# Unraveling the Dyslipidemic Landscape in Moyamoya Disease: OxLDL as a Key Biomarker

## TL;DR

This study identifies oxidized low-density lipoprotein (oxLDL) as a key biomarker in moyamoya disease, suggesting a link between dyslipidemia and the condition's development.

## Contribution

The study is the first to systematically characterize dyslipidemic profiles in moyamoya disease and establish oxLDL as a pivotal risk factor.

## Key findings

- MMD patients had significantly higher levels of oxLDL, sdLDL, and lipoprotein(a) compared to healthy controls.
- OxLDL was identified as an independent risk factor for MMD with a strong adjusted odds ratio.
- WQS and BKMR analyses confirmed oxLDL's dominant role and its synergistic interaction with homocysteine.

## Abstract

The pathogenic mechanisms of moyamoya disease (MMD) remain unrecognized. Although genetic predisposition and hemodynamic changes have been focused on, emerging evidence suggests dyslipidemia may also contribute to MMD. Here, we performed a comprehensive analysis of lipid profiles, aiming to elucidate potential mechanisms in MMD.

In this prospective case–control study, 222 MMD patients and 231 healthy controls (HCs) were enrolled. The comprehensive lipid profiling was performed, encompassing standard lipids, apolipoproteins, oxidized low‐density lipoprotein (oxLDL), and small dense LDL (sdLDL). Statistical models of weighted quantile sum (WQS) and Bayesian kernel machine regression (BKMR) were applied to capture individual and joint lipid effects on MMD risk.

Compared with HCs, MMD patients exhibited significantly higher oxLDL, sdLDL, and lipoprotein(a) (p < 0.05). OxLDL emerged as a robust independent risk factor for MMD (adjusted OR 1.146, 95% CI 1.102–1.210, p < 0.001). WQS analysis further identified oxLDL as the single greatest contributor to MMD risk, with additional support from BKMR showing marked synergistic interactions between oxLDL and homocysteine.

The study revealed a comprehensive dyslipidemic landscape in MMD, highlighting oxLDL as a pivotal biomarker. The results underscored the significance of lipid metabolism in MMD pathogenesis, warranting further investigation to guide novel diagnostic and therapeutic strategies.

Our study systematically characterized the dyslipidemic profiles of patients with moyamoya disease (MMD) and uncovered a pivotal role of oxLDL in MMD pathogenesis. Higher level of oxLDL was closely associated with increased disease risk, indicating the potential value as diagnostic and therapeutic targets. These findings highlighted the significance of lipid metabolism in guiding future risk stratification and management strategies in MMD.