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Ischemic heart disease
Ischemic Heart Disease Steven Kick, MD, MSPH DEPARTMENT OF PSYCHIATRY AND MEDICINE, UNIVERSITY OF COLORADO HEALTH SCIENCES CENTER, DENVER, COLORADO
Cardiovascular Update Abstract
Introduction
Ischemic Heart Disease (IHD) is the single most important preventable disease in the U.S. Risk factors for the development of IHD have been well described, and treatment strategies for the primary, secondary, and tertiary prevention of this disease are available. Because of the prevalence of IHD, and known benefits of intervention, psychiatrists should be familiar with screening and treatment. This paper describes the screening and intervention strategies suitable for psychiatrists caring for patients at risk for IHD. © 1998 Elsevier Science Inc. MEDICAL UPDATE FOR PSYCHIATRISTS 3;5:148–152, 1998.
Cardiovascular disease remains a leading cause of morbidity and mortality in this country. In 1993, there were 400,000 deaths attributed to ischemic heart disease (1), and in 1995 an estimated 1.5 million persons had their first myocardial infarction (MI), with at least 30% not surviving (1). The pathologic process in the majority of these cases is atherosclerotic disease of the coronary arteries, of which the risk factors of male sex, postmenopausal women, hypertension, diabetes, cigarette smoking, elevated serum lipids and family history are the most significant. Newer information, however, supports a number of other possible risk factors including elevated serum homocysteine (2,3). Because of the prevalence of ischemic heart disease (IHD), and specifically the above risk factors, psychiatrists will invariably see patients with or at risk for IHD. This paper will review important points for the psychiatrist, including the relationship of psychiatric illness to IHD, an update on common treatment modalities and drug interactions, and the role of the psychiatrist in primary and secondary prevention of IHD. Because other cardiovascular diseases such as congestive heart failure (CHF), valvular heart disease, and arrhythmias are less prevalent, they will not be discussed in this paper. Relationship of Psychiatric Illness to Cardiovascular Disease
Numerous studies have shown strong and consistent associations between psychiatric illness and heart disease. This has been most thoroughly studied with acute MIs, in which both antecedent and subsequent depression have been shown to influence prognosis. The
© 1998 Elsevier Science Inc. ISSN 1082-7579/98/$19.00 PII S1082-7579(98)00020-X
Address reprint requests to: Steven Kick, MD, MSPH, Assistant Professor Psychiatry and Medicine, University of Colorado Health Science Center, 4200 E. 9th Avenue, Denver, CO 80262.
symptoms of depression are associated with a first non-fatal MI (4). Following an MI, depression may be seen in almost half of patients (5). Unfortunately, this depression is an independent predictor of mortality, with an adjusted hazard ratio of 4.3 (6). Not only is depression associated with mortality, it is also associated with recurrent angina, continued cigarette smoking, post-MI dyspnea, and arrhythmias (7). Anxiety has also been shown to be associated with MI. Anxious symptoms are common after an MI (8), and post-traumatic stress syndrome-like symptoms have been documented among men having had an MI or coronary artery bypass surgery (CABG; Reference 9). From the Framingham study, Eaker et al., demonstrated that the psychological factors of anxiety/tension, loneliness, and difficulty sleeping, were associated with incident MIs among women followed in the study (10). Clearly, the presence of anxiety or depression unfavorably influences the development and prognosis of ischemic heart disease. Unfortunately, few data support the idea that treatment of psychiatric symptoms or disorders in the setting of heart disease improves mortality, although mental stress-induced myocardial ischemia may be reduced through psychotherapy (11). In two small studies, the use of psychotropic medication of any class was associated with incident MIs (12,13). Since psychiatric patients may commonly complain of symptoms suggestive of heart disease (shortness of breath, chest pain, palpitations, paresthesias), the assessment of these symptoms may be difficult for both the psychiatrist and non-psychiatrist. Current Therapy for Ischemic Heart Disease
The pathology of ischemic heart disease involves the formation of subintimal plaques in the coronary arteries. These plaques consist of cells, fat and debris that accumulate through the interaction
MEDICAL UPDATE
FOR
PSYCHIATRISTS
Ischemic Heart Disease
Table 1. Primary Prevention of Ischemic Heart Disease (IHD)—Strategies for the
Psychiatrist Risk Factor
Intervention/Screening
Family history of premature IHD Elevated serum lipids Hypertension
Take the medical history and record Random serum cholesterol History of hypertension; take blood pressure History and random serum glucose Take exercise history; recommend exercise for fitness 1. Advise smoking cessation 2. Discuss behavioral techniques 3. Offer nicotine replacement for dependent patients 4. Discuss antidepressant therapy as an adjunct
Diabetes Lack of exercise Smoking
of monocytes and platelets. When these plaques reach a sufficient size to impede blood flow, angina occurs. When a thrombus forms at the site of an atheromatous plaque or when a plaque ruptures, an infarction in the distribution of that artery may occur. The treatment of IHD consists of primary prevention (i.e., modification of risk factors before the development of disease), secondary prevention (i.e., limiting the progression of disease), and acute interventions for both angina and MI. While there are accepted standards of care for these conditions, controversies still exist, particularly the decision about thrombolytic therapy versus immediate angioplasty for acute MI. At all stages in the disease process, the psychiatrist may contribute to the care of these patients. Primary Prevention
