Cardiovascular Autonomic Function Changes and Predictors During a 2-Year Physical Activity Program in Rheumatoid Arthritis: A PARA 2010 Substudy

David Hupin; Philip Sarajlic; Ashwin Venkateshvaran; Cecilia Fridén; Birgitta Nordgren; Christina H Opava; Ingrid E Lundberg; Magnus Bäck

doi:10.3389/fmed.2021.788243

Cardiovascular Autonomic Function Changes and Predictors During a 2-Year Physical Activity Program in Rheumatoid Arthritis: A PARA 2010 Substudy

Front Med (Lausanne). 2021 Dec 15:8:788243. doi: 10.3389/fmed.2021.788243. eCollection 2021.

Authors

David Hupin^{1

2

3

4}, Philip Sarajlic^{1

2}, Ashwin Venkateshvaran^{2

5}, Cecilia Fridén⁶, Birgitta Nordgren^{6

7}, Christina H Opava^{6

8}, Ingrid E Lundberg^{8

9}, Magnus Bäck^{1

2

5}

Affiliations

¹ Translational Cardiology, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
² Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
³ INSERM, U1059, SAINBIOSE, Université de Lyon, Université Jean-Monnet, Saint-Etienne, France.
⁴ Department of Clinical and Exercise Physiology, University Hospital of Saint-Etienne, Saint-Etienne, France.
⁵ Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden.
⁶ Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
⁷ Women's Health and Allied Health Professionals Theme, Medical Unit Occupational Therapy and Physiotherapy, Karolinska University Hospital, Stockholm, Sweden.
⁸ Rheumatology, Inflammation and Ageing Theme, Karolinska University Hospital, Stockholm, Sweden.
⁹ Department of Medicine Solna, Division of Rheumatology, Karolinska Institutet, Stockholm, Sweden.

Abstract

Background: Chronic inflammation leads to autonomic dysfunction, which may contribute to the increased risk of cardiovascular diseases (CVD) in patients with rheumatoid arthritis (RA). Exercise is known to restore autonomic nervous system (ANS) activity and particularly its parasympathetic component. A practical clinical tool to assess autonomic function, and in particular parasympathetic tone, is heart rate recovery (HRR). The aim of this substudy from the prospective PARA 2010 study was to determine changes in HRR post-maximal exercise electrocardiogram (ECG) after a 2-year physical activity program and to determine the main predictive factors associated with effects on HRR in RA. Methods: Twenty-five participants performed physiotherapist-guided aerobic and muscle-strengthening exercises for 1 year and were instructed to continue the unsupervised physical activity program autonomously in the next year. All participants were examined at baseline and at years 1 and 2 with a maximal exercise ECG on a cycle ergometer. HRR was measured at 1, 2, 3, 4, and 5 min following peak heart rate during exercise. Machine-learning algorithms with the elastic net linear regression models were performed to predict changes in HRR1 and HRR2 at 1 year and 2 years of the PARA program. Results: Mean age was 60 years, range of 41-73 years (88% women). Both HRR1 and HRR2 increased significantly from baseline to year 1 with guided physical activity and decreased significantly from year 1 to year 2 with unsupervised physical activity. Blood pressure response to exercise, low BMI, and muscular strength were the best predictors of HRR1/HRR2 increase during the first year and HRR1/HRR2 decrease during the second year of the PARA program. Conclusion: ANS activity in RA assessed by HRR was improved by guided physical activity, and machine learning allowed to identify predictors of the HRR response at the different time points. HRR could be a relevant marker of the effectiveness of physical activity recommended in patients with RA at high risk of CVD. Very inactive and/or high CVD risk RA patients may get substantial benefits from a physical activity program.

Keywords: autonomic nervous system; blood pressure; cardiovascular disease; heart rate recovery; inflammation; muscular strength; physical activity; rheumatoid arthritis.