Mental Stress-induced Myocardial Ischemia Research Articles

Stress-Induced Autonomic Dysfunction is Associated With Mental Stress-Induced Myocardial Ischemia in Patients With Coronary Artery Disease.

Mental stress-induced myocardial ischemia (MSIMI) is associated with adverse cardiovascular outcomes in individuals with coronary artery disease, but the mechanisms underlying this phenomenon are unknown. We examined the relationship between stress-induced autonomic dysfunction, measured by low heart rate variability (HRV) in response to stress, and MSIMI in patients with stable coronary artery disease. We hypothesized that stress-induced autonomic dysfunction is associated with higher odds of MSIMI. In 735 participants with stable coronary artery disease, we measured high- and low-frequency HRV in 5-minute intervals before and during a standardized laboratory-based speech stressor using Holter monitoring. HRV at rest and stress were categorized into low HRV (first quartile) versus high HRV (second to fourth quartiles); the low category was used as an indicator of autonomic dysfunction. Multivariable logistic regression models were used to examine the association of autonomic dysfunction with MSIMI. The mean age was 58 (SD, ±10) years, 35% were women, 44% were Black participants, and 16% developed MSIMI. Compared with high HRV during stress, low HRV during stress (both high and low frequencies) was associated with higher odds of MSIMI after adjusting for demographic and clinical factors (odds ratio for high-frequency HRV, 2.1 [95% CI, 1.3-3.3]; odds ratio for low-frequency HRV, 2.1 [95% CI, 1.3-3.3]). Low-frequency HRV at rest was also associated with MSIMI but with slightly reduced effect estimates. In individuals with coronary artery disease, mental stress-induced autonomic dysfunction may be a mechanism implicated in the causal pathway of MSIMI.

Mental Stress-Induced Myocardial Ischemia Detected by Global Longitudinal Strain and Quantitative Myocardial Contrast Echocardiography in Women With Nonobstructive Coronary Artery Disease

The utility of radionuclide myocardial perfusion imaging including positron emission tomography (PET) for diagnosing mental stress-induced myocardial ischemia (MSIMI) is clinically restricted. This study aims to assess the diagnostic performance of novel echocardiographic techniques, including automated strain and quantitative myocardial contrast echocardiography (MCE) with dedicated software and deep neural network model, for MSIMI detection. The secondary objective was to explore the correlation between changes in myocardial blood flow and MSIMI. Seventy-two female patients ages 18 to 75 with angina and nonobstructive coronary artery disease (ANOCA) and 23 healthy controls were prospectively recruited. Both echocardiography with contrast agent and PET imaging were performed during structured mental stress testing. Mental stress-induced myocardial ischemia was defined as a summed difference score ≥3 on PET. Echocardiographic parameters including left ventricular global longitudinal strain, β, and A×β were obtained, and their trends during mental stress testing were observed. ΔGLS was defined as the ratio of difference between global longitudinal strain values at stress and rest to the rest data. β reserve and A×β reserve were respectively calculated. Thirty-two ANOCA patients (44%) and 1 control (4%) were diagnosed with MSIMI (P<.01). For ANOCA patients with MSIMI, left ventricular GLS, β, and A×β declined to varied extents during mental stress testing compared with those without MSIMI and the controls (P<.05). Bland-Altman plots demonstrated good consistency between β reserve and A×β reserve output by the deep neural network model and iMCE software. Receiver operating characteristic curve analyses showed that ΔGLS, β reserve, and A×β reserve demonstrated favorable ability to predict MSIMI, especially the combination of A×β reserve using iMCE analysis and ΔGLS (area under the curve, 0.94; sensitivity, 83%; specificity, 97%). Novel technologies in echocardiography exhibit the potential to be a clinical alternative to cardiac PET for effectively detecting MSIMI. Attenuated myocardial blood flow response during structured mental stress testing was correlated with MSIMI, providing a reasonable explanation for the chest discomfort persisting in ANOCA women.