Modifiable risk factors for heart disease include cigarette smoking, hypertension, diabetes, serum lipids and exercise. The psychiatrist can help modify these risk factors, either by screening directly, or by supporting the treatments prescribed by the primary care physician. Psychiatrists should obtain a medical history including a review of cardiovascular risk factors, previous history of cardiac disease, and family history of cardiac disease. A prior history of MI, arrhythmias or congestive heart failure (CHF) should alert the psychiatrist to future cardiac events. A family history of early cardiac events (MI before the age of 50) or of elevated lipids should be recorded. Screening total
cholesterol (14) and glucose tests (1) can be inexpensively added to other blood work, and if elevated (total cholesterol greater than 200 mg/dl and fasting glucose greater than 140 mg/dl) should be further evaluated. Interestingly, attention to psychological stress might help reduce serum lipids (15). Patients should be asked about recent blood pressure checks, or better, have their blood pressure taken on at least one occasion. It may be important for the psychiatrist to initiate these screens, particularly because for many persons with psychiatric illnesses, the psychiatrist may be the only medical doctor they see. Perhaps more importantly is the question of smoking cessation with psychiatric patients. Persons with psychiatric symptoms, particularly depression and schizophrenia, have smoking rates above that of the general population (16,17). Among depressed smokers, cessation from smoking is more difficult (18), and withdrawal symptoms worse (19 –21), than among non-depressed persons. Depressive symptoms may be a more powerful predictor of cigarette smoking than anxious symptoms, despite the commonly-held belief that persons smoke because of anxiety (22,23). Often, mental health care workers are reluctant to recommend smoking cessation to their patients because of perceived barriers to quitting (“high stress”), or because of the belief that the nicotine may help control psychiatric symptoms. Despite these considerations, cigarette smoking remains the single most important modifiable car149
diac risk factor, and has been shown in at least one study to markedly influence mortality when compared with other addictive substances (24). Physician advice alone will impact smoking cessation (25), but psychiatrists should also be aware of smoking-cessation techniques, particularly when they involve psychotropic medications, such as extendedrelease buproprion, recently released as an adjunct for smoking cessation (26). Nicotine replacement therapy, and behavioral interventions remain the cornerstone of smoking cessation, and nicotine replacement is safe among persons with IHD (27). Psychiatrists and other mental health professionals are uniquely positioned to help their clients quit cigarette smoking, an important risk for not only heart disease, but a number of other chronic medical conditions. The use of antioxidants, particularly vitamin E, have been shown in epidemiologic studies to be inversely related to IHD (28). There are, however, no current recommendations for their use. These primary prevention interventions, suitable for the psychiatrist, are listed in Table I. Secondary Prevention
The goals of secondary prevention are to minimize disease progression and to promote disease regression in persons already suffering from the illness. This usually means aggressive treatment of risk factors, such as lowering serum low density lipoprotein (LDL) levels to below 100 mg/dL (14). Avoiding medications that might complicate heart disease is another important consideration. The untoward effects of tricyclic antidepressants (TCAs) are well known. They act as Type Ia antiarrhythmics, and thus should be used cautiously in persons with IHD (29). They are probably best avoided among persons with known ventricular arrhythmias, but in other persons, can be safely used with attention to serum levels, and the monitoring of the electrocardiogram for conduction abnormalities. For all patients, the interaction of some psychotropic medications with other agents that compete for similar hepatic P450 enzyme systems should be avoided. These interactions may cause prolongation of the QT interval, and subsequent ventricular tachycardia, particularly
S. Kick
among people at risk (i.e., those with IHD). The most important agents to watch for include cisapride, and the antihistamines terfenadine and astemizole in combination with fluvoxamine and nefazodone (30). At least one study has shown that the antioxidant probucol reduces restenosis after coronary angioplasty (31). Patients on disulfiram who have heart disease should be cautioned about the very serious potential interaction of the drug with alcohol. Current Therapy for IHD
Angina Angina occurs when myocardial oxygen demand exceeds supply. The nature of the pain is classically described as a heavy or pressing retro-sternal discomfort, worse with exertion and relieved with rest. Large meals and exposure to cold may also precipitate angina, and the pain may be located in the neck, jaw or arms, or may only be manifested by signs of left ventricular dysfunction (dyspnea on exertion, orthopnea, paroxysmal nocturnal dyspnea and peripheral edema). Psychiatrists should be familiar with the symptoms of angina, since this may represent serious IHD, particularly with new-onset angina, or progressive worsening of the frequency or severity of the pain (unstable angina). The treatment of angina continues to be the reduction of myocardial oxygen demand, or the improvement in oxygen supply. Nitrates remain a mainstay of treatment, either acutely with sublingual nitroglycerin, or with longer acting agents such as transdermal nitroglycerin or isosorbide dinitrate. These agents improve coronary blood flow, but are often limited by the development of tolerance. An increase in the amount of sublingual nitroglycerin may be a sign of worsening angina, and should be evaluated. Likewise, patients should be instructed to keep a fresh bottle of nitroglycerin with them (replaced every 6 months). Aspirin has been shown in some studies to lower the risk of an MI in persons at risk; however, bleeding complications, particularly upper gastrointestinal bleeding suggests cautious use. Aspirin has been shown to prevent MI in women (32). In these studies, it appears that low dose aspirin (80 to 160 mg/day, or 325 mg every other day) has the most
MEDICAL UPDATE
