The association between hepatic steatosis and incident cardiovascular disease, cancer, and all-cause mortality in a US multicohort study

Abstract

Background and Aims: NAFLD strongly associates with cardiovascular disease (CVD) risk factors; however, the association between NAFLD and incident CVD, CVD-related mortality, incident cancer, and all-cause mortality is unclear. Approach and Results: We included 10,040 participants from the Framingham Heart Study, the Coronary Artery Risk Development in Young Adults Study, and the Multi-ethnic Study of Atherosclerosis to assess the longitudinal association between liver fat (defined on CT) and incident CVD, CVD-related mortality, incident cancer, and all-cause mortality. We performed multivariable-adjusted Cox regression models including age, sex, diabetes, systolic blood pressure, alcohol use, smoking, HDL, triglycerides, and body mass index at baseline or time-varying covariates. The average age was 51.3±3.3 years and 50.6% were women. Hepatic steatosis was associated with all-cause mortality after 12.7 years of mean follow-up when adjusting for baseline CVD risk factors, including body mass index (HR: 1.21, 1.04–1.40); however, the results were attenuated when utilizing time-varying covariates. The association between hepatic steatosis and incident CVD was not statistically significant after we accounted for body mass index in models considering baseline covariates or time-varying covariates. We observed no association between hepatic steatosis and CVD-related mortality or incident cancer. Conclusions: In this large, multicohort study of participants with CT-defined hepatic steatosis, accounting for change in CVD risk factors over time attenuated associations between liver fat and overall mortality or incident CVD. Our work highlights the need to consider concurrent cardiometabolic disease when determining associations between NAFLD and CVD and mortality outcomes.

Validation of the Fatty Liver Index for identifying non‐alcoholic fatty liver disease in a Kenyan population

“…Growing evidence suggests that risk factors for NAFLD, its progression and severity are also greatly influenced by ethnicity, which involves genetic and epigenetic background, lifestyle components such as diet, physical activity and cardiorespiratory fitness, socio-economic variables and other environmental factors [6,[44][45][46]. Only a few studies have examined the ethnic differences in the underlying mechanisms involved in the association between adiposity, insulin resistance, NAFLD and the risk of cardiovascular diseases [46][47][48]. Despite having an increased risk of T2DM and cardiovascular diseases, African-descent populations have consistently been shown to have lower levels of TG, compared to their European descent counterparts [49,50].…”

Letter to the Editor: The associations between hepatic steatosis and incident cardiovascular disease and all-cause mortality

“…In addition, we noted that Ahmed et al [1] adjusted for the risk factors of CVD together. However, it seemed that not all included risk factors were associated with NAFLD-related CVD events.…”

“…To the editor, We read with great interest the recent article in Hepatology by Ahmed et al [1] Impressively, Ahmed and colleagues not only adjusted for cardiovascular disease (CVD) risk factors in baseline but also adjusted for changes in CVD risk factors over time. The associations between hepatic steatosis and incident CVD and all-cause mortality were attenuated when accounting for a change in CVD risk factors over time.…”

Hepatic steatosis provides the terroir that promotes the development of cardiovascular risk factors and disease

“…In this issue of HEPATOLOGY, Ahmed et al [4] report the findings of a detailed evaluation of incident CVD and CVD-related mortality, together with incident extrahepatic malignancy in 3 well phenotyped cohorts. These cohorts were initially developed for the purpose of cardiovascular risk prediction and had data on all conventional CVD risk factors along with liver fat measured by CT.…”