Sex differences in the association of sleep spindle density and cognitive performance among community-dwelling middle-aged and older adults with obstructive sleep apnea.

Recent studies have found associations between obstructive sleep apnea and cognitive decline. The underlying mechanisms are still unclear. Here, we investigate the associations between changes in micro-architecture, specifically sleep spindles, and cognitive function in community-dwelling middle-aged and older adults, some with obstructive sleep apnea, with a focus on sex differences. A total of 125 voluntary participants (mean age 66.0 ± 6.4 years, 64 females) from a larger cohort (participants of the Brain in Motion Studies I and II) underwent 1 night of in-home polysomnography and a neuropsychological battery (sleep and cognitive testing were conducted within 2 weeks of each other). A semi-automatic computerized algorithm was used to score polysomnography data and detect spindle characteristics in non-rapid eye movement Stages 2 and 3 in both frontal and central electrodes. Based on their apnea-hypopnea index, participants were divided into those with no obstructive sleep apnea (apnea-hypopnea index < 5 per hr, n = 21), mild obstructive sleep apnea (5 ≥ apnea-hypopnea index < 15, n = 47), moderate obstructive sleep apnea (15 ≥ apnea-hypopnea index < 30, n = 34) and severe obstructive sleep apnea (apnea-hypopnea index ≥ 30, n = 23). There were no significant differences in spindle characteristics between the four obstructive sleep apnea severity groups. Spindle density and percentage of fast spindles were positively associated with some verbal fluency measures on the cognitive testing. Sex might be linked with these associations. Biological sex could play a role in the associations between spindle characteristics and some verbal fluency measures. Obstructive sleep apnea severity was not found to be a contributing factor in this non-clinical community-dwelling cohort.

Impact of obstructive sleep apnoea and intermittent hypoxia on blood rheology: a translational study.

BACKGROUND: Haemorheological alterations are reported in obstructive sleep apnoea (OSA) and reversed with continuous positive airway pressure (CPAP), observations potentially explained by intermittent hypoxia (IH)-induced oxidative stress. Our objective was to investigate whether IH causes haemorheological alterations via oxidative stress. METHODS: Wistar rats were exposed to normoxia (n=7) or IH (n=8) for 14 days. 23 moderate-to-severe OSA patients were assessed at three time-points: baseline, after randomisation to either 2 weeks of nocturnal oxygen (n=13) or no treatment (n=10) and after 1 month of CPAP treatment (n=17). Furthermore, an OSA-free control group (n=13) was assessed at baseline and after time-matched follow-up. We measured haemorheological parameters (haematocrit, blood viscosity, plasma viscosity (rats only), erythrocyte aggregation and deformability (humans only)) and redox balance (superoxide dismutase (SOD), glutathione peroxidase, protein oxidation (advanced oxidation protein products (AOPPs)) and lipid peroxidation (malondialdehyde)). We also tested the haemorheological sensitivity of erythrocytes to reactive oxygen species (ROS) in our human participants using the oxidant t-butyl hydroperoxide (TBHP). RESULTS: In rats, IH increased blood viscosity by increasing haematocrit without altering the haemorheological properties of erythrocytes. IH also reduced SOD activity and increased AOPPs. In humans, baseline haemorheological properties were similar between patients and control participants, and properties were unaltered following oxygen and CPAP, except erythrocyte deformability was reduced following oxygen therapy. Redox balance was comparable between patients and control participants. At baseline, TBHP induced a greater reduction of erythrocyte deformability in patients while CPAP reduced TBHP-induced increase in aggregation strength. CONCLUSIONS: IH and OSA per se do not cause haemorheological alterations despite the presence of oxidative stress or higher sensitivity to ROS, respectively.

Recruitment of patients with chronic kidney disease and obstructive sleep apnoea for a clinical trial.

