Exploring the Antihypertensive and Vascular-Protective Effects of Blueberries in Middle-Aged/Older Men: Study Protocol

Abstract Objectives Previous research has demonstrated the antihypertensive and vascular-protective effects of blueberries in postmenopausal women with elevated blood pressure (BP) or stage 1-hypertension (HTN). However, this has not been explored in men with elevated BP or HTN. The objective of the present study is to examine effects of blueberry (BB) on BP, endothelial function, and arterial stiffness in men with elevated BP or stage 1-HTN, and baseline endothelial dysfunction, as well as to investigate possible mechanisms involved with BB on vascular health. Methods In a randomized, double-blind, placebo-controlled, parallel-arm trial, men with elevated BP or stage 1-HTN (systolic BP of 120–139 mmHg, and a diastolic BP < 90 mmHg), and endothelial dysfunction (reactive hyperemia index, RHI) <1.67, but otherwise healthy, will be randomized to receive either 22 g/day of freeze-dried wild BB powder or 22 g/day of placebo powder for 12 weeks. Primary outcomes for this study are BP and RHI, which is a measure of vascular endothelial function assessed using peripheral arterial tonometry. Secondary outcomes include analysis of arterial stiffness, measured by pulse wave velocity (PWV), as well as blood biomarkers of cardiovascular and metabolic health that include blood lipids, hemoglobin A1c, oxidized LDL, nitric oxide, and adhesion molecules. Furthermore, endothelial cells will be biopsied to provide mechanistic insight on how BB consumption might affect the vascular system by utilizing quantitative immunofluorescence. Results We hypothesize that 22 g/day of BB consumption (∼1 cup) for 12 weeks will improve endothelial function, arterial stiffness, and BP in men with elevated BP and/or stage 1-HTN. We also hypothesize that these improvements will be mediated by reductions in vascular oxidative stress and inflammation, and increased nitric oxide bioavailability. Conclusions This study has potential to provide unique in vivo (functional) and ex vivo (molecular) support for the hypothesis that BB consumption may attenuate endothelial dysfunction, arterial stiffness, and high BP that occurs with aging. Funding Sources Wild Blueberry Association of North America.

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Arterial elasticity, endothelial function and intracranial vascular health: A multimodal MRI study

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x20956950 ◽

2020 ◽

pp. 0271678X2095695

Author(s):

Wenjin Liu ◽

Zhensen Chen ◽

Dakota Ortega ◽

Xuebing Liu ◽

Xiaoqin Huang ◽

...

Keyword(s):

Endothelial Dysfunction ◽

Arterial Stiffness ◽

Endothelial Function ◽

Small Vessel Disease ◽

Reactive Hyperemia ◽

Brain Perfusion ◽

Cerebrovascular Diseases ◽

White Matter Hyperintensity ◽

Arterial Elasticity ◽

Vascular Health

Vascular dysfunctions, including arterial stiffness and endothelial dysfunction, are prevalent in hypertensive subjects. We aimed to study their relations to subclinical intracranial vascular health in this study. A total of 200 older hypertensive males without overt cardiovascular or cerebrovascular diseases were recruited. Arterial elasticity was measured as carotid-femoral pulse wave velocity (cfPWV) and endothelial function was measured as digital reactive hyperemia index (RHI). Cerebrovascular health was evaluated using MRI in four aspects: intracranial atherosclerosis, brain perfusion as cerebral blood flow (CBF), vascular rarefaction analyzed as visible arterial branches on angiography using a custom-developed analysis technique and small vessel disease measured as white matter hyperintensity (WMH). There was a significant negative association between cfPWV and CBF, suggesting a link between arterial stiffness and CBF decline. Higher cfPWV was also associated with presence of intracranial stenotic plaque and greater WMH volume. RHI was positively related to CBF, indicating that endothelial dysfunction was associated with reduced CBF. All the associations remained significant after adjustment for confounding variables. Arterial stiffness and endothelial dysfunction are associated with reduced brain perfusion in older hypertensive males. Arterial stiffness is also associated with global cerebral vascular injury, affecting both small and medium-to-large arteries.

