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1、Wei Jiang, MD Associate Professor Internal Medicine Psychiatry & Behavioral Sciences Duke University Medical Center,Emotional Distress & Mental Stress Induced Myocardial Ischemia _ An Invisible Killer,Purgason K. Dimensions of Critical Care Nursing. 2006;25:247-53,A 64yo WF presents to a local ER, c
2、omplaining of 2-h substernal chest pain Mild dyspnea with HR 72 bpm, BP 136/72 mm Hg, RR 20/min, T 97.9F, and O2 saturation 96% on RA No past medical history, postmenopausal, walks daily, and on balanced diet 12-lead EKG shows ST elevation in leads V3-V6, troponin 3.5 ng/dL and CPK 275 m/L, LVEF 40%
3、 with moderate ventricle dysfunction, apical akinesis, and preserved basal function by Echocardiograpm The patient received news that her daughter had been severely injured in a car accident several hours before her onset of chest pain,A Typical Case:,“I have always been impressed by the probability
4、 of an important relationship between personality attributes, stress coping strategies and heart disease with myocardial infarction in particular. I have witnessed several friends die suddenly this way. They did not smoke, were not overweight, and their cholesterol levels were unremarkable. But I kn
5、ew them to be under considerable strain as the result of professional and personal stressors, and I have always believed that their lack of insight, resilience, and emotional resourcefulness, along with their characteristic pattern of responding to stress with helpless anger, significantly contribut
6、ed to their demise.” _An anonymous Cardiologist,A Quote from a Cardiologist,Ampulla cardiomyopathy (Takotusbo cardiomyopathy) -reversible left ventricular dysfunction: with ST segment elevation 8 elderly women and one middle-aged man are studied. All coronary arteriograms are normal, though 7 of the
7、m had ST elevation on electrocardiogram. Coronary spasm was positive in only 2 of the 7 patients who received provocation tests Biopsy specimens revealed focal myocyte injury Normal coronary arteriograms during ST elevation and the presence of pathologic myocardial lesions were not consistent with a
8、 concept of stunned myocardium. The presence of myocardial lesions suggested that focal and disseminated myocardial damage had occurred.,Kawai, et al. Jpn Circ J 2000;64:237,Autopsy Findings following an Earthquake,Formal autopsy findings from 111 earthquake-related deaths The median extrication tim
9、e for 99 of 102 victims buried or trapped in collapsed buildings was 2.1 (range 0.1-7.8) days Deaths were cause by blunt injuries, asphyxia and myocardial infarction. Injuries impaired the airway, breathing, circulation, and brain or spinal functions in 10.5, 61.9, 46.6 and 57.1% of the victims, res
10、pectively.,Papadopoulos et al. J Surgery. 2004;91:1633-40,Kloner et al J Am Coll Cardiol. 1998;32:553-4,Increased MI following an Earthquake _ U.S.A,Increased MI following an Earthquake _ Japan,Matsuo et al. Int J Hematol 1998; 67: 1239,Tsai et al. Psychosomatics. 45(6):477-82, 2004 Nov-Dec.,Increas
11、ed MI following an Earthquake _ Taiwan,Mental stress-Induced Myocardial Ischemic Activity,Myocardial Ischemia occurs when the demand on the myocardium is not met by the blood supply High myocardium demandanything increases activities of myocardium, most notably, physical exercise or condition causin
12、g elevation of heart rate Low blood supplyconstriction of coronary arteries anatomically or hemodynamically Myocardial Ischemia occurs transiently in relationship of the alteration of the balance between demand and supply,Mechanism of Myocardial Ischemia,Demand HR Double Product,Supply Stenosis Vess
13、el Constriction,Mental Stress-Induced Myocardial Ischemic Activity,Myocardial ischemia induced in the laboratory is, in general, based on the mechanism of increasing myocardium demand, i.e. high systolic blood pressure and rapid heart rate; by means of exercise or pharmacological intervention Myocar
14、dial ischemia occurs during daily living not necessarily related to increased physical intensity, it occurs during mental activities as well Myocardial Ischemia may be detected by electrocardiogram in the laboratory and during daily living, and myocardium imaging in laboratory setting Occurrence of
15、myocardial ischemia is associated with poorer prognosis in patients with coronary artery disease,Mental Stress-Induced Myocardial Ischemic Activity,Barry J et al. Am J Cardiol 1988;61:989-93,Total of 372 ischemic episodes,Mental Stress Tasks,Commonly Utilized Mental Tasks in Laboratory Setting: Ment
16、al Arithmetic Public Speech Mirror Trace Stroop Color Word Reading Type A Personality Interview Start with a brief introduction, followed by a 30-second preparation. The tasks last 3-5 minutes,Mental Stress-Induced Myocardial Ischemic Activity,Deanfield et al. Lancet 1984;92:2102-8,Deanfield et al.
