Sleep disordered breathing and mortality: eighteen-year follow-up of the Wisconsin sleep cohort

BACKGROUND: Sleep-disordered breathing (SDB) is a treatable but markedly under-diagnosed condition of frequent breathing pauses during sleep. SDB is linked to incident cardiovascular disease, stroke, and other morbidity. However, the risk of mortality with untreated SDB, determined by polysomnography screening, in the general population has not been established. METHODS: An 18-year mortality follow-up was conducted on the population-based Wisconsin Sleep Cohort sample (n = 1522), assessed at baseline for SDB with polysomnography, the clinical diagnostic standard. SDB was described by the number of apnea and hypopnea episodes/hour of sleep; cutpoints at 5, 15 and 30 identified mild, moderate, and severe SDB, respectively. Cox proportional hazards regression was used to estimate all-cause and cardiovascular mortality risks, adjusted for potential confounding factors, associated with SDB severity levels. RESULTS: All-cause mortality risk, adjusted for age, sex, BMI, and other factors was significantly increased with SDB severity. The adjusted hazard ratio (HR, 95% CI) for all-cause mortality with severe versus no SDB was 3.0 (1.4,6.3). After excluding persons who had used CPAP treatment (n = 126), the adjusted HR (95% CI) for all-cause mortality with severe versus no SDB was 3.8 (1.6,9.0); the adjusted HR (95% CI) for cardiovascular mortality was 5.2 (1.4,19.2). Results were unchanged after accounting for daytime sleepiness. CONCLUSIONS: Our findings of a significant, high mortality risk with untreated SDB, independent of age, sex, and BMI underscore the need for heightened clinical recognition and treatment of SDB, indicated by frequent episodes of apnea and hypopnea, irrespective of symptoms of sleepiness.     

Sleep in overweight adolescents: shorter sleep, poorer sleep quality, sleepiness, and sleep-disordered breathing

OBJECTIVE: To document the sleep of overweight adolescents and to explore the degree to which weight-related sleep pathology might account for diminished psychosocial outcome. METHODS: Sixty children aged 10-16.9 from a weight-management clinic were compared to 22 healthy controls using comprehensive actigraphic, polysomnographic, and parent- and self-report questionnaire assessments. RESULTS: Overweight participants averaged more symptoms of sleep-disordered breathing, later sleep onset, shorter sleep time, and more disrupted sleep than controls. Although the groups did not differ in self-reported sleep habits, multiple concerns were reported by parents of overweight participants, including daytime sleepiness, parasomnias, and inadequate sleep. Group differences in academic grades and depressive symptoms were at least partially accounted for by short sleep and daytime sleepiness. CONCLUSIONS: Excessive weight is associated with an increased risk of sleep problems. There is a need for further research in this area and for clinicians who work with overweight children to evaluate their sleep.     

Polysomnographic indicators of restorative sleep and body mass trajectories in the Wisconsin Sleep Cohort Study

Study ObjectivesPrevious research suggests that reductions in restorative, slow-wave (N3), and rapid eye movement (REM) sleep are associated with weight gain and obesity in mid-to-late life. We extend prior work by examining how within-person (WP) changes and between-person (BP) differences in restorative sleep over several years are associated with body mass trajectories among participants in the Wisconsin Sleep Cohort Study (WSCS).MethodsWe used data from 4,862 polysomnographic (PSG) sleep studies and physical exams collected from 1,187 WSCS participants over an average duration of 14.9 years. Primary measures of interest included body mass index (BMI = kg/m²) and the percentages of time spent in N3 and REM sleep. We estimated a series of linear mixed regression models to examine how WP changes and BP differences in N3 and REM sleep affected BMI trajectories, controlling for other sleep measures, demographic characteristics, and health behaviors as potential confounders.ResultsWomen in the WSCS experienced more rapid BMI gain than men. With some variation by sex, we found that (1) below-average N3 and REM sleep is associated with above-average BMI, and (2) within-person decreases in N3 and REM sleep over time are associated with gains in BMI. These findings persisted after adjustment for sleep duration and other potential confounders.ConclusionsOur findings highlight the importance of PSG indices of restorative sleep in mid-to-late life, suggesting that future clinical treatments and public health policies will benefit from heightened attention to sleep quality.     

