Cardiorespiratory Fitness Attenuates the Deleterious Effects of Sleep Apnea on Cerebral Structure and Perfusion in the Wisconsin Sleep Cohort Study.

BACKGROUND: Emerging evidence suggests that age-related changes in cerebral health may be sensitive to vascular risk modifiers, such as physical activity and sleep. OBJECTIVE: We examine whether cardiorespiratory fitness modifies the association of obstructive sleep apnea (OSA) severity with MRI-assessed measures of cerebral structure and perfusion. METHODS: Using data from a cross-sectional sample of participants (n = 129, 51% female, age range 49.6-85.3 years) in the Wisconsin Sleep Cohort study, we estimated linear models of MRI-assessed total and regional gray matter (GM) and white matter (WM) volumes, WM hyperintensity (WMH:ICV ratio), total lesion volume, and arterial spin labeling (ASL) cerebral blood flow (CBF), using an estimated measure of cardiorespiratory fitness (CRF) and OSA severity as predictors. Participants' sleep was assessed using overnight in-laboratory polysomnography, and OSA severity was measured using the apnea-hypopnea index (AHI), or the mean number of recorded apnea and hypopnea events per hour of sleep. The mean±SD time difference between PSG data collection and MRI data collection was 1.7±1.5 years (range: [0, 4.9 years]). RESULTS: OSA severity was associated with reduced total GM volume (ß=-0.064; SE = 0.023; p = 0.007), greater total WM lesion volume (interaction p = 0.023), and greater WMHs (interaction p = 0.017) in less-fit subjects. Perfusion models revealed significant differences in the association of AHI and regional CBF between fitness groups (interaction ps < 0.05). CONCLUSION: This work provides new evidence for the protective role of cardiorespiratory fitness against the deleterious effects of OSA on brain aging in late-middle age to older adults.

The Survey of the Health of Wisconsin (SHOW) Program: An Infrastructure for Advancing Population Health.

Introduction: The Survey of the Health of Wisconsin (SHOW) was established in 2008 by the University of Wisconsin (UW) School of Medicine and Public Health (SMPH) with the goals of (1) providing a timely and accurate picture of the health of the state residents; and (2) serving as an agile resource infrastructure for ancillary studies. Today, the SHOW program continues to serve as a unique and vital population health research infrastructure for advancing public health. Methods: SHOW currently includes 5,846 adult and 980 minor participants recruited between 2008 and 2019 in four primary waves. WAVE I (2008-2013) includes annual statewide representative samples of 3,380 adults ages 21 to 74 years. WAVE II (2014-2016) is a triannual statewide sample of 1,957 adults (age ≥18 years) and 645 children (age 0-17). WAVE III (2017) consists of follow-up of 725 adults from the WAVE I and baseline surveys of 222 children in selected households. WAVEs II and III include stool samples collected as part of an ancillary study in a subset of 784 individuals. WAVE IV consists of 517 adults and 113 children recruited from traditionally under-represented populations in biomedical research including African Americans and Hispanics in Milwaukee, Wisconsin. Findings to Date: The SHOW resource provides unique spatially granular and timely data to examine the intersectionality of multiple social determinants and population health. SHOW includes a large biorepository and extensive health data collected in a geographically diverse urban and rural population. Over 60 studies have been published covering a broad range of topics including, urban and rural disparities in cardio-metabolic disease and cancer, objective physical activity, sleep, green-space and mental health, transcriptomics, the gut microbiome, antibiotic resistance, air pollution, concentrated animal feeding operations and heavy metal exposures. Discussion: The SHOW cohort and resource is available for continued follow-up and ancillary studies including longitudinal public health monitoring, translational biomedical research, environmental health, aging, microbiome and COVID-19 research.

The Survey of the Health of Wisconsin (SHOW) Program: An infrastructure for Advancing Population Health Sciences.

