The assessment and characterisation of obstructive sleep apnoea in severe obesity

Abstract Background Obstructive Sleep Apnoea (OSA) is associated with cardiovascular disease. The current evidence regarding the effects of OSA in individuals with severe obesity is limited and has hitherto been largely unexplored. With the growing population of diabetes and obesity globally, the identification of severely obese individuals who have OSA is important given the risk of adverse outcomes associated with OSA. In this regard, the use of urinary proteomic (urinary peptide) profiling as a potential tool to characterise adult severely obese patients for the diagnostic assessment of OSA remains to be investigated. Aims The aims of the studies described in this thesis were to (1) investigate the effects of OSA in severe obesity in relation to measures related to cardiovascular risk, specifically, arterial stiffness and serum urate; (2) assess current clinical practice of OSA assessment; and (3) explore the use of urinary proteomics in characterising subjects with severe obesity and OSA. Methods In the arterial stiffness, urate and urinary proteomic studies, patients with severe obesity, were assessed at baseline and at follow-up. Anthropometric, respiratory and cardio-metabolic parameters were measured. All subjects had overnight polysomnography. Subjects with OSA were initially naive to OSA treatment at baseline were subsequently offered CPAP. For the arterial stiffness studies, pulse wave analysis (PWA) was performed. In the urate studies, serum urate measurements were taken to identify associations between OSA and urate at baseline; and CPAP with change in urate at follow-up. OSA assessment in diabetes clinical practice was explored by a national survey in relation to the International Diabetes Federation (IDF) guidance. In the urinary proteomics studies, urine samples were analysed by capillary electrophoresis-mass spectrometry (CE-MS) at baseline and at follow-up. Results Severely obese patients with OSA had increased arterial stiffness. Although sleepiness and blood pressure improved with CPAP in severe obesity, CPAP alone was not sufficient to modify PWA measures to levels comparable with non-OSA patients. In the urate study, serum urate was associated with OSA in severely obese females and there was a trend for reduced urate levels in CPAP-treated patients. The questionnaire study revealed a disappointing low awareness of the IDF statements and of the perceived importance of assessing for OSA in type 2 diabetes. The urinary proteomic studies identified trends in the urinary peptide profiles suggesting that there may be inherent differences between OSA and non-OSA patients, even following a period of effective CPAP treatment. The identified peptide panel included collagens, cadherin and fibrinogen subtypes. Conclusions The theme that links the studies in this thesis has been the importance of OSA in relation to cardiovascular risk. Severely obese patients with OSA have increased arterial stiffness that may increase cardiovascular risk. Likewise, in severely obese individuals with OSA who have hyperuricaemia or recurrent gout, there may be a need to consider OSA assessment as elevated urate levels are associated with increased cardiovascular risk. From the questionnaire study, it is clear that more work needs to be done to raise awareness about OSA assessment in diabetes teams as obesity is a risk factor for type 2 diabetes. Urinary proteomic CE-MS profiling has provided novel insights into the urinary proteome in OSA, with and without CPAP. Although there is insufficient evidence to support its use for OSA diagnosis, the urinary peptides identified may be linked with mechanisms underlying cardiovascular disease in OSA and may be associated with treatment effects of CPAP on OSA progression that influences expression of urinary peptides

Urinary proteomic profiling in severe obesity and obstructive sleep apnoea with CPAP treatment.

