Lifelong De Novo Aneurysm Risk After Aneurysmal Subarachnoid Hemorrhage in Young Survivors

Abstract

Importance Young survivors of aneurysmal subarachnoid hemorrhage (aSAH) risk de novo aneurysm formation, yet population-based lifetime estimates are lacking, and prior studies were limited by selection bias and short follow-up. Objective To determine lifetime cumulative incidence, risk factors, and rupture rate of radiologically detected de novo aneurysm formation in young survivors of aSAH and the association with smoking cessation. Design, Setting, and Participants This cohort study used a prospective regional register cross-linked with national health and death registers, with index events from 1967 to 2014. Participants were residents of the Stockholm region, Sweden, and younger than 40 years with an index saccular aSAH. Eligibility required concurrent 4-vessel angiography and retention of original imaging and medical records. Radiological follow-up reached 57 years; de novo aneurysm detection, treatment, recurrent hemorrhage, and vital status were ascertained nationwide through December 31, 2025, and validated longitudinally. Exposures Age, sex, smoking status, family history, hypertension, and multiple aneurysms. Main Outcomes and Measures Cumulative incidence of de novo formation, independent risk factors, annual rupture rate, and smoking-cessation association. Results Of 6521 patients of all ages with regional saccular aSAH, 986 (15.1%) were younger than 40 years. After eligibility criteria were assessed, there were 544 survivors (83.3%). Among them, 313 were female (57.5%) and 231 (42.5%) male; the median (IQR) age was 33 (28-36) years. Over 13 738 person-years, 106 patients (19.5%) developed 158 de novo aneurysms; 23 ruptured. The Fine-Gray cumulative incidence was 30.2% (95% CI, 24.7%-35.7%) at 40 years, without a plateau. Independent risk factors were female sex (hazard ratio [HR], 1.76; 95% CI, 1.16-2.69), smoking (HR, 1.75; 95% CI, 1.13-2.71), and family history (HR, 2.17; 95% CI, 1.22-3.87). Smoking cessation was associated with lower, dose-dependent de novo risk. The annual rupture rate was 153 per 100 000 person-years. No ruptures occurred under systematic surveillance; one-third occurred more than 20 years after the index event. Conclusions and Relevance This study found that young survivors of aSAH face a substantial lifetime risk of de novo aneurysm formation that does not plateau over 4 decades. Female sex, smoking status, and family history are independent risk factors; smoking cessation is a modifiable prevention target. These findings support lifelong surveillance and address current guideline gaps.