beneficial effects with the fewest adverse events. Uncommon complications of aspirin include exacerbation of asthma and tinnitus. Agents that decrease myocardial oxygen demand include beta-blockers and calcium channel antagonists. Because of recent concerns for incident MIs among persons taking short-acting calcium channel blockers for hypertension, investigators are conducting studies to address this. It appears at this time that long-acting calcium-channel antagonists may be safer than short-acting ones, particularly of the dihydropyridine class of agents (33). The drug amlodipine may be safe to use in patients with diminished left ventricular function (33). Because of these concerns, most physicians would prescribe betablockers if there are no significant contraindications, such as reactive airways disease. Although these agents may cause fatigue that mimics depression, they do not cause the syndrome of major depression, and can be safely used. The even more recent use of pindolol to augment antidepressant therapy, might prove to be an excellent choice for patients with depression and concomitant heart disease (34). Lipid lowering agents, specifically the “statin” drugs such as simvastatin and pravastatin, in addition to their effects on serum lipids, may show improvement in cardiac event rates through the stabilization of atherosclerotic plaques via unknown mechanisms. The above mentioned agents have been shown to reduce mortality, pravastatin for primary prevention, and simvastatin for secondary prevention (35). Estrogen replacement therapy for post-menopausal women has been shown to reduce the incidence of cardiac events (36). Recent concern over the risk of breast cancer has however, made many women reluctant to consider estrogens. The risk of breast cancer is related to the dose and duration of the estrogen, as well as known risk factors such as a first-degree relative with breast cancer and/or a previous history of breast cancer (1). Many primary care physicians are now counseling women about their risks for both breast cancer and IHD. Since IHD is much more prevalent than breast cancer, if a woman is at risk for heart disease, and does not have known risks for breast cancer, clinicians should recom150
FOR
PSYCHIATRISTS
mend that she take estrogen. If however, the risks of breast cancer are high, one should discuss whether there might be other reasons to consider estrogen replacement (i.e., protection from osteoporosis). Since estrogen replacement may be an important adjunct for antidepressant therapy (37), psychiatrists should be familiar with the discussions about estrogen therapy. Myocardial Infarction The main treatment of acute MIs is the establishment of vascular flow through the occluded vessel, either with the use of thrombolytic agents, or angioplasty/ CABG. Following a non-fatal MI, a number of agents have been shown useful besides the modification of known risk factors. Beta adrenergic blockers are routinely prescribed in the absence of contraindications, because of their proven benefit in the prevention of subsequent cardiac events. If left ventricular dysfunction is present, the use of angiotensin-converting enzyme inhibitors has also been proven beneficial in reducing mortality. Newer studies are evaluating the treatment of increased serum homocysteine, and the use of antioxidants for the treatment of post-MI patients. To date, there are no standard protocols by which patients are given these agents. As mentioned, aggressive treatment of concomitant risk factors is essential. Advances in the treatment of acute MI include the use of newer thrombolytic agents, the use of coronary stents, and newer devices to restore coronary flow. Whether the use of antioxidants will become standard therapy is still unproven, although patients commonly ask about the use of vitamins C and E to reduce the risk of heart disease (28,35). Whether treatment of peri-infarct depression will improve patient outcomes is unknown at this time. Psychiatrists should work closely with primary care and cardiology physicians to insure the best treatment strategies. Choice of Psychotropic Agents for Persons with IHD
A handful of studies have shown an increased risk of cardiac events among persons prescribed psychotropic medi-
MEDICAL UPDATE
FOR
PSYCHIATRISTS
cations. These small studies have included benzodiazepines, as well as antidepressants. Although earlier data suggested that TCAs could be safely used in persons with IHD, the results of some larger trials now would suggest that Type I antiarrhythmic agents (such as TCAs) should be avoided. Selective serotonin reuptake agents (SSRIs) may be safer, although they are associated with bradycardia (30). Buproprion also appears to be a safe alternative. If TCAs must be used, careful monitoring of serum levels and electrocardiograms seems prudent, and any symptoms referable to cardiac disease (chest pain, dyspnea, palpitations) should be promptly evaluated. Whether other psychotropic agents per se are associated with IHD is unclear, since these small studies did not evaluate the role of psychologic stress, a known predictor of IHD. Since interventions to reduce psychologic stress appear useful among patients with IHD, newer studies will need to evaluate the relative importance of the behavioral intervention versus psychopharmacologic interventions. Conclusions
Psychiatrists are in a unique position to help in the care of the person with heart disease. Primary and secondary prevention through risk factor modification remains the single most important aspect that psychiatrists can influence. Among these modifications, smoking cessation is extremely important, particularly because of the high prevalence of smoking among psychiatric patients. Psychiatrists should be familiar with symptoms referable to the cardiovascular system, and promptly refer patients for evaluation, if needed. When in doubt, psychiatrists should consult the medical physician regarding the choice of psychotropic medication. Tricyclic antidepressants are probably best avoided among persons with IHD, and if needed, should be carefully monitored with electrocardiograms and symptom review. References 1. U.S. Preventive Services Task Force. Guide to clinical preventive services, 2nd ed. Baltimore: Williams & Wilkins; 1996.
