Elevated Blood Pressure, Endothelial Dysfunction, Hypertension, Menopause
Conditions
Keywords
Blueberries, Polyphenols, Cardiovascular Disease, Atherosclerosis, Oxidative Stress, Inflammmation, Endothelium, Vasodilation, Blood Pressure, Menopause, Women's Health, Functional Food, Bioactive Compounds, Dietary Supplements, Aging
Brief summary
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.
Interventions
DIETARY_SUPPLEMENTBlueberry Powder
22 g/day freeze-dried blueberry powder for 12 weeks
DIETARY_SUPPLEMENTPlacebo Powder
22 g/day placebo powder for 12 weeks
Sponsors
U.S. Highbush Blueberry Council
Colorado State University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
45 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Endothelium-dependent dilation | Baseline to 12 Weeks | Assessed as brachial artery flow-mediated dilation in a study subset of participants |
| Blood pressure | Baseline to 12 weeks | Assessed using an automated blood pressure monitor (SphgmoCor) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Gut microbiota | Baseline to 12 weeks | Determine the effects on stool sample microbial populations |
| Endothelial cell nitric oxide production, oxidative stress, and inflammation | Baseline and 12 weeks | Protein expression markers will be measured by quantitative immunofluorescence in biopsied venous endothelial cells in a study subset of participants |
| Systemic markers of cardiometabolic health | Baseline and 12 weeks | Circulating markers of lipid and glucose metabolism, nitric oxide, and inflammation |
| Plasma blueberry polyphenol metabolites | Baseline and 12 weeks | Targeted analysis of plasma metabolites by GC-MS and LC-MS |
| Endothelium-independent dilation | Baseline to 12 weeks | Assessed as brachial artery diameter responses to sublingual nitroglycerin in a study subset of participants |
| Augmentation index | Baseline to 12 weeks | Arterial stiffness assessed as augmentation index using the SphygmoCor XCEL |
| Pulse wave velocity | Baseline to 12 weeks | Arterial stiffness assessed as carotid-femoral pulse wave velocity using the SphygmoCor XCEL |
| Vascular oxidative stress | Baseline and 12 weeks | 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 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Executive function and attention | Baseline and 12 weeks | Exploratory measures assessed using the NIH Cognitive Toolbox iPad app |
| Episodic memory | Baseline and 12 weeks | Exploratory measures assessed using the NIH Cognitive Toolbox iPad app |
| Peripheral blood mononuclear cell inflammation and oxidative stress | Baseline and 12 weeks | Exploratory measures analyzed by gene expression |
| Working memory | Baseline and 12 weeks | Exploratory measures assessed using the NIH Cognitive Toolbox iPad app |
| Language | Baseline and 12 weeks | Exploratory measures assessed using the NIH Cognitive Toolbox iPad app |
| Processing speed | Baseline and 12 weeks | Exploratory measures assessed using the NIH Cognitive Toolbox iPad app |
Countries
United States
Outcome results
None listed