Microvascular AnginaPhase 2NCT00123617
The Impact of Cardiac Rehabilitation Participation on Cardiac Syndrome X
A Phase 2 study testing Phase III group-based cardiac rehabilitation in people with Microvascular Angina, run by National Heart and Lung Institute at 1 site in United Kingdom.
Trial summary
The study is designed to test the hypothesis that participation in a standard phase III group based cardiac rehabilitation programme will improve psychological morbidity, quality of life and cardiovascular risk factors, along with chest pain severity and frequency in women with cardiac syndrome X. Read more about this study
- Who is it for?
- Ages 30 to 80 years, women only
- Conditions the study is for
- Microvascular Angina
- What is being tested?
- Phase III group-based cardiac rehabilitation
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 64 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jan 2003to May 2005
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 to 80 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Women
- Aged 30 to 80 years
- Postmenopausal > 1 year since last menstrual period
- Angiographically normal coronary arteries
- Positive treadmill exercise test for myocardial ischemia
- Reported angina pectoris > 2 episodes per week
- Diagnosis > 6 months
- Willing to give written informed consent
Who cannot join
- History of psychiatric illness
- History of any other chronic illness
- Participation in another research study within the previous 60 days
- Suffer any physical condition for which exercise is a contra-indication.
- Unwilling to give written informed consent
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
National Heart and Lung Institute, Imperial College London
London, SW3 6LY
About this study
Official title: The Impact of Cardiac Rehabilitation on Angina Frequency, Psychological Morbidity and Quality of Life in Women With Syndrome X
The study is designed to test the hypothesis that participation in a standard phase III group based cardiac rehabilitation programme will improve psychological morbidity, quality of life and cardiovascular risk factors, along with chest pain severity and frequency in women with cardiac syndrome X.
Read the detailed description
Very few clinicians treating patients with Syndrome X could dispute that despite an excellent prognosis, the debilitating symptomology and ineffective treatment regimes typical in this condition give patients a miserable quality of life. First identified by Kemp (1), the triad of angina pectoris, a positive exercise test for myocardial ischemia and angiographically smooth coronary arteries continues to perplex clinician seeking a useful treatment regime.
The possible pathophysiology of chest pain associated with Syndrome X is poorly understood in these patients. Suggested mechanisms include abnormal myocardial flow reserve due to coronary microvascular dysfunction ('microvascular angina') (2) or a generalised disorder of vascular function (3),(4) early signs of abnormal left ventricular function (5), which in some patients may deteriorate over time,(6) and abnormal visceral pain perception (7). Some patients exhibit insulin resistance (8). However, there have been few adequate systematic explorations of the psychological and social aspects of Syndrome X.
Several studies have found increased levels of anxiety in patients with normal or near normal coronary arteries in the presence of accompanying chest pain (9). Ruggeri et al (10) found higher level of neuroticism and anxiety in small group of patients with Syndrome X in comparison with patients with confirmed coronary artery disease. Panic disorders, sometimes associated with chest pain, are also often presented with depression, hypochondriasis or other somatoform disorders (11). Studies investigating various non-therapeutic treatment regimes have repeatedly shown that relaxation and stress reduction lead to fewer incidence of chest pain in Syndrome X patients (12). However, the same is also true for patients with CAD (13) along with many other conditions and disorders with related chronic pain (14).
Frequency and severity of chest pain has been shown to have a direct effect on quality of life in Syndrome X patients (15). Sand (16) found that over a 7-year follow-up, a higher percentage of Syndrome X patients had given up work, reduced their daily activities and reported worsening chest pain in comparison to patients with confirmed coronary disease. Persistent functional incapacity with concomitant high levels of chest pain in patients with normal or near normal coronary arteries was also found after an 11-year follow-up (9). Use of anti-anginals was higher, as was their self reported burden on the health service.
The Collins team recently performed the largest psychosocial investigation of postmenopausal women with Syndrome X ever undertaken (17). The Hearts and Minds Study, which involved 100 Syndrome X patients, 100 patients with CHD and 100 healthy volunteers found that Syndrome X patients suffered significantly higher levels of anxiety than CHD patients or healthy controls. A greater number of Syndrome X patients suffered clinical levels of anxiety and depression than CHD patients and healthy volunteers, along with suffering significantly higher levels of psychological suffering as measured by the Health Anxiety Questionnaire than healthy controls. We also found that Syndrome X patients with a small social network had higher levels of anxiety than their counterparts with a larger social support structure.
In order to address these findings, it is important to identify an intervention which not only reduces anxiety, but also promotes wellbeing, improves quality of life and augments the social support resource network available to Syndrome X patients. Cardiac Rehabilitation (CR) has consistently been shown to improve the psychological wellbeing in cardiac patients, as recent reviews have highlighted the beneficial effects of CR on symptoms of angina and dyspnoea, stress level and psychological functioning (18). CR has been shown to have a positive affect on reducing anxiety levels in cardiovascular patients (19), while high levels of depression, a frequent co-morbidity in MI patients, have been reduced by CR (20). Women in particular seem to gain most benefit from CR, as improvements in functional capacity, coronary risk and psychosocial wellbeing were equal or greater in women than men following rehabilitation (21). It has been suggested that CR may reduce anxiety in CHD patients by reducing uncertainty, providing patients with an optimistic yet realistic outlook of recovery, as well as providing psychological support and promoting coping (18). Few could argue that a similar outcome in Syndrome X patients would not be beneficial.