PURPOSE: The Survey of the Health of Wisconsin (SHOW) was established in 2008 by the University of Wisconsin (UW) School of Medicine and Public Health (SMPH) with the goals of 1) providing a timely and accurate picture of the health of the state residents; and 2) serving as an agile resource infrastructure for ancillary studies. Today SHOW continues to serve as a vital population health research infrastructure. PARTICIPANTS: SHOW currently includes 5,846 adult and 980 minor participants recruited between 2008-2019 in four primary waves. WAVE I (2008-2013) includes annual statewide representative samples of 3,380 adults ages 21 to 74 years. WAVE II (2014-2016) is a triannual statewide sample of 1957 adults (age ≥18 years) and 645 children. WAVE III (2017) consists of follow-up of 725 adults from the WAVE I and baseline surveys of 222 children in selected households. WAVEs II and III include stool samples collected as part of an ancillary study in a subset of 784 individuals. WAVE IV consist of 517 adults and 113 children recruited from traditionally under-represented populations in biomedical research including African Americans and Hispanics in Milwaukee county, WI. FINDINGS TO DATE: The SHOW provides extensive data to examine the intersectionality of multiple social determinants and population health. SHOW includes a large biorepository and extensive health data collected in a geographically diverse urban and rural population. Over 60 studies have been published covering a broad range of topics including, urban and rural disparities in cardio-metabolic disease and cancer, objective physical activity, sleep, green-space and mental health, transcriptomics, the gut microbiome, antibiotic resistance, air pollution, concentrated animal feeding operations and heavy metal exposures. FUTURE PLANS: The SHOW cohort is available for continued longitudinal follow-up and ancillary studies including genetic, multi-omic and translational environmental health, aging, microbiome and COVID-19 research. ARTICLE SUMMARY: Strengths and limitations: The Survey of the Health of Wisconsin (SHOW) is an infrastructure to advance population health sciences including biological sample collection and broader data on individual and neighborhood social and environmental determinants of health.The extensive data from diverse urban and rural populations offers a unique study sample to compare how socio-economic gradients shape health outcomes in different contexts.The objective health data supports novel interdisciplinary research initiatives and is especially suited for research in causes and consequences of environmental exposures (physical, chemical, social) across the life course on cardiometabolic health, immunity, and aging related conditions.The extensive biorepository supports novel omics research into common biological mechanisms underlying numerous complex chronic conditions including inflammation, oxidative stress, metabolomics, and epigenetic modulation.Ancillary studies, such as the Wisconsin Microbiome Study, have expanded the utility of the study to examine human susceptibility to environmental exposures and opportunities for investigations of the role of microbiome in health and disease.Long-standing partnerships and recent participation among traditionally under-represented populations in biomedical research offer numerous opportunities to support community-driven health equity work.No biological samples were collected among children.The statewide sampling frame may limit generalizability to other regions in the United States.

Association of Rapid Eye Movement Sleep With Mortality in Middle-aged and Older Adults.

