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1.  The Sleep-Time Cost of Parenting: Sleep Duration and Sleepiness Among Employed Parents in the Wisconsin Sleep Cohort Study 
American Journal of Epidemiology  2013;177(5):394-401.
Insufficient sleep is associated with poor health and increased mortality. Studies on whether parenthood (including consideration of number and ages of children) is associated with sleep duration or sleep problems are scant and inconclusive. Using data collected in the Wisconsin Sleep Cohort Study (n = 4,809) between 1989 and 2008, we examined cross-sectional associations of number and ages of children with self-reported parental sleep duration, daytime sleepiness, and dozing among employed adults. Longitudinal change in sleep duration over 19 years was examined to evaluate changes in parental sleep associated with children transitioning into adulthood (n = 833). Each child under age 2 years was associated with 13 fewer minutes of parental sleep per day (95% confidence interval (CI): 5, 21); each child aged 2–5 years was associated with 9 fewer minutes of sleep (95% CI: 5, 13); and each child aged 6–18 years was associated with 4 fewer minutes (95% CI: 2, 6). Adult children were not associated with shorter parental sleep duration. Parents of children over age 2 years were significantly more likely to experience daytime sleepiness and dozing during daytime activities. Parents of minor children at baseline had significantly greater increases in sleep duration over 19 years of follow-up. Parenting minor children is associated with shorter sleep duration. As children age into adulthood, the sleep duration of parents with more children approaches that of parents with fewer children.
doi:10.1093/aje/kws246
PMCID: PMC3626047  PMID: 23378502
adult; cohort studies; humans, middle aged; parents; sleep; sleep duration
2.  Perceived neighborhood quality, sleep quality, and health status: Evidence from the Survey of the Health of Wisconsin 
Why does living in a disadvantaged neighborhood predict poorer mental and physical health? Recent research focusing on the Southwestern United States suggests that disadvantaged neighborhoods favor poor health, in part, because they undermine sleep quality. Building on previous research, we test whether this process extends to the Midwestern United States. Specifically, we use cross-sectional data from the Survey of the Health of Wisconsin (SHOW), a statewide probability sample of Wisconsin adults, to examine whether associations among perceived neighborhood quality (e.g., perceptions of crime, litter, and pleasantness in the neighborhood) and health status (overall self-rated health and depression) are mediated by overall sleep quality (measured as self-rated sleep quality and physician diagnosis of sleep apnea). We find that perceptions of low neighborhood quality are associated with poorer self-rated sleep quality, poorer self-rated health, and more depressive symptoms. We also observe that poorer self-rated sleep quality is associated with poorer self-rated health and more depressive symptoms. Our mediation analyses indicate that self-rated sleep quality partially mediates the link between perceived neighborhood quality and health status. Specifically, self-rated sleep quality explains approximately 20% of the association between neighborhood quality and self-rated health and nearly 19% of the association between neighborhood quality and depression. Taken together, these results confirm previous research and extend the generalizability of the indirect effect of perceived neighborhood context on health status through sleep quality.
doi:10.1016/j.socscimed.2012.07.021
PMCID: PMC3733364  PMID: 22901794
Sleep; Sleep quality; Neighborhood context; Neighborhood quality; Self-rated health; Depression; Wisconsin; USA
3.  Sleep-disordered breathing and retinal microvascular diameter 
Atherosclerosis  2012;226(1):124-128.
Background
Sleep-disordered breathing (SDB) is an emerging risk factor for cardiovascular disease (CVD). Microvascular dysfunction has been proposed as a potential mechanism in the pathogenesis of CVD in SDB. The retinal vasculature offers a unique opportunity to investigate the systemic effects of microvascular dysfunction as it can be viewed non-invasively and is also structurally and functionally similar to microvasculature elsewhere in the body. We therefore examined the association between SDB and retinal microvascular diameter after adjusting for major confounders.
Methods
We examined n=476 participants from the Wisconsin Sleep Cohort Study. SDB was characterized using the apnea-hypopnea index (AHI) as <5 events/hr, 5-14.9 events/hr, and ≥15 events/hr. Outcomes of interest included the presence of retinal arteriolar narrowing (mean retinal arteriolar diameter <141.0 um) and retinal venular widening (mean venular diameter >223.0 um).