17、Lancet 1984;92:2102-8,Mental Stress-Induced Myocardial Ischemic Activity,A comparative study among patients with positive exercise testing and normal controls with low IHD probability,Rozanski et al. NEJM 1988;318:1005,* Those abnormalities occurred exclusively in association with LVWMA,Mental Stres
18、s-Induced Myocardial Ischemic Activity,Scintographically Recorded Responses to Exercise and Mental Arithmetic testing,Giubbini et al. Circulation 1991;83:II100,Mental Stress-Induced Myocardial Ischemic Activity,Blumenthal 92:2102-8,Flow mal-distribution,Hypoperfusion,Diastolic dysfunction,Systolic d
19、ysfunction,ECG changes,Angina,Perfusion Imaging,Echocardiography,Tissue Doppler Echo,Cascade of Myocardial Ischemia,Mental Stress-Induced Myocardial Ischemic Activity,Mental stress induced myocardial ischemia usually asymptomatic MSIMI does not have to occur in patients without significant stenosis
20、of coronary arteries Patients with mental stress induced ischemia had increased risk for death or revascularizations over a 5-year follow-up, especially for those whose resting LVEF 60% Neither exercise induced ischemia nor ischemic activities detected during daily living was associated with increas
21、ed poor outcome in the same group of patients.,Jiang W et al. JAMA 1996;275:1651-6,Mental Stress-Induced Myocardial Ischemic Activity,What happens emotionally when patients exhibited daily ischemia which is not related to physical activity or myocardial ischemia during mental stress testing?,Mental
22、Stress-Induced Myocardial Ischemic Activity,Gullette, E et al, JAMA 1997;277:1521-1526,Percentage of hours with Ischemia and Level of Emotion,Mental Stress-Induced Myocardial Ischemic Activity,Emotional Responses to Mental Stress and Exercise Testing,Depression and Mortality Post Myocardial infarcti
23、on (N=222),Mental Stress-Induced Myocardial Ischemic Activity -a potential mechanism,Are patients with depression more likely to experience mental stress-induced ischemia?,Mental Stress-Induced Myocardial Ischemic Activity,Percentage of Patients Developed WMA During Mental Stress Testing,Mental Stre
24、ss-Induced Myocardial Ischemic Activity,Relationship of Depressive Symptomatology and Mental Stress Induced WMA,Mental Stress-Induced Myocardial Ischemic Activity,Estimated RR of Depression for the Likelihood of MSIMI,Kop. Psychosomatic Medicine 1999;61:476-487,Mental Stress-Induced Myocardial Ische
25、mic Activity,Hemo-dynamic responses to mental stress and exercise,Mental Stress-Induced Myocardial Ischemic Activity,Rozanski A et al. N eng J med 1988;318:1005-12,Mental Stress-Induced Myocardial Ischemic Activity,SBP Reaction,Blumenthal JA et al. Circulation 1995;92:2102-8,Mental Stress-Induced My
26、ocardial Ischemic Activity,DBP Reaction,Blumenthal JA et al. Circulation 1995;92:2102-8,Mental Stress-Induced Myocardial Ischemic Activity,HR Reaction,Blumenthal JA et al. Circulation 1995;92:2102-8,Mental Stress-Induced Myocardial Ischemic Activity,Double-product = SBP x HR _ an indicator of myocar
27、dium demand,Mental Stress-Induced Myocardial Ischemic Activity,Uniqueness of Coronary Circulation,Epicardial coronary arteries give off small tranmural penetrating arteries into the myocardial layers, i.e. arterioles which terminates in capillary vessels that directly supply cardial myocytes. Non-st
28、enosed epicardial coronary artery plays a minor role in the regulation of coronary vascular resistance Most of the resistance arises from coronary arterioles which opposes coronary blood flow,Microcirculation,Distribution of Coronary Resistance in Coronary Bed,In response to vessel wall injury, alte
29、rations of blood flow (“shear stress“), or chemical stimuli (eg, thrombin or catecholamines), platelets manifest a series of linked functional responses (ie, adhesion, secretion, and aggregation) The surface of activated platelets expresses procoagulant phospholipids and binding sites for FV and FVI
30、II that constitute the platelet coagulation activity referred to as platelet factor 3 Hemostatic function is closely related to vWF, that is stored in endothelial cells and platelets. vWF is crucial for both platelet adhesion to injured subendothelial structures and platelet aggregation. In addition