Importance: Rapid eye movement (REM) sleep has been linked with health outcomes, but little is known about the relationship between REM sleep and mortality. Objective: To investigate whether REM sleep is associated with greater risk of mortality in 2 independent cohorts and to explore whether another sleep stage could be driving the findings. Design, Setting, and Participants: This multicenter population-based cross-sectional study used data from the Outcomes of Sleep Disorders in Older Men (MrOS) Sleep Study and Wisconsin Sleep Cohort (WSC). MrOS participants were recruited from December 2003 to March 2005, and WSC began in 1988. MrOS and WSC participants who had REM sleep and mortality data were included. Analysis began May 2018 and ended December 2019. Main Outcomes and Measures: All-cause and cause-specific mortality confirmed with death certificates. Results: The MrOS cohort included 2675 individuals (2675 men [100%]; mean [SD] age, 76.3 [5.5] years) and was followed up for a median (interquartile range) of 12.1 (7.8-13.2) years. The WSC cohort included 1386 individuals (753 men [54.3%]; mean [SD] age, 51.5 [8.5] years) and was followed up for a median (interquartile range) of 20.8 (17.9-22.4) years. MrOS participants had a 13% higher mortality rate for every 5% reduction in REM sleep (percentage REM sleep SD = 6.6%) after adjusting for multiple demographic, sleep, and health covariates (age-adjusted hazard ratio, 1.12; fully adjusted hazard ratio, 1.13; 95% CI, 1.08-1.19). Results were similar for cardiovascular and other causes of death. Possible threshold effects were seen on the Kaplan-Meier curves, particularly for cancer; individuals with less than 15% REM sleep had a higher mortality rate compared with individuals with 15% or more for each mortality outcome with odds ratios ranging from 1.20 to 1.35. Findings were replicated in the WSC cohort despite younger age, inclusion of women, and longer follow-up (hazard ratio, 1.17; 95% CI, 1.03-1.34). A random forest model identified REM sleep as the most important sleep stage associated with survival. Conclusions and Relevance: Decreased percentage REM sleep was associated with greater risk of all-cause, cardiovascular, and other noncancer-related mortality in 2 independent cohorts.

Reasons Behind Preferences for Community-Based Continence Promotion.

OBJECTIVES: This study aimed to understand the potential reach of continence promotion intervention formats among incontinent women. METHODS: The Survey of the Health of Wisconsin conducts household interviews on a population-based sample. In 2016, 399 adult women were asked about incontinence and likelihood of participation in continence promotion via 3 formats: single lecture, interactive 3-session workshop, or online. Descriptive analyses compared women likely versus unlikely to participate in continence promotion. To understand format preferences, modified grounded theory was used to conduct and analyze telephone interviews. RESULTS: One hundred eighty-seven (76%) of 246 incontinent women reported being likely to attend continence promotion: 111 (45%) for a single lecture, 43 (17%) for an interactive 3-session workshop, and 156 (64%) for an online program. Obesity, older age, nonwhite race, prior health program participation, and Internet use for health information were associated with reported continence promotion participation. Cited advantages of a single lecture included convenience and ability to ask questions. A workshop offered accountability, hands-on learning, and opportunity to learn from others; online format offered privacy, convenience, and self-directed learning. CONCLUSIONS: Most incontinent women are willing to participate in continence promotion, especially online.

Subjective sleep measurement: comparing sleep diary to questionnaire.

PURPOSE: The sleep diary is the gold standard of self-reported sleep duration, but its comparability to sleep questionnaires is uncertain. The purpose of this study was to compare self-reported sleep duration between a sleep diary and a sleep questionnaire and to test whether sleep-related disorders were associated with diary-questionnaire differences in sleep duration. PARTICIPANTS AND METHODS: We compared self-reported sleep duration from 5,432 questionnaire-sleep diary pairs in a longitudinal cohort of 1,516 adults. Participants reported sleep information in seven-day sleep diaries and in questionnaires. Research staff abstracted average sleep durations for three time periods (overall; weekday; weekend) from diaries and questionnaires. For each time period, we evaluated diary-questionnaire differences in sleep duration with Welch's two-sample t-tests. Using linear mixed effects regression, we regressed overall diary-questionnaire sleep duration difference on several participant characteristics: reporting any insomnia symptoms, having sleep apnea, sex, body mass index, smoking status, Short Form-12 Physical Health Composite Score, and Short Form-12 Mental Health Composite Score. RESULTS: The average diary-reported overall sleep duration (7.76 hrs) was longer than that of the questionnaire (7.07 hrs) by approximately 41 mins (0.69 hrs, 95% confidence interval: 0.62, 0.76 hrs). Results were consistent across weekday- and weekend-specific differences. Demographic-adjusted linear mixed effects models tested whether insomnia symptoms or sleep apnea were associated with diary-questionnaire differences in sleep duration. Insomnia symptoms were associated with a 17 min longer duration on the diary relative to the questionnaire (ß=0.28 hrs, 95% confidence interval: 0.22, 0.33 hrs), but sleep apnea was not significantly associated with diary-questionnaire difference. Female sex was associated with greater diary-questionnaire duration differences, whereas better self-reported health was associated with lesser differences. CONCLUSION: Diaries and questionnaires are somewhat disparate methods of assessing subjective sleep duration, although diaries report longer duration relative to questionnaires, and insomnia symptoms may contribute to greater perceived differences.

Multiethnic Meta-Analysis Identifies RAI1 as a Possible Obstructive Sleep Apnea-related Quantitative Trait Locus in Men.

Obstructive sleep apnea (OSA) is a common heritable disorder displaying marked sexual dimorphism in disease prevalence and progression. Previous genetic association studies have identified a few genetic loci associated with OSA and related quantitative traits, but they have only focused on single ethnic groups, and a large proportion of the heritability remains unexplained. The apnea-hypopnea index (AHI) is a commonly used quantitative measure characterizing OSA severity. Because OSA differs by sex, and the pathophysiology of obstructive events differ in rapid eye movement (REM) and non-REM (NREM) sleep, we hypothesized that additional genetic association signals would be identified by analyzing the NREM/REM-specific AHI and by conducting sex-specific analyses in multiethnic samples. We performed genome-wide association tests for up to 19,733 participants of African, Asian, European, and Hispanic/Latino American ancestry in 7 studies. We identified rs12936587 on chromosome 17 as a possible quantitative trait locus for NREM AHI in men (N = 6,737; P = 1.7 × 10-8) but not in women (P = 0.77). The association with NREM AHI was replicated in a physiological research study (N = 67; P = 0.047). This locus overlapping the RAI1 gene and encompassing genes PEMT1, SREBF1, and RASD1 was previously reported to be associated with coronary artery disease, lipid metabolism, and implicated in Potocki-Lupski syndrome and Smith-Magenis syndrome, which are characterized by abnormal sleep phenotypes. We also identified gene-by-sex interactions in suggestive association regions, suggesting that genetic variants for AHI appear to vary by sex, consistent with the clinical observations of strong sexual dimorphism.

Sleep and Breathing and Cancer?

Sleep, like eating and breathing, is an essential part of the daily life cycle. Although the science is still emerging, sleep plays an important role in immune, cardiovascular, and neurocognitive function. Despite its great importance, nearly 40% of U.S. adults experience problems with sleep ranging from insufficient total sleep time, trouble initiating or maintaining sleep (Insomnia), circadian rhythm disorders, sleep-related movement disorders, and sleep-related breathing disorders such as obstructive sleep apnea (OSA). Herein, we discuss new evidence that suggests that sleep may also affect carcinogenesis. Specifically, we review recent epidemiologic data suggesting links between cancer and OSA. As OSA is a common, underdiagnosed, and undertreated condition, this has public health implications. Intriguing animal model data support a link between cancer and sleep/OSA, although mechanisms are not yet clear. Leaders in the fields of sleep medicine, pulmonology, and oncology recently met to review and discuss these data, as well as to outline future directions of study. We propose a multidisciplinary, three-pronged approach to studying the associations between cancer and sleep, utilizing mutually interactive epidemiologic studies, preclinical models, and early-phase clinical trials. Cancer Prev Res; 9(11); 821-7. ©2016 AACR.

Subjective and Objective Measures of Hypersomnolence Demonstrate Divergent Associations with Depression among Participants in the Wisconsin Sleep Cohort Study.

