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Association of C-Terminal Pro-Endothelin-1 with Mortality in the Population-Based KORA F4 Study

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, caroti...

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Autores principales: Then, Cornelia, Sujana, Chaterina, Herder, Christian, Then, Holger, Heier, Margit, Meisinger, Christa, Peters, Annette, Koenig, Wolfgang, Rathmann, Wolfgang, Maalmi, Haifa, Ritzel, Katrin, Roden, Michael, Stumvoll, Michael, Thorand, Barbara, Seissler, Jochen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9078871/
https://www.ncbi.nlm.nih.gov/pubmed/35535305
http://dx.doi.org/10.2147/VHRM.S363814
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author Then, Cornelia
Sujana, Chaterina
Herder, Christian
Then, Holger
Heier, Margit
Meisinger, Christa
Peters, Annette
Koenig, Wolfgang
Rathmann, Wolfgang
Maalmi, Haifa
Ritzel, Katrin
Roden, Michael
Stumvoll, Michael
Thorand, Barbara
Seissler, Jochen
author_facet Then, Cornelia
Sujana, Chaterina
Herder, Christian
Then, Holger
Heier, Margit
Meisinger, Christa
Peters, Annette
Koenig, Wolfgang
Rathmann, Wolfgang
Maalmi, Haifa
Ritzel, Katrin
Roden, Michael
Stumvoll, Michael
Thorand, Barbara
Seissler, Jochen
author_sort Then, Cornelia
collection PubMed
description 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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spelling pubmed-90788712022-05-08 Association of C-Terminal Pro-Endothelin-1 with Mortality in the Population-Based KORA F4 Study Then, Cornelia Sujana, Chaterina Herder, Christian Then, Holger Heier, Margit Meisinger, Christa Peters, Annette Koenig, Wolfgang Rathmann, Wolfgang Maalmi, Haifa Ritzel, Katrin Roden, Michael Stumvoll, Michael Thorand, Barbara Seissler, Jochen Vasc Health Risk Manag Original Research 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. Dove 2022-05-03 /pmc/articles/PMC9078871/ /pubmed/35535305 http://dx.doi.org/10.2147/VHRM.S363814 Text en © 2022 Then et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Then, Cornelia
Sujana, Chaterina
Herder, Christian
Then, Holger
Heier, Margit
Meisinger, Christa
Peters, Annette
Koenig, Wolfgang
Rathmann, Wolfgang
Maalmi, Haifa
Ritzel, Katrin
Roden, Michael
Stumvoll, Michael
Thorand, Barbara
Seissler, Jochen
Association of C-Terminal Pro-Endothelin-1 with Mortality in the Population-Based KORA F4 Study
title Association of C-Terminal Pro-Endothelin-1 with Mortality in the Population-Based KORA F4 Study
title_full Association of C-Terminal Pro-Endothelin-1 with Mortality in the Population-Based KORA F4 Study
title_fullStr Association of C-Terminal Pro-Endothelin-1 with Mortality in the Population-Based KORA F4 Study
title_full_unstemmed Association of C-Terminal Pro-Endothelin-1 with Mortality in the Population-Based KORA F4 Study
title_short Association of C-Terminal Pro-Endothelin-1 with Mortality in the Population-Based KORA F4 Study
title_sort association of c-terminal pro-endothelin-1 with mortality in the population-based kora f4 study
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9078871/
https://www.ncbi.nlm.nih.gov/pubmed/35535305
http://dx.doi.org/10.2147/VHRM.S363814
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