Relationship between sleep-disordered breathing and markers of systemic inflammation in women from the general population

Sleep‐disordered breathing (SDB) is a risk factor for cardiovascular disease (CVD). The underlying pathogenesis is not clear. In patients with obstructive sleep apnoea syndrome (OSAS) elevated levels of inflammatory markers, such as C‐reactive protein (CRP), interleukin‐6 (IL‐6) and tumour necrosis factor α (TNFα) have been found. These markers have also been shown as independent markers of CVD in other populations. The aim of the study was to investigate the association between SDB and systemic inflammation in a population‐based cohort of women. From 6817 women who previously answered a questionnaire concerning snoring habits, 230 habitually snoring women and 170 women regardless of snoring status went through polysomnography, anthropometric measurements and blood sampling. Analyses were made for CRP, TNFα, IL‐6, myeloperoxidase (MPO) and lysozyme. The levels of CRP, IL‐6 and lysozyme were significantly higher in subjects with apnoea–hypopnoea index (AHI) ≥15 compared with women with lower AHI. All inflammatory markers except MPO correlated to AHI and oxygen desaturation measures, and to waist circumference. In multiple linear regressions adjusting for age, waist circumference and smoking, independent correlations between oxygen desaturation indices (ODI) and inflammation were found for IL‐6 (P = 0.03 for % sleep time with saturation <90%) and TNFα (P = 0.03 for ODI 3%). No significant correlations were found between AHI and inflammation. Also, for women from the general population there is an independent correlation between SDB and inflammation, even after adjusting for obesity. The results indicate that intermittent hypoxia, and not the AHI, is related to systemic inflammation seen in OSAS.     

Sleep-disordered breathing and self-reported general health status in the Wisconsin Sleep Cohort Study

OBJECTIVE: To determine the relationship between sleep-disordered breathing and self-reported general health status. breathing status assessed by overnight in-laboratory polysomnography. SETTING: General Community. SUBJECTS: Employed men (n=421) and women (n=316), ages 30-60 years, enrolled in the Wisconsin Sleep Cohort Study. INTERVENTIONS: None. OUTCOME MEASURE: Self-reported general health profile and life satisfaction measured by the Medical Outcomes Survey Short Form-36 and obtained by interview. RESULTS: Sleep-disordered breathing was associated with lower general health status before and after adjustment for age, sex, body mass index, smoking status, alcohol usage, and a history of cardiovascular conditions. Even mild sleep-disordered breathing (apnea-hypopnea index = 5) was associated with decrements in the Medical Outcomes Short Form 36 Survey health constructs comparable to the magnitude of decrements linked to other chronic conditions such as arthritis, angina, hypertension, diabetes, and back problems. CONCLUSIONS: Sleep-disordered breathing is independently related to lower general health status, and this relationship is of clinical significance. Given the growing emphasis of the importance of patients' perceptions of health, these findings are relevant to estimating the overall impact of sleep-disordered breathing.     

