Protocol for the Stimulating β-Adrenergic Receptors for Peripheral Artery Disease (STAR-PAD) trial: a double-blinded, randomised, placebo-controlled study evaluating the effects of mirabegron on functional performance in patients with peripheral arterial disease.

Introduction: There is currently only one approved medication effective at improving walking distance in people with intermittent claudication. Preclinical data suggest that the β-adrenergic receptor agonist (mirabegron) could be repurposed to treat intermittent claudication associated with peripheral artery disease. The aim of the Stimulating β-Adrenergic Receptors for Peripheral Artery Disease (STAR-PAD) trial is to test whether mirabegron improves walking distance in people with intermittent claudication.

Extensive pulmonary artery embolisation caused by cardiac hydatid cyst rupture.

This case study is a rare example of cardiac hydatidosis in a high-income country, where a middle-aged man presented with a ruptured right ventricular cyst causing anaphylaxis, pulmonary emboli and dissemination of throughout the lung. He survived the cyst rupture and underwent cardiac surgery but had incomplete resection and experienced progressive cardiopulmonary hydatidosis despite antihelminthic therapy. As a result, he experienced an array of cardiopulmonary sequelae over his lifespan.

Renal Denervation for the Management of Refractory Ventricular Arrhythmias: A Systematic Review.

Objectives: The authors performed a systematic review and meta-analysis to determine the efficacy of renal denervation (RDN) in patients with refractory ventricular arrhythmias (VA) or electrical storm (ES).

Background: Although catheter ablation is efficacious for the treatment of structural heart disease ventricular tachycardia (VT), there are proportion of patients who have refractory VT despite multiple procedures. In this setting, novel adjunctive therapies such as renal denervation have been performed.

Fenofibrate effects on carotid artery intima-media thickness in adults with type 2 diabetes mellitus: A FIELD substudy.

Aim: Dyslipidemia in type 2 diabetes contributes to an increased risk of cardiovascular disease. Fenofibrate, a lipid-regulating peroxisome proliferator-activated receptor-α (PPARα) agonist, has been shown to reduce vascular complications in adults with type 2 diabetes. The mechanisms for such benefit, however, are not yet well understood.

Carotid extramedial thickness is associated with local arterial stiffness in children.

Objectives: Experimental evidence suggests that structural changes to the arterial adventitia may be a key vascular determinant of early arterial stiffening, although this has not been directly studied. Accordingly, we hypothesized that in young children, in whom this relationship would not be altered by atheroma, carotid extramedial thickness (EMT), a measure that incorporates the thickness of the arterial adventitia, perivascular tissues and the internal jugular venous wall, would be associated with localized arterial stiffness of the same arterial region.

Methods: We studied 248 healthy prepubescent children (aged 8 years).

Telomere length in early childhood: Early life risk factors and association with carotid intima-media thickness in later childhood.

Background: Reduced telomere length is a measure of biological aging that is predictive of cardiac events in adults, and has been mechanistically implicated in the onset and progression of atherosclerosis. We sought to describe the early life factors associated with leukocyte telomere length in early childhood, and to determine whether telomere length measured during early childhood is associated with arterial wall thickening later in childhood.

Design: A longitudinal birth cohort recruited antenatally in Sydney from 1997 to 1999.

Fenofibrate effects on arterial endothelial function in adults with type 2 diabetes mellitus: A FIELD substudy.

Objective: Dislipidaemia in type 2 diabetes mellitus contributes to arterial endothelial dysfunction and an increased risk of cardiovascular disease. Fenofibrate, a lipid-regulating peroxisome proliferator-activated receptor-α (PPARα) agonist, has been shown to reduce vascular complications in adults with type 2 diabetes. However, the mechanisms for such benefit are not well understood.

Cigarette smoking and albuminuria are associated with impaired arterial smooth muscle function in patients with type 2 diabetes mellitus: a FIELD substudy.

Aim: Impaired arterial function has been implicated in diabetes-related atherosclerosis, but its determinants in high-risk adults have not been well characterised. We investigated factors associated with impaired arterial function in adults with type 2 diabetes.

Methods: Flow-mediated dilatation (a marker of endothelial function) and dilator response to glyceryl trinitrate (to assess smooth muscle function) of the brachial artery were assessed at baseline in 193 patients with type 2 diabetes from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study.

Weight gain in infancy is associated with carotid extra-medial thickness in later childhood.

Objective: Early life is an important period for determining future risk of cardiovascular disease. Carotid extra-medial thickness is a novel noninvasive measure that estimates arterial adventitial thickness, information concerning vascular health not captured by assessment of arterial intima-media thickness alone. We sought to determine whether fetal growth and early postnatal growth are associated with carotid extra-medial thickness in 8 year old children.

Weight gain in infancy and vascular risk factors in later childhood.

Objective: We hypothesized that early weight gain would be associated with incident obesity, higher blood pressure, systemic inflammation, and arterial wall thickening in later childhood.

Methods: A longitudinal birth cohort was recruited antenatally from 2 maternity hospitals in Sydney, Australia, between September 1997 and December 1999. Three hundred ninety-five nondiabetic children who were followed to age 8 years had complete data for early weight gain and arterial wall thickness.

High plasma thiocyanate levels modulate protein damage induced by myeloperoxidase and perturb measurement of 3-chlorotyrosine.

