Brachial artery ultrasound is commonly employed for noninvasive assessment of endothelial function. However, analysis is observer dependent and susceptible to errors. We describe studies on a computerized edge-detection and wall-tracking software program to allow more accurate and reproducible measurement. In study 1, three purpose-built Perspex phantom arteries, 3.00, 4.00, and 6.00 mm in diameter, were measured with the software. There was a mean bias of 11 microm (P < 0.001 at each level) between known and measured values; the mean resolving power of the software was estimated as 8.3 microm. In study 2, the mean intraobserver coefficient of variation of repeated measures of flow-mediated dilation (FMD) using the software (6.7%) was significantly lower than that for traditional manual measurements using the intima-lumen interfaces (24.8%, P < 0.05) and intima-media interfaces (32.5%, P < 0.05). In study 3, 24 healthy volunteers underwent repeat testing twice within 1 wk; the coefficients of variation for between-visit reproducibility of FMD and response to glyceryl trinitrate using the software were 14.7 and 17.6%, respectively. Assuming 80% power and an alpha of 0.05, eight subjects with matched controls would be required, in a parallel designed study, to detect an absolute 2.5% change in FMD. In summary, we have developed a semiautomated computerized vascular ultrasound analysis system that will improve the power of clinical intervention studies to detect small changes in arterial diameter.

BackgroundPulmonary hypertension (PHT) lacks community prevalence and outcome data.ObjectiveTo characterise minimum ‘indicative’ prevalences and mortality data for all forms of PHT in a selected population with an elevated estimated pulmonary artery systolic pressure (ePASP) on echocardiography.DesignObservational cohort study.SettingResidents of Armadale and the surrounding region in Western Australia (population 165 450) referred to our unit for transthoracic echocardiography between January 2003 and December 2009.ResultsOverall, 10 314 individuals (6.2% of the surrounding population) had 15 633 echo studies performed. Of these, 3320 patients (32%) had insufficient TR to ePASP and 936 individuals (9.1%, 95% CI 8.6% to 9.7%) had PHT, defined as, ePASP>40 mm Hg. The minimum ‘indicative’ prevalence for all forms of PHT is 326 cases/100 000 inhabitants of the local population, with left heart disease-associated PHT being the commonest cause (250 cases/100 000). 15 cases of pulmonary arterial hypertension/100 000 inhabitants were identified and an additional 144 individuals (15%) with no identified cause for their PHT. The mean time to death for those with ePASP >40 mm Hg, calculated from the first recorded ePASP, was 4.1 years (95% CI 3.9 to 4.3). PHT increased mortality whatever the underlying cause, but patients with PHT from left heart disease had the worst prognosis and those with idiopathic pulmonary arterial hypertension receiving disease-specific treatment the best prognosis. Risk of death increased with PHT severity: severe pulmonary hypertension shortened the lifespan by an average of 1.1 years compared with mild pulmonary hypertension.ConclusionsIn this cohort, PHT was common and deadly. Left heart disease was the most common cause and had the worst prognosis and treated pulmonary arterial hypertension had the best prognosis.

