Men deny and women cry, but who dies? Do the wages of "denial" include early ischemic coronary heart disease?

OBJECTIVES: In this study patients with documented ischemic coronary heart disease (ICHD; prior MI or CAD per catheterization) were tested for the association of various measures of emotional distress with Age at Initial Diagnosis. METHODS: The measures were chosen because of a published track record at predicting mortality in this population. Females were oversampled to achieve equivalent numbers of each sex (n=50), and thus equivalent statistical power. In a subset of patients (38 males and 32 females), Spouse/Friend Ketterer Stress Symptom Frequency Checklists (KSSFCs) were received. RESULTS: Females reported more depression and anxiety than males. However, spouses or friends reported more anger for males. Denial (spouse/friend minus self-ratings) was greater in males for all three scales of the KSSFC (Anger, P=.005; Depression, P=.024; Anxiety, P=.001). Although females showed the same trend, self and spouse or friend ratings of distress were significantly associated with Age at Initial Diagnosis only in males. When split at the sample mean on the Spouse/Friend KSSFC AIAI (Anger) scale, Age at Initial Diagnosis occurred 14.2 years earlier in males. CONCLUSIONS: Use of a significant other in assessing psychosocial/emotional distress in males may confer greater accuracy, and therefore predictive power for clinical endpoints.

Sex differences in chest pain in patients with documented coronary artery disease and exercise-induced ischemia: Results from the PIMI study.

BACKGROUND: Sex differences in the pathophysiologic course of coronary artery disease (CAD) are widely recognized, yet accurate diagnosis of coronary artery disease in women remains challenging. METHODS: To determine sex differences in the clinical manifestation of CAD, we studied chest pain reported during daily activities, exercise, and mental stress in 170 men and 26 women. All patients had documented CAD (>50% narrowing in at least 1 major coronary artery or prior myocardial infarction) and all had 1-mm ST-segment depression on treadmill exercise. We collected psychologic test results, serum samples (potassium, epinephrine, norepinephrine, cortisol, b-endorphin, and glucose), and cardiac function, sensory threshold, and autonomic function data at specified times before, during, or after exercise and mental stress tests to assess measures of depression, anxiety, and neurohormonal and thermal pain perception. RESULTS: Women reported chest pain more often than men during daily activities (P =.04) and during laboratory mental stressors (P =.01) but not during exercise. Men had lower scores than women on measures of depression, trait anxiety, harm avoidance, and reward dependence (P <.05 for all). Women had significantly lower plasma b-endorphin levels at rest (4.2 +/- 3.9 vs 5.0 +/- 2.5 pmol/L for men, P =.005) and at maximal mental stress (6.4 +/- 5.1 vs 7.4 +/- 3.5 pmol/L for men, P <.01). A higher proportion of women than men had marked pain sensitivity to graded heat stimuli applied to skin (hot pain threshold <41 degrees C, 33% vs 10%, P =.001). CONCLUSIONS: Our results reflect sex differences in the affective and discriminative aspects of pain perception and may help explain sex-related differences in clinical presentations.

Chest pain and the treatment of psychosocial/emotional distress in CAD patients.

Treatment of psychosocial/emotional distress as a strategy for diminishing chest pain in such patients remains entirely unutilized in standard care. Sixty-three patients with known or suspected CAD were entered in an aggressive lifestyle modification program. Patients completed the Symptom Checklist 90-Revised (SCL90R) at the diagnostic interview session, at 3 and at 12 months. Statistically significant drops were observed on multiple scales of the SCL90R at both 3 and 12 months. An item from the SCL90R was used as a proxy for angina. Multiple measures of emotional distress at baseline were found to correlate with chest pain at baseline, but not a number of traditional cardiovascular risk factors. The chest pain item displayed improvement at both 3 and 12 months. Improvement on all scales of the SCL90R correlated with improvement in chest pain. It may be possible to control chest pain in some CAD patients with psychosocial interventions.

Psychological factors affecting a medical condition: ischemic coronary heart disease.

The criteria for scientific validation of the entities currently subsumed under the DSM-IV category of "Psychological Factors Affecting a Medical Condition" have never been clearly enumerated. Historically, its precursor category ("Psychophysiological Disorder") was rarely used, and predicated upon clinical observation of personality styles among patients with specific physical illnesses, or clinical observations relating psychosocial events and symptom exacerbation. Because of logical flaws with either of these methods, clarification of the most rigorous criteria for demonstrating a cause-effect relationship is necessary. With the increase in well-designed and carefully executed epidemiological and treatment studies, this diagnostic category has evolved into an arena where cutting-edge insights and therapies are becoming available for a growing variety of medical conditions, especially ischemic coronary heart disease. The present article reviews the nature of the scientific evidence necessary to accept an etiological or aggravating role for psychological events.