Ischemic Heart Disease
2. Nygard O, Vollset SE, Refsum H, Stensvold I, Tverdal A, Nordrehaug JE, Ueland M, Kvale G. Total plasma homocysteine and cardiovascular risk profile. The Hordaland homocysteine study. JAMA 1995;274:1526 –1533. 3. Stampfer MJ, Malinow MR, Willett WC, Newcomer LM, Upson B, Ullmann D, Tishler PV, Hennekens CH. A prospective study of plasma homocysteine and risk of myocardial infarction in US physicians. JAMA 1992;268:877. 4. VanDiest R, Appels A. Vital exhaustion and depression: a conceptual study. J Psychosomatic Res 1991;35:535– 44. 5. Schleifer SJ, Macari–Hinson MM, Coyle DA, Slater WR, Kahn M, Gorlin R, Zucker HD. The nature and course of depression following myocardial infarction. Arch Int Med 1989;149: 1785–9. 6. Frasure–Smith N, Lesperance F, Talajic M. Depression following myocardial infarction: impact on 6-month survival. JAMA 1993;270:1819 –26. 7. Ladwig KH, Rol G, Breirhardt G, Budde T, Borggrefe M. Post-infarction depression and incomplete recovery 6 months after acute myocardial infarction. Lancet 1994;343:20 –3. 8. Crowe JM, Runions J, Effesen LS, Oldridge NB, Streiner DL. Anxiety and depression after acute myocardial infarction. Heart and Lung 1996;25:98 –107. 9. Doerfler LA, Pbert L, DeCosimo D. Symptoms of posttraumatic stress disorder following myocardial infarction and coronary artery bypass surgery. Gen Hosp Psychiatry 1994;16:193–9. 10. Eaker ED, Pinsky J, Castelli WP. Myocardial infarction and coronary death among women; psychosocial predictors from a 20-year follow-up of women in the Framingham study. Am J Epidemiol 1991;135:854 – 64. 11. Jiang W, Babyak M, Krantz DS. Mental stress-induced myocardial ischemia and cardiac events. JAMA 1996;275:1651– 56. 12. Penttinen J, Valonen P. Use of psychotropic drugs and risk of myocardial infarction: a case-control study in Finnish farmers. Int J Pei 1996;25:760 –2. 13. Thorogood M, Cowen P, Mann J, Murphy M, Vessey M. Fatal myocardial infarction and use of psychotropic drugs in young women. Lancet 1992;340: 1067– 8. 14. American College of Physicians, Guidelines for using serum cholesterol, highdensity lipoprotein cholesterol, and triglyceride levels as screening tests for preventing coronary heart disease in adults. Ann Int Med 1996;124:515–531. 15. Muldoon MF, Herbert TB, Patterson SM, Kameneva M, Raible R, Manuck SB. Effects of acute psychological stress 151
16.
17.
18. 19.
20.
21.
22.
23.
24.
25.
26. 27.
28.
29.
