Ischemic Stroke in Young Adults at High Altitude: Different Etiology and Pathogenesis

Tang, Mingyu, Zhuoga Cidan, Yang Ci, Yaxiong Hu, Yuhua Zhao, Fei Han, Lixin Zhou, and Jun Ni. Ischemic stroke in young adults at high altitude: different etiology and pathogenesis. <i>High Alt Med Biol.</i> 00:00-00, 2025. <b><i>Introduction:</i></b> Current knowledge indicates that exposure to high altitude increases the risk of ischemic stroke. However, its impact on ischemic stroke in young adults is still unknown. <b><i>Methods:</i></b> This two-center retrospective study analyzed 451 patients aged 18-50 years who experienced a first-ever ischemic stroke and were hospitalized at Peking Union Medical College Hospital (44 m) or Tibet Autonomous Region People's Hospital (3,650 m) between 2013 and 2021. Clinical characteristics, stroke etiology, and the results of auxiliary tests were compared. <b><i>Results:</i></b> A total of 451 patients were enrolled in this study, with a median age of 43, and 66.5% were male. At high altitude, hypertension (41.0% vs. 52.7%, <i>p</i> < 0.05) and diabetes mellitus (11.8% vs. 25.9%, <i>p</i> < 0.05) were less prevalent, whereas small-vessel occlusion stroke (21.7% vs. 8.0%, <i>p</i> < 0.01) was more common. Elevated levels of D-dimer (51.5% vs. 39.3%, <i>p</i> < 0.05) and hemoglobin (11.8% vs. 0%, <i>p</i> < 0.01) were observed more at high altitude. High altitude was associated with small-vessel occlusion stroke (odds ratio [OR] = 3.26, 95% confidence interval [CI] = 1.56-6.82, <i>p</i> < 0.01). <b><i>Conclusion:</i></b> The etiology of ischemic stroke in young adults at high altitude differs from that at low altitude. The higher frequency of hyperhemoglobinemia and hypercoagulable status suggests a distinct pathophysiological mechanism resulting from chronic high-altitude exposure.