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Associations of total homocysteine and kidney function with all-cause and cause-specific mortality in hypertensive patients: a mediation and joint analysis

Hypertension Research volume 47, pages 1500–1511 (2024)Cite this article

A Comment to this article was published on 15 May 2024

Abstract

Plasma total homocysteine (tHcy) and kidney function are both associated with mortality risk, but the degree to which kidney function modifies the impact of tHcy on mortality remains unknown. This prospective cohort study included a total of 14,225 hypertensive adults. Cox proportional hazard regression was used to analyze the separate and combined association of tHcy and estimated glomerular filtration rate (eGFR) with all-cause and cause-specific mortality. Mediation analysis was conducted to explore the mediating effect of eGFR. During a median follow-up of 4.0 years, 805 deaths were identified, including 397 deaths from cardiovascular disease (CVD). There were significant, positive relationships of tHcy with all-cause mortality (per 5 μmol/L; HR: 1.09; 95% CI: 1.07, 1.11), CVD mortality (HR: 1.11; 95% CI: 1.08, 1.13), and non-CVD mortality (HR: 1.07; 95% CI: 1.04, 1.10). The proportions of eGFR mediating these relationships were 39.1%, 35.7%, and 49.7%, respectively. There were additive interactions between tHcy and eGFR. Compared with those with low tHcy (<15 μmol/L) and high eGFR (≥90 mL·min−1·1.73 m−2), participants with high tHcy (≥20 μmol/L) and low eGFR (<60 mL·min−1·1.73 m−2) had the highest risk of all-cause mortality (HR: 4.89; 95% CI: 3.81, 6.28), CVD mortality (HR: 5.80; 95% CI: 4.01, 8.40), and non-CVD mortality (HR: 4.25; 95% CI: 3.02, 5.97). In conclusion, among Chinese hypertensive adults, high tHcy and impaired kidney function were independently and jointly associated with higher risks of all-cause and cause-specific mortality. Importantly, kidney function explained most (nearly 40%) of the increased risk of mortality conferred by high tHcy.

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Acknowledgements

Thank you to Dr. Xiping Xu from the Shenzhen Evergreen Medical Institute, who provided critical insights in the early stages of the work.

Funding

This study was supported by funding from the following: Cultivation of backup projects for National Science and Technology Awards (20223AEI91007), Jiangxi Science and Technology Innovation Base Plan - Jiangxi Clinical Medical Research Center (20223BCG74012), Science and Technology Innovation Base Construction Project (20221ZDG02010), Jiangxi Provincial Natural Science Foundation (20212ACB206019, 20224BAB206090, 20232BAB206140), Fund project of the Second Affiliated Hospital of Nanchang University (2021efyA01, 2022YNFY2017).

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Authors and Affiliations

  1. Department of Cardiovascular Medicine, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China

    Congcong Ding, Junpei Li, Weiguo Fan, Yumeng Shi, Chuanli Yu, Ting Yuan, Peixu Zhao, Xiao Huang, Huihui Bao & Xiaoshu Cheng

  2. Jiangxi Provincial Cardiovascular Disease Clinical Medical Research Center, Nanchang, Jiangxi, China

    Congcong Ding, Junpei Li, Yumeng Shi, Chuanli Yu, Ting Yuan, Peixu Zhao, Wei Zhou, Chao Yu, Tao Wang, Lingjuan Zhu, Xiao Huang, Huihui Bao & Xiaoshu Cheng

  3. Jiangxi Sub-center of National Clinical Research Center for Cardiovascular Diseases, Nanchang, Jiangxi, China

    Congcong Ding, Junpei Li, Yumeng Shi, Chuanli Yu, Ting Yuan, Peixu Zhao, Wei Zhou, Chao Yu, Tao Wang, Lingjuan Zhu, Xiao Huang, Huihui Bao & Xiaoshu Cheng

  4. College of Food Sciences and Nutritional Engineering, China Agricultural University, Beijing, China

    Yaping Wei

  5. Biological anthropology, University of California Santa Barbara, Santa Barbara, CA, USA

    Tianyu Cao

  6. Queen Mary School, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China

    Zihan Chen

  7. Center for Prevention and Treatment of Cardiovascular Diseases, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China

    Wei Zhou, Chao Yu, Tao Wang, Lingjuan Zhu, Xiao Huang, Huihui Bao & Xiaoshu Cheng

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Contributions

CD: study concept and design, acquisition of data, data analysis, data interpretation, drafting of the manuscript, and revision of the manuscript for important intellectual content. JL, YW, WF, TC, ZC, YS, CY, TY, PZ, WZ, CY, TW and LZ: acquisition of data, critical review and revision of the manuscript for important intellectual content. XH, HB and XC: study concept and design, acquisition of data, data management, critical review and revision of the manuscript for important intellectual content.

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Correspondence to Xiao Huang, Huihui Bao or Xiaoshu Cheng.

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Ding, C., Li, J., Wei, Y. et al. Associations of total homocysteine and kidney function with all-cause and cause-specific mortality in hypertensive patients: a mediation and joint analysis. Hypertens Res 47, 1500–1511 (2024). https://doi.org/10.1038/s41440-024-01613-x

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