30.
on serum lipid levels, hemoconcentration, and blood viscosity. Arch Intern Med 1995;155:615–20. Lindemann E. Cigarette smoking in schizophrenia: relationship to psychopathology and medication side effects. Am J Psychiatr 1992;149:1189 –1194. de Leon J, Dadvand M, Canuso C, et al. Schizophrenia and smoking: an epidemiological survey in a state hospital. Am J Psychiatr 1995;152:453–55. Anda RF, Williamson DF, Escobedo LG, et al. Depression and the dynamics of smoking. JAMA 1990;264:1541– 45. Breslau N, Kilbey M, Andreski P. Nicotine dependence and major depression: new evidence from a prospective investigation. Arch Gen Psychiatr 1993;50:31–5. Glassman AH, Helzer JE, Covey LS, et al. Smoking, smoking cessation, and major depression. JAMA 1990;264:1546 – 49. Breslau N, Kilbey MM, Andreski P. Nicotine withdrawal symptoms and psychiatric disorders: findings from an epidemiologic study of young adults. Am J Psychiatr 1992;149:464 – 69. Daughton DM, Dewolf R, Patil KD, et al. Smoking cessation in the workplace: evaluation of relapse factors. Prev Med 1990;19:227–30. Kick SD, Cooley DD. Depressive, not anxiety, symptoms are associated with current cigarette smoking among university internal medicine patients. Psychosomatics 1997;38:132–9. Hurt RD, et al. Mortality following inpatient addiction treatment. Role of tobacco use in a community-based cohort. JAMA 1996;275:1097–103. Gilpin EA, Pierce JP, Johnson M, Bal D. Physician advice to quiet smoking: results from the 1990 California tobacco survey. J Gen Int Med 1993;8:549 –53. Glaxo Wellcome company publication. Joseph AM, Norman SM, Ferry LH, et al. The safety of transdermal nicotine as an aid to smoking cessation in patients with cardiac disease. N Engl J Med 1996;335:1792–98. Diaz MN, Frei B, Vita JA, Keaney JF. Antioxidants and atherosclerotic heart disease. N Engl J Med 1997;337:408 – 415. CAPS Coordinating Center, University of Washington, Seattle, Effects of encainide, flecainide, imipramine and moricizine on ventricular arrhythmias during the year after acute myocardial infarction: The CAPS. Cardiac Arrythmia Pilot Study (CAPS) investigators. Am J Cardiol 1988;61:501–9. Sheline YI, Freedland KE, Carney RM. How safe are serotonin reuptake inhibitors for depression in patients with cor-
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onary heart disease? Am J Med 1997; 102:54 –9. 31. Tardif JC, Cote G, Lesperance J, Bourassa M, Lambert J, Doucet S, Bilodeau L, Nattel S, de Guise P. Probucol and multivitamins in the prevention of restenosis after coronary angioplasty. N Engl J Med 1997;337:365–72. 32. Harpaz D, Benderly M, Goldbourt U, Kishon Y, Behar S. Effect of aspirin on
MEDICAL UPDATE
mortality in women with symptomatic or silent myocardial ischemia. Israeli BIP Study Group. Am J Card 1996;78:1215–9. 33. Opie LH. Calcium channel blockers for hypertension: dissecting the evidence for adverse effects. Am J Hypertension 1997;10:565–77. 34. Perez V, Gilaberte I, Faries D, Alvarez E, Artigas F. Randomised, double-blind, placebo-controlled trial of pindolol in com-
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bination with fluoxetine antidepressant treatment. Lancet 1997;349:1594 –7. 35. Alpert JS, Cheitlin MD. Update in cardiology. Ann Intern Med 1996;125:40 – 6. 36. Farhat MY, Lavigne MC, Ramwell DW. The vascular protective effects of estrogen. FASEB J 1996;10:615–24. 37. Halbreich U. Role of estrogen in postmenopausal depression. Neurology 1997;48(5 Suppl 7):S16 –19.
Cardiovascular Update Abstract
Introduction
Ischemic Heart Disease (IHD) is the single most important preventable disease in the U.S. Risk factors for the development of IHD have been well described, and treatment strategies for the primary, secondary, and tertiary prevention of this disease are available. Because of the prevalence of IHD, and known benefits of intervention, psychiatrists should be familiar with screening and treatment. This paper describes the screening and intervention strategies suitable for psychiatrists caring for patients at risk for IHD. © 1998 Elsevier Science Inc. MEDICAL UPDATE FOR PSYCHIATRISTS 3;5:148–152, 1998.
Cardiovascular disease remains a leading cause of morbidity and mortality in this country. In 1993, there were 400,000 deaths attributed to ischemic heart disease (1), and in 1995 an estimated 1.5 million persons had their first myocardial infarction (MI), with at least 30% not surviving (1). The pathologic process in the majority of these cases is atherosclerotic disease of the coronary arteries, of which the risk factors of male sex, postmenopausal women, hypertension, diabetes, cigarette smoking, elevated serum lipids and family history are the most significant. Newer information, however, supports a number of other possible risk factors including elevated serum homocysteine (2,3). Because of the prevalence of ischemic heart disease (IHD), and specifically the above risk factors, psychiatrists will invariably see patients with or at risk for IHD. This paper will review important points for the psychiatrist, including the relationship of psychiatric illness to IHD, an update on common treatment modalities and drug interactions, and the role of the psychiatrist in primary and secondary prevention of IHD. Because other cardiovascular diseases such as congestive heart failure (CHF), valvular heart disease, and arrhythmias are less prevalent, they will not be discussed in this paper. Relationship of Psychiatric Illness to Cardiovascular Disease
Numerous studies have shown strong and consistent associations between psychiatric illness and heart disease. This has been most thoroughly studied with acute MIs, in which both antecedent and subsequent depression have been shown to influence prognosis. The
© 1998 Elsevier Science Inc. ISSN 1082-7579/98/$19.00 PII S1082-7579(98)00020-X
Address reprint requests to: Steven Kick, MD, MSPH, Assistant Professor Psychiatry and Medicine, University of Colorado Health Science Center, 4200 E. 9th Avenue, Denver, CO 80262.
