Psychotropic medication use and risk of adverse cardiovascular events in women with suspected coronary artery disease: outcomes from the Women's Ischemia Syndrome Evaluation (WISE) study.

OBJECTIVE: This study investigated the relation between psychotropic medication use and adverse cardiovascular (CV) events in women with symptoms of myocardial ischaemia undergoing coronary angiography. METHOD: Women enrolled in the Women's Ischemia Syndrome Evaluation (WISE) were classified into one of four groups according to their reported antidepressant and anxiolytic medication usage at study intake: (1) no medication (n = 352); (2) anxiolytics only (n = 67); (3) antidepressants only (n = 58); and (4) combined antidepressant and anxiolytics (n = 39). Participants were followed prospectively for the development of adverse CV events (for example, hospitalisations for non-fatal myocardial infarction, stroke, congestive heart failure and unstable angina) or all-cause mortality over a median of 5.9 years. RESULTS: Use of antidepressant medication was associated with subsequent CV events (HR 2.16, 95% CI 1.21 to 3.93) and death (HR 2.15, 95% CI 1.16 to 3.98) but baseline anxiolytic use alone did not predict subsequent CV events and death. In a final regression model that included demographics, depression and anxiety symptoms, and risk factors for cardiovascular disease, women in the combined medication group (that is, antidepressants and anxiolytics) had higher risk for CV events (HR 3.98, CI 1.74 to 9.10, p = 0.001 and all-cause mortality (HR 4.70, CI 1.7 to 2.97, p = 0.003) compared to those using neither medication. Kaplan-Meier survival curves indicated that there was a significant difference in mortality among the four medication groups (p = 0.001). CONCLUSIONS: These data suggest that factors related to psychotropic medication such as depression refractory to treatment, or medication use itself, are associated with adverse CV events in women with suspected myocardial ischaemia.

Major life changes before and after the onset of chronic daily headache: a population-based study.

Chronic daily headache (CDH), when defined as > or = 15 headache days per month, affects 3-5% of the adult population. Major life changes are putative precipitating events for onset of chronic pain, including chronic headache. This study compared the occurrence of specific life events between CDH cases and episodic headache controls in a community sample. CDH cases (180+ headache days per year: n = 206) and episodic headache controls (2-104 headache days per year: n = 507) were identified from a randomly selected adult US population. Subjects were interviewed about the occurrence of certain major life changes or events (change of residence, employment status, marital status, related to their children, deaths of relatives or close friends, and 'extremely stressful' ongoing situations) occurring in a defined time period. Events that occurred during the same year or year before frequent headache onset in cases or in an equivalent time period in controls were considered to be antecedent events. Those that occurred after this time were considered subsequent events. Compared with episodic headache controls, CDH cases had more major life changes in the year before or same year as CDH onset. After adjusting for age, gender, headache type and year of event, the odds of CDH increased additionally with each antecedent event [odds ratio (OR) 1.20 (1.1, 1.3), P < 0.001], but not with subsequent events [OR 0.94 (0.8, 1.1), P < 0.4]. In secondary analyses, the association between antecedent events and CDH was significant only for the approximately half of CDH cases who were aged >/= 40 years [OR 1.33 (1.2, 1.50) vs. OR 1.04 (0.9, 1.2), P < 0.05 for interaction by age]. These results suggest that major life changes are associated with the onset of chronic daily headache, particularly in middle age.

Changes in heart rate and heart rate variability before ambulatory ischemic events(1).

OBJECTIVES: The aim of this study was to determine the time course of autonomic nervous system activity preceding ambulatory ischemic events. BACKGROUND: Vagal withdrawal can produce myocardial ischemia and may be involved in the genesis of ambulatory ischemic events. We analyzed trajectories of heart rate variability (HRV) 1 h before and after ischemic events, and we examined the role of exercise and mental stress in preischemic autonomic changes. METHODS: Male patients with stable coronary artery disease (n = 19; 62.1 +/- 9.3 years) underwent 48-h ambulatory electrocardiographic monitoring. Frequency domain HRV measures were assessed for 60 min before and after each of 68 ischemic events and during nonischemic heart rate-matched control periods. RESULTS: High-frequency HRV decreased from -60, -20 to -10 min before ischemic events (4.8 +/- 1.3; 4.6 +/- 1.3; 4.4 +/- 1.2 ln [ms(2)], respectively; p = 0.04) and further from -4, -2 min, until ischemia (4.4 +/- 1.3; 4.1 +/- 1.3; 3.7 +/- 1.2 ln [ms(2)]; p's < 0.01). Low frequency HRV decreases started at -4 min (p < 0.05). Ischemic events occurring at high mental activities were preceded by depressed high frequency HRV levels compared with events at low mental activity (p = 0.038 at -4 min, p = 0.045 at -2 min), whereas the effects of mental activities were not observed during nonischemic control periods. Heart rate variability measures remained significantly decreased for 20 min after recovery of ST-segment depression when events were triggered by high activity levels. CONCLUSIONS: Autonomic changes consistent with vagal withdrawal can act as a precipitating factor for daily life ischemia, particularly in episodes triggered by mental activities.