Prediction of sleep-disordered breathing by unattended overnight oximetry

Between January 1994 and July 1997, 793 patients suspected of having sleep-disordered breathing had unattended overnight oximetry in their homes followed by laboratory polysomnography. From the oximetry data we extracted cumulative percentage time at SaO2 < 90% (CT90) and a saturation variability index (delta Index, the sum of the differences between successive readings divided by the number of readings - 1). CT90 was weakly correlated with polysomnographic apnea/hypopnea index (AHI). (Spearman rho = 0.36, P < 0.0001) and with delta Index (rho = 0.71, P < 0.0001). delta Index was more closely correlated with AHI (rho = 0.59, P < 0.0001). In a multivariate model, only delta Index was significantly related to AHI, the relationship being AHI = 18.8 delta Index + 7.7. The 95% CI for the coefficient were 16.2, 21.4, and for the constant were 5.8, 9.7. The sensitivity of a delta Index cut-off of 0.4 for the detection of AHI > or = 15 was 88%, for detection of AHI > or = 20 was 90% and for the detection of AHI > or = 25 was 91%. The specificity of delta Index > or = 0.4 for AHI > or = 15 was 40%. In 113 further patients, oximetry was performed simultaneously with laboratory polysomnography. Under these circumstances delta Index was more closely correlated with AHI (rho = 0.74, P < 0.0001), as was CT90 (rho = 0.58, P < 0.0001). Sensitivity of delta Index > or = 0.4 for detection of AHI > or = 15 was not improved at 88%, but specificity was better at 70%. We concluded that oximetry using a saturation variability index is sensitive but nonspecific for the detection of obstructive sleep apnea, and that few false negative but a significant proportion of false positive results arise from night-to-night variability.     

Obstructive Sleep Apnea and Aldosterone

Background:

Obstructive sleep apnea (OSA) is a major risk factor for hypertension and has been associated with increased risk for cardiovascular morbidity. A dysregulated renin-angiotensin-aldosterone system may contribute to excess sodium retention and hypertension and may be activated in OSA. We tested the hypothesis that serum levels of aldosterone and plasma renin activity (PRA) are increased by apneic sleep in subjects without cardiovascular disease, compared to healthy control subjects.

Methods and Results:

Plasma aldosterone level was measured in 21 subjects with moderate to severe OSA and was compared to 19 closely matched healthy subjects. Plasma renin activity (PRA) was measured in 19 OSA patients and in 20 healthy controls. Aldosterone and PRA were measured before sleep (9pm), after 5 hrs of untreated OSA (2am) and in the morning after awakening (6am). There were no baseline (9pm) differences in serum aldosterone levels and PRA between the healthy controls and OSA patients (aldosterone: 55.2 ± 9 vs 56.0 ± 9 pg/mL; PRA: 0.99 ± 0.15 vs 1.15 ± 0.15 ng/mL/hr). Neither several hours of untreated severe OSA nor CPAP treatment affected aldosterone levels and PRA in OSA patients. Diurnal variation of both aldosterone and PRA was observed in both groups, in that morning renin and aldosterone levels were higher than those measured at night before sleep.

Conclusions:

Our study shows that patients with moderate to severe OSA without co-existing cardiovascular disease have plasma aldosterone and renin levels similar to healthy subjects. Neither untreated OSA nor CPAP treatment acutely affect plasma aldosterone or renin levels.

Citation:

Svatikova A; Olson LJ; Wolk R; Phillips BG; Adachi T; Schwartz GL; Somers VK. Obstructive sleep apnea and aldosterone. SLEEP 2009;32(12):1589-1592.     

Effect of sleep disordered breathing on the sleep of bed partners in the Sleep Heart Health Study

