Original Research
15 September 2015

Patients With Ankylosing Spondylitis Have Increased Cardiovascular and Cerebrovascular Mortality: A Population-Based Study

Publication: Annals of Internal Medicine
Volume 163, Number 6



Ankylosing spondylitis (AS) is a chronic inflammatory arthritis affecting the spine in young adults. It is associated with excess cardiovascular and cerebrovascular morbidity.


To determine whether patients with AS are at increased risk for cardiovascular and cerebrovascular mortality.


Population-based retrospective cohort study using administrative health data.


Ontario, Canada.


21 473 patients with AS aged 15 years or older and 86 606 comparators without AS, matched for age, sex, and location of residence.


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.


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.


Diagnosis codes for AS were not validated in Ontario.


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.

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Information & Authors


Published In

cover image Annals of Internal Medicine
Annals of Internal Medicine
Volume 163Number 615 September 2015
Pages: 409 - 416


Published online: 15 September 2015
Published in issue: 15 September 2015




Nisha Nigil Haroon, MD, DM, DNB, MSc
From the University of Toronto; Institute for Clinical Evaluative Sciences; Institute of Health Policy, Management and Evaluation; University Health Network; and Toronto Western Research Institute, Toronto, and McMaster University, Hamilton, Ontario, Canada.
J. Michael Paterson, MSc
From the University of Toronto; Institute for Clinical Evaluative Sciences; Institute of Health Policy, Management and Evaluation; University Health Network; and Toronto Western Research Institute, Toronto, and McMaster University, Hamilton, Ontario, Canada.
Ping Li, PhD
From the University of Toronto; Institute for Clinical Evaluative Sciences; Institute of Health Policy, Management and Evaluation; University Health Network; and Toronto Western Research Institute, Toronto, and McMaster University, Hamilton, Ontario, Canada.
Robert D. Inman, MD
From the University of Toronto; Institute for Clinical Evaluative Sciences; Institute of Health Policy, Management and Evaluation; University Health Network; and Toronto Western Research Institute, Toronto, and McMaster University, Hamilton, Ontario, Canada.
Nigil Haroon, MD, PhD, DM
From the University of Toronto; Institute for Clinical Evaluative Sciences; Institute of Health Policy, Management and Evaluation; University Health Network; and Toronto Western Research Institute, Toronto, and McMaster University, Hamilton, Ontario, Canada.
Disclaimer: The opinions, results, and conclusions reported in this article are those of the authors and are independent from the funding sources. No endorsement by ICES or the Ontario Ministry of Health and Long-Term Care is intended or should be inferred. Parts of this material are based on data and information compiled and provided by CIHI; however, the analyses, conclusions, opinions, and statements expressed herein are those of the authors and not necessarily those of CIHI.
Grant Support: By the Arthritis Center of Excellence; The Arthritis Society; and ICES, which is funded by a grant from the Ontario Ministry of Health and Long-Term Care.
Disclosures: Dr. N. Haroon reports grants from the Arthritis Society, nonfinancial support from the Institute of Clinical Evaluative Sciences, and grants from Toronto General and Western Hospital Foundation during the conduct of the study and personal fees from AbbVie, Amgen, Celgene, Janssen, UCB, and Hospira outside the submitted work. Authors not named here have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOf InterestForms.do?msNum=M14-2470.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer.
Reproducible Research Statement: Study protocol and statistical code: Available from Dr. Nigil Haroon (e-mail, [email protected]). Data set: Not available.
Corresponding Author: Nigil Haroon, MD, PhD, DM, Toronto Western Hospital, 1E-425, 399 Bathurst Street, Toronto Western Hospital, Toronto, Ontario M5T 2S8, Canada; e-mail, [email protected].
Current Author Addresses: Dr. N.N. Haroon: Department of Medicine, University of Toronto, 200 Elizabeth Street, 7th Floor, OP Program, Toronto, Ontario M5G 2C4, Canada.
Mr. Paterson and Dr. Li: Institute for Clinical Evaluative Sciences, G106-2075 Bayview Avenue, Toronto, Ontario M4N 3M5, Canada.
Dr. Inman: Toronto Western Hospital, 1EW-423, 399 Bathurst Street, Toronto, Ontario M5T 2S8, Canada.
Dr. N. Haroon: Toronto Western Hospital, 1EW-425, 399 Bathurst Street, Toronto, Ontario M5T 2S8, Canada.
Author Contributions: Conception and design: N.N. Haroon, J.M. Paterson, P. Li, R.D. Inman, N. Haroon.
Analysis and interpretation of the data: N.N. Haroon, J.M. Paterson, P. Li, R.D. Inman, N. Haroon.
Drafting of the article: N.N. Haroon, R.D. Inman, N. Haroon.
Critical revision of the article for important intellectual content: N.N. Haroon, J.M. Paterson, P. Li, R.D. Inman, N. Haroon.
Final approval of the article: N.N. Haroon, J.M. Paterson, R.D. Inman, N. Haroon.
Statistical expertise: N.N. Haroon, P. Li, N. Haroon.
Obtaining of funding: R.D. Inman, N. Haroon.
Administrative, technical, or logistic support: J.M. Paterson, P. Li, R.D. Inman.
This article was published online first at www.annals.org on 11 August 2015.

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Nisha Nigil Haroon, J. Michael Paterson, Ping Li, et al. 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

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