Effects of mental stress on coronary epicardial vasomotion and flow velocity in coronary artery disease: relationship with hemodynamic stress responses.

OBJECTIVES: This study examines the prevalence and hemodynamic determinants of mental stress-induced coronary vasoconstriction in patients undergoing diagnostic coronary angiography. BACKGROUND: Decreased myocardial supply is involved in myocardial ischemia triggered by mental stress, but the determinants of stress-induced coronary constriction and flow velocity responses are not well understood. METHODS: Coronary vasomotion was assessed in 76 patients (average age 59.9 +/- 10.4 years; eight women). Coronary flow velocity responses were assessed in 20 of the 76 patients using intracoronary Doppler flow. Repeated angiograms were obtained after a baseline control period, a 3-min mental arithmetic task and administration of 200 microg intracoronary nitroglycerin. Arterial blood pressure (BP) and heart rate assessments were made throughout the procedure. RESULTS: Mental stress resulted in significant BP and heart rate increases (p < 0.001). Coronary constriction (>0.15 mm) was observed in 11 of 59 patients with coronary artery disease (CAD) (18.6%). Higher mental stress pressor responses were associated with more constriction in diseased segments (rdeltaSBP = -0.26, rdeltaDBP = -0.30, rdeltaMAP = -0.29; p's < 0.05) but not with responses in nonstenotic segments. The overall constriction of diseased segments was not significant (p > 0.10), whereas a small but significant constriction occurred in nonstenotic segments (p = 0.04). Coronary flow velocity increased in patients without CAD (32.2%; p = 0.008), but not in patients with CAD (6.4%; p = ns). Cardiovascular risk factors were not predictive of stress-induced vasomotion in patients with CAD. CONCLUSIONS: Coronary vasoconstriction in angiographically diseased arteries varies with hemodynamic responses to mental arousal. Coronary flow responses are attenuated in CAD patients. Thus, combined increases in cardiac demand and concomitant reduced myocardial blood supply may contribute to myocardial ischemia with mental stress.

Mental stress as a trigger of acute cardiac events: the role of laboratory studies.

Mental stress has long been implicated as a potential trigger of myocardial infarction and sudden cardiac death. This article reviews research conducted in the past two decades utilizing laboratory studies to investigate behaviorally-induced pathophysiological effects (including increased cardiac demand, decreased myocardial supply, and impaired dilation of coronary resistance vessels), in patients with coronary artery disease. The clinical significance of mental stress-induced ischemia is supported by findings of a predictive relationship of mental stress-induced ischemia for ambulatory ischemia and subsequent cardiac events. Mental stress-induced ventricular fibrillation, ventricular tachycardia, and T-wave alternans are also being explored as possible markers of arrhythmic vulnerability in human and animal models. T-wave alternans comparable to exercise can be induced by an anger-like state in an animal model, and with mental stress in patients with implantable cardioverter-defibrillators. Future directions for research on mental stress and cardiac events are suggested, including further studies of mechanisms of mental stress-induced arrhythmia and ischemia, additional studies of the prognostic significance of stress-induced ischemia and T-wave alternans, and use of pharmacological and psychosocial treatments for preventing stress-induced cardiac events.

Frontal electrocortical and cardiovascular reactivity during happiness and anger.