As well as promoting psychological wellbeing, CR also provides patients with a social support resource network. The adequacy of social support has been investigated in relation the prognosis of patients with CHD (22) when it was noted that inadequate tangible support was a significant predictor of both morbidity and mortality. Population based studies have consistently identified a link between social support and CHD morbidity and mortality in men, while disease severity and proliferation have been shown to be related to a lack of support in women (23). Epidemiological studies have also consistently found a link between depression, social isolation and predicted morbidity and mortality in CAD patients (24). It has been argued that CR provides the social context through which coronary prevention interventions are delivered (25) and that this extra social support may have an important part to play in the patients recovery from, and adaptation to, chronic illness (26).
The effect of exercise intervention on the frequency and severity of angina has been the object of investigation for many years. Some studies have reported a reduction in mean weekly episodes of angina of up to 91% using an acute exercise intervention in CHD patients (13) and while other studies have been unable to replicate such results, almost all highlight the beneficial effect of exercise on angina frequency. Nevertheless, very few studies have investigated the impact of exercise on Syndrome X, either from a psychosocial or physiological view-point. Erikkson et al (27) addressed the physical deconditioning apparent in many Syndrome X patients through the use of 8 weeks moderate intensity exercise. Time to pain improved dramatically, with no increase in maximum pain experienced, while peak exercise capacity, heart rate and systolic blood pressure also showed improvements. Exercise capacity and quality of life were also shown to increase following 8 weeks of physical training in separate group of Syndrome X patients (28).
Aerobic exercise has been repeatedly shown to have positive effects on psychological wellbeing, anxiety and depression (29). Patients suffering clinical levels of anxiety and depression have shown a reduction in the severity of their symptoms(30)while athletes and the very active became depressed when they were prevented from exercising(31). Studies involving exercise, anxiety and wellbeing the older population are limited, however subjective health and psychological wellbeing have been shown to be higher among older people who partake in regular exercise (32). Anxiety reduction and increased wellbeing has also been shown in elderly men following an 8-week weekly exercise intervention (33).
Therefore, we would like to explore the beneficial effects of cardiac rehabilitation in Syndrome X patients. Exercise is not currently recognised as a treatment regime for Syndrome X, either as a stand- alone intervention or in conjunction with any other therapy. Patients are currently given little advice or guidance relating to physical activity due to the lack of research and information regarding the potential benefit of exercise available to practitioners. Our previous investigations of Syndrome X have demonstrated a need for an intervention which would not only reduce the patients reported levels of anxiety, but also increase their perceived social support, psychological wellbeing and quality of life. CR has been shown to improve quality of life, reduce anxiety and decrease frequency of angina episodes in CHD patients through the use of exercise intervention and tangible social support. Therefore, we would like to investigate the following research questions:
Does cardiac rehabilitation:
- Reduce the frequency and severity of angina attacks in Syndrome X?
- Reduce anxiety, depression and health related worry found in Syndrome X?
- Improve the quality of life of Syndrome X patients?
Reference List
- Kemp HG, Jr., Vokonas PS, Cohn PF, Gorlin R. The anginal syndrome associated with normal coronary arteriograms. Report of a six year experience. Am J Med 1973; 54(6):735-742.
- Cannon RO, III, Epstein SE. "Microvascular angina" as a cause of chest pain with angiographically normal coronary arteries. Am J Cardiol 1988; 61(15):1338-1343.
- Raymond C. Chest pain not always what it seems; panic disorder may be cause in some. JAMA 1989; 261(8):1101-1102.
- Sax FL, Cannon RO, III, Hanson C, Epstein SE. Impaired forearm vasodilator reserve in patients with microvascular angina. Evidence of a generalized disorder of vascular function? N Engl J Med 1987; 317(22):1366-1370.
- Cannon RO, III, Bonow RO, Bacharach SL, Green MV, Rosing DR, Leon MB et al. Left ventricular dysfunction in patients with angina pectoris, normal epicardial coronary arteries, and abnormal vasodilator reserve. Circulation 1985; 71(2):218-226.
- Opherk D, Schuler G, Wetterauer K, Manthey J, Schwarz F, Kubler W. Four-year follow-up study in patients with angina pectoris and normal coronary arteriograms ("syndrome X"). Circulation 1989; 80(6):1610-1616.
- Shapiro LM, Crake T, Poole-Wilson PA. Is altered cardiac sensation responsible for chest pain in patients with normal coronary arteries? Clinical observation during cardiac catheterisation. Br Med J (Clin Res Ed) 1988; 296(6616):170-171.
- Dean JD, Jones CJ, Hutchison SJ, Peters JR, Henderson AH. Hyperinsulinaemia and microvascular angina ("syndrome X"). Lancet 1991; 337(8739):456-457.
- Potts SG, Bass CM. Psychological morbidity in patients with chest pain and normal or near- normal coronary arteries: a long-term follow-up study . Psychol Med 1995; 25(2):339-347.
- Ruggeri A, Taruschio G, Loricchio ML, Samory G, Borghi A, Bugiardini R. [The correlation between the clinical characteristics and psychological status in syndrome X patients]. Cardiologia 1996; 41(6):551-557.
- Mayou R. Chest pain, palpitations and panic. J Psychosom Res 1998; 44(1):53-70.
