Subtype-specific risk patterns and asymptomatic progression in moyamoya disease: angiographic biomarkers for clinical stratification

OBJECTIVE: The pathophysiological distinctions and modifiable risk factors underlying ischemic versus hemorrhagic conversion in moyamoya disease (MMD) remain incompletely characterized, hindering subtype-specific management. This study aimed to delineate subtype-specific risk patterns and validate biomarkers for asymptomatic progression. METHODS: The authors analyzed the medical records of 774 adult MMD patients from Nanjing Jinling Hospital (2010-2020) and Nanjing Drum Tower Hospital (2013-2020). MMD was stratified as asymptomatic (n = 139), ischemic (n = 450), or hemorrhagic (n = 185). Multivariable logistic regression and Cox proportional hazards models were used to evaluate metabolic profiles, angiographic features (posterior cerebral artery [PCA] involvement and choroidal and lenticulostriate anastomoses), and longitudinal outcomes. RESULTS: Symptomatic patients demonstrated higher PCA involvement prevalence versus asymptomatic patients (p < 0.001). Ischemic MMD was independently associated with male sex (OR 2.00, 95% CI 1.30-3.07; p = 0.002), hypertension (OR 2.30, 95% CI 1.49-3.54; p < 0.001), hypertriglyceridemia (OR 1.36, 95% CI 1.01-1.83; p = 0.04), hyperglycemia (OR 1.22, 95% CI 1.03-1.45; p = 0.02), and PCA involvement (OR 2.43, 95% CI 1.40-4.20; p = 0.001). Hemorrhagic MMD correlated with BMI (OR 0.88 per kg/m2, 95% CI 0.81-0.97; p = 0.007), hypercholesterolemia (OR 1.53, 95% CI 1.14-2.07; p = 0.005), choroidal anastomosis formation (OR 2.38, 95% CI 1.21-4.70; p = 0.01), and PCA involvement (OR 3.41, 95% CI 1.76-6.61; p < 0.001). During the median 44-month follow-up, asymptomatic patients with PCA involvement (adjusted hazard ratio [HR] 4.86, 95% CI 1.07-22.14; p = 0.04) or choroidal anastomosis (adjusted HR 5.92, 95% CI 1.27-27.62; p = 0.02) exhibited an elevated risk of symptomatic conversion. CONCLUSIONS: Ischemic MMD was independently associated with male predominance, hypertension, and dyslipidemia, while hemorrhagic transformation correlated with lower BMI, hypercholesterolemia, and choroidal anastomosis. PCA involvement and choroidal anastomosis emerged as critical biomarkers for asymptomatic risk stratification.