Abstract P241: Stress-Induced Autonomic Dysfunction is Associated With Mental Stress-Induced Myocardial Ischemia in Patients With Coronary Artery Disease

Background: Mental stress-induced myocardial ischemia (MSIMI) is associated with adverse cardiovascular outcomes in individuals with coronary artery disease (CAD), but the mechanisms underlying this phenomenon are unknown. We examined the relationship between stress-induced autonomic dysfunction, measured by lower heart rate variability (HRV) in response to stress, and MSIMI in patients with stable CAD. We hypothesized that stress-induced autonomic dysfunction is associated with higher odds of MSIMI. Methods: In 735 participants with stable CAD, we measured high frequency (HF) and low frequency (LF) HRV in 5-minute intervals before and during a standardized laboratory-based speech stressor using Holter monitoring. MSIMI was evaluated with single-photon emission computed tomography myocardial perfusion imaging. HRV at rest and stress were categorized into low (lowest quartile) versus high (upper three quartiles) categories; low category was used as an indicator of autonomic dysfunction. Multivariable logistic regression models were used to examine the association of autonomic dysfunction with MSIMI. Results: The mean age was 58 (SD ±10) years, 35% were women, 44% were Black participants, and 16% developed MSIMI. Compared with high stress HRV, low stress HRV (both HF and LF) was associated with higher odds of MSIMI after adjusting for demographic and clinical factors. LF HRV at rest was also significantly associated with MSIMI with slightly reduced effect estimates. Conclusions: In individuals with CAD, mental stress-induced autonomic dysfunction may be an independent mechanism in the pathogenesis of MSIMI.

Multiomics on Mental Stress-Induced Myocardial Ischemia: A Narrative Review

Abstract Accumulating multiomics studies have been developed to gain new insights into complex diseases, including mental stress-induced diseases and myocardial ischemia. Multiomics techniques integrate multiple layers of biological data, such as genomics, transcriptomics, proteomics, and metabolomics, to obtain a more comprehensive understanding of the molecular mechanisms underlying these diseases. Despite the potential benefits of applying multiomics approaches to the study of mental stress-induced myocardial ischemia (MSIMI), such studies are relatively limited. The etiology of MSIMI remains poorly understood, highlighting the need for further research in this field. This review first discusses the current state of knowledge on MSIMI and highlights the research gaps in this field. Then, we provide an overview of recent studies that have used multiomics approaches to expand insights into mental stress-induced diseases and myocardial ischemia, respectively. Finally, we propose possible research directions that can be pursued to improve our knowledge of MSIMI and the potential benefits of applying multiomics approaches to this domain. While still in its early stages, multiomics research holds great promise for improving the recognition of MSIMI and developing more effective clinical interventions.

Obstructive Sleep Apnea as a Key Contributor to Mental Stress-Induced Myocardial Ischemia in Female Angina Patients with No Obstructive Coronary Artery Disease.

Mental stress induced myocardial ischemia (MSIMI) is regarded as the primary cause of the angina with no obstructive coronary artery disease (ANOCA). Obstructive sleep apnea (OSA) is autonomously linked to obstructive coronary heart disease, hypertension, and sudden cardiac death. Similar to the impact of psychological stress on the cardiovascular system, individuals with OSA experience periodic nocturnal hypoxia, resulting in the activation of systemic inflammation, oxidative stress, endothelial dysfunction, and sympathetic hyperactivity. The contribution of OSA to MSIMI in ANOCA patients is unclear. To explore the prevalence of OSA in ANOCA patients and the correlation between OSA and MSIMI, a prospective cohort of female ANOCA patients was recruited. We recruited female patients aged 18 to 75 years old with ANOCA and evaluated MSIMI using positron emission tomography-computed tomography. Subsequently, Level III portable monitors was performed to compare the relationship between OSA and MSIMI. There is higher REI (7.8 vs 2.6, P=0.019), ODI (4.7 vs 9.2, P=0.028) and percentage of OSA (67.74% vs 33.33%, P=0.004) in MSIMI patients. The patients diagnosed with OSA demonstrated higher myocardial perfusion imaging scores (SSS: 1.5 vs 3, P = 0.005, SDS: 1 vs 3, P = 0.007). Adjusted covariates, the risk of developing MSIMI remained 3.6 times higher in OSA patients (β=1.226, OR = 3.408 (1.200-9.681), P = 0.021). Patients with MSIMI exhibit a greater prevalence of OSA. Furthermore, the myocardial blood flow perfusion in patients with OSA is reduced during mental stress.

