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.

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 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.

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).

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.

ß2 adrenergic receptor polymorphisms and nocturnal blood pressure dipping status in the Wisconsin Sleep Cohort Study.

Nondipping nocturnal blood pressure (BP) is associated with target organ damage and cardiovascular disease. We hypothesized that ß1- and ß2-AR-associated single nucleotide polymorphisms (SNPs) would associate with nondipping 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. Nondipping was defined as less than a 10% dip in sleep BP compared with wake BP. Dipping ratios were calculated as sleep/wake BP. Single nucleotide polymorphisms in the ß1-AR (rs7076938, tagging for Gly389Arg) and ß2-AR (rs17778257 and rs2400707, tagging for Arg16Gly and Gln27Glu) were selected. ß2-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 = .015). Diastolic dip ratios were: GG = 0.807; AG = 0.815; AA = 0.824 (P = .026). The ß2-AR rs17778257/rs2400707 A/A haplotype was associated with dipping ratios and systolic nondipping status (nondipping odds radio 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 ß2-AR polymorphisms. Nocturnal dipping patterns may be modulated by ß2-AR polymorphisms.

Long-term outcomes of a primary care faculty development program at the University of Wisconsin.

BACKGROUND AND OBJECTIVES: To meet a need for primary care teachers, the Bureau of Health Professions funds faculty development programs for primary care preceptors. The purpose of this study was to determine how graduates of our faculty development program identified its long-term effect on professional outcomes. METHODS: Our program was a year-long series of five weekend workshops focusing on the preparation of preceptors to teach curricular areas relatively new to medical education--evidence-based medicine, teaching skills, technology tools, doctor-patient communication, quality improvement, and advocacy. Participants included physicians in community-based practices and university-based physicians. We surveyed the first 100 graduates of our program about professional and academic outcomes they attributed to program participation. Outcomes were categorized using the Kirkpatrick evaluation model; open-ended comments were analyzed thematically. RESULTS: Eighty responses were received (80% response rate). Ninety percent of respondents were teaching medical students and residents. Outcomes attributed to the program included improvement in teaching skills, improvement in clinical skills, intrapersonal growth and increased self-confidence, and increased interdisciplinary networking and mentoring. Ninety-one percent had recommended the program to others. CONCLUSIONS: Graduates identified positive outcomes and found the fellowship useful for developing the skills and self-confidence required of teachers. This training may be valuable for teachers in today's learning environment.

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.

Electrocardiographically indicated cardiovascular disease in sleep-disordered breathing.

The evidence for a role of sleep-disordered breathing (SDB) in cardiovascular disease (CVD) is inconclusive and limited to clinic-based studies or population-based studies using historical CVD data. The authors investigated cross-sectional association of SDB, assessed by overnight polysomnography and described by frequency of apnea/hypopnea episodes (Apnea-Hypopnea Index, AHI), with screen-detected CVD consisting of cardiologist-confirmed, electrocardiographically indicated coronary artery disease (ECG-CAD), left ventricular hypertrophy (ECG-LVH), arrhythmias, and conduction abnormalities in a general population. Using multiple logistic regression with adjustments for covariables, there was no significant association of AHI with ECG-CAD, ECG-LVH by voltage, arrhythmias, or conduction abnormalities. There was, however, an association between AHI and ECG-LVH by Cornell criteria. Using AHI as categorical variable, the adjusted odds of ECG-CAD in AHI >or= 5 vs <5 was increased, but not significantly, at 1.30, 95% confidence interval (CI) 0.67, 2.51. The adjusted odds of ECG-LVH by Cornell criteria in AHI >or= 15 vs <5 was significant at 3.19, 95% CI 1.16, 8.76. The authors found a weak or no association between screen-detected CVD and sleep apnea, but did find a threefold increased odds of screen-detected LVH, using Cornell criteria, in moderate or worse SDB. These findings contribute to accumulating evidence of possible association between CVD and sleep apnea in the general population and underscore the need to better understand how SDB affects cardiovascular pathology.

A weekend program model for faculty development with primary care physicians.

BACKGROUND: Medical teachers are expected to be proficient at teaching students and residents about the changing health care system. The University of Wisconsin established a faculty development fellowship program to better prepare clinical teachers in family medicine, general pediatrics, and general internal medicine. This paper describes our fellowship program, presents data on program accomplishments, and discusses what we have learned. METHODS: We developed a year-long series of five weekend workshops. A core group of faculty provided 2- to 4- hour sessions on topics including evidence-based medicine, physician leadership, advocacy, doctor-patient communication, quality, technology tools, and teaching skills. Evaluation data were used to shape the program, make improvements, and assess impact. Fellows self-assessed their ability to perform skills at the beginning and ending of the year; paired t tests were used to compare these changes. RESULTS: Attendance and program completion rates were more than 94% for the 84 fellows taught over 6 years. Individual sessions and the overall program were well-rated by fellows. Participants reported improvements in targeted skills; statistical analyses confirmed many significant pre-post improvements. LESSONS LEARNED: To obtain high ratings, faculty must apply adult learning and active learning principles; lectures were not well tolerated. Initial technology skills were often low; computer labs needed many helpers. Participants needed extensive faculty support on their projects. It facilitated coordination and learning to have a core group of fellowship faculty who did most of the teaching. Graduates have become enthusiastic recruiters for new fellows. Our 5-weekend program has proven to be an effective faculty development model.