Association Between Asymmetric Dimethylarginine, Its Change, and Subclinical Carotid Atherosclerosis in Metabolic Dysfunction–Associated Steatotic Liver Disease

Abstract

Objective: To examine whether baseline levels and short-term changes of asymmetric dimethylarginine (ADMA) are associated with subclinical carotid atherosclerosis (SCA) and its progression in adults with metabolic dysfunction–associated steatotic liver disease (MASLD).

Methods: A total of 600 adults with MASLD were prospectively recruited and followed annually for 2 years. Serum ADMA was measured at baseline and 1-year follow-up. SCA, defined as increased carotid intima-media thickness or carotid plaque, was assessed at baseline, 1- and 2-year follow-up. Multivariable regression and propensity score-based analyses were performed to assess the associations between baseline ADMA or change in ADMA and SCA risk.

Results: Increased baseline ADMA level was significantly associated with SCA. Each 1-standard deviation (SD) increase in baseline ADMA was associated with higher odds of SCA (odds ratio 2.24, 95% confidence interval [CI] 1.66–3.01), with a dose–response relationship across ADMA quartiles. Baseline ADMA was not associated with SCA progression; however, dynamic increase in ADMA over time was strongly associated with SCA progression at both 1 and 2 years. Each 1-SD increase in absolute and relative changes of ADMA was associated with higher risks of SCA progression at 1 year (relative risk [RR] 1.82, 95% CI 1.60–2.07; RR 1.44, 95% CI 1.29–1.61) and 2 years (RR 1.52, 95% CI 1.36–1.70; RR 1.31, 95% CI 1.20–1.42). Associations were more pronounced among participants with pre-existing SCA.

Conclusion: ADMA is associated with the prevalence of SCA, and short-term dynamic changes in ADMA may represent early indicators for SCA progression in adults with MASLD.

Keywords

asymmetric dimethylarginine / carotid intima-media thickness / carotid plaque / cohort studies / metabolic dysfunction–associated steatotic liver disease

RIGHTS & PERMISSIONS

2026 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.