• Cognitive performance
• Elderly
• Fitness
• Mediating effect
• Physical exercise

• Humans
• Male
• Female
• Aged
• Cross-Sectional Studies
• Exercise/psychology
• Exercise/physiology
• Cognition/physiology
• Independent Living/statistics & numerical data
• Independent Living/psychology
• Physical Fitness/physiology
• Physical Fitness/psychology
• Aged, 80 and over

• cardiovascular disease
• exercise
• frailty
• low intensity
• sarcopenia

• Adolescence
• Microvascular endothelial function
• Peripheral arterial tonometry
• Repaired congenital heart disease

• Humans
• Adolescent
• Female
• Male
• Heart Defects, Congenital/surgery
• Heart Defects, Congenital/physiopathology
• Manometry/methods
• Endothelium, Vascular/physiopathology
• Child
• Case-Control Studies
• Fontan Procedure/adverse effects
• Hyperemia/physiopathology
• Atherosclerosis

• forearm vascular conductance
• small muscle mass exercise
• sympathoexcitation
• sympatholysis

• Humans
• Vasoconstriction
• Male
• Sympathetic Nervous System/physiopathology
• Female
• Heart Failure/physiopathology
• Stroke Volume
• Middle Aged
• Exercise
• Hand Strength
• Forearm/blood supply
• Aged
• Regional Blood Flow
• Case-Control Studies
• Ventricular Function, Left
• Cold Temperature
• Arterial Pressure
• Rest

• PGSD3 - 518590 - 2018 Canadian Government | Natural Sciences and Engineering Research Council of Canada (NSERC)
• Establishment Grant #3468 Saskatchewan Health Research Foundation (SHRF)
• G-16-00014255 Heart and Stroke Foundation of Canada (HSF)

• cardiovascular system
• endothelium
• exercise

• Cardiac rehabilitation
• Exercise training
• Heart failure
• Hemodynamics
• Individual response

• endothelial function
• flow-mediated dilatation
• people living with HIV
• physical activity
• sedentary lifestyle

• Humans
• HIV Infections/complications
• Exercise
• Atherosclerosis
• Endothelium, Vascular
• Vasodilation

• Cardiac rehabilitation
• Exercise training
• Heart failure

• Humans
• Cardiac Rehabilitation
• Quality of Life
• Heart Failure/diagnosis
• Heart Failure/therapy
• Exercise Therapy/adverse effects
• Dyspnea

• Endothelial function
• anti-hypertensive drugs
• blood pressure variability
• vascular inflammation

• Humans
• Middle Aged
• Aged
• Amlodipine/pharmacology
• Amlodipine/therapeutic use
• Antihypertensive Agents/pharmacology
• Antihypertensive Agents/therapeutic use
• Blood Pressure
• Hypertension/diagnostic imaging
• Hypertension/drug therapy
• Hypertension/complications
• Angiotensin Receptor Antagonists/pharmacology
• Angiotensin Receptor Antagonists/therapeutic use
• Angiotensin-Converting Enzyme Inhibitors/pharmacology
• Angiotensin-Converting Enzyme Inhibitors/therapeutic use
• Calcium Channel Blockers/pharmacology
• Calcium Channel Blockers/therapeutic use
• Essential Hypertension/complications
• Essential Hypertension/drug therapy
• Inflammation/diagnostic imaging
• Inflammation/complications
• Drug Therapy, Combination

• Blood pressure
• Cadmium
• Hypertension
• Interaction
• Lead
• Physical activity

• cardiovascular drugs
• carotid baroreceptor stimulation
• chronic heart failure
• endothelial function
• physical training
• rehabilitation
• renal denervation
• sympathetic activity

• analgesic effect
• analgesic mechanisms
• complex regional pain syndrome
• exercise
• pain

• Science and Technology Commission of Shanghai Municipality

• Arterial stiffness
• Arterial tonometry
• Chronic heart failure
• Exercise
• Meta-analysis

• Chronic Disease
• Exercise
• Exercise Tolerance
• Heart Failure/diagnosis
• Heart Failure/therapy
• Humans
• Manometry
• Stroke Volume

• Charité - Universitätsmedizin Berlin (3093)

Individuals with a higher lifelong cardiorespiratory fitness show better vascular health with aging. Studies on fitness-related effects on endothelial function either analyzed samples with a narrow age-range or incompletely assessed endothelial responsiveness. This study aims to assess the impact of cardiorespiratory fitness on the association of brachial-arterial flow-mediated vasodilation (FMD) and low flow-mediated vasoconstriction (L-FMC) with age in healthy adults and patients with cardiovascular diseases.

