Aspirin Use and Mediterranean Diet Adherence as Factors Associated With Overall Mortality in Patients With MASLD in NHANES

ABSTRACT Aim Full approval for new non‐cirrhotic metabolic dysfunction‐associated steatohepatitis (MASH) therapies requires demonstrating improved mortality. As cardiovascular disease (CVD) is the leading cause of death in metabolic dysfunction‐associated steatotic liver disease (MASLD), we identified factors of all‐cause mortality in a nationally representative cohort, focusing on aspirin and diet. Methods We analyzed 4541 adults (40–79 years) with MASLD from the National Health and Nutrition Examination Survey (NHANES) 2011–2018. Key exposures were aspirin use and adherence to the Mediterranean diet, assessed by the Mediterranean diet score (MDS). Advanced fibrosis was defined as FIB‐4 > 2.67 and included as a covariate in all multivariable Cox models. To adjust for confounding, propensity scores were estimated using multivariable logistic regression that incorporated the complex NHANES survey design. Results In a cohort of 2175 patients with MASLD followed for a mean of 4.5 years, 124 deaths occurred. Among adults > 65 years without prior history of CVD, aspirin use was associated with higher all‐cause mortality (hazard ratio [HR] 9.82; 95% confidence interval [CI] 1.15–83.69); this association was weaker at higher MDS (interaction p = 0.04). In adults with a history of CVD, aspirin use was not associated with survival, whereas higher MDS was independently associated with lower mortality (HR 0.61; 95% CI 0.41–0.93). No material associations were observed in younger adults. MDS was inversely related to inflammatory markers in older patients. Conclusions Aspirin use is independently associated with a several‐fold increased mortality risk in older MASLD patients without prior CVD, an effect partly mitigated by high adherence to the Mediterranean diet. Aspirin for primary CVD prevention should be used with caution in this population. Aspirin use and diet are important, often uncontrolled factors associated with mortality in MASLD clinical trials.