Cardiovascular autonomic dysfunction in patients with rheumatoid arthritis: contribution of peripheral chemoreflex, impact on cerebral blood flow and associations with physical inactivity.

• Grant number: 22/08603-5
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: June 01, 2023
• End date: October 31, 2026
• Field of knowledge: Biological Sciences - Physiology - Physiology of Effort
• Principal Investigator: Hamilton Augusto Roschel da Silva
• Grantee: Indyanara Cristina Ribeiro
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 25/05527-4 - Assessment of cerebral blood flow regulation using arterial spin labelling MRI: an exploratory investigation in individuals with lupus, BE.EP.DR

Abstract

RA presents increased cardiovascular risk, which can be caused by cardiovascular autonomic dysfunction, namely an increase in sympathetic activity and a reduction in parasympathetic activity. Impairment in cardiovascular reflex control exerted by the peripheral chemoreceptors may contribute to autonomic dysfunction in this population, however, this has not yet been investigated. Furthermore, autonomic dysfunction in RA can lead to alterations in blood flow regulation to various organs and tissues, including the brain. Changes in cerebral blood flow (CBF) regulation may increase the risk of cerebrovascular events and cognitive decline in these patients. However, there is a lack of studies that have assessed the contribution of the chemoreflex to the pathophysiology of autonomic dysfunction in RA and the impact of this dysfunction on CBF regulation. Lastly, it is important to note that typical behaviors in RA, such as physical inactivity and sedentary behavior, may contribute to the worsening of cardiovascular autonomic dysfunction in RA. However, potential associations between physical inactivity and autonomic function have not yet been investigated in RA. Hence, this project involves three studies with distinct objectives. Study 1 will investigate the effects of the peripheral chemoreflex on cardiovascular autonomic control in RA patients. Assessment of peripheral chemoreflex will be done by exposing participants to different concentrations of gases (e.g., normoxia, hypoxia, and hyperoxia). For this, 16 RA women and 16 age-, BMI- and cardiovascular risk-matched controls will be recruited.HR, BP, muscle blood flow, and V¿E will be recorded during chemoreflex evaluation. These parameters will be compared between sessions and groups using mixed model analysis (p<0.05). Study 2 will investigate whether RA individuals exhibit impairments in CBF regulation, as well as examine associations between autonomic dysfunction, CBF, and cognitive function in these individuals. To achieve this, 16 women with RA and 16 controls will be recruited and matched for age, BMI, and cardiovascular risk parameters. CBF will be assessed using transcranial Doppler ultrasound positioned via assessments of the middle cerebral artery blood velocity. Additionally, cardiovascular variables (HR and BP) and respiratory variables (V¿E and PETCO2) will be measured. CBF regulation will be evaluated by assessing cerebral autoregulation (i.e., time series of mean BP and CBF velocity in the middle cerebral artery) and neurovascular coupling (i.e., CBF velocity responses in the middle cerebral artery during cognitive tests) in supine and orthostatic positions. Autonomic function will be assessed via analyses of heart rate variability and baroreflex sensitivity. These parameters will be compared between groups and between supine and orthostatic positions using mixed model analysis, and associations will be evaluated using Pearson or Spearman correlation (p<0.05). Study 3 will investigate the associations between physical activity/sedentary behavior levels and cardiovascular autonomic function in RA patients. This study will include 30 women with RA. Autonomic function will be assessed during a continuous 10-minute recording of beat-by-beat HR and BP in the supine position, for the subsequent analysis of heart rate variability and baroreflex sensitivity. Physical activity levels will be continuously assessed over 7 days using accelerometers (ActivPAL and Actigraph). Associations between autonomic function and physical activity outcomes will be tested using simple and multiple regressions (p<0.05). The results obtained from these studies will provide a better understanding of the underlying mechanisms contributing to increased cardiovascular risk in RA and could be used to support pharmacological or non-pharmacological interventions for cardiovascular management in this population.