Effect of CPAP on arterial stiffness in severely obese patients with obstructive sleep apnoea.

BACKGROUND: Obstructive sleep apnoea (OSA) may independently increase cardiovascular risk in obesity. Although there is evidence that arterial stiffness is altered in OSA, knowledge of these effects with continuous positive airway pressure (CPAP) in severe obesity (body mass index (BMI) ≥ 35 kg/m(2)) is limited. This study aimed to explore how arterial stiffness, as measured by the augmentation index (Aix), changed in severely obese patients with OSA who were treated with CPAP and in patients without OSA. METHODS: Forty-two patients with severe obesity-22 with OSA, 20 without OSA-were recruited at baseline and followed-up after a median of 13.5 months. Pulse wave analysis (PWA) was performed using applanation tonometry at the radial artery to measure augmentation index (Aix), augmentation pressure (AP) and subendocardial viability ratio (SEVR). Cardiovascular parameters and body composition were also measured. RESULTS: There were significant improvements in Aix, AP (both P < 0.001) and SEVR (P = 0.021) in OSA patients on CPAP compared with subjects without OSA. Epworth scores (P < 0.001), systolic (P < 0.001) and mean arterial pressures (P = 0.002) improved with CPAP. Regression showed that CPAP was significantly associated with change in arterial stiffness from baseline. However, patients with OSA on CPAP continued to have increased arterial stiffness (Aix) (P < 0.001), AP (P = 0.028) and reduced SEVR (P = 0.002) relative to non-OSA patients. CONCLUSION: Although sleepiness and blood pressure improve with CPAP in severe obesity, CPAP alone is not sufficient to modify PWA measures to levels comparable with non-OSA patients. This supports a need for a multifaceted approach when managing cardiovascular risk in patients with severe obesity and obstructive sleep apnoea receiving CPAP therapy.

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.

Urinary proteomics in obstructive sleep apnoea and obesity.

BACKGROUND: Obstructive sleep apnoea (OSA) is a common complication of obesity and can have a substantial negative impact on a patient's quality of life and risk of cardiovascular disease. The aim of this case-control study was to undertake discovery profiling of urinary peptides using capillary electrophoresis-mass spectrometry (CE-MS) in obese subjects with and without OSA, without a history of coronary artery disease. MATERIALS AND METHODS: Urinary samples were analysed by CE-MS. Body composition and blood pressure measurements were recorded. Overnight polysomnography was conducted to confirm or refute OSA. OSA patients were naïve to continuous positive airway pressure treatment. RESULTS: Sixty-one subjects with OSA (age 47 ± 9 years, BMI 43 ± 8 kg/m(2)) and 31 controls (age 49 ± 10 years, BMI 40 ± 5 kg/m(2)) were studied; P = ns for age and BMI. Apnoea-hypopnoea Index was higher in patients with OSA (24 ± 18·6) than controls without OSA (non-OSA) (2·6 ± 1·1; P < 0·0001). Metabolic syndrome was present in 35 (57%) of those with OSA compared with 4 (13%) of controls (P < 0·0001). Twenty-four polypeptides were candidates for differential distribution (P < 0·01), although these differences did not reach significance after multiple testing. Sequences were determined for eight peptides demonstrating origins from collagens and fibrinogen alpha. CONCLUSIONS: In this study, we report for the first time, urinary proteomic profile analyses using CE-MS in OSA and non-OSA obese groups. The differences in urinary proteomic profiles prior to adjustment for multiple testing, with increased metabolic syndrome in obese OSA subjects, suggest that there may be a role for CE-MS in characterising urinary profiles in severely obese populations with OSA.

Obstructive sleep apnea is associated with increased arterial stiffness in severe obesity.

Obstructive sleep apnea is associated with obesity and metabolic syndrome, leading to greater cardiovascular risk. Severely obese patients with obstructive sleep apnea may still be at risk of adverse health outcomes, even without previous cardiovascular disease. Pulse wave analysis non-invasively measures peripheral pulse waveforms and derives measures of haemodynamic status, including arterial stiffness, augmentation pressure and subendocardial viability ratio. We hypothesized that the presence of obstructive sleep apnea in severe obesity, even in the absence of an antecedent history of cardiovascular disease, would affect measurements derived from pulse wave analysis. Seventy-two severely obese adult subjects [obstructive sleep apnea 47 (body mass index 42 ± 7 kg m(-2) ), without obstructive sleep apnea (non-OSA) 25 (body mass index 40 ± 5 kg m(-2) )] were characterised using anthropometric, respiratory and cardio-metabolic parameters. Groups were similar in age, body mass index and gender. More subjects with obstructive sleep apnea had metabolic syndrome [obstructive sleep apnea 60%, without obstructive sleep apnea (non-OSA) 12%]. Those with obstructive sleep apnea had greater arterial stiffness, augmentation pressure and decreased subendocardial viability ratio (all P < 0.001), with significantly higher systolic (P = 0.003), diastolic (P = 0.04) and mean arterial pressures (P = 0.004) than patients without obstructive sleep apnea (non-OSA). Arterial stiffness correlated with mean arterial blood pressure (P = 0.003) and obstructive sleep apnea severity (apnea-hypopnea index; P < 0.001). apnea-hypopnea index significantly predicted arterial stiffness in multiple regression analysis, but components of the metabolic syndrome did not. Thus, patients with obstructive sleep apnea with severe obesity have increased arterial stiffness that may potentially influence cardiovascular risk independently of metabolic abnormalities. The presence of obstructive sleep apnea in severe obesity identifies a group at high cardiovascular risk; clinicians should ensure that risk factors are managed appropriately in this group whether or not treatment of obstructive sleep apnea is offered or accepted by patients.