FMD, L-FMC and V.O₂peak were prospectively measured in a population-based sample including 360 healthy adults and 99 patients with cardiovascular disease of European descend. Non-linear models were applied to assess V.O₂peak-associated variations in age-related differences of endothelial function independent of classical cardiovascular risk factors.

FMD was negatively associated with age in healthy adults (adjusted R² = 0.27, partial R² = 0.07, p < 0.001) and in cardiovascular patients (adjusted R² = 0.29, partial R² = 0.05, p = 002). L-FMC showed no association with age. In models predicting the change of FMD with higher age, V.O₂peak accounted for 2.8% of variation in FMD (χ²(5) = 5.37, p = 0.372, s = 1.43). Thereby, V.O₂peak-stratified changes of FMD started to fan out at around 30 years of age in women and 50 years of age in men, with 7–12% lower values at old age with V.O₂peak ≤3rd percentile compared to V.O₂peak ≥97th percentile) in both, the healthy sample and in cardiovascular patients.

The statistical effect of cardiorespiratory fitness on the association of FMD with age independent of classical cardiovascular risk factors was small in both, healthy aging adults as well as patients with cardiovascular diseases. Its clinical significance should be assessed further.

• aging
• atherosclerosis
• cardiovascular disease
• peripheral vascular disease
• primary prevention
• secondary prevention
• ultrasound

The international recommendations tend to avoid physical activity (PA) for patients with Marfan syndrome (MFS). However, exceptions have recently been made in the most recent recommendations for these patients, suggesting benefits from doing PA at low intensity only. Furthermore, there is no evidence that moderate aerobic or weight training can worsen the disease symptoms and increase mortality of MFS patients. The present review sums up the work carried out in the field of PA and MFS. The review aims to (1) identify the different types of exercise testing and training protocols and (2) discuss the feasibility and potentially beneficial nature of PA as an innovative way to manage MFS patients.

The scientific literature was reviewed using the following words: Marfan syndrome, training, physical activity, evaluation, weight training, arterial disease, aneurysms, lung damage, aortic dissection, rupture. A total of 345 studies were prospected and 43 studies were included.

A limited number of studies were done in humans, however one demonstrated the feasibility of the management of MFS patients with PA. There were potential beneficial effects of PA on arterial structures, but this review also showed deleterious effects when PA was conducted at high intensities, corresponding to 75–85% of the maximal oxygen uptake. However, these effects have only been reported in animal studies.

• Blood pressure
• Delphi
• Isometric resistance training

• grip strength
• home blood pressure
• hypertension
• isometric handgrip training
• non-pharmacological treatment

• Blood Pressure
• Cross-Over Studies
• Female
• Hand Strength
• Humans
• Hypertension/diagnosis
• Isometric Contraction
• Male
• Middle Aged

• cardiac stem cells
• exercise
• nitric oxide

• PRIN2017NKB2N4_005 Ministero dell'Istruzione, dell'Università e della Ricerca

• athletic
• endothelial
• microRNA
• vascular

• Entresto
• flow-mediated dilation
• heart failure
• reactive hyperemia

• Aminobutyrates
• Angiotensin Receptor Antagonists
• Biphenyl Compounds
• Drug Combinations
• Heart Failure
• Humans
• Inflammation
• Prospective Studies
• Stroke Volume
• Tetrazoles
• Treatment Outcome
• Valsartan
• Ventricular Function, Left

• E1697-R VA
• R56 AG057584 NIA NIH HHS
• RX001311 VA
• T32 HL139451 NHLBI NIH HHS
• E6910-R VA
• E1572-P VA
• E9275-L VA
• R01 HL118313 NHLBI NIH HHS
• 18POST33960192 American Heart Association-American Stroke Association
• I01 RX001311 RRD VA
• E1433-P VA

•

Peripheral endothelial dysfunction (PED) predicts adverse outcomes in patients with stage B HF.

