Coronary Microvascular Dysfunction
Conditions
Keywords
Coronary Microvascular Dysfunction, Plant-Based Diet, Flow-Mediated Dilation
Brief summary
This study will evaluate whether a fully provided, unrefined, polyphenol-rich plant-based diet can improve blood vessel function in adults with coronary microvascular dysfunction (CMD), a condition that causes reduced blood flow in the small vessels of the heart despite the absence of major coronary artery blockages. Participants will follow the diet for 12 weeks while continuing their usual medical care. Researchers will assess changes in vascular function, symptoms, blood pressure, blood lipids, and other health measures throughout the study. Participants have up to 60 days after consent to complete screening and pre-intervention baseline assessments, potentially over two visits. Day 0 is counseling/education, and diet initiation. Weeks 4, 8, and 12 are measured from Day 0.
Detailed description
Coronary microvascular dysfunction (CMD) is characterized by impaired coronary microvascular vasodilation and reduced coronary flow reserve in the absence of obstructive epicardial coronary artery disease. CMD is a common cause of ischemic symptoms and is associated with persistent angina, reduced quality of life, and increased cardiovascular risk. Existing therapies are largely directed toward symptom management, and additional strategies that address underlying disease mechanisms are needed. Oxidative stress, impaired nitric oxide bioavailability, and abnormalities in vascular function are believed to contribute to CMD pathophysiology. Diets rich in unrefined plant foods contain polyphenols and other bioactive compounds that may favorably affect vascular biology, endothelial function, and redox balance. However, the effects of a polyphenol-rich plant-based dietary intervention in individuals with CMD have not been well characterized. The purpose of this study is to evaluate the effects of an unrefined, polyphenol-rich plant-based dietary pattern on vascular function in adults with CMD and to explore potential biological pathways associated with response to the intervention. The study will also assess the impact of the dietary intervention on symptoms, cardiometabolic health, and measures related to vascular and redox biology. Findings from this study may improve understanding of the role of dietary modification as a potential adjunctive approach for CMD and help inform future dietary and lifestyle interventions targeting coronary microvascular disease.
Interventions
OTHERPolyphenol-Rich Plant-Based Diet
A fully provided, weight-maintaining, unrefined, polyphenol-rich plant-based dietary intervention administered for 12 weeks. The diet is designed around whole plant foods, including fruits, vegetables, legumes, whole grains, nuts, and seeds, and excludes animal products, refined grains, added sugars, sugar-sweetened beverages, and commercially processed plant-based meat or cheese substitutes. Participants receive nutrition education, ongoing dietary counseling, meal provision, and vitamin B12 supplementation throughout the intervention period
Sponsors
Emory University
National Heart, Lung, and Blood Institute (NHLBI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
45 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Women must be postmenopausal. * History of angina, ischemic symptoms, or symptoms consistent with ischemia in the absence of obstructive coronary artery disease. * No obstructive coronary artery disease (\<50% stenosis in any epicardial coronary artery or fractional flow reserve \>0.80). * Clinically documented coronary microvascular dysfunction (CMD), including coronary flow reserve \<2.5 and/or index of microcirculatory resistance ≥25, or equivalent documentation in the medical record. * Stable cardiometabolic medication regimen for at least 2 months before enrollment. * Willingness to consume the study-provided plant-based diet and complete all study procedures. * Ability to provide informed consent Exclusion: * Obstructive coronary artery disease or prior coronary revascularization (PCI or CABG). * Recent acute coronary syndrome, unstable angina, decompensated heart failure, or other clinically unstable cardiovascular disease. * Significant structural heart disease, uncontrolled arrhythmia, severe uncontrolled hypertension, or symptomatic hypotension. * Severe renal disease (eGFR \<30 mL/min/1.73 m²) or significant liver disease. * Current vegetarian or vegan diet, or habitual consumption of ≤4 servings of animal products per week. * Severe food allergies, dietary restrictions, or gastrointestinal conditions that would prevent adherence to the study diet. * Current use of weight-loss medications, including GLP-1 receptor agonists. * Active eating disorder. * Recent (\>5%) intentional or unintentional weight change within the previous 3 months. * Participation in another interventional study that could affect study outcomes. * Any medical, psychiatric, or social condition that, in the investigator's judgment, would make participation unsafe or interfere with study completion.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Brachial Artery Flow-Mediated Dilation (FMD) | Baseline (pre-intervention), Week 4, Week 8, and Week 12 | Brachial artery flow-mediated dilation (FMD) will be assessed by ultrasound and reported as the percentage increase in brachial artery diameter from the resting pre-occlusion diameter to the peak post-occlusion diameter. FMD is a continuous physiological measurement. Higher FMD percentages indicate greater endothelium-dependent vasodilation and better peripheral endothelial function. Change from baseline will be calculated as the FMD percentage at each post-baseline visit minus the baseline FMD percentage and reported in percentage points. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Cutaneous Microvascular Function | Baseline, Week 4, Week 8, and Week 12 | Cutaneous microvascular function will be assessed using laser Doppler flowmetry during standardized local heating. Mean cutaneous vascular conductance during the stable local-heating plateau will be calculated by dividing laser Doppler flux by concurrently measured mean arterial pressure and reported in perfusion units per millimeter of mercury (PU/mmHg). Cutaneous vascular conductance is a continuous physiological measurement. Higher values during local heating indicate greater cutaneous microvascular vasodilatory responsiveness. Change from baseline will be calculated as the value at each post-baseline visit minus the baseline value. |
| Change in Digital Endothelial Function | Baseline, Week 4, Week 8, and Week 12 | Digital endothelial function will be assessed using peripheral arterial tonometry and reported as the Reactive Hyperemia Index (RHI). RHI is a continuous, dimensionless physiological index derived from the post-occlusion digital pulse-amplitude response and normalized to the control finger. RHI has no fixed minimum or maximum. Higher RHI values indicate better digital endothelial function. Change from baseline will be calculated as the value at each post-baseline visit minus the baseline value. |
| Change in Central Arterial Stiffness | Baseline, Week 4, Week 8, and Week 12. | Central arterial stiffness assessed by carotid-femoral pulse wave velocity (PWV) using the SphygmoCor system. Pulse wave velocity will be analyzed in meters per second, with lower values reflecting lower arterial stiffness. |
| Change in Systemic Redox Status | Baseline, Week 4, Week 8, and Week 12. | Plasma aminothiol redox status measured by concentrations of reduced and oxidized aminothiol species, including cysteine, cystine, glutathione, and glutathione disulfide. |
| Change in Total cholesterol concentration | Baseline, Week 4, Week 8, and Week 12 | Fasting blood total cholesterol concentration will be measured at baseline and each post-baseline assessment. Change from baseline will be calculated as the post-baseline concentration minus the baseline concentration and reported in milligrams per deciliter (mg/dL). |
| Change in Low-Density Lipoprotein Cholesterol Concentration | Baseline, Week 4, Week 8, and Week 12 | Fasting blood low-density lipoprotein (LDL) cholesterol concentration will be measured at baseline and each post-baseline assessment. Change from baseline will be calculated as the post-baseline concentration minus the baseline concentration and reported in milligrams per deciliter (mg/dL). |
| Change in High-Density Lipoprotein Cholesterol Concentration | Baseline, Week 4, Week 8, and Week 12 | Fasting blood high-density lipoprotein (HDL) cholesterol concentration will be measured at baseline and each post-baseline assessment. Change from baseline will be calculated as the post-baseline concentration minus the baseline concentration and reported in milligrams per deciliter (mg/dL). |
| Change in Triglyceride Concentration | Baseline, Week 4, Week 8, and Week 12 | Fasting blood triglyceride concentration will be measured at baseline and each post-baseline assessment. Change from baseline will be calculated as the post-baseline concentration minus the baseline concentration and reported in milligrams per deciliter (mg/dL). |
| Change in Apolipoprotein B Concentration | Baseline, Week 4, Week 8, and Week 12 | Fasting blood apolipoprotein B (ApoB) concentration will be measured at baseline and each post-baseline assessment. Change from baseline will be calculated as the post-baseline concentration minus the baseline concentration and reported in milligrams per deciliter (mg/dL). |
| Change in Apolipoprotein A-I Concentration | Baseline, Week 4, Week 8, and Week 12 | Fasting blood apolipoprotein A-I (ApoA-I) concentration will be measured at baseline and each post-baseline assessment. Change from baseline will be calculated as the post-baseline concentration minus the baseline concentration and reported in milligrams per deciliter (mg/dL). |
| Change in Lipoprotein(a) Concentration | Baseline, Week 4, Week 8, and Week 12 | Fasting blood lipoprotein(a) concentration will be measured at baseline and each post-baseline assessment. Change from baseline will be calculated as the post-baseline concentration minus the baseline concentration and reported in nanomoles per liter (nmol/L). |
| Change in Blood Glucose Concentration | Baseline, Week 4, Week 8, and Week 12. | Fasting blood glucose concentration will be measured at baseline and each post-baseline assessment. Change from baseline will be calculated as the post-baseline concentration minus the baseline concentration and reported in milligrams per deciliter (mg/dL). |
| Change in Blood Urea Nitrogen | Baseline, Week 4, Week 8, and Week 12. | Blood urea nitrogen (BUN) will be measured at baseline and each post-baseline assessment. Change from baseline will be calculated as the post-baseline value minus the baseline value and reported in milligrams per deciliter (mg/dL). |
