Rebecca H. Mason

Obstructive sleep apnea in patients with abdominal aortic aneurysms: highly prevalent and associated with aneurysm expansion.

RATIONALE Abdominal aortic aneurysms (AAA) are associated with life-threatening complications. The likelihood that an AAA will rupture is influenced by the aneurysm diameter and its expansion rate; reasons for rapid expansion are largely unknown. OBJECTIVES To determine the prevalence of obstructive sleep apnea (OSA) in patients with AAA, and investigate a possible association between OSA and rate of AAA expansion. METHODS A total of 127 patients (11 females), included in an AAA surveillance program, agreed to participate and underwent a sleep study. Annual AAA expansion was determined retrospectively from available ultrasound measurements. OSA was characterized using both oxygen desaturation index (ODI) and apnea-hypopnea index (AHI). Univariate and multivariate analysis was performed to assess the effect of OSA severity on AAA expansion. MEASUREMENTS AND MAIN RESULTS Mean age was 67.9 (SD, 6) years. Median interval between the first and last AAA measurements was 18 (range, 2-113) months. An ODI or AHI of greater than 10 was found in 40.5% and 41.5% of the patients, respectively. Patients with an ODI greater than 30 (n = 12) had a significantly faster median yearly AAA expansion rate (2.9; quartiles 2/5.7 mm/y) than patients with an ODI 0-5 (n = 47; 1.2; quartiles 0/3.1 mm/y) or 6-15 (n = 43; 1.3; quartiles 0/2.7 mm/y) (P < 0.05). In multivariate regression analysis, controlling for cardiovascular risk factors and medications, ODI greater than 30 remained an independent risk factor for AAA expansion. CONCLUSIONS In patients with AAA, OSA is highly prevalent. Severe OSA may be a causal factor for faster AAA expansion, but this needs to be proved in a randomized controlled intervention trial.

High prevalence of sleep disordered breathing in patients with diabetic macular edema.

Background: Diabetic retinopathy is more common and severe in patients with sleep disordered breathing (SDB). This study aimed to establish whether this is also true for patients with diabetic clinically significant macular edema (CSME). It is hypothesized that SDB, through intermittent hypoxia and blood pressure oscillations, might provoke worsening of CSME. Methods: Patients with CSME had a home sleep study (ApneaLink; ResMed) to identify SDB. These results were compared with relevant control populations. Macular thickness was measured using optical coherence tomography, and retinal photographs were graded to assess the severity of retinopathy. Results: Eighty of 195 patients (40 men) consented, with average age of 64.7 (11.7) years, neck circumference of 40.4 (5.4) cm, body mass index of 30.2 (6.2) kg/m2, glycosylated hemoglobin (HbA1c) 7.8% (1.4%) [62 (8.0) mmol/mol], and Epworth sleepiness scale of 7.4 (4.8). Overall, 54% had an oxygen desaturation index ≥10, and 31% had an apnea-hypopnea index ≥15. This SDB prevalence is probably higher than would be expected from the available matched control data. Those with SDB were not sleepier, but they were older and more obese. No significant relationship was identified between the degree of macular thickness and the severity of SDB. Conclusion: Individuals with CSME have a high prevalence of SDB. Sleep disordered breathing may contribute to the pathophysiology of CSME, but the mechanism remains unclear. Given the high prevalence, retinal specialists should perhaps consider a diagnosis of SDB in patients with CSME.

Visual improvement following continuous positive airway pressure therapy in diabetic subjects with clinically significant macular oedema and obstructive sleep apnoea: proof of principle study.

Background: Diabetic retinopathy and diabetic macular oedema are more prevalent in patients with coexistent obstructive sleep apnoea (OSA). Objectives: We assessed if treatment of OSA with continuous positive airway pressure (CPAP) might improve visual acuity (VA). Methods: A total of 35 patients with clinically significant macular oedema (CSMO) and OSA [oxygen desaturation index (ODI) ≥10 or apnoea-hypopnoea index (AHI) ≥15] were identified and agreed to be studied. VA (expressed as the logarithm of the minimum angle of resolution, logMAR), macular thickness, fundal photographs, glycosylated haemoglobin (HbA1c) and rhodopsin mRNA were measured twice at baseline and at 3 and 6 months post-CPAP. Fluorescein angiography and the Epworth Sleepiness Scale (ESS) were obtained once at baseline and at 6 months. Results: Three patients withdrew before the first trial visit. Thus, a total of 32 patients (17 males) entered the study, and 4 subsequently withdrew; thus 28 completed 6 months of follow-up. Baseline characteristics of the subjects were as follows [mean (SD or inter-quartile range)]: age 66.2 (7.1) years, body mass index 31.7 (6.3), HbA1c 7.4% (1.44) [57.1 (15.7) mmol/mol], AHI 16.5 (11–25), ODI 16.0 (12–25), ESS 6.5 (4.0–12.0) and duration of diabetes 9.5 years (5.0–16.5). Participants were divided into 13 high and 15 low CPAP compliers (≥ and <2.5 h/night over the 6 months, respectively). At 6 months, the adjusted treatment effect on VA of high compliance versus low compliance was 0.11 (95% confidence interval 0.21 to –0.002; p = 0.047), equivalent to a one-line improvement on the logMAR chart. There was no significant improvement in macular oedema or fundal photographs. Conclusions: This hypothesis-generating, uncontrolled study suggests that ≥2.5 h/night CPAP usage over 6 months in individuals with CSMO and OSA may be associated with improvement in VA. This provides justification for a randomised controlled trial of CPAP therapy in such patients.

