Evidence-based Cardiology – part 3 pptx

Physical activity and exercise 175 training improves social adjustment and functioning and is therefore recommended in the care of cardiac patients. The social benefits from participation in exercise and cardiac rehabilitation are a favorable result. More research is needed to evaluate the impact of cardiac rehabilitation on social adjustment and functioning. 6 Body weight Thirty-four studies – 11 RCTs, seven non-randomized stud- ies, and 16 observational studies – provide evidence that exercise training alone has inconsistent effects on controlling excess body weight and is not recommended as a sole inter- vention for this risk factor. Optimal management of over- weight patients requires multifactorial intervention including intensive nutritional education, counseling and behavioral modification as an adjunct to exercise training. The panel 6 concluded that after a review of behavioral therapy literature involving obese patients, state of the art weight loss pro- grams were shown to be successful. Results of a meta- analysis of 70 studies indicated that weight reduction through dieting can also help normalize plasma lipids and lipoprotein levels in overweight individuals. 15 It is essential to note that the comprehensive use of exercise, education, counseling, and behavioral interventions as a multifactorial approach has consistently yielded much stronger evidence, in terms of health outcomes, than exercise programs alone. Pathophysiologic measures Atherosclerosis Nine studies – five RCTs, one non-randomized study, and three observational studies – provide convincing evidence that exercise training as a sole intervention does not result in regression, limitation or progression of angiographically documented coronary atherosclerosis. But regression or lim- itation in progression of atherosclerosis may occur when exercise training is combined with intense dietary interven- tion, with or without lipid lowering drugs. 6 Hemodynamic measurement Five observational studies provide evidence that exercise training has no effect on development of coronary collateral circulation and produces no consistent changes in cardiac hemodynamic measurements during cardiac catheter- ization. Exercise training in patients with heart failure and depressed ventricular ejection fraction produces favor- able hemodynamic changes in the skeletal musculature. Therefore, cardiac rehabilitation exercise training is recom- mended to improve skeletal muscle function; however, it does not enhance cardiac hemodynamic function or pro- mote development of collateral coronary circulation. 6 Myocardial perfusion/myocardial ischemia Eleven studies – six RCTs, two non-randomized studies, and three observational studies – provide evidence that exercise training decreases myocardial ischemia as measured by exercise ECG testing, ambulatory ECG recording, and radionuclide perfusion imaging. Exercise training is recom- mended to improve the measures of myocardial ischemia. 6 Myocardial contractility, ventricular wall motion abnormalities, and/or ventricular ejection fraction Twenty-two studies – nine RCTs, five non-randomized stud- ies, and eight observational studies – document that exer- cise training has little effect on ventricular ejection fraction and regional wall motion abnormalities. The effect of exer- cise training on left ventricular function in patients after anterior wall Q wave MI with LV dysfunction is inconsis- tent. Exercise training is not recommended to improve measures of ventricular systolic function. 6 Other clinical populations Heart failure and cardiac transplantation Heart failure patients Twelve studies – five RCTs, three non-randomized, and four observational studies – provide evidence for the benefit of exercise training in the heart failure population. Exercise training in patients with heart failure and moderate to severe LV dysfunction improves functional capacity and symptoms, without changes in LV function. Exercise train- ing is recommended in these patients to attain functional and symptomatic improvement but there is a potentially higher likelihood of adverse events. In summary, although these studies had small numbers and populations of young patients, predominantly male, and CAD was the major etiol- ogy of heart failure, exercise training in patients with heart failure and diminished ventricular systolic dysfunction resulted in documented improvement in functional capacity. The benefits are thought to be due predominantly to adapta- tion in peripheral circulation and skeletal musculature. 6 Cardiac transplantation patients Seven studies – one non-randomized study and six observa- tional studies – suggest that exercise training following car- diac transplantation improves exercise tolerance and is recommended for this purpose. These trials demonstrated Evidence-based Cardiology 176 that participation in an exercise program produced physio- logical training responses that included: increased peak oxy- gen uptake, resting heart rate, decreased peak exercise heart rate, increased resting blood pressure, and decreased peak systolic blood pressure compared with normal controls. No change was observed in peak systolic blood pressure or pres- sure rate product. However, these studies were uncon- trolled and therefore these changes could be either the result of spontaneous improvement or a treatment effect. While there are few studies in this area and no RCTs, initial observations demonstrate efficacy of this intervention. In addition, it is believed that strength training before the transplantation may help enhance recovery after the opera- tion. However, more research is needed in this area to iden- tify the extent of spontaneous recovery versus the added benefit from exercise intervention. 6 Changes in cardiac arrhythmias Five studies – four RCTs and one observational study – provide evidence for the role of exercise in patients with arrhythmias. Two of the four RCTs showed that exercising patients, but not the controls, had a reduction in ventricular arrhythmias. 