Se Craig

CPAP and measures of cardiovascular risk in males with OSAS

Obstructive sleep apnoea syndrome (OSAS) has been associated with hypertension, stroke and myocardial ischaemia in epidemiological and observational studies. Continuous positive airway pressure (CPAP) is the treatment of choice for OSAS, but the impact of this intervention on established risk factors for cardiovascular disease remains incompletely understood. A total of 102 males with moderate-to-severe OSAS were randomised to therapeutic (nu200a=u200a51) or subtherapeutic (nu200a=u200a51) CPAP treatment for 4u2005weeks to investigate the effects of active treatment on 24-h urinary catecholamine excretion, baroreflex sensitivity (BRS), arterial stiffness (augmentation index) and 24-h ambulatory blood pressure (ABP). After 4u2005weeks of therapeutic CPAP, significant reductions were seen in urine normetanephrine excretion (from mean±sd 179.7±80.1 to 132.7±46.5u2005µmol·mol−1 creatinine) and augmentation index (from 14.5±11.3 to 9.1±13.8%) compared with the subtherapeutic control group. Furthermore, therapeutic CPAP significantly improved BRS (from 7.1±3.3 to 8.8±4.2u2005ms·mmHg−1) and reduced mean arterial ABP by 2.6±5.4u2005mmHg. In conclusion, treatment of obstructive sleep apnoea with continuous positive airway pressure may lower cardiovascular risk by reducing sympathetic nerve activity, ambulatory blood pressure and arterial stiffness and by increasing sensitivity of the arterial baroreflex.

Circulating cell-derived microparticles in patients with minimally symptomatic obstructive sleep apnoea.

Moderate–severe obstructive sleep apnoea (OSA) has been associated with several pro-atherogenic mechanisms and increased cardiovascular risk, but it is not known if minimally symptomatic OSA has similar effects. Circulating cell-derived microparticles have been shown to have pro-inflammatory, pro-coagulant and endothelial function-impairing effects, as well as to predict subclinical atherosclerosis and cardiovascular risk. In 57 patients with minimally symptomatic OSA, and 15 closely matched control subjects without OSA, AnnexinV-positive, platelet-, leukocyte- and endothelial cell-derived microparticles were measured by flow cytometry. In patients with OSA, median (interquartile range) levels of AnnexinV-positive microparticles were significantly elevated compared with control subjects: 2,586 (1,566–3,964)u2005μL−1 versus 1,206 (474–2,501)u2005μL−1, respectively. Levels of platelet-derived and leukocyte-derived microparticles were also significantly higher in patients with OSA (2,267 (1,102–3,592)u2005μL−1 and 20 (14–31)u2005μL−1, respectively) compared with control subjects (925 (328–2,068)u2005μL−1 and 15 (5–23)u2005μL−1, respectively). Endothelial cell-derived microparticle levels were similar in patients with OSA compared with control subjects (13 (8–25)u2005μL−1 versus 11 (6–17)u2005μL−1). In patients with minimally symptomatic obstructive sleep apnoea, levels of AnnexinV-positive, platelet- and leukocyte-derived microparticles are elevated when compared with closely matched control subjects without obstructive sleep apnoea. These findings suggest that these patients may be at increased cardiovascular risk, despite being minimally symptomatic.

S13 The primary results of the MOSAIC trial: does CPAP for minimally symptomatic OSA reduce daytime sleepiness or calculated vascular risk?

