Myocardial ischemia that results from emotional provocation occurs in as many as 30% to 50% of patients with coronary artery disease during the discourse of their lives. This emotionally provoked or mental stress ischemia is associated with poor prognosis, with emerging treatment strategies. This article outlines the conceptual constructs that support the pathophysiologic underpinnings, and biobehavioral aspects associated with this mental stress ischemia. We review a biobehavioral model in which cognitive stress is transduced in the brain. The response of the brain to psychosocial stress is a highly sophisticated and integrated process by which sensory inputs are evaluated and appraised for their importance in relation to previous experience and current goals. The biologic consequences of such stress transduced in the central nervous system has its effect on cardiovascular flow and function through changes in autonomic balance, which result in various biologic processes that culminate in the perturbation of flow and function of the heart.
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References and Recommended Reading
Damasio A, ed: Descartes’ Error: Emotion, Reason, and the Human Brain. New York: Avon Books; 1994.
Ruberman W, Weinblatt E, Goldberg JD, Chaudhary BS:Psychosocial influences on mortality after myocardial infarction. N Engl J Med 1984, 311:552–559.
Marmot MG, Smith GD, Stansfeld S, et al.: Health inequalities among British civil servants: the Whitehall II study. Lancet 1981, 337:1387–1393.
Sasaki N, Kinugawa T, Yamawaki M, et al.: Transient left ventricular apical ballooning in a patient with bicuspid aortic valve created a left ventricular thrombus leading to acute renal infarction. Circ J 2004, 68:1081–1083.
Wittstein IS, Thiemann DR, Lima JA: Neurohumoral features of myocardial stunning due to sudden emotional stress. N Engl J Med 2005, 352:539–548.
Mittleman MA, Maclure M, Sherwood JB, et al.: Triggering of acute myocardial infarction onset by episodes of anger. Circulation 1995, 92:1720–1725.
Goldberg AD, Becker LC, Bonsall R, et al.: Ischemic, hemodynamic, and neurohormonal responses to mental and exercise stress. Experience from the Psychophysiological Investigations of Myocardial Ischemia Study (PIMI). Circulation 1996, 94:2402–2409.
Lampert R, Jain D, Burg MM, et al.: Destabilizing effects of mental stress on ventricular arrhythmias in patients with implantable cardioverter-defibrillators. Circulation 2000, 101:158–164.
Burg MM, Jain D, Soufer R, et al.: Role of behavioral and psychological factors in mental stress-induced silent left ventricular dysfunction in coronary artery disease. J Am Coll Cardiol 1993, 22:440–448.
Barry J, Selwyn AP, Nabel EG, et al.: Frequency of ST-segment depression produced by mental stress in stable angina pectoris from coronary artery disease. Am J Cardiol 1998, 61:989–993.
Specchia G, Falcone C, Traversi E, et al.: Mental stress as a provocative test in patients with various clinical syndromes of coronary heart disease. Circulation 1981, 83:II108–II114.
Stern S, Tzivoni D: Early detection of silent ischemic heart disease by twenty four hours electrocardiographic of active subject. Br Heart J 1974, 36:481–486.
Schang SJ, Peppine C: Transient asymptomatic S-T segment depression during daily activity. Am J Cardiol 1977, 39:396–402.
Powell LH, Thoresen CE: Behavioral and physiologic determinants of long term prognosis after myocardial infarction. J Chronic Dis 1985, 38:253–263.
Jain D, Burg M, Soufer R, Zaret BL: Prognostic implications of mental stress-induced silent left ventricular dysfunction in patients with stable angina pectoris. Am J Cardiol 1995, 76:31–35.
Sheps DS, McMahon RP, Becker L, et al.: Mental stress-induced ischemia and all-cause mortality in patients with coronary artery disease: results from the Psychophysiological Investigations of Myocardial Ischemia study. Circulation 2002, 105:1780–1784.
Jiang W, Babyak M, Krantz DS, et al.: Mental stress-induced myocardial ischemia and cardiac events. JAMA 1996, 275:1651–1656.
Rosengren A, Tibblin G, Wilhelmsen L: Self-perceived psychological stress and incidence of coronary artery disease in middle-aged men. Am J Cardiol 1981, 68:1171–1175.
Chi JS, Poole WK, Kandefer SC, Kloner RA: Cardiovascular mortality in New York City after September 11, 2001. Am J Cardiol 2003, 92:857–861.
Gurfinkel EP, Bozovich GE, Dabbous O, et al.: Socio economic crisis and mortality. Epidemiological testimony of the financial collapse of Argentina. Thromb J 2005, 3:22.
Bakaeen FG, Huh J, Chu D, et al.: Hurricane Katrina: impact on cardiac surgery case volume and outcomes. Tex Heart Inst J 2008, 35:273–278.