17,18 One demonstrated no statistically signifi- cant difference between exercise patients and controls when monitoring ventricular arrhythmia frequency or severity with 24 hour ambulatory ECG. 19 One RCT reported more malignant premature ventricular contractions (PVCs) on 24 hour ambulatory ECG monitoring during exercise training days in exercise patients compared to control patients. 20 The one observational study showed no difference in PVCs at baseline versus after exercise training. Exercise training has inconsistent effects on ventricular arrhythmias. Special populations Elderly patients Elderly patients constitute a high percentage of those with MI, CABG, and PTCA and are also at high risk of disability following a coronary event. Seven studies – one non- randomized study and six observational studies – provide the evidence for this review. 6 Also, the Surgeon General’s report 5 concludes that physical activity, including strength training (resistance) exercise, appears to be protective against falling and fractures among elderly people, probably by increasing muscle strength and balance. Elderly coronary patients have exercise trainability comparable to younger patients participating in similar exercise rehabilitation. Elderly female and male patients show comparable improve- ment, but referral to and participation in exercise rehabilita- tion is less frequent for elderly patients, 5 especially females. Physical activity need not be strenuous to achieve health benefits. 11 No complications or adverse outcomes of exer- cise training in elderly subjects were described in any study. Although few studies and no randomized controlled trials specifically addressed the efficacy and safety of exercise training and multifactorial rehabilitation in elderly people, the available studies provide important new information of beneficial functional improvement from exercise training for current clinical practice. Elderly patients of both genders should be strongly encouraged to participate in exercise-based cardiac rehabilitation and special effort should be taken to overcome the obstacles to entry and par- ticipation in cardiac rehabilitation services for elderly patients. Women The scientific evidence was either lacking altogether or small numbers of women were included in RCTs, making separate analyses for benefit impossible. This practice resulted in lack of information at best and confusion at worst. If indeed women do experience differing responses than men in exercise training then the effects are likely to be diluted for men and non-informative for women. The consensus of the expert panel 6 was that in most instances women can benefit from exercise training. However, women have unique considerations that require special attention. In studies of CAD patients women tend to be older, live alone more often (they are widowed or divorced), and have fewer economic and social resources. These cir- cumstances require that women be given special attention to minimize the barriers to enrollment in exercise programs and to continuation with the program. The Center for Women’s Health at the National Institutes of Health has as its primary goal compensation for this scien- tific deficit regarding women’s health. Until these new initia- tives have been completed and reported in the literature, only scant scientific evidence exists to guide the physician regard- ing specific recommendations for women. 21 Many studies are now in progress or have already been completed since the formulation of the Center for Women’s Health in 1980. People with physical disabilities With the passing of the Americans with Disabilities Act (1990), physicians in the USA are now required to address the special exercise training needs of patients with a variety of physical disabilities. People with physical disabilities are advised to see a physician before starting a program of physical activity that is new to them. 11 In particular, physi- cally disabled patients with CVD should be referred to the cardiologist for physical therapy or exercise prescription. A recent comprehensive review is available for the reader who requires greater detail than is possible here. 22,23 Physical activity and exercise 177 General safety issues Patients with chronic health problems, such as heart disease or diabetes, should first obtain medical clearance before beginning a new exercise program. Skeletal muscle and other injury can be avoided by beginning exercises slowly and gradually building up to the desired amount of exercise (duration, frequency, and intensity) to give skeletal muscles and the cardiovascular system time to adapt. It is recom- mended that men over 40 and women over 50 consult a physician prior to beginning a vigorous physical activity pro- gram. This is to ensure that the patient does not have un- diagnosed heart disease or other health problems that may place them at increased risk and that may require special modification in the exercise prescription or the monitoring of their response to the exercise. 5 The ACSM, 24 AHA, 25 and AACVPR 26 have issued guidelines for assessment of an exercise facility prior to beginning an exercise program. A medical evaluation, including an exercise test, is recom- mended for individuals with known coronary risk factors or a strong family history of CVD. Exercise testing is recom- mended for persons over 40 years of age, especially if they have two or more risk factors for CVD. But it is not recommended for apparently healthy individuals less than 40 years due to the relatively low predictive value of a positive test. 25 Other organizational and clinical issues Adherence to exercise The evidence for exercise interventions for cardiovascular risk reduction has been provided in the preceding pages. However, the extent to which exercise is effective may depend in large part on adherence. 