Blueberries for Improving Vascular Endothelial Function in Postmenopausal Women With Elevated Blood Pressure

Study Overview
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Brief Summary
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Postmenopausal women are at an increased risk of developing cardiovascular disease (CVD) largely due to accelerated aging-related modifications to vascular health following menopause. The vascular endothelium is responsible for producing chemicals that are essential for proper vasodilation and blood flow and therefore is involved in maintaining normal blood pressure. A major modification that occurs during aging and is accelerated during menopause is termed vascular endothelial dysfunction which is characterized by impaired endothelium-dependent dilation. This can lead to increased blood pressure, atherosclerosis, and increased risk of CVD and death. Nitric oxide (NO) is a chemical produced by the endothelium and is essential for normal endothelial function and cardiovascular health. Vascular endothelial dysfunction is primarily caused by reduced NO bioavailability secondary to excessive oxidative stress. Approximately 3/4 of postmenopausal women have elevated blood pressure or hypertension which further worsens endothelial function and increases CVD risk through increased oxidative stress and inflammation. Blueberries are rich in phytochemicals including anthocyanins, phenolic acids, and pterostilbene. These phytochemicals and their metabolites are known to attenuate oxidative stress and inflammation. The overall goal of the current study is to assess the efficacy of blueberries to improve vascular endothelial dysfunction in this high-risk population and to gain insight into underlying mechanisms. 58 postmenopausal women with elevated blood pressure and stage 1-HTN will be asked to consume 22 grams freeze-dried blueberry powder or placebo powder per day for 12 weeks. Vascular endothelial function will be assessed at baseline and 12 weeks. Measurements indicative of vascular nitric oxide production, oxidative stress, inflammation, cardiometabolic health, cognitive function, and blueberry phytochemical metabolism will be measured at baseline and 12 weeks. Blood pressure will be assessed at baseline and 4, 8, and 12 weeks.

Official Title
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Blueberry Consumption for Improving Vascular Endothelial Dysfunction in Postmenopausal Women With Elevated Blood Pressure and Stage 1-Hypertension

Conditions
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Menopause, Elevated Blood Pressure, Hypertension, Endothelial Dysfunction

Intervention / Treatment
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* Dietary Supplement: Blueberry Powder
* Dietary Supplement: Placebo Powder


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 45-65 years Postmenopausal women (≥ 1 years postmenopausal; natural or surgical menopause; confirmed by measurement of estradiol at a level < 30 pg/mL and follicle-stimulating hormone at a level ≥ 30 mIU/mL) Elevated or stage 1-HTN (confirmed as resting seated systolic blood pressure < 120 or ≥ 139 mmHg and/or a diastolic blood pressure ≥ 90 mmHg using an average of 3 measurements, on 2 separate occasions - screening and baseline visits) Ability to provide informed consent Exclusion Criteria: Systolic blood pressure < 120 or ≥ 139 mm Hg and/or diastolic blood pressure ≥ 90 mmHg Taking > 1 antihypertensive medication and/or taking the antihypertensive medication for < 3 months Diagnosed cancer, cardiovascular disease, diabetes, or gastrointestinal, kidney, liver, and/or pancreatic disease Triglycerides > 350 mg/dL, low-density lipoprotein cholesterol (LDL-C) ≥ 190 mg/dL, and/or taking a lipid-lowering medication Hormone replacement therapy use 6 months prior to study start Taking phosphodiesterase-5 inhibitors Weight change ≥ 3 kg in the past 3 months, actively trying to lose weight, or unwilling to remain weight stable throughout the study Current smokers or history of smoking in the past 12 months Binge and/or heavy drinker (>3 drinks on any given occasion and/or >7 drinks/week for women, and >4 drinks on any given occasion and/or >14 drinks/week for men) Body mass index < 18.5 or > 40 kg/m2 Active infection or antibiotic therapy Allergies or contraindication to study treatments, pharmacological agents, or procedures

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Blueberry<br>22 g/day freeze-dried blueberry powder for 12 weeks | Dietary Supplement: Blueberry Powder<br>* 22 g/day freeze-dried blueberry powder for 12 weeks<br>|
| Placebo Comparator: Control<br>22 g/day placebo powder for 12 weeks | Dietary Supplement: Placebo Powder<br>* 22 g/day placebo powder for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endothelium-dependent dilation | Assessed as brachial artery flow-mediated dilation in a study subset of participants | Baseline to 12 Weeks | 
| Blood pressure | Assessed using an automated blood pressure monitor (SphgmoCor) | Baseline to 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vascular oxidative stress | Change in brachial artery flow-mediated dilation following acute infusion of ascorbic acid (a dose known to scavenge superoxide) as an index of vascular oxidative stress in a study subset of participants | Baseline and 12 weeks | 
| Endothelial cell nitric oxide production, oxidative stress, and inflammation | Protein expression markers will be measured by quantitative immunofluorescence in biopsied venous endothelial cells in a study subset of participants | Baseline and 12 weeks | 
| Systemic markers of cardiometabolic health | Circulating markers of lipid and glucose metabolism, nitric oxide, and inflammation | Baseline and 12 weeks | 
| Plasma blueberry polyphenol metabolites | Targeted analysis of plasma metabolites by GC-MS and LC-MS | Baseline and 12 weeks | 
| Endothelium-independent dilation | Assessed as brachial artery diameter responses to sublingual nitroglycerin in a study subset of participants | Baseline to 12 weeks | 
| Augmentation index | Arterial stiffness assessed as augmentation index using the SphygmoCor XCEL | Baseline to 12 weeks | 
| Pulse wave velocity | Arterial stiffness assessed as carotid-femoral pulse wave velocity using the SphygmoCor XCEL | Baseline to 12 weeks | 
| Gut microbiota | Determine the effects on stool sample microbial populations | Baseline to 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Endothelium, Blueberries, Polyphenols, Cardiovascular Disease, Atherosclerosis, Oxidative Stress, Inflammmation, Vasodilation, Blood Pressure, Menopause, Women's Health, Functional Food, Bioactive Compounds, Dietary Supplements, Aging