Rheumatology International

, Volume 34, Issue 2, pp 255–263 | Cite as

Increased risk of stroke among patients with ankylosing spondylitis: a population-based matched-cohort study

  • Joseph J. Keller
  • Jung-Lung Hsu
  • Shiue-Ming Lin
  • Chia-Chi Chou
  • Li-Hsuan Wang
  • Jui Wang
  • Chyi-Huey BaiEmail author
  • Hung-Yi Chiou
Original Article


Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease. Although two prior studies detected increased prevalence ratios of cerebrovascular disease among AS patients, the results of the two studies investigating AS and stroke are in conflict. Therefore, the present cohort study set out to estimate the risk of subsequent stroke in AS patients compared with matched controls using a population-based dataset in Taiwan. This investigation analyzed administrative claims data sourced from the Taiwan National Health Insurance Database. Our study consisted of a study cohort comprising 1,479 AS patients and a comparison cohort of 5,916 subjects without AS. Cox proportional hazards regressions were performed to estimate the risk of subsequent stroke during the follow-up period. We also conducted additional analyses investigating the risk of subsequent stroke by gender and pharmaceutical prescription. After adjusting for chronic lower respiratory diseases, type 2 diabetes mellitus, hypertension, hyperlipidemia, renal disease, coronary heart disease, atrial fibrillation, income, and urbanization, compared with comparison patients, the hazard ratio for subsequent stroke among patients with AS was 2.3 (95 % CI 1.9–2.8). We also stratified our results by both gender and pharmaceutical prescription, but did not find a statistically significant difference for the risk of subsequent stroke either between men and women, or between AS patients taking various pharmaceutical regimens and the overall AS population. This is the first study to report an increased hazard ratio for subsequent stroke among AS patients when compared with matched comparison patients without AS.


Ankylosing spondylitis Stroke Epidemiology Taiwan 



This study is based in part on data from the National Health Insurance Research Database provided by the Bureau of National Health Insurance, Department of Health and managed by National Health Research Institutes.