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Consumption of High-Polyphenol Dark Chocolate Improves Endothelial Function in Individuals with Stage 1 Hypertension and Excess Body Weight

International Journal of Hypertension ◽

10.1155/2012/147321 ◽

2012 ◽

Vol 2012 ◽

pp. 1-9 ◽

Cited By ~ 21

Author(s):

Lívia de Paula Nogueira ◽

Marcela Paranhos Knibel ◽

Márcia Regina Simas Gonçalves Torres ◽

José Firmino Nogueira Neto ◽

Antonio Felipe Sanjuliani

Keyword(s):

Blood Pressure ◽

Body Weight ◽

Endothelial Function ◽

Oxidized Ldl ◽

Reactive Hyperemia ◽

Dark Chocolate ◽

Excess Body Weight ◽

Anthropometric Parameters ◽

Post Intervention ◽

Stage 1

Background. Hypertension and excess body weight are important risk factors for endothelial dysfunction. Recent evidence suggests that high-polyphenol dark chocolate improves endothelial function and lowers blood pressure. This study aimed to evaluate the association of chocolate 70% cocoa intake with metabolic profile, oxidative stress, inflammation, blood pressure, and endothelial function in stage 1 hypertensives with excess body weight.Methods. Intervention clinical trial includes 22 stage 1 hypertensives without previous antihypertensive treatment, aged 18 to 60 years and presents a body mass index between 25.0 and 34.9 kg/m2. All participants were instructed to consume 50 g of chocolate 70% cocoa/day (2135 mg polyphenols) for 4 weeks. Endothelial function was evaluated by peripheral artery tonometry using Endo-PAT 2000 (Itamar Medical).Results. Twenty participants (10 men) completed the study. Comparison of pre-post intervention revealed that (1) there were no significant changes in anthropometric parameters, percentage body fat, glucose metabolism, lipid profile, biomarkers of inflammation, adhesion molecules, oxidized LDL, and blood pressure; (2) the assessment of endothelial function through the reactive hyperemia index showed a significant increase: 1.94 ± 0.18 to 2.22 ± 0.08,P=0.01.Conclusion.In individuals with stage 1 hypertension and excess body weight, high-polyphenol dark chocolate improves endothelial function.

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Physical activity, vasomotor endothelial function, and arterial stiffness

CARDIOVASCULAR THERAPY AND PREVENTION ◽

10.15829/1728-8800-2012-6-29-32 ◽

2012 ◽

Vol 11 (6) ◽

pp. 29-32

Author(s):

S. M. Noskov ◽

A. A. Zavodchikov ◽

A. V. Evgenyeva ◽

A. A. Lavrukhina ◽

A. N. Chamorovskyi ◽

...

Keyword(s):

