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Association of tricarboxylic acid cycle related-metabolites with hypertension in older adults: a community-based cross-sectional study

Journal of Human Hypertension volume 39, pages 51–57 (2025)Cite this article

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Abstract

Hypertension is still a common chronic disease worldwide and seriously affects human health. Aim of this study was to investigate the association between tricarboxylic acid (TCA) cycle-related metabolites and hypertension in older adults. A total of 1127 community-dwelling older adults were included in this cross-sectional analysis, of whom 609 were assigned to the hypertension group and 518 to the no-hypertension group. Plasma concentrations of 8 TCA cycle-related metabolites (citrate, cis-aconitate, isocitrate, 2-oxoglutarate, succinate, maleate, fumarate, and malate) were determined by gas chromatography–triple quadrupole mass spectrometry. Multivariate logistic regression was used to assess the association between these metabolites and hypertension risk. After adjustment for covariates, we found that the increased plasma concentrations of 2-oxoglutarate and malate were significantly associated with hypertension. These two associations remained unchanged after using the false discovery rate (FDR)-adjustment method (both FDR-adjusted P-trend <0.05). In stratified analysis, these two associations were not modified by overweight, physical activity, and current drinking (all P-interaction >0.05). In the multivariate diagnostic model, the inclusion of these two metabolites modestly and significantly improved the diagnosis of hypertension (AUC = 0.64, 95% CI: 0.60–0.67). These results indicated that plasma 2-oxoglutarate and malate might be the candidate metabolic markers of hypertension among older adults. However, further longitudinal and experimental studies are necessary to confirm this finding.

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Fig. 1: The Spearman’s rank correlation matrix of TCA cycle-related metabolites levels in our study population.
Fig. 2: ROC curves for performance comparison of hypertension diagnostic models.

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Data availability

The data that support the findings of this study are available on request from the corresponding author.

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Funding

This work was supported by the Project of Special Foundation for Science and Technology Development of Central Government Guiding Locals (grant number: 202007d07050008), and the Scientific Research Project for Health Commission of Anhui Province (grant number: AHWJ2021a026).

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Authors and Affiliations

  1. Ma’anshan Center for Disease Control and Prevention, Ma’anshan, China

    Qi-Rong Qin & Jian Chen

  2. The Affiliated Ma’anshan Center for Disease Control and Prevention of Anhui Medical University, Ma’anshan, China

    Qi-Rong Qin & Jian Chen

  3. Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, China

    Qi-Rong Qin, Wen-Lei Hu, Jian-Jun Liu, Meng-Yu Liu & Fen Huang

  4. Department of Health Management Center, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China

    Ming-Jun Hu

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  1. Qi-Rong Qin
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Contributions

Qi-Rong Qin: Conceptualization, Funding acquisition, Data curation, Writing - original draft. Jian Chen: Conceptualization, Project administration. Wen-Lei Hu, Jian-Jun Liu, Meng-Yu Liu: Investigation, Data curation. Fen Huang: Conceptualization, Methodology, Project administration. Ming-Jun Hu: Conceptualization, Methodology, Formal analysis, Writing - review & editing.

Corresponding author

Correspondence to Ming-Jun Hu.

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The authors declare no competing interests.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by the Bioethics Committee of Ma’anshan Center for Disease Control (No. 2020001).

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Qin, QR., Chen, J., Hu, WL. et al. Association of tricarboxylic acid cycle related-metabolites with hypertension in older adults: a community-based cross-sectional study. J Hum Hypertens 39, 51–57 (2025). https://doi.org/10.1038/s41371-024-00976-5

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