Risk factors for atherosclerotic plaque formation in MASLD patients: insights from cross-sectional and Mendelian...

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major contributor to chronic liver disease worldwide, yet the risk factors for carotid plaque in MASLD patients remain unclear. This study aimed to identify these risk factors.

We performed a retrospective cross-sectional analysis of 5372 participants, of whom 2673 met the 2023 MASLD criteria. The MASLD cohort was randomly divided into a training set (70%) and a validation set (30%) to develop a predictive model for carotid atherosclerosis risk. The model's performance and goodness-of-fit were assessed via internal and external validation. Additionally, Mendelian randomization (MR) analysis was performed to investigate the causal relationships between identified risk factors and carotid atherosclerosis. MASLD was significantly associated with carotid plaque formation (P < 0.001). Multivariate analysis identified age, sex, fasting plasma glucose (FPG), and systolic blood pressure (SBP) as independent risk factors, which were used to construct a predictive model (AUC = 0.801, 95% CI: 0.782-0.821). Subgroup analysis indicated that MASLD patients with glucose metabolism abnormalities had a higher plaque risk. MR analysis provided genetic evidence suggesting that genetically proxied SBP (P = 0.018) and FPG (P = 0.004) were associated with carotid atherosclerosis.

A novel predictive model (XY-CPRM) can identify the risk of carotid plaque in the MASLD population. Intensive management of blood glucose and blood pressure is a critical strategy to mitigate cardiovascular risk in MASLD population.