Metabolic dysfunction associated steatotic liver disease (MASLD), previously known as nonalcoholic fatty liver disease (NAFLD), is the umbrella term which includes metabolic dysfunction associated fatty liver, and metabolic dysfunction associated steatohepatitis (MASH).1 MASLD is assumed to affect 10%-30% of the general U.S. population and, at more advanced stages, can progress to cirrhosis and liver cancer.2,3 Further, the incidence of MASLD diagnosis in the U.S. has increased 5‐fold over the last two decades with a disproportionate increase among young adults.4 In patients with MASLD, advanced liver fibrosis is linked to worse clinical outcomes including all-cause mortality.5 Cardiovascular disease (CVD) is one of the leading causes of mortality among patients with MASLD and growing evidence suggests that MASLD is an independent risk factor for CVD.6,7

Similar to MASLD, heart failure (HF) is marked by high cardiovascular morbidity and mortality that has reached epidemic proportions.4 HF is now amongst the top causes of hospitalization in patients over the age of 60.8 Mounting evidence suggests that MASLD, independent of other established risk factors for HF, is associated with left ventricular remodeling and diastolic dysfunction.9, 10, 11, 12 Specifically, a link between MASLD and heart failure with preserved ejection fraction (HFpEF) has been proposed on the basis of shared pathophysiologic characteristics such as metabolic syndrome, insulin resistance, systemic inflammation, and altered cardiac energy metabolism. Independent of HF subtype, patients with concomitant MASLD and clinical HF are at a 5-fold higher risk for re-hospitalization for HF related causes and greater degree of liver fibrosis is associated with a worse clinical course.13, 14, 15

Existing literature demonstrates that not all adiposity is the same; specifically, different phenotypes of fat deposition portend different risk.16 Recognizing this existing literature and the fact that increased body mass index (BMI) is associated with increased liver fat, we investigated disproportionate liver fat (DLF), or liver adiposity that is not otherwise predicted by BMI, as a metric that may predict indolent cardiotoxicity by investigating its association with known CVD risk factors. Individuals with high DLF represent those with liver fat levels that are elevated out of proportion to what would be predicted by their BMI. We evaluated the association of disproportionate liver fat, cardiotoxic metabolic profiles, and structural and functional parameters which may present upstream of both MASLD and HFpEF in the Multi-Ethnic Study of Atherosclerosis (MESA).