Psychosocial factors in coronary and cerebral vascular disease
- Geoffrey H Tofler, MD
Geoffrey H Tofler, MD
- Professor of Cardiology
- University of Sydney, Australia
- Research Fellow
- Harvard Medical School
Although recent attention has focused on the role of psychosocial factors in the acute precipitation of myocardial infarction and sudden cardiac death, psychosocial factors may also contribute to the early development of atherosclerosis . The link between psychologic stress and atherosclerosis may be both direct, via damage of the endothelium, and indirect, via aggravation of traditional risk factors such as smoking, hypertension, and lipid metabolism.
Unfortunately, human studies of stress and coronary atherosclerosis have been limited in scope, due primarily to the difficulty in quantifying the degree of atherosclerosis in asymptomatic subjects. Thus, although angiographic data suggest that more extensive atherosclerosis is seen in patients with type A personality , confounding issues limit the interpretation. Stronger epidemiologic studies have linked psychosocial factors such as bereavement, loss of job, and depression with hard end points such as myocardial infarction and sudden death . One study which followed 1592 men and women for five years reported that the personality trait of submissiveness, a marker for type B behavior, was protective against nonfatal and total myocardial infarction, particularly in women (relative risk 0.59 and 0.69, respectively) .
Depression screening — Depression is associated with increased morbidity and mortality in patients with established coronary heart disease. We agree with the 2008 American Heart Association scientific advisory on Depression and Coronary Heart Disease which recommends screening for depressive symptoms in such patients . (See "Screening for depression in adults".)
STUDIES IN ANIMALS
The best insights into the role of psychological stress in atherosclerosis come from animal studies, in particular a series of experiments using cynomolgus monkeys . When fed a diet sufficiently rich in saturated fat and cholesterol, these monkeys develop atherosclerosis very rapidly with lesions similar to those seen in humans. Also similar to humans, premenopausal female monkeys are relatively protected from atherosclerosis.
These animals display complex patterns of social interaction characterized by hierarchies of dominant (aggressive) and subordinate (submissive) animals. Since the monkeys respond aggressively to new animals attempting to join their social groupings, the placement of strangers within groups forms the basis for a stressful challenge.To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Rozanski A, Blumenthal JA, Kaplan J. Impact of psychological factors on the pathogenesis of cardiovascular disease and implications for therapy. Circulation 1999; 99:2192.
- Krantz DS, Schaeffer MA, Davia JE, et al. Extent of coronary atherosclerosis, type A behavior, and cardiovascular response to social interaction. Psychophysiology 1981; 18:654.
- Theorell T, Lind E, Floderus B. The relationship of disturbing life-changes and emotions to the development of myocardial infarction and other serious diseases. Int J Epidemiol 1975; 4:281.
- Whiteman MC, Deary IJ, Lee AJ, Fowkes FG. Submissiveness and protection from coronary heart disease in the general population: Edinburgh Artery Study. Lancet 1997; 350:541.
- Lichtman JH, Bigger JT Jr, Blumenthal JA, et al. Depression and coronary heart disease: recommendations for screening, referral, and treatment: a science advisory from the American Heart Association Prevention Committee of the Council on Cardiovascular Nursing, Council on Clinical Cardiology, Council on Epidemiology and Prevention, and Interdisciplinary Council on Quality of Care and Outcomes Research: endorsed by the American Psychiatric Association. Circulation 2008; 118:1768.
- Kaplan JR, Adams MR, Clarkson TB, et al. Social behavior and gender in biomedical investigations using monkeys: studies in atherogenesis. Lab Anim Sci 1991; 41:334.
- Manuck SB, Kaplan JR, Matthews KA. Behavioral antecedents of coronary heart disease and atherosclerosis. Arteriosclerosis 1986; 6:2.
- Williams JK, Vita JA, Manuck SB, et al. Psychosocial factors impair vascular responses of coronary arteries. Circulation 1991; 84:2146.
- Manuck SB, Kaplan JR, Clarkson TB. Behaviorally induced heart rate reactivity and atherosclerosis in cynomolgus monkeys. Psychosom Med 1983; 45:95.
- Kaplan JR, Manuck SB, Adams MR, et al. Inhibition of coronary atherosclerosis by propranolol in behaviorally predisposed monkeys fed an atherogenic diet. Circulation 1987; 76:1364.
- McCabe PM, Gonzales JA, Zaias J, et al. Social environment influences the progression of atherosclerosis in the watanabe heritable hyperlipidemic rabbit. Circulation 2002; 105:354.
- Corse CD, Manuck SB, Cantwell JD, et al. Coronary-prone behavior pattern and cardiovascular response in persons with and without coronary heart disease. Psychosom Med 1982; 44:449.
- Kamarck TW, Everson SA, Kaplan GA, et al. Exaggerated blood pressure responses during mental stress are associated with enhanced carotid atherosclerosis in middle-aged Finnish men: findings from the Kuopio Ischemic Heart Disease Study. Circulation 1997; 96:3842.