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Gran JT, Husby G (1993) The epidemiology of AS. A review. Semin Arthr Rheum 22:319–334CrossRefGoogle Scholar
  2. 2.
    Braun J, Bollow M, Remlinger G, Eggens U, Rudwaleit M, Distler A, Sieper J (1998) Prevalence of spondylarthropathies in HLA-B27 positive and negative blood donors. Arthritis Rheum 41:58–67PubMedCrossRefGoogle Scholar
  3. 3.
    Donnan GA, Fisher M, Macleod M, Davis SM (2008) Stroke. Lancet 371:1612–1623PubMedCrossRefGoogle Scholar
  4. 4.
    Libby P (2002) Inflammation in atherosclerosis. Nature 420:868–874PubMedCrossRefGoogle Scholar
  5. 5.
    Papagoras C, Voulgari PV, Drosos AA (2013) Atherosclerosis and cardiovascular disease in the spondyloarthritides, particularly ankylosing spondylitis and psoriatic arthritis. Clin Exp Rheumatol 31:612–620Google Scholar
  6. 6.
    Choy E, Sattar N (2009) Interpreting lipid levels in the context of high grade inflammatory states with a focus on rheumatoid arthritis: a challenge to conventional cardiovascular risk actions. Ann Rheum Dis 68:460–469PubMedCrossRefGoogle Scholar
  7. 7.
    Goodson NJ, Wiles NJ, Lunt M, Barrett EM, Silman AJ, Symmons DP (2002) Mortality in early inflammatory polyarthritis: cardiovascular mortality is increased in seropositive patients. Arthritis Rheum 46:2010–2019PubMedCrossRefGoogle Scholar
  8. 8.
    Meune C, Touzé E, Trinquart L, Allanore Y (2010) High risk of clinical cardiovascular events in rheumatoid arthritis: levels of associations of myocardial infarction and stroke through a systematic review and meta-analysis. Arch Cardiovasc Dis 103:253–261PubMedCrossRefGoogle Scholar
  9. 9.
    McCarey D, Sturrock RD (2009) Comparison of cardiovascular risk in ankylosing spondylitis and rheumatoid arthritis. Clin Exp Rheumatol 27:S124–S126PubMedGoogle Scholar
  10. 10.
    Peters MJ, van der Horst-Bruinsma IE, Dijkmans BA, Nurmohamed MT (2004) Cardiovascular risk profile of patients with spondylarthropathies, particularly ankylosing spondylitis and psoriatic arthritis. Semin Arthritis Rheum 34:585–592PubMedCrossRefGoogle Scholar
  11. 11.
    Mathieu S, Gossec L, Dougados M, Soubrier M (2011) Cardiovascular profile in ankylosing spondylitis: a systematic review and meta-analysis. Arthritis Care Res (Hoboken) 63:557–563CrossRefGoogle Scholar
  12. 12.
    Brophy S, Cooksey R, Atkinson M, Zhou SM, Husain MJ, Macey S, Rahman MA, Siebert S (2012) No increased rate of acute myocardial infarction or stroke among patients with ankylosing spondylitis—a retrospective cohort study using routine data. Semin Arthritis Rheum 42:140–145PubMedCrossRefGoogle Scholar
  13. 13.
    Zöller B, Li X, Sundquist J, Sundquist K (2012) Risk of subsequent ischemic and hemorrhagic stroke in patients hospitalized for immune-mediated diseases: a nationwide follow-up study from Sweden. BMC Neurol 12:41PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Han C, Robinson DW Jr, Hackett MV, Paramore LC, Fraeman KH, Bala MV (2006) Cardiovascular disease and risk factors in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. J Rheumatol 33:2167–2172PubMedGoogle Scholar
  15. 15.
    Szabo SM, Levy AR, Rao SR, Kirbach SE, Lacaille D, Cifaldi M, Maksymowych WP (2011) Increased risk of cardiovascular and cerebrovascular diseases in individuals with ankylosing spondylitis: a population-based study. Arthritis Rheum 63:3294–3304PubMedCrossRefGoogle Scholar
  16. 16.
    Braunstein EM, Martel W, Moidel R (1982) Ankylosing spondylitis in men and women: a clinical and radiographic comparison. Radiology 144:91–94PubMedGoogle Scholar
  17. 17.
    Jimenez-Balderas FJ, Mintz G (1993) Ankylosing spondylitis: clinical course in women and men. J Rheumatol 20:2069–2072PubMedGoogle Scholar
  18. 18.
    Resnick D, Dwosh IL, Goergen TG, Shapiro RF, Utsinger PD, Wiesner KB, Bryan BL (1976) Clinical and radiographic abnormalities in ankylosing spondylitis: a comparison of men and women. Radiology 119:293–297PubMedGoogle Scholar
  19. 19.
    Feldtkeller E, Bruckel J, Khan MA (2000) Scientific contribution of ankylosing spondylitis patient advocacy groups. Curr Opin Rheumatol 12:239–247PubMedCrossRefGoogle Scholar
  20. 20.
    Gran JT, Ostensen M, Husby G (1985) A clinical comparison between males and females with ankylosing spondylitis. J Rheumatol 12:126–129PubMedGoogle Scholar
  21. 21.