31、, vWF binds to and protects FVIII from proteolysis,Homeostasis Pathways,Disturbed Homeostasis,A hypercoagulable state prior to overt thrombosis resulting from an imbalance between the coagulation and fibrinolysis systems is related to cardiovascular disease progression and acute coronary syndromes,D
32、isturbed Homeostasis,Search of literature on coagulation, anticoagulation, and fibrinolysis measures in conjunction with mental stress, psychosocial strain, and psychiatric disorders in MEDLINE from 1966 conducted, identifying 68 articles.,Disturbed Homeostasis,In healthy subjects, acute mental stre
33、ss simultaneously activates coagulation (ie, fibrinogen or vWF) and fibrinolysis (ie, tissue-type PA) within a physiological range. In patients with atherosclerosis and impaired endothelial anticoagulant function, however, procoagulant responses to acute stressors may outweigh anticoagulant mechanis
34、ms and thereby promote a hypercoagulable state. Chronic psychosocial stressors (job strain or low socioeconomic status) are related to a hypercoagulable state reflected by increased procoagulant molecules (ie, fibrinogen or factor VII) and by reduced fibrinolytic capacity. There is also some evidenc
35、e that points to hypercoagulability in depression.,Mental Stress-Induced Myocardial Ischemic Activity,Significant coronary vasoconstriction was observed when infusing acetylcholine during mental stress testing _ Yeung AC et al, N Eng J Med 1991;325:1551-6 Boltwood MD et al, Am J Cardiol 1993;72:1361
36、-5 Coronary circulation was observed to fail to dilate during mental stress testing _ Dakak N et al, Am J Cardiol 1995;76:125-30,Stress,Stress in Chinese means Pressure & Strength or power If there is no stress, there will be no strength,Emotional Distress,Anger or Hostility Depression Anxiety Negat
37、ivity, like the “half glass empty” Hopeless Social Isolation Interpersonal Conflict Job Stress,Perception Vs. Reality,Threat of Emotional Distress,Severity and/or intensity of stress Duration of stress Susceptibility of individual Negative cognition Coping skills Underlying medical or psychiatric co
38、nditions Burned out,Threat of Emotional Distress,Mental stress induced LV dysfunction is associated with 3-fold increase in risk of cardiac events during a 2-year follow-up; BB use have no effect _ Jain et al. Am J Cardiol 1995;76:31 Over a 5-year f/u, MSIMI was associated with increased cardiac eve
39、nts during a 5-year follow-up (OR 2.8; 95% CI 1.0-7.7), independent of age, history of prior myocardial infarction, and baseline cardiac function. However, exercise-induced ischemia did not predict for adverse cardiac events (OR, 1.5; 95% CI, 0.6-3.9) in the same sample _ Jiang et al. JAMA 1996;275:
40、1651-6 New or worsened wall motion abnormalities during the speech test is significantly predicted death (OR 3.0; 95% CI, 1.04 to 8.36) over 5-year _ Sheps et al. Circulation 2002;105:1780,Threat of Emotional Distress,Implicated therapeutic modality is limited Beta blocker: may be helpful among ones
41、 with large HR increase Cognitive-behavioral therapy Aerobic exercise Others?,Emotional Stress & MSIMI _ An Example of Mind-Body Interaction,Example questions need to be answered: Are all emotional stress bad? Should it be defined as emotional distress? Will a healthy cardiovascular system responses
42、 same to emotional stress? How will other system or organs respond to emotional stress? Similar process? What kind of therapeutic modalities may modify the adverse responses of CV system to emotional stress? Exercise? Relaxation? Psychotherapy? Drugs? etc?,Threat of Emotional Distress,Selective Sero
43、tonin Reuptake Inhibitors Reduce depression _ CNS modulation Reduce platelet activity _ peripheral modulation Others?,Stable patients with documented coronary disease & BDI score 5,Laboratory mental stress & exercise testing, Platelet study,Escitalopram 5-20 mg/day,Placebo,Primary Endpoint: Reductio
44、n of MSIMI Secondary Endpoints: CV reactivity during mental stress testing Platelet activity Correlation of depressive symptoms, cardiovascular reactivity and MSIMI as well as exercise induced ischemia Others?,NHLBI REMIT Study Response of Myocardial Ischemia to SSRI Treatment,Patients who develop MSIMI,Repeat above laboratory tests,Thank You !,