Mental Stress Reactivity in Women With CMD

Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexFemale
Age45+
SponsorEmory University

About this trial

Coronary Microvascular Dysfunction (CMD) occurs when there are problems in the small blood vessels/arteries of the heart, resulting in persistent chest pain that affects 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 and 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 track their mood, stress level, and symptoms for one week. Data and specimens will be saved for future research.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Symptomatic postmenopausal women with chest pain

age≥45 years old

willing to undergo cardiac MIBG scan

willing to undergo mental stress testing

Disqualifiers

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

Trial design

Design model

Parallel

Treatments tested in this trial

  • Study Procedures

    Other intervention

    All participants will answer a series of questionnaires that address several factors such as patient medical history, family history, medication usage, health behaviors, psychological factors, etc. Questionnaires related to symptoms, psychological factors, depression, anxiety, and quality of life will be taken. All participants will undergo 123I-MIBG SPECT imaging in the morning in a fasting state. Mental Stress Testing will be conducted in the Laboratory in the morning after fasting for at least 4 hours and withdrawal of all vasoactive medications, caffeine, and tobacco 24-48 hours before testing. Participants will also undergo 1-week of Home Monitoring using a single-use, noninvasive, water-resistant, 7-day ambulatory ECG monitoring, which offers the advantage of direct access to raw data that can be downloaded from the device after use. A 3-day food recall diary, cognitive assessments via the NIH Toolbox, and a Sleep diary during home monitoring will be collected.

Treatment groups

150 Participants
are divided into 3 treatment groups
Group A: Symptomatic women with no obstructive CAD who have CMDExperimental treatment 1 intervention
Group B: Symptomatic women with chronic obstructive CAD (oCAD)Experimental treatment 1 intervention
Group C: Asymptomatic control women with no prior history of CAD or anginaActive comparator 1 intervention

Trial outcomes

Primary outcomes

1

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.

Time frame
At the end of MIBG procedure
2

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

Time frame
Baseline (prior to stress testing) and during mental stress test
3

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.

Time frame
Baseline (prior to stress testing) and during mental stress test

Secondary outcomes

1

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.

Time frame
Baseline (prior to stress testing) and at the end of the mental stress test
2

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 minutes, the blood pressure cuff will be deflated, but to obtain the final tracings, the participant should lie still for another 5-10 minutes.

Time frame
Baseline (prior to stress testing) and at the end of the mental stress test
3

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.

Time frame
At the end of 1 week of monitoring

Other outcomes

1

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.

Time frame
At the end of 1 week of monitoring
2

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.

Time frame
Baseline and 12 months
3

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.

Time frame
Baseline and 12 months
4

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.

Time frame
Baseline and at the end of the mental stress test

Sponsors and contacts

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Emory University

Lead sponsor

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator