MASLD and cardiovascular disease: a state-of-the-art review

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly nonalcoholic fatty liver disease, is the most prevalent chronic liver disease worldwide, affecting more than 30% of adults and up to 70–90% of individuals with obesity or type 2 diabetes mellitus. Cardiovascular disease (CVD) represents the leading cause of mortality in this population. MASLD is increasingly recognized as an independent cardiovascular risk factor beyond traditional metabolic comorbidities. This narrative review summarizes epidemiologic, mechanistic, and clinical evidence linking MASLD with cardiovascular disease, with a focus on population-based cohort studies, imaging-based assessments of subclinical cardiovascular disease, and fibrosis-based risk stratification. Population-based cohorts, including the Framingham Heart Study and the Multi-Ethnic Study of Atherosclerosis, demonstrate that hepatic steatosis is associated with a 1.5–2.0-fold increased risk of incident cardiovascular events after adjustment for age, sex, body mass index, diabetes, and lipid levels. MASLD is characterized by insulin resistance, increased visceral adiposity, atherogenic dyslipidemia with elevated triglycerides, small dense low-density lipoprotein particles, and reduced high-density lipoprotein cholesterol. Patients exhibit systemic low-grade inflammation with elevated tumor necrosis factor-α, interleukin-6, and high-sensitivity C-reactive protein, alongside altered adipokine and hepatokine signaling, including reduced adiponectin and increased leptin, resistin, fetuin-A, and fibroblast growth factor 21. Imaging studies identify higher carotid intima–media thickness, increased coronary artery calcium scores, and early left ventricular diastolic dysfunction in patients with MASLD compared with controls. Fibrosis stage has emerged as the strongest hepatic predictor of cardiovascular outcomes. Individuals with advanced fibrosis have significantly higher rates of cardiovascular events and mortality compared with those without fibrosis, independent of traditional risk factors. Emerging data also implicate gut–liver axis dysfunction and increased intestinal permeability in amplifying systemic inflammation and vascular injury. MASLD is closely linked to cardiovascular disease through shared metabolic, inflammatory, and fibrotic pathways. Cardiovascular risk in MASLD is driven primarily by fibrosis severity rather than steatosis burden. Incorporation of liver disease assessment, particularly fibrosis evaluation, into cardiovascular risk stratification may improve identification of high-risk individuals and support integrated cardiometabolic care.