Mental Stress-induced Ischemia Research Articles

Association Between Symptoms of Chronic Psychological Distress and Myocardial Ischemia Induced by Mental Stress in Patients With Coronary Artery Disease.

Background Mental stress-induced myocardial ischemia is a frequent phenomenon in patients with coronary artery disease and is associated with a greater risk of future cardiovascular events. The association between chronic symptoms of psychological distress and mental stress-induced ischemia is not clear. Methods and Results We used a composite score of psychological distress derived from symptoms of depression, posttraumatic stress disorder, anxiety, anger, and perceived general stress. Participants underwent myocardial perfusion imaging with both mental (public speaking task) and conventional (exercise or pharmacological) stress testing. Overall, 142 (15.9%) patients experienced mental stress-induced myocardial ischemia. After adjusting for demographic factors, medical history, and medication use, patients in the highest tertile of psychological distress score had 35% higher odds of having mental stress-induced ischemia compared to those in the lowest tertile (odds ratio [OR], 1.35 [95% CI, 1.06-2.22]). Stratified analyses showed that the association between psychological distress score and mental stress-induced myocardial ischemia was significantly associated only within the subgroup of patients with a prior myocardial infraction, with patients with a prior myocardial infarction in the highest tertile having a 93% higher odds of developing myocardial ischemia with mental stress (95% CI, 1.07-3.60). There was no significant association between psychological distress and conventional stress-induced ischemia (OR, 1.19 [95% CI, 0.87-1.63]). Conclusions Among patients with a history of myocardial infarction, a higher level of psychosocial distress is associated with mental stress-induced myocardial ischemia but not with ischemia induced by a conventional stress test.

A Pilot Study of Neurobiological Mechanisms of Stress and Cardiovascular Risk.

Coronary heart disease is a leading cause of death and disability. Although psychological stress has been identified as an important potential contributor, mechanisms by which stress increases risk of heart disease and mortality are not fully understood. The purpose of this study was to assess mechanisms by which stress acts through the brain and heart to confer increased CHD risk. Coronary Heart Disease patients (N=10) underwent cardiac imaging with [Tc-99m] sestamibi single photon emission tomography at rest and during a public speaking mental stress task. Patients returned for a second day and underwent positron emission tomography imaging of the brain, heart, bone marrow, aorta (indicating inflammation) and subcutaneous adipose tissue, after injection of [18F]2-fluoro-2-deoxyglucose for assessment of glucose uptake followed mental stress. Patients with (N=4) and without (N=6) mental stress-induced myocardial ischemia were compared for glucose uptake in brain, heart, adipose tissue and aorta with mental stress. Patients with mental stress-induced ischemia showed a pattern of increased uptake in the heart, medial prefrontal cortex, and adipose tissue with stress. In the heart disease group as a whole, activity increase with stress in the medial prefrontal brain and amygdala correlated with stress-induced increases in spleen (r=0.69, p=0.038; and r=0.69, p=0.04 respectfully). Stress-induced frontal lobe increased uptake correlated with stress-induced aorta uptake (r=0.71, p=0.016). Activity in insula and medial prefrontal cortex was correlated with post-stress activity in bone marrow and adipose tissue. Activity in other brain areas not implicated in stress did not show similar correlations. Increases in medial prefrontal activity with stress correlated with increased cardiac glucose uptake with stress, suggestive of myocardial ischemia (r=0.85, p=0.004). These findings suggest a link between brain response to stress in key areas mediating emotion and peripheral organs involved in inflammation and hematopoietic activity, as well as myocardial ischemia, in Coronary Heart Disease patients.

Association of Mental Stress–Induced Myocardial Ischemia With Cardiovascular Events in Patients With Coronary Heart Disease