OBJECTIVE: To study the sleep quality of bed partners of persons with sleep disordered breathing in a non-clinical population based sample in a home environment. DESIGN: Cross-sectional study in a community sample. METHODS: 110 pairs of subjects living in the same household from the Tucson, Minnesota, and Pittsburgh sites of the Sleep Heart Health Study (SHHS) were included if both partners had an in-home, unattended polysomnogram (PSG) performed as a part of SHHS exam cycle 2. Sleep disordered breathing (SDB) was considered present if the respiratory disturbance index (RDI) was > or =10 events/h and no SDB if RDI was <5 events/h. Pairs were classified according to their SDB status and assigned to one of 3 groups: 1) NoSDB-NoSDB (n = 46), 2) NoSDB-SDB (n = 42), and 3) SDB-SDB (n = 22). RESULTS: There were no differences between the NoSDB-NoSDB and the SDB-SDB partners in their demographic, PSG, or quality of life variables. However, within the NoSDB-SDB group, NoSDB in comparison to their SDB partners weighed less (mean BMI: 26 vs. 29 kg/m2, P < 0.0003), had decreased stage 2% (55 vs. 64, P < 0.0001), increased stage 3 and 4% (21 vs. 11, P <0.0005) and a lower arousal index (13.8 vs. 20 events/h, P < 0.0001). When comparing the NoSDB subjects from the NoSDB-SDB group to subjects in the NoSDB-NoSDB group and to subjects in the SDB-SDB group, significant differences were seen for RDI and BMI but not for any other parameter. CONCLUSION: In a non-clinical population based sample, the sleep quality of bed partners of SDB subjects without SDB is better than their SDB bed partner. However, their sleep quality was not different in comparison to the sleep of those without SDB who also had a bed partner without SDB.     

A randomized placebo-controlled trial of an NMDA receptor antagonist in sleep-disordered breathing

Hypoxemia is a powerful stimulus of glutamate release in the central nervous system (CNS) and a hallmark phenomenon in sleep disordered breathing (SDB). Glutamate effects that include neuronal damage and apoptosis following hypoxemia and apnea following microinjections in animal models are in part mediated via postjunctional N-methyl-D-aspartate (NMDA) receptors. This was a double blind, randomized, placebo-controlled single dose cross-over study of the NMDA receptor antagonist AR-R15896AR in 15 male patients with moderate to severe SDB. Seven patients received 120 mg and eight patients received 350 mg AR-R15896AR or corresponding placebo (given by 2 h infusion) starting half an hour before estimated sleep onset. AR-R15896AR concentrations were in line with the predicting kinetic model. A standard polysomnographic montage was applied. Repeated plasma samples were obtained in nine patients for analysis of plasma glutamate. Glutamate concentration in plasma did not change overnight and was unrelated to severity of SDB. Overall AHI (apnea-hypopnea index; primary efficacy variable) or investigated oxygen saturation variables were not significantly changed after AR-R15896AR at either dosage level. Side effects were mostly confined to the higher dose level and included vivid dreams, nightmares as well as in two cases mild hallucinations. The previously postulated role of glutamate in SDB could not be confirmed after AR-R15896AR induced NMDA-receptor blockade.     

Minimal nocturnal oxygen saturation predicts future subclinical carotid atherosclerosis: the Wisconsin sleep cohort

Previous data on the associations between nocturnal oxygen saturation parameters and carotid atherosclerosis are conflicting. We examined the prospective associations of nocturnal oxygen saturation (SaO₂) and cardiovascular disease (CVD) risk factors with carotid intima‐media thickness (IMT) and plaques. We used data on 689 Wisconsin sleep cohort participants who had baseline overnight polysomnography followed by carotid ultrasonography a mean (SD) of 7.8 (2.5) years later. Far wall common carotid IMT was measured using B‐mode ultrasound. Bilateral common, bifurcation and internal carotid artery segments were evaluated for plaque score. Participants (8) were aged 56 years (55% male); 32% had hypertension and mean body mass index (BMI) was 31 (7) kg m². Mean and minimum nocturnal SaO₂ were 95% (2) and 86% (7), respectively. Mean percentage sleep time with SaO₂ < 90% was 2% (8). Both mean (odds ratio [OR]: 0.60 lower plaque count per 5% higher mean SaO₂, 95% confidence interval [CI]: 0.38–0.96, P = 0.033) and minimum SaO₂ (OR: 0.88 lower plaque count per 5% higher minimum SaO₂, 95% CI: 0.80–0.97, P = 0.013) predicted carotid plaque score after adjusting for age, sex and BMI. Minimum SaO₂ predicted future plaque score after adding adjustment for traditional CVD risk factors (OR: 0.90 lower plaque count per 5% higher minimum SaO₂, 95% CI: 0.81–0.99, P = 0.038). Mean SaO₂ was not associated with carotid IMT after CVD risk factor adjustment. We conclude that minimum nocturnal SaO₂ is an independent predictor of future carotid plaque burden. Other nocturnal SaO₂ parameters are not associated with future carotid IMT or plaques after adjusting for traditional CVD risk factors.     

