Interplay between cardiometabolic risk factors in metabolic dysfunction-associated steatotic liver disease: Clinical evidence on cardiovascular disease

Table 3 Network of cardiometabolic risk factors between metabolic dysfunction-associated steatotic liver disease and cardiovascular disease

Factor	Key drivers/mechanisms	Relationship to MASLD and CVD
Obesity and visceral fat	High energy intake leads to hypertrophy of adipocytes in the adipose tissue	BMI and waist circumference positively correlate with MASLD progression. Visceral adipose tissue mediates the majority of cardiometabolic risk by promoting insulin resistance
Insulin resistance	Disruption of metabolic pathways in muscle, liver, and adipose tissue. Driven by hyperinsulinemia and lipotoxicity	Creates a vicious cycle with hepatic steatosis. Insulin resistance exacerbates dyslipidemia and endothelial dysfunction and is the most important factor driving atherosclerotic CVD
Dyslipidemia	Increased VLDL-cholesterol synthesis, elevated triglycerides, and reduced HDL-cholesterol (atherogenic profile)	Enhance atherogenesis. Affects a high percentage of MASLD/MASH patients. Promotes plaque formation and increased risk of myocardial infarction
Systemic inflammation	Secretion of pro-inflammatory adipokines (TNF-α, IL-6, CRP) and reduced adiponectin	Cytokines from the diseased liver drain into circulation, intensifying a systemic pro-inflammatory state that leads to CVD. Promotes vascular injury, atherosclerosis
Oxidative stress	Imbalance between ROS and antioxidants (e.g., low glutathione)	High ROS levels cause mitochondrial dysfunction and hepatocyte apoptosis, leading to fibrosis (MASH). Promotes plaque instability
Endothelial dysfunction	Reduced nitric oxide bioavailability and increased ADMA or endothelin-1	An early event linking MASLD to CVD. Correlates with the severity of liver steatosis and arterial stiffening. Promotes thrombosis
Hypertension	Activation of the RAAS and sympathetic nervous system	Bidirectional relationship: Hypertension aggravates liver damage, while MASLD influences high blood pressure development

VLDL: Very low-density lipoprotein; HDL: High-density lipoprotein; TNF-α: Tumor necrosis factor-alpha; IL-6: Interleukin-6; CRP: C-reactive protein; ROS: Reactive oxygen species; ADMA: Asymmetric dimethylarginine; RAAS: Renin-angiotensin-aldosterone system; MASLD: Metabolic dysfunction-associated steatotic liver disease; BMI: Body mass index; CVD: Cardiovascular disease; MASH: Metabolic dysfunction-associated steatohepatitis.