Objective: Our objective was to assess effects of dietary supplementation with coenzyme Q 10 (CoQ) on blood pressure and glycaemic control in subjects with type 2 diabetes, and to consider oxidative stress as a potential mechanism for any effects. Subjects and design: Seventy-four subjects with uncomplicated type 2 diabetes and dyslipidaemia were involved in a randomised double blind placebo-controlled 2Â2 factorial intervention. Setting: The study was performed at the University of Western Australia, Department of Medicine at Royal Perth Hospital, Australia. Interventions: Subjects were randomly assigned to receive an oral dose of 100 mg CoQ twice daily (200 mg=day), 200 mg fenofibrate each morning, both or neither for 12 weeks. Main outcome measures: We report an analysis and discussion of the effects of CoQ on blood pressure, on long-term glycaemic control measured by glycated haemoglobin (HbA 1c ), and on oxidative stress assessed by measurement of plasma F 2 -isoprostanes. Results: Fenofibrate did not alter blood pressure, HbA 1c , or plasma F 2 -isoprostanes. There was a 3-fold increase in plasma CoQ concentration (3.4 AE 0.3 mmol=l, P < 0.001) as a result of CoQ supplementation. The main effect of CoQ was to significantly decrease systolic ( 7 6.1 AE 2.6 mmHg, P ¼ 0.021) and diastolic ( 7 2.9 AE 1.4 mmHg, P ¼ 0.048) blood pressure and HbA 1c ( 7 0.37 AE 0.17%, P ¼ 0.032). Plasma F 2 -isoprostane concentrations were not altered by CoQ (0.14 AE 0.15 nmol=l, P ¼ 0.345). Conclusions: These results show that CoQ supplementation may improve blood pressure and long-term glycaemic control in subjects with type 2 diabetes, but these improvements were not associated with reduced oxidative stress, as assessed by F 2 -isoprostanes.

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The R222Q SCN5A variant has an activating effect on sodium channel function and is associated with reversible ventricular ectopy and DCM. Elucidation of the genetic basis of familial DCM can enable effective gene-targeted therapy to be implemented.

In Type II (non-insulin-dependent) diabetes mellitus the pathogenesis of vascular disease, its most common complication, remains unclear [1]. Endothelial dysfunction reflects the disordered physiology of several endothelium-derived vasoactive factors, in particular nitric oxide [2]. Endothelial dysfunction occurs commonly in diabetes and is an early feature of vasculopathy [3,4]. Increased oxidative stress due to the effects of hyperglycaemia and its sequelae is a recognized feature of diabetes [5]. It might cause endothelial dysfunction through the inactivation and Abstract Aim/hypothesis. We assessed whether dietary supplementation with coenzyme Q 10 improves endothelial function of the brachial artery in patients with Type II (non-insulin-dependent) diabetes mellitus and dyslipidaemia. Methods. A total of 40 patients with Type II diabetes and dyslipidaemia were randomized to receive 200 mg of coenzyme Q 10 or placebo orally for 12 weeks. Endothelium-dependent and independent function of the brachial artery was measured as flowmediated dilatation and glyceryl-trinitrate-mediated dilatation, respectively. A computerized system was used to quantitate vessel diameter changes before and after intervention. Arterial function was compared with 18 non-diabetic subjects. Oxidative stress was assessed by measuring plasma F 2 -isoprostane concentrations, and plasma antioxidant status by oxygen radical absorbance capacity. Results. The diabetic patients had impaired flow-mediated dilation [3.8 % (SEM 0.5) vs 6.4 % (SEM 1.0), p = 0.016], but preserved glyceryl-trinitrate-mediated dilation, of the brachial artery compared with non-diabetic subjects. Flow-mediated dilation of the brachial artery increased by 1.6 % (SEM 0.3) with coenzyme Q 10 and decreased by ±0.4 % (SEM 0.5) with placebo (p = 0.005); there were no group differences in the changes in pre-stimulatory arterial diameter, post-ischaemic hyperaemia or glyceryl-trinitrate-mediated dilation response. Coenzyme Q 10 treatment resulted in a threefold increase in plasma coenzyme Q 10 (p < 0.001) but did not alter plasma F 2 -isoprostanes, oxygen radical absorbance capacity, lipid concentrations, glycaemic control or blood pressure. Conclusion/interpretation. Coenzyme Q 10 supplementation improves endothelial function of conduit arteries of the peripheral circulation in dyslipidaemic patients with Type II diabetes. The mechanism could involve increased endothelial release and/or activity of nitric oxide due to improvement in vascular oxidative stress, an effect that might not be reflected by changes in plasma F 2 -isoprostane concentrations. [Diabetologia (2002) 45: 420±426]

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