Becker LC, Pepine CJ, Bonsall R, et al.: Left ventricular, peripheral vascular, and neurohumoral responses to mental stress in normal middle-aged men and women. Reference Group for the Psychophysiological Investigations of Myocardial Ischemia (PIMI) Study. Circulation 1996, 94:2768–2777.
Jain D, Shaker SM, Burg M, et al.: Effects of mental stress on left ventricular and peripheral vascular performance in patients with coronary artery disease. J Am Coll Cardiol 1998, 31:1314–1322.
Burg MM, Vashist A, Soufer R: Mental stress ischemia: present status and future goals. J Nucl Cardiol 2005, 12:523–529.
Rozanski A, Bairey CN, Krantz DS, et al.: Mental stress and the induction of silent myocardial ischemia in patients with coronary artery disease. N Engl J Med 1998, 318:1005–1012.
Soufer R, Bremner JD, Arrighi JA, et al.: Cerebral cortical hyperactivation in response to mental stress in patients with coronary artery disease. Proc Natl Acad Sci U S A 1998, 95:6454–6459.
Thayer J, Lane RD: A model of neurovisceral integration in emotion regulation and dysregulation. J Affect Disord 2000, 61:201–216.
Davidson RJ, Irwin W: The functional neuroanatomy of emotion and affective style. Trends Cogn Sci 1999, 3:11–21.
Bush G, Luu P, Posner MI: Cognitive and emotional influences in anterior cingulate cortex. Trends Cogn Sci 2000, 4:215–222.
Simpson JR Jr, Drevets WC, Snyder AZ, et al.: Emotion-induced changes in human medial prefrontal cortex: II. During anticipatory anxiety. Proc Natl Acad Sci U S A 2001, 98:688–693.
Ahern DK, Gorkin L, Anderson JL, et al.: Biobehavioral variables and mortality or cardiac arrest in the Cardiac Arrhythmia Pilot Study (CAPS). Am J Cardiol 1990, 66:59–62.
Shah R, Burg MM, Vashist A, et al.: C-reactive protein and vulnerability to mental stress-induced myocardial ischemia. Mol Med 2006, 12:269–274.
Vashist A, Burg MM, Arrighi JA, et al.: Central nervous system correlates of myocardial ischemia: neurocardiac distinctions between mental stress and dobutamine provocation. Psychosom Med 2005, 67:A8–A9.
Soufer R, Bremner JD, Burg MM: Gender differences among normal and coronary disease subjects during mental stress: a positron emission tomography study. Presented at the American Psychosomatic Society 63rd Annual Meeting. Vancouver, BC, Canada; March 2–5, 2005.
Soufer R: Neurocardiac interaction during stress-induced myocardial ischemia: how does the brain cope? Circulation 2004, 110:1710–1713.
Rozanski A, Blumenthal JA, Davidson KW, et al.: The epidemiology, pathophysiology, and management of psychosocial risk factors in cardiac practice: the emerging field of behavioral cardiology. J Am Coll Cardiol 2005, 45:637–651.
Lampert R, Shusterman V, Burg M, et al.: Anger-induced T-wave alternans predicts future ventricular arrhythmias in patients with implantable cardioverter-defibrillators. J Am Coll Cardiol 2009 (in press).
Tracey KJ. Physiology and immunology of the cholinergic antiinflammatory pathway. J Clin Inv 2007, 117:289–296.
Borovikova LV, Ivanova S, Zhang M, et al.: Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature 2000, 405:458–462.
Pavlov VA, Wang H, Czura CJ, et al.: The cholinergic anti-inflammatory pathway: a missing link in neuroimmunomodulation. Mol Med 2003, 9:125–134.
Lane RD, Reiman EM, Ahern GL, Thayer JF: Activity in medial prefrontal cortex correlates with vagal component of heart rate variability during emotion. Rothman Institute Abstracts 2001:97–100.
Honzikova N, Semrad B, Fiser B, Labrova R: Baroreflex sensitivity determined by spectral method and heart rate variability, and two-year mortality in patients after myocardial infarction. Physiol Res 2000, 49:643–650.
Nobrega AC, Loures DL, Pontes PV, et al.: Cholinergic stimulation with pyridostigmine prevents the impairment in ventricular function during mental stress in coronary artery disease patients. Int J Cardiol 2008, 125:418–421.
Fukudo S, Lane JD, Anderson NB, et al.: Accentuated vagal antagonism of beta-adrenergic effects on ventricular repolarization. Evidence of weaker antagonism in hostile type A men. Circulation 1992, 85:2045–2053.
Torre-Amione G, Kapadia S, Lee J, et al.: Expression and functional significance of tumor necrosis factor receptors in human myocardium. Circulation 1995, 92:1487–1493.