- Kral BG, Becker LC, Blumenthal RS, et al. Exaggerated reactivity to mental stress is associated with exercise-induced myocardial ischemia in an asymptomatic high-risk population. Circulation 1997; 96:4246.
- Keys A, Taylor HL, Blackburn H, et al. Mortality and coronary heart disease among men studied for 23 years. Arch Intern Med 1971; 128:201.
- Wei J, Rooks C, Ramadan R, et al. Meta-analysis of mental stress-induced myocardial ischemia and subsequent cardiac events in patients with coronary artery disease. Am J Cardiol 2014; 114:187.
- O'Malley PG, Jones DL, Feuerstein IM, Taylor AJ. Lack of correlation between psychological factors and subclinical coronary artery disease. N Engl J Med 2000; 343:1298.
- Sesso HD, Kawachi I, Vokonas PS, Sparrow D. Depression and the risk of coronary heart disease in the Normative Aging Study. Am J Cardiol 1998; 82:851.
- Januzzi JL Jr, Stern TA, Pasternak RC, DeSanctis RW. The influence of anxiety and depression on outcomes of patients with coronary artery disease. Arch Intern Med 2000; 160:1913.
- Kawachi I, Sparrow D, Spiro A 3rd, et al. A prospective study of anger and coronary heart disease. The Normative Aging Study. Circulation 1996; 94:2090.
- Siegman AW, Kubzansky LD, Kawachi I, et al. A prospective study of dominance and coronary heart disease in the Normative Aging Study. Am J Cardiol 2000; 86:145.
- Chang PP, Ford DE, Meoni LA, et al. Anger in young men and subsequent premature cardiovascular disease: the precursors study. Arch Intern Med 2002; 162:901.
- Knox SS, Siegmund KD, Weidner G, et al. Hostility, social support, and coronary heart disease in the National Heart, Lung, and Blood Institute Family Heart Study. Am J Cardiol 1998; 82:1192.
- Kop WJ, Krantz DS, Howell RH, et al. Effects of mental stress on coronary epicardial vasomotion and flow velocity in coronary artery disease: relationship with hemodynamic stress responses. J Am Coll Cardiol 2001; 37:1359.
- Billing E, Hjemdahl P, Rehnqvist N. Psychosocial variables in female vs male patients with stable angina pectoris and matched healthy controls. Eur Heart J 1997; 18:911.
- Ruo B, Rumsfeld JS, Hlatky MA, et al. Depressive symptoms and health-related quality of life: the Heart and Soul Study. JAMA 2003; 290:215.
- Spertus JA, McDonell M, Woodman CL, Fihn SD. Association between depression and worse disease-specific functional status in outpatients with coronary artery disease. Am Heart J 2000; 140:105.
- Sullivan MD, LaCroix AZ, Spertus JA, Hecht J. Five-year prospective study of the effects of anxiety and depression in patients with coronary artery disease. Am J Cardiol 2000; 86:1135.
- Angerer P, Siebert U, Kothny W, et al. Impact of social support, cynical hostility and anger expression on progression of coronary atherosclerosis. J Am Coll Cardiol 2000; 36:1781.
- Horsten M, Mittleman MA, Wamala SP, et al. Depressive symptoms and lack of social integration in relation to prognosis of CHD in middle-aged women. The Stockholm Female Coronary Risk Study. Eur Heart J 2000; 21:1072.
- Schulz R, Beach SR, Ives DG, et al. Association between depression and mortality in older adults: the Cardiovascular Health Study. Arch Intern Med 2000; 160:1761.
- Surtees PG, Wainwright NW, Luben RN, et al. Depression and ischemic heart disease mortality: evidence from the EPIC-Norfolk United Kingdom prospective cohort study. Am J Psychiatry 2008; 165:515.
- Scheier MF, Matthews KA, Owens JF, et al. Optimism and rehospitalization after coronary artery bypass graft surgery. Arch Intern Med 1999; 159:829.
- Connerney I, Shapiro PA, McLaughlin JS, et al. Relation between depression after coronary artery bypass surgery and 12-month outcome: a prospective study. Lancet 2001; 358:1766.
- Blumenthal JA, Lett HS, Babyak MA, et al. Depression as a risk factor for mortality after coronary artery bypass surgery. Lancet 2003; 362:604.
- Mallik S, Krumholz HM, Lin ZQ, et al. Patients with depressive symptoms have lower health status benefits after coronary artery bypass surgery. Circulation 2005; 111:271.
- Knox SS, Adelman A, Ellison RC, et al. Hostility, social support, and carotid artery atherosclerosis in the National Heart, Lung, and Blood Institute Family Heart Study. Am J Cardiol 2000; 86:1086.
- Dong JY, Zhang YH, Tong J, Qin LQ. Depression and risk of stroke: a meta-analysis of prospective studies. Stroke 2012; 43:32.
- Pan A, Sun Q, Okereke OI, et al. Depression and risk of stroke morbidity and mortality: a meta-analysis and systematic review. JAMA 2011; 306:1241.