The present study investigated electrocortical and cardiovascular reactivity during positive and negative emotion, and examined the relation of asymmetric frontal lobe activation to cardiovascular responses. Participants were 30 healthy, right-handed university students (mean age, 23.9; 60% female; 76% Caucasian). Electroencephalographic (EEG), blood pressure (BP), and heart rate (HR) responses were assessed while subjects engaged in laboratory tasks (personally-relevant recall tasks and film clips) designed to elicit happiness or anger. Happiness-inducing tasks evoked more prominent left than right frontal EEG activation, and greater left frontal EEG activation than anger-inducing tasks. However, anger-inducing tasks were, on average, associated with comparable left and right frontal EEG activation. Irrespective of emotional valence, cardiovascular activation was more pronounced during personally-relevant recall tasks than during the viewing of film clips. During anger recall, both greater left frontal EEG response (r=-0.46, P<0.02) and greater right frontal EEG response (r=-0.45, P<0.02) were correlated significantly with increased HR reactivity during the task. In addition, a right lateralized frontal EEG response during anger-inducing tasks was associated with greater concomitant systolic BP (P<0.03) and diastolic BP (P<0.008) reactivity. Exploratory analyses also indicated that men who displayed a left lateralized frontal EEG response during happiness-inducing tasks showed the greatest concomitant systolic BP and HR reactivity (P's<0.03). These findings suggest that asymmetric frontal EEG responses to emotional arousal may elicit different patterns of cardiovascular reactivity in healthy adults.

Relationship between left ventricular mass and hemodynamic responses to physical and mental stress.

OBJECTIVE: Increased left ventricular mass (LVM) is predictive of future cardiac morbidity and mortality. Although casual and ambulatory blood pressure (BP) predict LVM, other hemodynamic determinants of LVM are incompletely understood. The present study examines laboratory-induced hemodynamic responses (to exercise, cold, and mental stress) and 24-hour ambulatory measures as predictors of LVM. METHODS: Thirty-six healthy non-hypertensive subjects (mean age 33.9 +/- 9.4 years; 23 women, 13 men) were tested with mental stress, cold pressor, and treadmill exercise in the laboratory and 24-hour ambulatory BP monitoring. LVM was measured using two-dimensional targeted M-mode echocardiography and indexed for body surface area (LVMI). RESULTS: All laboratory tasks produced significant hemodynamic responses (p's < 0.01). Systolic blood pressure responses to mental stress (r = 0.42, p < 0.01) and cold pressor (r = 0.34, p < 0.05) were significantly related to LVM. After adjusting for body size, the mental stress-induced SBP responses was the only significant predictor of LVMI (r = 0.32, p < 0.05). Exercise SBP responses were associated to LVMI in men (r = 0.63, p = 0.02), but not in women (r = 0.02, p = n.s.). Multivariate regression analyses revealed that SBP during mental stress was significantly predictive of LVMI (beta = 0.65, p = 0.05), independent of baseline SBP, 24-hour ambulatory SBP, and other control variables. CONCLUSION: The present results indicate that SBP responses to mental stress are significantly related to LVM among healthy individuals, independently of baseline SBP, 24-hour ambulatory BP, age, body size, and sex. Blood pressure responses to exercise show a robust association with LVM in men but not in women. Hemodynamic responses elicited during laboratory tasks may therefore reveal important information about the pathophysiological processes involved in the development of cardiac end-organ damage.

Psychological Correlates of Mental Stress-induced Ischemia in the Laboratory: The Psychophysiological Investigation of Myocardial Ischemia (PIMI) Study.

Participants consisted of 184 patients (160 males, 24 females) with positive angiograms or prior myocardial infarctions who displayed at least 1 mm of ST segment depression on a standardized treadmill test. Mean scores on the Reward Dependence subscale of the Tridimensional Personality Questionnaire were higher in patients displaying ischemia during mental stress. Patients who reported higher levels of irritability/anger in response to the Speech stressor were also more likely to display ischemia. However, this result was primarily a result of the females in the sample whose ratings of interest and irritability were associated with ischemia during the Speech task. Psychometric measures previously found in prospective studies to predict acute cardiac events were unrelated to mental stress-induced ischemia in the laboratory.

Prognostic value of mental stress testing in coronary artery disease.

