Zeng Chaofan, Chen Haoyuan, Liu Jie, Bao Youyuan, Sun Xudong, Meng Fanbo, Xue Yimeng, Cui Yunhao, Zhao Qianjun, Zhang Jing, Li Hao, Zhang Dong, Wang Rong, Zhang Yan, Zhang Guojun, Zhao Jizong, Zhang Qian
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
China National Clinical Research Center for Neurological Diseases, Beijing, China.
CNS Neurosci Ther. 2025 May;31(5):e70441. doi: 10.1111/cns.70441.
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.
烟雾病(MMD)的发病机制仍未明确。尽管遗传易感性和血流动力学变化一直是研究重点,但新出现的证据表明血脂异常也可能与烟雾病有关。在此,我们对血脂谱进行了全面分析,旨在阐明烟雾病的潜在机制。
在这项前瞻性病例对照研究中,纳入了222例烟雾病患者和231名健康对照者(HCs)。进行了全面的血脂分析,包括标准脂质、载脂蛋白、氧化型低密度脂蛋白(oxLDL)和小而密低密度脂蛋白(sdLDL)。应用加权分位数和(WQS)统计模型和贝叶斯核机器回归(BKMR)来捕捉个体和联合脂质对烟雾病风险的影响。
与健康对照者相比,烟雾病患者的oxLDL、sdLDL和脂蛋白(a)显著更高(p < 0.05)。OxLDL成为烟雾病的一个强有力的独立危险因素(调整后的OR为1.146,95%CI为1.102 - 1.210,p < 0.001)。WQS分析进一步确定oxLDL是烟雾病风险的单一最大贡献因素,BKMR的额外支持表明oxLDL与同型半胱氨酸之间存在显著的协同相互作用。
该研究揭示了烟雾病中全面的血脂异常情况,突出了oxLDL作为关键生物标志物的地位。结果强调了脂质代谢在烟雾病发病机制中的重要性,并需要进一步研究以指导新的诊断和治疗策略。