27 Burke and col- leagues, 27 in their comprehensive review on adherence, fur- ther concluded that non-adherence, whether it occurs early or late in the treatment course, is one mediator of clinical outcomes. Hence, specific attention is given to adherence here. Barriers to exercise are twofold: the lack of physicians’ exercise prescription and patient non-adherence. Since physicians have had limited clear evidence on reduction of “hard events” until recently, coronary patients have not con- sistently received physician recommendations regarding exercise or have received suggestions that were too general to be beneficial. Cardiac rehabilitation programs are avail- able for referral by the physician in virtually every major city throughout the USA. Much of the information on adherence is derived from multifactorial cardiac rehabilitation studies that were designed not to evaluate or enhance adherence but to determine the effects of rehabilitation services on other out- comes. These studies demonstrate a progressive decline with longer treatment duration, with 20–25% of patients dropping out within the first 3 months, 40–50% between 6 and 12 months, and little further change occurring during the next 3–4 years. 28 Although not confirmed, this trend for high early dropout rates may relate to several factors: cost of the exercise program, insurance reimbursement, conven- ience associated with program scheduling and facility location, return to work or family demands or simply poor motivation. Alternatively, patients may have mastered their skills and dropped out because of adequate self-care. There are differences in adherence with different modes of delivery of exercise services; what is known about adher- ence to cardiac rehabilitation is based largely on studies conducted when cardiac rehabilitation content, duration, delivery, and goals were considerably different from what they are at present. Recommendations to improve adherence Adherence may be enhanced if the physician understands the factors that affect exercise behavior and accordingly devises an exercise program that is tailored to the needs, preferences, and health status of a given person. 29 Patients, in general, wish to be partners in healthcare decisions that affect them or their families and improving communication may be a potent adherence enhancing strategy. Attention to the interpersonal relationships between patient and provider can result in greater cooperation and greater patient and provider satisfaction, as well as improved adher- ence. 30 For example, increased involvement by the patient in clinical decision making has been shown to improve patient satisfaction, 27 patient adherence, and patient out- comes. 28 In addition, limited evidence supports the impor- tance of involving family members in promoting adherence to cardiac rehabilitation services. 35 If the objective of patient counseling is to permit the patient to make informed deci- sions about treatments, then a patient may decide to disre- gard some or all professional advice. This suggests that what is inappropriate behavior from the clinician’s perspective (that is, not following recommendations) may in fact be rational decision making from the patient’s perspective. Many patients make the best decisions they can without considering the importance or even the implications of adherence and carry out their own risk–benefit analysis for each treatment they are offered. 36 Other factors that may influence patient adherence include: emotional support; understanding the patient’s (and family’s) values, viewpoints, and preferences; integra- tion of the intervention into the patient’s lifestyle, as well as patient characteristics and demographic characteristics; aspects of treatment regimens including complexity, dura- tion, and convenience (such as cost, facility location, time of day); and disease factors such as severity of symptoms, among others. Patient perceptions, as well as personal and Evidence-based Cardiology 178 social circumstances, determine patient decisions about fol- lowing recommendations. Adherence to exercise is in general lower than that for pharmacologic interventions; Burke et al 27 suggest that the increased behavioral requirements for maintaining an exer- cise program may account for this. In general, adherence to the exercise program was better in the home exercise pro- grams than the community-based rehabilitation programs. 27 Most likely, the convenience factor can account for these improved rates of adherence. 27 Strategies to improve adherence Improving patient–provider communication with more information about CVD and its treatments would likely result in more informed decision making by the patient; pro- viding culturally sensitive care may also improve adherence and perhaps patient outcomes and is likely to improve patient and clinician satisfaction. 37,38 Successful strategies for adherence include: ● Clear communication between patient (family) and provider. ● Emotional support and alleviation of fears and anxieties. ● Understandable and practical explanations about regi- mens that are compatible with the patient’s values, preferences, and expressed needs, acknowledging the patient’s social and cultural needs. ● Integration and coordination of patient care to provide continuity of care between transitions. 6 Alternatives to monitored exercise training Eleven studies – seven RCTs and four non-randomized studies – informed this question. The evidence suggests that alternative approaches to the delivery of cardiac rehabilitative services, other than traditional supervised group interven- tions, can be implemented effectively and safely for carefully selected clinically stable patients. Transtelephonic and other means of monitoring and surveillance of patients can extend cardiac rehabilitative services beyond the setting of super- vised, structured, group-based rehabilitation (see Box 16.3 for guide to ECG monitoring). These alternative approaches have the potential to provide cardiac rehabilitation services to low- and moderate-risk patients, who comprise the majority of patients with stable coronary disease, most of whom do not currently participate in supervised, structured rehabilitation. (For risk stratification guidelines, see Box 16.4.) Box 16.3 Criteria for electrocardiographic monitoring 39 ● Two or more MIs ● New York Heart Association class 3 or greater ● Exercise capacity less than 6 METs Box 16.3 Continued ● Ischemic horizontal or downsloping ST depression of 4 mm or more or angina during exercise ● Fall in systolic blood pressure with exercise ● A medical problem that the physician believes may be life-threatening ● Previous episode of primary cardiac arrest ● Ventricular tachycardia at a workload of less than 6 METs Note: MET, metabolic equivalent units Box 16.4 Minimal guidelines for risk