Erika W. Hagen

Increased Prevalence of Sleep-Disordered Breathing in Adults

Sleep-disordered breathing is a common disorder with a range of harmful sequelae. Obesity is a strong causal factor for sleep-disordered breathing, and because of the ongoing obesity epidemic, previous estimates of sleep-disordered breathing prevalence require updating. We estimated the prevalence of sleep-disordered breathing in the United States for the periods of 1988-1994 and 2007-2010 using data from the Wisconsin Sleep Cohort Study, an ongoing community-based study that was established in 1988 with participants randomly selected from an employed population of Wisconsin adults. A total of 1,520 participants who were 30-70 years of age had baseline polysomnography studies to assess the presence of sleep-disordered breathing. Participants were invited for repeat studies at 4-year intervals. The prevalence of sleep-disordered breathing was modeled as a function of age, sex, and body mass index, and estimates were extrapolated to US body mass index distributions estimated using data from the National Health and Nutrition Examination Survey. The current prevalence estimates of moderate to severe sleep-disordered breathing (apnea-hypopnea index, measured as events/hour, ≥15) are 10% (95% confidence interval (CI): 7, 12) among 30-49-year-old men; 17% (95% CI: 15, 21) among 50-70-year-old men; 3% (95% CI: 2, 4) among 30-49-year-old women; and 9% (95% CI: 7, 11) among 50-70 year-old women. These estimated prevalence rates represent substantial increases over the last 2 decades (relative increases of between 14% and 55% depending on the subgroup).

Obstructive Sleep Apnea during REM Sleep and Hypertension. Results of the Wisconsin Sleep Cohort

RATIONALE Obstructive sleep apnea (OSA) is associated with hypertension. OBJECTIVES We aimed to quantify the independent association of OSA during REM sleep with prevalent and incident hypertension. METHODS We included adults enrolled in the longitudinal community-based Wisconsin Sleep Cohort Study with at least 30 minutes of REM sleep obtained from overnight in-laboratory polysomnography. Studies were repeated at 4-year intervals to quantify OSA. Repeated measures logistic regression models were fitted to explore the association between REM sleep OSA and prevalent hypertension in the entire cohort (n = 4,385 sleep studies on 1,451 individuals) and additionally in a subset with ambulatory blood pressure data (n = 1,085 sleep studies on 742 individuals). Conditional logistic regression models were fitted to longitudinally explore the association between REM OSA and development of hypertension. All models controlled for OSA events during non-REM sleep, either by statistical adjustment or by stratification. MEASUREMENTS AND MAIN RESULTS Fully adjusted models demonstrated significant dose-relationships between REM apnea-hypopnea index (AHI) and prevalent hypertension. The higher relative odds of prevalent hypertension were most evident with REM AHI greater than or equal to 15. In individuals with non-REM AHI less than or equal to 5, a twofold increase in REM AHI was associated with 24% higher odds of hypertension (odds ratio, 1.24; 95% confidence interval, 1.08-1.41). Longitudinal analysis revealed a significant association between REM AHI categories and the development of hypertension (P trend = 0.017). Non-REM AHI was not a significant predictor of hypertension in any of the models. CONCLUSIONS Our findings indicate that REM OSA is cross-sectionally and longitudinally associated with hypertension. This is clinically relevant because treatment of OSA is often limited to the first half of the sleep period leaving most of REM sleep untreated.