Mental stress-induced myocardial ischemia is a recognized phenomenon in patients with coronary heart disease (CHD), but its clinical significance in the contemporary clinical era has not been investigated. To compare the association of mental stress-induced or conventional stress-induced ischemia with adverse cardiovascular events in patients with CHD. Pooled analysis of 2 prospective cohort studies of patients with stable CHD from a university-based hospital network in Atlanta, Georgia: the Mental Stress Ischemia Prognosis Study (MIPS) and the Myocardial Infarction and Mental Stress Study 2 (MIMS2). Participants were enrolled between June 2011 and March 2016 (last follow-up, February 2020). Provocation of myocardial ischemia with a standardized mental stress test (public speaking task) and with a conventional (exercise or pharmacological) stress test, using single-photon emission computed tomography. The primary outcome was a composite of cardiovascular death or first or recurrent nonfatal myocardial infarction. The secondary end point additionally included hospitalizations for heart failure. Of the 918 patients in the total sample pool (mean age, 60 years; 34% women), 618 participated in MIPS and 300 in MIMS2. Of those, 147 patients (16%) had mental stress-induced ischemia, 281 (31%) conventional stress ischemia, and 96 (10%) had both. Over a 5-year median follow-up, the primary end point occurred in 156 participants. The pooled event rate was 6.9 per 100 patient-years among patients with and 2.6 per 100 patient-years among patients without mental stress-induced ischemia. The multivariable adjusted hazard ratio (HR) for patients with vs those without mental stress-induced ischemia was 2.5 (95% CI, 1.8-3.5). Compared with patients with no ischemia (event rate, 2.3 per 100 patient-years), patients with mental stress-induced ischemia alone had a significantly increased risk (event rate, 4.8 per 100 patient-years; HR, 2.0; 95% CI, 1.1-3.7) as did patients with both mental stress ischemia and conventional stress ischemia (event rate, 8.1 per 100 patient-years; HR, 3.8; 95% CI, 2.6-5.6). Patients with conventional stress ischemia alone did not have a significantly increased risk (event rate, 3.1 per 100 patient-years; HR, 1.4; 95% CI, 0.9-2.1). Patients with both mental stress ischemia and conventional stress ischemia had an elevated risk compared with patients with conventional stress ischemia alone (HR, 2.7; 95% CI, 1.7-4.3). The secondary end point occurred in 319 participants. The event rate was 12.6 per 100 patient-years for patients with and 5.6 per 100 patient-years for patients without mental stress-induced ischemia (adjusted HR, 2.0; 95% CI, 1.5-2.5). Among patients with stable coronary heart disease, the presence of mental stress-induced ischemia, compared with no mental stress-induced ischemia, was significantly associated with an increased risk of cardiovascular death or nonfatal myocardial infarction. Although these findings may provide insights into mechanisms of myocardial ischemia, further research is needed to assess whether testing for mental stress-induced ischemia has clinical value.

Association Between Mental Stress-Induced Inferior Frontal Cortex Activation and Angina in Coronary Artery Disease.

The inferior frontal lobe is an important area of the brain involved in the stress response, and higher activation with acute mental stress may indicate a more severe stress reaction. However, it is unclear if activation of this region with stress correlates with angina in individuals with coronary artery disease. Individuals with stable coronary artery disease underwent acute mental stress testing using a series of standardized speech/arithmetic stressors in conjunction with high resolution positron emission tomography imaging of the brain. Blood flow to the inferior frontal lobe was evaluated as a ratio compared with whole brain flow for each scan. Angina was assessed with the Seattle Angina Questionnaire's angina frequency subscale at baseline and 2 years follow-up. We analyzed 148 individuals with coronary artery disease (mean age [SD] 62 [8] years; 69% male, and 35.8% Black). For every doubling in the inferior frontal lobe activation, angina frequency was increased by 13.7 units at baseline ([Formula: see text], 13.7 [95% CI, 6.3-21.7]; P=0.008) and 11.6 units during follow-up ([Formula: see text], 11.6 [95% CI, 4.1-19.2]; P=0.01) in a model adjusted for baseline demographics. Mental stress-induced ischemia and activation of other brain pain processing regions (thalamus, insula, and amygdala) accounted for 40.0% and 13.1% of the total effect of inferior frontal lobe activation on angina severity, respectively. Inferior frontal lobe activation with mental stress is independently associated with angina at baseline and during follow-up. Mental stress-induced ischemia and other pain processing brain regions may play a contributory role.

Abnormal P-wave axis and myocardial ischemia development during mental stress

Exposure to psychological stress has been associated with the development of sustained arrhythmias. Acute changes in atrial electrophysiology may serve as intermediate phenotypes for stress-induced atrial arrhythmia such as atrial fibrillation. We examined if acute mental stress was associated with the development of abnormal P-wave axis (aPWA) and the role played by stress-induced myocardial ischemia. A total of 359 patients (mean age = 56 ± 9.9 years; 62% men; 43% white) with stable coronary heart disease and normal baseline P-wave axis (between 0° and 75°) were studied. All patients underwent mental stress testing (speech task). A total of 46 (13%) patients developed abnormal P-wave axis during either stress or recovery (stress: n = 43, 12%; recovery: n = 12, 3%). A rise in heart rate during mental stress was associated with an increased risk of an abnormal P-wave axis (per 5-unit increase: OR = 1.37, 95%CI = 1.03, 1.30). Myocardial ischemia induced by mental stress was associated with an increased risk of aPWA in women (OR = 5.2, 95%CI = 1.7, 15.6) and not in men (OR = 0.1, 95%CI = 0.01, 1.01), p-interaction = 0.004). In conclusion, in a sizable proportion of patients, acute mental stress results in the development of an abnormal P-wave axis, and this phenomenon is related to increases in heart rate and, among women, mental stress-induced ischemia. Our data suggest that acute psychological stress can promote adverse transient electrical changes in the atria that may predispose to AF.

