Post-menopause Clinical Trial
Official title:
Mental Stress Reactivity in Women With Coronary Microvascular Dysfunction
Coronary Microvascular Dysfunction (CMD) occurs when there are problems in small blood vessels/arteries in the heart and symptoms of persistent chest pain that impact women. There are an estimated 3 million women in the US with CMD and about 100,000 new cases annually. This research will investigate whether the stress response physiology and autonomic function in response to mental stress are different in women with CMD compared to other groups. The autonomic nervous system (ANS) controls normally involuntary activities, such as heart rate, respiration (breathing), body temperature, blood pressure, and urinary function. This study will also examine how chronic and daily life mental stress affects the heart, blood vessels. Participants from this study will be recruited mainly from Emory Healthcare-associated hospitals, the Emory Heart Disease Center for Prevention, and Emory Healthcare outpatient cardiology clinics. Participants will have physical exams, blood tests, stress tests, exercise tests, surveys, questionnaires, and images taken of their hearts and blood vessels. They will be asked to take home devices to monitor their autonomic function, sleep and to track their mood, stress level, and symptoms for one week. Data and specimens will be saved for future research.
Status | Recruiting |
Enrollment | 150 |
Est. completion date | December 31, 2026 |
Est. primary completion date | September 30, 2026 |
Accepts healthy volunteers | No |
Gender | Female |
Age group | 45 Years and older |
Eligibility | CMD Group Inclusion Criteria: - Symptomatic postmenopausal women with chest pain - age=50 years old - willing to undergo cardiac MIBG scan - willing to undergo mental stress testing - competent to give informed consent Exclusion Criteria: - Significant epicardial stenosis (defined by coronary stenosis = 70% in any epicardial coronary artery or hemodynamically significant stenosis determined by fractional flow reserve) - Left ventricular systolic dysfunction (ejection fraction = 50%) - Heart failure with a preserved ejection fraction - Significant anemia or blood dyscrasia - Severe uncontrolled hypertension >180/100 - Unable to lie flat for mental stress testing - Pre-menopausal - Pregnant - Pericarditis/myocarditis - History of percutaneous coronary intervention - Coronary artery bypass grafting - Acute myocardial infarction/acute coronary syndrome/unstable angina within 1 month - Significant valvular disease, including aortic or mitral stenosis - Sinus node dysfunction/pacemaker, 2nd or 3rd-degree atrioventricular block - Severe lung, renal, liver, or psychiatric illness - Current neoplasm - History of substance abuse - Acute illness such as infection in the previous 4 weeks - Life-expectancy less than 2 years - Unable to safely withdraw medications for mental stress testing - Significant psychiatric illness that precludes safe participation in the study - Conditions that preclude accurate or safe testing and patient refusal - Unable to consent Obstructive CAD (oCAD) Group Inclusion Criteria: - Symptomatic postmenopausal women with chest pain who have obstructive CAD in at least one epicardial coronary artery - willing to undergo cardiac MIBG scan - willing to undergo mental stress testing - competent to give informed consent Exclusion Criteria: - Significant epicardial stenosis (defined by coronary stenosis = 70% in any epicardial coronary artery or hemodynamically significant stenosis determined by fractional flow reserve) - Left ventricular systolic dysfunction (ejection fraction = 50%) - Heart failure with a preserved ejection fraction - Significant anemia or blood dyscrasia - Severe uncontrolled hypertension >180/100 - Unable to lie flat for mental stress testing - Pre-menopausal - Pregnant - Pericarditis/myocarditis - History of percutaneous coronary intervention - Coronary artery bypass grafting - Acute myocardial infarction/acute coronary syndrome/unstable angina within 1 month - Significant valvular disease, including aortic or mitral stenosis - Sinus node dysfunction/pacemaker, 2nd or 3rd-degree atrioventricular block - Severe lung, renal, liver, or psychiatric illness - Current neoplasm - History of substance abuse - Acute illness such as infection in the previous 4 weeks - Life-expectancy less than 2 years - Unable to safely withdraw medications for mental stress testing - Significant psychiatric illness that precludes safe participation in the study - Conditions that preclude accurate or safe testing and patient refusal - Unable to