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Lin, J. ; Petrera, A. ; Hauck, S.M. ; Müller, C.L. ; Peters, A. ; Thorand, B.

Associations of proteomics with hypertension and systolic blood pressure: KORA S4/F4/FF4 and KORA-Age1/Age2 Cohort Studies.

Hypertension 81, 1156-1166 (2024)
DOI PMC
Creative Commons Lizenzvertrag
Open Access Green as soon as Postprint is submitted to ZB.
BACKGROUND: Hypertension, a complex condition, is primarily defined based on blood pressure readings without involving its pathophysiological mechanisms. We aimed to identify biomarkers through a proteomic approach, thereby enhancing the future definition of hypertension with insights into its molecular mechanisms. METHODS: The discovery analysis included 1560 participants, aged 55 to 74 years at baseline, from the KORA (Cooperative Health Research in the Region of Augsburg) S4/F4/FF4 cohort study, with 3332 observations over a median of 13.4 years of follow-up. Generalized estimating equations were used to estimate the associations of 233 plasma proteins with hypertension and systolic blood pressure (SBP). For validation, proteins significantly associated with hypertension or SBP in discovery analysis were validated in the KORA-Age1/Age2 cohort study (1024 participants, 1810 observations). A 2-sample Mendelian randomization analysis was conducted to infer causalities of validated proteins with SBP. RESULTS: Discovery analysis identified 49 proteins associated with hypertension and 99 associated with SBP. Validation in the KORA-Age1/Age2 study replicated 7 proteins associated with hypertension and 23 associated with SBP. Three proteins, NT-proBNP (N-terminal pro-B-type natriuretic peptide), KIM1 (kidney injury molecule 1), and OPG (osteoprotegerin), consistently showed positive associations with both outcomes. Five proteins demonstrated potential causal associations with SBP in Mendelian randomization analysis, including NT-proBNP and OPG. CONCLUSIONS: We identified and validated 7 hypertension-associated and 23 SBP-associated proteins across 2 cohort studies. KIM1, NT-proBNP, and OPG demonstrated robust associations, and OPG was identified for the first time as associated with blood pressure. For NT-proBNP (protective) and OPG, causal associations with SBP were suggested.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Mendelian Randomization Analysis ; Blood Pressure ; Cohort Studies ; Hypertension ; Proteomics; Kidney Injury Molecule-1; Incident Hypertension; Natriuretic Peptide; Urine Biomarkers; Renal-function; Health; Population; Disease; Risk; Bias
ISSN (print) / ISBN 0194-911x
e-ISSN 1524-4563
Journal Hypertension
Quellenangaben Volume: 81, Issue: 5, Pages: 1156-1166 Article Number: , Supplement: ,
Publisher Lippincott Williams & Wilkins
Publishing Place Two Commerce Sq, 2001 Market St, Philadelphia, Pa 19103 Usa
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology II (EPI2)
CF Metabolomics & Proteomics (CF-MPC)
Institute of Computational Biology (ICB)
Grants Helmholtz Institute for Metabolic, Obesity and Vascular Research
State of Bavaria
German Research Center for Environmental Health - German Federal Ministry of Education and Research
Helmholtz Zentrum Munchen