stratification Risk level Characteristics Low No significant left ventricular dysfunction (that is, ejection fraction Ն50%) No resting- or exercise-induced myocar- dial ischemia manifested as angina and/ or ST-segment displacement No resting- or exercise-induced complex arrhythmias Uncomplicated myocardial infarction, coro- nary artery bypass surgery, angioplasty or atherectomy Functional capacity Ն6 METs on graded exercise test 3 or more weeks after clinical event Intermediate Mild to moderately depressed left ventri- cular function (ejection fraction 31–49%) Functional capacity Ͼ5–6 METs on graded exercise test 3 or more weeks after clinical event Patients who consistently exceed the intensity of their exercise prescription Exercise-induced myocardial ischemia (1–2 mm ST-segment depression) or reversible ischemic defects (echocardio- graphic or nuclear radiography) High Severely depressed left ventricular func- tion (ejection fraction Յ30%) Complex ventricular arrhythmias at rest or appearing or increasing with exercise Decrease in systolic blood pressure of Ͼ15 mmHg during exercise or failure to rise with increasing exercise workloads Survivor of sudden cardiac death Myocardial infarction complicated by con- gestive heart failure, cardiogenic shock, and/or complex ventricular arrhythmias Severe coronary artery disease and marked exercise-induced myocardial ischemia (Ͼ2mm ST-segment depression) MET, metabolic equivalent units Source : From Guidelines for rehabilitation programs (p. 14) by the American Association of Cardiovascular and Pulmonary Rehabilitation, Champaign, IL: Human Kinetics Books. Copyright 1995 by American Association of Cardio- vascular and Pulmonary Rehabilitation. Reprinted by permission. Physical activity and exercise 179 Recent studies have explored new approaches to deliver cardiac rehabilitation services, with the goals of increasing availability and decreasing costs, while preserving efficacy and safety. Case management approaches to exercise train- ing, smoking cessation, and diet drug management of hyper- lipidemia that rely on telephone contact can be provided to appropriately selected patients with coronary disease. Guidelines for participation in supervised and unsuper- vised exercise training programs are published by the American College of Sports Medicine. 24 In brief, supervi- sion is recommended for patients with two or more major CAD risk factors and patients with known CAD with less than 8 MET functional capacity. Supervision is not suggested in apparently healthy individuals or persons who have equal or more than 8 MET functional capacity. The generalizability of these case management systems to other treatment settings – including university centers, public and community hospitals, and clinics – will depend largely on formulas for reimbursement for services and the extent of physician support for this approach, as well as the state regulations regarding medical and health prac- tices. Within each of these settings, managed care programs seeking optimal methods for coronary risk factor reduction and exercise rehabilitation may favor case management systems that provide convenient, individualized health care at low cost. Risk stratification Appropriate risk stratification is recommended to minimize any adverse effects that patients might experience. This practice is also valuable in aiding the healthcare provider in deciding the type and intensity at which an exercise regi- men will be started and the degree of monitoring and super- vision. Furthermore, careful risk stratification also identifies the frequency of surveillance needed for a given patient, alerts the practitioner to respond promptly to changes in patient status, and promotes the safety of exercise training in any delivery system. 6 Focus of further scientific study Scientific studies should address the following areas: 6 ● Evaluate exercise training in special populations, including elderly people, women, members of different ethnic groups, and those of low educational and socio- economic status. ● Evaluate exercise therapy following contemporary ther- apies, including thrombolysis and acute angioplasty. ● Evaluate effects of exercise training using return to work as a primary outcome. ● Identify factors that promote adherence. ● Identify the optimum degree of supervision and moni- toring for high-risk groups, such as those with heart fail- ure, elderly patients, and those with complex medical problems. ● Evaluate the safety and benefit of exercise training in patients with compensated heart failure and impaired ventricular systolic function. ● Evaluate a variety of different delivery models of exer- cise therapy. ● Evaluate the safety and specific added benefits of resist- ance training on cardiac patient outcomes. Summary Clear evidence exists for the recommendation of exercise for all individuals for primary preventive purposes. The evi- dence for patients with CAD is also well substantiated. Further research is indicated to verify how exercise recom- mendations are best delivered given the current rapid change in healthcare practice. References 1.Blair SN, Kohl HW, Paffenbarger RS et al. Physical fitness and all cause mortality. A prospective study of healthy men and women. JAMA 1989;262:2395–401. 2.Blair SN, Kampert JB, Kohl HW et al. Influences of cardiovascular fitness and other precursors on cardiovascular disease and all cause mortality in men and women. JAMA 1996;276:205–10. 3.National Institutes of Health. Consensus Development Panel on Physical Activity and Cardiovascular Health. Physical activity and cardiovascular health. JAMA 1996;276:241–6. 4.Powell KE, Thompson PD, Caspers CJ, Kendricks JS. Physical activity and the incidence of coronary heart disease. Annu Rev Publ Health 1987;8:253–87. 5.US Department of Health and Human Services. Physical activity and health: a report of the Surgeon General. Atlanta, GA: US Department of Health and Human Services, Centers for Disease Control and Prevention, National Centers for Chronic Disease Prevention and Health Promotion, 1996. 6.Wenger MK, Froelicher ES, Smith LK et al. Cardiac rehabilita- tion. Clinical Practice Guideline No. 17. Rockville, MD: US Department of Health and Human Services, Public Health Service, Agency for Health Care Policy and Research and the National Heart, Lung and Blood Institute, 1995. 