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

Yifan Hu; Wenge Tang; Yujie Liu; Ning Zhang; Xingren Zhu; Dan Tang; Yuan Zhang; Hao Xu; Duoji Zhuoma; Tingting Yang; Zhimiao Yu; Chuanzhi Xu; Xiong Xiao; Xing Zhao

doi:10.1038/s41440-024-01708-5

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

Hypertens Res. 2024 May 17. doi: 10.1038/s41440-024-01708-5. Online ahead of print.

Authors

Yifan Hu^#¹, Wenge Tang^#², Yujie Liu¹, Ning Zhang¹, Xingren Zhu¹, Dan Tang¹, Yuan Zhang¹, Hao Xu³, Duoji Zhuoma⁴, Tingting Yang⁵, Zhimiao Yu⁶, Chuanzhi Xu⁷, Xiong Xiao⁸, Xing Zhao¹

Affiliations

¹ West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China.
² Chongqing Municipal Center for Disease Control and Prevention, Chongqing, China.
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.
⁴ High Altitude Health Science Research Center of Tibet University, Lhasa, China.
⁵ School of Public Health, the Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, China.
⁶ Chengdu Center for Disease Control and Prevention, Chengdu, China.
⁷ School of Public Health, Kunming Medical University, Kunming, China.
⁸ West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China. xiaoxiong.scu@scu.edu.cn.

^# Contributed equally.

PMID: 38760520
DOI: 10.1038/s41440-024-01708-5

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 β_FLI→SBP = 0.081, P < 0.001 versus β_SBP→FLI = 0.020, P = 0.031; β_FLI→DBP = 0.082, P < 0.001 versus β_DBP→FLI = -0.006, P = 0.480 for CEMC, and β_FLI→SBP = 0.057, P < 0.001 versus β_SBP→FLI = -0.001, P = 0.727; β_FLI→DBP = 0.061, P < 0.001, versus β_DBP→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.

Keywords: CVD; NAFLD; blood pressure; hepatic steatosis; temporal relationship..