Abstract MP59: The Association Between Acute Mental Stress and Abnormal P-wave Axis

Background: Exposure to psychological stress has been associated with the development of sustained arrhythmias. Acute changes in atrial electrophysiology may serve as intermediate phenotypes for stress-induced arrhythmia. The relationship between atrial electrical changes and stress related changes in heart rate and myocardial ischemia is unknown. We sought to study the effect of altered atrial electrophysiology and stress related rise in HR and myocardial ischemia in females and males. Methods: We examined if acute mental stress was associated with abnormal P-wave axis development in 359 patients (mean age=56 ± 9.9 years; 62% men; 43% white) with stable coronary heart disease and normal baseline P-wave axis (between 0° and 75°) who underwent mental stress testing (speech task). We computed the percentage of patients who had abnormal P-wave axis during stress and recovery. Sex-stratified analyses were performed. A multivariable logistic regression model was used to determine if mental stress ischemia independent predictors of abnormal P-wave axis development. Results: A total of 46 (13%) patients developed abnormal P-wave axis during either stress or recovery (stress: n=43, 12%; recovery: n=12, 3%). A rise in heart rate during mental stress was associated with an increased risk of abnormal P-wave axis development (per 5-unit increase: OR=1.37, 95%CI=1.03, 1.30). Mental stress-induced myocardial ischemia was associated with increased risk of abnormal P-wave axis in women (OR=5.2, 95%CI=1.7, 15.6) and not in men (OR=0.1, 95%CI=0.01, 1.01), p-interaction=0.004). Interactions were not detected for other characteristics. Conclusion: Acute mental stress results in the development of abnormal P-wave axis, and this phenomenon is related to increases in heart rate and, among women, mental stress-induced ischemia. Our data suggest that acute psychological stress can promote adverse transient electrical changes in the atria.

Abstract 21148: Stress-Induced Cardiac Repolarization Changes Are Associated With Mental Stress-Induced Mycoardial Ischemia

Introduction: Mental Stress-Induced Myocardial Ischemia (MSIMI) can occur in patients with coronary artery disease (CAD) during acute mental stress challenge and is associated with an increased risk of adverse cardiovascular events. Adverse dynamic changes in repolarization with stress may also be particularly important when assessing risk of MSIMI. Hypothesis: In subjects with CAD, dynamic ECG repolarization changes during stress and recovery are associated with MSIMI. Methods: We studied 419 individuals with CAD who underwent mental stress challenge via a standardized speech stressor. Digital 12-lead ECGs were collected at baseline during resting , 1 minute after speech started, immediately after speech, and during recovery (5 minutes after speech ended). Repolarization metrics, including QRS-T angle, T-axis, ST depression, and T wave area were quantified in all 12 leads. Heart rate was also included. Subjects with baseline artifact were excluded. Changes amongst baseline, stress, and recovery were analyzed. Forward selection with alpha=0.01 was used to help guide the final model. MSIMI was assessed via Tc99m myocardial perfusion imaging (read by experienced clinicians). Results: The mean (SD) age was 56 (10), 38% were women, and 17% had MSIMI. The most significant predictors of MSIMI, based on the multivariate model, are summarized in the table. The C-statistic was 0.73, but reduced to 0.71 after leave-one-out cross validation. Goodness of fit was adequate. No significant race or gender differences were noted. Conclusion: Baseline and dynamic ECG repolarization changes in recovery (but not peak stress) contribute to MSIMI classification, and may be useful for risk stratification of arrhythmia risk due to emotional triggers. While the mechanisms regarding the relationship of MSIMI and ECG metrics during recovery are unknown, they could be due to hysteresis phenomena and/or known autonomic changes during recovery from stress.

The human coronary vasodilatory response to acute mental stress is mediated by neuronal nitric oxide synthase.