- Cunningham C, Brown S, Kaski JC. Effects of transcendental meditation on symptoms and electrocardiographic changes in patients with cardiac syndrome X. Am J Cardiol 2000; 85(5):653-5, A10.
- Ornish D, Scherwitz LW, Doody RS, Kesten D, McLanahan SM, Brown SE et al. Effects of stress management training and dietary changes in treating ischemic heart disease. JAMA 1983; 249(1):54-59.
- Luebbert K, Dahme B, Hasenbring M. The effectiveness of relaxation training in reducing treatment-related symptoms and improving emotional adjustment in acute non-surgical cancer treatment: a meta-analytical review. Psychooncology 2001; 10(6):490-502.
- Atienza F, Velasco JA, Brown S, Ridocci F, Kaski JC. Assessment of quality of life in patients with chest pain and normal coronary arteriogram (syndrome X) using a specific questionnaire. Clin Cardiol 1999; 22(4):283-290.
- Sand NP, Juelsgaard P. [Syndrome X. Somatic and social prognosis of patients with angina pectoris and normal coronary arteriography]. Ugeskr Laeger 1994; 156(8):1131-1136.
- Asbury EA, Creed F, Collins P. Distinct psychosocial differences between women with coronary heart disease and cardiac syndrome X. Eur Heart J 2004; 25 (19):1695-1701.
- Grace SL, Abbey SE, Shnek ZM, Irvine J, Franche RL, Stewart DE. Cardiac rehabilitation I. review of psychosocial factors. Gen Hosp Psychiatry 2002; 24(3):121-126.
- Yoshida T, Kohzuki M, Yoshida K, Hiwatari M, Kamimoto M, Yamamoto C et al. Physical and psychological improvements after phase II cardiac rehabilitation in patients with myocardial infarction. Nurs Health Sci 1999; 1(3):163-170.
- Johnston M, Foulkes J, Johnston DW, Pollard B, Gudmundsdottir H. Impact on patients and partners of inpatient and extended cardiac counseling and rehabilitation: a controlled trial. Psychosom Med 1999; 61(2):225-233.
- O'Callaghan WG, Teo KK, O'Riordan J, Webb H, Dolphin T, Horgan JH. Comparative response of male and female patients with coronary artery disease to exercise rehabilitation. Eur Heart J 1984; 5(8):649-651.
- Woloshin S, Schwartz LM, Tosteson AN, Chang CH, Wright B, Plohman J et al. Perceived adequacy of tangible social support and health outcomes in patients with coronary artery disease. J Gen Intern Med 1997; 12(10):613-618.
- Horsten M, Mittleman MA, Wamala SP, Schenck-Gustafsson K, Orth-Gomer K. Depressive symptoms and lack of social integration in relation to prognosis of CHD in middle-aged women. The Stockholm Female Coronary Risk Study. Eur Heart J 2000; 21(13):1072-1080.
- Wenger NK. Social support and coronary heart disease in women: the challenge to learn more. Eur Heart J 1998; 19(11):1603-1605.
- Lindsay GM, Smith LN, Hanlon P, Wheatley DJ. The influence of general health status and social support on symptomatic outcome following coronary artery bypass grafting. Heart 2001; 85(1):80-86.
- Anderson D, Deshaies G, Jobin J. Social support, social networks and coronary artery disease rehabilitation: a review. Can J Cardiol 1996; 12(8):739-744.
- Eriksson BE, Tyni-Lenne R, Svedenhag J, Hallin R, Jensen-Urstad K, Jensen-Urstad M et al. Physical training in Syndrome X: physical training counteracts deconditioning and pain in Syndrome X. J Am Coll Cardiol 2000; 36(5):1619-1625.
- Tyni-Lenne R, Stryjan S, Eriksson B, Berglund M, Sylven C. Beneficial therapeutic effects of physical training and relaxation therapy in women with coronary syndrome X. Physiother Res Int 2002; 7(1):35-43.
- Salmon P. Effects of physical exercise on anxiety, depression, and sensitivity to stress: a unifying theory. Clin Psychol Rev 2001; 21(1):33-61.
- Craft LL, Landers D.M. The effect of exercise on clinical depression and depression resulting from mental illness: A meta analysis. Journal of Sport and Exercise Psychology 20, 339-357. 1998.
- Aidman EV, Woollard S. The influence of self-reported exercise addiction on acute emotional and physiological responses to brief exercise deprivation. Psychology of Sport and Exercise. 2002.
- Ransford HE, Palisi BJ. Aerobic exercise, subjective health and psychological well-being within age and gender subgroups. Soc Sci Med 1996; 42(11):1555-1559.
- Perrig-Chiello P, Perrig WJ, Ehrsam R, Staehelin HB, Krings F. The effects of resistance training on well-being and memory in elderly volunteers. Age Ageing 1998; 27(4):469-475.
- Conditions
- Microvascular Angina
- Being tested
- Phase III group-based cardiac rehabilitation
- Keywords
- Chest pain, Women, Syndrome X, Cardiac rehabilitation, Psychological morbidity, Cardiovascular risk factors
- Medical subject headings
- Microvascular Angina, Chest Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Phase III group-based cardiac rehabilitationProcedure or surgery
Also called Cardiac rehab
Phase III group-based cardiac rehabilitation
| Study group | Role | What they receive |
|---|---|---|
| Phase III cardiac rehabilitation | Experimental | Phase III group-based cardiac rehabilitation classes, weekly Receives: Procedure: Phase III group-based cardiac rehabilitation |
| Monitoring | No intervention | Normal daily living, no extra visits to study centre |
What is being measured
The primary outcome is the main question the study is designed to answer.