Obstructive sleep apnoea is common in chronic kidney disease (CKD) and may accelerate the decline in kidney function. Recruitment for a randomised controlled trial to address whether treatment of sleep apnoea with continuous positive airway pressure (CPAP) slows the progression of kidney failure may be challenging because sleep apnoea is often asymptomatic in this patient population. The present report outlines recruitment challenges and how to address them. Adult patients with CKD were recruited for a 12-month randomised, controlled, non-blinded, parallel clinical trial to evaluate the impact of CPAP therapy on kidney function. Patients completed a home sleep apnoea test and those that met pre-specified sleep apnoea and nocturnal hypoxaemia severity criteria were randomised to receive CPAP or no therapy. Although 1,665 patients were eligible to participate in the study over 3 years, only 57 (3.4%) were ultimately randomised. The sequential reasons (and number of patients) for recruitment failure were: no show at clinic appointment (137), insufficient recruiters to approach every eligible patient (461), on therapy for sleep apnoea (122), unable to provide informed consent (67), refused consent (645), home sleep apnoea test not completed (47) or inclusion criteria not met (116), and declined pre-randomisation education session (12). Many challenges limit effective recruitment, which may be addressed by hiring additional recruiters and increasing the awareness of sleep apnoea among patients with CKD. These findings can be used to improve recruitment strategies and the design of future studies.

Association of sleep spindle characteristics with executive functioning in healthy sedentary middle-aged and older adults.

To determine the relationship between sleep spindle characteristics (density, power and frequency), executive functioning and cognitive decline in older adults, we studied a convenience subsample of healthy middle-aged and older participants of the Brain in Motion study. Participants underwent a single night of unattended in-home polysomnography with neurocognitive testing carried out shortly afterwards. Spectral analysis of the EEG was performed to derive spindle characteristics in both central and frontal derivations during non-rapid eye movement (NREM) Stage 2 and 3. Multiple linear regressions were used to examine associations between spindle characteristics and cognitive outcomes, with age, body mass index (BMI), periodic limb movements index (PLMI) and apnea hypopnea index (AHI) as covariates. NREM Stage 2 total spindle density was significantly associated with executive functioning (central: ß = .363, p = .016; frontal: ß = .408, p = .004). NREM Stage 2 fast spindle density was associated with executive functioning (central: ß = .351, p = .022; frontal: ß = .380, p = .009) and Montreal Cognitive Assessment score (MoCA, central: ß = .285, p = .037; frontal: ß = .279, p = .032). NREM Stage 2 spindle frequency was also associated with MoCA score (central: ß = .337, p = .013). Greater spindle density and fast spindle density were associated with better executive functioning and less cognitive decline in our study population. Our cross-sectional design cannot infer causality. Longitudinal studies will be required to assess the ability of spindle characteristics to predict future cognitive status.

Sex differences in renal hemodynamics and renin-angiotensin system activity post-CPAP therapy in humans with obstructive sleep apnea.

Men have faster loss of kidney function and greater renal renin-angiotensin system (RAS) activity compared with women. Obstructive sleep apnea (OSA) is common in chronic kidney disease; the vascular effects of OSA differ by sex, and OSA-associated glomerular hyperfiltration can be reversed by continuous positive airway pressure (CPAP) therapy. We evaluated sex differences in the effect of CPAP on renal hemodynamics and the renal RAS in OSA. Twenty-nine Na+-replete, otherwise healthy study participants with OSA (10 women and 19 men) with nocturnal hypoxemia were studied pre- and post-CPAP (>4 h/night for 4 wk). Renal hemodynamics [renal plasma flow (RPF), glomerular filtration rate (GFR), and filtration fraction(FF)] were measured at baseline and in response to ANG II challenge, as a marker of renal RAS activity, pre- and post-CPAP therapy for 1 mo. In women, CPAP was associated with increased RPF (626 ± 22 vs. 718 ± 43 mL/min, P = 0.007, pre- vs. post-CPAP), maintained GFR (108 ± 2 vs. 105 ± 3 mL/min, P = 0.8), and reduced FF (17.4 ± 0.8% vs. 15.0 ± 0.7%, P = 0.017). In men, CPAP was associated with maintained RPF (710 ± 37 vs. 756 ± 38 mL/min, P = 0.1), maintained GFR (124 ± 8 vs. 113 ± 6 mL/min, P = 0.055), and reduced FF (18.6 ± 1.7% vs. 15.5 ± 1.1%, P = 0.035). Pre-CPAP, there were no sex differences in renal hemodynamic responses to ANG II. CPAP use was associated with a greater renovasoconstrictive response to ANG II in women (RPF at Δ30 min: -100 ± 27 vs. -161 ± 25 mL/min, P = 0.007, and RPF at Δ60 min: -138 ± 27 vs. -206 ± 32 mL/min, P = 0.007) but not men. CPAP use was associated with improved renal hemodynamics in both sexes and downregulated renal RAS activity in women but not men.

