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 m(2). 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.

Obstructive sleep apnea is associated with future subclinical carotid artery disease: thirteen-year follow-up from the Wisconsin sleep cohort.

OBJECTIVE: To determine the longitudinal associations between obstructive sleep apnea, carotid artery intima-media thickness (IMT), and plaque. APPROACH AND RESULTS: This is a population-based, prospective cohort study conducted from July, 1989, to November, 2012, on 790 randomly selected Wisconsin residents who completed a mean of 3.5 (range, 1-6) polysomnograms during the study period. Obstructive sleep apnea was characterized by the apnea-hypopnea index (AHI, events/h). Common carotid artery IMT and plaque were assessed by B-mode ultrasound. The mean (SD) time from the first polysomnograms to carotid ultrasound was 13.5 (3.6) years. Multivariable regression models were created to estimate the independent associations of baseline and cumulative obstructive sleep apnea exposure with subsequent carotid IMT and plaque. At baseline, the mean age of participants was 47.6 (7.7) years (55% men, 97% white). AHI was 4.4 (9.0) events/h (range, 0-97); 7% had AHI >15 events/h. Carotid IMT was 0.755 (0.161) mm; 63% had plaque. Adjusting for age, sex, body mass index, systolic blood pressure, smoking, and use of lipid-lowering, antihypertensive, and antidiabetic medications, baseline AHI independently predicted future carotid IMT (ß=0.027 mm/unit log10[AHI+1]; P=0.049), plaque presence (odds ratio, 1.55 [95% confidence intervals, 1.02-2.35]; P=0.041) and plaque score (odds ratio, 1.30 [1.05-1.61]; P=0.018). In cumulative risk factor-adjusted models, AHI independently predicted future carotid plaque presence (P=0.012) and score (P=0.039), but not IMT (P=0.608). CONCLUSIONS: Prevalent obstructive sleep apnea is independently associated with increased carotid IMT and plaque more than a decade later, indicating increased future cardiovascular disease risk.

Burden of sleep apnea: rationale, design, and major findings of the Wisconsin Sleep Cohort study.

CONTEXT: Untreated sleep apnea is a prevalent but treatable condition of breathing pauses during sleep. With approximately 15% of the US population affected, understanding of the total health burden is necessary to guide policy, population initiatives, and clinical practice to reduce the prevalence of this condition. OBJECTIVE: To outline the history and need for a population approach to understanding sleep apnea and provide a review of the first longitudinal population study of this disorder. DATA SOURCE: The results of cross-sectional and longitudinal data from 1500 participants in the Wisconsin Sleep Cohort, initiated 2 decades ago, illustrate the population burden of sleep apnea. RESULTS: The prevalence of sleep apnea is increasing with trends of increased obesity. Prospective findings from 4- to 15-year follow-up data indicate untreated sleep apnea predicts increased blood pressure, hypertension, stroke, depression, and mortality. CONCLUSIONS: The high prevalence of untreated sleep apnea and links to serious morbidity and mortality underscore the population burden of this condition and the need for greater clinical recognition and strategies to reduce prevalence.

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.

Longitudinal association of sleep-related breathing disorder and depression.

BACKGROUND: Sleep-related breathing disorder (SRBD) and depression have each been independently associated with substantial morbidity, impairment, and disability. The development of clinical strategies for screening and managing depression in patients with SRBD requires elucidation of the association between the 2 conditions. This population-based epidemiological study assesses SRBD as a longitudinal predictor of depression. METHODS: Men (n = 788) and women (n = 620) randomly selected from a working population were evaluated for SRBD by in-laboratory polysomnography and for depression by the Zung depression scale. Results of multiple studies, performed at 4-year intervals, were available for most participants. Sleep-related breathing disorder was characterized by the apnea-hypopnea index (AHI; events per hour) categories: AHI = 0, no SRBD; 0 < AHI < 5, minimal SRBD; 5 < or = AHI < 15, mild SRBD; and AHI > or = 15, moderate or worse SRBD. Depression was defined as a score of 50 or higher on the Zung scale or use of antidepressants. Potential confounding, interacting, and mediating factors were assessed by clinical measurements and questionnaires. RESULTS: In purely longitudinal models, an increase of 1 SRBD category (eg, from minimal to mild SRBD) was associated with a 1.8-fold (95% confidence interval, 1.3-2.6) increased adjusted odds for development of depression. In adjusted models combining longitudinal and cross-sectional associations, compared with participants with no SRBD, the odds for development of depression were increased by 1.6-fold (95% confidence interval, 1.2-2.1) in participants with minimal SRBD, by 2.0-fold (95% confidence interval, 1.4-2.9) in participants with mild SRBD, and by 2.6-fold (95% confidence interval, 1.7-3.9) in those with moderate or worse SRBD. CONCLUSION: Our longitudinal findings of a dose-response association between SRBD and depression provide evidence consistent with a causal link between these conditions and should heighten clinical suspicion of depression in patients with SRBD.