This study assesses the prognostic value of mental stress-induced ischemic left ventricular wall motion abnormalities and hemodynamic responses in patients with stable coronary artery disease (CAD). Seventy-nine patients (76 men and 3 women) with prior positive exercise test results were exposed to mental arithmetic and a simulated public speech stress in 2 prior studies. Ischemic wall motion abnormalities were monitored using echocardiography or radionuclide ventriculography (RNV). During mental stress testing, new or worsened ischemic wall motion abnormalities to mental stress and exercise were ascertained, as were peak changes in blood pressure and heart rate to mental stress. The occurrence of subsequent cardiac events (including cardiac death, nonfatal myocardial infarction, or revascularization procedures) was ascertained. New cardiac events were observed in 28 of 79 patients (35%) after a median follow-up duration of 3.5 years (range 2.7 to 7.3). Survival analysis indicated that 20 of 45 patients with mental stress ischemia (44%) experienced new cardiac events more frequently than those without mental stress ischemia (8 of 34; 23%; p = 0.048). Type of cardiac event did not differ between mental stress-positive and stress-negative patients. After controlling for baseline blood pressure and study group status (echocardiography vs RNV), there was a significantly higher relative risk of subsequent events for patients with high versus low peak stress-induced diastolic blood pressure responses (RR = 2.4, confidence interval 1.1 to 5.2; p = 0.03). These results demonstrate that ischemic and hemodynamic measures obtained from mental stress testing may be useful in assessing prognosis in CAD patients with prior positive exercise test results.

Relationship among mental stress-induced ischemia and ischemia during daily life and during exercise: the Psychophysiologic Investigations of Myocardial Ischemia (PIMI) study.

OBJECTIVES: The purposes of this database study were to determine: 1) the relationship between mental stress-induced ischemia and ischemia during daily life and during exercise; 2) whether patients who exhibited daily life ischemia experienced greater hemodynamic and catecholamine responses to mental or physical stress than patients who did not exhibit daily life ischemia, and 3) whether patients who experienced daily life ischemia could be identified on the basis of laboratory-induced ischemia using mental or exercise stress testing. BACKGROUND: The relationships between mental stress-induced ischemia in the laboratory and ischemia during daily life and during exercise are unclear. METHODS: One hundred ninety-six stable patients with documented coronary disease and a positive exercise test underwent mental stress testing and bicycle exercise testing. Radionuclide ventriculography and electrocardiographic (ECG) monitoring were performed during the mental stress and bicycle tests. Patients underwent 48 h of ambulatory ECG monitoring. Hemodynamic and catecholamine responses were obtained during mental stress and bicycle tests. RESULTS: Ischemia (reversible left ventricular dysfunction or ST segment depression > or = 1 mm) developed in 106 of 183 patients (58%) during the mental stress test. There were no significant differences in clinical characteristics of patients with, compared with those without, mental stress-induced ischemia. Patients with mental stress ischemia more often had daily life ischemia than patients without mental stress ischemia, but their exercise tests were similar. Patients with daily life ischemia had higher ejection fraction and cardiac output, and lower systemic vascular resistance during mental stress than patients without daily life ischemia. Blood pressure and catecholamine levels at rest and during the mental stress tests were not different in patients with, compared with those without, daily life ischemia. Patients with daily life ischemia had a higher ejection fraction at rest and at peak bicycle exercise compared with patients without daily life ischemia, but there were no other differences in peak hemodynamic or catecholamine responses to exercise. The presence of ST segment depression during routine daily activities was best predicted by ST segment depression during mental or bicycle exercise stress, although ST segment depression was rare during mental stress. CONCLUSIONS: Patients with daily life ischemia exhibit a heightened generalized response to mental stress. ST segment depression in response to mental or exercise stress is more predictive of ST segment depression during routine daily activities than other laboratory-based ischemic markers. Therapeutic management strategies might therefore focus on patients with these physiologic responses to stress and on whether lessening such responses reduces ischemia.

Cardiovascular stress response and coronary artery disease: evidence of an adverse postmenopausal effect in women.