Endothelial Dysfunction ◽

Arterial Stiffness ◽

Endothelial Function ◽

Muscle Mass ◽

Subclinical Atherosclerosis ◽

Reactive Hyperemia ◽

Intima Media Thickness ◽

Control Group ◽

Total Body Mass ◽

Metabolic Equivalents

Aim. To study the prevalence of selected parameters of subclinical atherosclerosis and their association with muscle function and muscle volume in patients with different levels of cardiovascular risk (CVR). Material and methods. The study included 20 patients (11 men and 9 women; mean age 54,5±8,5 years) with chronic coronary heart disease (CCHD; mean duration 6,4±2,3 years) in the main group (MG), as well as 20 CCHD-free people in the control group (CG). Arterial stiffness was assessed by pulse wave velocity (PWV) and calculated carotid-femoral index (CFI). Endothelial function was assessed by endothelium-dependent vasodilatation (EDVD) in the reactive hyperemia (RH) test. Common carotid artery (CCA) ultrasound was performed in order to assess intima-media thickness (IMT) of carotid arteries. All participants underwent veloergometry (VEM); exercise capacity (EC) was measured by calculated metabolic equivalents (MET). Muscle tissue volume was assessed using a bioelectrical impedance analyser. The percentage of active muscle mass (%AMM) and fat-free muscle mass (%FFM), out of the total body mass, was calculated. Results. Increased CFI values >12 m/s, as a marker of adverse prognosis, were observed in 20% CCHD patients and in 10% of controls (z=0,17; p=0,87). Vasomotor endothelial dysfunction (EDVD <10%) was registered in 65% and 50%, respectively (z=0,74; p=0,46), while increased IMT values >0,9 mm were observed in 55% and 15%, respectively (z=2,3; p=0,02). Most patients with pathologically increased arterial stiffness and vasomotor endothelial dysfunction had low EC. In CCHD patients with low EC, CFI significantly correlated with %AMM and %FFM (r=-0,32; p<0,05; and r=-0,36; p<0,05, respectively). EDVD significantly correlated with both %AMM and %FFM (r=0,47; p<0,05; and r=0,5; p<0,05, respectively). There was a significant correlation between CFI and EDVD (r=-0,3; p<0,05). In CG participants with low EC, EDVD correlated with %AMM and %FFM (r=0723; p<0,05 and r=0,7; p<0,05, respectively). In both groups, %AMM and %FFM correlated with MET (r=0,49; p<0,05 and r=0,55; p<0,05, respectively; r=0,34; p<0,05 and r=0,31; p<0,05, respectively). Conclusion. EDVD and PWV reflect the lower PA levels and functional disadaptation of CCHD patients, which can result in a faster progression of atherosclerosis.

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Abstract 109: Association of Endothelial Dysfunction with Non-invasive Measures of Vascular Stiffness in Young-middle Aged Non-hypertensive Individuals

Hypertension ◽

10.1161/hyp.68.suppl_1.109 ◽

2016 ◽

Vol 68 (suppl_1) ◽

Author(s):

Cynthia Cheng ◽

Raymond Townsend ◽

Julio A Chirinos ◽

Scott Keith

Keyword(s):

Cardiovascular Risk ◽

Endothelial Dysfunction ◽

Arterial Stiffness ◽

Endothelial Function ◽

Reactive Hyperemia ◽

Systolic Pressure ◽

Vascular Stiffness ◽

Wave Reflections ◽

Middle Aged ◽

Study Objective

Arterial stiffness and enhanced wave reflections independently predict cardiovascular risk. Wave reflections augment central (aortic) pulse pressure (PP), an index of arterial stiffness, and systolic pressure. Increased wave reflections and PP have previously been associated with endothelial dysfunction in hypertensive and healthy middle-aged adults. The study objective was to determine whether endothelial dysfunction is associated with PP and other measures of vascular stiffness in young normotensive and prehypertensive subjects. We measured office, central, and 24-hour measurements in 102 (64 female, 38 male) non-hypertensive, non-diabetic participants. Endothelial function was assessed non-invasively using post-ischemic reactive hyperemia with strain-gauge plethysmography. The racially diverse subject pool was comprised of 60% Caucasians, 18% African Americans, and 24% Asians, with mean age 30, mean BMI 25.6, mean office SBP/DBP = 110 ± 13 mm Hg/70 ± 9 mm Hg. Endothelial function was highly associated with office (β= - 4.2 mm Hg, p<0.001) and 24-hour PP (β= - 1.4 mm Hg, p=0.008), along with central measures of wave reflection: ((augmentation pressure (β= - 2.1 mm Hg), augmentation index (β= - 3.7): both p<0.001). Beta values correspond to the change noted for one standard deviation in endothelial function. In conclusion, endothelial dysfunction is significantly and consistently associated with arterial stiffness and increased wave reflections in young non-hypertensive adults. Identification of endothelial dysfunction in otherwise healthy young individuals may provide an opportunity to reduce vascular stiffness and associated cardiovascular risk.