Association Between Asthma and Risk of Developing Obstructive Sleep Apnea

IMPORTANCE Obstructive sleep apnea (OSA) is more common among patients with asthma; whether asthma is associated with the development of OSA is unknown. OBJECTIVE To examine the prospective relationship of asthma with incident OSA. DESIGN, SETTING, AND PARTICIPANTS Population-based prospective epidemiologic study (the Wisconsin Sleep Cohort Study) beginning in 1988. Adult participants were recruited from a random sample of Wisconsin state employees to attend overnight polysomnography studies at 4-year intervals. Asthma and covariate information were assessed during polysomnography studies through March 2013. Eligible participants were identified as free of OSA (apnea-hypopnea index [AHI] of <5 events/h and not treated) by 2 baseline polysomnography studies. There were 1105 4-year follow-up intervals provided by 547 participants (52% women; mean [SD] baseline age, 50 [8] years). EXPOSURES Questionnaire-assessed presence and duration of self-reported physician-diagnosed asthma. MAIN OUTCOMES AND MEASURES The associations of presence and duration of asthma with 4-year incidences of both OSA (AHI of ≥5 or positive airway pressure treatment) and OSA concomitant with habitual daytime sleepiness were estimated using repeated-measures Poisson regression, adjusting for confounders. RESULTS Twenty-two of 81 participants (27% [95% CI, 17%-37%]) with asthma experienced incident OSA over their first observed 4-year follow-up interval compared with 75 of 466 participants (16% [95% CI, 13%-19%]) without asthma. Using all 4-year intervals, participants with asthma experienced 45 cases of incident OSA during 167 4-year intervals (27% [95% CI, 20%-34%]) and participants without asthma experienced 160 cases of incident OSA during 938 4-year intervals (17% [95% CI, 15%-19%]); the corresponding adjusted relative risk (RR) was 1.39 (95% CI, 1.06-1.82), controlling for sex, age, baseline and change in body mass index, and other factors. Asthma was also associated with new-onset OSA with habitual sleepiness (RR, 2.72 [95% CI, 1.26-5.89], P = .045). Asthma duration was related to both incident OSA (RR, 1.07 per 5-year increment in asthma duration [95% CI, 1.02-1.13], P = .01) and incident OSA with habitual sleepiness (RR, 1.18 [95% CI, 1.07-1.31], P = .02). CONCLUSIONS AND RELEVANCE Asthma was associated with an increased risk of new-onset OSA. Studies investigating the mechanisms underlying this association and the value of periodic OSA evaluation in patients with asthma are warranted.

Coronary heart disease incidence in sleep disordered breathing: the Wisconsin Sleep Cohort Study.

STUDY OBJECTIVES The aim of the study was to determine the association of objectively measured sleep disordered breathing (SDB) with incident coronary heart disease (CHD) or heart failure (HF) in a nonclinical population. DESIGN Longitudinal analysis of a community-dwelling cohort followed up to 24 y. SETTING Sleep laboratory at the Clinical Research Unit of the University of Wisconsin Hospital and Clinics. PARTICIPANTS There were 1,131 adults who completed one or more overnight polysomnography studies, were free of CHD or HF at baseline, were not treated by continuous positive airway pressure (CPAP), and followed over 24 y. INTERVENTIONS None. MEASUREMENTS AND RESULTS In-laboratory overnight polysomnography was used to assess SDB, defined by the apnea-hypopnea index (AHI) using apnea and hypopnea events per hour of sleep. Incident CHD or HF was defined by new reports of myocardial infarction, coronary revascularization procedures, congestive heart failure, and cardiovascular deaths. We used baseline AHI as the predictor variable in survival analysis models predicting CHD or HF incidence adjusted for traditional confounders. The incidence of CHD or HF was 10.9/1,000 person-years. The mean time to event was 11.2 ± 5.8 y. After adjusting for age, sex, body mass index, and smoking, estimated hazard ratios (95% confidence interval) of incident CHD or HF were 1.5 (0.9-2.6) for AHI > 0-5, 1.9 (1.05-3.5) for AHI 5 ≤ 15, 1.8 (0.85-4.0) for AHI 15 ≤ 30, and 2.6 (1.1-6.1) for AHI > 30 compared to AHI = 0 (P trend = 0.02). CONCLUSIONS Participants with untreated severe sleep disordered breathing (AHI > 30) were 2.6 times more likely to have an incident coronary heart disease or heart failure compared to those without sleep disordered breathing. Our findings support the postulated adverse effects of sleep disordered breathing on coronary heart disease and heart failure.

