Impact of Physical Activity on Cardiovascular Outcomes in Metabolic Dysfunction‐Associated Steatotic Liver Disease

ABSTRACT Aim We investigated whether accelerometer‐assessed moderate‐to‐vigorous physical activity (MVPA) is associated with cardiovascular mortality among individuals with metabolic dysfunction‐associated steatotic liver disease (MASLD) in the United States. Methods We performed a longitudinal analysis using the 2003–2006 US National Health and Nutrition Examination Survey data among adults, with mortality follow‐up through December 2019. We defined MASLD primarily using the Hepatic Steatosis Index (HSI), followed by current cardiometabolic criteria; we used the US Fatty Liver Index (USFLI) in sensitivity analyses. We classified accelerometer‐assessed PA as MVPA, total PA, and sedentary behavior. Results Among 2785 individuals with HSI‐defined MASLD, 584 deaths occurred, including 198 cardiovascular deaths, over a median follow‐up of 14.7 years. A higher level of PA is associated with a more favorable predicted cardiovascular risk profile at baseline. Among individuals with MASLD, increasing MVPA was nonlinearly associated with reduced all‐cause mortality in a multivariable model (hazard ratio [HR]: 0.80, 95% CI: 0.71–0.91 per 10‐min increase; P for trend < 0.001). Furthermore, higher MVPA was nonlinearly associated with a lower risk of cardiovascular mortality in MASLD (HR: 0.72, 95% CI: 0.53–0.99 per 10‐min increase; P for trend = 0.009). Although higher total PA was also associated with reduced mortality, the point estimate was substantially weaker than that observed for MVPA. Sensitivity analyses using the USFLI definition showed directionally similar but attenuated associations. Increased sedentary behavior did not impact mortality in the MASLD group. Conclusions Higher MVPA is nonlinearly associated with cardiovascular mortality in individuals with MASLD.