Cardiovascular responses to experimental weight gain in humans: a feasibility study.

Objective: Obesity and hypertension share a well known association. However, the mechanisms underlying their relationship are not well understood. Our goal was to assess the feasibility of a longitudinal, interventional weight gain study with detailed cardiovascular measurements in humans.

Quantitative F-fluorodeoxyglucose positron emission tomography/computed tomography to assess pulmonary inflammation in COPD.

Rationale: COPD and smoking are characterised by pulmonary inflammation. F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) imaging may improve knowledge of pulmonary inflammation in COPD patients and aid early development of novel therapies as an imaging biomarker.

Objectives: To evaluate pulmonary inflammation, assessed by FDG uptake, in whole and regional lung in "usual" (smoking-related) COPD patients, alpha-1 antitrypsin deficiency (αATD) COPD patients, smokers without COPD and never-smokers using FDG PET/CT.

Mechanisms Underlying Vascular Endothelial Growth Factor Receptor Inhibition-Induced Hypertension: The HYPAZ Trial.

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Cardiovascular risk prediction using physical performance measures in COPD: results from a multicentre observational study.

Objectives: Although cardiovascular disease (CVD) is a common comorbidity associated with chronic obstructive pulmonary disease (COPD), it is unknown how to improve prediction of cardiovascular (CV) risk in individuals with COPD. Traditional CV risk scores have been tested in different populations but not uniquely in COPD. The potential of alternative markers to improve CV risk prediction in individuals with COPD is unknown.

Role of Vascular Adaptation in Determining Systolic Blood Pressure in Young Adults.

Background Two individuals can have a similar pulse pressure (PP) but different levels of systolic blood pressure (SBP), although the underlying mechanisms have not been described. We hypothesized that, for a given level of PP, differences in SBP relate to peripheral vascular resistance (PVR); and we tested this hypothesis in a large cohort of healthy young adults. Methods and Results Demographic, biochemical, and hemodynamic data from 3103 subjects were available for the current analyses.

Vascular consequences of inflammation: a position statement from the ESH Working Group on Vascular Structure and Function and the ARTERY Society.

: Inflammation is a physiological response to aggression of pathogenic agents aimed at eliminating the aggressor agent and promoting healing. Excessive inflammation, however, may contribute to tissue damage and an alteration of arterial structure and function. Increased arterial stiffness is a well recognized cardiovascular risk factor independent of blood pressure levels and an intermediate endpoint for cardiovascular events.

Uses of Arterial Stiffness in Clinical Practice.

As far back as the ancient Egyptians and Greeks, physicians have observed and interpreted the arterial pulse to diagnose disease. In the last 20 years, advances in modern engineering have rendered quantitative pulse wave analysis widely available, reliable, and reproducible. To date, measurement of arterial stiffness has remained almost exclusively a research activity.

Investigating the lowest threshold of vascular benefits from LDL cholesterol lowering with a PCSK9 mAb inhibitor (alirocumab) in healthy volunteers - a mechanistic physiological study (INTENSITY-LOW): protocol and study rationale.

Whether reducing low density lipoprotein cholesterol (LDL-C) is associated with cardiovascular benefits in low risk normocholesterolaemic subjects is unknown. The INTENSITY LOW [Investigating the lowest threshold of vascular benefits from LDL-cholesterol lowering with a PCSK9 mAb inhibitor (alirocumab) in healthy volunteers] study aims to assess whether lowering LDL-C by alirocumab monotherapy can improve endothelial-dependent vascular function compared with placebo (primary objective) in low-risk normocholesterolaemic healthy individuals. Changes in endothelial-dependent or endothelial-independent vascular function, arterial stiffness and biomarkers of systemic inflammation by alirocumab, atorvastatin or their combination are secondary objectives.

Cardiovascular Phenotype of Elevated Blood Pressure Differs Markedly Between Young Males and Females: The Enigma Study.

Blood pressure (BP) in young adults predicts BP in later life. We aimed to identify metabolic, hemodynamic, and autonomic characteristics associated with raised BP in young adults and whether these differ between males and females. Three thousand one hundred forty-five healthy subjects, aged 18 to 40 years, were grouped according to sex and BP category following the recent reclassification of BP as part of American Heart Association/American College of Cardiology 2017 guidelines.

Evaluation of inert gas rebreathing for determination of cardiac output: influence of age, gender and body size.

The aim of this study was to evaluate an inert gas rebreathing method (Innocor) for measurement of cardiac output and related haemodynamic variables and to provide robust normative data describing the influence of age, gender and body size on these variables. Four separate studies were conducted: measurement repeatability (study 1, n = 45); postural change (study 2, n = 40); response to submaximal cycling exercise (study 3, n = 20); and the influence of age, gender and body size (study 4, n = 1400). Repeated measurements of cardiac output, stroke volume and heart rate were similar, with low mean (±SD) differences (0.

The p38 mitogen activated protein kinase inhibitor losmapimod in chronic obstructive pulmonary disease patients with systemic inflammation, stratified by fibrinogen: A randomised double-blind placebo-controlled trial.

Background: Cardiovascular disease is a major cause of morbidity and mortality in COPD patients. Systemic inflammation associated with COPD, is often hypothesised as a causal factor. p38 mitogen-activated protein kinases play a key role in the inflammatory pathogenesis of COPD and atherosclerosis.

Surrogate Markers of Cardiovascular Risk and Chronic Obstructive Pulmonary Disease: A Large Case-Controlled Study.