7.Faigenbaum AD, Skrinar GS, Cesare WF, Kraemer WJ, Thomas HE. Physiologic and symptomatic responses of cardiac patients to resistance exercise. Arch Phys Med Rehabil 1990;71:395–8. 8.Featherstone JF, Holly RG, Amsterdam EA. Physiologic response to weight lifting in coronary artery disease. Am J Cardiol 1993;71:287–92. 9.Sheldahl M, Wilke NA, Tristani FE, Kalbfleisch JH. Responses of patients after myocardial infarction to carrying a graded series of weight loads. Am J Cardiol 1983;52:689–703. Evidence-based Cardiology 180 10.Buchner DM. Understanding variability in studies of strength training in older adults: meta-analytic perspective. Top Geriatric Rehabil 1993;8:1–21. 11.Leon AS, ed. Physical activity and cardiovascular health. A national consensus. Champaign, IL: Human Kinetics, 1997. 12.Stewart AL, Greenfield S, Hays RD et al. Functional status and well-being of patients with chronic conditions: results from the medical outcomes study. JAMA 1989;262:907–13. 13.Fiori MC, Bailey WC, Cohen SJ et al. Smoking cessation. Clinical Practice Guideline No. 18. Rockville, MD: US Department of Health and Human Services, Public Health Service, Agency for Health Care Policy and Research, 1996. 14.National High Blood Pressure Education Program. The fifth report of the Joint National Committee on detection, evalua- tion and treatment of high blood pressure. NIH publication no. 93–1088. Bethesda, MD: National Institutes of Health, National Heart, Lung and Blood Institute, 1993. 15.Dattilo AM, Kris-Etherton PM. Effects of weight reduction on blood lipids and lipoprotein: a meta-analysis. Am J Clin Nutr 1992;56:320–8. 16.Shephard JR. Responses of the cardiac transplant patient to exer- cise and training. Exerc Sports Sci Rev 1992;20:297–320. 17.DeBusk RF, Houston N, Haskell W, Fry F, Parker M. Exercise training soon after myocardial infarction. Am J Cardiol 1979; 44:1223–9. 18.Hamalainen H, Luurila OJ, Kallio V, Astrila M, Hakkila J. Long- term reduction in sudden deaths after a multifactorial intervention programme in patients with myocardial infarction: 10-year results of a controlled follow-up study. Eur Heart J 1989;10:55–62. 19.Todd IC, Ballantyne D. Effects of exercise training on the total ischaemic burden: an assessment by 24 hour ambulatory electrocardiographic monitoring. Br Heart J 1992;68:560–6. 20.Hogberg E, Schuler G, Kunze B et al. Silent myocardial ischemia as a potential link between lack of premonitoring symptoms and increased risk of cardiac arrest during physical strain. Am J Cardiol 1990;65:853–9. 21.Healy B. Narrowing the gender gaps in biomedical research. J Myocardial Ischemia 1992;4:14–24. 22.Fletcher BJ, Dunbar SB, Felner JM et al. Exercise testing and training in physically disabled men with clinical evidence of coronary artery disease. Am J Cardiol 1994;73:170–4. 23.Heath GW, Fentem PH. Physical activity among persons with disabilities – a public health perspective (Review). Exerc Sports Sci Rev 1997;25: 195–234. 24.American College of Sports Medicine (ACSM). ACSM’s guide- lines for exercise testing and prescription. Baltimore, MD: Williams and Wilkins, 1995. 25.American Heart Association. Strategic plan for promoting physical activity. Dallas: American Heart Association, 1995. 26.American Association of Cardiovascular and Pulmonary Rehabilitation. Guidelines for cardiac rehabilitation programs, 2nd edn. Champaign, IL: Human Kinetics, 1995. 27.Burke LE, Dunbar-Jacob JM, Hill MN. Compliance with cardio- vascular disease prevention strategies: a review of the research. Ann Behav Med 1997;19:239–63. 28.Oldridge NB. Compliance and dropout in cardiac rehabilitation. J Cardiac Rehab 1984;4:166–77. 29.Blumenthal JA, Gullette ED, Napolitano M, Szczepanski R. Behavioral and psychological issues of cardiac rehabilitation. In Leon AS, ed. Physical activity and cardiovascular health. A national consensus. Champaign, IL: Human Kinetics, 1997. 30.Ewart CK, Stewart KL, Gillilan RE, Kelemen MH. Self-efficacy mediates strength gains during circuit weight training in men with coronary artery disease. Med Sci Sports Exerc 1986; 18:531–640. 31.Gould KL. Reversal of coronary atherosclerosis: clinical promise as a basis of noninvasive management of coronary artery dis- ease. Circulation 1994;90:1558–71. 32.Andrew GM, Oldridge NB, Parker JO et al. Reasons for dropout from exercise programs in post-coronary patients. Med Sci Sports Exerc 1981;13:164–8. 33.Roter DL. Patient participation in patient–provider interaction: the effects of patient questions asking on the quality of interac- tion, satisfaction, and compliance. Health Educ Monogr 1977; 5:281–315. 34.Kaplan FH, Greenfield S, Ware JE Jr. Assessing the effect of physician–patient interaction on the outcome of chronic dis- ease. Med Care 1989;27:S110–27. 35.Sotile WM, Sotile MO, Ewen GS, Sotile LJ. Marriage and family factors relevant to effective cardiac rehabilitation: a review of risk factor literature. Sports Med Training Rehabil 1993;4: 115–28. 36.Donavan JL, Blake DR. Patient non-compliance: deviance or reasoned decision-making? Soc Sci Med 1992;34: 507–13. 37.Epstein LH, Cluss PA. A behavioral medicine perspective on adherence to long-term medical regimens. J Consult Clin Psychol 1982;50:950–71. 38.Morris LS, Schulz RM. Patient compliance – an overview. J Clin Pharm Ther 1992;17:283–95. 39.Fletcher GF, Balady G, Froelicher VF, Hartley LH, Haskell WL, Pollock ML. Exercise standards. A statement for healthcare pro- fessionals from the American Heart Association. Circulation 1996;86:340–4. Key points There is widespread belief among the general public, fostered by the media, that psychologic and social factors influence the risk of disease. Over the last three decades the scientific community has picked up this interest in psychosocial fac- tors – that is, those factors (such as work characteristics, depression, and social support) that link psychologic phe- nomena to the social environment. Much of this research has focused on the effect of psychosocial factors on health, in particular coronary heart disease (CHD), in part because they may mediate the association between social class and health. Our previous systematic review of prospective studies published up until 1997 investigated the association between psychosocial factors and CHD etiology and prog- nosis. 