Association of NAFLD with cardiovascular disease and all-cause mortality: a large-scale prospective cohort study based on UK Biobank

OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) is considered as the hepatic manifestation of metabolic syndrome, sharing the similar cardiometabolic risk factors with cardiovascular disease (CVD). Whether NAFLD by itself is associated with increased cardiovascular events and death remain an issue to debate. This study aimed to further investigate the association between NAFLD and adverse CVD outcomes. METHODS: Participants were followed up until the end of 2020 in current analysis. NAFLD is defined using fatty liver index (FLI). Cox proportional hazard model was used to analyze the association between NAFLD and all-cause mortality, major adverse cardiovascular events (MACEs), CVD mortality, fatal/nonfatal acute myocardial infarction (AMI), and fatal/nonfatal stroke. C-index was calculated to evaluate the model enhancement when adding NAFLD factor. RESULTS: After screening the data of 502,492 participants in the original cohort, 215,245 eligible participants were included in this study for MACEs outcome. Compared with non-NAFLD participants, the multivariable adjusted hazard ratios of NAFLD group was 1.25 (1.14–1.36) for MACEs; 1.14 (1.08–1.20) for all-cause mortality; 1.61(1.42–1.82) for CVD mortality; 1.58(1.19–2.11) for AMI mortality; and 1.18 (0.85–1.64) for stroke mortality. When adding FLI, C-index of NAFLD model improved for all-cause mortality, MACEs, and CVD mortality compared with that in the traditional CVD risk factor model. CONCLUSION: NAFLD is an independent risk factor for all-cause mortality and adverse CVD outcomes. Based on the traditional CVD risk factor model, additionally screening NAFLD could improve the prediction efficiency for adverse CVD outcomes.