Abstract 13787: Restricted Coronary Flow Reserve of Mental Stress Induced Myocardial Ischemia in Angina and No Obstructive Coronary Artery Disease

Background: The myocardial blood flow (MBF) mechanism in mental stress-induced myocardial ischemia (MSIMI) in angina with no obstructive coronary artery disease (ANOCA) population is unknown. Methods: 13-NH 3 cardiac PET-CT was utilized to assess MBF and perfusion changes under mental stress (ms) and adenosine stress (as) in ANOCA subjects and gender- and age-matched healthy controls. MSIMI was defined as an increase in perfusion defect score of ≥3 points. Results: Among the 126 participants enrolled, ANOCA women showed a significantly higher prevalence of MSIMI compared to the healthy controls (36/84 vs. 1/42, p &lt;0.001). Perfusion defects under ms occurred synchronously however more pronounced in the left anterior descending and right coronary artery territories, consistent with a significantly higher MBF hyperemia in the left circumflex territory. MBF ms shows a close correlation with rate-pressure product (RPP ms ) ( p &lt;0.05 in ANOCA&amp;MSIMI+, ANOCA&amp;MSIMI-, and control groups with r pearson ranging from 0.39-0.65). Although no differences existed in absolute MBF ms values between groups, there were notable increasing trends among the three groups in corrected MBF, which reflected blood flow supply-demand balance (ANOCA&amp;MSIMI+: 0.96±0.23 vs. control group: 1.10±0.29, p =0.020), and in coronary flow reserve (CFR) (ANOCA&amp;MSIMI+: 2.41±0.75 vs. control group: 2.89±0.77, p =0.016). Furthermore, after adjusting for confounding factors, only subjects in ANOCA&amp;MSIMI+ group did not exhibit a corresponding increase in MBF ms matching MBF as . Conclusion: Restricted CFR, indicating impaired coronary microvascular function, and mismatch between myocardial blood supply and demand together constitute the pathogenic mechanism of MSIMI in ANOCA population. More researches are still needed in exploring the brain-heart interaction in MSIMI.

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.

The prognostic study of mental stress-induced myocardial ischemia in coronary revascularization patients with depression/anxiety: rationale and design

BackgroundMental stress-induced myocardial ischemia (MSIMI) frequently occurs in patients with coronary artery disease (CAD), and is even more common in patients with co-occurring CAD and depression/anxiety. MSIMI appears to be a poor prognostic factor for CAD, but existing data on depression/anxiety patients are limited.MethodsThis cohort study will consecutively screen 2,647 CAD patients between 2023 and 2025. Included subjects will need to have received coronary revascularization and also have depression and/or anxiety at baseline. This study will enroll 360 subjects who meet the criteria. Two mental stress tests will be carried out in each patient at 1 month and 1 year timelines after coronary revascularization, using Stroop color word tests. MSIMI will be assessed by 99 m−Tc-sestamibi myocardial perfusion imaging. The endothelial function will be assessed by EndoPAT. Furthermore, we will dynamically monitor patients’ health and mental conditions every 3 months. The mean follow-up time will be 1 year. The primary endpoint is the major adverse cardiac events, a composite of all-cause death, cardiac death, myocardial infarction, stroke, or unplanned revascularization. Secondary endpoints will include overall health and mental conditions. The reproducibility of mental stress combined with myocardial perfusion for detecting MSIMI and comparisons between coronary stenosis and ischemic segments will also be included.ConclusionsThis cohort study will provide information on MSIMI outcomes in CAD patients who also have comorbid depression/anxiety after revascularization. In addition, understanding the long-term dynamics of MSIMI and the match between coronary stenosis and ischemia will provide insight into MSIMI mechanisms.Trail RegistrationChiCTR2200055792, 2022.1.20, www.medresman.org.cn;

