Patients With Ankylosing Spondylitis Have Increased Cardiovascular and Cerebrovascular Mortality: A Population-Based Study
Submit a Comment
Contributors must reveal any conflict of interest. Comments are moderated. Please see our information for authorsregarding comments on an Annals publication.
Abstract
Background:
Ankylosing spondylitis (AS) is a chronic inflammatory arthritis affecting the spine in young adults. It is associated with excess cardiovascular and cerebrovascular morbidity.
Objective:
To determine whether patients with AS are at increased risk for cardiovascular and cerebrovascular mortality.
Design:
Population-based retrospective cohort study using administrative health data.
Setting:
Ontario, Canada.
Patients:
21 473 patients with AS aged 15 years or older and 86 606 comparators without AS, matched for age, sex, and location of residence.
Measurements:
The primary outcome was a composite of cardiovascular and cerebrovascular death. Hazard ratios (HRs) for vascular death were calculated; adjusted for history of cancer, diabetes, dementia, inflammatory bowel disease, hypertension, chronic kidney disease, and peripheral vascular disease; and, among those aged 66 years or older, relevant drug therapies. Independent risk factors for vascular mortality were identified in patients with AS.
Results:
The mean age of patients with AS was 46 years, and 53% were male. Patients and comparators were followed for 166 920 and 686 461 patient-years, respectively. Adjusted HRs for vascular death in AS were 1.36 (95% CI, 1.13 to 1.65) overall, 1.46 (CI, 1.13 to 1.87) in men, and 1.24 (CI, 0.92 to 1.67) in women. Significant risk factors for vascular death were age; male sex; lower income; dementia; chronic kidney disease; peripheral vascular disease; and, among patients aged 65 years or older, lack of exposure to nonsteroidal anti-inflammatory drugs and statins.
Limitation:
Diagnosis codes for AS were not validated in Ontario.
Conclusion:
Ankylosing spondylitis is associated with increased risk for vascular mortality. A comprehensive strategy to screen and treat modifiable vascular risk factors in AS is needed.
Primary Funding Source:
The Arthritis Program, University Health Network, Toronto; and The Arthritis Society, Canada.
Get full access to this article
View all available purchase options and get full access to this article.
References
1.
Azevedo VF, Pecoits-Filho R. Atherosclerosis and endothelial dysfunction in patients with ankylosing spondylitis. Rheumatol Int. 2010;30:1411-6. [PMID: 20349072] doi: 10.1007/s00296-010-1416-3
2.
Vallance P, Collier J, Bhagat K. Infection, inflammation, and infarction: does acute endothelial dysfunction provide a link? Lancet. 1997;349:1391-2. [PMID: 9149715]
3.
Boring L, Gosling J, Cleary M, Charo IF. Decreased lesion formation in CCR2-/- mice reveals a role for chemokines in the initiation of atherosclerosis. Nature. 1998;394:894-7. [PMID: 9732872]
4.
Gu L, Okada Y, Clinton SK, Gerard C, Sukhova GK, Libby P, et al. Absence of monocyte chemoattractant protein-1 reduces atherosclerosis in low density lipoprotein receptor-deficient mice. Mol Cell. 1998;2:275-81. [PMID: 9734366]
5.
Bodnár N, Kerekes G, Seres I, Paragh G, Kappelmayer J, Némethné ZG, et al. Assessment of subclinical vascular disease associated with ankylosing spondylitis. J Rheumatol. 2011;38:723-9. [PMID: 21239756] doi: 10.3899/jrheum.100668
6.
Mathieu S, Joly H, Baron G, Tournadre A, Dubost JJ, Ristori JM, et al. Trend towards increased arterial stiffness or intima-media thickness in ankylosing spondylitis patients without clinically evident cardiovascular disease. Rheumatology (Oxford). 2008;47:1203-7. [PMID: 18524805] doi: 10.1093/rheumatology/ken198
7.
Papagoras C, Voulgari PV, Drosos AA. Atherosclerosis and cardiovascular disease in the spondyloarthritides, particularly ankylosing spondylitis and psoriatic arthritis. Clin Exp Rheumatol. 2013;31:612-20. [PMID: 23406817]
8.
Peters MJ, vanEijk IC, Smulders YM, Serne E, Dijkmans BA, van der Horst-Bruinsma IE, et al. Signs of accelerated preclinical atherosclerosis in patients with ankylosing spondylitis. J Rheumatol. 2010;37:161-6. [PMID: 19955053] doi: 10.3899/jrheum.090667
9.