Results
Higher AHI was found to be positively associated with retinal venular dilatation, independent of body mass index, hypertension, diabetes, and lipid levels. Compared to an AHI of <5 events/hr (referent), the multivariable-adjusted odds ratio of retinal venular widening for an AHI of 5-14.9 events/hr was 1.31(0.75-2.28) and for an AHI of >15 events/hr was 2.08 (1.03-2.16); p-trend=0.045. In contrast, there was no association between AHI and retinal arteriolar narrowing (p-trend=0.72).
Conclusion
Higher AHI, a marker of SDB, was positively associated with wider retinal venules, independent of age, gender, BMI, hypertension, diabetes, and lipid levels. These data suggest that the association of SDB with cardiovascular disease may be mediated, in part, by microvasculature.
doi:10.1016/j.atherosclerosis.2012.10.046
PMCID: PMC3529805  PMID: 23137824
SDB; retinal arteriolar diameter; AHI
4.  Aging reduces the association between sleepiness and sleep-disordered breathing 
Aim
To investigate age-related changes in sleepiness symptoms associated with sleep disordered breathing (SDB).
Methods
Wisconsin Sleep Cohort participants were assessed with polysomnography, Epworth Sleepiness Scale (ESS) and Multiple Sleep Latency Test (MSLT). SDB was defined as an apnea/hypopnea index≥15 events/hour, sleepiness as ESS≥10 and MSLT≤5 minutes. Odds ratios were calculated using generalized estimating equations associating sleepiness with SDB, and conditional logistic regression examining changes in longitudinal sleepiness status (ESS only). Models were, a priori, stratified by gender.
Results
ESS was measured in 1281 participants and MSLT in 998, at multiple time points (ESS n=3695; MSLT n=1846). Significant interactions were found between SDB and age in men, but not women. The odds ratios (OR) modeled for sleepiness in a 40 year old male with SDB were significant, compared to a male without SDB (OR: ESS 2.1; MSLT 2.9); however, these associations were not significant at 60 years. The within-subject odds ratio for sleepiness was also significant at 40 years (OR: 3.4), but not at 60 years.
Conclusion
The age-related reductions in the association between sleepiness and SDB may have clinical implications for the diagnosis and treatment of SDB in older people since sleepiness is often used as a therapeutic marker.
doi:10.1183/09031936.00177411
PMCID: PMC3608395  PMID: 22241742
Sleep disordered breathing; Obstructive sleep apnea; Aging; Sleepiness
5.  Sleep-disordered Breathing and Cancer Mortality 
Rationale: Sleep-disordered breathing (SDB) has been associated with total and cardiovascular mortality, but an association with cancer mortality has not been studied. Results from in vitro and animal studies suggest that intermittent hypoxia promotes cancer tumor growth.
Objectives: The goal of the present study was to examine whether SDB is associated with cancer mortality in a community-based sample.
Methods: We used 22-year mortality follow-up data from the Wisconsin Sleep Cohort sample (n = 1,522). SDB was assessed at baseline with full polysomnography. SDB was categorized using the apnea-hypopnea index (AHI) and the hypoxemia index (percent sleep time below 90% oxyhemoglobin saturation). The hazards of cancer mortality across levels of SDB severity were compared using crude and multivariate analyses.
Measurements and Main Results: Adjusting for age, sex, body mass index, and smoking, SDB was associated with total and cancer mortality in a dose–response fashion. Compared with normal subjects, the adjusted relative hazards of cancer mortality were 1.1 (95% confidence interval [CI], 0.5–2.7) for mild SDB (AHI, 5–14.9), 2.0 (95% CI, 0.7–5.5) for moderate SDB (AHI, 15–29.9), and 4.8 (95% CI, 1.7–13.2) for severe SDB (AHI ≥ 30) (P-trend = 0.0052). For categories of increasing severity of the hypoxemia index, the corresponding relative hazards were 1.6 (95% CI, 0.6–4.4), 2.9 (95% CI, 0.9–9.8), and 8.6 (95% CI, 2.6–28.7).
