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

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

Dietary patterns and metabolic dysfunction-associated fatty liver disease in China's multi-ethnic regions.

BACKGROUND: The prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) has been rising rapidly in western China. Diet acts as an effective therapy for MAFLD. However, there has been scarce research on the association between a posteriori diet patterns (DPs) and MAFLD in this region. METHOD: We identified three a posteriori DPs which were "Sichuan Basin pattern" characterized by a high intake of fish/seafood, poultry, fresh fruit and vegetables, indicating a balanced and modern DP; the "Yunnan-Guizhou Plateau dietary pattern" characterized mainly by a high intake of animal oil and salt, indicating an agricultural and poor DP; and the "Qinghai-Tibet Plateau dietary pattern" characterized by a high intake of coarse grains, wheat products, tubers and tea, respectively, indicating a high-altitude DP. Then, we performed marginal structural models that combined logistic regression and inverse probability exposure weighting (IPEW) to examine the associations between MAFLD and these a posteriori DPs. RESULT: We found the "Yunnan-Guizhou Plateau dietary pattern" revealed stronger positive association (OR = 1.50, 95% CI 1.40-1.60) with MAFLD than that of the "Qinghai-Tibet Plateau dietary pattern" (OR = 1.21, 95% CI 1.14-1.30). In contrast, the "Sichuan Basin dietary pattern" showed no significant association with MAFLD. In the further stratified analysis, we found those above associations were stronger in ethnic minorities and rural residents than their counterparts. CONCLUSION: Our study implied the unfavourable effects of "Yunnan-Guizhou Plateau dietary pattern" on MAFLD and provided evidence that reducing the intake of oil and sodium may be optimal for MAFLD control in the multi-ethnic region in western China.

Age at menarche and metabolic dysfunction-associated fatty liver disease: Evidence from a large population-based epidemiological study in Southwest China.

BACKGROUND: The relationship between age at menarche and metabolic dysfunction-associated fatty liver disease remains largely not clear. The objective of this study was to examine the association between age at menarche (AAM) and metabolic dysfunction-associated fatty liver disease (MAFLD) in Chinese women and whether any observed associations were mediated by early adulthood adiposity. METHODS: The cross-sectional study included 46,873 Chinese women, aged 30-79 from baseline data of the China Multi-Ethnic Cohort study. Logistic regression models were used to evaluate the association between AAM and MAFLD. Mediation analysis was adopted to examine whether early adulthood adiposity (around 25 years) mediated the association between AAM and MAFLD. RESULTS: AAM was linearly and inversely associated with the risk of MAFLD (P for nonlinearity =0.743). In a multivariable-adjusted model, the odds ratios and 95% confidence interval (ORs (95% CI)) for MAFLD comparing menarche at <12, 12, 13, 15, 16, 17, ≥18 years to menarche at 14 years were 1.290 (1.082-1.537), 1.172 (1.068-1.285), 1.042 (0.960-1.131), 0.937 (0.861-1.020), 0.911(0.835-0.994), 0.868 (0.786-0.959), and 0.738 (0.670-0.814), respectively (P for trend <0.001). The 6.4% increased MAFLD risk was associated with each preceding year in AAM. The association between AAM and MAFLD was modified by age, ethnicity, and menopause. Early adulthood adiposity partially mediated this association. CONCLUSION: The findings of this study suggest that obesity prevention strategies are needed from young adulthood in women who undergo early menarche to reduce the risk of MAFLD.