Sleep-disordered breathing, type 2 diabetes and the metabolic syndrome.

Sleep-disordered breathing (SDB) encompasses a spectrum of conditions that can lead to altered sleep homeostasis. In particular, obstructive sleep apnoea (OSA) is the most common form of SDB and is associated with adverse cardiometabolic manifestations including hypertension, metabolic syndrome and type 2 diabetes, ultimately increasing the risk of cardiovascular disease. The pathophysiological basis of these associations may relate to repeated intermittent hypoxia and fragmented sleep episodes that characterize OSA which drive further mechanisms with adverse metabolic and cardiovascular consequences. The associations of OSA with type 2 diabetes and the metabolic syndrome have been described in studies ranging from epidemiological and observational studies to controlled trials investigating the effects of OSA therapy with continuous positive airway pressure (CPAP). In recent years, there have been rising prevalence rates of diabetes and obesity worldwide. Given the established links between SDB (in particular OSA) with both conditions, understanding the potential influence of OSA on the components of the metabolic syndrome and diabetes and the underlying mechanisms by which such interactions may contribute to metabolic dysregulation are important in order to effectively and holistically manage patients with SDB, type 2 diabetes or the metabolic syndrome. In this article, we review the literature describing the associations, the possible underlying pathophysiological mechanisms linking these conditions and the effects of interventions including CPAP treatment and weight loss.

How to approach endocrine assessment in severe obesity?

The increasing numbers of severely obese patients (body mass index BMI >40 kg/m(2) ) represent a significant management challenge. These patients are at risk of obesity-related complications that may be driven by changes in endocrine function. Their care may potentially be complex at times, and therefore, an appropriate assessment strategy will be relevant to timely diagnosis and management. In this article, we discuss an approach to the endocrine assessment of the severely obese patient. We consider the clinical question in three categories that may also represent different complexities in terms of subsequent management: (i) obesity as a consequence of structural lesions at the hypothalamic-pituitary region; (ii) obesity as a consequence of inherited and genetic syndromes; and (iii) functional neuroendocrine hormone abnormalities relating to obesity. The first two categories are associated with hypothalamic dysfunction, of which hypothalamic obesity is a consequence. Additionally, the implications and difficulties associated with imaging severely obese patients are discussed from an endocrinological perspective and we provide practical guidance on which to base practice.

Screening for obstructive sleep apnoea in obesity and diabetes--potential for future approaches.

BACKGROUND: It is recognised that sleep-disordered breathing (SDB), in particular, obstructive sleep apnoea (OSA) is associated with obesity and diabetes. The complications of OSA include dysregulation of metabolic and cardiovascular homeostasis. With the growing population of diabetes and obesity globally, it is becoming apparent that identifying and screening patients who are at risk is becoming increasingly crucial. Many patients may remain unaware of the potential diagnosis and continue to be undiagnosed. The high prevalence of OSA poses a demanding challenge to healthcare providers in order to provide sufficient resources and facilities for patient diagnosis and treatment. DESIGN: In this article, we review the evidence in favour of screening populations deemed to be at increased risk of OSA, with particular reference to patients with obesity and diabetes. We consider the recent advances in potential screening methods that may allow new prognostic and predictive tools to be developed. A detailed search of Medline and Web of Science electronic databases for relevant articles in English was performed. RESULTS: Apart from the use of screening tools such as questionnaires and clinical decision models, there is increasing evidence to suggest that there are differences in biological parameters in patients with OSA. Although further studies are required, there may be potential for such biomarkers to contribute to and augment the screening process. However, the significance of such biological tools remains to be elucidated. CONCLUSIONS: A fundamental role for improved screening in patients with conditions such as obesity and diabetes can enable early interventions that may improve health outcomes relating to the adverse consequences of OSA. The future will see further research being carried out in the development of potential screening methods with emphasis on the selection of patients at risk of sleep disorders, thereby allowing more detailed physiological studies to be carried out where needed.

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.

Low dietary sodium in diabetes nephropathy.

In a meta-analysis that investigated the effects of dietary sodium restriction in diabetes nephropathy, although blood pressure fell, there were significant increases in plasma renin and aldosterone levels. In this article, we hypothesise that in diabetic nephropathy, ACE-I or ARB treatment attenuates any rise in RAS hormones that might result from dietary salt restriction and that the beneficial effects of the salt restriction such as a lower blood pressure outweigh any potentially negative consequences of RAS activation such as a rise in intraglomerular pressure because of the synergistic effects of sodium restriction and RAS antagonist therapy.

Treating diabetes mellitus in Prader-Willi syndrome with Exenatide.

We report the use of Exenatide, a GLP-1 agonist, in the management of diabetes mellitus in a 19 year-old female with Prader-Willi syndrome. The beneficial effects of Exenatide in weight reduction and appetite suppression provide a promising strategy for the treatment of obesity and diabetes mellitus in Prader-Willi syndrome.

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

INTRODUCTION: 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. CASE PRESENTATION: 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. CONCLUSIONS: 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.

Renal infarction in patients presenting with suspected renal colic.

Acute renal infarction is a serious medical emergency. The diagnosis is often delayed or missed as it is not common. Hence, the exact incidence of acute renal infarction is not known. Failure to consider renal infarction in the initial differential diagnosis results in a delay in diagnosis and treatment, which in turn leads to permanent loss of renal function. We present two cases of acute kidney infarction that were initially treated as renal colic. In addition, we present a third case when a kidney was saved with reperfusion therapy.