)
Publ. Version/Full Text DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Introduction: Endothelin-1 and its prohormone C-terminal pro-endothelin-1 (CT-proET-1) have been linked to metabolic alterations, inflammatory responses and cardiovascular events in selected study populations. We analyzed the association of CT-proET-1 with cardiovascular events and mortality, carotid intima-media-thickness as surrogate for early atherosclerotic lesions, biomarkers of subclinical inflammation and adipokines in a population-based study. Methods: The cross-sectional and prospective analyses used data from the KORA F4 study with a median follow-up time of 9.1 (8.8-9.4) years. Data on CT-proET-1 and mortality were available for 1554 participants, data on the other outcomes in subgroups (n = 596-1554). The associations were estimated using multivariable linear regression and Cox proportional hazard models adjusted for sex, age, body mass index, estimated glomerular filtration rate, arterial hypertension, diabetes, low-density and high-density lipoprotein cholesterol, current and former smoking and physical activity. The Bonferroni method was used to correct for multiple testing. Results: In the fully adjusted model, CT-proET-1 was associated with cardiovascular (hazard ratio (HR) per standard deviation increase: 1.66; 95% confidence interval (CI): 1.10-2.51; p = 0.017) and all-cause mortality (HR: 2.03; 95% CI 1.55-2.67; p < 0.001), but not with cardiovascular events, and was inversely associated with the intima-media thickness (β: -0.09 ± 0.03; p = 0.001). CT-proET-1 was positively associated with five out of ten biomarkers of subclinical inflammation and with two out of five adipokines after correction for multiple testing. After inclusion of biomarkers of subclinical inflammation in the Cox proportional hazard model, the association of CT-proET-1 with all-cause mortality persisted (p < 0.001). Conclusion: These results emphasize the complexity of endothelin-1 actions and/or indicator functions of CT-proET-1. CT-proET-1 is a risk marker for all-cause mortality, which is likely independent of vascular endothelin-1 actions, cardiovascular disease and inflammation.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Cardiovascular Events ; Ct-proet-1 ; Endothelin ; Intima-media Thickness ; Mortality ; Subclinical Inflammation
ISSN (print) / ISBN 1176-6344
e-ISSN 1178-2048
Journal Vascular Health and Risk Management
Quellenangaben Volume: 18, Issue: , Pages: 335-346 Article Number: , Supplement: ,
Publisher Dove Medical Press
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology II (EPI2)
Independent Research Group Clinical Epidemiology (KEPI)
Grants Deutsches Forschungszentrum für Gesundheit und Umwelt, Helmholtz Zentrum München
Deutsche Diabetes Gesellschaft
Bundesministerium für Gesundheit
Bundesministerium für Bildung und Forschung
Deutsche Forschungsgemeinschaft
Virtual Diabetes Institute
Ministry of Culture and Science of the state North Rhine Westphalia
German Diabetes Center
German Center for Diabetes Research