Mental stress-induced ischemia approximately doubles the risk of cardiac events in patients with coronary artery disease, yet the mechanisms underlying changes in coronary blood flow in response to mental stress are poorly characterized. Neuronal nitric oxide synthase (nNOS) regulates basal coronary blood flow in healthy humans and mediates mental stress-induced vasodilation in the forearm. However, its possible role in mental stress-induced increases in coronary blood flow is unknown. We studied 11 patients (6 men and 5 women, mean age: 58 ± 14 yr) undergoing elective diagnostic cardiac catheterization and assessed the vasodilator response to mental stress elicited by the Stroop color-word test. Intracoronary substance P (20 pmol/min) and isosorbide dinitrate (1 mg) were used to assess endothelium-dependent and -independent vasodilation, respectively. Coronary blood flow was estimated using intracoronary Doppler recordings and quantitative coronary angiography to measure coronary artery diameter. Mental stress increased coronary flow by 34 ± 7.0% over the preceding baseline during saline infusion (P < 0.01), and this was reduced to 26 ± 7.0% in the presence of the selective nNOS inhibitor S-methyl-l-thiocitrulline (0.625 µmol/min, P < 0.001). Mental stress increased coronary artery diameter by 6.9 ± 3.7% (P = 0.02) and 0.5 ± 2.8% (P = 0.51) in the presence of S-methyl-l-thiocitrulline. The response to substance P did not predict the response to mental stress (r2 = -0.22, P = 0.83). nNOS mediates the human coronary vasodilator response to mental stress, predominantly through actions at the level of coronary resistance vessels.NEW & NOTEWORTHY Acute mental stress induces vasodilation of the coronary microvasculature. Here, we show that this response involves neuronal nitric oxide synthase in the human coronary circulation.Listen to this article's corresponding podcast at http://ajpheart.podbean.com/e/nnos-and-coronary-flow-during-mental-stress/.

Body Mass Index and Risk for Mental Stress Induced Ischemia in Coronary Artery Disease.

Acute emotionally reactive mental stress (MS) can provoke prognostically relevant deficits in cardiac function and myocardial perfusion, and chronic inflammation increases risk for this ischemic phenomenon. We have described parasympathetic withdrawal and generation of inflammatory factors in MS. Adiposity is also associated with elevated markers of chronic inflammation. High body mass index (BMI) is frequently used as a surrogate for assessment of excess adiposity, and associated with traditional CAD risk factors, and CAD mortality. BMI is also associated with autonomic dysregulation, adipose tissue derived proinflammatory cytokines, which are also attendant to emotion provoked myocardial ischemia. Thus, we sought to determine if body mass index (BMI) contributes to risk of developing myocardial ischemia provoked by mental stress. We performed a prospective interventional study in a cohort of 161 patients with stable CAD. They completed an assessment of myocardial blood flow with single photon emission computed tomography (SPECT) simultaneously during 2 conditions: laboratory mental stress and at rest. Multivariate logistic regression determined the independent contribution of BMI to the occurrence of mental-stress induced ischemia. Mean age was 65.6 ±9.0 years; 87.0% had a history of hypertension, and 28.6% had diabetes. Mean BMI was 30.4 ± 4.7. Prevalence of mental stress ischemia was 39.8%. BMI was an independent predictor of mental stress ischemia, OR=1.10, 95% CI [1.01-1.18] for one-point increase in BMI and OR=1.53, 95% CI [1.06-2.21] for a 4.7 point increase in BMI (one standard deviation beyond the cohort BMI mean), p=0.025 for all. These data suggest that BMI may serve as an independent risk marker for mental stress ischemia. The factors attendant with greater BMI, which include autonomic dysregulation and inflammation, may represent pathways by which high BMI contribute to this risk and serve as a conceptual construct to replicate these findings in larger CAD populations.

Abstract 17545: Vasoconstriction During Mental Stress Predicts Severity of Mental Stress Induced Myocardial Ischemia

Background: Evidence supports that peripheral vasoconstriction during mental stress predicts mental stress induced ischemia (MSIMI). However, whether a dose response relationship exists with ischemia severity has not been evaluated; additionally, whether peripheral vascular function during the recovery phase is also related to MSIMI is not known. Hypothesis: We hypothesized that increased digital microvascular constriction during both mental stress and recovery are predictive of increased severity of mental stress ischemia. Methods: We evaluated 204 patients with stable CAD with high quality vascular data using a standardized mental stress test using a public speaking task. Peripheral artery tonometry (PAT) (Itamar Inc) was used to assess digital microvascular tone. Vasoconstriction was calculated as the ratio of pulse wave amplitude during speech/recovery and the last 3 minutes of baseline, with lower ratio indicating more vasoconstriction. 99mTc sestamibi myocardial perfusion imaging was performed at rest and with mental stress. A summed difference score (SDS) quantifying severity of reversible perfusion defects (inducible ischemia) comparing rest and stress images was computed using a standard 17-segment model. Four categories of increasing severity were based on cut points of 0, 3, and 6. Results: The mean (SD) age was 64 (8), 16% were women, and 28% were African American. Each category of increase in ischemia severity was associated with a 10% (p=0.04) decrease in speech PAT ratio (Figure) and 11% (p=0.02) decrease in recovery PAT ratio. After multivariable adjustment for sociodemographics, traditional risk factors, medical history, medication use, and psychological risk factors, the associations persisted, with B=-11%, p=0.02 for speech PAT ratio, and B=-8%, p=0.04 for recovery ratio. Conclusion: Peripheral vasoconstriction during mental stress speech as well as recovery predicts MSI severity in a dose-response relationship.