Augmentation index and central aortic blood pressure in patients with abdominal aortic aneurysms.

Objective Abdominal aortic aneurysm (AAA) is a life-threatening disease as rupture of the aneurysm is associated with high mortality. The likelihood that an AAA will rupture is particularly influenced by the diameter of the aneurysm and the rate of expansion; the reasons for fast expansion are largely unknown. Applanation tonometry (APT) can predict outcome in certain cardiovascular diseases by measuring arterial stiffness (augmentation index, AIx) and central aortic blood pressure (CABP). We tested the hypothesis that AIx and CABP would be higher in patients with fast-progressing AAA. Methods We performed APT and peripheral blood pressure measurements in 114 patients with AAA (11 women) with a mean ± SD age of 67.4±6.1 years. Annual AAA progression rate was determined by ultrasound. Patients were grouped into fast progressors (progression ≥2 mm/year) and slow progressors (progression <2 mm/year). Results Mean follow-up time after inclusion into the AAA surveillance programme was 22.1 ± 16.3 months. AIx was similar in fast progressors (27.3 ± 13.0%) and slow progressors (26.5 ± 12.6%) (P = 0.73). Fast progressors had a significantly higher CABP during systole (116.0 ± 16.0 mmHg) and diastole (95.7 ± 12.6 mmHg) than slow progressors (109.5 ± 16.3 and 90.0 ± 13.2 mmHg) (P = 0.04 and P = 0.02, respectively). Mean peripheral blood pressure was significantly higher in fast progressors (102.7 ± 12.8 mmHg) than in slow progressors (97.7 ± 12.9 mmHg) (P = 0.04). Conclusion Augmentation index did not differ in patients with fast and slow-progressing AAA. However, fast progressors had higher central aortic blood pressures suggesting that elevated aortic blood pressure is a risk factor for faster AAA progression, but this needs to be proven in controlled interventional studies.

Snoring and severity of symptomatic and asymptomatic carotid stenosis: a population-based study.

BACKGROUND Obstructive sleep apnea has increasingly been linked to cardiovascular damage. More recently, the snoring component itself has been independently linked to the presence of carotid atheroma, via local arterial trauma. We aimed to identify whether a snoring history is a risk factor for carotid stenosis in individuals presenting with a TIA or ischemic stroke. METHODS Participants in the Oxford Vascular Study (OXVASC) were asked about their snoring history as part of an entry questionnaire. In 561 individuals with a recent TIA or stroke, who had both a complete snoring questionnaire and carotid imaging, the relationship between presence and severity of snoring and the degree of carotid artery stenosis in both the symptomatic (culprit) and asymptomatic (non-culprit) sides. RESULTS Of 561 participants (287 male, mean/SD age = 73.3/11.0 years), 90 (16.0%) had ≥ 50% carotid stenosis, and 154 (27.5%) snored frequently (≥ 1-2 times/week). No significant associations were identified between frequency of self-reported snoring, and the degree of culprit and non-culprit carotid vessel stenosis, or plaque morphology. CONCLUSIONS No significant association could be identified between a history of frequent snoring and the presence of carotid atheroma, degree of stenosis, or plaque type.

Leukoaraiosis on MRI in patients with minimally symptomatic obstructive sleep apnoea.

Background: Obstructive sleep apnoea (OSA) is associated with hypertension, nocturnal blood pressure (BP) surges, and increased risk of stroke. It may therefore also be associated with a higher risk of developing leukoaraiosis. Only few data about the prevalence of leukoaraiosis in patients with OSA, and any association between degrees of severity of either condition, exist. Methods: We studied patients who were part of a clinical trial (MOSAIC) in minimally symptomatic OSA. All patients had brain MRI (T2, FLAIR) at baseline. A single observer assessed the images for the presence and severity of leukoaraiosis (ARWMC-score). We related the extent of leukoaraiosis to the severity of OSA (measured by oxygen desaturation index [ODI]) and the presence of other vascular risk factors. Results: 183 patients (156 men, 85.2%; mean age ± SD = 57.7 ± 7.4 years; median oxygen desaturation index = 9.6, interquartile range = 4.6-16.0) took part in the study. Although 135 (74%) patients had some leukoaraiosis, this was generally mild. We confirmed the well-known risk factor associations between leukoaraiosis, increasing age (p < 0.0001) and hypertension (p = 0.003), but we did not find any association between OSA and leukoaraiosis (p = 0.33), despite both conditions being associated with increasing current BP and a history of hypertension. Conclusion: Our data confirm the well-known association between leukoaraiosis, age and increasing BP. However, we found no association between OSA and leukoaraiosis despite some shared risk factor associations. Our findings suggest that OSA is not a strong independent risk factor for leukoaraiosis. Confounding by hypertension may explain any apparent association in previously reported studies of patients with severer OSA.

