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

BACKGROUND: Mental 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. METHODS: This 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. CONCLUSIONS: This 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 REGISTRATION: ChiCTR2200055792, 2022.1.20, www.medresman.org.cn.

Effects of Psychological Stress on Vascular Physiology: Beyond the Current Imaging Signal.

PURPOSE OF REVIEW: This review describes the effects of psychological stress on the physiology of the entire vascular system, from individual cellular components to macrovascular and microvascular responses, and highlights the importance of the vascular system in the context of current limitations in cardiac imaging for evaluation of the cardiovascular response to mental stress. RECENT FINDINGS: The physiological responses that mediate vascular changes are based on evolutionary needs, but there is increasing evidence that the long-term consequences of psychological stress can precipitate the development and progression of cardiovascular disease (CVD). While there is an extensive body of literature describing localized physiological responses or overt cardiovascular manifestations, often framed within the organ-specific scope of cardiovascular imaging, there has not been a comprehensive description of the global vascular effects of psychological stress. Given the global nature of these processes, targeted cardiovascular imaging modalities may be insufficient. Here we approach the vascular response to mental stress systematically, describing the effects on the endothelium, vascular smooth muscle, and adventitia. We then address the mental stress effects on large vessels and the microvascular compartment, with a discussion of the role of microvascular resistance in the pathophysiology of mental stress-induced myocardial ischemia. Vascular responses to psychological stress involve complex physiological processes that are not fully characterized by routine cardiovascular imaging assessments. Future research incorporating standardized psychological assessments targeted toward vascular mechanisms of stress responses is required to guide the development of behavioral and therapeutic interventions.

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

BACKGROUND: 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. METHODS: 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, ß, and A × ß 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. ß reserve and A×ß reserve were respectively calculated. RESULTS: Thirty-two ANOCA patients (44%) and 1 control (4%) were diagnosed with MSIMI (P < .01). For ANOCA patients with MSIMI, left ventricular GLS, ß, and A × ß 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 ß reserve and A × ß reserve output by the deep neural network model and iMCE software. Receiver operating characteristic curve analyses showed that ΔGLS, ß reserve, and A × ß reserve demonstrated favorable ability to predict MSIMI, especially the combination of A × ß reserve using iMCE analysis and ΔGLS (area under the curve, 0.94; sensitivity, 83%; specificity, 97%). CONCLUSIONS: 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.

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

Purpose: 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. Patients and Methods: 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. Results: 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 (ß=1.226, OR = 3.408 (1.200-9.681), P = 0.021). Conclusion: Patients with MSIMI exhibit a greater prevalence of OSA. Furthermore, the myocardial blood flow perfusion in patients with OSA is reduced during mental stress.

Objective Ischemia, Subjective Angina, and Psychological Distress in Angina With No Obstructive Coronary Disease.

BACKGROUND: Angina with no obstructive coronary disease (ANOCA) and ischemia with no obstructive coronary disease, prevalent yet underrecognized conditions, mostly affect women. Previous studies rarely distinguished between them. We aimed to compare the prevalence of objective ischemia through various examinations in women with ANOCA and assess the impact of objective and subjective ischemia on their mental health. METHODS AND RESULTS: A total of 84 eligible women with ANOCA and 42 controls underwent mental stress, pharmacological stress, exercise stress, and Holter testing. Objective evidence of myocardial ischemia was assessed by positron emission tomography-computed tomography and ECG, and subjective symptoms were graded using the Canadian Cardiovascular Society scale (CCS). Psychological assessments were conducted using 6 scales. Among 84 women with ANOCA, 37 (44%) received a diagnosis of ischemia with no obstructive coronary disease following mental stress testing, 20 (28.6%) through pharmacological stress testing, 14 (21.2%) via exercise stress testing, and 24 (32.9%) from Holter. Mental stress-induced myocardial ischemia was more prevalent (P<0.05). Among 54 patients with ANOCA who completed all tests, 30% showed no ischemia, and only 1 (1.9%) showed ischemia in all tests. In addition, patients with ANOCA had higher psychological scores than controls (P<0.01). No significant differences was observed in psychological scores between ANOCA with positive and negative ischemia test results (P>0.05). However, ANOCA with milder angina (CCS I) exhibited higher scores across the Hospital Anxiety and Depression Scale, State-Trait Anxiety Inventory, Perceived Stress Scale, and Posttraumatic Stress Disorder Checklist-Civilian Version and a higher prevalence of Type D personality traits (P<0.05). CONCLUSIONS: In patients with ANOCA, the positive rate of myocardial ischemia exhibits variability among several noninvasive tests. A worsened psychological state is more closely linked to milder angina symptoms than to ischemia performance, highlighting the importance of focusing on symptom management in their psychological care. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03982901.

Depressive symptoms and mental stress-induced myocardial ischemia in patients with coronary heart disease.