ACC/AHA guidelines recognize the progressive nature of heart failure (HF). Patients with risk factors (Stage A) are at risk for developing asymptomatic cardiac dysfunction (Stage B), which may then lead to symptomatic HF (Stage C). As such, therapies targeting abnormalities in stages A and B may protect against development of symptomatic HF. peripheral endothelial dysfunction (PED) is an independent predictor of adverse outcomes in patients with stage C HF. The aim of the current study was to evaluate whether PED might be associated with Stage B HF, where therapeutic interventions to prevent progression might be more efficacious.

We performed a retrospective cross-sectional analysis of patients who were referred for routine cardiovascular evaluation that included an assessment of peripheral endothelial function with reactive hyperemia-peripheral arterial tonometry. Individuals in this study underwent routine clinically indicated echocardiography within 2 months of testing for PED. Patients with clinical HF were excluded.

The study included 355 patients (mean age 51.5 ± 14.6 years, 231 (65.1%) female). There was a significant association between PED and Stage B HF (Odds Ratio (OR) 6.38; P < 0.0001) that persisted after stratifying by sex. In multivariate analyses PED was significantly associated with Stage B HF (OR 5.33; P = 0.0038), and was also associated with progression to overt stage C HF (OR 4.63; P = 0.033).

Peripheral endothelial dysfunction is risk factor for Stage B HF, even in low risk individuals. Further study is warranted to better understand the mechanistic basis of PED in HF to reduce the risk of symptomatic progression.

• BMI, body mass index
• CAD, coronary artery disease
• CV, cardiovascular
• EF, ejection fraction
• HF, heart failure
• Heart Failure
• LV, left ventricular
• Novel risk factor
• Peripheral endothelial dysfunction
• RH-PAT, reactive hyperemia-peripheral arterial tonometry
• Systolic dysfunction

• Asymptomatic
• heart failure
• left ventricular dysfunction
• systolic impairment

• Cardiac rehabilitation
• Exercice
• Exercise
• Heart failure
• Insuffisance cardiaque
• Quality of life
• Qualité de vie
• Réadaptation cardiaque

• Cardiac rehabilitation
• Cardiopulmonary exercise test
• Dilated cardiomyopathy
• Echocardiography

• Atherosclerosis
• endothelial function
• extremities
• muscle strength
• vasodilatory capacity

• Cardiac patients
• Microvasculature
• Rehabilitation
• Retinal blood vessels

Nitric oxide (NO) facilitates anti-atherosclerotic effects. Vegetables are a major source of dietary nitrate. Experimental data indicates that dietary nitrate can significantly reduce major risk factors for atherosclerosis and subsequent cardiovascular disease (CVD), as nitrate can be metabolized to produce NO via the nitrate-nitrite-NO pathway. The purpose of this study was to prospectively investigate the association between habitual dietary nitrate intakes and the incidence of self-reported CVD-related complications within a representative sample of middle-aged Australian women (1946–1951 cohort of the Australian Longitudinal Study on Women’s Health). Women free from disease at baseline who had completed the food frequency questionnaire data were included. Generalized estimating equations were used to estimate odds ratios (OR) and 95% confidence intervals (95% CI) across quartiles for nitrate intakes. Of the 5324 women included for analysis, there were 1951 new cases of CVD-related complications over 15-years of follow-up. Women reporting higher total dietary nitrate intakes (Q4 > 78.2 mg/day) and vegetable nitrate intakes (Q4 > 64.4 mg/day) were 25% and 27% reduced risk of developing CVD-related complications respectively, compared with women reporting low total (Q1 < 45.5 mg/day) and vegetable nitrate intakes (Q1 < 34.8 mg/day). Our findings were consistent with other observational data indicating that dietary nitrate may explain some of the cardiovascular benefits of vegetable consumption.