Sari I, Okan T, Akar S, Cece H, Altay C, Secil M, et al. Impaired endothelial function in patients with ankylosing spondylitis. Rheumatology (Oxford). 2006;45:283-6. [PMID: 16204374]
10.
van Eijk IC, Peters MJ, Serné EH, van der Horst-Bruinsma IE, Dijkmans BA, Smulders YM, et al. Microvascular function is impaired in ankylosing spondylitis and improves after tumour necrosis factor alpha blockade. Ann Rheum Dis. 2009;68:362-6. [PMID: 18390569] doi: 10.1136/ard.2007.086777
11.
Szabo SM, Levy AR, Rao SR, Kirbach SE, Lacaille D, Cifaldi M, et al. Increased risk of cardiovascular and cerebrovascular diseases in individuals with ankylosing spondylitis: a population-based study. Arthritis Rheum. 2011;63:3294-304. [PMID: 21834064] doi: 10.1002/art.30581
12.
Vinsonneau U, Brondex A, Mansourati J, Saraux A, Cornily JC, Arlès F, et al. Cardiovascular disease in patients with spondyloarthropathies. Joint Bone Spine. 2008;75:18-21. [PMID: 17913549]
13.
Lautermann D, Braun J. Ankylosing spondylitis—cardiac manifestations. Clin Exp Rheumatol. 2002;20:S11-5. [PMID: 12463440]
14.
Dik VK, Peters MJ, Dijkmans PA, Van der Weijden MA, DeVries MK, Dijkmans BA, et al. The relationship between disease-related characteristics and conduction disturbances in ankylosing spondylitis. Scand J Rheumatol. 2010;39:38-41. [PMID: 20132069] doi: 10.3109/03009740903096101
15.
Peters MJ, Visman I, Nielen MM, VanDillen N, Verheij RA, van der Horst-Bruinsma IE, et al. Ankylosing spondylitis: a risk factor for myocardial infarction? Ann Rheum Dis. 2010;69:579-81. [PMID: 19403516] doi: 10.1136/ard.2009.110593
16.
Huang YP, Wang YH, Pan SL. Increased risk of ischemic heart disease in young patients with newly diagnosed ankylosing spondylitis—a population-based longitudinal follow-up study. PLoS One. 2013;8:e64155. [PMID: 23691161] doi: 10.1371/journal.pone.0064155
17.
Hollan I, Saatvedt K, Almdahl SM, Mikkelsen K, Moer R, Halvorsen P, et al. Spondyloarthritis: a strong predictor of early coronary artery bypass grafting. Scand J Rheumatol. 2008;37:18-22. [PMID: 18189190] doi: 10.1080/03009740701716868
18.
Brophy S, Cooksey R, Atkinson M, Zhou SM, Husain MJ, Macey S, et al. No increased rate of acute myocardial infarction or stroke among patients with ankylosing spondylitis-a retrospective cohort study using routine data. Semin Arthritis Rheum. 2012;42:140-5. [PMID: 22494565] doi: 10.1016/j.semarthrit.2012.02.008
19.
Lehtinen K. Mortality and causes of death in 398 patients admitted to hospital with ankylosing spondylitis. Ann Rheum Dis. 1993;52:174-6. [PMID: 8484668]
20.
Khan MA, Khan MK, Kushner I. Survival among patients with ankylosing spondylitis: a life-table analysis. J Rheumatol. 1981;8:86-90. [PMID: 7218263]
21.
Zochling J, Braun J. Mortality in ankylosing spondylitis. Clin Exp Rheumatol. 2008;26:S80-4. [PMID: 19026148]
22.
Zochling J, Braun J. Mortality in rheumatoid arthritis and ankylosing spondylitis. Clin Exp Rheumatol. 2009;27:S127-30. [PMID: 19822059]
23.
Mok CC, Kwok CL, Ho LY, Chan PT, Yip SF. Life expectancy, standardized mortality ratios, and causes of death in six rheumatic diseases in Hong Kong, China. Arthritis Rheum. 2011;63:1182-9. [PMID: 21391198] doi: 10.1002/art.30277
24.
Bakland G, Gran JT, Nossent JC. Increased mortality in ankylosing spondylitis is related to disease activity. Ann Rheum Dis. 2011;70:1921-5. [PMID: 21784726] doi: 10.1136/ard.2011.151191
25.
Haroon N, Inman RD, Learch TJ, Weisman MH, Lee M, Rahbar MH, et al. The impact of tumor necrosis factor a inhibitors on radiographic progression in ankylosing spondylitis. Arthritis Rheum. 2013;65:2645-54. [PMID: 23818109] doi: 10.1002/art.38070
26.
