Stress Response Study for Heart Issues
Recruiting in Palo Alto (17 mi)
+3 other locations
Age: 18+
Sex: Female
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: Emory University
Must not be taking: Cardiac medications
Disqualifiers: Hypertension, Diabetes, Hyperlipidemia, others
No Placebo Group
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?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.
Will I have to stop taking my current medications?
The trial requires that participants be able to safely withdraw medications for mental stress testing. If you cannot safely stop your medications, you may not be eligible to participate.
What evidence supports the effectiveness of the drugs used in the Stress Response Study for Heart Issues?
Research shows that ACE inhibitors, like ramipril, can reduce the risk of heart attacks and strokes in people with cardiovascular risks, even if they don't have heart failure. Angiotensin receptor blockers also help reduce heart-related problems, especially in those who can't tolerate ACE inhibitors.
12345Is ranolazine safe for humans?
Ranolazine is generally considered safe for treating chronic stable angina, with side effects like dizziness, constipation, nausea, and a potential for affecting heart rhythm. It does not significantly alter heart rate or blood pressure, making it a safe option in combination with other heart medications.
678910How does this drug differ from other treatments for stress-related heart issues?
This drug may differ from other treatments by specifically targeting stress-induced changes in heart rate and blood pressure, potentially using a unique mechanism or combination of effects not seen in standard treatments. For example, some drugs like calcium antagonists can reduce blood pressure response to stress while preserving normal heart function, which might not be achieved by other medications.
1112131415Eligibility Criteria
This trial is for women over 50 with menopause-related chest pain and Coronary Microvascular Dysfunction (CMD), who can consent to tests. They must be willing to undergo a cardiac scan, mental stress testing, and have no acute illnesses or diabetes. Excluded are those with severe heart issues, uncontrolled hypertension, recent heart attacks, certain blood conditions, or significant artery blockages.Inclusion Criteria
Willing to sign the informed consent
I have never been diagnosed with heart disease.
I am healthy with no heart disease risk factors.
+9 more
Exclusion Criteria
My blood pressure is not higher than 180/100.
I have a serious blood disorder or significant anemia.
LDL >120 mg/dL
+26 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Baseline Assessment
Participants undergo baseline assessments including physical exams, blood tests, and stress tests
1 week
1 visit (in-person)
Mental Stress Testing
Participants undergo mental stress tests including speech and math tasks, with monitoring of autonomic and vascular responses
1 week
Multiple visits (in-person)
Home Monitoring
Participants use home devices to monitor autonomic function, sleep, mood, and stress levels
1 week
Follow-up
Participants are monitored for changes in quality of life and anginal symptoms
12 months
Periodic follow-up visits
Participant Groups
The study investigates how mental stress affects the autonomic function in postmenopausal women with CMD compared to others. It involves physical exams, blood tests, imaging of the heart and vessels, plus home monitoring of autonomic function and daily stress levels for one week.
3Treatment groups
Experimental Treatment
Active Control
Group I: Symptomatic women with no obstructive CAD who have CMDExperimental Treatment1 Intervention
Symptomatic women with chest pain and no obstructive CAD who have an abnormal myocardial flow reserve (MFR \< 2.5)
Group II: Symptomatic women with chronic obstructive CAD (oCAD)Experimental Treatment1 Intervention
This group will serve as one comparison group since these women represent the prevailing paradigm of ischemia from obstructive stenosis while sharing common cardiovascular risk factors with the CMD group.
Group III: Asymptomatic control women with no prior history of CAD or anginaActive Control1 Intervention
Asymptomatic control women with no prior history of CAD or angina, who are age-matched to the CMD women; not on any cardiac medications, who will also have to pass a maximal Bruce protocol exercise treadmill test.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Emory ClinicAtlanta, GA
Emory HospitalAtlanta, GA
Emory Hospital MidtownAtlanta, GA
Emory Saint Joseph's HospitalAtlanta, GA
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Who Is Running the Clinical Trial?