Determining optimal sleep position in patients with positional sleep-disordered breathing using response surface analysis

A lateral position (LP) during sleep is effective in reducing sleep disorder symptoms in mild or moderate sleep apnea patients. However, the effect of head and shoulder posture in LP on reducing sleep disorders has not been reported. In this study, effective sleeping positions and a combination of sleep position determinants were evaluated with respect to their ability to reduce snoring and apnea. The positions evaluated included the following: cervical vertebrae support with head tilting (CVS-HT), scapula support (SS), and LP. A central composite design was applied for response surface analysis (RSA). Sixteen patients with mild or moderate positional sleep apnea and snoring who underwent polysomnography for two nights were evaluated. Based on an estimated RSA equation, LP (with a rotation of at least 30°) had the most dominant effect [ P  = 0.0057 for snoring rate, P  = 0.0319 for apnea–hypopnea index (AHI)]. In addition, the LP was found to interact with CVS-HT ( P  = 0.0423) for snoring rate and CVS-HT ( P  = 0.0310) and SS ( P  = 0.0265) for AHI. The optimal sleep position reduced mild snoring by more than 80% (i.e. snoring rate in the supine position was <20%) and the snoring rate was approximately zero with a 40° rotation. To achieve at least 80% reduction of AHI, LP and SS should be >30° and/or 20 mm respectively. To determine an effective sleep position, CVS-HT and SS, as well as the degree of the LP, should be concurrently considered in patients with positional sleep apnea or snoring.     

The association of sleep-disordered breathing and sleep symptoms with quality of life in the Sleep Heart Health Study

This study assessed the extent to which sleep-disordered breathing (SDB), difficulty initiating and maintaining sleep (DIMS), and excessive daytime sleepiness (EDS) were associated with impairment of quality of life (QoL) using the SF-36. Participants (n=5,816; mean age=63 years; 52.5% women) were enrolled in the nation-wide population-based Sleep Heart Health Study (SHHS) implemented to investigate sleep-disordered breathing as a risk factor in the development of cardiovascular disease. Each transformed SF-36 scale was analyzed independently using multiple logistic regression analysis with sleep and other potential confounding variables (e.g., age, ethnicity) included as independent variables. Men (11.6%) were significantly more likely to have SDB compared to women (5.6%), while women (42.4%) were significantly more likely to report DIMS than men (32.5%). Vitality was the sole SF-36 scale to have a linear association with the clinical categories of SDB (mild, moderate, severe SDB). However, individuals with severe SDB indicated significantly poorer QoL on several SF-36 scales. Both DIMS and EDS were strongly associated with reduced QoL even after adjusting for confounding variables for both sexes. Findings suggest 1) mild to moderate SDB is associated with reduced vitality, while severe SDB is more broadly associated with poorer QoL, 2) subjective sleep symptoms are comprehensively associated with poorer QoL, and 3) SF-36 mean score profiles for SDB and sleep symptoms are equivalent to other chronic diseases in the U.S. general population.     