Baraliakos X, Haibel H, Listing J, Sieper J, Braun J. Continuous long-term anti-TNF therapy does not lead to an increase in the rate of new bone formation over 8 years in patients with ankylosing spondylitis. Ann Rheum Dis. 2014;73:710-5. [PMID: 23505240] doi: 10.1136/annrheumdis-2012-202698
27.
Williams JI, Young W. A summary of studies on the quality of health care administrative databases in Canada. In: Goel V, Williams J, Anderson G, Blackstien-Hirsch P, Fooks C, Naylor D, eds. Patterns of Health Care in Ontario: The ICES Practice Atlas. 2d ed. Ottawa, ON, Canada: Canadian Med Assoc; 1996:339-45.
28.
Juurlink D, Preyra C, Croxford R, Chong A, Austin P, Tu J, et al. Canadian Institute for Health Information Discharge Abstract Database: A Validation Study. Toronto, Ontario, Canada: Institute for Clinical Evaluative Sciences; 2006.
29.
Balzi D, Barchielli A, Battistella G, Gnavi R, Inio A, Tessari R, et al. [Ischemic heart disease prevalence estimated using a standard algorithm based on electronic health data in various areas of Italy]. Epidemiol Prev. 2008;32:22-9. [PMID: 18928235]
30.
Roger VL, Killian J, Henkel M, Weston SA, Goraya TY, Yawn BP, et al. Coronary disease surveillance in Olmsted County objectives and methodology. J Clin Epidemiol. 2002;55:593-601. [PMID: 12063101]
31.
Wannamethee SG, Shaper AG, Lennon L. Cardiovascular disease incidence and mortality in older men with diabetes and in men with coronary heart disease. Heart. 2004;90:1398-403. [PMID: 15547012]
32.
Stavem K, Rønning OM. Survival of unselected stroke patients in a stroke unit compared with conventional care. QJM. 2002;95:143-52. [PMID: 11865169]
33.
Tu K, Campbell NR, Chen ZL, Cauch-Dudek KJ, McAlister FA. Accuracy of administrative databases in identifying patients with hypertension. Open Med. 2007;1:e18-26. [PMID: 20101286]
34.
Hux JE, Ivis F, Flintoft V, Bica A. Diabetes in Ontario: determination of prevalence and incidence using a validated administrative data algorithm. Diabetes Care. 2002;25:512-6. [PMID: 11874939]
35.
Benchimol EI, Guttmann A, Mack DR, Nguyen GC, Marshall JK, Gregor JC, et al. Validation of international algorithms to identify adults with inflammatory bowel disease in health administrative data from Ontario, Canada. J Clin Epidemiol. 2014;67:887-96. [PMID: 24774473] doi: 10.1016/j.jclinepi.2014.02.019
36.
Shah BR, Chiu M, Amin S, Ramani M, Sadry S, Tu JV. Surname lists to identify South Asian and Chinese ethnicity from secondary data in Ontario, Canada: a validation study. BMC Med Res Methodol. 2010;10:42. [PMID: 20470433] doi: 10.1186/1471-2288-10-42
37.
Elit L, Saskin R, Raut R, Elliott L, Murphy J, Marrett L. Sociodemographic factors associated with cervical cancer screening coverage and follow-up of high grade abnormal results in a population-based cohort. Gynecol Oncol. 2013;128:95-100. [PMID: 23085459] doi: 10.1016/j.ygyno.2012.10.006
38.
Wilkins R. PCCF+ Version 3G User's Guide (Geocodes/PCCF). Automated Geographic Coding Based on the Statistics Canada Postal Code Conversion Files, Including Postal Codes to June 2001. Ottawa, Ontario, Canada: Statistics Canada; 2001.
39.
Mamdani M, Sykora K, Li P, Normand SL, Streiner DL, Austin PC, et al. Reader's guide to critical appraisal of cohort studies: 2. Assessing potential for confounding. BMJ. 2005;330:960-2. [PMID: 15845982]
40.
Thakkar B, Hur K, Henderson WG, Oprian C. A method to generate Kaplan-Meier and adjusted survival curves using SAS. In: Proceedings of the Twenty-Third Annual SAS Users Group International (SUGI) Conference; Nashville, Tennessee;. 22–25 March 1998:226-8.
41.