Mental Stress-Induced Change in Plasma Stromal Cell-Derived Factor-1 and Adverse Cardiovascular Outcomes: A Cohort Study

BackgroundAcute psychological stress can provoke mental stress-induced myocardial ischemia (MSIMI) in coronary artery disease (CAD). Stromal cell-derived factor 1 (SDF1) is released in response to hypoxia, and higher levels of SDF1 are associated with adverse outcomes. We examined whether an increase in SDF1 level in response to mental stress predicts adverse outcomes in CAD patients. MethodsA total of 554 patients with stable CAD (mean age 63 years; 76% male; 26% Black) underwent standardized mental stress testing. Plasma SDF1 levels were measured at rest and 90 minutes after mental stress, and MSIMI was evaluated by 99mTc-sestamibi perfusion imaging. Participants were followed for 5 years for the primary endpoint of composite of death and myocardial infarction (MI) and the secondary endpoint of composite of death, MI, and heart failure hospitalization. Cox hazard models were used to assess the association between SDF1 change and incident adverse events. ResultsMean (standard deviation) SDF1 change with mental stress was +56.0 (230) pg/mL. During follow-up, a rise of 1 standard deviation in SDF1 with mental stress was associated with a 32% higher risk for the primary endpoint of death and MI (95% confidence interval, 6%-64%), independent of the resting SDF1 level, demographic and clinical risk factors, and presence of ischemia. A rise of 1 standard deviation in SDF1 was associated with a 33% (95% confidence interval, 11%-59%) increase in the risk for the secondary endpoint, independent of the resting SDF1 level, demographic, and clinical risk factors and presence of ischemia. ConclusionsAn increase in SDF1 level in response to mental stress is associated with a higher risk of adverse events in stable CAD, independent of MSIMI.

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.

Mental Stress-Induced Myocardial Ischemia.

To summarize recent evidence on mental stress-induced myocardial ischemia (MSIMI), its mechanisms, and clinical significance. MSIMI can occur in patients with normal cardiac stress testing, is only weakly related to severity of coronary artery disease (CAD), and it is often silent. Among patients with CAD, MSIMI is associated with a twofold increased risk of major adverse cardiovascular events compared to those who do not have MSIMI. Certain groups such as young women with myocardial infarction and those with psychological comorbidities are more susceptible to MSIMI. Abnormal microvascular vasoreactivity and inflammation are implicated mechanisms in MSIMI. Increased brain activity in regions that modulate autonomic reactivity to emotional stress and fear is associated with MSIMI. MSIMI has important prognostic implications in patients with CAD. Stress can no longer be ignored as a risk factor in cardiology care. Clinical trials testing effective strategies to target MSIMI are needed.

The Impact of Mental Stress on Cardiovascular Health-Part II.

