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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2063-2072 |
| Number of pages | 10 |
| Journal | Hepatology |
| Volume | 77 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jun 2023 |
Funding
J. Jeffrey Carr received grants from Thera Technologies. Lisa B. VanWagner consults for Noble Insights, Slingshot Insights and Gerson Lehrman Group. He received grants from W.L. Gore and Associates. Yuankai Huo received grants from IBM. Michelle T. Long is employed by and owns stock in Novo Nordisk. The remaining authors have no conflict of interest to declare. The Framingham Heart Study is supported in part by the National Heart, Lung, and Blood Institute contracts N01-HC-25195, HHSN268201500001, and 75N92019D00031. The Coronary Artery Risk Development in Young Adults Study (CARDIA) is supported by contracts HHSN268201800003I, HHSN268201800004I, HHSN268201800005I, HHSN268201800006I, HHSN268201800007I, and R01-HL098445 from the National Heart, Lung, and Blood Institute (NHLBI). The Multi-ethnic Study of Atherosclerosis (MESA) is supported by contracts 75N92020D00001, HHSN268201500003I, N01-HC-95159, 75N92020D00005, N01-HC-95160, 75N92020D00002, N01-HC-95161, 75N92020D00003, N01-HC-95162, 75N92020D00006, N01-HC-95163, 75N92020D00004, N01-HC-95164, 75N92020D00007, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, and N01-HC-95169 from the National Heart, Lung, and Blood Institute, and by grants UL1-TR-000040, UL1-TR-001079, and UL1-TR-001420 from the National Center for Advancing Translational Sciences (NCATS). Michelle T. Long is supported in part by the National Institute of Diabetes and Digestive and Kidney Diseases K23 DK113252, the Doris Duke Charitable Foundation Grant #2019085, Gilead Sciences Research Scholars Award, the Boston University School of Medicine Department of Medicine Career Investment Award, and the Boston University Clinical Translational Science Institute UL1 TR001430. Heidi S. Ahmed is supported in part by the National Institute of Health T32 DK 720142. Lisa B. VanWagner is supported in part by the National Heart, Lung, and Blood Institute K23 HL136891. Emelia J. Benjamin is supported by R01HL092577; American Heart Association AHA_18SFRN34110082.
ASJC Scopus subject areas
- Hepatology
