The Impact of Cardiac Rehabilitation Participation on Cardiac Syndrome X
Condition: Microvascular Angina
MeSH terms: Microvascular Angina
Study type: Interventional
Phase: Phase 2

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.
    

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:

        1. Reduce the frequency and severity of angina attacks in Syndrome X?

        2. Reduce anxiety, depression and health related worry found in Syndrome X?

        3. Improve the quality of life of Syndrome X patients?

      Reference List

        1. 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.

        2. 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.

        3. Raymond C. Chest pain not always what it seems; panic disorder may be cause in some.
           JAMA 1989; 261(8):1101-1102.

        4. 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.

        5. 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.

        6. 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.

        7. 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.

        8. Dean JD, Jones CJ, Hutchison SJ, Peters JR, Henderson AH. Hyperinsulinaemia and
           microvascular angina ("syndrome X"). Lancet 1991; 337(8739):456-457.

        9. 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.

       10. 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.

       11. Mayou R. Chest pain, palpitations and panic. J Psychosom Res 1998; 44(1):53-70.

       12. 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.

       13. 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.

       14. 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.

       15. 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.

       16. 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.

       17. 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.

       18. 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.

       19. 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.

       20. 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.

       21. 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.

       22. 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.

       23. 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.

       24. Wenger NK. Social support and coronary heart disease in women: the challenge to learn
           more. Eur Heart J 1998; 19(11):1603-1605.

       25. 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.

       26. 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.

       27. 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.

       28. 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.

       29. Salmon P. Effects of physical exercise on anxiety, depression, and sensitivity to
           stress: a unifying theory. Clin Psychol Rev 2001; 21(1):33-61.

       30. 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.

       31. 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.

       32. 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.

       33. 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.
    

Intervention name(s): Phase III group-based cardiac rehabilitation
Intervention type(s): Procedure
Intervention description(s): Phase III group-based cardiac rehabilitation
Other intervention name(s): Cardiac rehab
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Chest pain; Women; Syndrome X; Cardiac rehabilitation; Psychological morbidity; Cardiovascular risk factors