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Inflammatory markers, endothelial function and cardiovascular risk

Jornal Vascular Brasileiro ◽

10.1590/jvb.2014.054 ◽

2014 ◽

Vol 13 (2) ◽

pp. 108-115 ◽

Cited By ~ 22

Author(s):

Bruno Costa Teixeira ◽

André Luiz Lopes ◽

Rodrigo Cauduro Oliveira Macedo ◽

Cleiton Silva Correa ◽

Thiago Rozales Ramis ◽

...

Keyword(s):

Nitric Oxide ◽

Cardiovascular Diseases ◽

Endothelial Dysfunction ◽

Endothelial Function ◽

Inflammatory Markers ◽

Cardiovascular Events ◽

Vascular System ◽

Systematic Analysis ◽

Reactive Protein ◽

Endothelial Nitric Oxide

The need to study cardiovascular diseases (CVD) has become more and more relevant as their prevalence has increased over the years. An intact endothelial wall is essential to vascular health. Certain factors are responsible for maintaining this tissue intact, including nitric oxide (NO), which provokes dilation of blood vessels in response to shear stress. Expression of the endothelial nitric oxide synthase (eNOS) enzyme, which produces nitric oxide in response to increases in blood flow, is of fundamental importance to maintenance of the vascular system. When this enzyme is inhibited, nitric oxide production is reduced, causing endothelial dysfunction. Since C-reactive protein inhibits production of nitric oxide by the eNOS enzyme, it is one of the causes of endothelial dysfunction and cardiovascular events. The objective of the present study was to review scientific articles in the literature related to the subject 'inflammatory markers and endothelial function'. A wide-ranging review of the current literature was conducted, using systematic analysis of bibliographic references indexed in PubMed, Scielo, Medline and LILACS database, for the years 1992 to 2013. The studies reviewed show that increases in inflammation causes reductions in NO and increases in cardiovascular events. Increased inflammation is associated with higher incidence of cardiovascular diseases.

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AHA/ACC-defined stage 1 hypertensive adults do not display cutaneous microvascular endothelial dysfunction

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00179.2020 ◽

2020 ◽

Vol 319 (3) ◽

pp. H539-H546

Author(s):

Gabrielle A. Dillon ◽

Jody L. Greaney ◽

Sean Shank ◽

Urs A. Leuenberger ◽

Lacy M. Alexander

Keyword(s):

Nitric Oxide ◽

Blood Pressure ◽

Endothelial Dysfunction ◽

Endothelial Function ◽

Clinical Guidelines ◽

American Heart Association ◽

American Heart ◽

Heart Association ◽

Microvascular Endothelial ◽

Stage 1

This is the first study to pharmacologically assess the mechanistic regulation of endothelial function in adults with hypertension, classified according to the 2017 clinical guidelines set for by the American Heart Association (AHA) and American College of Cardiology (ACC). Compared with that in normotensive adults, nitric oxide-mediated endothelium-dependent dilation is impaired in adults with stage 2, but not stage 1, hypertension. Adults lacking a nighttime dip in blood pressure demonstrated reductions in endothelium-dependent dilation.

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Assessment of endothelial function and arterial rigidity in patients with type 1 diabetes at different stages of diabetic nephropathy

Diabetes Mellitus ◽

10.14341/2072-0351-6225 ◽

2011 ◽

Vol 14 (3) ◽

pp. 55-59

Author(s):

Evgenia Pavlovna Kosobyan ◽

Ivona Renata Yarek-Martynova ◽

Alexander Sergeevich Parfenov ◽

Lyubov' Leonidovna Bolotskaya ◽

Marina Vladimirovna Shestakova

Keyword(s):