Anxiety
Measured: Measured at baseline then every 8 weeks for 16 weeks
Depression
Measured: Measured at baseline then every 8 weeks for 16 weeks
Health anxiety
Measured: Measured at baseline then every 8 weeks for 16 weeks
Cardiac anxiety
Measured: Measured at baseline then every 8 weeks for 16 weeks
Quality of life
Measured: Measured at baseline then every 8 weeks for 16 weeks
Symptom severity
Measured: Measured at baseline then continuously for 16 weeks
Symptom frequency
Measured: Measured at baseline then continuously for 16 weeks
Secondary outcomes (3)
Cardiovascular risk factors
Measured: Measured at baseline, 8 weeks and 16 weeks.
Physical ability
Measured: Baseline and at 8 weeks
Time to pain
Measured: Baseline and 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jul 2005 (estimated)
- Study startJan 2003
- Primary completionMay 2005
- Study completionMay 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (31)Papers the sponsor has linked to this study.
- Other trials for Microvascular AnginaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 64 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Heart and Lung Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Royal Brompton & Harefield NHS Foundation Trust
- Responsible party
- Principal investigator, Prof. Peter Collins, National Heart and Lung Institute
- Investigators
- Peter Collins, MD FRCP, Principal investigator, National Heart and Lung Institute, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00123617
- Sponsor's protocol ID
- 02-239
- Status last verified
- Apr 2015
- First submitted
- 21 Jul 2005
- Last updated
- 22 Apr 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Kemp HG Jr, Vokonas PS, Cohn PF, Gorlin R. The anginal syndrome associated with normal coronary arteriograms. Report of a six year experience. Am J Med. 1973 Jun;54(6):735-42. doi: 10.1016/0002-9343(73)90060-0. No abstract available.
PubMed 4196179Cannon RO 3rd, Epstein SE. "Microvascular angina" as a cause of chest pain with angiographically normal coronary arteries. Am J Cardiol. 1988 Jun 1;61(15):1338-43. doi: 10.1016/0002-9149(88)91180-0. No abstract available.
PubMed 3287885Raymond C. Chest pain not always what it seems; panic disorder may be cause in some. JAMA. 1989 Feb 24;261(8):1101-2. No abstract available.
PubMed 2915426Sax FL, Cannon RO 3rd, Hanson C, Epstein SE. Impaired forearm vasodilator reserve in patients with microvascular angina. Evidence of a generalized disorder of vascular function? N Engl J Med. 1987 Nov 26;317(22):1366-70. doi: 10.1056/NEJM198711263172202.
PubMed 3683470Cannon RO 3rd, Bonow RO, Bacharach SL, Green MV, Rosing DR, Leon MB, Watson RM, Epstein SE. Left ventricular dysfunction in patients with angina pectoris, normal epicardial coronary arteries, and abnormal vasodilator reserve. Circulation. 1985 Feb;71(2):218-26. doi: 10.1161/01.cir.71.2.218.
PubMed 3965167Opherk D, Schuler G, Wetterauer K, Manthey J, Schwarz F, Kubler W. Four-year follow-up study in patients with angina pectoris and normal coronary arteriograms ("syndrome X"). Circulation. 1989 Dec;80(6):1610-6. doi: 10.1161/01.cir.80.6.1610.
PubMed 2598425Shapiro LM, Crake T, Poole-Wilson PA. Is altered cardiac sensation responsible for chest pain in patients with normal coronary arteries? Clinical observation during cardiac catheterisation. Br Med J (Clin Res Ed). 1988 Jan 16;296(6616):170-1. doi: 10.1136/bmj.296.6616.170-a. No abstract available.
PubMed 3122985Dean JD, Jones CJ, Hutchison SJ, Peters JR, Henderson AH. Hyperinsulinaemia and microvascular angina ("syndrome X"). Lancet. 1991 Feb 23;337(8739):456-7.
PubMed 1671472Potts SG, Bass CM. Psychological morbidity in patients with chest pain and normal or near-normal coronary arteries: a long-term follow-up study. Psychol Med. 1995 Mar;25(2):339-47. doi: 10.1017/s0033291700036242.
PubMed 7675922Ruggeri A, Taruschio G, Loricchio ML, Samory G, Borghi A, Bugiardini R. [The correlation between the clinical characteristics and psychological status in syndrome X patients]. Cardiologia. 1996 Jun;41(6):551-7. Italian.
PubMed 8766418Mayou R. Chest pain, palpitations and panic. J Psychosom Res. 1998 Jan;44(1):53-70. doi: 10.1016/s0022-3999(97)00209-2.
PubMed 9483464Cunningham C, Brown S, Kaski JC. Effects of transcendental meditation on symptoms and electrocardiographic changes in patients with cardiac syndrome X. Am J Cardiol. 2000 Mar 1;85(5):653-5, A10. doi: 10.1016/s0002-9149(99)00828-0.
