Increasing Cardiovascular Disease–Related Mortality Burden in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) in the United States

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a complex multisystem disorder, with cardiovascular disease (CVD) representing the most common cause of mortality. This study aims to analyze trends in MASLD and CVD-related mortality in the United States. Methods: Mortality data for individuals aged 25 years and older from 1999 to 2024 were obtained from the CDC WONDER database. Age-adjusted mortality rates (AAMRs) per 100,000 population were calculated among patients with MASLD and CVD. Temporal trends were assessed using Joinpoint regression analysis to estimate the annual percent change (APC) and average annual percent change (AAPC) in mortality rates. Results: Between 1999 and 2024, a total of 55,788 deaths were identified related to MASLD and CVD among adults aged 25 years or older. The number of deaths increased from 1044 in 1999 to 5216 in 2024, reflecting a 400% increase in mortality. The most common causes of CVD-related mortality were hypertension and ischemic heart disease. The total number of deaths among men was higher compared to women (30,201 vs. 25,587), and the rate of increase in mortality was higher among women (7.60, 95% CI: 7.07-8.35 vs. 3.42, 95% CI: 2.78-4.17). Conclusion: Our analysis highlights acceleration in CVD-related mortality among MASLD patients with widening disparities. These findings highlight MASLD as a growing contributor to cardiovascular mortality, and targeted prevention, along with reduction strategies, are urgently needed to mitigate this rising burden.