Endothelial dysfunction is one of the earliest manifestations of atherosclerosis, contributing to its development and progression. Mental stress induces endothelial dysfunction through increased activity of the sympathetic nervous system, release of corticotropin-releasing hormone from the hypothalamus, inhibition of nitric oxide (NO) synthesis by cortisol, and increased levels of pro-inflammatory cytokines. Mental-stress-induced increased output of the sympathetic nervous system and concomitant withdrawal of the parasympathetic inflammatory reflex results in systemic inflammation and activation of a neural–hematopoietic–arterial axis. This includes the brainstem and subcortical regions network, bone marrow activation, release of leukocytes into the circulation and their migration to the arterial wall and atherosclerotic plaques. Low-grade, sterile inflammation is involved in all steps of atherogenesis, from coronary plaque formation to destabilisation and rupture. Increased sympathetic tone may cause arterial smooth-muscle-cell proliferation, resulting in vascular hypertrophy, thus contributing to the development of hypertension. Emotional events also cause instability of cardiac repolarisation due to brain lateralised imbalance of cardiac autonomic nervous stimulation, which may lead to asymmetric repolarisation and arrhythmia. Acute emotional stress can also provoke severe catecholamine release, leading to direct myocyte injury due to calcium overload, known as myocytolysis, coronary microvascular vasoconstriction, and an increase in left ventricular afterload. These changes can trigger a heart failure syndrome mimicking acute myocardial infarction, characterised by transient left ventricular dysfunction and apical ballooning, known as stress (Takotsubo) cardiomyopathy. Women are more prone than men to develop mental-stress-induced myocardial ischemia (MSIMI), probably reflecting gender differences in brain activation patterns during mental stress. Although guidelines on CV prevention recognise psychosocial factors as risk modifiers to improve risk prediction and decision making, the evidence that their assessment and treatment will prevent CAD needs further evaluation.

Mental Stress and Cardiovascular Health-Part I.

Epidemiological studies have shown that a substantial proportion of acute coronary events occur in individuals who lack the traditional high-risk cardiovascular (CV) profile. Mental stress is an emerging risk and prognostic factor for coronary artery disease and stroke, independently of conventional risk factors. It is associated with an increased rate of CV events. Acute mental stress may develop as a result of anger, fear, or job strain, as well as consequence of earthquakes or hurricanes. Chronic stress may develop as a result of long-term or repetitive stress exposure, such as job-related stress, low socioeconomic status, financial problems, depression, and type A and type D personality. While the response to acute mental stress may result in acute coronary events, the relationship of chronic stress with increased risk of coronary artery disease (CAD) is mainly due to acceleration of atherosclerosis. Emotionally stressful stimuli are processed by a network of cortical and subcortical brain regions, including the prefrontal cortex, insula, amygdala, hypothalamus, and hippocampus. This system is involved in the interpretation of relevance of environmental stimuli, according to individual’s memory, past experience, and current context. The brain transduces the cognitive process of emotional stimuli into hemodynamic, neuroendocrine, and immune changes, called fight or flight response, through the autonomic nervous system and the hypothalamic–pituitary–adrenal axis. These changes may induce transient myocardial ischemia, defined as mental stress-induced myocardial ischemia (MSIMI) in patients with and without significant coronary obstruction. The clinical consequences may be angina, myocardial infarction, arrhythmias, and left ventricular dysfunction. Although MSIMI is associated with a substantial increase in CV mortality, it is usually underestimated because it arises without pain in most cases. MSIMI occurs at lower levels of cardiac work than exercise-induced ischemia, suggesting that the impairment of myocardial blood flow is mainly due to paradoxical coronary vasoconstriction and microvascular dysfunction.

Adenosine-Induced Myocardial Ischemia in a Patient with Myocardial Bridge

The adenosine stress test and exercise stress test have been widely used in the diagnosis of coronary heart disease, which has high sensitivity and specificity for diagnosis of coronary heart disease. The myocardial bridge is a congenital dysplasia of the coronary artery which may cause severe myocardial ischemia, acute myocardial infarction, arrhythmia, and sudden death. Although drug therapy for this disease is clear and widely used, indication for open-chest surgery is still vague. This case shows a patient with long-term chest pain undergoing the coronary computed tomographic angiography in our hospital 1 month ago, which showed the mild myocardial bridge in the left anterior descending (LAD) branch. Then, she did the mental stress-induced myocardial ischemia and cardiopulmonary exercise test which the results were negative. After the informed consent, the patient took the adenosine stress test and severe angina occurred during the test. Later, coronary angiography showed that the myocardial bridge caused 70% contraction of the middle segment of the LAD branch. In the case of long-term ineffective drug treatment, the patient underwent a open-chest surgery called coronary artery myotomy and her chest discomfort eventually recovered. To a degree, adenosine stress test may be more sensitive than exercise stress test in predicting the severity of coronary artery stenosis. Moreover, we may provide a unique direction of indication for surgeons to operate open-chest surgery on the myocardial bridge.