consent Asymptomatic Control Group Inclusion Criteria: - Asymptomatic postmenopausal women, age = 50 years old - Healthy volunteer with no cardiac risk factors - No history or diagnosis of heart disease - Not on any cardiac medications - Normal maximal exercise treadmill stress testing (ETT) - Fully understanding and willing to undergo mental stress testing - Willing to sign the informed consent Exclusion Criteria: - Significant epicardial stenosis (defined by coronary stenosis = 70% in any epicardial coronary artery or hemodynamically significant stenosis determined by fractional flow reserve) - Left ventricular systolic dysfunction (ejection fraction = 50%) - Heart failure with a preserved ejection fraction - Significant anemia or blood dyscrasia - Severe uncontrolled hypertension >180/100 - Unable to lie flat for mental stress testing - Pre-menopausal - Pregnant - Pericarditis/myocarditis - History of percutaneous coronary intervention - Coronary artery bypass grafting - Acute myocardial infarction/acute coronary syndrome/unstable angina within 1 month - Significant valvular disease, including aortic or mitral stenosis - Sinus node dysfunction/pacemaker, 2nd or 3rd-degree atrioventricular block - Severe lung, renal, liver, or psychiatric illness - Current neoplasm - History of substance abuse - Acute illness such as infection in the previous 4 weeks - Life-expectancy less than 2 years - Unable to safely withdraw medications for mental stress testing - Significant psychiatric illness that precludes safe participation in the study - Orthopedic limitation that will prevent ETT - LDL >120 mg/dL - Fasting blood glucose >95 mg/dL - Hypertension, defined as resting BP >120/80 - Diabetes - Hyperlipidemia - Smoking - Conditions that preclude accurate or safe testing and patient refusal - Unable to consent |
Country | Name | City | State |
---|---|---|---|
United States | Emory Clinic | Atlanta | Georgia |
United States | Emory Hospital | Atlanta | Georgia |
United States | Emory Hospital Midtown | Atlanta | Georgia |
United States | Emory Saint Joseph's Hospital | Atlanta | Georgia |
Lead Sponsor | Collaborator |
---|---|
Emory University | National Heart, Lung, and Blood Institute (NHLBI) |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Stressor frequency over 7 days | Participants will use the Actiwatch® Spectrum Pro (Philips-Respironics, Inc.) wristwatch-style actigraphs containing a calibrated accelerometer that records movement activity in discrete epochs and detects physical activity as well as onset and offset of sleep. It provides sleep quality parameters which will be a useful addition to our analysis, as sleep quality is related to stress. | At the end of 1 week of monitoring | |
Other | Assessment of quality of life and relationship to anginal symptoms | Anginal symptoms and quality of life will be assessed at 12 months of follow-up. MACE and angina hospitalization will also be obtained. Participants will complete the Seattle Angina Questionnaire (SAQ). SAQ asks questions about daily activities and how many limitations they experience due to chest pain, chest tightness, or angina over the past 4weeks.scored by assigning each response an ordinal value, beginning with 1 for the response that implies the lowest level of functioning, and summing across items within each of the five scales. Scale scores are then transformed into a 0- 100 range by subtracting the lowest possible scale score, dividing by the range of the scale, and multiplying by 100. Because each scale monitors a unique dimension of coronary artery disease, no summary score is generated. | Baseline and 12 months | |
Other | Assessment of general health status | SF-36v2 Health Survey measures functional health and well-being from the patient's point of view. It consists of eight scales yielding two summary measures: physical and mental health. The physical health measure includes four scales of physical functioning, role-physical, bodily pain, and general health. The mental health measure is composed of vitality, social functioning, role-emotional, and mental health. A final item, termed self-reported health transition, is answered but is not included in the scoring process. The SF-36 offers a choice of recall format: standard (4 weeks) or acute (1 week) time frame. Likert scales and yes/no options are used to assess function and well-being. To score the SF-36, scales are standardized with a scoring algorithm or by the SF-36v2 scoring software to obtain a score ranging from 0 to 100. Higher scores indicate better health status, and a mean score of 50 has been articulated as a normative value for all scales. | Baseline and 12 months | |