Preconception Mental Health Predicts Pregnancy Complications and Adverse Birth Outcomes: A National Population-Based Study

Pregnancy complications and poor birth outcomes can affect the survival and long-term health of children. The preconception period represents an opportunity to intervene and improve outcomes; however little is known about women’s mental health prior to pregnancy as a predictor of such outcomes. We sought to determine if and to what extent women’s preconception mental health status impacted subsequent pregnancy complications, non-live birth, and birth weight using a nationally representative, population-based sample. We used pooled 1996–2006 data from the nationally-representative Medical Expenditure Panel Survey (MEPS). Poor preconception mental health was defined as women’s global mental health rating of “fair” or “poor” before conception. Logistic regression was used to assess the association between preconception mental health and pregnancy complications, non-live birth, and having a low birth weight baby within the follow up period. Poor preconception mental health was associated with increased odds of experiencing any pregnancy complication (AOR 1.40, 95% CI: 1.02–1.92), having a non-live birth (AOR 1.48, 95% CI: 0.96–2.27), and having a low birth weight baby (AOR 1.99, 95% CI: 1.00–3.98), all controlling for maternal age, race/ethnicity, marital status, education, health insurance status, income, and number of children in the household. Significant racial and ethnic disparities exist for pregnancy complications and non-live births, but not for low birth weight. Women’s preconception mental health is a modifiable risk factor that stands to reduce the incidence of adverse pregnancy complications and birth outcomes.

The prevalence and determinants of antepartum mental health problems among women in the USA: a nationally representative population-based study

Mental health problems disproportionately affect women, particularly during childbearing years. We sought to estimate the prevalence of antepartum mental health problems and determine potential risk factors in a representative USA population. We examined data on 3,051 pregnant women from 11 panels of the 1996–2006 Medical Expenditure Panel Survey. Poor antepartum mental health was defined by self report of mental health conditions or symptoms or a mental health rating of “fair” or “poor.” Multivariate regression analyses modeled the odds of poor antepartum mental health; 7.8% of women reported poor antepartum mental health. A history of mental health problems increased the odds of poor antepartum mental health by a factor of 8.45 (95% CI, 6.01–11.88). Multivariate analyses were stratified by history of mental health problems. Significant factors among both groups included never being married and self-reported fair/poor health status. This study identifies key risk factors associated with antepartum mental health problems in a nationally representative sample of pregnant women. Women with low social support, in poor health, or with a history of poor mental health are at an increased risk of having antepartum mental health problems. Understanding these risk factors is critical to improve the long-term health of women and their children.

Obstructive sleep apnoea during REM sleep and incident non-dipping of nocturnal blood pressure: a longitudinal analysis of the Wisconsin Sleep Cohort

Background Non-dipping of nocturnal blood pressure (BP) is associated with target organ damage and cardiovascular disease. Obstructive sleep apnoea (OSA) is associated with incident non-dipping. However, the relationship between disordered breathing during rapid eye movement (REM) sleep and the risk of developing non-dipping has not been examined. This study investigates whether OSA during REM sleep is associated with incident non-dipping. Methods Our sample included 269 adults enrolled in the Wisconsin Sleep Cohort Study who completed two or more 24 h ambulatory BP studies over an average of 6.6 years of follow-up. After excluding participants with prevalent non-dipping BP or antihypertensive use at baseline, there were 199 and 215 participants available for longitudinal analysis of systolic and diastolic non-dipping, respectively. OSA in REM and non-REM sleep were defined by apnoea hypopnoea index (AHI) from baseline in-laboratory polysomnograms. Systolic and diastolic non-dipping were defined by systolic and diastolic sleep/wake BP ratios >0.9. Modified Poisson regression models estimated the relative risks for the relationship between REM AHI and incident non-dipping, adjusting for non-REM AHI and other covariates. Results There was a dose–response greater risk of developing systolic and diastolic non-dipping BP with greater severity of OSA in REM sleep (p-trend=0.021 for systolic and 0.024 for diastolic non-dipping). Relative to those with REM AHI<1 event/h, those with REM AHI≥15 had higher relative risk of incident systolic non-dipping (2.84, 95% CI 1.10 to 7.29) and incident diastolic non-dipping (4.27, 95% CI 1.20 to 15.13). Conclusions Our findings indicate that in a population-based sample, REM OSA is independently associated with incident non-dipping of BP.

