Sonya Craig

Endothelial Function and Arterial Stiffness in Minimally Symptomatic Obstructive Sleep Apnea

RATIONALE Moderate-severe obstructive sleep apnea (OSA) is associated with endothelial dysfunction, increased arterial stiffness, and hypertension. It is not known whether minimally symptomatic OSA is also associated with impaired vascular function. OBJECTIVES To determine whether minimally symptomatic OSA is associated with impaired vascular function. METHODS In 64 patients (7 females) with minimally symptomatic OSA (oxygen desaturation index, 23.1 [SD, 15.6]; Epworth Sleepiness Scale score, 8 [SD, 3.8]), and 15 matched control subjects without OSA, endothelial function was assessed by ultrasonographic measurement of flow-mediated dilatation, and by applanation tonometry-derived pulse wave analysis (forearm ischemia and salbutamol-induced changes in augmentation index, AI(x)). Arterial stiffness was assessed by AI(x) and ambulatory blood pressure (ABP) was measured over 1 week. MEASUREMENTS AND MAIN RESULTS In patients with OSA, flow-mediated dilatation was significantly lower than in control subjects (5.0% [SD, 2.7%] and 7.5% [SD, 3.3%], respectively; P = 0.003). AI(x) was significantly higher in the OSA group compared with the control group (26.0% [interquartile range (IQR), 19.0-29.5%] and 21.0% [IQR, 8.0-27.0%], respectively; P = 0.04). Change in AI(x) after both forearm ischemia and salbutamol was significantly smaller in patients with OSA (-2.0% [IQR, -5.0 to +4.0%] and -3.0% [IQR, -7.0 to 0.0%], respectively), than in control subjects (-6.0% [IQR, -8.0 to -5.0%] and -7.0% [IQR, -10.0 to -3.0%]; P = 0.005 and P = 0.04, respectively). ABP was similar (97.6 mm Hg [SD, 7.9 mm Hg] and 94.8 mm Hg [SD, 7.4 mm Hg], OSA and control groups, respectively; P = 0.21). CONCLUSIONS In patients with minimally symptomatic OSA, diverse properties of endothelial function are impaired and arterial stiffness is increased. Although this was not associated with a significantly increased ABP, the findings suggest that patients with minimally symptomatic OSA are at increased cardiovascular risk.

Effects of continuous positive airway pressure on systemic inflammation in patients with moderate to severe obstructive sleep apnoea: a randomised controlled trial

Background: Obstructive sleep apnoea syndrome (OSAS) has been associated with cardiovascular disease in epidemiological and observational studies. Continuous positive airway pressure (CPAP) is the treatment of choice for OSAS, but the impact of this intervention on systemic inflammation involved in the atherosclerotic process remains unclear. Methods: 100 men with moderate–severe OSAS were randomised to therapeutic (n = 51) or subtherapeutic (n = 49) CPAP treatment for 4 weeks to investigate the effects of active treatment on inflammatory markers such as highly sensitive C reactive protein (hsCRP), interleukin (IL)6, interferon γ (IFNγ) and anti-inflammatory adiponectin. Results: 4 weeks of therapeutic CPAP did not significantly change blood levels of hsCRP compared with the subtherapeutic control group (difference between median changes −0.24 mg/l (95% CI −0.88 to +0.24); p = 0.30). Plasma levels of IL6 and IFNγ did not change significantly following therapeutic compared with subtherapeutic CPAP (difference between median changes +0.52 and −0.07 pg/ml (95% CI −0.72 to +1.94 and −0.81 to +0.44); p = 0.45 and p = 0.82, respectively). Furthermore, 4 weeks of therapeutic CPAP did not significantly change levels of adiponectin in plasma compared with the subtherapeutic control group (difference between median changes +0.05 pg/ml (95% CI −0.36 to +0.47); p = 0.84). If patients with hsCRP values above 8 mg/l at baseline were excluded, differences between the changes in hsCRP, IL6, IFNγ and adiponectin after 4 weeks of CPAP were smaller, and again not statistically different between groups. Conclusions: 4 weeks of CPAP treatment has no beneficial effect on blood markers of inflammation and adiponectin in patients with moderate–severe obstructive sleep apnoea.

