The findings suggest emphysema’s link to rupture is independent of other known risk factors.
A diagnosis of emphysema is associated with an increased risk of subarachnoid hemorrhage (SAH) and aortic aneurysm rupture, suggesting a potential shared pathway in pathogenesis, according to research published March 19, 2019, in Stroke. The authors postulate that protease/antiprotease imbalance may play a role in all these conditions.
“Our findings build on . . . prior studies by indicating that emphysema may be associated with aneurysm rupture independently of other established risk factors, including documented tobacco use,” write Ali Mahta, MD (Rhode Island Hospital, Brown University, Providence, RI), and colleagues. They point out in their paper that imbalances in protease/antiprotease activity lead to cascades of inflammation, oxidative stress, and vessel-wall weakening, which may play a role in aneurysm formation and rupture. A similar process is also thought to occur in lung diseases such as emphysema.
For the study, Mahta and colleagues used outpatient and inpatient claims data from 2008 to 2014 from a nationally representative sample of Medicare beneficiaries ≥ 66 years of age. They identified 133,972 patients with a diagnosis of emphysema among a total sample of 1,670,915. Patients with emphysema were more likely than those without emphysema to be older (77 vs 74 years of age), less likely to be female (52% vs 58%), and more likely to have hypertension, diabetes, and both tobacco and alcohol use.
During a mean follow-up period of 4.3 years, there were 4,835 cases of aneurysm rupture. Of these, 433 occurred in patients with emphysema. The annual incidence of aneurysm rupture was 6.5 per 10,000 in patients without emphysema and 14.6 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 (HR 1.7; 95% CI 1.5-1.9). Emphysema was also associated with both aneurysmal SAH (HR 1.5; 95% CI 1.3-1.7) and ruptured aortic aneurysm (HR 2.3; 95% CI 1.9-2.8). In sensitivity analyses excluding patients with documented tobacco use disorder, a similar association was seen between emphysema and aneurysm rupture (HR 1.7; 95% CI 1.5-1.9).
Focus on Prevention
“At this stage, the main clinical implication[s] of this study [are] awareness of this association and [the need to] work on modifiable risk factors aiming for prevention of aneurysm formation,” Mahta told Neurovascular Exchange in an email. “For instance, we can advise patients with emphysema to stop smoking and monitor their blood pressure carefully, as these two are well-known risk factors for aneurysm formation and rupture.
“I don't think there's any role for surveillance cerebrovascular imaging for all patients with emphysema,” he continued, “but we can consider it in special contexts, such as presence of family history of cerebral aneurysm. On the other hand, the association between emphysema and ruptured aortic aneurysm was slightly higher (HR 2.3, 95% CI 1.9-2.8), so there might be a role for surveillance aortic ultrasound, which is noninvasive and can be done at bedside.”
Mahta acknowledged the study’s limitations. “We used ICD-9 codes to identify diseases and risk factors,” he said. “We don't have details about disease severity or how it was diagnosed or things like quantity of smoking. In addition, as expected, we don't have information about imaging details or any lab values or biomarkers.”
Topics for future study, according to Mahta, include “exact molecular mechanisms of aneurysm formation and rupture; the role of biomarkers, inflammatory cytokines, and protective proteins; and future potential therapeutic options for cerebral and aortic aneurysms.”
Mahta A, Merkler AE, Reznik ME, et al. Emphysema: A potential risk factor for subarachnoid hemorrhage and ruptured aortic aneurysm. Stroke. 2019;Epub ahead of print.
Mahta reports no relevant conflicts of interest.