Nitric Oxide ◽

Type 1 Diabetes ◽

Diabetic Nephropathy ◽

Endothelial Dysfunction ◽

Endothelial Function ◽

Pulse Wave ◽

Reactive Hyperemia ◽

Control Group ◽

Number Of Patients

Aim. Assessment of vascular stiffness and endothelial function in patients with type 1 diabetes at different stages of diabetic nephropathy and without it. Materials and methods. We examined 93 patients with DM1 aged 18 to 40 years, and disease duration of more than 5 years. The criterion for forming groups is the stage of diabetic nephropathy. Control group consisted of 23 healthy people. The study included an evaluation of the contour of pulse wave analysis, and conducting tests with reactive hyperemia on the unit Angioskan (LTD Angioskan, Russia). Prior to the study of each patients written informed consent. Results. In conducting the analysis of the pulse wave contour index of aortic stiffness was significantly higher in all groups of patients with diabetic nephropathy (DN) compared with healthy subjects. However, when comparing patients with T1D without DN and the control group, significant differences of stiffness index (SI) was not been determined. It should be noted that the increase in value of SI is almost independent of the presence of hypertension in the patient groups. In the analysis of reflection index (RI) values of statistically significant relationships were found. In analyzing the test data with reactive hyperemia we showed a reduction in growth of the signal amplitude in a significant number of patients, which is a sign of endothelial dysfunction, and occurs even in patients without clinical and laboratory signs of kidney damage. However, along with a decrease of this index, a large number of patients have paradoxically high its value, which may indicate a high level of basal nitric oxide. Conclusion. Increase in the stiffness of the aorta, the progression of DN may be an early marker of macrovascular lesions even in patients without hypertension. Reduced growth of the amplitude of the signal after occlusion in patients with no signs of kidney disease, indicates the presence of endothelial dysfunction even in the preclinical stage of diabetic nephropathy. Paradoxically high increase of the amplitude of the signal can indicate the presence of abnormally high basal level of nitric oxide, which is a marker of inflammation, high-risk factor of progression of angiopathies and fibrosis.

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Therapeutic Potential of Phosphodiesterase Inhibitors for Endothelial Dysfunction- Related Diseases

Current Pharmaceutical Design ◽

10.2174/1381612826666200403172736 ◽

2020 ◽

Vol 26 (30) ◽

pp. 3633-3651 ◽

Cited By ~ 2

Author(s):

Javier Blanco-Rivero ◽

Fabiano E. Xavier

Keyword(s):

Nitric Oxide ◽

Endothelial Dysfunction ◽

Endothelial Function ◽

Therapeutic Potential ◽

Treatment Strategies ◽

Phosphodiesterase Inhibitors ◽

Developed Countries ◽

Major Health Problem ◽

Pde Inhibitors ◽

Pharmaceutical Industries

Cardiovascular diseases (CVD) are considered a major health problem worldwide, being the main cause of mortality in developing and developed countries. Endothelial dysfunction, characterized by a decline in nitric oxide production and/or bioavailability, increased oxidative stress, decreased prostacyclin levels, and a reduction of endothelium-derived hyperpolarizing factor is considered an important prognostic indicator of various CVD. Changes in cyclic nucleotides production and/ or signalling, such as guanosine 3', 5'-monophosphate (cGMP) and adenosine 3', 5'-monophosphate (cAMP), also accompany many vascular disorders that course with altered endothelial function. Phosphodiesterases (PDE) are metallophosphohydrolases that catalyse cAMP and cGMP hydrolysis, thereby terminating the cyclic nucleotide-dependent signalling. The development of drugs that selectively block the activity of specific PDE families remains of great interest to the research, clinical and pharmaceutical industries. In the present review, we will discuss the effects of PDE inhibitors on CVD related to altered endothelial function, such as atherosclerosis, diabetes mellitus, arterial hypertension, stroke, aging and cirrhosis. Multiple evidences suggest that PDEs inhibition represents an attractive medical approach for the treatment of endothelial dysfunction-related diseases. Selective PDE inhibitors, especially PDE3 and PDE5 inhibitors are proposed to increase vascular NO levels by increasing antioxidant status or endothelial nitric oxide synthase expression and activation and to improve the morphological architecture of the endothelial surface. Thereby, selective PDE inhibitors can improve the endothelial function in various CVD, increasing the evidence that these drugs are potential treatment strategies for vascular dysfunction and reinforcing their potential role as an adjuvant in the pharmacotherapy of CVD.