STUDY OBJECTIVES: To examine associations of depression with habitual sleep duration, daytime sleepiness, and objective sleep propensity in a nonclinical population. METHODS: Data from adults participating in the Wisconsin Sleep Cohort Study were utilized in analyses. There were 1,287 adults (3,324 observations) who were used in the analysis of subjective hypersomnolence measures; 1,155 adults (2,981 observations) were used in the analysis of objective sleep propensity assessed by the multiple sleep latency test (MSLT). Repeated-measures logistic regression estimated associations between presence of depression (defined as modified Zung Self-Rating Depression Scale ≥ 50 or use of antidepressant medications) and three primary hypersomnolence measures: subjective excessive daytime sleepiness (Epworth Sleepiness Scale [ESS] ≥ 11), self-reported sleep duration ≥ 9 h/d, and objective sleep propensity (MSLT mean sleep latency < 8 min). RESULTS: After adjusting for age, sex, body mass index, chronic medical conditions, sedative hypnotic medication use, caffeine, tobacco, and alcohol use, sleep disordered breathing, as well as insomnia and sleep duration when appropriate, estimated odd ratios (95% confidence interval) for depression were: 1.56 (1.31,1.86) for ESS ≥ 11; 2.01 (1.49, 2.72) for habitual sleep time ≥ 9 h; and 0.76 (0.63-0.92) for MSLT mean sleep latency < 8 min. CONCLUSIONS: Our results demonstrate divergent associations between subjective and objective symptoms of hypersomnolence and depression, with subjective sleepiness and excessive sleep duration associated with increased odds of depression, but objective sleep propensity as measured by the MSLT associated with decreased odds of depression. Further research is indicated to explain this paradox and the impact of different hypersomnolence measures on the course of mood disorders. COMMENTARY: A commentary on this article appears in this issue on page 467.

Relationships between sleep apnea, cardiovascular disease risk factors, and aortic pulse wave velocity over 18 years: the Wisconsin Sleep Cohort.

PURPOSE: The purpose of this study is to determine if apnea-hypopnea index (AHI) severity predicts future aortic pulse wave velocity (PWV) in the Wisconsin Sleep Cohort. METHODS: Applanation tonometry was used to derive carotid-to-femoral PWV a mean of 18 years (standard deviation 4) after overnight polysomnography. Multivariable regression models were created to describe prospective associations between baseline AHI and future PWV. RESULTS: The 618 adults were mean 65 (7) years old (55 % male) with a mean body mass index of 31 (7) kg/m(2) at the tonometry visit. Mean baseline AHI was 4.6 (9.7) events/h. In multiple linear regression models adjusted for age (ß = 0.13/year, standard error [SE] = 0.01, p < 0.001) and sex, higher log10AHI (ß = 0.43/events/h, SE = 0.18, p = 0.02) was associated with PWV. After adjustment for waist circumference (ß = 0.01/cm, SE = 0.01, p = 0.05) and height, the association between baseline log10AHI and future PWV was not statistically significant (p = 0.11), although the association with age persisted unchanged. Addition of covariates such as smoking status (current smoker ß = 0.66, SE = 0.22, p = 0.002), diabetes mellitus status (ß = 2.89, SE = 0.59, p < 0.001), and systolic blood pressure (BP, ß = 0.03/mmHg, SE = 0.01, p < 0.001) did not change the association. AHI did not interact with age or smoking status to predict PWV. A secondary analysis of nocturnal oxygen saturation parameters in 517 participants, 9 (2) years prior also did not show any significant relationships with future PWV. CONCLUSIONS: The prospective association between AHI and PWV is confounded by body size and influenced by smoking, diabetes mellitus, and BP. Weight management, BP control, and smoking cessation may help prevent arterial stiffening associated with obstructive sleep apnea.

Association of low ferritin with PLM in the Wisconsin Sleep Cohort.