Psychosocial and traditional risk factors in early ischaemic heart disease: cross-sectional correlates.

BACKGROUND: Psychosocial/emotional distress has been repeatedly found to be a correlate of the onset/aggravation of ischaemic heart disease. METHODS: Eighty-three patients (63 men and 20 women) with known coronary artery disease who entered an aggressive lifestyle modification programme were administered a clinical/demographic history and the Symptom Checklist 90--Revised at baseline. Several measures of social isolation/alienation (shyness/self-consciousness, feeling lonely, feeling abused and overall) were derived from the the Symptom Checklist 90--Revised. RESULTS: Univariate tests of the association of known cardiovascular risk factors and the Symptom Checklist 90--Revised scales with age at initial diagnosis yielded several significant results for history of hypercholesterolaemia (P = 0.018), history of hypertension (P = 0.030), somatization (P = 0.007), obsessive-compulsive (P = 0.009), depression (P = 0.006), anxiety (P = 0.021), hostility (P = 0.003), paranoia (P = 0.050), psychoticism (P = 0.029), the Global Severity Index (P = 0.007), the Positive Symptom Distress Index (P = 0.005), the Positive Symptom Total Score (P = 0.003) and feeling abused (P = 0.037). Only history of hypertension, history of hypercholesterolaemia and the hostility scale (overall F = 6.08 and P = 0.0009) emerged as unique correlates of age at initial diagnosis in a multiple regression using only the significant univariate predictors. CONCLUSIONS: Psychosocial factors are sufficiently confounded with one another that they lose their predictive value once one is entered in the equation. High scores on the hostility scale were associated with a 5.7 year differential in age at initial diagnosis. The younger a patient is at initial diagnosis, the more likely he/she is to have high levels of emotional distress.

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.

Cognitive/behavioral therapy of anxiety in the medically ill: cardiac settings.

Anxiety appears to be a strong risk factor for ischemic heart disease (IHD) and specifically fatal IHD. However, no randomly assigned, controlled, clinical trial targeting anxiety yet exists demonstrating an impact on objective cardiac outcomes. Situational anxiety is frequent in cardiac populations and can diminish quality-of-life by increasing symptoms/disability and result in unnecessary medical system utilization. "Noncardiac" chest pain is common both in patients with objective coronary disease and in patients whose cardiac workup is negative. Both presentations of chest pain respond to cognitive/behavioral therapy, and imipramine has been found to be effective for chest pain unaccompanied by coronary disease. Because anxiety-like symptoms overlap with symptoms of IHD (eg, chest pain, dyspnea, dizziness, palpitations) and can be caused by organic factors, the diagnosis and treatment of anxiety in these populations require special considerations.

Five-year follow-up for adverse outcomes in males with at least minimally positive angiograms: importance of "denial" in assessing psychosocial risk factors.

The purpose of this study was to test the role of "denial" (spouse/friend minus self-ratings on parallel versions of the same questionnaire) in diluting the predictive value of emotional distress for cardiac events (deaths, new MIs, and/or revascularizations). One hundred forty-four men with no history of prior revascularization who had at least minimally positive diagnostic coronary angiograms, and someone they selected as "someone who knows you well," completed parallel versions of the Ketterer Stress Symptom Frequency Checklist (KSSFC). They were followed up by phone an average of 59.7 months after recruitment. Length of follow-up, baseline cardiac risk factors, and a number of baseline-obtained psychosocial risk factors were tested as prospective predictors of combined events (death by any cause, new MIs, and/or revascularizations) and current anginal frequency. Only spouse/friend observed anxiety on the KSSFC predicted current anginal frequency (p = 0.001). On the self-report version of the KSSFC, patients with one or more events reported less anger (p = 0.031), depression (p = 0.008), and anxiety (p = 0.003). These results may be attributable to "denial" because there were no differences in spouse/friend ratings, and difference scores (spouse/friend minus patient) on the KSSFC scales, particularly anger, were also related to events: AIAI (p = 0.002); depression (p = 0.063); and anxiety (p = 0.010). Denial may be a major limiting factor in accurately assessing emotional distress in cardiac populations, and may help account for a number of the previous findings.

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.

Psychosocial factors related to noncardiac chest pain during treadmill exercise.

The authors examined historical, concurrent, and potentially secondary psychosocial problems related to noncardiac chest pain during exercise. The patients reporting chest pain during treadmill testing but who lacked cardiac ischemia (determined via nuclear scanning) were compared with the patients having both ischemia and chest pain, and with patients having neither ischemia nor chest pain. The noncardiac chest pain patients had the highest levels of 1) parental divorce and personal psychiatric treatment; 2) current depression, somatic awareness, and anger control; and 3) negative attitudes toward the health care system. The findings suggest that psychosocial problems predate, coexist with, and may result from noncardiac chest pain.