symptoms of depression are associated with a first non-fatal MI (4). Following an MI, depression may be seen in almost half of patients (5). Unfortunately, this depression is an independent predictor of mortality, with an adjusted hazard ratio of 4.3 (6). Not only is depression associated with mortality, it is also associated with recurrent angina, continued cigarette smoking, post-MI dyspnea, and arrhythmias (7). Anxiety has also been shown to be associated with MI. Anxious symptoms are common after an MI (8), and post-traumatic stress syndrome-like symptoms have been documented among men having had an MI or coronary artery bypass surgery (CABG; Reference 9). From the Framingham study, Eaker et al., demonstrated that the psychological factors of anxiety/tension, loneliness, and difficulty sleeping, were associated with incident MIs among women followed in the study (10). Clearly, the presence of anxiety or depression unfavorably influences the development and prognosis of ischemic heart disease. Unfortunately, few data support the idea that treatment of psychiatric symptoms or disorders in the setting of heart disease improves mortality, although mental stress-induced myocardial ischemia may be reduced through psychotherapy (11). In two small studies, the use of psychotropic medication of any class was associated with incident MIs (12,13). Since psychiatric patients may commonly complain of symptoms suggestive of heart disease (shortness of breath, chest pain, palpitations, paresthesias), the assessment of these symptoms may be difficult for both the psychiatrist and non-psychiatrist. Current Therapy for Ischemic Heart Disease
The pathology of ischemic heart disease involves the formation of subintimal plaques in the coronary arteries. These plaques consist of cells, fat and debris that accumulate through the interaction
MEDICAL UPDATE
FOR
PSYCHIATRISTS
Ischemic Heart Disease
Table 1. Primary Prevention of Ischemic Heart Disease (IHD)—Strategies for the
Psychiatrist Risk Factor
Intervention/Screening
Family history of premature IHD Elevated serum lipids Hypertension
Take the medical history and record Random serum cholesterol History of hypertension; take blood pressure History and random serum glucose Take exercise history; recommend exercise for fitness 1. Advise smoking cessation 2. Discuss behavioral techniques 3. Offer nicotine replacement for dependent patients 4. Discuss antidepressant therapy as an adjunct
Diabetes Lack of exercise Smoking
of monocytes and platelets. When these plaques reach a sufficient size to impede blood flow, angina occurs. When a thrombus forms at the site of an atheromatous plaque or when a plaque ruptures, an infarction in the distribution of that artery may occur. The treatment of IHD consists of primary prevention (i.e., modification of risk factors before the development of disease), secondary prevention (i.e., limiting the progression of disease), and acute interventions for both angina and MI. While there are accepted standards of care for these conditions, controversies still exist, particularly the decision about thrombolytic therapy versus immediate angioplasty for acute MI. At all stages in the disease process, the psychiatrist may contribute to the care of these patients. Primary Prevention
Modifiable risk factors for heart disease include cigarette smoking, hypertension, diabetes, serum lipids and exercise. The psychiatrist can help modify these risk factors, either by screening directly, or by supporting the treatments prescribed by the primary care physician. Psychiatrists should obtain a medical history including a review of cardiovascular risk factors, previous history of cardiac disease, and family history of cardiac disease. A prior history of MI, arrhythmias or congestive heart failure (CHF) should alert the psychiatrist to future cardiac events. A family history of early cardiac events (MI before the age of 50) or of elevated lipids should be recorded. Screening total
cholesterol (14) and glucose tests (1) can be inexpensively added to other blood work, and if elevated (total cholesterol greater than 200 mg/dl and fasting glucose greater than 140 mg/dl) should be further evaluated. Interestingly, attention to psychological stress might help reduce serum lipids (15). Patients should be asked about recent blood pressure checks, or better, have their blood pressure taken on at least one occasion. It may be important for the psychiatrist to initiate these screens, particularly because for many persons with psychiatric illnesses, the psychiatrist may be the only medical doctor they see. Perhaps more importantly is the question of smoking cessation with psychiatric patients. Persons with psychiatric symptoms, particularly depression and schizophrenia, have smoking rates above that of the general population (16,17). Among depressed smokers, cessation from smoking is more difficult (18), and withdrawal symptoms worse (19 –21), than among non-depressed persons. Depressive symptoms may be a more powerful predictor of cigarette smoking than anxious symptoms, despite the commonly-held belief that persons smoke because of anxiety (22,23). Often, mental health care workers are reluctant to recommend smoking cessation to their patients because of perceived barriers to quitting (“high stress”), or because of the belief that the nicotine may help control psychiatric symptoms. Despite these considerations, cigarette smoking remains the single most important modifiable car149