Marine subsidies mediate patterns in avian island biogeography.

The classical theory of island biogeography, which predicts species richness using island area and isolation, has been expanded to include contributions from marine subsidies, i.e. subsidized island biogeography (SIB) theory. We tested the effects of marine subsidies on species diversity and population density on productive temperate islands, evaluating SIB predictions previously untested at comparable scales and subsidy levels. We found that the diversity of terrestrial breeding bird communities on 91 small islands (approx. 0.0001-3 km2) along the Central Coast of British Columbia, Canada were correlated most strongly with island area, but also with marine subsidies. Species richness increased and population density decreased with island area, but isolation had no measurable influence. Species richness was negatively correlated with marine subsidy, measured as forest-edge soil δ15N. Density, however, was higher on islands with higher marine subsidy, and a negative interaction between area and subsidy indicates that this effect is stronger on smaller islands, offering some support for SIB. Our study emphasizes how subsidies from the sea can shape diversity patterns on islands and can even exceed the importance of isolation in determining species richness and densities of terrestrial biota.

Vascular responses to hypoxia are not impaired in obstructive sleep apnoea patients free of overt cardiovascular disease.

NEW FINDINGS: What is the central question of this study? Does treatment of obstructive sleep apnoea (OSA) with nocturnal oxygen or continuous positive airway pressure (CPAP) improve hypoxic vascular responses, which are reportedly impaired in OSA? What is the main finding and its importance? Cerebrovascular and cardiovascular hypoxic responses were not impaired in OSA patients free of overt cardiovascular disease and known risk factors, and were not altered by nocturnal oxygen or CPAP treatment. We conclude that this OSA patient phenotype has normal vascular responses to hypoxia and is unlikely to obtain long term cardiovascular benefits from nocturnal oxygen or CPAP therapy. ABSTRACT: Cerebral blood flow (CBF) and cardiovascular responses to hypoxia are reportedly impaired in obstructive sleep apnoea (OSA) patients and corrected by continuous positive airway pressure (CPAP), beneficial effects that are ascribed to correction of OSA-related intermittent hypoxia (IH). However, CPAP corrects both IH and ancillary OSA features (i.e. intermittent hypercapnia, sympathetic activation, blood pressure surges, negative intrathoracic pressure swings and sleep fragmentation). Whether correction of these ancillary OSA features contribute to CPAP's beneficial effects on vascular hypoxic responses is unknown. Nocturnal oxygen corrects OSA-induced IH, but apnoeas and ancillary features persist. Thus, we examined the effects of nocturnal oxygen and CPAP on cerebrovascular and cardiovascular hypoxic responses in untreated OSA patients. Responses were assessed in 52 OSA patients free of overt cardiovascular disease and known risk factors at baseline, after 2 weeks of nocturnal oxygen (n = 26) or no treatment (n = 26), and after ∼4 weeks of CPAP treatment (n = 40). Twenty-two age-matched controls were assessed at baseline and follow-up visits. Resting, isocapnic euoxia mean blood pressure was decreased following nocturnal oxygen (-3.6 ± 6.0 mmHg; P = 0.006) and CPAP (-4.5 ± 7.5 mmHg; P < 0.001) while cerebrovascular conductance was increased with CPAP (P = 0.001). However, these changes were not different from controls. Unexpectedly, OSA patients and controls had similar hypoxic vascular responses at baseline that were not changed by either nocturnal oxygen or CPAP. We conclude that OSA patients free of overt cardiovascular disease and known risk factors did not have impaired cerebrovascular or cardiovascular responses to hypoxia and are unlikely to obtain long term cardiovascular benefits from nocturnal oxygen or CPAP therapy.