| Change in Blood Creatinine Concentration | Baseline, Week 4, Week 8, and Week 12. | Blood creatinine concentration will be measured at baseline and each post-baseline assessment. Change from baseline will be calculated as the post-baseline concentration minus the baseline concentration and reported in milligrams per deciliter (mg/dL). |
| Change in Blood Sodium Concentration | Baseline, Week 4, Week 8, and Week 12. | Blood sodium concentration will be measured at baseline and each post-baseline assessment. Change from baseline will be calculated as the post-baseline concentration minus the baseline concentration and reported in millimoles per liter (mmol/L). |
| Change in Blood Potassium Concentration | Baseline, Week 4, Week 8, and Week 12. | Blood potassium concentration will be measured at baseline and each post-baseline assessment. Change from baseline will be calculated as the post-baseline concentration minus the baseline concentration and reported in millimoles per liter (mmol/L). |
| Change in Blood Chloride Concentration | Baseline, Week 4, Week 8, and Week 12. | Blood chloride concentration will be measured at baseline and each post-baseline assessment. Change from baseline will be calculated as the post-baseline concentration minus the baseline concentration and reported in millimoles per liter (mmol/L). |
| Change in Blood Carbon Dioxide Concentration | Baseline, Week 4, Week 8, and Week 12. | Blood total carbon dioxide, reflecting serum bicarbonate, will be measured at baseline and each post-baseline assessment. Change from baseline will be calculated as the post-baseline concentration minus the baseline concentration and reported in millimoles per liter (mmol/L). |
| Change in Blood Calcium Concentration | Baseline, Week 4, Week 8, and Week 12. | Blood calcium concentration will be measured at baseline and at each post-baseline assessment. Change from baseline will be calculated as the post-baseline concentration minus the baseline concentration and reported in milligrams per deciliter (mg/dL). |
| Change in Blood Total Protein Concentration | Baseline, Week 4, Week 8, and Week 12. | Blood total protein concentration will be measured at baseline and each post-baseline assessment. Change from baseline will be calculated as the post-baseline concentration minus the baseline concentration and reported in grams per deciliter (g/dL). |
| Change in Total Blood Albumin Concentration | Baseline, Week 4, Week 8, and Week 12. | Blood albumin concentration will be measured at baseline and at each post-baseline assessment. Change from baseline will be calculated as the post-baseline concentration minus the baseline concentration and reported in grams per deciliter (g/dL). |
| Change in Total Bilirubin Concentration | Baseline, Week 4, Week 8, and Week 12. | Blood total bilirubin concentration will be measured at baseline and each post-baseline assessment. Change from baseline will be calculated as the post-baseline concentration minus the baseline concentration and reported in milligrams per deciliter (mg/dL). |
| Change in Alkaline Phosphatase Activity | Baseline, Week 4, Week 8, and Week 12. | Blood alkaline phosphatase activity will be measured at baseline and each post-baseline assessment. Change from baseline will be calculated as the post-baseline value minus the baseline value and reported in units per liter (U/L). |
| Change in Alanine Aminotransferase Activity | Baseline, Week 4, Week 8, and Week 12. | Blood alanine aminotransferase (ALT) activity will be measured at baseline and each post-baseline assessment. Change from baseline will be calculated as the post-baseline value minus the baseline value and reported in units per liter (U/L). |
| Change in Aspartate Aminotransferase Activity | Baseline, Week 4, Week 8, and Week 12. | Blood aspartate aminotransferase (AST) activity will be measured at baseline and each post-baseline assessment. Change from baseline will be calculated as the post-baseline value minus the baseline value and reported in units per liter (U/L). |
| Change in Complete Blood Count With Differential | Baseline, Week 4, Week 8, and Week 12. | Changes in hematologic measures obtained from complete blood count with differential testing. |
| Change in Angina Burden and Disease-Specific Quality of Life | Baseline, Week 4, Week 8, and Week 12. | The Seattle Angina Questionnaire (SAQ) is a validated disease-specific patient-reported outcome measure for patients with angina and ischemic heart disease. The SAQ will be used to assess changes in angina burden and disease-specific quality of life during the 12-week plant-based dietary intervention. Higher scores indicate better health status and fewer angina-related limitations. |
| Change in Body Weight | Baseline, Week 4, Week 8, and Week 12. | Body weight measured during study visits and home monitoring to evaluate weight stability during the intervention. |
| Change in Blood Pressure | Baseline, Week 4, Week 8, and Week 12. | Blood pressure measured during study visits and through home monitoring to assess hemodynamic response to the dietary intervention |
Countries
United States
Contacts
CONTACTRami S Najjar, PhD
CONTACTRami Najjar
PRINCIPAL_INVESTIGATORRami Najjar, PhD
Emory University
Outcome results
None listed