Conclusions: Our study suggests that baseline SDB is associated with increased cancer mortality in a community-based sample. Future studies that replicate our findings and look at the association between sleep apnea and survival after cancer diagnosis are needed.
doi:10.1164/rccm.201201-0130OC
PMCID: PMC3406081  PMID: 22610391
cancer; cohort study; mortality; obstructive sleep apnea; sleep-disordered breathing
6.  Exercise is associated with a reduced incidence of sleep-disordered breathing 
The American Journal of Medicine  2012;125(5):485-490.
Background
The effect of exercise on sleep-disordered breathing is unknown. While diet and weight loss have been shown to reduce the severity of sleep-disordered breathing, it is unclear whether exercise has an independent effect.
Methods
A population-based longitudinal epidemiologic study of adults measured the association between exercise and incidence and severity of sleep-disordered breathing. Hours of weekly exercise were assessed by two mailed surveys (1988 and 2000). Sleep-disordered breathing was assessed by 18-channel in-laboratory polysomnography at baseline and at follow up.
Results
Associations were modeled using linear and logistic regression, adjusting for body mass index, age, sex, and other covariates. Hours of exercise were associated with reduced incidence of mild (Odds Ratio = 0.76, p= 0.011) and moderate (Odds Ratio = 0.67, p= 0.002) sleep-disordered breathing. Also a decrease in exercise duration was associated with worsening sleep-disordered breathing, as measured by the apnea-hypopnea index, AHI (ß = 2.368, p= 0.048). Adjustment for body mass index attenuated these effects.
Conclusions
Exercise is associated with a reduced incidence of mild and moderate sleep-disordered breathing and decreasing exercise is associated with worsening of sleep-disordered breathing. The effect of exercise on sleep-disordered breathing appears to be largely, but perhaps not entirely, mediated by changes in body habitus.
doi:10.1016/j.amjmed.2011.11.025
PMCID: PMC3339801  PMID: 22482846
Exercise; Sleep Apnea
7.  The Impact of Obesity on Oxygen Desaturation during Sleep-disordered Breathing 
Rationale: Obesity increases the risk and severity of sleep-disordered breathing. The degree to which excess body weight contributes to blood oxygen desaturation during hypopneic and apneic events has not been comprehensively characterized.
Objectives: To quantify the association between excess body weight and oxygen desaturation during sleep-disordered breathing.
Methods: A total of 750 adult participants in the Wisconsin Sleep Cohort Study were assessed for body mass index (BMI) (kg/m2) and sleep-disordered breathing. The amount of SaO2, duration, and other characteristics of 37,473 observed breathing events were measured during polysomnography studies. A mixed-effects linear regression model estimated the association of blood oxygen desaturation with participant-level characteristics, including BMI, gender, and age, and event-level characteristics, including baseline SaO2, change in Vt, event duration, sleep state, and body position.
Measurements and Main Results: BMI was positively associated with oxygen desaturation severity independent of age, gender, sleeping position, baseline SaO2, and event duration. BMI interacted with sleep state such that BMI predicted greater desaturation in rapid eye movement (REM) sleep than in non-REM sleep. Each increment of 10 kg/m2 BMI predicted a 1.0% (SE, 0.2%) greater mean blood oxygen desaturation for persons in REM sleep experiencing hypopnea events associated with 80% Vt reductions.
Conclusions: Excess body weight is an important predictor of the severity of blood oxygen desaturation during apnea and hypopnea events, potentially exacerbating the impact of sleep-disordered breathing in obese patients.
doi:10.1164/rccm.200905-0773OC
PMCID: PMC2778152  PMID: 19644043
sleep apnea; overweight; hypoxia
8.  β2 adrenergic receptor polymorphisms and nocturnal blood pressure dipping status in the Wisconsin Sleep Cohort Study 
Non-dipping nocturnal blood pressure (BP) is associated with target organ damage and cardiovascular disease. We hypothesized that β1- and β2-AR-associated SNPs would associate with non-dipping BP patterns. Participants (N=497, age range 30–74 years, 40% female) of the Wisconsin Sleep Cohort Study with at least one ambulatory BP monitoring test were included. Non-dipping was defined as less than a 10% dip in sleep BP compared to wake BP. Dipping ratios were calculated as sleep/wake BP. Single nucleotide polymorphisms in the β1-AR (rs7076938, tagging for Gly389Arg) and β2-AR (rs17778257 and rs2400707, tagging for Arg16Gly and Gln27Glu) were selected. β2-AR SNP rs2400707 A-positive subjects (tagging for Glu27) had higher systolic and diastolic dipping ratios in a dose-response fashion. Systolic dipping ratios were: GG=0.846; AG=0.854; AA=0.861 (p-trend=0.015). Diastolic dip ratios were: GG=0.807; AG=0.815; AA=0.824 (p-trend=0.026). The β2-AR rs17778257/rs2400707 A/A haplotype was associated with dipping ratios and systolic non-dipping status (non-dipping OR 2.0 [1.0, 3.8] for A/A versus A/G). Results were similar when models included participants on antihypertensive medications. Higher dipping ratios indicating a lack of nocturnal BP dipping are associated with β2-AR polymorphisms. Nocturnal dipping patterns may be modulated by β2-AR polymorphisms.
