Mari Palta

The Occurrence of Sleep-Disordered Breathing among Middle-Aged Adults

BACKGROUND Limited data have suggested that sleep-disordered breathing, a condition of repeated episodes of apnea and hypopnea during sleep, is prevalent among adults. Data from the Wisconsin Sleep Cohort Study, a longitudinal study of the natural history of cardiopulmonary disorders of sleep, were used to estimate the prevalence of undiagnosed sleep-disordered breathing among adults and address its importance to the public health. METHODS A random sample of 602 employed men and women 30 to 60 years old were studied by overnight polysomnography to determine the frequency of episodes of apnea and hypopnea per hour of sleep (the apnea-hypopnea score). We measured the age- and sex-specific prevalence of sleep-disordered breathing in this group using three cutoff points for the apnea-hypopnea score (> or = 5, > or = 10, and > or = 15); we used logistic regression to investigate risk factors. RESULTS The estimated prevalence of sleep-disordered breathing, defined as an apnea-hypopnea score of 5 or higher, was 9 percent for women and 24 percent for men. We estimated that 2 percent of women and 4 percent of men in the middle-aged work force meet the minimal diagnostic criteria for the sleep apnea syndrome (an apnea-hypopnea score of 5 or higher and daytime hypersomnolence). Male sex and obesity were strongly associated with the presence of sleep-disordered breathing. Habitual snorers, both men and women, tended to have a higher prevalence of apnea-hypopnea scores of 15 or higher. CONCLUSIONS The prevalence of undiagnosed sleep-disordered breathing is high among men and is much higher than previously suspected among women. Undiagnosed sleep-disordered breathing is associated with daytime hypersomnolence.

Prospective Study of the Association between Sleep-Disordered Breathing and Hypertension

BACKGROUND Sleep-disordered breathing is prevalent in the general population and has been linked to chronically elevated blood pressure in cross-sectional epidemiologic studies. We performed a prospective, population-based study of the association between objectively measured sleep-disordered breathing and hypertension (defined as a laboratory-measured blood pressure of at least 140/90 mm Hg or the use of antihypertensive medications). METHODS We analyzed data on sleep-disordered breathing, blood pressure, habitus, and health history at base line and after four years of follow-up in 709 participants of the Wisconsin Sleep Cohort Study (and after eight years of follow-up in the case of 184 of these participants). Participants were assessed overnight by 18-channel polysomnography for sleep-disordered breathing, as defined by the apnea-hypopnea index (the number of episodes of apnea and hypopnea per hour of sleep). The odds ratios for the presence of hypertension at the four-year follow-up study according to the apnea-hypopnea index at base line were estimated after adjustment for base-line hypertension status, body-mass index, neck and waist circumference, age, sex, and weekly use of alcohol and cigarettes. RESULTS Relative to the reference category of an apnea-hypopnea index of 0 events per hour at base line, the odds ratios for the presence of hypertension at follow-up were 1.42 (95 percent confidence interval, 1.13 to 1.78) with an apnea-hypopnea index of 0.1 to 4.9 events per hour at base line as compared with none, 2.03 (95 percent confidence interval, 1.29 to 3.17) with an apnea-hypopnea index of 5.0 to 14.9 events per hour, and 2.89 (95 percent confidence interval, 1.46 to 5.64) with an apnea-hypopnea index of 15.0 or more events per hour. CONCLUSIONS We found a dose-response association between sleep-disordered breathing at base line and the presence of hypertension four years later that was independent of known confounding factors. The findings suggest that sleep-disordered breathing is likely to be a risk factor for hypertension and consequent cardiovascular morbidity in the general population.

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 Apnea and Hypertension: A Population-based Study