Abstract MP45: Metabolomic Profiling Provides Novel Insights Into The Biochemical Mechanism Of Mental Stress-induced Ischemia

Introduction: Mental stress-induced myocardial ischemia (MSI) is a marker of future cardiovascular events. The underlying biochemical mechanisms of this cardiovascular condition are poorly understood. Our objective was to use metabolic profiling to identify biochemical changes associated with mental stress (MS) in patients with stable coronary artery disease (CAD) and investigate differential pathways that are involved in MSI. Methods: A total of 110 Individuals with stable CAD who participated in the Mental Stress Ischemia Prognosis Study (MIPS) underwent a standardized mental stress to provoke of myocardial ischemia, detected with single-photon emission tomography. Plasma samples were obtained before and after MS at 45 and 90 minutes and metabolomic profiling was performed using liquid chromatography/mass spectrometry using a confirmed 500 compounds. Metabolomic features and pathways associated with ischemia using metabolome-wide association studies and Mummichog, respectively. Results: The sample involved a subset case-control for (MSI+ vs MSI-). At 45 minutes and 90 minutes, there were significant stress-induced changes in several compounds. There was a significant upregulation of metabolites associated with lipid signaling et ( p = 0.025, Inosine diphosphate). A comparison between the MSI+ and MS- groups showed differential upregulation of DNA methylation metabolites ( p = .036, 5-Methylcytosine hydrochloride) at 45 minutes and microbiome-related metabolites at 90 minutes (P=0.041, N, N-dimethyl-1,4-phenylenediamine). Pathway analyses were consistent with the aforementioned findings. Conclusion: Upregulation of metabolic pathways involved in DNA methylation and microbial metabolism is differentially associated with MSI. These findings provide novel mechanistic insights into the association between acute mental stress and myocardial ischemia as a marker for cardiovascular vulnerability in patients with CAD

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.

Everyday Discrimination and Mental Stress-Induced Myocardial Ischemia.

Mental stress-induced myocardial ischemia (MSIMI), a transient myocardial ischemic response to mental stress, is associated with poorer outcomes among patients with coronary heart disease and is more likely to occur among women. However, predictors of MSIMI are not well explored. The current study investigated the association between experiences of everyday discrimination and MSIMI among patients with recent myocardial ischemia and contrasted the results with conventional stress-induced myocardial ischemia (CSIMI). We examined sex differences in associations. We studied 295 post-MI patients (145 women, 150 men). Provocation of myocardial ischemia with mental stress (speech task) and conventional stress (exercise or pharmacologic) was assessed by myocardial perfusion imaging. Frequency of exposure to everyday discrimination was assessed via questionnaire using the Everyday Discrimination Scale (EDS). The mean age was 51 years in both women and men, and the EDS score ranged from 10 to 38 (mean [standard deviation] = 17 [6] years). After multivariable analysis, each standard deviation increase in the EDS score (more frequent exposure) was associated with an increased odds of MSIMI (odds ratio [OR] = 1.57 [1.10-2.23]). The EDS score was not associated with CSIMI (OR = 0.86 [0.64-1.17]). Women demonstrated a twofold increase (OR = 1.96 [1.13-3.38], p = .02) in the adjusted odds of MSIMI, with each standard deviation increase in the EDS score compared with a 1.4-fold increase (OR = 1.40 [0.80-2.44], p = .24) among men; however, interaction was not statistically significant. Among post-MI patients, everyday discrimination was positively associated with occurrence of MSIMI, but not with CSIMI; associations were more pronounced among women.