INTRODUCTION: Obstructive sleep apnoea (OSA) is common in obesity and is associated with cardiovascular and metabolic complications. Continuous positive airway pressure (CPAP) in OSA may lead to physiological changes reflected in the urinary proteome. The aim of this study was to characterise the urinary proteome in severely obese adult subjects with OSA who were receiving CPAP compared with severely obese subjects without OSA. METHODS: Severely obese subjects with and without OSA were recruited. Subjects with OSA were receiving CPAP. Body composition and blood pressure measurements were recorded. Urinary samples were analysed by Capillary Electrophoresis-Mass Spectrometry (CE-MS). RESULTS: Twenty-seven subjects with OSA-on-CPAP (age 49±7years, BMI 43±7 kg/m(2)) and 25 controls without OSA (age 52±9years, BMI 39±4 kg/m(2)) were studied. Age and BMI were not significantly different between groups. Mean CPAP use for OSA patients was 14.5±1.0 months. Metabolic syndrome was present in 14(52%) of those with OSA compared with 6(24%) of controls (p=0.039). A urinary proteome comprising 15 peptides was identified showing differential expression between the groups (p<0.01). Although correction for multiple testing did not reach significance, sequences were determined for 8 peptides demonstrating origins from collagens, fibrinogen beta chain and T-cadherin that may be associated with underlying cardiovascular disease mechanisms in OSA. CONCLUSIONS: The urinary proteome is compared in OSA with CPAP and without OSA in severe obesity. The effects of CPAP on OSA may lead to changes in the urinary peptides but further research work is needed to investigate the potential role for urinary proteomics in characterising urinary peptide profiles in OSA

Bleeding from ruptured hepatic metastases as a cause of syncope in an octogenarian: a case report

<p>Abstract</p> <p>Introduction</p> <p>Acute hemoperitoneum as a result of hemorrhage from liver metastases is an uncommon but serious condition. The use of appropriate imaging is important in the diagnosis and can have a profound impact on subsequent management. This case is important because the presentation was of recurrent syncopal episodes with an unusual underlying cause. This case highlights the need to consider this diagnosis in the differential in patients presenting with collapse in the acute setting.</p> <p>Case presentation</p> <p>We present the case of an 85-year-old Caucasian man who was admitted following a collapse episode and was found to be persistently hypotensive despite aggressive resuscitation. An acute intra-peritoneal bleed originating from hepatic metastases from an unknown primary was identified promptly with computed tomography imaging and was subsequently managed conservatively.</p> <p>Conclusions</p> <p>This case aims to convey key teaching points: (A) the need to consider intra-abdominal hemorrhage in the differential diagnosis when assessing patients with collapse; and (B) the use of appropriate imaging such as computed tomography can facilitate a prompt diagnosis and appropriate management steps can then be taken accordingly.</p

Serum urate and obstructive sleep apnoea in severe obesity

Obstructive sleep apnoea (OSA) may increase the risk of hyperuricaemia and predispose to gout. The evidence for the effects of OSA on serum urate in severe obesity is limited. This study investigated whether OSA was associated with serum urate in severe obesity and whether continuous positive airway pressure (CPAP) treatment was associated with a fall in urate. Severely obese subjects without known OSA or gout were recruited. Baseline assessments included urate, metabolic parameters, spirometry and overnight polysomnography. OSA patients were initially naive to treatment and were offered CPAP. At follow-up, change in urate was compared between CPAP-treated and non-CPAP-treated subjects. A high urate was defined as greater than the median. Logistic regression was performed to identify associations between (1) OSA and high urate at baseline and (2) use of CPAP and change in urate at follow-up. In total, 92 subjects were recruited (61 (66%) OSA and 31 (34%) non-OSA). Median urate was 345 μmol/L. OSA was associated with high urate in females at baseline after adjusting for confounders (adjusted odds ratio ORadj = 10.2; 95% CI: 1.1, 93.5). At follow-up (14 months), 58 subjects (28 on CPAP and 30 not on CPAP) were reassessed. CPAP was significantly associated with a fall to a low urate category at follow-up ( = 0.017). Regression revealed a trend for a fall in urate category in the CPAP-treated group (ORadj = 9.3; 95% CI: 0.8, 97). Serum urate is associated with OSA in severely obese females and CPAP may reduce levels in patients with OSA. There may be a need to consider and assess for OSA in obese patients with hyperuricaemia and recurrent attacks of gout. </jats:p

Research update for articles published in EJCI in 2014

Our findings showed that p53 mRNA expression levels are upregulated in epicardial adipose tissue (EAT) from patients with heart failure (HF). This upregulation was also found in myocardium [2]. Our group have described its upregulation in EAT by sympathetic system