diac risk factor, and has been shown in at least one study to markedly influence mortality when compared with other addictive substances (24). Physician advice alone will impact smoking cessation (25), but psychiatrists should also be aware of smoking-cessation techniques, particularly when they involve psychotropic medications, such as extendedrelease buproprion, recently released as an adjunct for smoking cessation (26). Nicotine replacement therapy, and behavioral interventions remain the cornerstone of smoking cessation, and nicotine replacement is safe among persons with IHD (27). Psychiatrists and other mental health professionals are uniquely positioned to help their clients quit cigarette smoking, an important risk for not only heart disease, but a number of other chronic medical conditions. The use of antioxidants, particularly vitamin E, have been shown in epidemiologic studies to be inversely related to IHD (28). There are, however, no current recommendations for their use. These primary prevention interventions, suitable for the psychiatrist, are listed in Table I. Secondary Prevention
The goals of secondary prevention are to minimize disease progression and to promote disease regression in persons already suffering from the illness. This usually means aggressive treatment of risk factors, such as lowering serum low density lipoprotein (LDL) levels to below 100 mg/dL (14). Avoiding medications that might complicate heart disease is another important consideration. The untoward effects of tricyclic antidepressants (TCAs) are well known. They act as Type Ia antiarrhythmics, and thus should be used cautiously in persons with IHD (29). They are probably best avoided among persons with known ventricular arrhythmias, but in other persons, can be safely used with attention to serum levels, and the monitoring of the electrocardiogram for conduction abnormalities. For all patients, the interaction of some psychotropic medications with other agents that compete for similar hepatic P450 enzyme systems should be avoided. These interactions may cause prolongation of the QT interval, and subsequent ventricular tachycardia, particularly
S. Kick
among people at risk (i.e., those with IHD). The most important agents to watch for include cisapride, and the antihistamines terfenadine and astemizole in combination with fluvoxamine and nefazodone (30). At least one study has shown that the antioxidant probucol reduces restenosis after coronary angioplasty (31). Patients on disulfiram who have heart disease should be cautioned about the very serious potential interaction of the drug with alcohol. Current Therapy for IHD
Angina Angina occurs when myocardial oxygen demand exceeds supply. The nature of the pain is classically described as a heavy or pressing retro-sternal discomfort, worse with exertion and relieved with rest. Large meals and exposure to cold may also precipitate angina, and the pain may be located in the neck, jaw or arms, or may only be manifested by signs of left ventricular dysfunction (dyspnea on exertion, orthopnea, paroxysmal nocturnal dyspnea and peripheral edema). Psychiatrists should be familiar with the symptoms of angina, since this may represent serious IHD, particularly with new-onset angina, or progressive worsening of the frequency or severity of the pain (unstable angina). The treatment of angina continues to be the reduction of myocardial oxygen demand, or the improvement in oxygen supply. Nitrates remain a mainstay of treatment, either acutely with sublingual nitroglycerin, or with longer acting agents such as transdermal nitroglycerin or isosorbide dinitrate. These agents improve coronary blood flow, but are often limited by the development of tolerance. An increase in the amount of sublingual nitroglycerin may be a sign of worsening angina, and should be evaluated. Likewise, patients should be instructed to keep a fresh bottle of nitroglycerin with them (replaced every 6 months). Aspirin has been shown in some studies to lower the risk of an MI in persons at risk; however, bleeding complications, particularly upper gastrointestinal bleeding suggests cautious use. Aspirin has been shown to prevent MI in women (32). In these studies, it appears that low dose aspirin (80 to 160 mg/day, or 325 mg every other day) has the most
MEDICAL UPDATE
beneficial effects with the fewest adverse events. Uncommon complications of aspirin include exacerbation of asthma and tinnitus. Agents that decrease myocardial oxygen demand include beta-blockers and calcium channel antagonists. Because of recent concerns for incident MIs among persons taking short-acting calcium channel blockers for hypertension, investigators are conducting studies to address this. It appears at this time that long-acting calcium-channel antagonists may be safer than short-acting ones, particularly of the dihydropyridine class of agents (33). The drug amlodipine may be safe to use in patients with diminished left ventricular function (33). Because of these concerns, most physicians would prescribe betablockers if there are no significant contraindications, such as reactive airways disease. Although these agents may cause fatigue that mimics depression, they do not cause the syndrome of major depression, and can be safely used. The even more recent use of pindolol to augment antidepressant therapy, might prove to be an excellent choice for patients with depression and concomitant heart disease (34). Lipid lowering agents, specifically the “statin” drugs such as simvastatin and pravastatin, in addition to their effects on serum lipids, may show improvement in