Abstract 014: Posttraumatic Stress Disorder, Mental Stress-induced Myocardial Ischemia And Cardiovascular Outcomes In Patients With CAD

Introduction: Mental stress-induced myocardial ischemia (MSI) is a risk marker for adverse outcomes among coronary artery disease (CAD) that is more prevalent among patients with posttraumatic stress disorder (PTSD). Hypothesis: CAD patients with PTSD who develop MSI experience a higher risk of adverse cardiovascular events compared with those who do not develop MSI. Methods: We studied 995 individuals with stable CAD who participated in two contemporary cohort studies with similar protocols, the Mental Stress Ischemia Prognosis Study (MIPS), and the Myocardial Infarction and Mental Stress Study (MIMS). Provocation of myocardial ischemia with a standardized mental stress test (speech task) was assessed with single-photon emission computed tomography. PTSD was assessed with the structured clinical interviews for DSM-IV. Participants were categorized into four groups based on their MSI and PTSD status. The primary endpoint was a composite outcome of cardiovascular death or nonfatal myocardial infarction (MI), stroke, or heart failure hospitalization. Cox regression models were used to investigate the interaction of PTSD and MSI on the study endpoint in the two samples pooled with meta-analysis. Results: In total, 603 participants in MIPS and 392 in MIMS were included. MSI occurred in 16% of the patients in MIPS and 17% in MIMS. Over a 5-year median follow-up, there were 126 outcome events in MIPS and 117 in MIMS. In Cox regression models with adjustment for demographic and clinical risk factors, participants with both MSI and PTSD had a higher risk for the study endpoint, compared to those with neither. In contrast, participants with PTSD or MSI but not both were not at a higher risk ( p interaction=0.01). Separate analyses in the two studies were consistent. Conclusions: There is a synergistic association of PTSD and MSI on adverse outcomes in CAD patients. These findings support the confluence of chronic mental health vulnerability with acute stress responses in defining elevated risk in CAD patients.patients.

Mental Stress-Induced Myocardial Ischemia and Associated Mechanisms in Women With Angina and No Obstructive Coronary Artery Disease (ANOCA): A Mechanistic Clinical Trial

Mental Stress-Induced Myocardial Ischemia and Associated Mechanisms in Women With Angina and No Obstructive Coronary Artery Disease (ANOCA): A Mechanistic Clinical Trial

Mental stress-induced myocardial ischemia and cognitive impairment in coronary atherosclerosis

ObjectiveTo understand if presence of mental stress-induced myocardial ischemia (MSIMI) is associated with higher prevalence of cognitive impairment at baseline and its decline over time. MethodsA cohort of participants with stable coronary atherosclerosis underwent acute mental stress testing using a series of standardized speech/arithmetic stressors. The stress/rest digital vasomotor response to mental stress (sPAT) was assessed to measure microvascular constriction during mental stress. Patients received 99mTc-sestamibi myocardial perfusion imaging at rest, with mental stress and with conventional (exercise/pharmacological) stress. Cognitive function was assessed both at baseline and at a 2 year follow-up using the Trail Making Test parts A and B and the verbal and visual memory subtests of the Wechsler Memory Scale. ResultsWe studied 486 individuals (72% male, 32.1% Black, 62 ± 9 (mean ± SD) years old). After multivariable adjustment for baseline demographics, risk factors, and medication use, presence of MSIMI was associated with 21% and 20% slower completion of Trail-A and Trail-B, respectively (p for all <0.01). After a 2-year follow-up period, presence of MSIMI was associated with a 33% slower completion of Trail-B, denoting cognitive decline (B = 0.33, 95% CI, 0.04, 0.62). A lower sPAT, indicating greater vasoconstriction, mediated the association between MSIMI and worsening Trail-B performance by 18.2%. Ischemia with a conventional stress test was not associated with any of the cognitive tests over time. ConclusionMSIMI is associated with slower visuomotor processing and worse executive function at baseline and with greater decline in these abilities over time.