Young women post-MI have higher plasma concentrations of interleukin-6 before and after stress testing

ObjectivesYoung women have poorer prognosis after myocardial infarction (MI) and a higher rate of mental stress-induced ischemia compared with similarly aged men. A higher inflammatory status may help explain these sex differences. MethodsWe examined 98 patients (49 women and 49 men) age 18–59years with recent MI (past 6months). Women and men were matched for age, type of MI, and time since MI. Interleukin 6 (IL-6) concentrations were measured at baseline, after mental stress using a speech task, and after exercise/pharmacologic stress (60 and 90min). Depressive symptoms were measured with the Beck Depression Inventory (BDI-II) and angiographic coronary artery disease (CAD) severity was quantified with the Gensini score. Single-photon emission computed tomography (SPECT) was used to obtain a computerized measurement of stress-induced ischemia (summed difference score, or SDS) and determine whether severity of stress-induced ischemia affects the inflammatory response to stress. Analysis was stratified by the median age of 50. Geometric mean concentrations of IL-6 were obtained from general linear regression models. ResultsIn both age groups, women had less angiographic CAD and a similar level of conventional risk factors compared with men. Despite this, baseline IL-6 geometric means before both mental and physical stress were twice as high in women ⩽50years of age compared to age-matched men (3.8 vs. 1.8pg/mL, p=0.001, across both conditions), while they were similar in women and men age >50years (2.3 vs. 2.2pg/mL, p=0.83). After mental stress, IL-6 concentrations increased in both women and men in a similar fashion and remained twice as high in women ⩽50years than men at both 60min (5.4 vs. 2.6pg/mL, p=0.002) and 90min (5.9 vs. 3.4pg/mL, p=0.01). No significant difference was found between women and men >50years of age at any time point after mental stress. Results were similar for physical stress. After accounting for SDS, IL-6 concentrations in young women remained higher after both mental and physical stress. Baseline IL-6 concentrations were not significantly related to inducible ischemia. ConclusionsAfter MI, young women aged 50years or younger, compared with age-matched men, have remarkably higher concentrations of inflammation at baseline and after both mental and physical stress, with a similar inflammatory response to both stressors. Sustained concentrations of inflammation in young women, not their response to stress, may contribute to their adverse outcomes post-MI.

High Concordance Between Mental Stress-Induced and Adenosine-Induced Myocardial Ischemia Assessed Using SPECT in Heart Failure Patients: Hemodynamic and Biomarker Correlates.

Mental stress can trigger myocardial ischemia, but the prevalence of mental stress-induced ischemia in congestive heart failure (CHF) patients is unknown. We characterized mental stress-induced and adenosine-induced changes in myocardial perfusion and neurohormonal activation in CHF patients with reduced left-ventricular function using SPECT to precisely quantify segment-level myocardial perfusion. Thirty-four coronary artery disease patients (mean age±SD, 62±10 y) with CHF longer than 3 mo and ejection fraction less than 40% underwent both adenosine and mental stress myocardial perfusion SPECT on consecutive days. Mental stress consisted of anger recall (anger-provoking speech) followed by subtraction of serial sevens. The presence and extent of myocardial ischemia was quantified using the conventional 17-segment model. Sixty-eight percent of patients had 1 ischemic segment or more during mental stress and 81% during adenosine. On segment-by-segment analysis, perfusion with mental stress and adenosine were highly correlated. No significant differences were found between any 2 time points for B-type natriuretic peptide, tumor necrosis factor-α, IL-1b, troponin, vascular endothelin growth factor, IL-17a, matrix metallopeptidase-9, or C-reactive protein. However, endothelin-1 and IL-6 increased, and IL-10 decreased, between the stressor and 30 min after stress. Left-ventricular end diastolic dimension was 179±65 mL at rest and increased to 217±71 after mental stress and 229±86 after adenosine (P<0.01 for both). Resting end systolic volume was 129±60 mL at rest and increased to 158±66 after mental stress (P<0.05) and 171±87 after adenosine (P<0.07), with no significant differences between adenosine and mental stress. Ejection fraction was 30±12 at baseline, 29±11 with mental stress, and 28±10 with adenosine (P=not significant). There was high concordance between ischemic perfusion defects induced by adenosine and mental stress, suggesting that mental stress is equivalent to pharmacologic stress in eliciting clinically significant myocardial perfusion defects in CHF patients. Cardiac dilatation suggests clinically important changes with both conditions. Psychosocial stressors during daily life may contribute to the ischemic burden of CHF patients with coronary artery disease.