Correlates of unrecognized acute myocardial infarction detected via perfusion imaging.

Research using the electrocardiogram (ECG) indicates that about 1/3 of acute myocardial infarctions (AMIs) are unrecognized. To date, no studies of unrecognized AMIs have employed perfusion imaging, although it is more sensitive than the ECG and provides more information about infarct characteristics, such as size and location. In this study, 82 of 258 consecutive patients (31.8%) undergoing exercise testing with technetium-99m sestamibi perfusion imaging had fixed, nonartifactual perfusion defects, suggesting AMI. These patients were interviewed regarding their recognition of AMI; 27 patients (32.9%) had unrecognized AMI. Unrecognized AMI was significantly associated with (1) smaller infarcts, (2) infarcts not in the apical or septal regions, (3) diabetes mellitus, (4) lack of angina, (5) a negative family history for cardiac disease, and (6) being African-American. Many of these variables were significantly intercorrelated, and in multivariate analysis, unrecognized AMI remained significantly predicted by a smaller infarct and lack of angina. This study suggests that the incidence of unrecognized AMI detected via perfusion imaging on a clinic population is similar to that detected via electrocardiographic studies on community samples. This study also replicates prior findings of the medical history and demographic correlates of unrecognized AMI, and indicates that infarct size and location are also associated with unrecognized AMI.

Silent versus symptomatic myocardial ischemia: the role of psychological and medical factors.

This study examined the relationship of psychological, cardiac, and general medical history factors to asymptomatic (silent) versus symptomatic myocardial ischemia among 102 patients who underwent treadmill exercise testing and had perfusion imaging indicative of ischemia. During exercise, 68 patients exhibited silent ischemia, and 34 experienced chest pain. Patients with silent ischemia rated higher than symptomatic patients on anger control, externally oriented thinking, and somatosensory amplification, but did not differ on depression or global alexithymia. Anger control and externally oriented thinking remained independent correlates in multivariate analysis, controlling for demographic and cardiac factors. Groups did not differ on general medical or cardiac variables. Thus, this study suggests that affective and cognitive factors, but not biomedical factors, are associated with silent, as opposed to symptomatic, ischemia during exercise testing.

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.

Emotional distress among males with "syndrome X".

The present study examined traditional risk factors and various indices of emotional distress in males with positive angiograms (N = 122), "syndrome X" males with negative or nominal results on angiogram (N = 53), and age- and socioeconomic status-matched males with no manifest history of otherosclerotic disease (N = 56). Syndrome X patients reported more depression on the Ketterer Stress Symptom Frequency Checklist (KSSFC) than positive angiographic patients. And compared with healthy controls, they were more likely to be perceived by a spouse/friend as depressed and anxious on the KSSFC, scored higher on the Framingham Type A Scale, and reported more unprovoked nocturnal awakening. Syndrome X patients generally appear to be similar to patients with positive angiograms with regard to traditional risk factor history but are more distressed than healthy controls. This becomes most evident when denial is circumvented by discussion with significant others or inquiries are "framed" appropriately.

Is aspirin, as used for antithrombosis, an emotion-modulating agent?

Antiplatelet substances, generally aspirin, have become widely used for secondary prevention of ischemic heart disease. Used in relatively small doses, it is generally assumed that aspirin has no psychoactive effect. The present study took advantage of a sample of 174 males undergoing coronary angiography to see if regular aspirin use as prophylactic therapy for ischemic heart disease was associated with one or more of a number of measures of emotional distress. Aspirin use was found to be associated with less depression and anxiety or worry, as reported by the patient and as perceived by a significant other. Despite a significant association of aspirin use with the presence of documented coronary artery disease, the association of aspirin use and diminished distress could not be accounted for by the previously observed high prevalence of depressed/anxious individuals among patients with negative or nominal results on angiography, or by a number of other demographic or clinical variables such as age and socioeconomic status. Although only correlational in nature, present results raise the question of whether aspirin may have a beneficial mood-modulating effect.

Denial of depression as an independent correlate of coronary artery disease.

A number of psychosocial measures were tested as correlates of coronary artery disease (CAD) in 122 males with positive coronary angiograms and 56 males with no manifest history of atherosclerotic disease who were selected to approximate the patients' age and socio economic status. Only denial of depression as indexed by spouse/friend-minus-self scores on the Ketterer Stress Symptom Frequency Checklist and number of unprovoked nocturnal awakenings were independently and positively related to CAD severity in multivariate regression analyses which controlled for jointly associated cardiac risk factors and commonly used cardiovascular medications. Denial of depression and unprovoked nocturnal awakening appear to be independent correlates of coronary artery disease.