Wild Blueberries and Cardiovascular Health in Middle-aged/Older Men and Postmenopausal Women

Study Overview
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Brief Summary
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Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. Aging is the primary risk factor for CVD, in large part due to adverse modifications to the arteries. These modifications include vascular endothelial dysfunction and arterial stiffness. Vascular endothelial dysfunction is an initiating step in atherosclerosis, and is primarily caused by reduced nitric oxide (NO) bioavailability secondary to excessive superoxide-driven oxidative stress and inflammation. Endothelial dysfunction leads to arterial stiffness and the development of hypertension (HTN) which further increases CVD. Greater than 2/3 of the US population has elevated blood pressure or stage 1-HTN. As such, interventions that improve vascular endothelial dysfunction by increasing NO bioavailability and mitigating excessive oxidative stress and inflammation are needed. Blueberries are rich in bioactive compounds including flavonoids, phenolic acids, and pterostilbene. These compounds and their metabolites have been shown to attenuate oxidative stress and inflammation. The primary goal of this study is to assess the efficacy of blueberries to improve reduce blood pressure and improve vascular endothelial dysfunction and arterial stiffness in middle-aged/older men with elevated blood pressure or stage 1-HTN.

Official Title
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Antihypertensive and Vascular-Protective Effects of Wild Blueberries in Middle-Aged/Older Men and Postmenopausal Women.

Conditions
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Hypertension, Aging, Endothelial Dysfunction, Men

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: Men and postmenopausal women Aged 45-70 years Elevated blood pressure or stage 1-Hypertension Ability to provide informed consent Exclusion Criteria: Have had a menstrual cycle within the past year Blood Pressure < 120 (systolic BP) or ≥ 140/90 mm Hg Reactive hyperemia index > 3.00% Taking > 1 antihypertensive medication, taking 1 antihypertensive medication more than 1 time per day, and/or taking the antihypertensive medication for < 3 months Diagnosed cancer, cardiovascular disease, diabetes, or gastrointestinal, kidney, liver, lung, and/or pancreatic disease Triglycerides > 350 mg/dL, low-density lipoprotein cholesterol (LDL-C) ≥ 190 mg/dL, hemoglobin A1c ≥ 6.5%, and/or taking a lipid-lowering or glucose-lowering medication Testosterone or estrogen replacement therapy use 6 months prior to study start 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 Antibiotic therapy within past two months Allergies or contraindication to study treatments or procedures

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Blueberry<br>22 g blueberry powder per day | Dietary Supplement: Blueberry Powder<br>* 22 g/day wild blueberry powder<br>|
| Placebo Comparator: Control<br>22 g placebo control powder per day | Dietary Supplement: Placebo Powder<br>* 22 g/day placebo powder<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reactive hyperemia index | Endothelial function assessed as reactive hyperemia index using peripheral arterial tonometry (EndoPat) | Baseline to 12 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Augmentation index | Arterial stiffness assessed as augmentation index using an automated blood pressure monitor (SphygmoCor) | Baseline to 12 Weeks | 
| Pulse wave velocity | Arterial stiffness assessed as carotid-femoral pulse wave velocity using an automated blood pressure monitor (SphygmoCor) | Baseline to 12 Weeks | 
| Endothelial cell protein expression | Protein expression will be assessed as an exploratory analysis for markers of nitric oxide bioavailability, inflammation, and/or oxidative stress will be measured by quantitative immunofluorescence in biopsied venous endothelial cells | Baseline to 12 Weeks | 
| Hemoglobin A1c | Blood hemoglobin A1C will be measured | Baseline to 12 Weeks | 
| Lipid profile | Blood lipid profiles will be measured | Baseline to 12 Weeks | 
| Nitric oxide metabolites | Blood nitrate/nitrite will be measured | Baseline to 12 Weeks | 
| ICAM-1 | Blood ICAM-1 will be measured | Baseline to 12 Weeks | 
| VCAM-1 | Blood VCAM-1 will be measured | Baseline to 12 Weeks | 
| Blood pressure | Brachial and Aortic blood pressure (systolic blood pressure, diastolic blood pressure, pulse pressure, aortic pressure) assessed using an automated blood pressure monitor (SphygmoCor) | Baseline to 12 Weeks | 
| Gut microbiota | Determine the effects on stool sample microbial populations | Baseline to 12 Weeks | 
| Plasma blueberry polyphenol metabolites | Targeted analysis of plasma metabolites by GC-MS and LC-MS | Baseline to 12 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cardiovascular Disease, Blueberries, Hypertension, Vascular Dysfunction, Atherosclerosis, Aging