Asymmetric Dimethylarginine as an Integrative Biomarker of Endothelial, Cardiometabolic and Hepatic Dysfunction in...

Background: Coronary artery disease (CAD) frequently coexists with cardiometabolic and hepatic dysfunction, yet accessible biomarkers capturing this convergence remain limited. Asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, has been proposed as an integrative marker of endothelial and metabolic impairment. This study aimed to evaluate the diagnostic value of ADMA as a unified biomarker of endothelial dysfunction (ED), cardiometabolic burden, and metabolic dysfunction-associated steatotic liver disease (MASLD) in patients with stable CAD. Methods: In this cross-sectional study, 298 patients with stable CAD (functional class I-II) were enrolled at two centers in Tashkent, Uzbekistan. Serum ADMA was measured by ELISA; endothelial function was assessed by flow-mediated dilation (FMD). Associations between ADMA, metabolic indices, MASLD, and CAD severity were analyzed. Results: MASLD was present in 48.3% of CAD patients and metabolic syndrome (MetS) in 62.4%. Patients with MASLD had more severe angina, reduced exercise tolerance, and greater ischemic burden than those without. ADMA correlated positively with BMI, waist circumference, TyG index, and TG/HDL-C ratio (all p < 0.001), with the TyG index showing the strongest predictive value for elevated ADMA (AUC 0.76). A dose-response relationship linked rising ADMA to worsening FMD; concentrations >160 ng/mL conferred markedly increased odds of overt ED (OR 114.8, 95% CI 6.8-1935.0) and were disproportionately prevalent in patients with MASLD (93.1% vs. 61.0%, p < 0.001). Conclusions: ADMA is markedly elevated in stable CAD and closely tracks endothelial, metabolic, and hepatic dysfunction. These cross-sectional associations position ADMA as a promising, hypothesis-generating integrative biomarker; prospective longitudinal studies are needed before its use for risk stratification in primary and cardiovascular care can be recommended.