    Hill HFH, Hill AGS, Bodmer JG (1976) Clinical diagnosis of ankylosing spondylitis in women and relation to presence of HLA-B27. Ann Rheum Dis 35:267–270PubMedCrossRefGoogle Scholar
  22. 22.
    Carbone LD, Cooper C, Michet CJ, Atkinson EJ, O’Fallon WM, Melton LJ (1992) Ankylosing spondylitis in Rochester, Minnesota, 1935–1989: is the epidemiology changing? Arthritis Rheum 35:1476–1482PubMedCrossRefGoogle Scholar
  23. 23.
    Gomez KS, Raza K, Jones SD, Kennedy LG, Calin A (1997) Juvenile onset ankylosing spondylitis more girls than we thought. J Rheumatol 24:737Google Scholar
  24. 24.
    Dessein PH, Joffe BI, Stanwix AE (2002) Effects of disease modifying agents and dietary intervention on insulin resistance and dyslipidemia in inflammatory arthritis: a pilot study. Arthritis Res 4:R12PubMedCentralPubMedCrossRefGoogle Scholar
  25. 25.
    Geirsson AJ, Eyjolfsdottir H, Bjornsdottir G, Kristjansson K, Gudbjornsson B (2010) Prevalence and clinical characteristics of ankylosing spondylitis in Iceland—a nationwide study. Clin Exp Rheumatol 28:333–340PubMedGoogle Scholar
  26. 26.
    Gran JT, Husby G, Hordvik M (1985) Prevalence of ankylosing spondylitis in males and females in a young middle-aged population of Tromsø, northern Norway. Ann Rheum Dis 44:359–367PubMedCrossRefGoogle Scholar
  27. 27.
    Mijiyawa M (1993) Spondyloarthropathies in patients attending the rheumatology unit of Lomé hospital. J Rheumatol 20:1167–1169PubMedGoogle Scholar
  28. 28.
    Zeng QY, Chen R, Darmawan J, Xiao ZY, Chen SB, Wigley R, Le Chen S, Zhang NZ (2008) Rheumatic diseases in China. Arthritis Res Ther 10:R17PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    Chou CH, Lin MC, Peng CL, Wu YC, Sung FC, Kao CH, Liu SH (2013). A nationwide population-based retrospective cohort study: increased risk of acute coronary syndrome in patients with ankylosing spondylitis. Scand J Rheumatol (Epub ahead of print)Google Scholar
  30. 30.
    Bai CH, Chen JR, Chiu HC, Pan WH (2007) Lower blood flow velocity, higher resistance index, and larger diameter of extracranial carotid arteries are associated with ischemic stroke independently of carotid atherosclerosis and cardiovascular risk factors. J Clin Ultrasound 35:322–330PubMedCrossRefGoogle Scholar
  31. 31.
    Chuang SY, Bai CH, Chen JR, Yeh WT, Cheng HJ, Chiu HC, Shiu RS, Pan WH (2011) Common carotid end-diastolic velocity and intima-media thickness jointly predict ischemic stroke in Taiwan. Stroke 42:1338–1344PubMedCrossRefGoogle Scholar
  32. 32.
    Pischon N, Pischon T, Gülmez E, Kröger J, Purucker P, Kleber BM, Landau H, Jost-Brinkmann PG, Schlattmann P, Zernicke J, Burmester GR, Bernimoulin JP, Buttgereit F, Detert J (2010) Periodontal disease in patients with ankylosing spondylitis. Ann Rheum Dis 69:34–38PubMedCrossRefGoogle Scholar
  33. 33.
    Wolf PA, D’Agostino RB, Kannel WB, Bonita R, Belanger AJ (1988) Cigarette smoking as a risk factor for stroke. The Framingham study. JAMA 259:1025–1029PubMedCrossRefGoogle Scholar
  34. 34.
    Hermann M (2009) Cardiovascular risk associated with nonsteroidal anti-inflammatory drugs. Curr Rheumatol Rep 11:31–35PubMedCrossRefGoogle Scholar
  35. 35.
    Farkouh ME, Greenberg BP (2009) An evidence-based review of the cardiovascular risks of nonsteroidal anti-inflammatory drugs. Am J Cardiol 103:1227–1237PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Joseph J. Keller
    • 1
  • Jung-Lung Hsu
    • 5
    • 6
    • 7
  • Shiue-Ming Lin
    • 1
  • Chia-Chi Chou
    • 2
    • 3
  • Li-Hsuan Wang
    • 4
  • Jui Wang
    • 1
  • Chyi-Huey Bai
    • 1
    • 10
    Email author
  • Hung-Yi Chiou
    • 1
    • 8
    • 9
  1. 1.School of Public Health, College of Public Health and NutritionTaipei Medical UniversityTaipeiTaiwan
  2. 2.Department of Internal MedicineChang Gung Memorial HospitalKeelungTaiwan
  3. 3.School of MedicineChang Gung UniversityTaoyuanTaiwan
  4. 4.School of Pharmacy, College of PharmacyTaipei Medical UniversityTaipeiTaiwan
  5. 5.Graduate Institute of Biomedical InformaticsTaipei Medical UniversityTaipeiTaiwan
  6. 6.Department of NeurologyShin Kong Wu Ho-Su Memorial HospitalTaipeiTaiwan
  7. 7.Institute of Biomedical EngineeringNational Taiwan UniversityTaipeiTaiwan
  8. 8.Stroke Research CenterTaipei Medical UniversityTaipeiTaiwan
  9. 9.Health and Clinical Research Data CenterTaipei Medical UniversityTaipeiTaiwan
  10. 10.Department of Public Health, College of MedicineTaipei Medical UniversityTaipeiTaiwan

Personalised recommendations