Depressive symptoms are associated with mental stress-induced myocardial ischemia after acute myocardial infarction.

ObjectivesDepression is an adverse prognostic factor after an acute myocardial infarction (MI), and an increased propensity toward emotionally-driven myocardial ischemia may play a role. We aimed to examine the association between depressive symptoms and mental stress-induced myocardial ischemia in young survivors of an MI.MethodsWe studied 98 patients (49 women and 49 men) age 38–60 years who were hospitalized for acute MI in the previous 6 months. Patients underwent myocardial perfusion imaging at rest, after mental stress (speech task), and after exercise or pharmacological stress. A summed difference score (SDS), obtained with observer-independent software, was used to quantify myocardial ischemia under both stress conditions. The Beck Depression Inventory-II (BDI-II) was used to measure depressive symptoms, which were analyzed as overall score, and as separate somatic and cognitive depressive symptom scores.ResultsThere was a significant positive association between depressive symptoms and SDS with mental stress, denoting more ischemia. After adjustment for demographic and lifestyle factors, disease severity and medications, each incremental depressive symptom was associated with 0.14 points higher SDS. When somatic and cognitive depressive symptoms were examined separately, both somatic [β = 0.17, 95% CI: (0.04, 0.30), p = 0.01] and cognitive symptoms [β = 0.31, 95% CI: (0.07, 0.56), p = 0.01] were significantly associated with mental stress-induced ischemia. Depressive symptoms were not associated with ischemia induced by exercise or pharmacological stress.ConclusionAmong young post-MI patients, higher levels of both cognitive and somatic depressive symptoms are associated with a higher propensity to develop myocardial ischemia with mental stress, but not with physical (exercise or pharmacological) stress.

Abstract MP86: Depressive Symptoms are Associated with Mental Stress-Induced Myocardial Ischemia After Acute Myocardial Infarction

Objectives: Previous studies indicated that depressed mood may act as a trigger of acute coronary syndromes, although the mechanisms are not clear. We aimed to examine the association between depression and mental stress-induced myocardial ischemia in young survivors of a myocardial infarction (MI), and the possible differential association of somatic and cognitive depressive symptom dimensions. Hypothesis: Higher levels of depressive symptoms are associated with a higher propensity to develop myocardial ischemia with mental stress. Methods: We studied 98 patients (49 women and 49 men) age 38-59 years who were hospitalized for acute MI in the previous 6 months. Patients underwent myocardial perfusion imaging with [99mTc]sestamibi single-proton emission computed tomography at rest, after mental stress (speech task), and after exercise treadmill stress. If unable to exercise (N=16), patients underwent pharmacological stress test with regadenoson. Myocardial perfusion defect scores were obtained with observer-independent software. A summed difference score, the difference between stress and rest perfusion defect scores, was used to quantify myocardial perfusion defects due to ischemia under both stress conditions. The Beck Depression Inventory-II (BDI-II) was used to measure depressive symptoms. Two separate scores of somatic and cognitive depressive symptoms were calculated. Multivariate linear regression models were used in the analysis. Results: There was a significant and graded positive association between depressive symptoms and summed difference score with mental stress. After adjustment for demographical and lifestyle factors, severity of coronary heart disease and medications, each incremental depressive symptom was associated with 0.14 higher ischemia perfusion defect score [β=0.14, 95% CI: (0.03, 0.24), p=0.01]. When somatic and cognitive depressive symptoms were examined separately, both somatic symptoms [β=0.17, 95% CI: (0.04, 0.30), p=0.01] and cognitive symptoms [β=0.31, 95% CI: (0.07, 0.56), p=0.01] showed a significant association with mental stress-induced ischemia. Depressive symptoms were not associated with ischemia induced by exercise or pharmacological stress. Conclusion: Among young post-MI patients, higher levels of both cognitive and somatic depressive symptoms are associated with a higher propensity to develop myocardial ischemia with mental stress, but not with exercise/pharmacological stress. Future studies should explore whether mental stress-induced ischemia explains the poorer prognosis associated with depressive symptoms in post-MI patients.

