Emphysema: A Potential Risk Factor for Subarachnoid Hemorrhage and Ruptured Aortic Aneurysm

Background and Purpose— Protease/antiprotease imbalance is implicated in the pathogenesis of emphysema and may also lead to vessel wall weakening, aneurysm development, and rupture. However, it is unclear whether emphysema is associated with cerebral and aortic aneurysm rupture. Methods— We performed a retrospective cohort study using outpatient and inpatient claims data from 2008 to 2014 from a nationally representative sample of Medicare beneficiaries ≥66 years of age. Our predictor variable was emphysema, and our outcome was hospitalization for either aneurysmal subarachnoid hemorrhage or a ruptured aortic aneurysm. All predictors and outcomes were defined using previously reported International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code algorithms. Survival statistics and Cox regression were used to compare risk between patients with and without emphysema. Results— We identified 1 670 915 patients, of whom 133 972 had a diagnosis of emphysema. During a mean follow-up period of 4.3 (±1.9) years, we identified 4835 cases of aneurysm rupture, 433 of which occurred in patients with emphysema. The annual incidence of aneurysm rupture was 6.5 (95% CI, 6.4–6.8) per 10 000 in patients without emphysema and 14.6 (95% CI, 13.3–16.0) per 10 000 in patients with emphysema. After adjustment for demographics and known risk factors for aneurysmal disease, emphysema was independently associated with aneurysm rupture (hazard ratio, 1.7; 95% CI, 1.5–1.9). Emphysema was associated with both aneurysmal subarachnoid hemorrhage (hazard ratio, 1.5; 95% CI, 1.3–1.7) and ruptured aortic aneurysm (hazard ratio, 2.3; 95% CI, 1.9–2.8). Conclusions— Patients with emphysema face an increased risk of developing subarachnoid hemorrhage and aortic aneurysm rupture, potentially consistent with shared pathways in pathogenesis.