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

Association of circulating MR-proADM with all-cause and cardiovascular mortality in the general population: Results from the KORA F4 cohort study.

PLoS ONE 17:e0262330 (2022)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
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BACKGROUND AND AIM: Despite its vasodilatory effect, adrenomedullin and its surrogate mid-regional pro-adrenomedullin (MR-proADM) have been found to be positively associated with all-cause and cardiovascular mortality. However, the underlying mechanisms thereof remain unclear and the associations were mostly shown in geriatric cohorts or in patients with chronic diseases. Therefore, we aimed to investigate the possible involvement of abdominal obesity, selected adipokines, and biomarkers of subclinical inflammation in the association of MR-proADM with mortality in a population based study cohort. METHODS: Prospective analysis of the KORA F4 study; median follow-up 9.1 (8.8-9.4) years. Complete data on MR-proADM and mortality was available for 1551 participants, aged 56.9±12.9 years (mean±SD). Correlation and regression analyses of MR-proADM with overall (BMI) and abdominal obesity (waist circumference), selected adipokines and biomarkers of subclinical inflammation. Cox proportional hazard models on the association of MR-proADM with all-cause and cardiovascular mortality with adjustment for cardiovascular risk factors and selected biomarkers in study subgroups (n = 603-1551). RESULTS: MR-proADM associated with all-cause (HR (95%CI): 2.37 (1.72-3.26) and 2.31 (1.67-3.20)) and cardiovascular mortality (4.28 (2.19-8.39) and 4.44 (2.25-8.76)) after adjustment for traditional cardiovascular risk factors including BMI or waist circumference, respectively. MR-proADM was further associated with four out of seven examined adipokines (leptin, retinol-binding protein-4, chemerin, and adiponectin) and with five out of eleven examined biomarkers of subclinical inflammation (high-sensitivity C-reactive protein, interleukin-6, myeloperoxidase, interleukin-22, and interleukin-1 receptor antagonist) after multivariable adjustment and correction for multiple testing. However, only IL-6 substantially attenuated the association of MR-proADM with all-cause mortality. CONCLUSIONS: We found an association of MR-proADM with (abdominal) obesity, selected adipokines, and biomarkers of subclinical inflammation. However, the association of MR-proADM with mortality was independent of these parameters. Future studies should investigate the role of IL-6 and further characteristics of subclinical inflammation in the association between MR-proADM and all-cause mortality.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
ISSN (print) / ISBN 1932-6203
Journal PLoS ONE
Quellenangaben Volume: 17, Issue: 1, Pages: , Article Number: e0262330 Supplement: ,
Publisher Public Library of Science (PLoS)
Publishing Place Lawrence, Kan.
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) CCG Biomarker for the subclassification of T2DM (KKG-KDB)
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 Health
Ministry of Culture and Science of the state North Rhine Westphalia
German Diabetes Center