Cardiovascular disease is a common comorbidity and cause of mortality in chronic obstructive pulmonary disease. A better understanding of mechanisms of cardiovascular risk in chronic obstructive pulmonary disease patients is needed to improve clinical outcomes. We hypothesized that such patients have increased arterial stiffness, wave reflections, and subclinical atherosclerosis compared with controls and that these findings would be independent of smoking status and other confounding factors.

Novel Mechanism for Buffering Dietary Salt in Humans: Effects of Salt Loading on Skin Sodium, Vascular Endothelial Growth Factor C, and Blood Pressure.

High dietary sodium intake triggers increased blood pressure (BP). Animal studies show that dietary salt loading results in dermal Na accumulation and lymphangiogenesis mediated by VEGF-C (vascular endothelial growth factor C), both attenuating the rise in BP. Our objective was to determine whether these mechanisms function in humans.

The Role of the Autonomic Nervous System in the Regulation of Aortic Stiffness.

The autonomic nervous system is important in regulating blood pressure, but whether it regulates aortic stiffness is more contentious. We conducted 3 studies in young, healthy individuals to address this important question. Study 1 was a cross-sectional study of 347 subjects with detailed measurements of hemodynamics and heart rate variability.

Tetrahydrobiopterin Supplementation Improves Endothelial Function But Does Not Alter Aortic Stiffness in Patients With Rheumatoid Arthritis.

Background: Rheumatoid arthritis is a systemic inflammatory condition associated with increased cardiovascular risk that may be due to underlying endothelial dysfunction and subsequent aortic stiffening. We hypothesized that supplementation with tetrahydrobiopterin (BH4) would recouple endothelial nitric oxide synthase and thus improve endothelial function and consequently reduce aortic stiffness.

Methods And Results: We conducted 2 randomized, double-blinded, placebo-controlled crossover studies examining 2 separate regimens: an acute regimen, with a single dose of BH4 400 mg versus placebo (n=18), and a short-term regimen, composed of a 1-week treatment with BH4 400 mg once daily versus placebo (n=15).

Mechanisms underlying elevated SBP differ with adiposity in young adults: the Enigma study.

Objectives: The positive association between adiposity and hypertension is well recognized. However, not all overweight individuals have elevated blood pressure (BP). Moreover, different factors may be associated with high BP in normal-weight versus overweight individuals.

Effects of oral lycopene supplementation on vascular function in patients with cardiovascular disease and healthy volunteers: a randomised controlled trial.

Aims: The mechanisms by which a 'Mediterranean diet' reduces cardiovascular disease (CVD) burden remain poorly understood. Lycopene is a potent antioxidant found in such diets with evidence suggesting beneficial effects. We wished to investigate the effects of lycopene on the vasculature in CVD patients and separately, in healthy volunteers (HV).

Therapeutic potential of p38 MAP kinase inhibition in the management of cardiovascular disease.

p38 mitogen-activated protein kinases (p38 MAPKs) are key signalling molecules that regulate cellular behavior in response to environmental stresses. They regulate pro-inflammatory cytokines and therefore p38 MAPKs are implicated in the pathogenesis of many inflammatory-driven conditions, including atherosclerosis. Therapeutic inhibition of p38 MAPKs to attenuate inflammation has been the focus of comprehensive research in the last 2 decades, following the discovery of p38α as the molecular target of pyrindinyl imidazole compounds, which suppress the cytokines tumor necrosis factor-α and interleukin-1.

A comprehensive study of clinical, biochemical, radiological, vascular, cardiac, and sleep parameters in an unselected cohort of patients with acromegaly undergoing presurgical somatostatin receptor ligand therapy.

Context: Attainment of safe GH and IGF-1 levels is a central goal of acromegaly management.

Objective: The aim of this study was to determine the extent to which reductions in GH and IGF-1 concentrations correlate with amelioration of radiological, metabolic, vascular, cardiac, and respiratory sequelae in a single unselected patient cohort.

Study Design: This was a prospective, within-subject comparison in 30 patients with newly diagnosed acromegaly (15 women and 15 men: mean age, 54.

Habitual exercise and blood pressure: age dependency and underlying mechanisms.

Background: Regular exercise is associated with a reduction in cardiovascular risk, but the precise mechanisms responsible are unknown. The aim of the current study was to examine the relationship between regular exercise, aortic stiffness, and wave reflections, and to determine whether this relationship differs by age.

Methods: Younger (<30 years) and older (>50 years) individuals, who were either sedentary or undertook regular aerobic exercise, were drawn from the Anglo-Cardiff Collaborative Trial population.

Anti-tumor necrosis factor-α therapy reduces aortic inflammation and stiffness in patients with rheumatoid arthritis.

Background: Rheumatoid arthritis (RA) is a systemic inflammatory condition associated with increased cardiovascular risk. This is not fully explained by traditional risk factors, but direct vascular inflammation and aortic stiffening may play a role. We hypothesized that patients with RA exhibit aortic inflammation, which can be reversed with anti-tumor necrosis factor-α therapy and correlates with aortic stiffness reduction.

The impact of birth weight on blood pressure and arterial stiffness in later life: the Enigma Study.

Background: Accumulating evidence suggests that low birth weight is associated with increased cardiovascular risk. However, the relationship between birth weight, blood pressure, arterial stiffness and wave reflections as putative mechanisms is controversial.

Method: Data from 882 participants (mean age 21 years) were analysed.