Sleep-disordered breathing and cardiovascular disease in the Bay Area Sleep Cohort

STUDY OBJECTIVES: To examine the relationship between sleep-disordered breathing (SDB) and cardiovascular disease among community-dwelling older adults. Previous studies have suggested relatively stronger associations between SDB and such morbidity in middle-aged, relative to elderly, populations. DESIGN: Cross-sectional analysis of an elderly ambulatory, non-clinic-based cohort (Bay Area Sleep Cohort, BASC) SETTING: Community population studied in a sleep laboratory PARTICIPANTS: One hundred twenty-nine older adults (mean [+/- SD] age = 72.6 [8.3]) (78 women; 51 men). INTERVENTIONS: NA. MEASUREMENTS: Complete clinical history including list of current medications, physical examination, selected blood chemistries, multiple blood pressure measurements, 12-lead electrocardiogram, and 2 consecutive nights of polysomnography. RESULTS: Fifty-one individuals (40%) were taking 1 or more cardiovascular medications and 24 (19%) had an apnea-hypopnea index (AHI) of 10 or more per hour of sleep. Cardiovascular medication use was related to cardiac events or procedures, history of angina, higher systolic or diastolic blood pressure, and abnormal electrocardiogram. Logistic regression showed statistically significant association between cardiovascular medication use and AHI of 10 or greater per hour, independent of age, sex, and body mass index. Supplementary analyses indicated that rapid eye movement AHI of 10 or greater per hour was significantly associated with elevated diastolic blood pressure. CONCLUSIONS: The results suggest that sleep-disordered breathing may contribute to increased cardiovascular morbidity in older adults.     

Day/Night Rhythm of Hemostatic Factors in Obstructive Sleep Apnea

Study Objectives:

To investigate the hypothesis that day/night patterns of prothrombotic activity differ between patients with obstructive sleep apnea (OSA) and individuals with no OSA.

Design:

Prothrombotic markers'' day/night rhythms recorded over one 24-h period.

Setting:

General clinical research center.

Patients:

38 untreated OSA patients as verified by polysomnography (apnea-hypopnea index ≥10/h sleep) and 22 non-OSA controls.

Measurements and Results:

Blood samples were collected every 2 h to measure plasma levels of fibrinolysis-inhibiting plasminogen activator inhibitor (PAI)-1 and the primary fibrin degradation product D-dimer. Day/night variation in hemostasis factors was examined using a cosinor analysis. Mesor (mean) PAI-1 over the 24-h period was higher (P = 0.015), and mesor of D-dimer was lower (P = 0.001) in patients with OSA than in the non-OSA controls. These group differences stayed significant when controlling for age and gender. After further adjustment for body mass index, mean arterial pressure, and smoking, the relationship between OSA and PAI-1 became non-significant, but the relationship between OSA and D-dimer continued to be significant (P = 0.006). In the fully adjusted analysis, the amplitude (peak) for D-dimer was lower in OSA patients than in non-OSA controls (P = 0.048). The acrophase (time of the peak) for PAI-1 and D-dimer did not significantly differ between groups.

Conclusions:

The relatively higher average level of PAI-1 and lower average level of D-dimer across the 24-h in OSA patients might reflect decreased fibrinolytic capacity and fibrin degradation, respectively. The findings provide some evidence for a prothrombotic state in OSA, but were only partially independent of metabolic variables.

Citation:

von Käanel R; Natarajan L; Ancoli-Israel S; Mills PJ; Loredo JS; Dimsdale JE. Day/night rhythm of hemostatic factors in obstructive sleep apnea. SLEEP 2010;33(3):371-377.     

Association of cardiac autonomic function measures with severity of sleep-disordered breathing in a community-based sample