Meldrum DR: Tumor necrosis factor in the heart. Am J Physiol 1998, 274:R577–R595.
Kop WJ, Weissman NJ, Zhu J, et al.: Effects of acute mental stress and exercise on inflammatory markers in patients with coronary artery disease and healthy controls. Am J Cardiol 2008, 101:767–773.
Deanfield JE, Shea M, Kensett M, et al.: Silent myocardial ischaemia due to mental stress. Lancet 1984, 2:1001–1005.
Giubbini R, Galli M, Campini R, et al.: Effects of mental stress on myocardial perfusion in patients with ischemic heart disease. Circulation 1981, 83:II100–II107.
Arrighi JA, Burg M, Cohen IS, et al.: Myocardial blood-flow response during mental stress in patients with coronary artery disease. Lancet 2000, 356:310–311.
Dakak N, Quyyumi AA, Eisenhofer G, et al.: Sympathetically medicated effects of mental stress on the cardiac microcirculation of patients with coronary artery disease. Am J Cardiol 1995, 76:125–130.
Yeung AC, Vekshtein VI, Krantz DS, et al.: The effect of atherosclerosis on the vasomotor response of coronary arteries to mental stress. N Engl J Med 1981, 325:1551–1556.
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, 37:1359–1366.
Dimsdale JE, Moss J: Plasma catecholamines in stress and exercise. JAMA 1980, 243:340–342.
Yang ZH, Richard V, von Segesser L, et al.: Threshold concentrations of endothelin-1 potentiate contractions to norepinephrine and serotonin in human arteries. A new mechanism of vasospasm? Circulation 1990, 82:188–195.
Spieker LE, Hürlimann D, Ruschitzka F, et al.: Mental stress induces prolonged endothelial dysfunction via endothelin-A receptors. Circulation 2002, 105:2817–2820.
Kahaleh MB, Fan PS: Effect of cytokines on the production of endothelin by endothelial cells. Clin Exp Rheumatol 1997, 15:163–167.
Woods M, Mitchell JA, Wood EG, et al.: Endothelin-1 is induced by cytokines in human vascular smooth muscle cells: evidence for intracellular endothelin-converting enzyme. Mol Pharmacol 1999, 55:902–909.
Hohlfeld T, Klemm P, Thiemermann C, et al.: The contribution of tumour necrosis factor-alpha and endothelin-1 to the increase of coronary resistance in hearts from rats treated with endotoxin. Br J Pharmacol 1995, 116:3309–3315.
Mizia-Stec K, Gasior Z, Zahorska-Markiewicz B, et al.: Serum tumour necrosis factor-alpha, interleukin-2 and interleukin-10 activation in stable angina and acute coronary syndromes. Coron Artery Dis 2003, 14:431–438.
Hassan M, York KM, Li H, et al.: Association of beta1-adrenergic receptor genetic polymorphism with mental stress-induced myocardial ischemia in patients with coronary artery disease. Arch Intern Med 2008, 168:763–770.
Krantz DS, Santiago HT, Kop WJ, et al.: Prognostic value of mental stress testing in coronary artery disease. Am J Cardiol 1999, 84:1292–1297.
Rosenman RH, Brand RJ, Jenkins D, et al.: Coronary heart disease in Western Collaborative Group Study: final follow-up experience of 8 1/2 years. JAMA 1975, 233:872–877.
Julkunen J, Salonen R, Kaplan GA, et al.: Hostility and the progression of carotid atherosclerosis. Psychosom Med 1994, 56:519–525.
Goodman M, Quigley J, Moran G, et al.: Hostility predicts restenosis after percutaneous transluminal coronary angioplasty. Mayo Clin Proc 1996, 71:729–734.
Blumenthal JA, Babyak M, Wei J, et al.: Usefulness of psychosocial treatment of mental stress-induced myocardial ischemia in man. Am J Cardiol 2002, 89:164–168.
Blumenthal JA, Jiang W, Babyak MA, et al.: Stress management and exercise training in cardiac patients with myocardial ischemia. Effects on prognosis and evaluation of mechanisms. Arch Intern Med 1997, 157:2213–2223.
Burg MM, Graeber B, Vashist A, et al.: Noninvasive detection of risk for emotion provoked myocardial ischemia. Psychosom Med 2008 Oct 21 (Epub ahead of print).
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Soufer, R., Jain, H. & Yoon, A.J. Heart-brain interactions in mental stress-induced myocardial ischemia. Curr Cardiol Rep 11, 133–140 (2009). https://doi.org/10.1007/s11886-009-0020-1
- Heart Rate Variability
- Myocardial Ischemia
- Nuclear Cardiology
- Mental Stress
- Parasympathetic Tone