doi:10.1016/j.jash.2011.01.005
PMCID: PMC3071556  PMID: 21414566
single nucleotide polymorphisms; sympathetic nervous system; ambulatory blood pressure
9.  Effects of Sleep-disordered Breathing on Cerebrovascular Regulation 
Rationale: Cerebrovascular regulation is impaired in patients with moderate to severe obstructive sleep apnea; however, it is unknown whether this impairment exists in individuals with less severe sleep-disordered breathing.
Objectives: To test the hypothesis that cerebrovascular responses to hypercapnia are attenuated in a nonclinical population-based cohort.
Methods: A rebreathing test that raised end-tidal CO2 tension by 10 mm Hg was performed during wakefulness in 373 participants of the Wisconsin Sleep Cohort.
Measurements and Main Results: We measured cerebral flow velocity (transcranial Doppler ultrasound); heart rate (electrocardiogram); blood pressure (photoplethysmograph); ventilation (pneumotachograph); and end-tidal CO2 (expired gas analysis). Cerebrovascular CO2 responsiveness was quantified as the slope of the linear relationship between flow velocity and end-tidal CO2 during rebreathing. Linear regression analysis was performed using cerebrovascular CO2 responsiveness as the outcome variable. Main independent variables were the apnea–hypopnea index and the mean level of arterial oxygen saturation during sleep. We observed a positive correlation between cerebrovascular CO2 responsiveness and the mean level of oxygen saturation during sleep that was statistically significant in unadjusted analysis and after adjustment for known confounders and the increase in arterial pressure during rebreathing. Each 5% decrease in SaO2 during sleep predicted a decrease in cerebrovascular reactivity of 0.4 ± 0.2 cm/second/mm Hg PETCO2. In contrast, the negative correlation between cerebrovascular CO2 responsiveness and apnea–hypopnea index was statistically significant only in the unadjusted analysis.
Conclusions: Hypercapnic vasodilation in the cerebral circulation is blunted in individuals with sleep-disordered breathing. This impairment is correlated with hypoxemia during sleep.
doi:10.1164/rccm.201002-0313OC
PMCID: PMC3029932  PMID: 20639438
sleep apnea syndromes; cerebrovascular circulation; blood flow velocity; hypercapnia; endothelial function
10.  Prospective Associations of Insomnia Markers and Symptoms With Depression 
American Journal of Epidemiology  2010;171(6):709-720.
Whether insomnia, a known correlate of depression, predicts depression longitudinally warrants elucidation. The authors examined 555 Wisconsin Sleep Cohort Study participants aged 33–71 years without baseline depression or antidepressant use who completed baseline and follow-up overnight polysomnography and had complete questionnaire-based data on insomnia and depression for 1998–2006. Using Poisson regression, they estimated relative risks for depression (Zung scale score ≥50) at 4-year (average) follow-up according to baseline insomnia symptoms and polysomnographic markers. Twenty-six participants (4.7%) developed depression by follow-up. Having 3–4 insomnia symptoms versus none predicted depression risk (age-, sex-, and comorbidity-adjusted relative risk (RR) = 3.2, 95% confidence interval: 1.1, 9.6). After multiple adjustments, frequent difficulty falling asleep (RR = 5.3, 95% confidence interval: 1.1, 27.9) and polysomnographically assessed (upper or lower quartiles) sleep latency, continuity, and duration (RRs = 2.2–4.7; P’s ≤ 0.05) predicted depression. Graded trends (P-trend ≤ 0.05) were observed with increasing number of symptoms, difficulty falling asleep, and difficulty returning to sleep. Given the small number of events using Zung ≥50 (depression cutpoint), a limitation that may bias multivariable estimates, continuous depression scores were analyzed; mean values were largely consistent with dichotomous findings. Insomnia symptoms or markers increased depression risk 2.2- to 5.3-fold. These results support prior findings based on self-reported insomnia and may extend similar conclusions to objective markers. Heightened recognition and treatment of insomnia may prevent subsequent depression.