OBJECTIVE: The origins of periodic leg movements (PLMs), a strong correlate of restless legs syndrome (RLS), are uncertain. This study was performed to assess the relationship between PLMs and peripheral iron deficiency, as measured with ferritin levels corrected for inflammation. METHODS: We included a cross-sectional sample of a cohort study of 801 randomly selected people (n = 1008 assays, mean age 58.6 ± 0.3 years) from Wisconsin state employee agencies. A previously validated automatic detector was used to measure PLMs during sleep. The patients were categorized into RLS symptoms-positive and RLS symptoms-negative based on a mailed survey response and prior analysis. Analyses were performed using a linear model with PLM category above and below 15 PLM/h (periodic leg movement index, PLMI) as the dependent variable, and adjusting for known covariates, including previously associated single-nucleotide polymorphisms (SNPs) within BTBD9, TOX3/BC034767, MEIS1, MAP2K5/SKOR1, and PTPRD. Ferritin and C-reactive protein (CRP) levels were measured in serum, and ferritin levels corrected for inflammation using CRP levels. RESULTS: After controlling for cofactors, PLMI ≥ 15 was associated with low (≤50 ng/mL) ferritin levels (OR = 1.55, p = 0.020). The best model was found using quasi-least squares regression of ferritin as a function of PLMI, with an increase of 0.0034 PLM/h predicted by a decrease of 1 ng/mL ferritin (p = 0.00447). CONCLUSIONS: An association was found between low ferritin and greater PLMs in a general population of older adults, independent of genetic polymorphisms, suggesting a role of low iron stores in the expression of these phenotypes. Patients with high PLMI may require to be checked for iron deficiency.

Menopausal hormone therapy and sleep-disordered breathing: evidence for a healthy user bias.

PURPOSE: Observational studies suggest that menopausal hormone therapy protects against sleep-disordered breathing, but such findings may be biased by a "healthy user effect." When the Women's Health Initiative Study reported in 2002 that estrogen-progestin therapy increases heart disease risk, many women discontinued hormone therapy. We investigate healthy user bias in the association of hormone therapy with sleep-disordered breathing in the Sleep in Midlife Women Study. METHODS: A total of 228 women aged 38 to 62 years were recruited from the Wisconsin Sleep Cohort Study. They underwent polysomnography to measure apnea-hypopnea index, at home semiannually from 1997 to 2006, and in the sleep laboratory every four years (n = 1828 studies). Hormone therapy was recorded monthly. Linear models with empirical standard errors regressed logarithm of apnea-hypopnea index on hormone use with a pre- or post-July 2002 interaction, adjusting for menopause and age. RESULTS: The association of hormone therapy and sleep-disordered breathing was heterogeneous (P < .01); apnea-hypopnea index among users was 15% lower in the early period (95% confidence interval, -27% to -1%), but similar to nonusers in the late. CONCLUSIONS: Hormone therapy was negatively associated with sleep-disordered breathing only until the Women's Health Initiative results were publicized. Hormone therapy may have been a marker for healthfulness in the early period, creating a spurious association with sleep-disordered breathing.

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.

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.

Sleep-disordered breathing and cancer mortality: results from the Wisconsin Sleep Cohort Study.

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.

Longitudinal association of sleep-disordered breathing and nondipping of nocturnal blood pressure in the Wisconsin Sleep Cohort Study.

STUDY OBJECTIVES: The association of sleep-disordered breathing (SDB) and blunting of normal nocturnal lowering of blood pressure (BP) (nondipping) has only been examined cross-sectionally. The purpose of this study is to investigate whether SDB is prospectively associated with nondipping. METHODS: The longitudinal association between SDB and incident nondipping was examined in a subsample of 328 adults enrolled in the Wisconsin Sleep Cohort Study who completed 2 or more 24-hour ambulatory BP studies over an average of 7.2 years of follow-up. SDB identified by baseline in-laboratory polysomnography was defined by apnea-hypopnea index (AHI) categories. Systolic and diastolic nondipping was defined by systolic and diastolic sleep-wake BP ratios > 0.9. All models were adjusted for age, sex, body mass index at baseline and follow-up, smoking, alcohol consumption, hypertension, sleep time, length of follow-up time, and antihypertensive medication use. RESULTS: There was a dose-response increased odds of developing systolic nondipping in participants with SDB. The adjusted odds ratios (95% confidence interval) of incident systolic nondipping for baseline AHI 5 to < 15 and AHI > or = 15, versus AHI < 5, were 3.1 (1.3-7.7) and 4.4 (1.2-16.3), respectively (P trend = 0.006). The adjusted odds ratios (95% confidence interval) of incident diastolic nondipping for corresponding SDB categories were not statistically significant: 2.0 (0.8-5.6) and 1.3 (0.2-7.1). CONCLUSIONS: Our longitudinal findings of a dose-response increase in development of systolic nondipping of BP with severity of SDB at baseline in a population-based sample provide evidence consistent with a causal link. Nocturnal systolic nondipping may be a mechanism by which SDB contributes to increased cardiovascular disease.