1 Here, in updating this review to June 2001, we have used better search methods (and identified 71 new papers), improved summaries of the results and discussed the find- ings in an explicit framework of causality. Our objective for this review is to assess the relative strength of the epidemio- logic evidence for causal links between psychosocial factors and CHD incidence among healthy populations, and progno- sis among CHD patients. Psychosocial factors as coronary risk factors Over time there have been improvements in the measure- ment of psychosocial factors, moving away from the general idea of “stress” to concepts based on theoretical models that can be tested. These psychosocial factors may relate to per- sonality factors, such as type A behavior and psychological disorders (for instance, depression and anxiety), and to fac- tors more explicitly involving the social environment, including work characteristics and social support. The valid- ity and reliability of the questionnaire-based instruments used to measure the psychosocial factors has been improved through the use of psychometric techniques; increasingly studies use identical measurement scales. However, such standardization is more apparent for some factors, such as depression, than others, such as work characteristics. Two aspects of the association between CHD and psy- chosocial factors have been researched intensively. The first aspect is the effect of psychosocial factors on CHD incidence, or newly diagnosed CHD. The second aspect is the impact of psychosocial factors on survival among people with CHD. Despite the large literature that has accumulated, the ques- tion of whether psychosocial factors are causally related to risk of, and survival from, CHD remains open for debate. This systematic review aims to highlight key issues in ascrib- ing causal status to one or more psychosocial factor. Are psychosocial CHD associations causal? An initial question to ask of an epidemiologic association between psychosocial factors and CHD is, Can it be explained by bias? Most attention has been paid to bias intrinsic to study design as reported within a publication. One example is self-report bias that may arise if study partici- pants tend to report adversely on both the psychosocial exposures and symptoms of heart disease. Our review addresses this issue by emphasizing death and non-fatal myocardial infarction (MI) as outcomes rather than softer end points, such as angina, which may be more prone to reporting bias. However, for a systematic review, a poten- tially more important set of biases lies extrinsic to individual published reports in the stages between hypothesis specifica- tion and communication to the scientific community. Of all the existing psychosocial CHD data, an unknown amount remains unreported. Positive studies may be more likely to be published than negative studies; and, once published, pos- itive studies may have greater impact than negative studies. However, notwithstanding these potential biases, Bradford Hill 2 outlined a set of interrelated criteria for judging an association to be causal. This is used as a framework for discussing the results of the studies. 181 17 Psychosocial factors in the primary and secondary prevention of coronary heart disease: an updated systematic review of prospective cohort studies Harry Hemingway, Hannah Kuper, Michael Marmot ● Consistency. Finding the same association in different studies, in different populations and under different circumstances – that is, consistency – strengthens the evidence for causation. As an example, depression is related to risk for CHD in Finland, 3 the USA 4 and the Netherlands, 5 as well as in both men and women. 6 However, as our review shows, studies are not unani- mous for any psychosocial factor. These inconsistencies in the data may arise from, inter alia, differences in study designs or ways of measuring the psychosocial factors. ● Temporal association. In order to address the require- ment that exposure should precede the disease, we lim- ited our review to prospective cohort studies. However, the presence of effects in shorter term follow up stud- ies, which are not found in longer term follow up, raises the possibility that early manifestations of disease might have caused the psychosocial exposure. ● Confounders, mediators, and biologic mechanisms. Demonstration of biologic pathways linking psychoso- cial factors and CHD might strengthen the evidence for a causal association. There are three plausible biologic pathways by which psychosocial factors could be linked to the incidence of CHD. These have been reviewed elsewhere. 7,8 First, psychosocial factors may influence health-related behaviors, such as smoking, diet, alcohol consumption, and exercise, which in turn have patho- physiologic consequences. 9,10 If this is true, then studies that treat health behaviors as potential confounders may be underestimating the effect of psychosocial factors. Nearly all studies do this in our review; we are therefore summarizing the direct effect of psychosocial factors on CHD events, net of lifestyle variables, and we are not assessing potential mediation of the association between psychosocial factors and CHD by health behaviors. Psychosocial factors themselves may contribute to the pathway by which social position is inversely associated with CHD. However, a minority of studies in the review considered social position. Second, psychosocial factors, including social support or depression, may produce real or apparent hurdles to help-seeking behavior and access to quality medical care, so that the progression of sub- clinical to clinical disease is more rapid in people with poor psychosocial characteristics. This possibility awaits adequate investigation. Third, psychosocial factors may produce direct or chronic physiologic changes that increase the risk for CHD. 11 Adverse psychosocial char- acteristics can induce biologic arousal through neuro- endocrine mechanisms affecting blood lipids, blood fibrinogen, and blood pressure, or neuroendocrine mechanisms that increase catecholamines and cortisol. ● Strength. Stronger associations are more likely to be causal. This means that larger relative risks (RR) give stronger evidence for causality than smaller relative risks, so an RR of 2·86 (95% CI 1·19–6·89) 12 is more indicative of an association between type A behavior and CHD than a RR of 1·43 (95% CI 0·63–3·26). 