Smokers have an elevated risk of atherosclerosis but the origin of this elevated risk is incompletely defined, though increasing evidence supports a role for the oxidant-generating enzyme myeloperoxidase (MPO). In previous studies we have demonstrated that smokers have elevated levels of thiocyanate ions (SCN(-)), relative to nonsmokers, and increased thiol oxidation, as SCN(-) is a favored substrate for MPO, and the resulting hypothiocyanous acid (HOSCN) targets thiol groups rapidly and selectively. In this study we show that increased HOSCN formation by MPO diminishes damage to nonthiol targets on both model proteins and human plasma proteins.

Carotid extra-medial thickness in childhood: early life effects on the arterial adventitia.

Objective: Structural modification of the arterial adventitia may be an early event in atherosclerosis. Carotid extra-medial thickness is a new measure of arterial adventitial thickness. We examined the association of cardiovascular risk factors with extra-medial thickness, in childhood.

Impaired fetal growth and arterial wall thickening: a randomized trial of ω-3 supplementation.

Objectives: Impaired fetal growth is an independent cardiovascular risk factor and is associated with arterial wall thickening in children. No preventive strategy has been identified. We sought to determine whether dietary ω-3 fatty acid supplementation during early childhood prevents the association between impaired fetal growth and carotid arterial wall thickening.

Lung function is associated with arterial stiffness in children.

Background: In older adults, an independent association exists between impaired lung function and cardiovascular disease. This interaction might be related to the effects of aging and/or smoking. In order to explore possible childhood antecedents to this association, we hypothesized that decreased lung function and vascular stiffness might be related, in early life.

High plasma thiocyanate levels in smokers are a key determinant of thiol oxidation induced by myeloperoxidase.

Smokers have an elevated risk of atherosclerosis but the origins of this elevated risk are incompletely defined, though evidence supports an accumulation of the oxidant-generating enzyme myeloperoxidase (MPO) in the inflamed artery wall. We hypothesized that smokers would have a high level of thiocyanate (SCN(-)), a preferred substrate for MPO, which in turn would predispose to thiol oxidation, an established independent risk factor for atherosclerosis. In this study it is shown that on exposure to MPO/H(2)O(2), thiols on plasma proteins from nonsmokers were increasingly oxidized with increasing added SCN(-) concentrations.

Maternal cigarette smoking is associated with reduced high-density lipoprotein cholesterol in healthy 8-year-old children.

Aims: Smoking in pregnancy is common. Its effects on lipoprotein levels and arterial structure in childhood are not well characterized. We aimed to determine the effects of maternal smoking in pregnancy on lipoprotein levels and arterial wall thickness in healthy pre-pubertal children.

Snoring is not associated with adverse effects on blood pressure, arterial structure or function in 8-year-old children: the Childhood Asthma Prevention Study (CAPS).

Aims: To study the association between childhood snoring and cardiovascular risk factors.

Methods: Cross-sectional analyses of a population-based birth cohort, who had been participants in a randomised controlled trial of interventions to prevent asthma and who were assessed at age 8 years. The presence and frequency of snoring were assessed by parent-completed questionnaire.

Severe obesity is associated with impaired arterial smooth muscle function in young adults.

The degree of arterial dilatation induced by exogenous nitrates (nitrate-mediated dilatation, NMD) has been similar in obese and normal-weight adults after single high-dose glyceryl trinitrate (GTN). We examined whether NMD is impaired in obesity by performing a GTN dose-response study, as this is a potentially more sensitive measure of arterial smooth muscle function. In this cross-sectional study, subjects were 19 obese (age 31.

Central arterial pulse wave augmentation is greater in girls than boys, independent of height.

Objectives: Central arterial pulse wave augmentation, quantified by the augmentation index (AIx), is a key marker of arterial health, an important contributor to cardiac afterload and is significantly greater in older women than men. We measured carotid AIx in 8-year-old children to examine the influences of sex, height and arterial stiffness on central arterial pulse wave augmentation

Methods: Four hundred and five children (age 8.0 +/- 0.

Postprandial vascular reactivity in obese and normal weight young adults.

As humans spend a significant amount of time in the postprandial state, we examined whether vascular reactivity (a key indicator of cardiovascular health) was different after a high-fat meal in 11 obese (median BMI 46.4, age 32.1 +/- 6.

Dietary supplementation with n-3 polyunsaturated fatty acids in early childhood: effects on blood pressure and arterial structure and function at age 8 y.

Background: n-3 Fatty acid supplementation in adults results in cardiovascular benefits. However, the cardiovascular effects of n-3 supplementation in early childhood are unknown.

Objective: The objective was to evaluate blood pressure (BP) and arterial structure and function in 8-y-old children who had participated in a randomized controlled trial of dietary n-3 and n-6 modification over the first 5 y of life.

HDL-cholesterol, blood pressure, and asymmetric dimethylarginine are significantly associated with arterial wall thickness in children.

Objective: Atherosclerosis is found at autopsy in the arteries of adolescents and young adults. Arterial wall thickening may be assessed in vivo by ultrasound measurement of the carotid intima media thickness (CIMT), a marker of subclinical atherosclerosis. As the determinants of arterial wall thickness in childhood are unknown, we assessed the influence of cardiovascular risk factors on CIMT in 8-year-old children.