Introduction CPAP treatment for symptomatic OSA improves sleepiness, and reduces vascular risk by reducing blood pressure (BP) and cholesterol. Minimally symptomatic OSA is far more prevalent than symptomatic disease, and treatment of this group is contentious. This trial describes the effect of CPAP on sleepiness and calculated vascular risk in minimally symptomatic OSA. Methods 391 patients from 10 centres, with proven OSA (sleep study ODI>7.5u2005h), but insufficient sleepiness for CPAP (based on established evidence), were randomised (minimisation by ODI, recruiting centre, and cardiovascular risk score (Pocock)), to either 6u2005months CPAP (ResMed Autoset S8 Spirit), or standard care. CPAP training and fitting was according to local clinical practice. Co-primary outcomes were the mean changes in Epworth Sleepiness Score (ESS) and the vascular risk score (comprising age, sex, systolic BP, smoking, diabetes, total cholesterol, height, creatinine, LVH on ECG, previous MI or stroke) from baseline to 6u2005months (intention to treat analysis). Home BP was measured in triplicate three times daily over 7u2005days at baseline and after 6u2005months, and the weekly average was used for further analysis. Results Of 391 randomised, 14 withdrew or were lost to follow-up and have been excluded from the primary analysis. 347 patients attended for their 6u2005month visit within the predefined time window. The study groups were well matched at baseline. Median CPAP use was 3.25u2005h/night. Full data on ESS and the cardiovascular risk score components were available from 341 and 310 patients respectively. Sleepiness outcome CPAP reduced daytime sleepiness (mean (SE) ESS change with CPAP −1.68 (0.24); control +0.32 (0.22), mean difference −2.00, 95% CI −1.37 to −2.64, p<0.0001), a cost effective outcome (UK NICE criteria). Cardiovascular risk outcome CPAP did not reduce cardiovascular risk score (mean (SE) cardiovascular risk score change with CPAP +0.08 (0.17); control −0.37 (0.17), mean difference +0.45, 95% CI −0.03 to +0.93, p=0.064); the small increase with CPAP is not clinically significant. Conclusions 6u2005months of CPAP in minimally symptomatic OSA is associated with a cost effective reduction in daytime sleepiness, but does not reduce calculated cardiovascular risk.Abstract S13 Table 1 Baseline values Standard care mean (SD) CPAP mean (SD) Age (years) 57.6 (7.5) 57.8 (7.2) BMI (kg/m2) 32.5 (5.6) 32.2 (5.6) ESS 8.01 (4.15) 7.95 (4.42) ODI (events/h) 12.7 (11.3) 13.8 (12.9) Cardiovascular risk score 34.9 (7.9) 34.3 (7.5)

Cardiovascular event rates in the MOSAIC trial: 2-year follow-up data

Abstract The Multicentre Obstructive Sleep Apnoea Intervention Cardiovascular (MOSAIC) trial investigated the effect of continuous positive airway pressure (CPAP) on both sleepiness and predicted cardiovascular risk over 6u2005months in minimally symptomatic patients with obstructive sleep apnoea. Although there was clear benefit in terms of Epworth Sleepiness Score, there was no improvement in blood pressure and predicted vascular risk score. In order to calculate the required size of future trials, with real vascular events as the endpoint, the rate of such events in this population is needed. 188 patients from the original trial were followed for 2u2005years. The overall number of new vascular events over the 2u2005years was 25, and all-cause mortality was 4. There was a weak statistically significant reduction in vascular events in the CPAP group (p=0.049). Large-scale randomised trials are needed to determine if CPAP causes a real reduction in vascular events in minimally symptomatic patients. Based on our figures, future trials of CPAP versus no treatment would need to randomise approximately 2540 patients to not miss a real reduction in vascular events and over 6000 for mortality.

S14 CPAP improves endothelial function in minimally symptomatic OSA patients: results from the MOSAIC trial

Background CPAP treatment for symptomatic OSA improves surrogate markers of cardiovascular risk, such as endothelial function and arterial stiffness, and may reduce actual cardiovascular events. Minimally symptomatic OSA is far more prevalent than symptomatic OSA but the effects of CPAP on endothelial function and arterial stiffness in minimally symptomatic patients are not known. Methods In two centres taking part in the MOSAIC trial (Oxford and Taunton), 253 patients with minimally symptomatic OSA (ODI>7.5u2005h) were randomised to either 6u2005months of CPAP or supportive care. 245 patients had measurements of arterial stiffness by pulse wave analysis at baseline (augmentation index, AIx) and in 64 patients endothelial function was assessed by brachial artery flow-mediated dilatation (FMD, expressed as % change from baseline arterial diameter) measurements by ultrasonography. Multivariable analyses adjusting for baseline FMD or AIx, ODI and Pocock vascular risk score (age, sex, systolic BP, smoking, diabetes, cholesterol, height, creatinine, LVH, previous MI or stroke) were performed to assess the effect of CPAP treatment on FMD and AIx. Results Of the 245 patients 8 withdrew or were lost to follow-up and in 8 patients pulse wave analysis was not possible at 6u2005months. All 64 patients who had FMD measurements at baseline attended follow-up measurements. Baseline characteristics of 229 patients with complete data on pulse wave analysis are shown in the table (values are mean (SD) were applicable). CPAP improved endothelial function (FMD at follow-up +1.97% with CPAP compared to control group, 95% CI +0.84 to +3.09%, p=0.001), but there was no evidence of an effect on arterial stiffness (AIx at follow-up −0.56% with CPAP compared to control group, 95% CI −2.87 to +1.75, p=0.64). CPAP improved daytime sleepiness as assessed by the Epworth sleepiness score (mean (SE) change −1.91 (0.30) with CPAP; control group +0.08 (0.26), mean difference −1.99, 95% CI −2.77 to −1.21, p<0.0001, assessed using an unpaired t-test). Conclusions 6u2005months of CPAP is associated with improved endothelial function, but does not reduce arterial stiffness in minimally symptomatic OSA. Thus patients with minimally symptomatic OSA may benefit from CPAP therapy in terms of cardiovascular risk reduction.Abstract S14 Table 1 Variable CPAP group Control group Age (years) 58.24 (7.21) 57.90 (7.55) Male/females 97/19 97/13 BMI (kg/m2) 32.69 (5.57) 32.58 (5.37) ESS 8.39 (4.12) 8.55 (4.31) ODI (events/h) 13.98 (14.14) 13.40 (11.38) FMD (%) 3.41 (3.41) 3.42 (2.36) AIx (%) 27.56 (9.32) 29.09 (10.54)