Access to Adequate Outpatient Depression Care for Mothers in the USA: A Nationally Representative Population-Based Study

Maternal depression is often untreated, resulting in serious consequences for mothers and their children. Factors associated with receipt of adequate treatment for depression were examined in a population-based sample of 2,130 mothers in the USA with depression using data from the 1996–2005 Medical Expenditure Panel Survey. Chi-squared analyses were used to evaluate differences in sociodemographic and health characteristics by maternal depression treatment status (none, some, and adequate). Multivariate regression was used to model the odds of receiving some or adequate treatment, compared to none. Results indicated that only 34.8% of mothers in the USA with depression received adequate treatment. Mothers not in the paid workforce and those with health insurance were more likely to receive treatment, while minority mothers and those with less education were less likely to receive treatment. Understanding disparities in receipt of adequate treatment is critical to designing effective interventions, reducing treatment inequities, and ultimately improving the mental health and health of mothers and their families.Maternal depression is often untreated, resulting in serious consequences for mothers and their children. Factors associated with receipt of adequate treatment for depression were examined in a population-based sample of 2,130 mothers in the USA with depression using data from the 1996–2005 Medical Expenditure Panel Survey. Chi-squared analyses were used to evaluate differences in sociodemographic and health characteristics by maternal depression treatment status (none, some, and adequate). Multivariate regression was used to model the odds of receiving some or adequate treatment, compared to none. Results indicated that only 34.8% of mothers in the USA with depression received adequate treatment. Mothers not in the paid workforce and those with health insurance were more likely to receive treatment, while minority mothers and those with less education were less likely to receive treatment. Understanding disparities in receipt of adequate treatment is critical to designing effective interventions, reducing treatment inequities, and ultimately improving the mental health and health of mothers and their families.

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 (&bgr;=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.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 (β=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. # Significance {#article-title-30}

School achievement in a regional cohort of children born very low birthweight.

Children born very low birthweight (VLBW, <=1500 g) have historically had lower average school achievement than their normal birthweight peers. However, perinatal care and survival have changed dramatically since prior cohorts accrued, prompting reassessment. Surfactant therapy became generally available 8/1/1990, and the use of ante- and postnatal steroids increased substantially around this time. Standardized test scores and teacher ratings in math, reading, science, and social studies were obtained at age 10 for a cohort of children admitted to six regional NICUs in Wisconsin and Iowa, 8/1/1988 - 6/30/1991. We compared achievement between the VLBW cohort and controls from the same school districts. Among VLBW children, we determined neonatal and early childhood factors associated with achievement on standardized tests (ordinal logistic regression) and teacher ratings (linear regression) and evaluated whether achievement differed by birth year. Compared to population controls, VLBW childrens greatest deficits occurred in mathematics. Scores on the standardized math exam and teacher ratings of overall achievement were positively associated with birthweight, social function measured at age five, and socioeconomic status. VLBW children born in the post-surfactant era (after 8/1/1990) had lower achievement on the standardized math exam than children born during the pre-surfactant era of the prior two years. Lower achievement in the post-surfactant era may be due to greater survival among less healthy neonates or increased exposure to postnatal steroids. VLBW children more likely to struggle academically could be identified by early childhood measures, allowing for targeted interventions to mitigate their difficulties.