LEAN VETERANS WITH MASLD HAVE SIGNIFICANTLY GREATER RISK OF CARDIOVASCULAR EVENTS AND ALL-CAUSE MORTALITY COMPARED TO OVERWEIGHT/OBESE VETERANS WITH MASLD

Background: Adults with metabolic dysfunction associated steatotic liver disease (MASLD) have high risk of cardiovascular disease (CVD) and CVD-related mortality. However, it remains unclear whether adults with lean vs. overweight/obese MASLD have significant differences in long-term risk of CVD and overall survival. We aimed to evaluate the impact of lean vs. overweight/obese body mass index (BMI) on the incidence of major adverse cardiovascular events (MACE) and long-term survival in a national cohort of U.S Veterans with MASLD.
Methods: We retrospectively evaluated the Veterans Affairs (VA) Corporate Data Warehouse from 2010-2023, which captures longitudinal data on all Veterans receiving health care at VA facilities across the U.S. MASLD was identified using established definitions: presence of hepatic steatosis (defined by hepatic steatosis index >36) plus >1 of the following: 1) body mass index >25 kg/m² in non-Asians or >23 kg/m² in Asians, 2) diabetes mellitus, or 3) >1 metabolic risk factors. Alcohol use was captured by AUDIT-C scores and Veterans who reported no alcohol use (AUDIT-C=0) were included in the analyses. BMI was categorized into lean vs. overweight groups based on BMI cutoffs (<25 kg/m² in non-Asians or <23 kg/m² in Asians). Incidence of MACE (identified via ICD-9/10) and long-term survival among non-cirrhotic MASLD was evaluated using competing-risks Nelson-Aalen cumulative hazards and Kaplan Meier methods, stratified by lean vs. overweight MASLD. Adjusted multivariate Cox proportional hazards models evaluated for predictors of MACE and all-cause mortality.
Results: Among 1,629,104 Veterans with non-cirrhotic MASLD (94.0% men, 65.6% non-Hispanic white), 92.9% were overweight and 7.1% were lean. Compared to overweight Veterans, lean MASLD Veterans were more likely to be age >60 years (71.7% vs 60.1% p<0.001) and more likely to have a FIB-4 index > 2.67 (15.6% vs 8.7%, p<0.001). The incidence of MACE was significantly higher in those with lean vs. overweight MASLD (11.79 vs. 8.32 per 100-person years, p<0.001) (Figure 1). Compared to overweight MASLD patients, overall 5-year survival was significantly lower in lean MASLD Veterans (70.3% vs. 87.8%, p<0.001) (Figure 1). On multivariate regression, compared to overweight MASLD, Veterans with lean MASLD had higher risks of MACE (HR 1.06, 95% CI 1.05-1.07, p<0.001) and all-cause mortality (HR 1.77, 95% CI 1.75-1.79, p<0.001) (Table 1).
Conclusion: Among a national cohort of U.S. Veterans with MASLD, lean BMI (vs overweight BMI) was associated with significantly higher incidence of MACE and significantly lower long-term survival. It is important to raise awareness of the poor outcomes in individuals with lean MASLD and address modifiable factors that may improve disparities between lean and overweight MASLD.