Serum alpha-1 antitrypsin in acute ischemic stroke: A prospective pilot study

Published:April 20, 2020DOI:


      • Alpha-1 antitrypsin (AAT) may play a protective role against atherosclerosis.
      • Low serum level of AAT maybe associated with atherosclerosis on major arteries.
      • Serum AAT maybe used as a biomarker to differentiate stroke mechanism.



      Alpha-1 antitrypsin (AAT) is a potent anti-protease enzyme which may play a role in arterial wall stability. A variant of its encoding gene has been recently linked to ischemic stroke due to large artery atherosclerosis (LAA). We sought to explore potential relationships between ischemic stroke mechanisms, atherosclerosis burden and serum AAT levels.


      We performed a prospective observational study of consecutive patients with acute ischemic stroke who were admitted to an academic comprehensive stroke center over a three-month period. Blood samples were collected within 24 h of hospital admission, and stroke subtype classification was determined based on modified TOAST criteria. Modified Woodcock scoring system was used to quantify calcification of major cervico-cranial arteries as a surrogate for atherosclerosis burden. Linear regression analysis was used to assess the association between serum AAT levels and calcification scores, both as continuous variables.


      Among eighteen patients met our inclusion criteria and were enrolled in our study, 10 patients (56%) were men; mean age was 66 (SD 12.5); median NIH stroke scale was 4 (IQR 9.5); 8 patients (44%) had stroke due to LAA. The median serum level of AAT was 140 mg/dl (IQR 41.7) for patients with LAA-related stroke, and 148.5 mg/dl (IQR 37.7) for patients with other stroke mechanisms (p = 0.26). Higher serum AAT levels was associated with lower modified Woodcock calcification scores. (p-value = 0.038)


      Measurement of AAT levels in patients with acute stroke is feasible, and there may be associations between AAT levels and stroke mechanism that warrant further study in larger samples.


