Metabolic Dysfunction-Associated Steatotic Liver Disease and Cardiovascular Disease: Shared Mechanisms and...

Metabolic dysfunction-associated steatotic liver disease (MASLD) affects ~25-30% of adults worldwide and is increasingly recognized as a systemic cardiometabolic disorder rather than an isolated liver condition. While MASLD can progress to advanced fibrosis and cirrhosis, cardiovascular disease (CVD) is the leading cause of morbidity and mortality in this population, surpassing liver-related deaths. Beyond shared risk factors such as obesity, insulin resistance, and type 2 diabetes, MASLD is independently linked to atherosclerotic CVD, heart failure-particularly heart failure with preserved ejection fraction-and atrial arrhythmias through mechanisms including lipotoxicity, chronic inflammation, endothelial dysfunction, and atherogenic dyslipidemia. This review summarizes evidence connecting MASLD pathobiology with CVD and evaluates emerging pharmacologic strategies that target metabolic dysfunction with relevance to both hepatic and cardiovascular outcomes. We highlight 3 mechanistically complementary therapeutic classes: thyroid hormone receptor-β agonists, glucagon-like peptide-1 receptor agonists, and sodium-glucose cotransporter-2 inhibitors. Thyroid hormone receptor-β agonism (resmetirom) improves hepatic lipid handling, steatosis, and fibrosis while lowering apolipoprotein B-containing lipoproteins, though cardiovascular outcomes data remain pending. Glucagon-like peptide-1 receptor agonists reduce weight, improve insulin sensitivity, and lower major adverse cardiovascular events. Sodium-glucose cotransporter-2 inhibitors provide strong protection against heart failure and chronic kidney disease while improving metabolic and hepatic parameters. Together, these therapies reinforce MASLD as a cardiovascular-relevant metabolic disease and support integrated cardiometabolic approaches to reduce CVD risk.