Does living in the Andes make cerebral arteriovenous malformations more dangerous? high altitude fails to predict hemorrhage in a large Ecuadorian cohort

Background: Chronic residence at high altitude (≥2500 masl) induces sustained physiological adaptations in cerebrovascular regulation, including hypoxia-driven angiogenesis, altered hemodynamics, and vascular remodeling. These mechanisms support the hypothesis that lifelong exposure to hypobaric hypoxia in the Ecuadorian Andes could modify the clinical presentation of cerebral arteriovenous malformations (AVMs), although direct evidence remains limited. Objective: To evaluate whether chronic residence at high altitude is associated with hemorrhagic presentation of cerebral AVMs in adult patients treated at a national tertiary referral center in Quito, Ecuador. Methods: We conducted an observational, cross-sectional study of 229 adults diagnosed with cerebral AVMs by digital subtraction angiography between 2016 and 2023. Demographic characteristics, residential altitude during early life (first 18 years) and recent adulthood (preceding 10 years), vascular risk factors, AVM intrinsic vascular morphological features, and Spetzler–Martin and Spetzler–Ponce classifications were analyzed. Associations with hemorrhagic presentation at diagnosis were assessed using chi-square or Fisher’s exact tests, Student’s t-tests, and descriptive modeling. Multivariable regression was explored but not performed due to limited variability in altitude exposure and collinearity among anatomical predictors. Results: Hemorrhagic presentation occurred in 61.1% of patients. >80% of the cohort resided at high altitude during both exposure periods. No statistically significant association was observed between high-altitude residence, either during early life or recent adulthood, and hemorrhagic presentation (p > 0.05). In contrast, intrinsic vascular morphological features showed significant associations with hemorrhage, including deep or subcortical nidus location and higher Spetzler–Martin and Spetzler–Ponce grades (p < 0.05). Traditional vascular risk factors, including hypertension and smoking, did not differ between altitude exposure groups. Conclusion: In this predominantly high-altitude Andean cohort, chronic residence at high altitude was not detectably associated with hemorrhagic presentation of cerebral AVMs. Instead, established intrinsic vascular morphological features remained the dominant predictors of rupture at diagnosis. Given the homogeneity of altitude exposure, these findings likely reflect limited power to detect subtle effects rather than definitive absence of an altitude influence. Multicenter studies with broader altitude variability, physiological markers of hypoxia, and longitudinal follow-up are needed to further clarify the role of environmental hypoxia in AVM natural history. © 2026 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license. http://creativecommons.org/licenses/by-nc-nd/4.0/