Emory UniversityLead Sponsor
National Heart, Lung, and Blood Institute (NHLBI)Collaborator
References
Angiotensin-converting-enzyme inhibitors in stable vascular disease without left ventricular systolic dysfunction or heart failure: a combined analysis of three trials. [2020]Angiotensin-converting-enzyme (ACE) inhibitors reduce cardiovascular mortality and morbidity in patients with heart failure or left ventricular systolic dysfunction (LVSD). Three large trials have assessed the effect of ACE inhibitors in stable patients without these conditions but with atherosclerosis. We undertook a systematic review of the Heart Outcomes Prevention Evaluation (HOPE), the European trial on Reduction Of cardiac events with Perindopril among patients with stable coronary Artery disease (EUROPA), and the Prevention of Events with ACE inhibition (PEACE) studies to determine the consistency with which ACE inhibitors reduce total mortality and fatal and non-fatal cardiovascular events.
The HOPE Study (Heart Outcomes Prevention Evaluation). [2013]The Heart Outcomes Prevention Evaluation (HOPE) study was designed to test the hypotheses that two preventive intervention strategies, namely angiotensin-converting enzyme (ACE) inhibition or vitamin E, would improve morbidity and mortality in patients at high risk of cardiovascular events compared with placebo. This review addresses the ACE inhibitor (ACE-I) (ramipril) arm of the study, both on the trial population as a whole, and on the large diabetic subgroup. Patients were included in the study who were considered to be at high risk of future fatal or non-fatal cardiovascular events, by virtue of their age (>55 years), existing or previous cardiovascular disease, or diabetes. Diabetics had at least one other risk factor, either known vascular disease or other factors such as cigarette smoking, high cholesterol or hypertension. Ramipril or placebo was added to concomitant medication, which included, in a substantial proportion of patients, antihypertensive drugs (excluding ACE-I), lipid-lowering agents or aspirin. As a result, despite a history of hypertension in nearly 50% of patients, blood pressure (BP) at baseline was normal and the reduction in BP attributable to ramipril modest (a fall of 3-4 mmHg systolic BP and 1-2 mmHg diastolic). The trial was stopped early on the advice of the Data Monitoring Committee because of convincing evidence of the benefit of ramipril treatment on the combined primary endpoint of cardiovascular death, non-fatal myocardial infarct (MI) and non-fatal stroke (14% vs. 17.8% on ramipril and placebo, respectively; relative risk reduction 22%, p
The anti-ischemic potential of angiotensin-converting enzyme inhibition: insights from the heart outcomes prevention evaluation trial. [2020]Therapy with an angiotensin-converting enzyme (ACE) inhibitor is established for reducing excessive blood pressure, reducing mortality in patients with congestive heart failure (CHF), preventing the development of CHF in patients with asymptomatic left ventricular (LV) dysfunction, and preventing death and CHF when initiated early after the onset of acute myocardial infarction (MI). Although these benefits have been attributed largely to hemodynamic mechanisms, recent preclinical and clinical evidence reveal ACE inhibition as potent in preventing ischemic events and in blocking an array of ischemic processes, including atherogenesis. A major contributor to this new evidence is the large, placebo-controlled Heart Outcomes Prevention Evaluation (HOPE) trial, which found that the ACE inhibitor ramipril ( 10 mg daily) prevented MI and other ischemic events in patients with a broad range of cardiovascular (CV) risks (including coronary artery disease, stroke, peripheral vascular disease, or diabetes plus one additional risk factor) but no LV dysfunction or history of heart failure at baseline. The data from the HOPE trial suggest a greatly expanded role for ramipril in the prevention and management of CV disease.
Heart failure guidelines: What's new? [2021]Heart Failure is a global epidemic, affecting approximately 5 million adults in the U.S.A. The cornerstone of contemporary pharmacological therapy targets the over activated renin-angiotensin-aldosterone and sympathetic autonomic systems. The 2016 focused pharmacologic update on the current Heart Failure Guidelines introduces the use of two newly approved regimens valsartan/sacubitril and ivabradine. Over the last two decades, guideline directed medical therapy has accomplished significant improvement in survival rates among heart failure patients; however these novel compounds were reported to exert additional mortality and morbidity benefits, in heart failure subpopulations with reduced ejection fraction.