OBJECTIVES: To test the hypothesis that postmenopausal women demonstrate greater vascular instability, measured by enhanced cardiovascular stress responses during mental stress, compared with men and premenopausal women. BACKGROUND: Recent data suggest that estrogen plays a role in regulating vascular tone. The possible consequences of estrogen deficiency during menopause on systemic vascular reactivity is largely unexplored. METHODS: One hundred subjects (84 men and 16 women) underwent mental stress testing with radionuclide ventriculo graphy. Study subjects included 19 normal volunteers, 23 control subjects with chest pain syndromes or hypertension but without coronary artery disease, and 58 coronary artery disease subjects. The subjects performed a series of three mental stress tasks, during which hemodynamic data and radionuclide ventriculograms were obtained. RESULTS: Overall, women demonstrated greater hemodynamic responses during mental stress measured by changes in heart rate, systolic and diastolic blood pressure, and double product compared with those of men (all p < 0.05). Women with coronary artery disease demonstrated greater heart rate, diastolic blood pressure, and double product stress responses than their male counterparts (all p < 0.05). Women of postmenopausal age demonstrated significantly greater systolic blood pressure reactivity than men or premenopausal women (p < 0.05). CONCLUSIONS: Women of postmenopausal age have greater cardiovascular responses to stress than men or premenopausal women. These findings suggest an additional mechanism by which estrogen deficiency conveys a poor prognosis in female patients with coronary artery disease.

Reproducibility of mental stress-induced myocardial ischemia in the Psychophysiological Investigations of Myocardial Ischemia (PIMI).

OBJECTIVE: Many patients with coronary artery disease (CAD) develop myocardial ischemia in response to mental stress. This has been documented both in the natural environment and in the laboratory. However, the reproducibility of laboratory mental stress-induced ischemia has not been investigated. METHOD: Sixty patients with documented CAD and a positive exercise stress test discontinued cardiac medications and underwent two standardized mental stress tests (a timed Stroop Color-Word test and a public speaking task) in a nuclear cardiology laboratory (Visit 1), and repeated this procedure between 2 and 8 weeks later (Visit 2). Measurements of cardiovascular function and neurohormonal responses were obtained throughout testing, and mood state was assessed before and after testing. RESULTS: Sixty-eight percent of the 56 patients with detailed radionuclide data from both visits had consistent responses (ie, ischemia either present during both sessions or absent during both) to the Stroop task (kappa = .29, p = .03), 61% had consistent responses to the speech task (kappa = .20, p = .12), and 60% had consistent responses when ischemia was considered present if it occurred during either the Stroop test, the speech task, or both, and absent if it did not occur during either task (kappa = .22, p = .07). Hemodynamic and neuroendocrine responses to the tests were moderately reproducible. CONCLUSIONS: We conclude that two popular laboratory tests for mental stress-induced myocardial ischemia are modestly reproducible. The relatively low reproducibility is probably influenced by uncertainties in detecting relatively small changes in wall motion, habituation of the patient to repeated exposure to psychological stressors, and physiological differences in threshold for ischemia on different days of testing.

The Psychophysiological Investigations of Myocardial Ischemia (PIMI) study: objective, methods, and variability of measures.

OBJECTIVE: This study evaluated physiological, neuroendocrine, and psychological status and functioning of patients with coronary artery disease in order to clarify their role in the expression of symptoms during myocardial ischemia (MI), and to establish repeatability of responses to mental stress. Design and methods of the study are presented. METHODS: One hundred ninety-six coronary artery disease patients were examined during physical and mental stress tests in four hospitals. Eligibility criteria included narrowing of at least 50% in the diameter of at least one major coronary artery or verified history of myocardial infarction, and evidence of ischemia on an exercise treadmill test. Psychological, biochemical, and autonomic function data were obtained before, during, and after exposure to mental and exercise stressors during 2 or 3 half-days of testing. Ventricular function was assessed by radionuclide ventriculography, and daily ischemia by ambulatory electrocardiography. Sixty patients returned for a short-term mental stress repeatability study. Twenty-nine individuals presumed to be free of coronary disease were also examined to establish reference values for cardiac responses to mental stress. RESULTS: Study participants were 41 to 80 years of age; 83 (42%) had a history of MI, 6 (3%) of congestive heart failure, and 163 (83%) of chest pain; 170 (87%) were men; and 90 (46%) had ischemia accompanied by angina during exercise treadmill testing. Ischemia during ambulatory monitoring was found in 35 of 90 (39%) patients with and 48 of 106 (45%) patients without angina during exercise-provoked ischemia. Intraobserver variability of ejection fraction changes during bicycle exercise and two mental stress tests (Speech and Stroop) was good (kappa = 1.0, .90, and .76, respectively; percent agreement = 100, 97.5, and 93.8%, respectively). Variability of assessed wall motion abnormalities during bicycle exercise was better (kappa, agreement = 85%) than during Speech or Stroop kappa and .57, percent agreement = 70% and 82.5%, respectively). CONCLUSIONS: Study design, quality control data, and baseline characteristics of patients enrolled for a clinical study of symptomatic and asymptomatic myocardial ischemia are described. Lower repeatability of reading wall motion abnormalities during mental stress than during exercise may be due to smaller effects on wall motion and lack of an indicator for peak mental stress.