Continuous positive airway pressure improves sleepiness but not calculated vascular risk in patients with minimally symptomatic obstructive sleep apnoea: the MOSAIC randomised controlled trial

Background Continuous positive airway pressure (CPAP) for symptomatic obstructive sleep apnoea (OSA) improves sleepiness and reduces vascular risk, but such treatment for the more prevalent, minimally symptomatic disease is contentious. Methods This multicentre, randomised controlled, parallel, hospital-based trial across the UK and Canada, recruited 391 patients with confirmed OSA (oxygen desaturation index >7.5/h) but insufficient symptoms to warrant CPAP therapy. Patients were randomised to 6 months of auto-adjusting CPAP therapy, or standard care. Coprimary endpoints were change in Epworth Sleepiness Score (ESS) and predicted 5-year mortality using a cardiovascular risk score (components: age, sex, height, systolic blood pressure, smoking, diabetes, cholesterol, creatinine, left ventricular hypertrophy, previous myocardial infarction or stroke). Secondary endpoints included some of the individual components of the vascular risk score, objectively measured sleepiness and self-assessed health status. Results Of 391 patients randomised, 14 withdrew, 347 attended for their follow-up visit at 6 months within the predefined time window, of which 341 had complete ESS data (baseline mean 8.0, SD 4.3) and 310 had complete risk score data. 22% of patients in the CPAP group reported stopping treatment and overall median CPAP use was 2 : 39 h per night. CPAP significantly improved subjective daytime sleepiness (adjusted treatment effect on ESS −2.0 (95% CI −2.6 to −1.4), p<0.0001), objectively measured sleepiness and self-assessed health status. CPAP did not improve the 5-year calculated vascular risk or any of its components. Conclusions In patients with minimally symptomatic OSA, CPAP can reduce subjective and objective daytime sleepiness, and improve self-assessed health status, but does not appear to improve calculated vascular risk.

CPAP Improves Endothelial Function in Patients With Minimally Symptomatic OSA : Results From a Subset Study of the MOSAIC Trial

BACKGROUND Minimally symptomatic OSA is a highly prevalent disorder, and the effects of CPAP on vascular function in these patients are unknown. This trial aimed to investigate whether CPAP improves vascular function in minimally symptomatic OSA. METHODS In two centers taking part in the MOSAIC (Multicentre Obstructive Sleep Apnoea Interventional Cardiovascular) trial, 253 patients with minimally symptomatic OSA were randomized to 6 months of CPAP or standard care. Two hundred eight patients attended their follow-up visit within the predefined time window and had complete measurements of arterial stiffness (augmentation index [AIx]), and 64 patients had endothelial function measurements by brachial artery flow-mediated dilatation (FMD). Multivariable analyses adjusting for baseline measurements and minimization factors were performed to assess the effect of CPAP treatment on FMD (% dilatation) and AIx (% augmentation) compared with standard care. RESULTS The mean ± SD baseline oxygen desaturation index and Epworth Sleepiness Score (ESS) of the 208 patients (age 58 ± 7.3 years, 31 women) were 13.7 ± 12.8 events/h and 8.3 ± 4.2, respectively. There was no CPAP treatment effect on arterial stiffness (AIx, -1.4%; 95% CI, -3.6 to +0.9%; P = .23), but CPAP improved endothelial function (FMD, +2.1%; 95% CI, +1.0 to +3.2%; P < .0001). CPAP reduced daytime sleepiness (ESS, -2.2; 95% CI, -3.0 to -1.5; P < .0001) compared with standard care. There was a larger improvement in FMD in patients using CPAP for > 4 h/night than those who used it less (P = .013). CONCLUSIONS CPAP improves endothelial function, but not arterial stiffness, in minimally symptomatic OSA. Thus, minimally symptomatic OSA may be a cardiovascular risk factor. TRIAL REGISTRY ISRCTN Register; No.: ISRCTN 34164388; URL: http://isrctn.org.

Original ResearchSleep DisordersCPAP Improves Endothelial Function in Patients With Minimally Symptomatic OSA: Results From a Subset Study of the MOSAIC Trial

BACKGROUND Minimally symptomatic OSA is a highly prevalent disorder, and the effects of CPAP on vascular function in these patients are unknown. This trial aimed to investigate whether CPAP improves vascular function in minimally symptomatic OSA. METHODS In two centers taking part in the MOSAIC (Multicentre Obstructive Sleep Apnoea Interventional Cardiovascular) trial, 253 patients with minimally symptomatic OSA were randomized to 6 months of CPAP or standard care. Two hundred eight patients attended their follow-up visit within the predefined time window and had complete measurements of arterial stiffness (augmentation index [AIx]), and 64 patients had endothelial function measurements by brachial artery flow-mediated dilatation (FMD). Multivariable analyses adjusting for baseline measurements and minimization factors were performed to assess the effect of CPAP treatment on FMD (% dilatation) and AIx (% augmentation) compared with standard care. RESULTS The mean ± SD baseline oxygen desaturation index and Epworth Sleepiness Score (ESS) of the 208 patients (age 58 ± 7.3 years, 31 women) were 13.7 ± 12.8 events/h and 8.3 ± 4.2, respectively. There was no CPAP treatment effect on arterial stiffness (AIx, -1.4%; 95% CI, -3.6 to +0.9%; P = .23), but CPAP improved endothelial function (FMD, +2.1%; 95% CI, +1.0 to +3.2%; P < .0001). CPAP reduced daytime sleepiness (ESS, -2.2; 95% CI, -3.0 to -1.5; P < .0001) compared with standard care. There was a larger improvement in FMD in patients using CPAP for > 4 h/night than those who used it less (P = .013). CONCLUSIONS CPAP improves endothelial function, but not arterial stiffness, in minimally symptomatic OSA. Thus, minimally symptomatic OSA may be a cardiovascular risk factor. TRIAL REGISTRY ISRCTN Register; No.: ISRCTN 34164388; URL: http://isrctn.org.