The goal of this study was to test the hypothesis that spectral indices of heart rate variability, such as high-frequency power (HFP), low-to-high frequency power (LHR), and their respiration-adjusted counterparts (HFPra, LHRra) are correlated with severity of sleep-disordered breathing (SDB), as quantified by the respiratory disturbance index (RDI). A total of 436 subjects, non-smoking, normotensive, and free of cardiovascular disease and diabetes were selected from the Sleep Heart Health Study (SHHS). Of these, 288 records with sufficiently high quality electrocardiogram signals were selected for further analysis [males/females: 221/67; age: 46.1 to 74.9 years; body mass index (BMI): 21.5 to 46.4 kg m⁻²; 0.3 < RDI < 85.0⁻¹]. From each polysomnogram, the respiration channels (thoracic and abdominal) and R-R interval (RRI) derived from the electrocardiogram were subjected to spectral analysis and autoregressive moving average modeling in consecutive 5-min segments. After adjusting for age and BMI, mean RRI was found to be negatively correlated with RDI in men in all sleep-wake states (all P  < 0.001). HFP and HFPra were negatively correlated with RDI in men only during wakefulness (all P  < 0.01). In women, LHR and LHRra were not correlated with RDI during wakefulness, but were positively correlated during non-rapid eye movement Stage 1 and 2 sleep (all P  < 0.01). These findings suggest that the indices of cardiac autonomic control are correlated with SDB severity, but gender and state affect the nature of these correlations. In both genders, however, vagal modulation of heart rate increases while sympathetic modulation decreases from wakefulness to sleep.     

Neurobehavioral correlates of sleep-disordered breathing in children

The effects of sleep-disordered breathing (SDB) on neurobehavioral function were examined in two matched groups of children from the general population. Thirty-five children with polysomnographically confirmed SDB were matched for ethnicity, age, gender, maternal educational attainment, and maternal smoking, to healthy children with no evidence of SDB. Children with SDB had significantly lower mean scores on the Differential Ability Scales for General Conceptual Ability (similar to IQ) and for the Non-verbal Cluster. On the neuropsychology assessment battery (NEPSY), children with SDB scored significantly lower than the control group on the attention/executive function domain and two subtests within that domain, one measuring visual attention and the other executive function. In addition, children with SDB scored significantly lower than the controls on one subtest from the NEPSY language domain: Phonological Processing. This subtest measures phonological awareness, a skill that is critical for learning to read. No differences in behavior, as measured by the Child Behavior Checklist (CBCL) or the Conners' Parent Rating Scale, were found between the two groups. Using a novel algorithm to assess sleep pressure, we found that children with SDB were significantly sleepier than controls. Furthermore, total arousal index was negatively correlated with neurocognitive abilities, suggesting a role for sleep fragmentation in pediatric SDB-induced cognitive dysfunction.     

Association between obstructive sleep apnea severity and endothelial dysfunction in an increased background of cardiovascular burden

The objective of this study is to examine whether increasing obstructive sleep apnea (OSA) severity is associated with worsening endothelial function. The design is a cross‐sectional examination of the baseline assessment of a multi‐centre randomized controlled clinical trial examining the effects of oxygen, continuous positive airway pressure (CPAP) therapy or lifestyle modifications on cardiovascular biomarkers. Participants were recruited from cardiology clinics at four sites. Participants with an apnea–hypopnea index (AHI) of 15–50 and known cardio/cerebrovascular disease (CVD) or CVD risk factors were included. OSA severity indices [oxygen desaturation index (ODI), AHI and percentage of sleep time below 90% oxygen saturation (total sleep time <90)] and a measure of endothelium‐mediated vasodilatation [Framingham reactive hyperaemia index (F‐RHI) derived from peripheral arterial tonometry (PAT)] were assessed. The sample included 267 individuals with a mean AHI of 25.0 ± 8.5 SD and mean F‐RHI 0.44 ± 0.38. In adjusted models, the slope of the relationship between ODI and F‐RHI differed above and below an ODI of 24.6 (P = 0.04), such that above an ODI of 24.6 there was a marginally significant decline in the geometric mean of the PAT ratio by 3% [95% confidence interval (CI): 0%, 5%; P = 0.05], while below this point, there was a marginally significant incline in the geometric mean of the PAT ratio by 13% (95% CI: 0%, 27%; P = 0.05) per 5‐unit increase in ODI. A similar pattern was observed between AHI and F‐RHI. No relation was noted with total sleep time <90 and F‐RHI. There was evidence of a graded decline in endothelial function in association with higher levels of intermittent hypoxaemia.