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Temporal relationship between hepatic steatosis and blood pressure elevation and the mediation effect in the development of cardiovascular disease

Hypertension Research (2024)Cite this article

Abstract

The temporal relationship between non-alcoholic fatty liver disease (NAFLD) and hypertension remains highly controversial, with ongoing debates on whether NAFLD induces hypertension or vice versa. We employed cross-lagged panel models to investigate the temporal relationship between hepatic steatosis (assessed by Fatty Liver Index [FLI] in the main analysis, and by Proton Density Fat Fraction [PDFF] in the validation study) and blood pressure (systolic and diastolic blood pressure [SBP/ DBP]). Subsequently, we employed causal mediation models to explore the mediation effect in CVD development, including ischemic heart disease and stroke. The main analysis incorporated repeated measurement data of 5,047 participants from the China Multi-Ethnic Cohort (CMEC) and 5,685 participants from the UK Biobank (UKB). In both cohorts, the path coefficients from FLI to blood pressure were significant and greater than the path from blood pressure to FLI, with βFLI→SBP = 0.081, P < 0.001 versus βSBP→FLI = 0.020, P = 0.031; βFLI→DBP = 0.082, P < 0.001 versus βDBP→FLI = −0.006, P = 0.480 for CEMC, and βFLI→SBP = 0.057, P < 0.001 versus βSBP→FLI = −0.001, P = 0.727; βFLI→DBP = 0.061, P < 0.001, versus βDBP→FLI = −0.006, P = 0.263 for UKB. The validation study with 962 UKB participants using PDFF consistently supported these findings. In the mediation analyses encompassing 11,108 UKB participants, SBP and DBP mediated 12.2% and 5.2% of the hepatic steatosis-CVD association, respectively. The proportions were lower for ischemic heart disease (SBP: 6.1%, DBP: non-statistically significant −6.8%), and relatively stronger for stroke (SBP: 19.4%, DBP: 26.1%). In conclusion, hepatic steatosis more strongly contributes to elevated blood pressure than vice versa. Blood pressure elevation positively mediates the hepatic steatosis-CVD association, particularly in stroke compared to ischemic heart disease.

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Data availability

The data from the China Multi-Ethnic Cohort can be obtained upon request from the author, Xing Zhao, via email at xingzhao@scu.edu.cn. Access to UK Biobank data can be requested through the official website (https://www.ukbiobank.ac.uk/).

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Acknowledgements

This research has been conducted using the UK Biobank resource under Application Number 117185.

Funding

This study was sponsored by the National Natural Science Foundation of China (Grant no. 82273740). The CMEC study was funded by the National Key R&D Program of China (Grant no. 2017YFCO907300).

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Author notes

  1. These authors contributed equally: Yifan Hu, Wenge Tang.

Authors and Affiliations

  1. West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China

    Yifan Hu, Yujie Liu, Ning Zhang, Xingren Zhu, Dan Tang, Yuan Zhang, Xiong Xiao & Xing Zhao

  2. Chongqing Municipal Center for Disease Control and Prevention, Chongqing, China

    Wenge Tang

  3. State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Research Unit of Oral Carcinogenesis and Management, Chinese Academy of Medical Sciences, West China Hospital of Stomatology, Sichuan University, Chengdu, China

    Hao Xu

  4. High Altitude Health Science Research Center of Tibet University, Lhasa, China

    Duoji Zhuoma

  5. School of Public Health, the Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, China

    Tingting Yang

  6. Chengdu Center for Disease Control and Prevention, Chengdu, China

    Zhimiao Yu

  7. School of Public Health, Kunming Medical University, Kunming, China

    Chuanzhi Xu

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Contributions

Study concept and design: YH, XX; acquisition of data: XZ, WT, HX, D, TY, ZY, CX; analysis and interpretation of data: YH, YL, NZ, XZ, DT, YZ; drafting of the manuscript: YH, critical revision of the manuscript: XX, XZ. All authors approved the final version of the article.

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Correspondence to Xiong Xiao.

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Hu, Y., Tang, W., Liu, Y. et al. Temporal relationship between hepatic steatosis and blood pressure elevation and the mediation effect in the development of cardiovascular disease. Hypertens Res (2024). https://doi.org/10.1038/s41440-024-01708-5

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