• cardiovascular disease
• dietary nitrate
• heart disease
• hypertension
• non-vegetable nitrate
• stroke
• thrombosis
• vegetable nitrate

The objective of this study is to test the hypothesis that increased muscle mass has positive effects on cardiovascular function. Specifically, we tested the hypothesis that increases in lean body mass caused by deletion of myostatin improves cardiac performance and vascular function. Echocardiography was used to quantify left ventricular function at baseline and after acute administration of propranolol and isoproterenol to assess β‐adrenergic reactivity. Additionally, resistance vessels in several beds were removed, cannulated, pressurized to 60 mmHg and reactivity to vasoactive stimuli was assessed. Hemodynamics were measured using in vivo radiotelemetry. Myostatin deletion results in increased fractional shortening at baseline. Additionally, arterioles in the coronary and muscular microcirculations are more sensitive to endothelial‐dependent dilation while nonmuscular beds or the aorta were unaffected. β‐adrenergic dilation was increased in both coronary and conduit arteries, suggesting a systemic effect of increased muscle mass on vascular function. Overall hemodynamics and physical characteristics (heart weight and size) remained unchanged. Myostatin deletion mimics in part the effects of exercise on cardiovascular function. It significantly increases lean muscle mass and results in muscle‐specific increases in endothelium‐dependent vasodilation. This suggests that increases in muscle mass may serve as a buffer against pathological states that specifically target cardiac function (heart failure), the β‐adrenergic system (age), and nitric oxide bio‐availability (atherosclerosis). Taken together, pharmacological inhibition of the myostatin pathway could prove an excellent mechanism by which the benefits of exercise can be conferred in patients that are unable to exercise.

• Augmented muscle mass
• cardiac function
• coronary microvasculature
• exercise
• myostatin
• nitric oxide
• β‐adrenergic

The family of vascular endothelial growth factors (VEGFs) are known for their regulation of vascularization. In the brain, VEGFs are important regulators of angiogenesis, neuroprotection and neurogenesis. Dysregulation of VEGFs is involved in a large number of neurodegenerative diseases and acute neurological insults, including stroke. Stroke is the main cause of acquired disabilities, and normally results from an occlusion of a cerebral artery or a hemorrhage, both leading to focal ischemia. Neurons in the ischemic core rapidly undergo necrosis. Cells in the penumbra are exposed to ischemia, but may be rescued if adequate perfusion is restored in time. The neuroprotective and angiogenic effects of VEGFs would theoretically make VEGFs ideal candidates for drug therapy in stroke. However, contradictory to what one might expect, endogenously upregulated levels of VEGF as well as the administration of exogenous VEGF is detrimental in acute stroke. This is probably due to VEGF-mediated blood–brain-barrier breakdown and vascular leakage, leading to edema and increased intracranial pressure as well as neuroinflammation. The key to understanding this Janus face of VEGF function in stroke may lie in the timing; the harmful effect of VEGFs on vessel integrity is transient, as both VEGF preconditioning and increased VEGF after the acute phase has a neuroprotective effect. The present review discusses the multifaceted action of VEGFs in stroke prevention and therapy.

• VEGF
• exercise
• growth factor
• ischemia
• stroke

• Blood-Brain Barrier/drug effects
• Blood-Brain Barrier/pathology
• Brain Ischemia/drug therapy
• Brain Ischemia/genetics
• Brain Ischemia/pathology
• Humans
• Neovascularization, Pathologic/drug therapy
• Neovascularization, Pathologic/genetics
• Neovascularization, Pathologic/pathology
• Neurons/metabolism
• Neuroprotective Agents/therapeutic use
• Stroke/drug therapy
• Stroke/genetics
• Stroke/pathology
• Vascular Endothelial Growth Factor A/genetics

• cardiac rehabilitation
• cardiorespiratory fitness
• exercise training
• heart failure

• Evidence-Based Medicine
• Exercise Therapy
• Exercise Tolerance/physiology
• Heart Failure/rehabilitation
• Humans
• Quality of Life
• Randomized Controlled Trials as Topic

