The Effects of Cardiac Rehabilitation Programme in Hypertensive Rheumatoid Arthritis Patients

The aim of this study is to investigate the beneficial impacts of the 6-week standardized CR program applied to hypertensive RA patients whose disease activity is under control with regular pharmacological treatment.

Subjects will be randomly assigned to one of two groups: 1.) standard of care (SOC) treatment or 2.) SOC plus a 6 week CR program.

Rheumatoid arthritis (RA) is a chronic systemic auto-immune disease characterized by inflammation and structural damage in synovial joints, but also has extra-articular involvements such as the cardiovascular system. RA patients have higher mortality rates than the general population, and approximately half of premature deaths are due to cardiovascular comorbidities. Traditional risk factors, especially hypertension (HTN), play a key role in the development of cardiovascular diseases (CVD).

In chronic inflammatory diseases such as RA, autoimmunity is a cause of HTN as well as a result of physical damage to the vascular wall. Mild blood pressure elevation caused by specific HTN triggers such as salt retention, angiotensin-II or genetic susceptibility leads to neoantigen release through tissue damage. These neoantigens are recognized by antigen-presenting cells and lead to the differentiation of CD4+ naïve-T lymphocytes into Th1 and Th17 cells. IL-17 and IFN-γ expression causes local inflammation in the vascular wall, endothelial dysfunction, and arterial stiffness. Thus, HTN causes an increase in CVD risk through a common pathogenesis mechanism with RA.

European League Against Rheumatism (EULAR) recommendations emphasize that rheumatologists should be responsible for CVD risk management in RA. However, both RA and HTN treatment is generally administered pharmacologically without focusing on CVD risk. Patients may be recommended regular exercise and lifestyle changes according to EULAR recommendation guide for CVD risk management. One possible intervention that could be used to decrease CVD risk caused by both diseases is cardiac rehabilitation (CR) program in which regular exercise is one of the main components. But RA patients, especially those with cardiovascular comorbidities, are rarely referred to the CR program.

This study will help to clarify the effects of the CR program added to the pharmacological treatment of these patients on cardiovascular mortality risk (Framingham risk score and QRISK-3 score), blood pressure (24-Hour holter monitoring), disease activity (DAS28-CRP), aerobic capacity (VO2max), quality of life (36-Item Short Form Survey) and psychological state (Beck depression inventory).

Eligibility Criteria:
Inclusion Criteria:

1. Patients diagnosed with RA according to ACR/EULAR 2010 criteria
2. Taking regular treatment for at least 1 month according to ACR/EULAR guidelines
3. Patients diagnosed with HT according to the 2018 European Society of Hypertension and European Society of Cardiology (ESH/ESC) guideline

Exclusion Criteria:

1. Refusing to participate in the program
2. Severe mental disorder
3. Neurological disease or deformity in the lower extremity that would prevent the patient from using the treadmill.
4. High-risk unstable angina and all acute cardiac diseases (acute myocardial infarction, acute endocarditis, myocarditis or pericarditis)
5. Uncontrolled HT, Diabetes, cardiac arrhythmia and heart failure
6. Symptomatic severe aortic stenosis
7. Acute pulmonary embolism or pulmonary infarction and severe pulmonary hypertension