Association between nonalcoholic fatty liver disease and cardiovascular-kidney-metabolic syndrome progression: evidence from UK biobank and Chinese cohort
W Li, W Chen, R HuangAbstract
Background
Nonalcoholic fatty liver disease (NAFLD), now termed metabolic dysfunction-associated steatotic liver disease (MASLD), is closely linked to insulin resistance and chronic inflammation, serving as a key driver of cardiovascular-kidney-metabolic (CKM) syndrome. However, its precise role in CKM progression remains poorly defined, particularly among non-obese individuals without overt metabolic dysfunction.
Purpose
To investigate the association between NAFLD status and CKM syndrome progression across diverse ethnic populations.
Methods
We conducted observational analyses utilizing data from UK Biobank (UKB) and Tongzhou Cohort (China). CKM progression was defined as transition to a higher stage (from Stage 0/1 to Stage 2 or 3, or from Stage 2 to Stage 3) during follow-up. Multivariable logistic regression was employed to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between NAFLD and CKM progression, with sequential adjustment for demographic and metabolic covariates.
Results
Pooled analyses of UK Biobank and Tongzhou Cohort revealed that prevalent NAFLD exhibited divergent associations with CKM progression across populations, demonstrating protective effects in the overall UK Biobank cohort (OR 0.541, 95% CI 0.369–0.763) and Tongzhou population (OR 0.876, 95% CI 0.784–0.978), but substantially elevated progression risk among Tongzhou individuals at CKM Stage 0/1 (OR 2.985, 95% CI 1.806–5.198). Furthermore, incident NAFLD in Tongzhou Cohort was consistently associated with increased CKM progression risk across all stages, with particularly pronounced effects observed among Stage 0/1 individuals (OR 3.156, 95% CI 2.473–4.050), remaining robust after full covariate adjustment.
Conclusion
Incident NAFLD robustly predicts CKM progression, particularly in early-stage individuals, underscoring the need for targeted prevention strategies.