Long-Term Risk of Stroke After Snake Envenomation: A Nationwide Population-Based Cohort Study in Korea

Snake envenomation causes acute cerebrovascular complications, but its long-term effect on stroke risk remains unclear. This study suggests that snake envenomation may be associated with long-term stroke risk. Using the Korean National Health Insurance Service database, we conducted a nationwide population-based cohort study to evaluate the long-term risk of stroke following snake envenomation. A total of 764 adult patients diagnosed with snake envenomation and treated with antivenom were identified and matched with 3056 control patients (1:4) by age, sex, and socioeconomic status, excluding those with prior cerebrovascular disease. Stroke outcomes were defined using ICD-10 diagnostic codes and healthcare utilization criteria. After a 1-year lag period was applied to minimize reverse causation, multivariable Cox proportional hazards models were used to estimate adjusted hazard ratios for total, ischemic, and hemorrhagic strokes. During 10 years of follow-up, snake envenomation was associated with a significantly increased risk of total stroke (aHR 1.42 (95% CI 1.01-1.99)), particularly hemorrhagic stroke (aHR 2.55 (95% CI 1.12-5.80)), whereas no significant association was observed with ischemic stroke. Interaction analyses showed a stronger association among men with diabetes mellitus, particularly for hemorrhagic stroke. In addition, severe envenomation with disseminated intravascular coagulation or requiring transfusion was associated with a higher long-term risk of hemorrhagic stroke. These findings highlight the need for further investigations of long-term cerebrovascular complications of snake envenomation, particularly hemorrhagic stroke in vulnerable populations.