cardiac event rates through the stabilization of atherosclerotic plaques via unknown mechanisms. The above mentioned agents have been shown to reduce mortality, pravastatin for primary prevention, and simvastatin for secondary prevention (35). Estrogen replacement therapy for post-menopausal women has been shown to reduce the incidence of cardiac events (36). Recent concern over the risk of breast cancer has however, made many women reluctant to consider estrogens. The risk of breast cancer is related to the dose and duration of the estrogen, as well as known risk factors such as a first-degree relative with breast cancer and/or a previous history of breast cancer (1). Many primary care physicians are now counseling women about their risks for both breast cancer and IHD. Since IHD is much more prevalent than breast cancer, if a woman is at risk for heart disease, and does not have known risks for breast cancer, clinicians should recom150
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mend that she take estrogen. If however, the risks of breast cancer are high, one should discuss whether there might be other reasons to consider estrogen replacement (i.e., protection from osteoporosis). Since estrogen replacement may be an important adjunct for antidepressant therapy (37), psychiatrists should be familiar with the discussions about estrogen therapy. Myocardial Infarction The main treatment of acute MIs is the establishment of vascular flow through the occluded vessel, either with the use of thrombolytic agents, or angioplasty/ CABG. Following a non-fatal MI, a number of agents have been shown useful besides the modification of known risk factors. Beta adrenergic blockers are routinely prescribed in the absence of contraindications, because of their proven benefit in the prevention of subsequent cardiac events. If left ventricular dysfunction is present, the use of angiotensin-converting enzyme inhibitors has also been proven beneficial in reducing mortality. Newer studies are evaluating the treatment of increased serum homocysteine, and the use of antioxidants for the treatment of post-MI patients. To date, there are no standard protocols by which patients are given these agents. As mentioned, aggressive treatment of concomitant risk factors is essential. Advances in the treatment of acute MI include the use of newer thrombolytic agents, the use of coronary stents, and newer devices to restore coronary flow. Whether the use of antioxidants will become standard therapy is still unproven, although patients commonly ask about the use of vitamins C and E to reduce the risk of heart disease (28,35). Whether treatment of peri-infarct depression will improve patient outcomes is unknown at this time. Psychiatrists should work closely with primary care and cardiology physicians to insure the best treatment strategies. Choice of Psychotropic Agents for Persons with IHD
A handful of studies have shown an increased risk of cardiac events among persons prescribed psychotropic medi-
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cations. These small studies have included benzodiazepines, as well as antidepressants. Although earlier data suggested that TCAs could be safely used in persons with IHD, the results of some larger trials now would suggest that Type I antiarrhythmic agents (such as TCAs) should be avoided. Selective serotonin reuptake agents (SSRIs) may be safer, although they are associated with bradycardia (30). Buproprion also appears to be a safe alternative. If TCAs must be used, careful monitoring of serum levels and electrocardiograms seems prudent, and any symptoms referable to cardiac disease (chest pain, dyspnea, palpitations) should be promptly evaluated. Whether other psychotropic agents per se are associated with IHD is unclear, since these small studies did not evaluate the role of psychologic stress, a known predictor of IHD. Since interventions to reduce psychologic stress appear useful among patients with IHD, newer studies will need to evaluate the relative importance of the behavioral intervention versus psychopharmacologic interventions. Conclusions
Psychiatrists are in a unique position to help in the care of the person with heart disease. Primary and secondary prevention through risk factor modification remains the single most important aspect that psychiatrists can influence. Among these modifications, smoking cessation is extremely important, particularly because of the high prevalence of smoking among psychiatric patients. Psychiatrists should be familiar with symptoms referable to the cardiovascular system, and promptly refer patients for evaluation, if needed. When in doubt, psychiatrists should consult the medical physician regarding the choice of psychotropic medication. Tricyclic antidepressants are probably best avoided among persons with IHD, and if needed, should be carefully monitored with electrocardiograms and symptom review. References 1. U.S. Preventive Services Task Force. Guide to clinical preventive services, 2nd ed. Baltimore: Williams & Wilkins; 1996.
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mortality in women with symptomatic or silent myocardial ischemia. Israeli BIP Study Group. Am J Card 1996;78:1215–9. 33. Opie LH. Calcium channel blockers for hypertension: dissecting the evidence for adverse effects. Am J Hypertension 1997;10:565–77. 34. Perez V, Gilaberte I, Faries D, Alvarez E, Artigas F. Randomised, double-blind, placebo-controlled trial of pindolol in com-
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