S29 Predictors of continuous positive airways pressure usage at six months in minimally symptomatic patients. Further data from the MOSAIC trial

Introduction Severity of OSA and early patterns of CPAP usage have previously been shown to determine subsequent long term CPAP use in patients with symptomatic moderate-to-severe disease.1 We wished to see if different factors influenced compliance in minimally symptomatic patients. Methods Patients were randomised to 6-months of CPAP or standard care if they had an ODI of >7.5 h due to OSA on a baseline sleep study, but had insufficient daytime OSA symptoms to mandate CPAP.2 Baseline characteristics (Table 1), medical history, ESS, SAQLI and SF-36 were recorded. Repeat overnight pulse oximetry was performed after entry for uniformity of trial ODI across recruiting centres.Abstract S29 Table 1 Baseline characteristics from all 195 patients randomised to CPAP with 6 month follow-up data Variable Mean (SD), Median (IQR) or Number (%) 100% Range Age (mean; SD) 57.9 (7.2) 45–75 Gender (number male;%) 153 (78.5%) - Ethnicity (number white;%) 188 (96.4%) - BMI (mean kg/m2; SD) 32.2 (5.6) 21.6–51.6 Smoking status (number;%) u2003Current 17 (8.7%) - u2003Ex-smoker 102 (52.3%) - u2003Never smoker 76 (39%) - Reported snoring (number yes;%) 190 (97.4%) - Reported apnoeas (number yes;%) 142 (72.8%) - Reported choking (number yes;%) 66 (33.8%) - Reported nocturia (number yes;%) 114 (58.5%) - Oxygen desaturation index (ODI, median; IQR) 10.2 (4.7, 17.5) 0.5–58.0 Epworth Sleepiness Score (ESS, mean; SD) 7.9 (4.4) –18 Short sleep apnoea quality of life index (SAQLI, mean; SD) 4.9 (1.1) 2.3–6.9 SF-36 Physical Summary (mean; SD) 42.0 (12.3) 9.4–61.3 SF- 36 Mental Summary (mean; SD) 48.1 (10.3) 19.9–63.7 CPAP usage data were downloaded at the 2–4 week assessment, and at the 6 month assessment. Those who withdrew were assumed to have 0:00 h/n usage. Correlations were calculated between CPAP usage at the 6 month assessment and both the baseline characteristics and to the 2–4 week CPAP usage data. Results Median CPAP usage at 2–4 week follow-up was low at 2:49 h/n (n = 174, IQR 0:44, 5:13). Median usage at 6 month follow-up was 2:17 h/n (n = 195, IQR 0:08, 4:54). At 6 months males had significantly greater mean usage at 2:56 h/n compared to 1:47 h/n in females (95% confidence intervals of the difference, -1:49 to -0:09 h/n, p = 0.02). There were no other significant predictors of 6 month usage (age, BMI, ODI, ESS, sleep symptoms, smoking status, ethnicity, SAQLI, SF-36). Average usage of CPAP at 2–4 week assessment was moderately correlated with the average usage at the 6 month assessment (r = 0.76, p < 0.001). Conclusions Male gender predicted greater CPAP usage at 6 months, but no other baseline characteristics were predictive of CPAP usage in these minimally symptomatic patients with generally mild OSA. 2–4 week CPAP usage was predictive of 6 month usage, but by no means could all patients’ usage be predicted at such an early stage. Thus in clinical practice, trials of CPAP are necessary in patients with minimally symptomatic OSA but it may be necessary for patients to try CPAP for longer than one month to determine those benefitting from treatment in the long term. References 1 Thorax 2010;65:829–32 2 Thorax 2012;67:1090-66