Impaired Resting Myocardial Annular Velocities Are Independently Associated With Mental Stress–Induced Ischemia in Coronary Heart Disease

The aim of this study was to investigate the association between resting myocardial function as assessed by tissue Doppler myocardial velocities and the propensity to develop mental stress-induced ischemia (MSIMI). Tissue Doppler myocardial velocities detect preclinical cardiac dysfunction and clinical outcomes in a range of conditions. However, little is known about the interrelationship between myocardial velocities and the propensity to develop MSIMI compared with exercise stress-induced myocardial ischemia. Resting annular myocardial tissue Doppler velocities were obtained in 225 patients with known coronary heart disease who were subjected to both conventional exercise stress testing as well asa battery of 3 mental stress tests. Diastolic early (e') and late (a') as well as systolic (s') velocities were obtained, and the eas index, an integrated measure of myocardial velocities, was calculated as e'/(a'× s'). MSIMI was defined as: 1) the development or worsening of regional wall motion abnormality; 2) a reduction in left ventricular ejection fraction ≥ 8%; and/or 3) ischemic ST-segment changes during 1or more of the 3 mental stress tests. A total of 98 of 225 patients (43.7%) exhibited MSIMI. Patients developing MSIMI had significantly lower s' (7.0 ± 1.7 vs. 7.5 ± 1.2, p= 0.016) and a' (8.9 ± 1.8 vs. 10.0 ± 1.9, p < 0.001) at baseline, whereas e' did not differ (6.5 ± 1.7 vs. 6.5 ± 1.8, p= 0.85). Furthermore, the eas index was significantly higher (0.11 ± 0.04 vs. 0.09 ± 0.03, p < 0.0001). The eas index remained significantly associated with the propensity to develop MSIMI (odds ratio per 0.05-U increase: 1.85; 95% confidence interval: 1.21 to 2.82; p= 0.004) after adjustment for resting left ventricular ejection fraction, resting wall motion index score, sex, and social circumstances of living. There was no association between resting eas index and exercise stress-induced myocardial ischemia. MSIMI but not exercise stress-induced myocardial ischemia is independently associated with resting abnormalities in myocardial systolic and late diastolic velocities as well as the integrated measure of the eas index in patients with known coronary artery disease. (Responses of Myocardial Ischemia to Escitalopram Treatment [REMIT]; NCT00574847).

Abstract P373: Cardiac Depolarization and Repolarization Changes with Mental Stress are Associated with Mental Stress- Induced Ischemia

Introduction: QRS duration and frontal QRS/T angle are simple and easily available electrocardiographic measures of cardiac depolarization and repolarization that predict cardiovascular disease (CVD) events and mortality. Such measures may be indicative of cardiac structural disease, ischemia, or primary conduction abnormalities. Mental stress-induced myocardial ischemia (MSI) is also associated with increased CVD risk, but the underlying mechanisms are unknown. We hypothesized that MSI is associated with stress-induced abnormalities in cardiac depolarization and repolarization, QRS duration and frontal QRS/T angle. Methods: We compared QRS duration &amp; frontal QRS/T angle during mental stress between coronary artery disease (CAD) patients who were MSI positive (MSI+) and CAD patients who were MSI negative (MSI-). For each MSI+ case (n=22), one or two MSI- controls were matched for age, gender and race- ethnicity (n=41). QRS duration and frontal QRS/T angle were automatically computed by a 12-lead ECG (GE MAC 5000). QRS/T angle was calculated as absolute minimal difference between the frontal R and T axes in patients with QRS duration &lt; 120 ms (n= 50). Mental stress was induced via speech stressor, and nuclear 99m-Tc-sestamibi gated Single-Photon Emission Computed Tomography (SPECT) was used to assess MSI. Results: Mean age was 65 years, 20 patients were black, and 55 were males. The two groups were similar in terms of demographics and past medical history. Both MSI+ and MSI- groups had similar QRS duration at baseline, but MSI+ patients had an adjusted 3.1 ms higher increase in QRS duration with mental stress than MSI- patients (95% CI: 0.5 to 5.7), after adjusting for CVD risk factors, hemodynamic changes during mental stress (blood pressure, heart rate), and baseline QRS duration. MSI+ patients had an adjusted 28.2 degrees larger QRS/T angle at baseline (95% CI: 2.5 to 53.9) compared to MSI- patients, but did not differ with regards to change in QRS/T angle with mental stress. However, among those with normal baseline conduction (QRS&lt;100 ms, n=36), MSI+ patients had an adjusted 17.8 degrees larger change in QRS/T angle with mental stress compared to MSI- patients (95% CI: 3.1 to 32.4). In patients with mildly abnormal conduction (QRS duration between 100 and 119 ms, n=14), no differences were found, p=0.059 for QRS duration x MSI interaction. Conclusion: CAD patients exhibit changes in cardiac depolarization and repolarization during acute mental stress. Those with MSI have greater baseline QRS/T angle and larger changes in QRS/T angle and QRS duration with mental stress. These findings may help to explain the pathophysiology linking mental stress and CVD, as well as the increased risk in patients with MSI.