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Endothelial Function and Arterial Stiffness Should Be Measured to Comprehensively Assess Obstructive Sleep Apnea in Clinical Practice

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.716916 ◽

2021 ◽

Vol 8 ◽

Author(s):

Jinmei Luo ◽

Xiaona Wang ◽

Zijian Guo ◽

Yi Xiao ◽

Wenhao Cao ◽

...

Keyword(s):

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

Arterial Stiffness ◽

Endothelial Function ◽

Augmentation Index ◽

Reactive Hyperemia ◽

Control Group ◽

Apnea Hypopnea Index ◽

Obstructive Sleep ◽

Tnf Α

Objective: An effective clinical tool to assess endothelial function and arterial stiffness in patients with obstructive sleep apnea (OSA) is lacking. This study evaluated the clinical significance of subclinical markers for OSA management in males without serious complications.Patients/Methods: Males without serious complications were consecutively recruited. Clinical data, biomarker tests, reactive hyperemia index (RHI), and augmentation index at 75 beats/min (AIx75) measured by peripheral arterial tonometry were collected. An apnea hypopnea index (AHI) cutoff of ≥15 events/h divided the patients into two groups.Results: Of the 75 subjects, 42 had an AHI ≥15 events/h. Patients with an AHI ≥15 events/h had higher high-sensitivity C-reactive protein, tumor necrosis factor-alpha (TNF-α), vascular endothelial growth factor, and AIx75 values than the control group but no statistical difference in RHI was observed. After controlling for confounders, TNF-α was negatively correlated with the average oxygen saturation (r = −0.258, P = 0.043). RHI was correlated with the rapid eye movement (REM) stage percentage (r = 0.306, P = 0.016) but not with AHI (P > 0.05). AIx75 was positively correlated with the arousal index (r = 0.289, P = 0.023) but not with AHI (r = 0.248, P = 0.052).Conclusions: In males with OSA without severe complications, TNF-α and AIx75 are independently related to OSA. The role of RHI in OSA management requires further elucidation. These markers combined can comprehensively evaluate OSA patients to provide more evidence for the primary prevention of coronary heart disease and treatment response assessment.

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Tackling endothelial dysfunction by modulating NOS uncoupling: new insights into its pathogenesis and therapeutic possibilities

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00540.2011 ◽

2012 ◽

Vol 302 (5) ◽

pp. E481-E495 ◽

Cited By ~ 125

Author(s):

Rinrada Kietadisorn ◽

Rio P. Juni ◽

An L. Moens

Keyword(s):

Nitric Oxide ◽

Endothelial Dysfunction ◽

Endothelial Function ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Therapeutic Interventions ◽

Enos Uncoupling ◽

Underlying Causes ◽

Oxide Synthase ◽

Endothelial Nitric Oxide

Endothelial nitric oxide synthase (eNOS) serves as a critical enzyme in maintaining vascular pressure by producing nitric oxide (NO); hence, it has a crucial role in the regulation of endothelial function. The bioavailability of eNOS-derived NO is crucial for this function and might be affected at multiple levels. Uncoupling of eNOS, with subsequently less NO and more superoxide generation, is one of the major underlying causes of endothelial dysfunction found in atherosclerosis, diabetes, hypertension, cigarette smoking, hyperhomocysteinemia, and ischemia/reperfusion injury. Therefore, modulating eNOS uncoupling by stabilizing eNOS activity, enhancing its substrate, cofactors, and transcription, and reversing uncoupled eNOS are attractive therapeutic approaches to improve endothelial function. This review provides an extensive overview of the important role of eNOS uncoupling in the pathogenesis of endothelial dysfunction and the potential therapeutic interventions to modulate eNOS for tackling endothelial dysfunction.

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