Stress management and exercise training in cardiac patients with myocardial ischemia. Effects on prognosis and evaluation of mechanisms.

BACKGROUND: Previous studies have demonstrated that myocardial ischemia can be elicited by mental stress in the laboratory and during daily life and that ischemia induced by mental stress is associated with an increased risk for future cardiac events in patients with coronary artery disease. OBJECTIVES: To examine the extent to which ischemia induced by mental stress can be modified by exercise stress management, and to evaluate the impact of these interventions on clinical outcomes. METHODS: One hundred seven patients with coronary artery disease and ischemia documented during mental stress testing or ambulatory electrocardiographic monitoring were randomly assigned to a 4-month program of exercise or stress management training. Patients living at a distance from the facility formed a nonrandom, usual care comparison group. Myocardial ischemia was reassessed following treatment, and patients were contacted annually for as long as 5 years to document cardiac events, including death, nonfatal myocardial infarction, and cardiac revascularization procedures. RESULTS: Twenty-two patients (21%) experienced at least 1 cardiac event during a mean (+/- SD) follow-up period of 38 +/- 17 months. Stress management was associated with a relative risk of 0.26 compared with controls. The relative risk for the exercise group also was lower than that of controls, but the effect did not reach statistical significance. Stress management also was associated with reduced ischemia induced by mental stress and ambulatory ischemia. CONCLUSION: These data suggest that behavioral interventions offer additional benefit over and above usual medical care in cardiac patients with evidence of myocardial ischemia.

Effects of mental stress on myocardial ischemia during daily life.

OBJECTIVE: To determine the relative risk of myocardial ischemia triggered by specific emotions during daily life. DESIGN AND SETTING: Relative risk was calculated by the recently developed case-crossover method, in which the frequency of a presumed trigger during nonischemic, or control, hours is compared with the trigger's frequency during ischemic, or case, hours. Outpatients at Duke University Medical Center, Durham, NC, underwent 48 hours of ambulatory electrocardiographic (ECG) monitoring with concurrent self-report measures of activities and emotions. Occurrences of negative emotions in the hour before the onset of myocardial ischemia were compared with their usual frequency based on all hours in which ischemia did not occur. SUBJECTS: From a sample of 132 patients with coronary artery disease and recent evidence of exercise-induced ischemia who underwent 48 hours of ambulatory ECG monitoring, 58 patients exhibited ambulatory ischemia and were included in the analysis. OUTCOME MEASURES: Myocardial ischemia during 48-hour ECG monitoring was defined as horizontal or downsloping ST-segment depression of 1 mm (0.1 mV) or more for 1 minute or longer compared with resting baseline. The ECG data were cross-tabulated with subjects' concurrent diary ratings of 3 negative emotions-tension, sadness, and frustration-and 2 positive emotions-happiness and feeling in contro-on a 5-point scale of intensity. RESULTS: The unadjusted relative risk of occurrence of myocardial ischemia in the hour following high levels of negative emotions was 3.0 (95% confidence interval [CI], 1.5-5.9; P<.01) for tension, 2.9 (95% CI, 1.0-8.0; P<.05) for sadness, and 2.6 (95% CI, 1.3-5.1; P<.01) for frustration. The corresponding risk ratios adjusted for physical activity and time of day were 2.2 (95% CI, 1.1 -4.5; P<.05) for tension, 2.2 (95% CI, 0.7-6.4; P=.16) for sadness, and 2.2 (95% CI, 1.1-4.3; P<.05) for frustration. CONCLUSIONS: Mental stress during daily life, including reported feelings of tension, frustration, and sadness, can more than double the risk of myocardial ischemia in the subsequent hour. The clinical significance of mental stress-induced ischemia during daily life needs to be further evaluated.

Ischemic, hemodynamic, and neurohormonal responses to mental and exercise stress. Experience from the Psychophysiological Investigations of Myocardial Ischemia Study (PIMI).