- Ghiadoni L, Donald AE, Cropley M, et al. Mental stress induces transient endothelial dysfunction in humans. Circulation 2000; 102:2473.
- Spieker LE, Hürlimann D, Ruschitzka F, et al. Mental stress induces prolonged endothelial dysfunction via endothelin-A receptors. Circulation 2002; 105:2817.
- Henry JP, Ely DL, Stephens PM, et al. The role of psychosocial factors in the development of arteriosclerosis in CBA mice. Observations on the heart, kidney and aorta. Atherosclerosis 1971; 14:203.
- Strawn WB, Bondjers G, Kaplan JR, et al. Endothelial dysfunction in response to psychosocial stress in monkeys. Circ Res 1991; 68:1270.
- Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 1993; 362:801.
- Goldberg RJ, Brady P, Muller JE, et al. Time of onset of symptoms of acute myocardial infarction. Am J Cardiol 1990; 66:140.
- Saxena PR, Villalón CM. Cardiovascular effects of serotonin agonists and antagonists. J Cardiovasc Pharmacol 1990; 15 Suppl 7:S17.
- Haft JI, Arkel YS. Effect of emotional stress on platelet aggregation in humans. Chest 1976; 70:501.
- Wagner CT, Kroll MH, Chow TW, et al. Epinephrine and shear stress synergistically induce platelet aggregation via a mechanism that partially bypasses VWF-GP IB interactions. Biorheology 1996; 33:209.
- Roux SP, Sakariassen KS, Turitto VT, Baumgartner HR. Effect of aspirin and epinephrine on experimentally induced thrombogenesis in dogs. A parallelism between in vivo and ex vivo thrombosis models. Arterioscler Thromb 1991; 11:1182.
- Adams DO. Molecular biology of macrophage activation: a pathway whereby psychosocial factors can potentially affect health. Psychosom Med 1994; 56:316.
- Cardillo C, Kilcoyne CM, Cannon RO 3rd, Panza JA. Impairment of the nitric oxide-mediated vasodilator response to mental stress in hypertensive but not in hypercholesterolemic patients. J Am Coll Cardiol 1998; 32:1207.
- Lindenthal JJ, Myers JK, Pepper MP. Smoking, psychological status and stress. Soc Sci Med 1972; 6:583.
- Dimsdale JE, Herd JA. Variability of plasma lipids in response to emotional arousal. Psychosom Med 1982; 44:413.
- Rahe RH, Rubin RT, Arthur RJ. The three investigators study. Serum uric acid, cholesterol, and cortisol variability during stresses of everyday life. Psychosom Med 1974; 36:258.
- Dimsdale JE, Herd JA, Hartley LH. Epinephrine mediated increases in plasma cholesterol. Psychosom Med 1983; 45:227.
- Henry JP, Meehan JP, Stephens PM. The use of psychosocial stimuli to induce prolonged systolic hypertension in mice. Psychosom Med 1967; 29:408.
- Krantz DS, Manuck SB. Acute psychophysiologic reactivity and risk of cardiovascular disease: a review and methodologic critique. Psychol Bull 1984; 96:435.
- Empana JP, Sykes DH, Luc G, et al. Contributions of depressive mood and circulating inflammatory markers to coronary heart disease in healthy European men: the Prospective Epidemiological Study of Myocardial Infarction (PRIME). Circulation 2005; 111:2299.
- Southam, MA, Agras, WS. Stress and stress management in coronary heart disease. In: Coronary prevention: A clinical guide, Hutchinson, RG (Ed), Year Book Medical Publishers, Chicago 1985. p.145.
- Blumenthal JA, Sherwood A, Babyak MA, et al. Effects of exercise and stress management training on markers of cardiovascular risk in patients with ischemic heart disease: a randomized controlled trial. JAMA 2005; 293:1626.
- Biofeedback for hypertension. Health and Public Policy Committee, American College of Physicians. Ann Intern Med 1985; 102:709.
- Agras WS. Behavioral approaches to the treatment of essential hypertension. Int J Obes 1981; 5 suppl 1:173.
- Benson H. The relaxation response: history, physiological basis and clinical usefulness. Acta Med Scand Suppl 1982; 660:231.
- Patel C, Carruthers M. Coronary risk factor reduction through biofeedback-aided relaxation and meditation. J R Coll Gen Pract 1977; 27:401.
- Thoresen CE, Friedman M, Gill JK, Ulmer DK. The recurrent coronary prevention project. Some preliminary findings. Acta Med Scand Suppl 1982; 660:172.
- Blumenthal JA, Williams RS, Williams RB Jr, Wallace AG. Effects of exercise on the Type A (coronary prone) behavior pattern. Psychosom Med 1980; 42:289.
- Depression screening
- STUDIES IN ANIMALS
- STUDIES IN HUMANS
- Development of coronary disease
- Coronary heart disease symptoms
- Progression of coronary heart disease
- Cardiovascular mortality
- Outcome after CABG
- Carotid artery atherosclerosis
- Effect on risk factors
- Association with inflammation
- SUMMARY AND RECOMMENDATIONS