FRAILTY could help identify people with metabolic dysfunction-associated steatotic liver disease (MASLD) who face a greater likelihood of cardiovascular events and death, according to findings from a large UK Biobank analysis. Researchers found that poorer frailty status was associated with worse cardiovascular and survival outcomes among adults with MASLD.
Frailty, often regarded as a marker of biological ageing, reflects reduced physiological reserve and greater vulnerability to health stressors. It has been linked to disability, falls and mortality, but its role in shaping cardiovascular outcomes in MASLD has remained unclear.
MASLD, one of the most common chronic liver diseases worldwide, affects an estimated 32% of the global population. The condition is characterised by excess fat accumulation in the liver, as well as metabolic dysfunction. MASLD can progress to inflammation, fibrosis, cirrhosis and hepatocellular carcinoma.
Given that cardiovascular disease is the leading cause of death among people with MASLD, accounting for approximately 41% of MASLD-related deaths, improving cardiovascular risk stratification has become a clinical priority.
Frailty May Refine Cardiovascular Risk Assessment in MASLD
Using data from the UK Biobank, investigators examined whether frailty influences cardiovascular outcomes in adults with MASLD. The analysis included 193,942 participants after exclusions, of whom 69,718 were diagnosed with MASLD.
The prevalence of both pre-frailty and frailty was higher among participants with MASLD than among those without the condition.
During a median follow-up of 14.7 years, 35,881 participants developed CVD, 2,937 died from cardiovascular causes and 15,777 died from any cause.
The study found that, among individuals with MASLD, those classified as frail had significantly lower survival probabilities than participants who were non-frail or pre-frail.
Across the entire cohort, frail individuals had lower survival probabilities for incident CVD, cardiovascular mortality and all-cause mortality regardless of MASLD status.
Stronger Associations Seen in Advanced Liver Disease
When researchers stratified participants by fibrosis stage, frailty remained linked to higher risks of cardiovascular events and death. The relationship appeared stronger among people with MASLD who had a greater fibrosis burden.
The analysis also identified associations between frailty and the incidence of coronary heart disease, heart failure and stroke in people with MASLD. Investigators observed a nonlinear positive relationship between frailty and both CVD and all-cause mortality, while the association with cardiovascular mortality followed a linear pattern.
Gait Speed Emerges as a Key Frailty Marker
Among the individual components of frailty, weight loss, exhaustion, low physical activity and slow gait speed were each associated with higher risks of incident CVD, cardiovascular mortality and all-cause mortality. Slow gait speed emerged as the strongest predictor across all three outcomes, making it the most informative individual frailty marker in the study.
Exhaustion ranked second for predicting cardiovascular events, while low physical activity was the second strongest predictor of cardiovascular mortality and all-cause mortality.
The findings suggest that gait speed, physical activity and fatigue may provide clinically useful information when assessing cardiovascular risk in people with MASLD, although it remains unclear whether interventions targeting these domains can reduce subsequent risk.
Findings Support Further Evaluation
The authors noted that the observed associations, particularly for pre-frailty, were modest and should not be interpreted as indicating large increases in risk for individual patients. Instead, frailty assessment may offer additional prognostic information to support broader risk stratification in a population already at elevated cardiometabolic risk.
The researchers highlighted several limitations, including the use of surrogate measures to identify liver steatosis and fibrosis, reliance on some self-reported data, potential residual confounding and limited generalisability beyond the predominantly White UK Biobank population.
While the observational findings do not establish causality, they support frailty assessment as a potentially useful adjunct for risk stratification in MASLD. Frailty measures may help identify patients who could benefit from more comprehensive cardiovascular and functional evaluation. Further studies are needed to determine whether incorporating frailty assessment into routine care improves clinical management or patient outcomes.
Reference
Ma F et al. The association of frailty with cardiovascular diseases and mortality in metabolic dysfunction-associated steatotic liver disease. Ann Hepatol. 2026;DOI:10.1016/j.aohep.2026.102214.
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