P199 Diabetic macular oedema (DME) and obstructive sleep apnoea (OSA)—visual improvement post CPAP therapy. Proof of principle study

Introduction and Objectives DME is an important cause of visual loss and is more advanced in patients with coexistent OSA.1OSA is very common in individuals with DME (54%), compared to unselected patients with type II diabetes (23%)2 and age matched controls (8%).3 This study was designed to see if CPAP could improve vision in patients with DME and coexistent OSA, perhaps via a reduction in intermittent hypoxia and/or blood pressure oscillations. Methods 35 patients with DME (identified by ocular coherence tomography, OCT) and OSA (oxygen desaturation index >10, or apnoea hypopnoea index >15) were identified. Visual acuity (VA, logMAR, similar to the Snellen chart) and OCT measurements were made twice at baseline (pre-CPAP), 3 and 6 months (post-CPAP). Results 32 patients (17 males) participated; 4 withdrew. 28 have 3-month follow-up data and, 24 have 6-month data. Average (SD) age 66.6 years, (8.3), BMI 31.8 Kg/m2 (6.7), HbA1c 7.5% (1.4%), ESS 7.9 (4.6), ODI 20.9 (14.8) and AHI 19.0(14.5). CPAP compliance was averaged over the 6 months and a median split into ‘high’ and ‘low’ compliers performed (> and <2.5 h/n). At 3 months VA improved significantly in both high (p=0.009) and low compliers (p=0.001). This was only sustained at 6 months in high compliers, p=0.004. (Low compliers p=0.52). There was no significant reduction in macular oedema at either 3 or n. Conclusions This hypothesis-generating uncontrolled study indicates that continued use of CPAP in individuals with DME and OSA was associated with sustained improvement in visual acuity. This result provides justification to perform an RCT and suggests that logMAR should be the primary endpoint whereas OCT measurements appear uninformative.Abstract P199 Figure 1 LogMAR after CPAP use, high versus low compliers (mean ± SEM).

P200 Snoring and carotid atheroma: no association

Background Obstructive Sleep apnoea (OSA) has increasingly been linked to cardiovascular endpoints including hypertension, stroke, myocardial infarction, and carotid atherosclerosis. Snoring is strongly associated with OSA. More recently, the snoring component of OSA, by producing local arterial trauma, has been independently linked to the presence of carotid but not femoral atheroma,1 and to acute carotid trauma in an animal model.2 The aim of this study was to identify whether this relationship could be established retrospectively in a high vascular risk cohort of individuals with a recent cerebrovascular event (TIA or stroke). Method Participants with a recent TIA or stroke in the Oxford Vascular Study (OXVASC) completed an entry questionnaire which included frequency of snoring (never, rarely (1–2/year), occasionally (4–8/year), sometimes (1–2/month), often (1–2/week), usually (3–5/week) and always (every night). A subset of 316 individuals (aged 62–84 years), with both a completed snoring questionnaire and carotid Doppler data, were included. This information was used to retrospectively assess a potential relationship between presence and severity of snoring, and degree of carotid artery stenosis and plaque type (echogenic/echolucent/mixed, calcified/non-calcified and smooth/irregular). Results 160 out of 316 participants were male, mean (SD) age 73.2 (11.22). No significant association could be identified between intensity of self-reported snoring and degree of carotid stenosis or plaque morphology. Conclusions No significant association could be identified between snoring and carotid atheroma. There are no obvious explanations for the discrepancy between this study and previous work, except that the original study measured snoring objectively during a one night in hospital study, whereas in our study snoring was subjectively assessed and perhaps better represents the usual situation at home. Furthermore, the femoral artery may not be an appropriate ‘control’ artery with which to compare the carotid for atheroma.Abstract P200 Table 1 Degree of carotid artery stenosis in ‘frequent’ and ‘non-frequent’ snorers ‘Frequent snorers’ ‘Non-frequent’ snorers p-Value Carotid stenosis ≥30% 43% 48% 0.44 Carotid stenosis ≥50% 16% 21% 0.42 ‘Frequent snoring’ = snoring stated as ≥ 1–2/times per week. p-Values all determined by Fishers Exact test.