PubMed 11078284Ornish D, Scherwitz LW, Doody RS, Kesten D, McLanahan SM, Brown SE, DePuey E, Sonnemaker R, Haynes C, Lester J, McAllister GK, Hall RJ, Burdine JA, Gotto AM Jr. Effects of stress management training and dietary changes in treating ischemic heart disease. JAMA. 1983 Jan 7;249(1):54-9.
PubMed 6336794Luebbert K, Dahme B, Hasenbring M. The effectiveness of relaxation training in reducing treatment-related symptoms and improving emotional adjustment in acute non-surgical cancer treatment: a meta-analytical review. Psychooncology. 2001 Nov-Dec;10(6):490-502. doi: 10.1002/pon.537.
PubMed 11747061Atienza F, Velasco JA, Brown S, Ridocci F, Kaski JC. Assessment of quality of life in patients with chest pain and normal coronary arteriogram (syndrome X) using a specific questionnaire. Clin Cardiol. 1999 Apr;22(4):283-90. doi: 10.1002/clc.4960220406.
PubMed 10198738
Study at a glance
From the registry record, last updated by the sponsor on 22 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Impact of Cardiac Rehabilitation on Angina Frequency, Psychological Morbidity and Quality of Life in Women With Syndrome X
- ClinicalTrials.gov ID
- NCT00123617
- Acronym / sponsor ID
- 02-239
- Conditions
- Microvascular Angina
- Keywords
- Chest pain, Women, Syndrome X, Cardiac rehabilitation, Psychological morbidity, Cardiovascular risk factors
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 64 participants (actual)
- Lead sponsor
- National Heart and Lung InstituteUniversity, hospital or other
- Collaborators
- Royal Brompton & Harefield NHS Foundation Trust
- Study start
- Jan 2003
- Primary completion
- May 2005 (actual)
- Study completion
- May 2005 (actual)
- First posted
- 25 Jul 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study is designed to test the hypothesis that participation in a standard phase III group based cardiac rehabilitation programme will improve psychological morbidity, quality of life and cardiovascular risk factors, along with chest pain severity and frequency in women with cardiac syndrome X.
Detailed description
Very few clinicians treating patients with Syndrome X could dispute that despite an excellent prognosis, the debilitating symptomology and ineffective treatment regimes typical in this condition give patients a miserable quality of life. First identified by Kemp (1), the triad of angina pectoris, a positive exercise test for myocardial ischemia and angiographically smooth coronary arteries continues to perplex clinician seeking a useful treatment regime.
The possible pathophysiology of chest pain associated with Syndrome X is poorly understood in these patients. Suggested mechanisms include abnormal myocardial flow reserve due to coronary microvascular dysfunction ('microvascular angina') (2) or a generalised disorder of vascular function (3),(4) early signs of abnormal left ventricular function (5), which in some patients may deteriorate over time,(6) and abnormal visceral pain perception (7). Some patients exhibit insulin resistance (8). However, there have been few adequate systematic explorations of the psychological and social aspects of Syndrome X.
Several studies have found increased levels of anxiety in patients with normal or near normal coronary arteries in the presence of accompanying chest pain (9). Ruggeri et al (10) found higher level of neuroticism and anxiety in small group of patients with Syndrome X in comparison with patients with confirmed coronary artery disease. Panic disorders, sometimes associated with chest pain, are also often presented with depression, hypochondriasis or other somatoform disorders (11). Studies investigating various non-therapeutic treatment regimes have repeatedly shown that relaxation and stress reduction lead to fewer incidence of chest pain in Syndrome X patients (12). However, the same is also true for patients with CAD (13) along with many other conditions and disorders with related chronic pain (14).
Frequency and severity of chest pain has been shown to have a direct effect on quality of life in Syndrome X patients (15). Sand (16) found that over a 7-year follow-up, a higher percentage of Syndrome X patients had given up work, reduced their daily activities and reported worsening chest pain in comparison to patients with confirmed coronary disease. Persistent functional incapacity with concomitant high levels of chest pain in patients with normal or near normal coronary arteries was also found after an 11-year follow-up (9). Use of anti-anginals was higher, as was their self reported burden on the health service.
The Collins team recently performed the largest psychosocial investigation of postmenopausal women with Syndrome X ever undertaken (17). The Hearts and Minds Study, which involved 100 Syndrome X patients, 100 patients with CHD and 100 healthy volunteers found that Syndrome X patients suffered significantly higher levels of anxiety than CHD patients or healthy controls. A greater number of Syndrome X patients suffered clinical levels of anxiety and depression than CHD patients and healthy volunteers, along with suffering significantly higher levels of psychological suffering as measured by the Health Anxiety Questionnaire than healthy controls. We also found that Syndrome X patients with a small social network had higher levels of anxiety than their counterparts with a larger social support structure.
In order to address these findings, it is important to identify an intervention which not only reduces anxiety, but also promotes wellbeing, improves quality of life and augments the social support resource network available to Syndrome X patients. Cardiac Rehabilitation (CR) has consistently been shown to improve the psychological wellbeing in cardiac patients, as recent reviews have highlighted the beneficial effects of CR on symptoms of angina and dyspnoea, stress level and psychological functioning (18). CR has been shown to have a positive affect on reducing anxiety levels in cardiovascular patients (19), while high levels of depression, a frequent co-morbidity in MI patients, have been reduced by CR (20). Women in particular seem to gain most benefit from CR, as improvements in functional capacity, coronary risk and psychosocial wellbeing were equal or greater in women than men following rehabilitation (21). It has been suggested that CR may reduce anxiety in CHD patients by reducing uncertainty, providing patients with an optimistic yet realistic outlook of recovery, as well as providing psychological support and promoting coping (18). Few could argue that a similar outcome in Syndrome X patients would not be beneficial.
