Physical Activity Volume, Intensity Influence Mortality Risk in MASLD

Individuals with metabolic dysfunction-associated steatotic liver disease (MASLD) may benefit from greater volume and intensity of physical activity as well as maintaining normal rest-activity rhythm, according to findings from a recent study.1

Leveraging data from the UK Biobank, the population-based cohort study found higher levels of volume and intensity of physical activity and normal rest-activity rhythm were associated with a reduced risk of all-cause and cardiovascular disease mortality.1

In the absence of pharmacologic treatment options for MASLD, disease management has historically relied on lifestyle modifications. Even with the FDA approval of resmetirom (Rezdiffra) as the first metabolic dysfunction-associated steatohepatitis treatment, diet and exercise continue to play a pivotal role in care for these patients.2

“Individuals with MASLD have a higher mortality risk, and physical activity is important to MASLD management,” Yu Peng, PhD, a professor at Tianjin Medical University in China, and colleagues wrote.1 “However, a comprehensive exploration of associations of volume and intensity of physical activity and rest-activity rhythm based on an accelerometer with all-cause and cause-specific mortality in MASLD individuals was scarce.”

To assess the association between physical activity and the risk of all-cause and cause-specific mortality among individuals with MASLD, investigators examined data for individuals who wore a wrist-worn accelerometer for a week as part of participation in the UK Biobank. They excluded those with cardiovascular disease or cancer, those who were missing variables to define MASLD or calculate fibrosis-4 score, those without MASLD, those with incomplete covariate data, and non-White participants.1

Volume and intensity of physical activity, including low-intensity physical activity (LPA), moderate-to-vigorous-intensity physical activity (MVPA), and sedentary time, were computed from accelerometer data, as was rest-activity rhythm, including amplitude, mesor, pseudo-F statistics, and acrophase.1

The primary outcome was all-cause, cardiovascular disease, and cancer mortality obtained from death registry records.1

A total of 10,143 participants were included in the present analysis. During a median of 7 years of follow-up, there were 352, 123, and 216 all-cause, cardiovascular disease, and cancer mortality events, respectively.1

Upon analysis, each standard deviation (SD) increase in LPA and MVPA was associated with a 23% and 26% reduced risk of all-cause mortality, respectively. With each increase in SD in LPA and MVPA, the risk of cardiovascular disease mortality decreased to 0.712 and 0.805.1

Investigators noted the risk of all-cause and cardiovascular disease mortality increased by 1.19 and 1.31 times per SD increase in sedentary time, but no statistical association was observed between LPA, MVPA, and sedentary time and cancer mortality risk.1

Compared to the least active participants with MASLD, both for LPA and MVPA, multivariable-adjusted hazard ratios (HRs) for all-cause mortality of those in the most active group were 0.720 (95% CI, 0.552–0.940) and 0.641 (95% CI, 0.499, 0.823), respectively.1

With each SD increase in the amplitude and mesor, the risk of all-cause mortality decreased (HR, 0.769; 95% CI, 0.680-0.870 and HR, 0.753; 95% CI, 0.663-0.855). Compared with the lowest tertile, the highest tertile of amplitude (HR, 0.634; 95% CI, 0.500-0.802) and mesor (HR, 0.706; 95% CI, 0.560-0.891) was associated with a reduced risk of all-cause mortality. With each SD increase in amplitude and mesor, the risk of cardiovascular disease mortality decreased to 0.770 (95% CI, 0.610-0.989) and 0.744 (95% CI, 0.584-0.927), respectively.1

Investigators noted the all-cause mortality risk attributable to lower MVPA, amplitude, mesor and LPA in individuals with MASLD was 15.3%, 15.0%, 12.0%, and 8.6%, respectively. An estimated 18.1% and 18.9% of cardiovascular disease mortality risk were attributable to lower MVPA and amplitude.1

Further analysis revealed MVPA, mesor, and amplitude as indicators of physical activity were relatively important risk factors for the risk of all-cause and cardiovascular disease mortality in individuals with MASLD, except for age.1

“This population-based cohort study suggested the importance of volume, intensity, and rhythm of physical activity for reducing the risk of all-cause and CVD mortality, especially all-cause mortality in MASLD individuals with common subtypes of multiple cardiometabolic abnormalities,” investigators concluded.1 “This finding provided valuable insights into health management for individuals with MASLD and may inform the development of relevant guidelines in the future.”

References

1. Peng Y, Liu F, Wang P, et al. Association Between Volume, Intensity and Rhythm of Physical Activity Measured by Accelerometer and Risk of All-Cause and Cause-Specific Mortality in Individuals With MASLD. Aliment Pharmacol Ther. doi:10.1111/apt.70169

2. Brooks A. Resmetirom (Rezdiffra) Receives Historic FDA Approval for Noncirrhotic NASH. HCPLive. March 14, 2024. Accessed April 24, 2025. https://www.hcplive.com/view/resmetirom-rezdiffra-receives-historic-fda-approval-for-noncirrhotic-nash