Effect of Obstructive Sleep Apnea Treatment on Renal Function in Patients with Cardiovascular Disease.

RATIONALE: Obstructive sleep apnea (OSA) is associated with impaired renal function, but uncertainty exists over whether OSA treatment can influence renal outcomes. OBJECTIVES: To determine the effects of continuous positive airway pressure (CPAP) on renal function in subjects with coexisting OSA and cardiovascular disease. METHODS: This was a substudy of the international SAVE (Sleep Apnea Cardiovascular Endpoints) trial, in which 2,717 patients with moderate to severe OSA and established coronary or cerebrovascular disease were randomized to receive either CPAP plus usual care or usual care alone. Renal function and adverse renal events were compared between the CPAP (n = 102) and usual care (n = 98) groups. Glomerular filtration rate was estimated at randomization and at the end of follow-up, and the urinary albumin-to-creatinine ratio was measured at study exit. MEASUREMENTS AND MAIN RESULTS: In 200 substudy participants (mean age, 64 yr; median, 4% oxygen desaturation index; 20 events/h; mean estimated glomerular filtration rate at baseline, 82 ml/min/1.73 m2), the median (interquartile range) changes in estimated glomerular filtration rate (ml/min/1.73 m2/yr) were -1.64 (-3.45 to -0.740) in the CPAP group and -2.30 (-4.53 to -0.71) in the usual care group (P = 0.21) after a median of 4.4 years. There were no between-group differences in end-of-study urinary albumin-to-creatinine ratio or in the occurrence of serious renal or urinary adverse events during the trial. The level of CPAP adherence did not influence the findings. CONCLUSIONS: CPAP treatment of OSA in patients with cardiovascular disease does not alter renal function or the occurrence of renal adverse events. Clinical trial registered with www.clinicaltrials.gov (NCT00738179).

Speciation and the Latitudinal Diversity Gradient: Insights from the Global Distribution of Endemic Fish.

The nearly universal pattern that species richness increases from the poles to the equator (the latitudinal diversity gradient [LDG]) has been of intense interest since its discovery by early natural-history explorers. Among the many hypotheses proposed to explain the LDG, latitudinal variation in (1) productivity, (2) time and area available for diversification, and (3) speciation and/or extinction rates have recently received the most attention. Because tropical regions are older and were formerly more widespread, these factors are often intertwined, hampering efforts to distinguish their relative contributions to the LDG. Here we examine the global distribution of endemic lake fishes to determine how lake age, area, and latitude each affect the probability of speciation and the extent of diversification occurring within a lake. We analyzed the distribution of endemic fishes worldwide (1,933 species and subspecies from 47 families in 2,746 lakes) and find that the probability of a lake containing an endemic species and the total number of endemics per lake increase with lake age and area and decrease with latitude. Moreover, the geographic locations of endemics in 34 of 41 families are found at lower latitudes than those of nonendemics. We propose that the greater diversification of fish at low latitudes may be driven in part by ecological opportunities promoted by tropical climates and by the coevolution of species interactions.

Impact of obstructive sleep apnoea and intermittent hypoxia on cardiovascular and cerebrovascular regulation.