Endothelial dysfunction is associated with increased cardiovascular mortality and morbidity; however, this dysfunction may be ameliorated by several therapies. For example, it has been reported that heat‐induced increases in blood flow and shear stress enhance endothelium‐mediated vasodilator function. Under these backgrounds, we expect that carbon dioxide (CO₂)‐rich water‐induced increase in skin blood flow improves endothelium‐mediated vasodilation with less heat stress. To test our hypothesis, we measured flow‐mediated dilation (FMD) before and after acute immersion of the lower legs and feet in mild warm (38°C) normal or CO₂‐rich tap water (1000 ppm) for 20 min in 12 subjects. Acute immersion of the lower legs and feet in mild warm CO₂‐rich water increased FMD (P < 0.01) despite the lack of change in this parameter upon mild warm normal water immersion. In addition, FMD was positively correlated with change in skin blood flow regardless of conditions (P < 0.01), indicating that an increase in skin blood flow improves endothelial‐mediated vasodilator function. Importantly, the temperature of normal tap water must reach approximately 43°C to achieve the same skin blood flow level as that obtained during mild warm CO₂‐rich water immersion (38°C). These findings suggest that CO₂‐rich water‐induced large increases in skin blood flow may improve endothelial‐mediated vasodilator function while causing less heat stress.

• Brachial‐ankle pulse wave velocity
• Doppler ultrasound
• flow‐mediated dilation

• Cardiac rehabilitation
• Flow-mediated dilation
• Heart failure with preserved ejection fraction
• Heart failure with reduced ejection fraction

• Endothelial function
• Endothelial progenitor cells
• Exercise
• Flow-mediated dilation
• Heart failure

Stable plasma nitric oxide (NO) metabolites (NO_M), composed predominantly of nitrate and nitrite, are attractive biomarkers of NO bioavailability. NO_M levels integrate the influence of NO‐synthase‐derived NO production/metabolism, dietary intake of inorganic nitrate/nitrite, and clearance of NO_M. Furthermore, nitrate and nitrite, the most abundant NO_M, can be reduced to NO via the nitrate‐nitrite‐NO pathway.

We compared serum NO_M among subjects without heart failure (n=126), subjects with heart failure and preserved ejection fraction (HFpEF; n=43), and subjects with heart failure and reduced ejection fraction (HFrEF; n=32). LV mass and extracellular volume fraction were measured with cardiac MRI. Plasma NO_M levels were measured after reduction to NO via reaction with vanadium (III)/hydrochloric acid. Subjects with HFpEF demonstrated significantly lower unadjusted levels of NO_M (8.0 μmol/L; 95% CI 6.2–10.4 μmol/L; ANOVA P=0.013) than subjects without HF (12.0 μmol/L; 95% CI 10.4–13.9 μmol/L) or those with HFrEF (13.5 μmol/L; 95% CI 9.7–18.9 μmol/L). There were no significant differences in NO_M between subjects with HFrEF and subjects without HF. In a multivariable model that adjusted for age, sex, race, diabetes mellitus, body mass index, current smoking, systolic blood pressure, and glomerular filtration rate, HFpEF remained a predictor of lower NO_M (β=−0.43; P=0.013). NO_M did not correlate with LV mass, or LV diffuse fibrosis.

HFpEF, but not HFrEF, is associated with reduced plasma NO_M, suggesting greater endothelial dysfunction, enhanced clearance, or deficient dietary ingestion of inorganic nitrate. Our findings may underlie the salutary effects of inorganic nitrate supplementation demonstrated in recent clinical trials in HFpEF.

• diastolic heart failure
• heart failure
• hypertrophy/remodeling
• myocardial fibrosis
• myocardial structure

• Blood Flow Velocity/physiology
• Brachial Artery/diagnostic imaging
• Brachial Artery/physiopathology
• Cytokines/blood
• Electric Stimulation Therapy
• Endothelium, Vascular/physiopathology
• Female
• Follow-Up Studies
• Heart Failure/immunology
• Heart Failure/physiopathology
• Heart Failure/therapy
• Humans
• Immunity, Cellular/physiology
• Male
• Middle Aged
• Severity of Illness Index
• Stroke Volume
• Treatment Outcome
• Ultrasonography, Doppler
• Vasodilation/physiology

• Endothelial dysfunction
• Heart failure with preserved ejection fraction
• Novel therapies
• Systemic inflammation

• Animals
• Endothelium, Vascular/physiopathology
• Heart Failure/diagnosis
• Heart Failure/metabolism
• Heart Failure/physiopathology
• Heart Failure/therapy
• Humans
• Inflammation/diagnosis
• Inflammation/metabolism
• Inflammation/physiopathology
• Inflammation/therapy
• Inflammation Mediators/metabolism
• Prognosis
• Risk Factors
• Signal Transduction
• Stroke Volume
• Ventricular Function, Left