Transient, nocturnal elevations of blood pressure have been observed during apneic episodes in the sleep apnea syndrome and may be caused by the acute consequences of sleep-disordered breathing such as arousals, high negative intrathoracic pressures, nocturnal desaturation of oxyhemoglobin, hypercapnia, or increased sympathetic nerve activity [1]. However, the mechanism by which these intermittent nocturnal events contribute to sustained, daytime hypertension is not known. It has been postulated that repetitive hemodynamic oscillations caused by frequent apneic episodes occurring in rapid succession may prevent systemic blood pressures from returning to baseline levels and that this may in turn result in neurohumoral or vascular changes leading to elevated waking pressures and sustained hypertension [2]. Several casecontrol and cross-sectional studies suggest that hypertension is highly prevalent (50% to 90%) in patients with the sleep apnea syndrome [1-5]. Sleep apnea has also been reported to occur frequently (22% to 62%) in patients with essential hypertension [6-9]. However, in these studies blood pressure readings were collected at one time of day in the clinic [6, 9] or from records of reported hypertension [7, 8] in highly selected patient populations such as patients with severe obstructive sleep apnea [1-5]. Some studies found a strong association between sleep apnea and hypertension whereas others failed to do so. Inconsistencies in the results are probably caused by nonuniform definitions of hypertension and apnea, differences in methods and populations studied, lack of appropriate control participants, and failure to control for confounding factors such as age, sex, and obesity. Self-reported habitual, heavy snoring has also been associated with hypertension [10-13]. Because most people with sleep apnea snore, however, polysomnographic data are needed to separate participants with sleep apnea and to assess the association with snoring alone. In the earlier surveys, no objective data on breathing during sleep were available, so it was not possible to determine if any or all of the measured association was caused by the inclusion of apneic persons among snorers. In recent epidemiologic studies that included polysomnographic data, it was found that once sleep apnea was incorporated into the analysis, snoring did not contribute independently to the prediction of hypertension [14]. The most compelling evidence that sleep apnea can cause sustained high blood pressure comes from studies that have shown a reduction in blood pressure after sleep apnea was treated [6, 15-22]. However, interpretation of these intervention studies is difficult because of the confounding effect of weight loss that occurred in several studies [17-19, 22] or lack of data on weight change [6, 12, 16, 20, 23]. Weight loss alone has been shown to reduce blood pressure [23]. Collectively, these studies suggest the hypothesis that sleep-disordered breathing plays a causal role in hypertension. In view of recent estimates of sleep apnea prevalence of 9% for women and 24% for men [24], there is a clear need to investigate how sleep-disordered breathing at the milder end of the severity spectrum, including habitual snoring without sleep apnea, is related to blood pressure. Our purpose was to determine how ambulatory blood pressure measurements obtained during an entire 24-hour period, while awake and asleep, differed among people with and without sleep-disordered breathing in the general population. To avoid previous problems of relying on casual blood pressure measurements, of difficulty in separating effects of snoring from those of sleep apnea, and of selection bias between groups, we studied 147 employed adults enrolled in a long-term study of risk factors, natural history, and health consequences of sleep-disordered breathing using 24-hour ambulatory blood pressure monitoring and overnight polysomnography. Methods One hundred and forty-seven persons were recruited from the Wisconsin Sleep Cohort Study, an ongoing prospective study of sleep-disordered breathing. The details of the design and sampling scheme for the Sleep Cohort Study have been described previously [24]. We used a two-stage sampling scheme designed to yield a cohort of men and women with a wide range of sleep-disordered breathing. For the first stage, all state employees, aged 30 to 60 years, from four large agencies were surveyed on sleep characteristics, health history, and sociodemographics by mailed questionnaire. For the second stage, all survey participants reporting habitual (almost every night) snoring, snorting, or breathing pauses, or extremely loud snoring (designated snorers) and a random sample of the remaining participants (designated nonsnorers) were recruited for laboratory sleep studies, with an overall ratio of one nonsnorer for every two snorers. During a 1-year period, 163 employees consecutively studied by overnight polysomnography in the Sleep Research Laboratory at the University of Wisconsin Clinical Research Center were asked to participate in the blood pressure study: Of these, 147 participants agreed and were successfully studied (90% response rate). The protocol was approved by the Human Subjects Committee at the University of Wisconsin Hospital and Clinics, and all participants gave written, informed consent. Data Collection Overnight polysomnography conducted in our sleep laboratory consisted of electroencephalography, electro-oculography, and electromyography to identify sleep stages [25]; measurements of nasal and oral airflow by end-tidal carbon dioxide detection and thermistry; oximetry for arterial oxyhemoglobin saturation; and inductance plethysmography to detect respiratory effort. Body weight and height were measured on all participants to calculate body mass index (kg/m2). Data on sleep problems, sociodemographics, and health history were collected via a structured questionnaire and personal interview. The complete sleep study protocol has been previously reported [24]. Criteria for Sleep Apnea and Habitual Snoring An abnormal breathing event was defined as either a complete cessation of airflow lasting 10 seconds or more (apnea) or a decrease in airflow accompanied by a 4% or greater decrease in arterial oxygen saturation (hypopnea). The average number of abnormal events per hour of sleep (apneahypopnea index) for each person was used as a measure of sleep apnea. For categorical data analysis, cut points were used to represent mild or worse sleep apnea (apneahypopnea index 5) and little or no sleep apnea (apneahypopnea index < 5). Participants with little or no sleep apnea were further categorized as snorers or nonsnorers based on self-reported habitual snoring (every night or almost every night). Criteria for Sleep-Disordered Breathing We categorized participants as participants with sleep-disordered breathing (those with apneahypopnea index 5 and nonapneic snorers with apneahypopnea index < 5) and participants with no sleep-disordered breathing (nonsnorers with apneahypopnea index < 5). Ambulatory Blood Pressure Measurements These measurements were obtained with the Accutracker II (Suntech Medical Instruments/Eutectics Electronics, Raleigh, North Carolina), a 24-hour blood pressure monitoring device that uses a modified auscultatory method of blood pressure measurement. The system consists of a portable two.25-kg console that is connected to three electrocardiographic leads, a cuff, and a microphone positioned over the left brachial artery. The console initiates inflation of the cuff. During the deflation of the cuff set at a rate of 3 mm Hg per second, the persons R-wave complex triggers the microphone to listen for Korotkoff sounds during a window period after a brief pulse-propagation delay. This system, called R-wave gating, reduces the effect of muscle artifact or amount of artifactual sound encountered in noisy environments outside of the office setting. Special computer software identifies the cuff pressures at the onset and disappearance of Korotkoff sounds for each cuff deflation cycle as systolic and diastolic pressures, respectively. At the beginning of all ambulatory blood pressure monitor placements, three seated and three standing pressures were obtained on each participant and calibrated to within 5 mm Hg of a standard mercury sphygmomanometer using a T-tube assembly. Blood pressures were measured at random intervals of 15 to 20 minutes during waking hours and every 30 minutes during periods of sleep. The deflation rate was set at 3 mm Hg per second. All measurements were done with the display monitor off to prevent anticipation of the readings by the participants. Ambulatory pressures while awake included those taken during activities of daily living such as sitting, standing, walking, and eating. Detailed diaries of activity, posture, bedtime, and time on awakening from sleep were kept by all the participants. Participants were instructed to refrain from vigorous exercises and arm movements during inflations. Specific information relevant to blood pressure such as data on history of hypertension and use of antihypertensive medications were obtained at the time of placement of the 24-hour blood pressure monitor. The ambulatory pressure data record for each person included individual readings of systolic blood pressure, diastolic blood pressure, mean arterial pressure, and heart rate at random intervals. The blood pressure data were edited using predetermined criteria and without knowledge of the sleep data. Criteria for deleting individual blood pressure readings included a pulse pressure that was greater than 120 mm Hg or less than 15 mm Hg (biologically implausible), an inconsistent increase or decrease in systolic or diastolic blood pressure greater than 30 mm Hg from previous or subsequent reading occurring during test codes indicating major arm movement, or weak Korotkoff sounds. The reproducibility of t