13 ● Dose response. The existence of a dose-response rela- tionship between the exposure and disease also supports causation, and an example of this is the higher relative risks for the association between major depression, than minor depression, and mortality in people with CHD. 14,15 ● Reversibility. Ultimately the purpose of cardiologic practice is to intervene and reduce the risk associated with psychosocial factors. Methods of systematic review The methods of this review, which updates our review of publications to 1997, 1 are similar to the first review in terms of qualitative data analysis, but are improved as regards searching for papers and summarizing data. A methodologic quality filter was used to determine inclusion of papers in the systematic review, so that the strength of evidence could be compared across psychosocial factors. For inclusion, papers had to meet four quality criteria relating to design, size, psychosocial variable specification, and outcomes. Study design Since cross-sectional and retrospective case–control studies are subject to recall bias, we limited the review to prospec- tive cohort studies. Nested case–control studies were not included in this review, because our search methods may not distinguish nested and retrospective case–control studies. Study size This review was limited to studies that included at least 500 participants (etiologic studies in healthy populations) or 100 participants (prognostic studies in populations of patients with CHD). The number of participants included was taken as the total number reported after exclusion of ineligible subjects. Therefore, we do not report the restric- tion of the cohort for subgroup analyses, which was occa- sionally substantial. Psychosocial variable specification Psychosocial factors were included if they were used in at least two eligible study populations. Unspecified “stress” was not considered a valid psychosocial factor, since it was too vague to be informative. 16,17 Papers had to specify pre- cisely which measurement scale was used. Outcomes Valid outcomes were limited to fatal CHD, sudden cardiac death, incident non-fatal MI, incident angina, incident heart failure, and, for prognostic studies only, all-cause mortality. Evidence-based Cardiology 182 Searching for eligible papers The principal method of identifying new papers for updating the review was through the Science Citation Index (accessed on the web of science at www.webofscience.com). In June 2001 the Science Citation Index was used to identify papers that cited any of the 65 papers included in our original review. This search method yielded more eligible papers, and missed none, compared to searches on PubMed. Abstracts of over 280 new papers identified with potentially relevant titles were extracted and those papers obviously not eligible were eliminated. Next, two independent researchers assessed full text versions of over 100 potentially relevant papers for inclusion criteria, as well as all the papers included in the first review. Finally, the bibliographies of all retrieved articles were manually searched to identify further studies, which lead to the inclusion of four more studies. Multiple papers from the same study were included if they met the eligibility criteria. Our search produced 71 new papers in total for this review, of which 41 were published from 1998 to June 2001. Summary of effect (Box 17.1) We used relative risks, where available, to summarize the association between the psychosocial factor and the out- come, and this included incidence rate ratios, cumulative incidence ratios, hazard ratios, and odds ratios (occasionally these were calculated). Unless otherwise stated, we took relative risks comparing the top (highest risk) versus bottom (lowest risk) category of exposure and statistical significance was inferred at P value of Յ0·05, and, unlike the earlier review, we report confidence intervals (CI). Where several effect estimates were reported, we took the most highly adjusted estimate, but avoided effect estimates that adjusted for other psychosocial factors, as this may reflect overadjust- ment. Effect estimates were reported separately for men and women and for different outcomes, data allowing. Number of citations per paper In order to explore the extent to which the scientific influence of each study might relate to the degree of study positivity, we recorded the number of times that each paper was cited as of September 2001 using the Science Citation Index. From this the mean number of citations across studies by the strength of the reported association was calculated separately for different years of publication. Results Type A behavior pattern (TABP) and hostility (Table 17.1) TABP is a personality trait characterized by hard driving and competitive behavior, excessive job involvement, impa- tience, hostility, and vigorous speech stylistics and psycho- motor activity. Early positive findings for the effect of TABP on CHD risk, reported by the Western Collaborative Group’s Study and the Framingham Study, 21–23 led to the National Institutes of Health declaring type A to be an inde- pendent risk factor for CHD and to the implementation of intervention trials. 24 As more data accumulated, however, the early positive findings were not confirmed and interest grew in hostility as the toxic component of TABP. In the current review 18 etiologic studies were included. As mentioned above, the three early studies provided mod- erate support for the hypothesis, 21–23 although two of these studies were published from the Western Collaborative Group Study, 21,22 and this association disappeared with extended follow up. 25 Subsequently, 12 studies that did not show a clear effect were published, including two very large studies (MRFIT 26 and the Scottish Heart Health Study 27 ), one of which showed evidence for a protective effect of TABP on CHD risk in women. 