NEW FINDINGS: What is the topic of this review? This review examines the notion that obstructive sleep apnoea (OSA) and intermittent hypoxia (IH) have hormetic effects on vascular health. What advances does it highlight? Clinical (OSA patient) and experimental animal and human models report that IH is detrimental to vascular regulation. However, mild IH and, by extension, mild OSA also have physiological and clinical benefits. This review highlights clinical and experimental animal and human data linking OSA and IH to vascular disease and discusses how hormetic effects of OSA and IH relate to OSA severity, IH intensity and duration, and patient/subject age. Obstructive sleep apnoea (OSA) is associated with increased risk of cardiovascular and cerebrovascular disease, a consequence attributed in part to chronic intermittent hypoxia (IH) resulting from repetitive apnoeas during sleep. Although findings from experimental animal, and human, models have shown that IH is detrimental to vascular regulation, the severity of IH used in many of these animal studies [e.g. inspired fraction of oxygen (FI,O2) = 2-3%; oxygen desaturation index = 120 events h-1 ] is considerably greater than that observed in the majority of patients with OSA. This may also explain disparities between animal and recently developed human models of IH, where IH severity is, by necessity, less severe (e.g. FI,O2 = 10-12%; oxygen desaturation index = 15-30 events h-1 ). In this review, we highlight the current knowledge regarding the impact of OSA and IH on cardiovascular and cerebrovascular regulation. In addition, we critically discuss the recent notion that OSA and IH may have hormetic effects on vascular health depending on conditions such as OSA severity, IH intensity and duration, and age. In general, data support an independent causal link between OSA and vascular disease, particularly for patients with severe OSA. However, the data are equivocal for older OSA patients and patients with mild OSA, because advanced age and short-duration, low-intensity IH have been reported to provide a degree of protection against IH and ischaemic events such as myocardial infarction and stroke, respectively. Overall, additional studies are needed to investigate the beneficial/detrimental effects of mild OSA on the various vascular beds.

Effects of continuous positive airway pressure and isocapnic-hypoxia on cerebral autoregulation in patients with obstructive sleep apnoea.

KEY POINTS: Altered cerebral autoregulation (CA) in obstructive sleep apnoea (OSA) patients may contribute to increased stroke risk in this population; the gold standard treatment for OSA is continuous positive airway pressure, which improves cerebrovascular regulation and may decrease the risk of stroke. Isocapnic-hypoxia impairs CA in healthy subjects, but it remains unknown in OSA whether impaired CA is further exacerbated by isocapnic-hypoxia and whether it is improved by treatment with continuous positive airway pressure. During normoxia, CA was altered in the more severe but not in the less severe OSA patients, while, in contrast, during isocapnic-hypoxia, CA was similar between groups and tended to improve in patients with more severe OSA compared to normoxia. From a clinical perspective, one month of continuous positive airway pressure treatment does not improve CA. From a physiological perspective, this study suggests that sympathetic overactivity may be responsible for altered CA in the more severe OSA patients. ABSTRACT: Cerebral autoregulation (CA) impairment may contribute to the increased risk of stroke associated with obstructive sleep apnoea (OSA). It is unknown if impaired CA is further exacerbated by isocapnic-hypoxia and whether it is improved by treatment of OSA with continuous positive airway pressure (CPAP). CA was assessed during wakefulness in 53 OSA patients (50.3 ± 9.3 years) and 21 controls (49.8 ± 8.6 years) at baseline and following a minimum of 1 month of effective CPAP therapy (OSA patients, n = 40). Control participants (n = 21) performed a follow-up visit to control for time effects within OSA patients between baseline and the post-CPAP visit. Beat-by-beat middle cerebral artery blood flow velocity and mean arterial blood pressure (MBP), and breath-by-breath end-tidal partial pressure of CO2 (P ET ,CO2) were monitored. CA was determined during normoxia and isocapnic-hypoxia using transfer function (phase and gain) and coherence analysis (including multiple and partial coherence (using MBP and P ET ,CO2 as inputs)) in the very low frequency range (0.03-0.07 Hz). OSA patients were divided into two subgroups (less severe and more severe) based upon the median respiratory disturbance index (RDI). During normoxia, the more severe OSA patients (RDI 45.9 ± 10.3) exhibited altered CA compared to controls and the less severe OSA patients (RDI 24.5 ± 5.9). In contrast, during isocapnic-hypoxia, CA was similar between groups. CPAP had no effect on CA. In conclusion, CA is altered in the more severe OSA patients during normoxia but not during isocapnic-hypoxia and CPAP treatment does not impact CA.

An observational study of the effectiveness of alternative care providers in the management of obstructive sleep apnea.