Update on therapy for heart failure. [2019]The success of angiotensin-converting enzyme (ACE) inhibitors in reducing morbidity and mortality in patients with heart failure has led to investigations of other inhibitors of the renin-angiotensin-aldosterone system. Although ACE inhibitors remain first-line drugs in the treatment of heart failure and left ventricular dysfunction, clinical evidence suggests that a newer class of agents--angiotensin II receptor blockers--may provide additional benefit by blocking the adverse effects of angiotensin II more completely. An improved adverse-effect profile also makes angiotensin II receptor blockers appropriate in patients who cannot tolerate ACE inhibitors. Clinical trials have demonstrated the beneficial effects of angiotensin II receptor blockers on the combined endpoints of morbidity and mortality in patients with heart failure. Aldosterone antagonism with spironolactone has additive benefits in patients receiving an ACE inhibitor. The most recent treatment guidelines for heart failure recommend the use of angiotensin II receptor blockers and spironolactone in selected patients.
Ranolazine: a novel agent that improves dysfunctional sodium channels. [2015]Treatment for coronary heart disease is usually directed at either increasing myocardial oxygen supply or decreasing myocardial oxygen demand. Although combination therapy with beta-blockers, calcium-channel blockers and nitrates are effective, many patients suffer from adverse effects of hypotension and bradycardia. Ranolazine is a novel medication that reduces ischaemia by preventing sodium induced calcium overload in myocardial cells without adversely affecting haemodynamic parameters. This agent is the first in the USA to be approved to treat angina in over 10 years. The purpose of this review is to evaluate the pharmacology, pharmacokinetics, clinical trials for safety and efficacy, precautions, adverse effects, drug interactions, and dosage and administration of ranolazine in the treatment of chronic stable angina and acute coronary syndrome.
[Ranolazine in the treatment of chronic stable angina]. [2015]Coronary artery disease is the leading cause of death in Europe and in the US and angina is the most common symptom associated with stable coronary artery disease. Despite receiving optimal antianginal therapy, based on agents such as beta-blockers, calcium channel antagonists and nitrates, many patients continue to experience angina. Furthermore, the administration of these drugs is limited by adverse effects such as bradycardia or hypotension. Ranolazine is a new antianginal agent, recently approved as add-on therapy in patients with stable angina. This review will focus on its mechanism of action, tolerability, highlighting the clinical benefit coming from its use.
[Ranolazine--an additional anti-anginal drug]. [2015]Ranolazine is a new drug for use in patients with stable angina pectoris. Unlike other antianginal drugs ranolazine does not alter heart rate or systemic blood pressure. Inhibition of the persistent or late sodium current (I(Na,late)) by ranolazine reduces [Na(+) ](i)-dependent Ca(2+) overload and the effects of ischaemia. Moreover, ranolazine holds potential promise to be effective in treatment of atrial fibrillation and diastolic heart failure.
[Triple antianginal combinations in the treatment of elderly and senile patients with stable angina]. [2018]To compare the efficiency and safety of antianginal therapy (AAT) using a combination of bisoprolol, ivabradine, and trimetazidine or ranolazine in elderly and senile patients with stable angina.
Ranolazine for chronic stable angina. [2015]Ranolazine is a new and unique antianginal drug that has been approved for the treatment of chronic stable angina pectoris. The drug is administered as a sustained-release formulation. Although the drug's mechanism of action has not been fully elucidated, current thinking is that ranolazine, a selective inhibitor of late sodium influx, attenuates the abnormalities of ventricular repolarisation and contractility associated with ischaemia. Three randomised trials have shown efficacy for ranolazine in increasing exercise testing or reducing anginal episodes or use of glyceryl trinitrate. Side-effects include dizziness, constipation, nausea, and the potential for prolongation of the QT(c) interval. Ranolazine seems to be a safe addition to current traditional drugs for chronic stable angina, especially in aggressive multidrug regimens.