Margel D, Urbach DR, Lipscombe LL, Bell CM, Kulkarni G, Austin PC, et al. Metformin use and all-cause and prostate cancer-specific mortality among men with diabetes. J Clin Oncol. 2013;31:3069-75. [PMID: 23918942] doi: 10.1200/JCO.2012.46.7043
42.
Levy AR, Szabo SM, Rao SR, Cifaldi M, Maksymowych WP. Estimating the occurrence of renal complications among persons with ankylosing spondylitis. Arthritis Care Res (Hoboken). 2014;66:440-5. [PMID: 24106183] doi: 10.1002/acr.22176
43.
Wallis D, Haroon N, Ayearst R, Carty A, Inman RD. Ankylosing spondylitis and nonradiographic axial spondyloarthritis: part of a common spectrum or distinct diseases? J Rheumatol. 2013;40:2038-41. [PMID: 24187102] doi: 10.3899/jrheum.130588
44.
Tournadre A, Pereira B, Lhoste A, Dubost JJ, Ristori JM, Claudepierre P, et al. Differences between women and men with recent-onset axial spondyloarthritis: results from a prospective multicenter French cohort. Arthritis Care Res (Hoboken). 2013;65:1482-9. [PMID: 23463610] doi: 10.1002/acr.22001
45.
Radford EP, Doll R, Smith PG. Mortality among patients with ankylosing spondylitis not given X-ray therapy. N Engl J Med. 1977;297:572-6. [PMID: 887115]
46.
Kaprove RE, Little AH, Graham DC, Rosen PS. Ankylosing spondylitis: survival in men with and without radiotherapy. Arthritis Rheum. 1980;23:57-61. [PMID: 7352944]
47.
Schisterman EF, Cole SR, Platt RW. Overadjustment bias and unnecessary adjustment in epidemiologic studies. Epidemiology. 2009;20:488-95. [PMID: 19525685] doi: 10.1097/EDE.0b013e3181a819a1
48.
Hamdi W, ChelliBouaziz M, Zouch I, Ghannouchi MM, Haouel M, Ladeb MF, et al. Assessment of preclinical atherosclerosis in patients with ankylosing spondylitis. J Rheumatol. 2012;39:322-6. [PMID: 22247364] doi: 10.3899/jrheum.110792
49.
Papadakis JA, Sidiropoulos PI, Karvounaris SA, Vrentzos GE, Spanakis EK, Ganotakis ES, et al. High prevalence of metabolic syndrome and cardiovascular risk factors in men with ankylosing spondylitis on anti-TNFα treatment: correlation with disease activity. Clin Exp Rheumatol. 2009;27:292-8. [PMID: 19473571]
50.
Chen HH, Yeh SY, Chen HY, Lin CL, Sung FC, Kao CH. Ankylosing spondylitis and other inflammatory spondyloarthritis increase the risk of developing type 2 diabetes in an Asian population. Rheumatol Int. 2014;34:265-70. [PMID: 24362789] doi: 10.1007/s00296-013-2927-5
51.
Kanathur N, Lee-Chiong T. Pulmonary manifestations of ankylosing spondylitis. Clin Chest Med. 2010;31:547-54. [PMID: 20692546] doi: 10.1016/j.ccm.2010.05.002
52.
Reveille JD, Hirsch R, Dillon CF, Carroll MD, Weisman MH. The prevalence of HLA-B27 in the US: data from the US National Health and Nutrition Examination Survey, 2009. Arthritis Rheum. 2012;64:1407-11. [PMID: 22139851] doi: 10.1002/art.33503
53.
Bhala N, Emberson J, Merhi A, Abramson S, Arber N, Baron JA, et al; Coxib and traditional NSAID Trialists' (CNT) Collaboration. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet. 2013;382:769-79. [PMID: 23726390] doi: 10.1016/S0140-6736(13)60900-9
54.
Watson DJ, Rhodes T, Cai B, Guess HA. Lower risk of thromboembolic cardiovascular events with naproxen among patients with rheumatoid arthritis. Arch Intern Med. 2002;162:1105-10. [PMID: 12020179]
55.
Lindhardsen J, Gislason GH, Jacobsen S, Ahlehoff O, Olsen AM, Madsen OR, et al. Non-steroidal anti-inflammatory drugs and risk of cardiovascular disease in patients with rheumatoid arthritis: a nationwide cohort study. Ann Rheum Dis. 2013. [PMID: 23749610]
56.
Singh JA, Holmgren AR, Krug H, Noorbaloochi S. Accuracy of the diagnoses of spondylarthritides in veterans affairs medical center databases. Arthritis Rheum. 2007;57:648-55. [PMID: 17471541]
57.
