The Effects of Cardiac Rehabilitation Programme in Hypertensive Rheumatoid Arthritis Patients

Hypertension Clinical Trial

— CARDIRA  

Official title:

The Effects of 6-week Cardiac Rehabilitation Programme on Cardiovascular Disease Risk, Systolic and Diastolic Blood Pressure and Disease Activity in Hypertensive Rheumatoid Arthritis Patients : A Randomised Controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06295848
• Other study ID #: KayseriCH005
• Status: Recruiting
• Phase: N/A
• Start date: December 15, 2022
• Est. completion date: June 15, 2024

Study information

• Verified date: March 2024
• Source: Kayseri City Hospital
• Contact: HAVVA TALAY ÇALIS, PROFESSOR
• Phone: +905326874541
• Email: htalaycalis[@]yahoo.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: June 15, 2024
• Est. primary completion date: April 15, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Cardiac Rehabilitation
• Hypertension
• Rheumatoid Arthritis

Intervention

Behavioral:
• Exercise
An individual program will be organized for each patient according to the exercise test result. Since the patients have both arthritis and HTN, aerobic exercises will be given at moderate intensity (40-60% VO2 reserve) according to ACMS recommendations. Xrcise Runner Med treadmill and Xrcise Care 2.5.8.3 software will be used for aerobic exercises. Resistant exercises will be given under the supervision of a physiotherapist, calculating 1 repetitation maximum (1-RM) in the main muscle groups.Patients will perform isotonic exercises with 3 sets of 15 repetitions with a resistance of 60% of 1-RM. The education sessions will be conducted by a multidisciplinary team of health professionals (nurse, physiotherapist and dietician) under the leadership of a clinician experienced in CR. Education topics will consist of 60-minute sessions covering heart-healthy eating, setting health-related goal, exercise, diet, healthy weight loss, smoking cessation, and stress/coping.

Locations

Country	Name	City	State
Turkey	Health Sciences University, Kayseri Medicine Faculty	Kayseri	Kocasinan

Sponsors (1)

Lead Sponsor	Collaborator
Kayseri City Hospital

Country where clinical trial is conducted

Turkey, 

References & Publications (16)

Agca R, Heslinga SC, Rollefstad S, Heslinga M, McInnes IB, Peters MJ, Kvien TK, Dougados M, Radner H, Atzeni F, Primdahl J, Sodergren A, Wallberg Jonsson S, van Rompay J, Zabalan C, Pedersen TR, Jacobsson L, de Vlam K, Gonzalez-Gay MA, Semb AG, Kitas GD, Smulders YM, Szekanecz Z, Sattar N, Symmons DP, Nurmohamed MT. EULAR recommendations for cardiovascular disease risk management in patients with rheumatoid arthritis and other forms of inflammatory joint disorders: 2015/2016 update. Ann Rheum Dis. 2017 Jan;76(1):17-28. doi: 10.1136/annrheumdis-2016-209775. Epub 2016 Oct 3. — View Citation

Almutairi K, Nossent J, Preen D, Keen H, Inderjeeth C. The global prevalence of rheumatoid arthritis: a meta-analysis based on a systematic review. Rheumatol Int. 2021 May;41(5):863-877. doi: 10.1007/s00296-020-04731-0. Epub 2020 Nov 11. — View Citation

Anyfanti P, Gkaliagkousi E, Triantafyllou A, Koletsos N, Gavriilaki E, Galanopoulou V, Aslanidis S, Douma S. Hypertension in rheumatic diseases: prevalence, awareness, treatment, and control rates according to current hypertension guidelines. J Hum Hypertens. 2021 May;35(5):419-427. doi: 10.1038/s41371-020-0348-y. Epub 2020 May 7. — View Citation

Avina-Zubieta JA, Choi HK, Sadatsafavi M, Etminan M, Esdaile JM, Lacaille D. Risk of cardiovascular mortality in patients with rheumatoid arthritis: a meta-analysis of observational studies. Arthritis Rheum. 2008 Dec 15;59(12):1690-7. doi: 10.1002/art.24092. — View Citation

Balady GJ, Ades PA, Comoss P, Limacher M, Pina IL, Southard D, Williams MA, Bazzarre T. Core components of cardiac rehabilitation/secondary prevention programs: A statement for healthcare professionals from the American Heart Association and the American Association of Cardiovascular and Pulmonary Rehabilitation Writing Group. Circulation. 2000 Aug 29;102(9):1069-73. doi: 10.1161/01.cir.102.9.1069. No abstract available. — View Citation

Chauhan K, Jandu JS, Brent LH, Al-Dhahir MA. Rheumatoid Arthritis. 2023 May 25. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from http://www.ncbi.nlm.nih.gov/books/NBK441999/ — View Citation

Gibofsky A. Epidemiology, pathophysiology, and diagnosis of rheumatoid arthritis: A Synopsis. Am J Manag Care. 2014 May;20(7 Suppl):S128-35. — View Citation

Hadwen B, Stranges S, Barra L. Risk factors for hypertension in rheumatoid arthritis patients-A systematic review. Autoimmun Rev. 2021 Apr;20(4):102786. doi: 10.1016/j.autrev.2021.102786. Epub 2021 Feb 18. — View Citation

Jagpal A, Navarro-Millan I. Cardiovascular co-morbidity in patients with rheumatoid arthritis: a narrative review of risk factors, cardiovascular risk assessment and treatment. BMC Rheumatol. 2018 Apr 11;2:10. doi: 10.1186/s41927-018-0014-y. eCollection 2018. — View Citation