Alternative care providers have been proposed as a substitute for physician-based management of obstructive sleep apnea. The purpose of this study was to describe the clinical course of patients with a new diagnosis of obstructive sleep apnea who were treated with continuous positive airway pressure and followed by alternative care providers at a tertiary care sleep clinic. It was hypothesized that care by alternative care providers would result in improvement of daytime sleepiness and satisfactory treatment adherence, and that a specific number of follow-up visits could be identified after which clinical outcomes no longer improved. The Epworth Sleepiness Scale score was measured for each patient at baseline and at each alternative care provider visit. Patients were discharged when they demonstrated a significant improvement in sleepiness and were adherent to therapy. The Epworth Sleepiness Scale score decreased by 3.9 points from baseline to discharge. Patients with three or more visits required more follow-up time to achieve the same clinical improvement as those with only two visits. Continuous positive airway pressure adherence was comparable to previous studies of physician-led care and improved with ongoing alternative care provider follow-up. The current results suggest that clinical care by alternative care providers leads to continued improvements in sleepiness in patients with obstructive sleep apnea who are treated with continuous positive airway pressure, and that a minority of patients require longer follow-up to achieve a satisfactory clinical response to therapy.

Nocturnal hypoxemia severity and renin-angiotensin system activity in obstructive sleep apnea.

RATIONALE: Obstructive sleep apnea (OSA) and nocturnal hypoxemia are associated with chronic kidney disease and up-regulation of the renin-angiotensin system (RAS), which is deleterious to renal function. The extent to which the magnitude of RAS activation is influenced by the severity of nocturnal hypoxemia and comorbid obesity has not been determined. OBJECTIVES: To determine the association between the severity of nocturnal hypoxemia and RAS activity and whether this is independent of obesity in patients with OSA. METHODS: Effective renal plasma flow (ERPF) response to angiotensin II (AngII) challenge, a marker of renal RAS activity, was measured by paraaminohippurate clearance technique in 31 OSA subjects (respiratory disturbance index, 51 ± 25 h(-1)), stratified according to nocturnal hypoxemia status (mean nocturnal SaO2, ≥90% [moderate hypoxemia] or <90% [severe hypoxemia]) and 13 obese control subjects. MEASUREMENTS AND MAIN RESULTS: Compared with control subjects, OSA subjects demonstrated decreased renovascular sensitivity (ERPF, -153 ± 79 vs. -283 ± 31 ml/min; P = 0.004) (filtration fraction, 5.4 ± 3.8 vs. 7.1 ± 2.6%; P = 0.0025) in response to 60 minutes of AngII challenge (mean ± SD; all P values OSA vs. control). The fall in ERPF in response to AngII was less in patients with severe hypoxemia compared with those with moderate hypoxemia (P = 0.001) and obese control subjects after 30 minutes (P < 0.001) and 60 minutes (P < 0.001) of AngII challenge, reflecting more augmented renal RAS activity. Severity of hypoxemia was not associated with the blood pressure or the systemic circulating RAS component response to AngII. CONCLUSIONS: The severity of nocturnal hypoxemia influences the magnitude of renal, but not the systemic, RAS activation independently of obesity in patients with OSA.

Human intermittent hypoxia-induced respiratory plasticity is not caused by inflammation.

Ventilatory instability, reflected by enhanced acute hypoxic (AHVR) and hypercapnic (AHCVR) ventilatory responses is a fundamental component of obstructive sleep apnoea (OSA) pathogenesis. Intermittent hypoxia-induced inflammation is postulated to promote AHVR enhancement in OSA, although the role of inflammation in intermittent hypoxia-induced respiratory changes in humans has not been examined. Thus, this study assessed the role of inflammation in intermittent hypoxia-induced respiratory plasticity in healthy humans.In a double-blind, placebo-controlled, randomised crossover study design, 12 males were exposed to 6 h of intermittent hypoxia on three occasions. Prior to intermittent hypoxia exposures, participants ingested (for 4  days) either placebo or the nonsteroidal anti-inflammatory drugs indomethacin (nonselective cyclooxygenase (COX) inhibitor) and celecoxib (selective COX-2 inhibitor). Pre- and post-intermittent hypoxia resting ventilation, AHVR, AHCVR and serum concentration of the pro-inflammatory cytokine tumour necrosis factor (TNF)-α were assessed.Pre-intermittent hypoxia resting ventilation, AHVR, AHCVR and TNF-α concentrations were similar across all three conditions (p≥0.093). Intermittent hypoxia increased resting ventilation and the AHVR similarly across all conditions (p=0.827), while the AHCVR was increased (p=0.003) and TNF-α was decreased (p=0.006) with only selective COX-2 inhibition.These findings indicate that inflammation does not contribute to human intermittent hypoxia-induced respiratory plasticity. Moreover, selective COX-2 inhibition augmented the AHCVR following intermittent hypoxia exposure, suggesting that selective COX-2 inhibition could exacerbate OSA severity by increasing ventilatory instability.