doi:10.1093/aje/kwp454
PMCID: PMC2842222  PMID: 20167581
depression; polysomnography; prospective studies; sleep; sleep initiation and maintenance disorders
11.  The Survey of the Health of Wisconsin (SHOW), a novel infrastructure for population health research: rationale and methods 
BMC Public Health  2010;10:785.
Background
Evidence-based public health requires the existence of reliable information systems for priority setting and evaluation of interventions. Existing data systems in the United States are either too crude (e.g., vital statistics), rely on administrative data (e.g., Medicare) or, because of their national scope (e.g., NHANES), lack the discriminatory power to assess specific needs and to evaluate community health activities at the state and local level. This manuscript describes the rationale and methods of the Survey of the Health of Wisconsin (SHOW), a novel infrastructure for population health research.
Methods/Design
The program consists of a series of independent annual surveys gathering health-related data on representative samples of state residents and communities. Two-stage cluster sampling is used to select households and recruit approximately 800-1,000 adult participants (21-74 years old) each year. Recruitment and initial interviews are done at the household; additional interviews and physical exams are conducted at permanent or mobile examination centers. Individual survey data include physical, mental, and oral health history, health literacy, demographics, behavioral, lifestyle, occupational, and household characteristics as well as health care access and utilization. The physical exam includes blood pressure, anthropometry, bioimpedance, spirometry, urine collection and blood draws. Serum, plasma, and buffy coats (for DNA extraction) are stored in a biorepository for future studies. Every household is geocoded for linkage with existing contextual data including community level measures of the social and physical environment; local neighborhood characteristics are also recorded using an audit tool. Participants are re-contacted bi-annually by phone for health history updates.
Discussion
SHOW generates data to assess health disparities across state communities as well as trends on prevalence of health outcomes and determinants. SHOW also serves as a platform for ancillary epidemiologic studies and for studies to evaluate the effect of community-specific interventions. It addresses key gaps in our current data resources and increases capacity for etiologic, applied and translational population health research. It is hoped that this program will serve as a model to better support evidence-based public health, facilitate intervention evaluation research, and ultimately help improve health throughout the state and nation.
doi:10.1186/1471-2458-10-785
PMCID: PMC3022857  PMID: 21182792
12.  Sleep Disordered Breathing and Metabolic Syndrome 
Background
Sleep disordered breathing (SDB) has been associated with cardiovascular disease, hypertension, and insulin resistance. This article examines the association between SDB and the prevalence of metabolic syndrome (MS) in a community-based sample.
Methods
A subset of participants in the Wisconsin Sleep Cohort Study (N=546) participated in an ancillary study to measure vascular and metabolic function. SDB was characterized using the apnea-hypopnea index (AHI) obtained in the polysomnography study closest to the collection of the metabolic measures. MS was defined using the National Cholesterol Education Program definition, and the homeostasis model assessment method (HOMA) was used to characterize insulin resistance.
Results
SDB was significantly correlated with insulin resistance (Spearman r correlation between AHI and HOMA=0.30, P<0.0001). Compared with those without SDB (AHI <5), the age-sex-adjusted odds ratios of MS associated with mild (AHA 5-14.9) and moderate/severe SDB (AHI >15 or CPAP) were 4.0 (95% CI 2.6, 6.3) and 5.3 (95% CI 3.2, 8.8), respectively. Additional adjustment for markers of sympathetic or neuroendocrine activation (urinary norepinephrine, cortisol, heart rate variability) did not materially alter these estimates. These associations were weaker but remained statistically significant after adjusting for body mass index.
Conclusion
SDB might be considered an integral component of MS.
PMCID: PMC2873189  PMID: 19743760
13.  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.
PMCID: PMC2858234  PMID: 19743755

Results 1-13 (13)