As well as promoting psychological wellbeing, CR also provides patients with a social support resource network. The adequacy of social support has been investigated in relation the prognosis of patients with CHD (22) when it was noted that inadequate tangible support was a significant predictor of both morbidity and mortality. Population based studies have consistently identified a link between social support and CHD morbidity and mortality in men, while disease severity and proliferation have been shown to be related to a lack of support in women (23). Epidemiological studies have also consistently found a link between depression, social isolation and predicted morbidity and mortality in CAD patients (24). It has been argued that CR provides the social context through which coronary prevention interventions are delivered (25) and that this extra social support may have an important part to play in the patients recovery from, and adaptation to, chronic illness (26).
The effect of exercise intervention on the frequency and severity of angina has been the object of investigation for many years. Some studies have reported a reduction in mean weekly episodes of angina of up to 91% using an acute exercise intervention in CHD patients (13) and while other studies have been unable to replicate such results, almost all highlight the beneficial effect of exercise on angina frequency. Nevertheless, very few studies have investigated the impact of exercise on Syndrome X, either from a psychosocial or physiological view-point. Erikkson et al (27) addressed the physical deconditioning apparent in many Syndrome X patients through the use of 8 weeks moderate intensity exercise. Time to pain improved dramatically, with no increase in maximum pain experienced, while peak exercise capacity, heart rate and systolic blood pressure also showed improvements. Exercise capacity and quality of life were also shown to increase following 8 weeks of physical training in separate group of Syndrome X patients (28).
Aerobic exercise has been repeatedly shown to have positive effects on psychological wellbeing, anxiety and depression (29). Patients suffering clinical levels of anxiety and depression have shown a reduction in the severity of their symptoms(30)while athletes and the very active became depressed when they were prevented from exercising(31). Studies involving exercise, anxiety and wellbeing the older population are limited, however subjective health and psychological wellbeing have been shown to be higher among older people who partake in regular exercise (32). Anxiety reduction and increased wellbeing has also been shown in elderly men following an 8-week weekly exercise intervention (33).
Therefore, we would like to explore the beneficial effects of cardiac rehabilitation in Syndrome X patients. Exercise is not currently recognised as a treatment regime for Syndrome X, either as a stand- alone intervention or in conjunction with any other therapy. Patients are currently given little advice or guidance relating to physical activity due to the lack of research and information regarding the potential benefit of exercise available to practitioners. Our previous investigations of Syndrome X have demonstrated a need for an intervention which would not only reduce the patients reported levels of anxiety, but also increase their perceived social support, psychological wellbeing and quality of life. CR has been shown to improve quality of life, reduce anxiety and decrease frequency of angina episodes in CHD patients through the use of exercise intervention and tangible social support. Therefore, we would like to investigate the following research questions:
Does cardiac rehabilitation:
- Reduce the frequency and severity of angina attacks in Syndrome X?
- Reduce anxiety, depression and health related worry found in Syndrome X?
- Improve the quality of life of Syndrome X patients?
Reference List
- Kemp HG, Jr., Vokonas PS, Cohn PF, Gorlin R. The anginal syndrome associated with normal coronary arteriograms. Report of a six year experience. Am J Med 1973; 54(6):735-742.
- Cannon RO, III, Epstein SE. "Microvascular angina" as a cause of chest pain with angiographically normal coronary arteries. Am J Cardiol 1988; 61(15):1338-1343.
- Raymond C. Chest pain not always what it seems; panic disorder may be cause in some. JAMA 1989; 261(8):1101-1102.
- Sax FL, Cannon RO, III, Hanson C, Epstein SE. Impaired forearm vasodilator reserve in patients with microvascular angina. Evidence of a generalized disorder of vascular function? N Engl J Med 1987; 317(22):1366-1370.
- Cannon RO, III, Bonow RO, Bacharach SL, Green MV, Rosing DR, Leon MB et al. Left ventricular dysfunction in patients with angina pectoris, normal epicardial coronary arteries, and abnormal vasodilator reserve. Circulation 1985; 71(2):218-226.
- Opherk D, Schuler G, Wetterauer K, Manthey J, Schwarz F, Kubler W. Four-year follow-up study in patients with angina pectoris and normal coronary arteriograms ("syndrome X"). Circulation 1989; 80(6):1610-1616.
- Shapiro LM, Crake T, Poole-Wilson PA. Is altered cardiac sensation responsible for chest pain in patients with normal coronary arteries? Clinical observation during cardiac catheterisation. Br Med J (Clin Res Ed) 1988; 296(6616):170-171.
- Dean JD, Jones CJ, Hutchison SJ, Peters JR, Henderson AH. Hyperinsulinaemia and microvascular angina ("syndrome X"). Lancet 1991; 337(8739):456-457.
- Potts SG, Bass CM. Psychological morbidity in patients with chest pain and normal or near- normal coronary arteries: a long-term follow-up study . Psychol Med 1995; 25(2):339-347.
- Ruggeri A, Taruschio G, Loricchio ML, Samory G, Borghi A, Bugiardini R. [The correlation between the clinical characteristics and psychological status in syndrome X patients]. Cardiologia 1996; 41(6):551-557.