Prevalence and Clinical Characteristics of Mental Stress–Induced Myocardial Ischemia in Patients With Coronary Heart Disease

The goal of this study was to evaluate the prevalence and clinical characteristics of mental stress-induced myocardial ischemia. Mental stress-induced myocardial ischemia is prevalent and a risk factor for poor prognosis in patients with coronary heart disease, but past studies mainly studied patients with exercise-induced myocardial ischemia. Eligible patients with clinically stable coronary heart disease, regardless of exercise stress testing status, underwent a battery of 3 mental stress tests followed by a treadmill test. Stress-induced ischemia, assessed by echocardiography and electrocardiography, was defined as: 1) development or worsening of regional wall motion abnormality; 2) left ventricular ejection fraction reduction ≥ 8%; and/or 3) horizontal or downsloping ST-segment depression ≥ 1 mm in 2 or more leads lasting for ≥ 3 consecutive beats during at least 1 mental test or during the exercise test. Mental stress-induced ischemia occurred in 43.45%, whereas exercise-induced ischemia occurred in 33.79% (p = 0.002) of the study population (N = 310). Women (odds ratio [OR]: 1.88), patients who were not married (OR: 1.99), and patients who lived alone (OR: 2.24) were more likely to have mental stress-induced ischemia (all p < 0.05). Multivariate analysis showed that compared with married men or men living with someone, unmarried men (OR: 2.57) and married women (OR: 3.18), or living alone (male OR: 2.25 and female OR: 2.72, respectively) had higher risk for mental stress-induced ischemia (all p < 0.05). Mental stress-induced ischemia is more common than exercise-induced ischemia in patients with clinically stable coronary heart disease. Women, unmarried men, and individuals living alone are at higher risk for mental stress-induced ischemia. (Responses of Myocardial Ischemia to Escitalopram Treatment [REMIT]; NCT00574847).

Prognosis After Change in Left Ventricular Ejection Fraction During Mental Stress Testing in Patients With Stable Coronary Artery Disease

Previous studies of patients with stable coronary artery disease have demonstrated that decreases in the left ventricular ejection fraction (LVEF) during acute mental stress are predictive of adverse clinical outcomes. The aim of the present study was to examine the prospective relation of mental stress on clinical outcomes in a sample of 138 patients with stable coronary artery disease. Patients underwent mental stress testing and were followed for a median of 5.9 years to assess the occurrence of the combined end point of myocardial infarction or all-cause mortality. There were 32 events (17 nonfatal myocardial infarctions and 15 deaths) over the follow-up period. Of the 26 patients who exhibited myocardial ischemia during mental stress testing, 11 (42%) sustained subsequent clinical events, compared to 21 of the 112 patients (19%) who showed no mental stress-induced ischemia. LVEF change during mental stress was also related to the clinical events in a graded, continuous fashion, with each 4% decrease from the LVEF at rest associated with an adjusted hazard ratio of 1.7, (95% confidence interval 1.1 to 2.6, p = 0.011). In conclusion, reductions in the LVEF during mental stress are prospectively associated with adverse clinical outcomes.

A Noninvasive Clinically Useful Predictor for Mental Stress-Induced Ischemia

Hassan, Mustafa MD; Quyyumi, Arshed A. MD, FRCP; Sheps, David S. MD, MSPH Author Information

Do Men and Women Differ on Measures of Mental Stress-Induced Ischemia?

To consider the effects of gender on ischemia in a larger sample, with broadly defined coronary artery disease (CAD). Mental stress has been shown to cause transient myocardial ischemia in a significant percentage of people with CAD. However, little is known about the effects of mental stress on ischemic processes in women. Most studies to date either had few women or required a positive exercise stress test. Participants (61 women, 93 men; average age = 63 years) had documented CAD (positive stress test, abnormal catheterization even with minimal disease, or previous myocardial infarction). They underwent mental stress testing and radionuclide perfusion imaging (stress/ rest). Cardiac function data were collected and stress was compared with baseline. The data were then submitted to a series of analyses of variance. A total of 50 (32%) participants exhibited reversible ischemia post psychological stress. This reflects a relative rate of 33% (n = 31 of 93) for men and 31% (n = 19 of 61) for women. No difference between men and women were observed on any measure of hemodynamic functioning (blood pressure, heart rate, or cardiac perfusion). Results of this study showed no significant differences between men and women on measures of hemodynamic functioning or cardiac perfusion.