Poddubnyy D, Haibel H, Listing J, Märker-Hermann E, Zeidler H, Braun J, et al. Baseline radiographic damage, elevated acute-phase reactant levels, and cigarette smoking status predict spinal radiographic progression in early axial spondylarthritis. Arthritis Rheum. 2012;64:1388-98. [PMID: 22127957] doi: 10.1002/art.33465
Comments
Sign In to Submit A CommentInformation & Authors
Information
Published In
Annals of Internal Medicine
Volume 163 • Number 6 • 15 September 2015
Pages: 409 - 416
History
Published online: 15 September 2015
Published in issue: 15 September 2015
Keywords
Copyright
© 2015 American College of Physicians.
Authors
Metrics & Citations
Metrics
Citations
If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. For an editable text file, please select Medlars format which will download as a .txt file. Simply select your manager software from the list below and click Download.
For more information or tips please see 'Downloading to a citation manager' in the Help menu.
Download article citation data for:
Patients With Ankylosing Spondylitis Have Increased Cardiovascular and Cerebrovascular Mortality: A Population-Based Study. Ann Intern Med.2015;163:409-416. [Epub 15 September 2015]. doi:10.7326/M14-2470
Patients With Ankylosing Spondylitis Have Increased Cardiovascular and Cerebrovascular Mortality: A Population-Based Study. Ann Intern Med.2015;163:409-416. [Epub 15 September 2015]. doi:10.7326/M14-2470
View More
Login Options:
Purchase
You will be redirected to acponline.org to sign-in to Annals to complete your purchase.
Access to EPUBs and PDFs for FREE Annals content requires users to be registered and logged in. A subscription is not required. You can create a free account below or from the following link. You will be redirected to acponline.org to create an account that will provide access to Annals. If you are accessing the Free Annals content via your institution's access, registration is not required.
Create your Free Account
You will be redirected to acponline.org to create an account that will provide access to Annals.
Patients with ankylosing spondylitis should periodically be screened for both overt and subclinical atherosclerotic cardiovascular diseases and preventive statin therapy may be considered
Ankylosing spondylitis is a genetically predisposed, chronic-inflammatory disease associated with increased pro-inflammatory cytokines; TNF-alpha, TGF-beta and IL-1. C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) may be elevated but normal CRP and ESR do not rule out the diagnosis of AS [3].
AS is associated with increase in blood pressure and dyslipidemia may lead to congestive heart failure and peripheral arterial disease [4]. Carotid intima media thickness (CIMT), a marker of subclinical atherosclerosis can be found in significant number of patients with AS [5][6].
Since AS is a life-long disease, along with NSAIDs, DMARDs, physiotherapy and or biologic, periodic cardiovascular risk assessment and statin therapy is required [7].
References:
1. Nisha Nigil Haroon, MD, DM, DNB, MSc; J. Michael Paterson, MSc; Ping Li, PhD; Robert D. Inman, MD; and Nigil Haroon, MD, PhD, DM. Patients With Ankylosing Spondylitis Have Increased Cardiovascular and Cerebrovascular Mortality: A Population-based Study. Ann Intern Med. Published online 11 August 2015
2. Schoenfeld SR, Lu L, Rai SK, Seeger JD, Zhang Y, Choi HK. Statin use and mortality in rheumatoid arthritis: a general population-based cohort study. Ann Rheum Dis. 2015 Aug 5
3. Spoorenberg A, van der Heijde D, de Klerk E, et al. Relative value of erythrocyte sedimentation rate and C-reactive protein in assessment of disease activity in ankylosing spondylitis. J Rheumatol. 1999;26:980-984
4. Han C, Robinson DW Jr, Hackett MV, Paramore LC, Fraeman KH, Bala MV. Cardiovascular disease and risk factors in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. J Rheumatol. 2006; 33: 2167–2172
5. Gonzalez-Gay MA, Gonzalez-Juanatey C, Piñeiro A, et al. High-grade C-reactive protein elevation correlates with accelerated atherogenesis in patients with rheumatoid arthritis. J Rheumatol. 2005;32(7):1219-23.
6. Carotid intima-media thickness in spondyloarthritis patients. Sao Paulo Med. J. vol.131 no.2 São Paulo 2013
7. Van Denderen, J C et al. “Statin Therapy Might Be Beneficial for Patients with Ankylosing Spondylitis.” Annals of the Rheumatic Diseases 65.5 (2006): 695–696. PMC. Web. 31 Aug. 2015.