- Mayou R. Chest pain, palpitations and panic. J Psychosom Res 1998; 44(1):53-70.
- Cunningham C, Brown S, Kaski JC. Effects of transcendental meditation on symptoms and electrocardiographic changes in patients with cardiac syndrome X. Am J Cardiol 2000; 85(5):653-5, A10.
- Ornish D, Scherwitz LW, Doody RS, Kesten D, McLanahan SM, Brown SE et al. Effects of stress management training and dietary changes in treating ischemic heart disease. JAMA 1983; 249(1):54-59.
- Luebbert K, Dahme B, Hasenbring M. The effectiveness of relaxation training in reducing treatment-related symptoms and improving emotional adjustment in acute non-surgical cancer treatment: a meta-analytical review. Psychooncology 2001; 10(6):490-502.
- Atienza F, Velasco JA, Brown S, Ridocci F, Kaski JC. Assessment of quality of life in patients with chest pain and normal coronary arteriogram (syndrome X) using a specific questionnaire. Clin Cardiol 1999; 22(4):283-290.
- Sand NP, Juelsgaard P. [Syndrome X. Somatic and social prognosis of patients with angina pectoris and normal coronary arteriography]. Ugeskr Laeger 1994; 156(8):1131-1136.
- Asbury EA, Creed F, Collins P. Distinct psychosocial differences between women with coronary heart disease and cardiac syndrome X. Eur Heart J 2004; 25 (19):1695-1701.
- Grace SL, Abbey SE, Shnek ZM, Irvine J, Franche RL, Stewart DE. Cardiac rehabilitation I. review of psychosocial factors. Gen Hosp Psychiatry 2002; 24(3):121-126.
- Yoshida T, Kohzuki M, Yoshida K, Hiwatari M, Kamimoto M, Yamamoto C et al. Physical and psychological improvements after phase II cardiac rehabilitation in patients with myocardial infarction. Nurs Health Sci 1999; 1(3):163-170.
- Johnston M, Foulkes J, Johnston DW, Pollard B, Gudmundsdottir H. Impact on patients and partners of inpatient and extended cardiac counseling and rehabilitation: a controlled trial. Psychosom Med 1999; 61(2):225-233.
- O'Callaghan WG, Teo KK, O'Riordan J, Webb H, Dolphin T, Horgan JH. Comparative response of male and female patients with coronary artery disease to exercise rehabilitation. Eur Heart J 1984; 5(8):649-651.
- Woloshin S, Schwartz LM, Tosteson AN, Chang CH, Wright B, Plohman J et al. Perceived adequacy of tangible social support and health outcomes in patients with coronary artery disease. J Gen Intern Med 1997; 12(10):613-618.
- Horsten M, Mittleman MA, Wamala SP, Schenck-Gustafsson K, Orth-Gomer K. Depressive symptoms and lack of social integration in relation to prognosis of CHD in middle-aged women. The Stockholm Female Coronary Risk Study. Eur Heart J 2000; 21(13):1072-1080.
- Wenger NK. Social support and coronary heart disease in women: the challenge to learn more. Eur Heart J 1998; 19(11):1603-1605.
- Lindsay GM, Smith LN, Hanlon P, Wheatley DJ. The influence of general health status and social support on symptomatic outcome following coronary artery bypass grafting. Heart 2001; 85(1):80-86.
- Anderson D, Deshaies G, Jobin J. Social support, social networks and coronary artery disease rehabilitation: a review. Can J Cardiol 1996; 12(8):739-744.
- Eriksson BE, Tyni-Lenne R, Svedenhag J, Hallin R, Jensen-Urstad K, Jensen-Urstad M et al. Physical training in Syndrome X: physical training counteracts deconditioning and pain in Syndrome X. J Am Coll Cardiol 2000; 36(5):1619-1625.
- Tyni-Lenne R, Stryjan S, Eriksson B, Berglund M, Sylven C. Beneficial therapeutic effects of physical training and relaxation therapy in women with coronary syndrome X. Physiother Res Int 2002; 7(1):35-43.
- Salmon P. Effects of physical exercise on anxiety, depression, and sensitivity to stress: a unifying theory. Clin Psychol Rev 2001; 21(1):33-61.
- Craft LL, Landers D.M. The effect of exercise on clinical depression and depression resulting from mental illness: A meta analysis. Journal of Sport and Exercise Psychology 20, 339-357. 1998.
- Aidman EV, Woollard S. The influence of self-reported exercise addiction on acute emotional and physiological responses to brief exercise deprivation. Psychology of Sport and Exercise. 2002.
- Ransford HE, Palisi BJ. Aerobic exercise, subjective health and psychological well-being within age and gender subgroups. Soc Sci Med 1996; 42(11):1555-1559.
- Perrig-Chiello P, Perrig WJ, Ehrsam R, Staehelin HB, Krings F. The effects of resistance training on well-being and memory in elderly volunteers. Age Ageing 1998; 27(4):469-475.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Phase III cardiac rehabilitation | Experimental | Procedure: Phase III group-based cardiac rehabilitationPhase III group-based cardiac rehabilitation classes, weekly |
| Monitoring | No intervention | –Normal daily living, no extra visits to study centre |
Who may qualify
- Ages
- 30 to 80 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Women
- Aged 30 to 80 years
- Postmenopausal > 1 year since last menstrual period
- Angiographically normal coronary arteries
- Positive treadmill exercise test for myocardial ischemia
Key exclusion criteria (5 listed)
- History of psychiatric illness
- History of any other chronic illness
- Participation in another research study within the previous 60 days
- Suffer any physical condition for which exercise is a contra-indication.
