Khin Mae Hla

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

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.

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.

Efficacy of patient letter reminders on cervical cancer screening: a meta-analysis.

OBJECTIVE: To perform a meta-analysis on existing randomized controlled trials to investigate the efficacy of patient letter reminders on increasing cervical cancer screening using Pap smears.METHODS: A search was conducted for all relevant published and unpublished studies between the years 1966 and 2000. Eligibility criteria included randomized controlled studies that examined populations due for Pap smear screening. The intervention studied was in the form of a reminder letter. The Mantel-Haenszel method was used to measure the summary effect of the intervention. A test for homogeneity using the Mantel-Haenszel method was performed.RESULTS: Ten articles fulfilled the inclusion criteria, including one unpublished study. The test for homogeneity showed evidence of heterogeneity (x2=31, 9 df, P<.001). An analysis for causes of heterogeneity was pursued. Division into subpopulations based on socioeconomic status resolved the heterogeneity (x2=5.2, 8 df, P=.75). The studies evaluating those in lower socioeconomic groups had a smaller response (odds ratio [OR], 1.16; 95% confidence interval [CI], 0.99 to 1.35) than those studies using mixed populations (OR, 2.02; 95% CI, 1.79 to 2.28). The pooled odds ratio showed that patients who received the intervention were significantly more likely to return for screening than those who did not (OR, 1.64; 95% CI, 1.49 to 1.80).CONCLUSIONS: Patient reminders in the form of mailed letters increase the rate of cervical cancer screening. Patient letter reminders have less efficacy in lower socioeconomic groups.

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 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.

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 ≥ 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 ≥ 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.

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

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

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 b1- and b2-AR-associated single nucleotide polymorphisms (SNPs) would associate with nondipping BP patterns. Participants (n ¼ 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 b1-AR (rs7076938, tagging for Gly389Arg) and b2-AR (rs17778257 and rs2400707, tagging for Arg16Gly and Gln27Glu) were selected. b2-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 ¼ 0.846; AG ¼ 0.854; AA ¼ 0.861 (P ¼ .015). Diastolic dip ratios were: GG ¼ 0.807; AG ¼ 0.815; AA ¼ 0.824 (P ¼ .026). The b2-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 b2-AR polymorphisms. Nocturnal dipping patterns may be modulated by b2-AR polymorphisms. J Am