Asthma Tied to Presence and Rupture of Abdominal Aortic Aneurysms, Potentially Linked by Inflammation

Patients who have a recent history of asthma or who have taken anti-asthma medications are more likely to have an abdominal aortic aneurysm (AAA) on screening and to have a rupture of an existing AAA, a study shows. The findings strengthen the link between AAA and asthma, both of which involve underlying inflammation.

“The results have implications for the development of much needed advances in the prevention, screening criteria, and treatment of AAA, [areas] for which we currently lack sufficiently effective approaches,” study authors led by Guo-Ping Shi, ScD, of Brigham and Women’s Hospital (Boston, MA), write.

The study, reported online ahead of print in the March issue of Arteriosclerosis, Thrombosis, and Vascular Biology, used data from 2 populations of patients from Denmark: 15,942 individuals (81.2% men; median age 74 years) with ruptured or nonruptured AAA included in the Danish National Registry of Patients between 1996 and 2012 and 18,749 men with or without AAA from the Viborg Vascular (VIVA) screening trial.

Using the registry data, the researchers compared the 146 patients with hospital-diagnosed asthma and a ruptured AAA with 654 age- and sex-matched controls. After adjustment for AAA-relevant comorbidities, various types of medication use, and other factors, asthma in general was not significantly associated with AAA rupture.

Patients with asthma diagnosed within 180 days of the index date, however, were about twice as likely to have a ruptured AAA after adjustment (OR 2.06; 95% CI 1.21-3.53).

Similarly, prehospitalization use of bronchodilators (including beta-2-adrenergic receptor agonists, anticholinergic agents, or both) was associated with greater chances of AAA rupture, with ORs ranging from 1.10 (95% CI 1.01-1.19) for ever using the agents to 1.31 (95% CI 1.18-1.46) for use within 90 days of the index date. Relationships also were observed for individual types of anti-asthma medications, including selective beta-2-adrenergic receptor agonists, anticholinergics, inhaled glucocorticoids, and theophylline.

The authors point out that “the lack of information on cigarette smoking among the [registry] population could confound our conclusion, as smoking is a known independent risk factor for [ruptured] AAA.”

That potential confounding was explored in the VIVA data, which had complete smoking history for all patients. In that population, bronchodilator use was associated with a greater likelihood of AAA after adjustment for current smoking and for additional AAA risk factors. Other factors independently associated with AAA risk were smoking, hypertension, blood pressure, body mass index, and age.

Other Evidence Supporting AAA-Asthma Relationship

Shi and colleagues note that several recent studies have provided either direct or indirect support for a link between asthma and AAA. They point to a study in mice showing an association between allergic airway inflammation and larger atherosclerotic plaques and elevated lesion inflammation and an analysis showing that patients taking medications for asthma have increased levels of inflammatory biomarkers and greater cardiovascular disease risk.

“Although atherosclerosis may not underlie all AAA, atherosclerosis usually accompanies aneurysmal dilation and constitutes a long-recognized risk factor of AAA,” they write.

Moreover, the authors previously showed that allergic lung inflammation doubles the size of experimental AAA in mice.

“The mechanisms by which humans and mice develop AAA and asthma or allergic lung inflammation can differ, but we found a comparable increase of plasma IgE in mice that developed AAA or allergic lung inflammation,” they write. “A synergistic increase of plasma IgE in mice with both AAA and allergic lung inflammation and beneficial effects on both human asthma and mouse AAA development of targeting IgE5 support the contribution of IgE to both diseases.”

“Because allergic inflammation with elevated plasma IgE may promote AAA pathogenesis,” they conclude, “other allergic inflammatory diseases, such as atopic dermatitis, allergic rhinitis, and several ocular allergic diseases, may carry similar risks as asthma for AAA formation and rupture.”
 

Source: 
Liu C-L, Wemmelund H, Wang Y, et al. Asthma associates with human abdominal aortic aneurysm and rupture. Arterioscler Thromb Vasc Biol. 2016;Epub ahead of print.

Disclosures:

• The study is supported by the mid region of Denmark and the European Commission Seventh Framework Program; the NIH; and the National Natural Science Foundation of China.
• Shi reports no relevant conflicts of interest.

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