Hemodynamic response patterns to mental stress: diagnostic and therapeutic implications. [2019]Stress has been identified as contributing to the development of cardiovascular disease. The pathophysiologic link between stress and disease still remains unclear. Because experimental stress testing in the laboratory permits the examination of the underlying mechanism for stress-induced blood pressure, analyses of cardiovascular reactivity during emotional stress could be of particular clinical importance. The analyses of pooled data during the past 6 years (n = 298, age from 20 to 60 years, normotensive subjects as well as patients with borderline and mild essential hypertension) reveal that stress-induced changes in stroke volume and especially in total peripheral resistance are crucial parameters to analyze the hemodynamic stress response. However, neither those simple nor complex response patterns such as "hot reactor" describe clinically distinct subgroups of persons. When physiologic testing was repeated in hypertensive patients after effective long-term antihypertensive therapy with clonidine, oxprenolol, nitrendipine, or enalapril, no attenuation of the stress-induced increase in blood pressure was found in any of these groups. However, heart rate reactivity and stress-induced changes in total peripheral resistance were altered significantly by oxprenolol and nitrendipine. The beta-adrenoceptor blocker decreased heart rate reactivity and increased reactivity of peripheral resistance; the calcium antagonist decreased stress-induced changes in peripheral resistance and increased the heart rate response. The centrally acting sympatholytic regimen and the angiotensin-converting enzyme inhibitor had no impact on the hemodynamic response pattern during emotional challenge.
[Cardiovascular response to mental and physical stress in hyper-reactive normotensive subjects. Beta blockade effect]. [2013]The aim of our study was to evaluate the cardiovascular reactivity in healthy normotensive subjects without medication, using mental and physical stress techniques: Stroop color word conflict test (SCWCT), anticipatory blood pressure response to exercise (ARE) and stress testing (ST). We analized the effects of a selective beta 1 betablocker: bisoprolol (B) on cardiovascular reactivity in our subjects (s). We studied 42 s, but only 30 (21 females and 9 males) were included who were hyperreactives. The mean age was 42.5 years. The higher values of systolic (SBP) and diastolic blood pressure (DBP) during the mental stress (MS) were taken as a measure of reactivity considering hyperreactive response an increase of 30 mm Hg or more and/or 15 mm Hg or more respectively. A prospective, randomized and double blind study on the effects of an oral daily doses of B (5 mg) vs placebo (P) was performed. Statistical analysis was realized with the Fisher exact test. In the results, we could observed a lower sensitivity of ARE and ST vs SCWCT. The 15 s who recieved P followed hyperreactives but 6 of 15 s treated with B were non reactives (p
Cardiovascular reactivity to stressors in Indian young adults with normotensive parents. [2021]Stress-induced increase in heart-rate and blood pressure is termed cardiovascular reactivity (CVR). Various studies are designed to monitor the CVR and use different types of experimental stressors. We have compared the CVR to three different stressors used in CVR based studies (cold pressor task, hand grip test, and video game) to identify the best suited stressor for any study design.
Pharmacological modulation of stress-induced cardiovascular hyperreactivity in essential hypertension. [2013]The effects of the calcium antagonist isradipine and the beta-blocker metoprolol, which are based on different antihypertensive therapeutic principles, were evaluated in 52 men with mild-to-moderate hypertension in a 6-week, double-blind, randomized study. Mental stress-testing was performed before and after active treatment. With isradipine (n = 26), the stress-induced responses of cardiac output and total peripheral resistance were not significantly changed, but the blood pressure (BP) response, specifically the diastolic response, was decreased. With metoprolol (n = 26), there was a decreased response of cardiac output and an increased response of total peripheral resistance, and the BP response was even greater than it had been before treatment. Thus, these results indicate that beta-blockade is effective in reducing cardiac responsiveness but, because of vascular counterregulatory mechanisms, BP responsiveness is not decreased. In contrast, calcium antagonism preserves the physiological hemodynamic profile while reducing BP responsiveness to stress.
Effect of calcium antagonists on stress-induced rise in blood pressure and heart rate: a double-blind, placebo-controlled study. [2019]The current study was designed to evaluate the effect of treatment with calcium antagonists on stress-induced increases in blood pressure and heart rate. SUBIECTS, MATERIAL AND METHODS: Two models of stress were chosen, cold stress and isometric handgrip exercise. Six healthy volunteers were randomized to receive amlodipine (5 mg), lacidipine (4 mg) for a two-day period in a double-blind, crossover design. Thirty hypertensive patients received the same treatment for a period of one week in a double-blind, parallel design. The effects of stress on blood pressure and heart rate were taken at baseline and after drug treatment.