Continuous positive airway pressure treatment for obstructive sleep apnoea reduces resting heart rate but does not affect dysrhythmias: a randomised controlled trial

Obstructive sleep apnoea (OSA) is associated with cardiovascular morbidity and may precipitate cardiac dysrhythmias. Uncontrolled reports suggest that continuous positive airway pressure (CPAP) may reduce dysrhythmia frequency and resting heart rate. We undertook a randomised controlled trial of therapeutic CPAP and compared with a subtherapeutic control which included an exploration of changes in dysrhythmia frequency and heart rate. Values are expressed as mean (SD). Eighty‐three men [49.5 (9.6) years] with moderate–severe OSA [Oxygen Desaturation Index, 41.2 (24.3) dips per hour] underwent 3‐channel 24‐h electrocardiograms during normal daily activities, before and after 1 month of therapeutic (n = 43) or subtherapeutic (n = 40) CPAP. Recordings were manually analysed for mean heart rate, pauses, bradycardias, supraventricular and ventricular dysrhythmias. The two groups were well matched for age, body mass index, OSA severity, cardiovascular risk factors and history. Supraventricular ectopics and ventricular ectopics were frequently found in 95.2% and 85.5% of patients, respectively. Less common were sinus pauses (42.2%), episodes of bradycardia (12%) and ventricular tachycardias (4.8%). Compared with subtherapeutic control, CPAP reduced mean 24‐h heart rate from 83.0 (11.5) to 79.7 (9.8) (P < 0.002) in the CPAP group compared with a non‐significant rise (P = 0.18) from 79.0 (10.4) to 79.9 (10.4) in the subtherapeutic group; this was also the case for the day period analysed separately. There was no significant change in the frequencies of dysrhythmias after CPAP. Four weeks of CPAP therapy reduces mean 24‐h heart rate possibly due to reduced sympathetic activation but did not result in a significant decrease in dysrhythmia frequency.

Markers of inflammation: data from the MOSAIC randomised trial of CPAP for minimally symptomatic OSA

ABSTRACT The Multi-centre Obstructive Sleep Apnoea Interventional Cardiovascular (MOSAIC) trial compared 6 months of CPAP therapy, versus no CPAP, in 391 patients with minimally symptomatic obstructive sleep apnoea (OSA). We now report some exploratory outcomes, markers of systemic inflammation (interleukin 6 (IL-6), IL-10, C reactive protein, tumour necrosis factor). We found no consistent changes (all p values >0.13). Trial registration number: ISRCTN 34164388.

Atherosclerosis and arterial stiffness in obstructive sleep apnea--a cardiovascular magnetic resonance study.

OBJECTIVE Obstructive sleep apnoea (OSA) has been linked to cardiovascular risk factors, such as hypertension, and clinical cardiovascular endpoints. Our aim was to assess whether OSA is independently associated with atherosclerosis and vascular dysfunction as assessed by cardiovascular magnetic resonance (CMR). METHODS 58 patients with OSA and 39 matched control subjects without OSA underwent CMR of the aorta and carotid arteries. Carotid and aortic wall thickness and aortic distensibility were measured. Multi-weighted, high resolution CMR imaging was used for carotid atheroma characterization according to the American Heart Association (AHA) atheroma classification, modified for CMR. RESULTS Carotid [1.47±0.03 mm vs. 1.26±0.05 mm, (P<0.01)] and aortic wall thickness [2.95±0.09 mm vs. 2.05±0.07 mm, (P<0.001)] were increased in patients with OSA compared to controls. Aortic distensibility was decreased in patients with OSA [3.62±0.3 vs. 4.75±0.2 mmHg(-1)×10(-3), (P<0.05)]. Prevalence of carotid plaque, average carotid atheroma class, and prevalence of high risk features of carotid atheroma were increased in patients with OSA (P<0.005 for all). On multivariate analysis, Oxygen desaturation index (ODI) emerged as an independent predictor of carotid and aortic wall thickness, but not of aortic stiffness. CONCLUSIONS OSA is associated with increased carotid and aortic atheroma burden and with advanced, high risk carotid atherosclerotic plaques, but not with aortic stiffening.

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.

Urinary proteomics in obstructive sleep apnoea and obesity

Obstructive sleep apnoea (OSA) is a common complication of obesity and can have a substantial negative impact on a patients 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.