Evaluation of continuous positive airway pressure therapy on renin-angiotensin system activity in obstructive sleep apnea.

RATIONALE: Obstructive sleep apnea (OSA) has been associated with kidney function loss, which may be related to changes in the renin-angiotensin system (RAS). OBJECTIVES: We sought to determine the effect of continuous positive airway pressure (CPAP) of patients with OSA on renal hemodynamics at baseline and in response to angiotensin II (AngII), which reflects RAS activity. METHODS: Twenty normotensive, nondiabetic, newly diagnosed OSA subjects (15 men, 5 women, 50 ± 2 yr, respiratory disturbance index [RDI] > 15 h(-1)) with nocturnal hypoxemia (SaO2 < 90% for >12% of the night) were studied in high-salt balance pre- and post-CPAP therapy (>4 h CPAP use/night for 1 mo). Glomerular filtration rate (GFR), renal plasma flow (RPF), and filtration fraction (FF) (a surrogate marker for intraglomerular pressure) were measured pre- and post-CPAP using inulin and para-aminohippurate clearance techniques at baseline and in response to graded AngII infusion (3 ng/kg/min × 30 min and 6 ng/kg/min × 30 min, respectively). MEASUREMENTS AND MAIN RESULTS: CPAP corrected OSA and hypoxemia (RDI: 42 ± 4 vs. 4 ± 1 h(-1), P < 0.001; duration SaO2 < 90%: 36% ± 5% vs. 6 ± 2%, P < 0.001). CPAP reduced GFR (124 ± 8 ml/min vs. 110 ± 6 ml/min, P = 0.014), increased RPF (692 ± 36 ml/min vs. 749 ± 40 ml/min, P = 0.059), and reduced baseline FF (18.9 ± 1.6% vs. 15.3 ± 1.0%, P = 0.004). Post-CPAP demonstrated a blunted GFR response (-9 ± 3 ml/min vs. -2 ± 2 ml/min, P = 0.033) and augmented RPF response (-182 ± 22 ml/min vs. -219 ± 25 ml/min, P = 0.024) to AngII. FF response was maintained (P = 0.4). CPAP reduced baseline mean arterial pressure (94 ± 2 vs. 89 ± 2 mm Hg, P = 0.002), plasma aldosterone (149 ± 18 vs. 109 ± 10 pmol/L, P = 0.003), and urinary protein excretion (61 [39-341] mg/day vs. 56 [22-204] mg/d, P = 0.003). CONCLUSIONS: CPAP therapy was associated with improved renal hemodynamics and down-regulation of renal RAS activity, suggesting a potential therapeutic benefit for kidney function.

Predictors of successful completion of diagnostic home sleep testing in patients with chronic kidney disease.

PURPOSE: Obstructive sleep apnea (OSA) is common among patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD). Home sleep testing is used to diagnose OSA in many studies investigating sleep-disordered breathing in this population. However, failure to successfully complete the test is a significant source of participant exclusion from research studies and delayed diagnosis in clinical practice. The objective of the study was to identify potential factors impeding acceptance and successful completion of home sleep testing in patients with kidney disease. METHODS: Four hundred and nineteen patients were recruited from nephrology clinics and dialysis units. Following completion of a sleep and medical history questionnaire, all patients were invited to perform a single night, home sleep study. Acceptance or refusal of the test was noted, as well as the success of the sleep study, as determined by a review of the raw data by a sleep medicine physician. RESULTS: Male gender (OR = 1.61, CI = 1.02-2.53), hypertension (OR = 2.01, CI = 1.17-3.45), and snoring (OR = 1.75, CI = 1.11-2.77) were associated with sleep test acceptance. Older patients were less likely to accept the test (OR = 0.48, CI = 0.30-0.76). Diabetics were less likely to complete the sleep test successfully (OR = 0.28, CI = 0.12-0.66). CONCLUSIONS: Advanced age is an important factor in test refusal and complications of diabetes contributes to test failure. Symptom matching may be a source of selection bias, as patients with risk factors for OSA are more likely to accept the diagnostic test.

