A Plant-Based Diet in the Treatment of Coronary Microvascular Dysfunction

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.

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.

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.

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.

Plasma aminothiol redox status measured by concentrations of reduced and oxidized aminothiol species, including cysteine, cystine, glutathione, and glutathione disulfide.

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

Changes in hematologic measures obtained from complete blood count with differential testing.

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.

Body weight measured during study visits and home monitoring to evaluate weight stability during the intervention.

Blood pressure measured during study visits and through home monitoring to assess hemodynamic response to the dietary intervention

Dietary adherence will be quantified using repeated Automated Self-Administered 24-Hour Dietary Assessment Tool (ASA24) recalls. Adherence will be calculated as the proportion of prescribed study foods reported as consumed relative to the foods assigned, expressed as a percentage. Possible values range from 0% to 100%, with higher percentages indicating greater adherence. Average adherence of at least 85% will define adherence for sensitivity analyses.

FoodSEQ will be performed on a randomly selected subset of stool specimens to determine whether animal-food-derived DNA is detected. The outcome will be reported as the number of participants with animal-food-derived DNA detected in at least one evaluable specimen. A lower number indicates greater biological corroboration of adherence to the prescribed plant-based diet.

The outcome will be reported as the number of enrolled participants who remain in the study through the end of the 12-week dietary intervention and complete the Week 12 assessment. Participants who withdraw before completing the intervention will not be counted as completers.