OBJECTIVES: The aim of this study was to examine the associations between depressive symptoms and mental stress-induced myocardial ischemia (MSIMI) in patients with coronary heart disease (CHD). METHODS: Adult patients with documented CHD were recruited for baseline mental stress and exercise stress screening testing as a part of the enrollment process of the Responses of Myocardial Ischemia to Escitalopram Treatment trial. Patients were administered the Beck Depression Inventory II and the Center for Epidemiologic Studies Depression Scale. After a 24-48-hour ß-blocker withdrawal, participants completed three mental stress tests followed by a treadmill exercise test. Ischemia was defined as a) any development or worsening of any wall motion abnormality and b) reduction of left ventricular ejection fraction at least 8% by transthoracic echocardiography and/or ischemic ST-segment change by electrocardiography during stress testing. MSIMI was considered present when ischemia occurred in at least one mental test. Data were analyzed using logistic regression adjusting for age, sex, and resting left ventricular ejection fraction. RESULTS: One hundred twenty-five (44.2%) of 283 patients were found to have MSIMI, and 93 (32.9%) had ESIMI. Unadjusted analysis showed that Beck Depression Inventory II scores were positively associated with the probability of MSIMI (odds ratio = 0.1.30: 95% confidence interval = 1.06-1.60, p = .013) and number of MSIMI-positive tasks (all p < .005). These associations were still significant after adjustment for covariates (p values <.05). CONCLUSIONS: In patients with CHD, depressive symptoms were associated with a higher probability of MSIMI. These observations may enhance our understanding of the mechanisms contributing to the association of depressive symptoms to future cardiovascular events. Trial Registration Clinicaltrials.gov identifier: NCT00574847.

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.

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.

Consistency of Positron Emission Tomography and Myocardial Contrast Echocardiography in Diagnosing Mental Stress-Induced Myocardial Ischemia: Study Protocol of a Prospective Study-Background, Design and Method.

Mental stress-induced myocardial ischemia (MSIMI) has attracted increasing attention in the last 30 y. Positron emission tomography/computed tomography (PET/CT) is among the most accurate methods for evaluating myocardial perfusion. Even so, echocardiography seems to be a more harmless option when the radiation exposure and high expense of PET/CT are considered. To date, no previous studies have compared the consistency between echocardiography and PET/CT in the diagnosis of MSIMI. The primary aim of this research was to compare the consistency of myocardial contrast echocardiography and PET/CT in diagnosing MSIMI in women with angina symptom/ischemia but no obstructive coronary artery disease (INOCA). Fifty adult female patients with INOCA were recruited for a 12-min-long mental stress test. Each patient underwent both echocardiography and PET/CT at baseline and during mental stress testing; the interval between the two examinations was 1-3 d and the sequence was assigned naturally. MSIMI is defined by a summed difference score (SDS) ≥3 on PET-CT during mental stress testing. It is also defined by new abnormal wall motion, ejection fraction reduction ≥5%, and/or development of ischemic ST change on the electrocardiogram during mental stress testing. This study examined the consistency of PET/CT and myocardial contrast echocardiography in diagnosing MSIMI.

The Incidence, Risk Factors, and Chronobiology of Acute Myocardial Infarction Ten Years After Hurricane Katrina.

OBJECTIVE: The purpose of this study was to investigate the 10-year impact of Hurricane Katrina on the incidence of acute myocardial infarction (AMI) along with contributing risk factors and any alteration in chronobiology of AMI. METHODS: A single-center, retrospective, comparison study of AMI incidence was performed at Tulane University Health Sciences Center from 2 years before Hurricane Katrina to 10 years after Hurricane Katrina. A 6-year, pre-Katrina and 10-year, post-Katrina cohort were also compared according to pre-specified demographic, clinical, and chronobiological data. RESULTS: AMI incidence increased from 0.7% (150/21,079) to 2.8% (2,341/84,751) post-Katrina (P<0.001). The post-Katrina cohort had higher rates of coronary artery disease (36.4% vs. 47.9%, P=0.01), diabetes mellitus (31.3% vs. 39.9%, P=0.04), hyperlipidemia (45.4% vs. 59.3%, P=0.005), smoking (34.4% vs. 53.8%, P<0.001), drug abuse (10.2% vs. 15.4%, P=0.02), psychiatric illness (6.7% vs. 14.9%, P<0.001), medication non-adherence (7.3% vs. 15.3%, P<0.001), and lack of employment (7.2% vs. 16.4%, P<0.001). The post-Katrina group had increased rates of AMI during nights (29.8% vs. 47.8%, P<0.001) and weekends (16.1% vs. 29.1%, P<0.001). CONCLUSIONS: Even 10 years after the storm, Hurricane Katrina continues to be associated with increased incidence of AMI, higher prevalence of traditional cardiovascular and psychosocial risk factors, and an altered chronobiology of AMI toward nights and weekends. (Disaster Med Public Health Preparedness. 2019;13:217-222).