BACKGROUND: The pathophysiology of mental stress-induced myocardial ischemia, which occurs at lower heart rates than during physical stress, is not well understood. METHODS AND RESULTS: The Psychophysiological Investigations of Myocardial Ischemia Study (PIMI) evaluated the physiological and neuroendocrine functioning in unmedicated patients with stable coronary artery disease and exercise-induced ischemia. Hemodynamic and neurohormonal responses to bicycle exercise, public speaking, and the Stroop test were measured by radionuclide ventriculography, ECG, and blood pressure and catecholamine monitoring. With mental stress, there were increases in heart rate, systolic blood pressure, cardiac output, and systemic vascular resistance that were correlated with increases in plasma epinephrine. During exercise, systemic vascular resistance fell, and there was no relationship between the hemodynamic changes and epinephrine levels. The fall in ejection fraction was greater with mental stress than exercise. During mental stress, the changes in ejection fraction were inversely correlated with the changes in systemic vascular resistance. Evidence for myocardial ischemia was present in 92% of patients during bicycle exercise and in 58% of patients during mental stress. Greater increases in plasma epinephrine and norepinephrine occurred with ischemia during exercise, and greater increases in systemic vascular resistance occurred with ischemia during mental stress. CONCLUSIONS: Mental stress-induced myocardial ischemia is associated with a significant increase in systemic vascular resistance and a relatively minor increase in heart rate and rate-pressure product compared with ischemia induced by exercise. These hemodynamic responses to mental stress can be mediated by the adrenal secretion of epinephrine. The pathophysiological mechanism involved are important in the understanding of the etiology of myocardial ischemia and perhaps in the selection of appropriate anti-ischemic therapy.

Heart rate variability reproducibility and stability using commercially available equipment in coronary artery disease with daily life myocardial ischemia.

Heart rate variability (HRV) appears to be a strong predictor of death. The reproducibility of HRV measurements in patients with stable coronary artery disease (CAD) who have daily life myocardial ischemia, however, is unknown. Thirty patients with stable CAD (25 men and 5 women; aged 62 +/- 8 years) with daily life ischemia were studied with 2 consecutive 24-hour Holter monitoring recordings. Intra- and interobserver reproducibility of the HRV measures was high, with correlations ranging from 0.990 to 0.999 (p < 0.0001). Strong correlations between time and frequency domain HRV measures were observed (range 0.912 to 0.963; p < 0.0001). Both the frequency and duration of ischemia, measured by ST change, varied significantly by day for each patient (s = 155.5; p < 0.0001; s = 232.5, p < 0.0001, respectively). Correlations for HRV measurements between days remained high (range 0.871 to 0.983; p < 0.0001), despite stratification by magnitude of daily ischemia. Thus, 24-hour HRV measurements are stable in CAD patients with daily life myocardial ischemia over a short period, despite varying magnitudes of daily ischemia. These results support the use of HRV as a clinical tool and an outcome measure in future CAD intervention studies using commercially available equipment.

Defensive hostility, gender and cardiovascular levels and responses to stress.

Prior studies have demonstrated inconsistent relationships between the trait of hostility and cardiovascular responses to stress. To examine the hypothesis that only a subset of hostile subjects demonstrates greater cardiovascular responses to stress, we assessed relationships among hostility, defensiveness, and cardiovascular responses to stress in 33 healthy men and 34 healthy women. Stressors used were math and speech tasks. Median splits on Cook-medley Hostility Inventory (Ho) and defensiveness [Marlowe-Crowne Social Desirability scale (MC)] classified subjects into four groups: (a) Defensive Hostile (DH--high Ho and MC), (b) Low Hostile (LH--low Ho and MC), (c) High Hostile (HH--high Ho, low MC), and (d) Defensive (Def--low Ho, high MC). Results indicate that Defensive Hostility is differentially related to cardiovascular levels in men and women. DH men exhibited greater systolic blood pressure (SBP) levels than LH, Def, and HH men. Analyses of diastolic blood pressures (DBPs) suggested a trend that LH and DH men demonstrated greater DBP levels than Def and HH men. In contrast, DH women were indistinguishable from HH and Def women with respect to blood pressure, and LH women demonstrated the lowest SBP and DBP levels. There were no personality differences in cardiovascular change scores to stress. Gender differences for affect were observed which may mediate the cardiovascular responses. These data suggest that the personality trait of Defensive Hostility may provide significant associations with blood pressure levels and coronary disease associations with blood pressure levels and coronary disease in studies that do not find associations using hostility alone.