MAFLD is associated with increased all-cause mortality in low cardiovascular-risk individuals but not in intermediate to high-risk individuals.

Background And Aims: Metabolic-associated fatty liver disease (MAFLD) is increasingly recognized as a systematic disease rather than just a liver disease alone, which raises concerns about its long-term impact on different populations. This study aimed to clarify the effects of MAFLD on long-term outcomes among different cardiovascular risk-stratified populations.

Methods And Results: Eligible individuals in the Third National Health and Nutrition Examination Surveys (NHANES Ⅲ, 1988-1994) were enrolled. Participants were classified into low, intermediate, or high cardiovascular-risk populations according to the Framingham general equations. Kaplan-Meier survival analysis and Cox regression models were used to investigate the association between MAFLD and long-term outcomes in different cardiovascular-risk populations. A total of 8897 adults were enrolled in the final analysis. The median ages in the non-MAFLD and MAFLD groups were 44 and 49 years old, respectively. During a median follow-up of 22.8 years, a total of 2991 deaths were recorded, including 1694 deaths (30.3%) in non-MAFLD and 1297 deaths (39.2%) in MAFLD (P < 0.001). In the low cardiovascular-risk population, MAFLD individuals had increased all-cause mortality than non-MAFLD individuals (HR = 1.206, 95% CI:1.0338-1.400, P = 0.014). However, similar results were not observed in intermediate or high-cardiovascular-risk individuals. Further analysis of cause-specific mortality suggested that MAFLD was associated with higher cancer-related mortality in the low-risk population (HR = 1.313, 95% CI:1.000-1.725, P = 0.049).

Conclusions: MAFLD was associated with increased all-cause mortality among individuals with low cardiovascular risk, rather than those with an intermediate or high cardiovascular risk.