      To read this article in full you will need to make a payment


      Subscribe to Journal of Clinical Neuroscience
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Sandhaus R.A.
        • Turino G.
        • Brantly M.L.
        • Campos M.
        • Cross C.E.
        • Goodman K.
        • et al.
        The diagnosis and management of alpha-1 antitrypsin deficiency in the adult.
        Chronic Obstr Pulm Dis. 2016; 3: 668-682
        • Curjuric I.
        • Imboden M.
        • Bettschart R.
        • Caviezel S.
        • Dratva J.
        • Pons M.
        • et al.
        Alpha-1 antitrypsin deficiency: From the lung to the heart?.
        Atherosclerosis. 2018; 270: 166-172
        • Schievink W.I.
        • Prakash U.B.
        • Piepgras D.G.
        • Mokri B.
        Alpha 1-antitrypsin deficiency in intracranial aneurysms and cervical artery dissection.
        Lancet. 1994; 343: 452-453
        • Mahta A.
        • Merkler A.E.
        • Reznik M.E.
        • Burch J.E.
        • Yaghi S.
        • Sellke F.W.
        • et al.
        Emphysema: A potential risk factor for subarachnoid hemorrhage and ruptured aortic aneurysm.
        Stroke. 2019; 50: 992-994
        • Malik R.
        • Dau T.
        • Gonik M.
        • Sivakumar A.
        • Deredge D.J.
        • Edeleva E.V.
        • et al.
        Common coding variant in serpina1 increases the risk for large artery stroke.
        Proc Natl Acad Sci U S A. 2017; 114: 3613-3618
        • Ferrarotti I.
        • Thun G.A.
        • Zorzetto M.
        • Ottaviani S.
        • Imboden M.
        • Schindler C.
        • et al.
        Serum levels and genotype distribution of alpha1-antitrypsin in the general population.
        Thorax. 2012; 67: 669-674
        • Shang W.
        • Liu J.
        Stroke subtype classification: A comparative study of asco and modified toast.
        J Neurol Sci. 2012; 314: 66-70
        • Subedi D.
        • Zishan U.S.
        • Chappell F.
        • Gregoriades M.L.
        • Sudlow C.
        • Sellar R.
        • et al.
        Intracranial carotid calcification on cranial computed tomography: Visual scoring methods, semiautomated scores, and volume measurements in patients with stroke.
        Stroke. 2015; 46: 2504-2509
        • Lange M.C.
        • Ribas G.
        • Scavasine V.
        • Ducci R.D.
        • Mendes D.C.
        • Zetola V.H.F.
        • et al.
        Stroke recurrence in the different subtypes of ischemic stroke. The importance of the intracranial disease.
        Arq Neuropsiquiatr. 2018; 76: 649-653
        • Yaghi S.
        • Prabhakaran S.
        • Khatri P.
        • Liebeskind D.S.
        Intracranial atherosclerotic disease.
        Stroke. 2019; 50: 1286-1293
        • Petersen E.
        • Wagberg F.
        • Angquist K.A.
        Serum concentrations of elastin-derived peptides in patients with specific manifestations of atherosclerotic disease.
        Eur J Vasc Endovasc Surg. 2002; 24: 440-444
        • Baydanoff S.
        • Nicoloff G.
        • Alexiev C.
        Age-related changes in the level of circulating elastin-derived peptides in serum from normal and atherosclerotic subjects.
        Atherosclerosis. 1987; 66: 163-168
        • Mochizuki S.
        • Brassart B.
        • Hinek A.
        Signaling pathways transduced through the elastin receptor facilitate proliferation of arterial smooth muscle cells.
        J Biol Chem. 2002; 277: 44854-44863
        • Ooyama T.
        • Fukuda K.
        • Oda H.
        • Nakamura H.
        • Hikita Y.
        Substratum-bound elastin peptide inhibits aortic smooth muscle cell migration in vitro.
        Arteriosclerosis. 1987; 7: 593-598
        • Durham A.L.
        • Speer M.Y.
        • Scatena M.
        • Giachelli C.M.
        • Shanahan C.M.
        Role of smooth muscle cells in vascular calcification: Implications in atherosclerosis and arterial stiffness.
        Cardiovasc Res. 2018; 114: 590-600
        • Maurice P.
        • Blaise S.
        • Gayral S.
        • Debelle L.
        • Laffargue M.
        • Hornebeck W.
        • et al.
        Elastin fragmentation and atherosclerosis progression: The elastokine concept.
        Trends Cardiovasc Med. 2013; 23: 211-221
        • Doherty T.M.
        • Asotra K.
        • Fitzpatrick L.A.
        • Qiao J.H.
        • Wilkin D.J.
        • Detrano R.C.
        • et al.
        Calcification in atherosclerosis: Bone biology and chronic inflammation at the arterial crossroads.
        Proc Natl Acad Sci U S A. 2003; 100: 11201-11206
        • Feng Y.
        • Hu L.
        • Xu Q.
        • Yuan H.
        • Ba L.
        • He Y.
        • et al.
        Cytoprotective role of alpha-1 antitrypsin in vascular endothelial cell under hypoxia/reoxygenation condition.
        J Cardiovasc Pharmacol. 2015; 66: 96-107
        • Talmud P.J.
        • Martin S.
        • Steiner G.
        • Flavell D.M.
        • Whitehouse D.B.
        • Nagl S.
        • et al.
        Progression of atherosclerosis is associated with variation in the alpha1-antitrypsin gene.
        Arterioscler Thromb Vasc Biol. 2003; 23: 644-649
        • Taggart C.
        • Cervantes-Laurean D.
        • Kim G.
        • McElvaney N.G.
        • Wehr N.
        • Moss J.
        • et al.
        Oxidation of either methionine 351 or methionine 358 in alpha 1-antitrypsin causes loss of anti-neutrophil elastase activity.
        J Biol Chem. 2000; 275: 27258-27265
        • Ehlers M.R.
        Immune-modulating effects of alpha-1 antitrypsin.
        Biol Chem. 2014; 395: 1187-1193
        • Lewis E.C.
        Expanding the clinical indications for alpha(1)-antitrypsin therapy.
        Mol Med. 2012; 18: 957-970