Effects of Obstructive Sleep Apnea and Obesity on Cardiac Remodeling: The Wisconsin Sleep Cohort Study.

STUDY OBJECTIVES: To characterize the prospective associations of obstructive sleep apnea (OSA) with future echocardiographic measures of adverse cardiac remodeling. METHODS: This was a prospective long-term observational study. Participants had overnight polysomnography followed by transthoracic echocardiography a mean (standard deviation) of 18.0 (3.7) y later. OSA was characterized by the apnea-hypopnea index (AHI, events/hour). Echocardiography was used to assess left ventricular (LV) systolic and diastolic function and mass, left atrial volume and pressure, cardiac output, systemic vascular resistance, and right ventricular (RV) systolic function, size, and hemodynamics. Multivariate regression models estimated associations between log10(AHI+1) and future echocardiographic findings. A secondary analysis looked at oxygen desaturation indices and future echocardiographic findings. RESULTS: At entry, the 601 participants were mean (standard deviation) 47 (8) y old (47% female). After adjustment for age, sex, and body mass index, baseline log10(AHI+1) was associated significantly with future reduced LV ejection fraction and tricuspid annular plane systolic excursion (TAPSE) ≤ 15 mm. After further adjustment for cardiovascular risk factors, participants with higher baseline log10(AHI+1) had lower future LV ejection fraction (ß = -1.35 [standard error = 0.6]/log10(AHI+1), P = 0.03) and higher odds of TAPSE ≤ 15 mm (odds ratio = 6.3/log10(AHI+1), 95% confidence interval = 1.3-30.5, P = 0.02). SaO2 desaturation indices were associated independently with LV mass, LV wall thickness, and RV area (all P < 0.03). CONCLUSIONS: OSA is associated independently with decreasing LV systolic function and with reduced RV function. Echocardiographic measures of adverse cardiac remodeling are strongly associated with OSA but are confounded by obesity. Hypoxia may be a stimulus for hypertrophy in individuals with OSA.

The effect of correction of sleep-disordered breathing on BP in untreated hypertension.

OBJECTIVES: To compare BP response to 3 weeks of nasal continuous positive airway pressure (CPAP) in hypertensive patients with and without sleep-disordered breathing (SDB). DESIGN: A controlled, interventional trial of nasal CPAP in patients with and without SDB. PARTICIPANTS AND SETTING: Twenty-four men, aged 30 to 60 years, with mild to moderate untreated hypertension recruited from employee health and primary care clinics. METHODS: Based on in-laboratory polysomnography, 14 hypertensive patients had SDB, defined by five or more episodes of apnea and hypopnea per hour of sleep (apnea-hypopnea index [AHI], > or = 5), and 10 had no SDB (AHI, < 5). We performed 24-h ambulatory BP monitoring on all patients at baseline, during CPAP, and after CPAP treatment. In patients with an AHI > or = 5, nasal CPAP was titrated to reduce the AHI to < 5. Patients with an AHI < 5 received CPAP of 5 cm H(2)O to control for any potential effect of CPAP per se on BP. Both groups received CPAP for 3 weeks. RESULTS: After adjusting for age and body mass index, the mean nocturnal systolic and diastolic BP changes after CPAP treatment in the SDB group were significantly different from those in the no-SDB group: -7.8 vs +0.3 mm Hg (p = 0.02), and -5.3 vs -0.7 mm Hg (p = 0.03), respectively. There was a similar, although statistically insignificant, difference in the adjusted mean daytime systolic and diastolic BP changes after CPAP treatment between the two groups (-2.7 vs +0.4 mm Hg and -2.3 vs -1.7 mm Hg, respectively). CONCLUSIONS: Three weeks of nasal CPAP treatment of SDB in hypertensive men caused the lowering of nocturnal systolic and diastolic BP values, suggesting that increased nocturnal BP in persons with hypertension was causally related to the apnea and hypopnea events of SDB.

Hemoglobinopathy case finding by pulse oximetry.

Pulse oximetry is a widely used, noninvasive instrument for monitoring oxygen saturation. Its use, however, is limited in the setting of dyshemoglobinemias. We report a case of hemoglobin Rothschild in an Asian patient diagnosed as a result of routine pulse oximetry. This case reiterates the limitations of pulse oximetry in patients with dyshemoglobinemias, while introducing its use as a case-finding tool for such conditions.