Other | Changes in injury and inflammation biomarker with mental stress among the three groups. | The research team will administer questionnaires and different types of mental stress tests, including a speech task over a situation that made participant upset or angry, and/or a math test. Blood will be drawn to measure inflammatory biomarker. | Baseline and at the end of the mental stress test | |
Other | Changes in catecholamines (norepinephrine and epinephrine) with mental stress among the three groups. | The research team will administer questionnaires and different types of mental stress tests, including a speech task over a situation that made you upset or angry, and/or a math test. Blood will be drawn to measure stress hormones. | Baseline and during mental stress test | |
Primary | Planar late Heart to Mediastinal Ratio (MIBG imaging) | The research team will compare resting sympathetic activity measured with 123I-meta-iodobenzylguanidine (MIBG) imaging between CMD women and the two control groups. The heart to the mediastinal ratio (HMR) which is an index of MIBG uptake will be calculated as per standard methods. The HMR reflects norepinephrine kinetics. Higher sympathetic activity and turnover cause less MIBG to be retained and result in a lower HMR. MIBG SPECT defect score will be determined by late (4 hours) MIBG uptake by visual blind scoring using the standard 17-segment model with 0=normal tracer uptake, 1=mildly reduced uptake, 2=moderately reduced uptake, 3=severely reduced uptake, 4=absent tracer uptake, as defined by Bax et al. | At the end of MIBG procedure | |
Primary | Changes in HRV with mental stress | The research team will also compare autonomic reactivity during a standardized mental stress test, including heart rate variability (HRV) between CMD women and the two control groups | Baseline (prior to stress testing) and during mental stress test | |
Primary | Changes in pre-ejection period (PEP) with mental stress | The research team will also compare autonomic reactivity during a standardized mental stress test, including the pre-ejection period (PEP) between CMD women and the two control groups. This measures systolic time interval and reflects cardiac contractility (which is under the beta-adrenergic influence). Impedance ECG measures PEP from the onset of ventricular depolarization (Q-wave on ECG) to the opening of the aortic valve for ejection of blood from the left ventricle. | Baseline (prior to stress testing) and during mental stress test | |
Secondary | Changes in flow mediated dilation (FMD test) to acute mental stress in CMD women. | The research team will compare peripheral microvascular vasoconstriction during mental stress, as well as changes in peripheral microvascular function and flow-mediated dilation with mental stress, between CMD women and the two control groups. Readings of blood flow in one of the arteries of the arm using an ultrasound. Then a blood pressure cuff will be placed around the forearm and will be inflated to stop the flow of blood for 5 minutes. After 5 minutes, the blood pressure cuff will be deflated and the readings taken again. | Baseline (prior to stress testing) and at the end of the mental stress test | |
Secondary | Changes in Peripheral arterial tonometry (PAT) test to acute mental stress in CMD women. | The research team will compare peripheral microvascular vasoconstriction during mental stress, as well as changes in peripheral microvascular function and flow-mediated dilation with mental stress, between CMD women and the two control groups. A blood pressure cuff will be placed on one arm and probes will be placed on the fingers. In order to get a good tracing, the participant will need to remain quiet and very still for at least 5 minutes. Then, the blood pressure cuff will be inflated for 5 minutes and more recordings will be done. At the end of the 5-minute period, the blood pressure cuff will be deflated but to obtain the final tracings, the participant should lie still for another 5-10 minutes. | Baseline (prior to stress testing) and at the end of the mental stress test | |
Secondary | Examine whether chronic stress burden and autonomic dysfunction during daily life is elevated in CMD women. | The research team will compare anginal symptoms, chronic and daily life stress, and autonomic function measured during one week of home monitoring between CMD and the two control groups. Participants will use a smartphone to track their symptoms and stress. | At the end of 1 week of monitoring |
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