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Does depression increase the risk of stroke in patients with rheumatoid arthritis? A population-based cohort study
  1. Tzung-Yi Tsai1,2,3,
  2. Ming-Chi Lu4,5,
  3. Hanoch Livneh6,
  4. Shan-Yun Chiu7,
  5. Ning-Sheng Lai4,5,
  6. How-Ran Guo2,8,9
  1. 1Department of Medical Research, Dalin Tzuchi Hospital, The Buddhist Tzuchi Medical Foundation, Chiayi, Taiwan
  2. 2Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan
  3. 3Department of Nursing, Tzu Chi University of Science and Technology, Hualien, Taiwan
  4. 4Division of Allergy, Immunology and Rheumatology, Dalin Tzuchi Hospital, The Buddhist Tzuchi Medical Foundation, Chiayi, Taiwan
  5. 5School of Medicine, Tzu Chi University, Hualien, Taiwan
  6. 6Rehabilitation Counseling Program, Portland State University, Portland, Oregon, USA
  7. 7Department of Nursing, Dalin Tzuchi Hospital, The Buddhist Tzuchi Medical Foundation, Chiayi, Taiwan
  8. 8Department of Occupational and Environmental Medicine, National Cheng Kung University Hospital, Tainan, Taiwan
  9. 9Occupational Safety, Health, and Medicine Research Center, National Cheng Kung University, Tainan, Taiwan
  1. Correspondence to Professor How-Ran Guo; hrguo{at}, or Dr. Ming-Chi Lu; e360187{at}


Objectives Comorbid depression is common and undertreated in patients with rheumatoid arthritis (RA). It remains uncertain whether comorbid depression provoked the risk of poor clinical outcome, stroke in particular, among patients with RA. This work aimed to determine if depression onset during the treatment process increases stroke risk for patients with RA as compared with those with (1) neither RA nor depression, (2) RA only and (3) depression only.

Design A nationwide, population-based cohort study.

Setting Taiwan's Longitudinal Health Insurance Database.

Participants We identified 8045 subjects with a newly diagnosed RA between 1997 and 2010, together with 32 600 subjects without RA matched by age, gender and index date. All subjects were further divided into four groups based on whether they were diagnosed with comorbid depression during the follow-up period.

Main outcome measure The incidence rate and HR for incident stroke were estimated by the end of 2012 using Cox proportional hazard regression.

Results We discovered that patients with RA with the comorbid depression exhibited the highest risk of stroke, with an adjusted HR of 2.18 (95% CI 1.87 to 2.54). Those with RA only or those with depression only still had the higher risk of stroke by 43% and 57% as compared with subjects without either condition. Multivariate analysis showed RA subjects who were male or older, incurred the onset of depression, or had comorbidities such as hypertension, diabetes as well as heart disease, had a greater risk of stroke.

Conclusions This study cleared up the significant association between RA and the subsequent risk of stroke, and further highlighted that the onset of depression within the treatment process may increase stroke risk for RA subjects. Findings could assist healthcare providers to pinpoint individuals with RA with a higher predisposition of stroke, which could facilitate the provision of appropriate rehabilitation.

  • rheumatoid arthritis
  • cohort study

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  • Contributors All the authors approved the contents of the submitted article. M-CL and H-RG contributed equally to this work. T-YT and S-YC conceived and designed the experiments. T-YT and H-RG analysed the data. T-YT, N-SL, M-CL and H-RG contributed in reagents/materials/analysis tools. TYT, HL and H-RG wrote the paper. T-YT, N-SL, HL, S-YC, M-CL, H-RG contributed in the final approval of manuscript.

  • Funding This research was supported by Dalin Tzuchi Hospital (grant number DTCRD103(2)-E-05) and DTCRD104(2)-I-07.

  • Disclaimer The interpretation and conclusions contained herein do not represent those of the Bureau of National Health Insurance, Department of Health or National Health Research Institutes.

  • Competing interests None declared.

  • Ethics approval This study was approved by the Research Ethics Committee of Dalin Tzuchi Hospital (No. B10004021-1).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement No additional data are available.

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