Association between sleep microarchitecture and cognition in obstructive sleep apnea.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) increases the risk of cognitive impairment. Measures of sleep microarchitecture from EEG may help identify patients at risk of this complication. METHODS: Participants with suspected OSA (n=1142) underwent in-laboratory polysomnography and completed sleep and medical history questionnaires, and tests of global cognition (Montreal Cognitive Assessment, MoCA), memory (Rey Auditory Verbal Learning Test, RAVLT) and information processing speed (Digit-Symbol Coding, DSC). Associations between cognitive scores and stage 2 NREM sleep spindle density, power, frequency and %-fast (12-16Hz), odds-ratio product (ORP), normalized EEG power (EEGNP) and the delta:alpha ratio were assessed using multivariable linear regression (MLR) adjusted for age, sex, education, and total sleep time. Mediation analyses were performed to determine if sleep microarchitecture indices mediate the negative effect of OSA on cognition. RESULTS: All spindle characteristics were lower in participants with moderate and severe OSA (p≤0.001, versus no/mild OSA) and positively associated with MoCA, RAVLT and DSC scores (false discovery rate corrected p-value, q≤0.026), except spindle power which was not associated with RAVLT (q=0.185). ORP during NREM sleep (ORPNREM) was highest in severe OSA participants (p≤0.001) but neither ORPNREM (q≥0.230) nor the delta:alpha ratio were associated with cognitive scores in MLR analyses (q≥0.166). In mediation analyses, spindle density and EEGNP (p≥0.048) mediated moderate-to-severe OSA's negative effect on MoCA scores while ORPNREM, spindle power and %-fast spindles mediated OSA's negative effect on DSC scores (p≤0.018). CONCLUSION: Altered spindle activity, ORP and normalized EEG power may be important contributors to cognitive deficits in patients with OSA.

All Obstructive Sleep Apnea Events Are Not Created Equal: The Relationship between Event-related Hypoxemia and Physiologic Response.

Rationale: Obstructive sleep apnea (OSA) severity is typically assessed by the apnea-hypopnea index (AHI), a frequency-based metric that allocates equal weight to all respiratory events. However, more severe events may have a greater physiologic impact. Objectives: The purpose of this study was to determine whether the degree of event-related hypoxemia would be associated with the postevent physiologic response. Methods: Patients with OSA (AHI, ⩾5/h) from the multicenter Canadian Sleep and Circadian Network cohort were studied. Using mixed-effect linear regression, we examined associations between event-related hypoxic burden (HBev) assessed by the area under the event-related oxygen saturation recording with heart rate changes (ΔHRev), vasoconstriction (vasoconstriction burden [VCBev] assessed with photoplethysmography), and electroencephalographic responses (power ratio before and after events). Results: Polysomnographic recordings from 658 patients (median [interquartile range] age, 55.00 [45.00, 64.00] yr; AHI, 27.15 [14.90, 64.05] events/h; 42% female) were included in the analyses. HBev was associated with an increase in all physiologic responses after controlling for age, sex, body mass index, sleep stage, total sleep time, and study centers; for example, 1 standard deviation increase in HBev was associated with 0.21 [95% confidence interval, 0.2, 0.22], 0.08 [0.08, 0.09], and 0.22 [0.21, 0.23] standard deviation increases in ΔHRev, VCBev, and ß-power ratio, respectively. Conclusions: Increased event-related hypoxic burden was associated with greater responses across a broad range of physiologic signals. Future metrics that incorporate information about the variability of these physiologic responses may have promise in providing a more nuanced assessment of OSA severity.