Metsios GS, Stavropoulos-Kalinoglou A, Veldhuijzen van Zanten JJ, Treharne GJ, Panoulas VF, Douglas KM, Koutedakis Y, Kitas GD. Rheumatoid arthritis, cardiovascular disease and physical exercise: a systematic review. Rheumatology (Oxford). 2008 Mar;47(3):239-48. doi: 10.1093/rheumatology/kem260. Epub 2007 Nov 28. — View Citation

Panoulas VF, Metsios GS, Pace AV, John H, Treharne GJ, Banks MJ, Kitas GD. Hypertension in rheumatoid arthritis. Rheumatology (Oxford). 2008 Sep;47(9):1286-98. doi: 10.1093/rheumatology/ken159. Epub 2008 May 8. Erratum In: Rheumatology (Oxford). 2009 Apr;48(4):458. — View Citation

Peynirci Cersit H, Yagci I, Cersit S. The improvement in aerobic capacity, disease activity, and function in patients with rheumatoid arthritis following cardiac rehabilitation program: A single-center, controlled study. Turk J Phys Med Rehabil. 2019 Apr 26;66(2):121-133. doi: 10.5606/tftrd.2020.3250. eCollection 2020 Jun. — View Citation

Sahin AA, Ozben B, Sunbul M, Yagci I, Sayar N, Cincin A, Gurel E, Tigen K, Basaran Y. The effect of cardiac rehabilitation on blood pressure, and on left atrial and ventricular functions in hypertensive patients. J Clin Ultrasound. 2020 Dec 1:e22956. doi: 10.1002/jcu.22956. Online ahead of print. — View Citation

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Whelton SP, Chin A, Xin X, He J. Effect of aerobic exercise on blood pressure: a meta-analysis of randomized, controlled trials. Ann Intern Med. 2002 Apr 2;136(7):493-503. doi: 10.7326/0003-4819-136-7-200204020-00006. — View Citation

* Note: There are 16 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Framingham Risk Score(FRS)	It is a common tool used to assess a patient's risk level of cardiovascular disease over the next 10 years. There are six coronary risk factors in the FRS calculation, including age, gender, total cholesterol, HDL cholesterol, smoking and systolic blood pressure. 10-year cardiovascular risk score can be derived as a percentage. Higher values indicate a worse, lower values indicate a better outcome.	0-week, 6-week,12-week,24-week
Primary	QRISK-3 Risk Score	It predicts a patient's risk of developing cardiovascular disease in the next 10 years. It includes many of the traditional risk factors featured in Framingham (such as age, gender, cholesterol/HDL ratio, blood pressure, diabetes and smoking status), but also includes important additional risk factors. 10-year cardiovascular risk score can be derived as a percentage. Higher values indicate a worse, lower values indicate a better outcome.	0-week, 6-week,12-week,24-week
Primary	24-Hour Ambulatory Blood Pressure	It is the gold standard for hypertension diagnosis and 24-hour blood pressure evaluation.	0-week, 6-week,12-week,24-week
Primary	DAS28	Rheumatoid arthritis severity will be determined using DAS28 score. The DAS28 score ranges score between 0 and 10, a larger number indicating more active disease. When using the score to assess response to treatment, a DAS-28 score reduction by 0.6 represents a moderate improvement, while a reduction more than 1.2 represents a major improvement. The score <2.6 suggests disease remission.	0-week, 6-week,12-week,24-week
Primary	Maximal oxygen consumption (VO2max)	VO2 max is the number of milliliters of oxygen used per kilogram of body weight in one minute (ml/kg/min). VO2 max is an objective measurement of cardiorespiratory capacity. Higher values indicate a worse, lower values indicate a better outcome.	0-week, 6-week,12-week,24-week
Secondary	The Six-Minute Walk Test (6MWT)	The Six-Minute Walk Test is a submaximal field test used to monitor exercise capacity and treatment effectiveness in cardiac rehabilitation.	0-week, 6-week,12-week,24-week
Secondary	The 36-Item Short Form Survey (SF-36)	Quality of life will be assessed using the short form of the 36-Item short form survey (SF-36). The SF-36 covers eight health concepts: physical functioning, bodily pain, role limitations due to physical health problems, role limitations due to personal or emotional problems, emotional well-being, social functioning, energy/fatigue, and general health perceptions. Scores for each domain range from 0 to 100, with a higher score defining a more favorable health state.	0-week, 6-week,12-week,24-week
Secondary	International Physical Activity Questionnaire (IPAQ) - Short Form	The IPAQ short form encompasses questions regarding time spent on walking, moderate-intensity, and high-intensity physical activities besides sitting. The IPAQ scoring protocol assigns the following MET values to walking, moderate, and vigorous intensity activity: 3.3 METs, 4.0 METs, and 8.0 METs, respectively. Total physical activity can be computed as the sum of walking + moderate intensity + high intensity MET-min/week scores. Higher values indicate a worse, lower values indicate a better outcome. There are three levels of physical activity suggested for classifying patients based on total weekly MET score: low, moderate and high. The "minutes" of sitting reported by the IPAQ are asessed independtly and reflect sedentary behaviour measurements.	0-week, 6-week,12-week,24-week
Secondary	Beck Depression Inventory (BDI)	The Beck Depression Inventory (BDI) is a 21-item, self-report rating inventory that measures characteristic attitudes and symptoms of depression. The minimum score is 0 and maximum score is 63. Higher scores indicate greater symptom severity.	0-week, 6-week,12-week,24-week