In this study, we review the roles of A1AT level and functionality as well as cigarette smoking in development, rupture and potential rebleeding of intracranial aneurysms.

Aneurysmal subarachnoid hemorrhage (aSAH) is a neurological emergency with significant mortality of up to 67% in different literature. Although the etiology of aSAH remains unclear, smoking is a known modifiable risk factor that can affect blood vessel walls at the molecular level and has been shown to have a significant role. Also, the literature advocates the role of biomarkers in formation, progression, rupture and rebleeding of aneurysms. Alpha-1 antitrypsin (A1AT) is the most physiologically potent inhibitor of elastase, a key enzyme whose equilibrium is crucial in the pathophysiology of aneurysmal rupture.

We performed a comprehensive review of English publications in peer-reviewed journals published between 1970-2018, using PubMed and Google Scholar, utilizing a wide-range of key terms and their combination including: A1AT, elastase, aneurysm, SAH, cigarettes, smoking, and tobacco. We reviewed both quantitative as well as qualitative deficiencies of A1AT in aSAH population, looking at several allelic variants. Then, we described the effects of cigarette smoking on A1AT and intracranial aneurysmal rupture. 

This review provides evidence that an increasing number of studies have described how smoking alters the functionality of A1AT. Augmentation therapy with A1AT is currently being used in patients with A1AT deficiency. Theoretically, it may be a beneficial method of treatment in aSAH patients by rectifying the protease-antiprotease imbalance and contribute to decreased breakdown of the arterial wall and a more rapid recovery. Further well designed studies and detailed understanding of the intimate relationship between A1AT and cigarette smoking are needed to validate the results of the limited number of current studies and guide future efforts in designing potential therapies for decreasing aneurysm rupture and rebleeding.