Association of alcohol consumption and sleep disordered breathing in men and women.

STUDY OBJECTIVES: Experimental evidence indicates that alcohol use near bedtime may exacerbate sleep disordered breathing (SDB). However, scarce research has examined the relation between moderate habitual alcohol use and objectively assessed SDB, and it is unclear whether patients with SDB, or those at risk for SDB, should be counseled to avoid alcohol regardless of proximity to bedtime. In this population-based epidemiology study, our objective is to measure the association of SDB with usual alcohol consumption habits. METHODS: Men (N = 775) and women (N = 645)--initially randomly selected from a working population--participating in the Wisconsin Sleep Cohort Study were evaluated for alcohol consumption and SDB. The apnea-hypopnea index (AHI, events/hour) was determined by in-laboratory polysomnography. AHI > 5 defined "mild or worse" SDB and AHI > 15 defined "moderate or worse" SDB. Alcohol consumption (drinks/day) was assessed by questionnaire. Potential confounding or interacting variables such as smoking, body mass index, and medication use, were measured by clinical assessment and questionnaire. RESULTS: Relative to men who consumed less alcohol, for each increment of one drink per day, men who consumed more alcohol had 25% greater odds of mild or worse SDB (OR = 1.25, 95% CI = 1.07-1.46, p = 0.006). Among women, minimal to moderate alcohol consumption was not significantly associated with increased risk of SDB. DISCUSSION: In men, increased usual alcohol consumption was associated with increased risk of mild or worse SDB. Persons with SDB might benefit from generally reduced alcohol consumption and not just avoidance near bedtime.

Trends in bariatric surgery for morbid obesity in Wisconsin.

BACKGROUND: Obesity is a national epidemic with rates in Wisconsin and the United States doubling over the past decade. Research of available treatments for morbid obesity (body mass index > or = 40 kg/m2) suggests that bariatric surgery may be the only modality that provides any significant long term weight loss. METHODS: Using the data from Centers for Disease Control and Prevention's Behavioral Risk Factor Surveillance System, we analyzed self-reported information on body weight and height among adults in Wisconsin. We used the WITHIN database for inpatient hospitalization and surgeries in Wisconsin to evaluate trends in gastric bypass surgery. Finally, we surveyed bariatric surgeons in Wisconsin to assess trends in bariatric surgery in the state. RESULTS: In Wisconsin, the percentage of the adults considered to be obese increased from 11% in 1990 to 22% in 2001. In 1999-2001, approximately 80,000 adults (2% of the population) were morbidly obese. The number of gastric bypass surgeries performed in Wisconsin more than doubled in 1 year, from 182 in 2001 to 426 in 2002. According to bariatric surgeons, gastric bypass accounts for approximately 90% of bariatric surgeries performed in Wisconsin. Thus, in 2002, there was roughly 1 bariatric surgery for every 200 morbidly obese Wisconsin adults. Most (84%) bariatric surgeons are planning to increase the number of procedures they perform, and 24% plan on adding an additional bariatric surgeon to their group. SUMMARY: Bariatric surgery rates are increasing in Wisconsin, yet the demand for surgery far exceeds current capacity of surgeons in the state.