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Low disease activity (DAS28≤3.2) reduces the risk of first cardiovascular event in rheumatoid arthritis: a time-dependent Cox regression analysis in a large cohort study
  1. Elke EA Arts1,
  2. Jaap Fransen2,
  3. Alfons A Den Broeder3,
  4. Piet L C M van Riel4,5,
  5. Calin D Popa1,3
  1. 1Department of Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands
  2. 2Department of Rheumatology, Medicines Evaluation Board, Utrecht, The Netherlands
  3. 3Department of Rheumatology, Sint Maartenskliniek, Nijmegen, The Netherlands
  4. 4Department of Rheumatology, Bernhoven, Uden, The Netherlands
  5. 5Department of Rheumatology, Radboud Institute for Health Sciences, IQ healthcare, Radboud University Medical Center, Nijmegen, The Netherlands
  1. Correspondence to Elke EA Arts, Department of Rheumatology, Radboud University Medical Centre, Geert Grooteplein 8, 6500 HB Nijmegen, The Netherlands; elkearts{at}, elkearts{at}


Objective Systemic inflammation appears to contribute to the excess risk of cardiovascular disease (CVD) in rheumatoid arthritis (RA). The objective of this study was to investigate the effect of different levels of disease activity over time, particularly low disease activity and remission, on CVD risk in patients with RA.

Methods Data from the Nijmegen early RA inception cohort were used. The primary outcome was first CVD events within the first 10 years of follow-up. Cut points of the DAS28 for remission (<2.6) and low (≤3.2), moderate (3.2–5.1) and high (>5.1) disease activity were used. The effect of disease activity on CVD risk was analysed using Cox-proportional hazards regression with DAS28 as a time-dependent covariate and also conventionally with time-averaged DAS28 as the primary dependent variable.

Results Low DAS28 (≤3.2) was significantly associated with a reduced risk of CVD (HR 0.65, 95% CI 0.43 to 0.99) compared with DAS28 >3.2, both when included as a time-dependent covariate and as time-averaged DAS28 ≤3.2 (HR 0.52, 95% CI 0.33 to 0.81). Remission had a modest, non-significant protective effect against CVD (HR 0.67, 95% CI 0.43 to 1.07).

Conclusion Results of this study suggest that low disease activity is sufficient to achieve a protective effect against CVD in RA. Apparently, remission defined as DAS28 <2.6 has no additional protective effect against CVD compared with low disease activity. Our results strengthen the use of tight control strategies in daily clinical practice to achieve low stable disease activity or remission in patients with RA as soon as possible.

  • Rheumatoid Arthritis
  • Cardiovascular Disease
  • Disease Activity

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  • Contributors All authors have given substantial contribution to the conception and design and/or analysis and interpretation of the data, have drafted and/or revised the manuscript critically for important intellectual content and have given final approval of the version to be submitted for publication. EEA had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the analysis.

  • Competing interests None delared.

  • Ethics approval CMO Arnhem Nijmegen.

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