27 Last, the three smallest studies strongly supported the hypothesis, 12,28,29 although for one the association was found only in women 29 and for the other only with respect to angina incidence. 28 For the prognostic studies, 10 were not supportive of the underlying hypothesis that TABP worsened prognosis in patients with CHD. Three studies actually showed a Psychosocial factors in the primary and secondary prevention of CHD 183 Box 17.1 The extent to which the paper supports the hypothesis that adverse psychosocial characteristics increase risk of, or mor- tality from, CHD, is summarized in a single symbol (Ϫ, 0, ϩ or ϩϩ). The description of the summary symbols is as follows: Ϫ Relative risk Ͻ0·75 “ finding counter to hypothesis ” Example: One SD increase on the Bortner type A behavior scale was protective for risk of mortality post MI (RR ϭ 0·70, 95% CI 0·51–0·96) 18 0 Relative risk 0·75–1·50 “ lack of clear association ” Example: Low social support was unrelated to risk of fatal CHD (RR ϭ 1·42, 95% CI 0·72–2·81) or risk of non-fatal MI (RR ϭ 1·00, 95% CI 0·58–1·71) 19 ϩ Relative risk Ն1·50 and Ͻ2·00 “ moderate association in line with hypothesis ” Example: Depression increased risk for fatal and non- fatal MI (RR ϭ1·70, 95% CI 1·23–2·34) 15 ϩϩ Relative risk Ն2·00 “ strong association in line with hypothesis ” Example: Job strain substantially increased the risk of fatal CHD and non-fatal CHD (RRϭ 4·95, P value ϭ 0·03) 20 [...]... MI: 2· 03 (0·8 7–4 ·74) Cardiac event: 2 35 (1·1 3 4 ·91) IHD event: 1·86 (0·9 4 3 ·71) Women: MI: 2·42 (0·7 0–8 37 ) No significant association in multivariate analyses Unadjusted analyses: White men: 1·4 (1· 0–2 ·0) Black men: 1·9 (0· 9–4 ·0) White women: 1 3 (0· 9–1 ·8) Black women: 0·8 (0· 3 2 ·0) Men: Fatal CHD: 2 34 (1·5 4 3 ·56) NF CHD: 1·71 (1·1 4–2 ·56) Women: Fatal CHD: 0·74 (0·4 0–1 ·48) NF CHD: 1· 73 (1·1 1–2 ·68)... (0 3 5–0 ·96) 21·10 (1·5 9–2 82) Total mortality: Men: 0·7 (0· 3 1 3) Women: 0·8 (0· 3 2 3) 7 17 17 4 177 29 182 91 0 0 0 0 Ϫ 0 Ͻ24 hours: 0 Ն24 hours: Ϫ ϩϩ 188 671 (17) patients 6–4 5 days post-MI 33 1 (34 ) patients 3 1 5 days post-MI 275 (16) patients 3 6 days post first MI Irvine, 1999, Canada, Canadian Amiodarone MI Arrhythmia Trial92 Kaufmann, 1999, USA, Pennsylvania 93 Welin, 2000, Sweden, Gothenburg48 3 0–6 5... 1·10 (0·7 2–1 ·69) Fatal CHD and NF MI: MMPI-2 D: 1·69 (0·7 0–4 ·05) MMPI-2 DEP: 1·88 (0·7 7–4 ·59) SCL-90: 0·67 (0·2 6–1 ·76) Angina: MMPI-2 D: 1 34 (0·6 3 2 ·82) MMPI-2 DEP: 2 30 (1·0 0–5 ·28) SCL-90: 3 33 (1·4 8–7 ·49) Compared to never depressed: Men: Newly depressed: 2· 03 (1·2 8 3 ·24) Chronically depressed: 1·19 (0·5 8–2 ·46) Women: Newly depressed: 1·22 (0·8 3 1 ·80) Chronically depressed: 1·12 (0·7 6–1 ·65) MI:... CHD: 0·98 (0·8 7–1 ·10) CHD: 0·98 (0·9 1–1 ·05) Women: Fatal CHD: 0·77 (0·6 0–0 ·99) CHD: 0·82 (0·7 3 0 · 93) 1· 43 (0·6 3 3 ·26) No association Men: 1·26 (0·7 8–2 · 03) Women: 2·95 (1 3 7–6 35 ) Cox regression coefficients: Fatal CHD/NF MI: Ϫ0·04 (ns) Fatal CHD: Ϫ0 31 (ns) Angina: no association Men: Fatal CHD/NF MI: 1·0 (0· 7–1 ·5) Angina: 2·2 (1· 2–4 ·0) Women: Fatal CHD/NF MI: 1·0 (0· 5–1 ·7) Angina: 2·6 (1· 4–4 ·9) Mortality:... Trait anxiety: 0·98 (0·9 3 1 ·02) 1 sd increase in score: Survival: 1·19 (1·0 8–1 ·28) Type D: 8·9 (3 2–2 4·7) Anxiety not significant Unadjusted analyses: Type D: 7·6 (2· 9–2 0·2) Anxiety: 2·0 (0· 8–4 ·8) Psychologic distress not associated Men: 2·58 (1·0 6–6 30 ) Women: 0· 63 (0·2 0–2 ·04) 1·89 (1·0 4 3 ·55) 1 1 1 3 9 31 3 0 0 Ϫ Type D: ϩϩ Anxiety: 0 0 Men: ϩϩ Women: Ϫ ϩ 202 34 4 (27) patients 3 days after hospitalization... Minor depression: 1·6 (1· 0–2 ·7) Major depression: 3 0 (1· 1–7 ·8) CHD mortality: Minor depression: 2·1 (1· 1 3 ·8) Major depression: 3 9 (1· 3 1 1·8) 1·15 (0·4 9–2 ·67) 6·24 (1·1 8 3 2·98) Total mortality: 1·75 (1·0 2–2 ·99) Fatal CHD: 3 16 (1 3 8–7 ·25) Depression unrelated to NF MI 6· 73 (2·4 3 1 8·64) No multivariate association Unadjusted analyses: 0·97 (0·5 5–1 ·70) 1 2 0 ϩ 1 1 1 ϩϩ 0 ϩϩ Total mortality: ϩ Fatal CHD:... (0·9 4–5 ·11) 31 24 7 73 59 93 83 ϩϩ 0 0 ϩϩ 0 ϩ 0 196 Total sample (% women) 671 (17) patients 6–4 5 days post-MI 33 1 (34 ) patients 3 1 5 days post-MI 119 (29) patients with congestive heart failure 61 months after diagnosis (mean) 1250 (18) patients with significant CAD 31 9 (8) patients in a cardiac rehabilitation program 5057 (26) patients referred to cardiology department for exercise testing 292 (100) 3 6 ... 3 44 (2·2 5–4 · 63) 1·08 (0·4 6–2 ·51) Medium depressive disorder: 2·8 Major depressive disorder: 4·9 P ϭ 0·07 1 sd increase in measure of depression: 1 38 (0·9 9–1 · 93) Minor depression: 0· 83 (0 3 3 2 ·04) Major depression: 0·79 (0·2 8–2 ·29) No association between depression and mortality Cardiac mortality: Minor depression: 1·5 (0· 9–2 ·6) Major depression: 3 9 (1· 4–1 0·9) CHD mortality: Minor depression: 1 3. .. 1·99 (0·9 2–4 31 ) Previous depression: 1·82 (0·8 5 3 ·90) Depressive symptoms: 6·64 (1·7 6–2 5·09) Major depression: 2·68 (0·7 7–9 31 ) Depression not significantly related total and cardiac mortality Unadjusted analyses: Total mortality: 4·57 (1 3 7–1 5·26) Fatal CHD: 5 38 (1·2 2–2 3 67) Severe depression: 2 31 (1·1 1–4 ·80) No association in multivariate analyses Survival at 3 years is 84% in depressed and 83% in... ϩϩ Men: 0 Ecologic: ϩ ϩϩ Summary 204 10 30 8 (33 ) 1727 (0) 35 75 (0) 10 30 8 (33 ) Lynch, 1997, Finland, Kuopio Ischemic Heart Disease Risk Factor Study 132 Steenland, 1997, USA, NHANES1 133 Bosma, 1998, UK, Whitehall II study 134 16 83 (0) Alterman, 1994, USA, Western Electric Study 130 Bosma, 1997, UK, Whitehall II study 131 1 638 (0) Total sample (% women) Suadicani, 19 93, Denmark, Copenhagen Male Study129 Author, . 0·6 (0· 3 1 ·5) Men: Ϫ Study 31 post-MI (67), fatal Women: 0·8 (0· 1–5 ·0) CHD (32 ), CHD death: recurrent MI (31 ) Men: 0·5 (0· 2–1 3) Women: 0·9 (0· 2–4 3) 187 Total mortality: Men: 0·7 (0· 3 1 3) Women:. of 1· 13 (0·8 9–1 ·41) Deviance angina (89) baseline vascular Angina: Scales) disease, social class 1·00 (0·7 4–1 35 ) Women: Total MI: 1· 03 (0·7 0–1 39 ) Angina: 1·06 (0·7 4–1 · 53) Kawachi, 1998, 130 5. men, 32 ,33 angina incidence 34 ,35 or major depression. 36 Interestingly, the three studies that sep- arated angina from other outcomes reported stronger effects of depression on angina, 3 4 3 6 suggesting