Author information
1Section of Gastroenterology, Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts, USA.
2Biostatistics and Epidemiology Data Analytics Center, Boston University School of Public Health, Boston, Massachusetts, USA.
3Department of Radiology and Radiological Services, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
4Section of Gerontology and Geriatric Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
5Division of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
6Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
7Department of Computer Science, Vanderbilt University School of Engineering, Nashville, Tennessee, USA.
8Section of Cardiology, Department of Medicine, Boston Medical Center/Boston University School of Medicine, and Epidemiology, Boston University School of Public Health, Boston, Massachusetts, USA.
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.