- Unwilling to give written informed consent
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Phase III group-based cardiac rehabilitationAlso: Cardiac rehabPhase III group-based cardiac rehabilitation | Procedure or surgery | Phase III cardiac rehabilitation |
Primary outcome
Anxiety
Time frame: Measured at baseline then every 8 weeks for 16 weeks
Depression
Time frame: Measured at baseline then every 8 weeks for 16 weeks
Health anxiety
Time frame: Measured at baseline then every 8 weeks for 16 weeks
Cardiac anxiety
Time frame: Measured at baseline then every 8 weeks for 16 weeks
Quality of life
Time frame: Measured at baseline then every 8 weeks for 16 weeks
Symptom severity
Time frame: Measured at baseline then continuously for 16 weeks
Symptom frequency
Time frame: Measured at baseline then continuously for 16 weeks
3 secondary outcomes
Cardiovascular risk factors
Time frame: Measured at baseline, 8 weeks and 16 weeks.
Physical ability
Time frame: Baseline and at 8 weeks
Time to pain
Time frame: Baseline and 8 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Apr 2015.
- Background: PubMed 4196179Kemp HG Jr, Vokonas PS, Cohn PF, Gorlin R. The anginal syndrome associated with normal coronary arteriograms. Report of a six year experience. Am J Med. 1973 Jun;54(6):735-42. doi: 10.1016/0002-9343(73)90060-0. No abstract available.
- Background: PubMed 3287885Cannon RO 3rd, Epstein SE. "Microvascular angina" as a cause of chest pain with angiographically normal coronary arteries. Am J Cardiol. 1988 Jun 1;61(15):1338-43. doi: 10.1016/0002-9149(88)91180-0. No abstract available.
- Background: PubMed 2915426Raymond C. Chest pain not always what it seems; panic disorder may be cause in some. JAMA. 1989 Feb 24;261(8):1101-2. No abstract available.
- Background: PubMed 3683470Sax FL, Cannon RO 3rd, Hanson C, Epstein SE. Impaired forearm vasodilator reserve in patients with microvascular angina. Evidence of a generalized disorder of vascular function? N Engl J Med. 1987 Nov 26;317(22):1366-70. doi: 10.1056/NEJM198711263172202.
- Background: PubMed 3965167Cannon RO 3rd, Bonow RO, Bacharach SL, Green MV, Rosing DR, Leon MB, Watson RM, Epstein SE. Left ventricular dysfunction in patients with angina pectoris, normal epicardial coronary arteries, and abnormal vasodilator reserve. Circulation. 1985 Feb;71(2):218-26. doi: 10.1161/01.cir.71.2.218.
- Background: PubMed 2598425Opherk D, Schuler G, Wetterauer K, Manthey J, Schwarz F, Kubler W. Four-year follow-up study in patients with angina pectoris and normal coronary arteriograms ("syndrome X"). Circulation. 1989 Dec;80(6):1610-6. doi: 10.1161/01.cir.80.6.1610.
- Background: PubMed 3122985Shapiro LM, Crake T, Poole-Wilson PA. Is altered cardiac sensation responsible for chest pain in patients with normal coronary arteries? Clinical observation during cardiac catheterisation. Br Med J (Clin Res Ed). 1988 Jan 16;296(6616):170-1. doi: 10.1136/bmj.296.6616.170-a. No abstract available.
- Background: PubMed 1671472Dean JD, Jones CJ, Hutchison SJ, Peters JR, Henderson AH. Hyperinsulinaemia and microvascular angina ("syndrome X"). Lancet. 1991 Feb 23;337(8739):456-7.
- Background: PubMed 7675922Potts SG, Bass CM. Psychological morbidity in patients with chest pain and normal or near-normal coronary arteries: a long-term follow-up study. Psychol Med. 1995 Mar;25(2):339-47. doi: 10.1017/s0033291700036242.
- Background: PubMed 8766418Ruggeri A, Taruschio G, Loricchio ML, Samory G, Borghi A, Bugiardini R. [The correlation between the clinical characteristics and psychological status in syndrome X patients]. Cardiologia. 1996 Jun;41(6):551-7. Italian.
- Background: PubMed 9483464Mayou R. Chest pain, palpitations and panic. J Psychosom Res. 1998 Jan;44(1):53-70. doi: 10.1016/s0022-3999(97)00209-2.
- Background: PubMed 11078284Cunningham C, Brown S, Kaski JC. Effects of transcendental meditation on symptoms and electrocardiographic changes in patients with cardiac syndrome X. Am J Cardiol. 2000 Mar 1;85(5):653-5, A10. doi: 10.1016/s0002-9149(99)00828-0.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Peter Collins, MD FRCP principal investigator
National Heart and Lung Institute, Imperial College London
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Phase III group-based cardiac rehabilitation in people with Microvascular Angina, run by National Heart and Lung Institute at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Anxiety (time frame: Measured at baseline then every 8 weeks for 16 weeks). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00123617, which also lists 31 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Apr 2015.