US norms for six generic health-related quality-of-life indexes from the National Health Measurement study.

Background:A number of indexes measuring self-reported generic health-related quality-of-life (HRQoL) using preference-weighted scoring are used widely in population surveys and clinical studies in the United States. Objective:To obtain age-by-gender norms for older adults on 6 generic HRQoL indexes in a cross-sectional US population survey and compare age-related trends in HRQoL. Methods:The EuroQol EQ-5D, Health Utilities Index Mark 2, Health Utilities Index Mark 3, SF-36v2™ (used to compute SF-6D), Quality of Well-being Scale self-administered form, and Health and Activities Limitations index were administered via telephone interview to each respondent in a national survey sample of 3844 noninstitutionalized adults age 35–89. Persons age 65–89 and telephone exchanges with high percentages of African Americans were oversampled. Age-by-gender means were computed using sampling and poststratification weights to adjust results to the US adult population. Results:The 6 indexes exhibit similar patterns of age-related HRQoL by gender; however, means differ significantly across indexes. Females report slightly lower HRQoL than do males across all age groups. HRQoL seems somewhat higher for persons age 65–74 compared with people in the next younger age decade, as measured by all indexes. Conclusions:Six HRQoL measures show similar but not identical trends in population norms for older US adults. Results reported here provide reference values for 6 self-reported HRQoL indexes.

The gender bias in sleep apnea diagnosis. Are women missed because they have different symptoms

BACKGROUND Population-based studies have shown that sleep apnea is underdiagnosed in women, relative to men. One hypothesis for this gender bias is that women with sleep apnea are missed because clinical guidelines for the evaluation and diagnosis of sleep apnea, established primarily on men, are not valid for women. In this investigation, data from the Wisconsin Sleep Cohort Study, a community-based study of the natural history of sleep apnea, were used to determine whether women with sleep apnea have unique symptoms or complaints. METHODS The sample comprised 551 men and 388 women, none of whom had ever been given a diagnosis of sleep apnea. Data on typical sleep apnea symptoms and other factors were obtained by interview and survey. Sleep apnea status was determined from the frequency of apneic and hypopneic events during sleep as recorded by in-laboratory, whole-night polysomnography. The sensitivity and relative predictive power of each symptom or factor for sleep apnea at different severity levels were calculated and compared by gender. RESULTS Regardless of severity level, women with sleep apnea did not report symptoms that differed significantly from those of men with the same level of sleep apnea. For men and women, snoring was the most sensitive and strongest predictor of sleep apnea. CONCLUSIONS Current clinical indications for sleep apnea evaluation are as appropriate for women as they are for men. Other reasons for the gender disparity in sleep apnea diagnosis, including the possibility that health care providers disregard typical symptoms in women, should be pursued.

Age-related maculopathy in a multiracial United States population: the National Health and Nutrition Examination Survey III.

OBJECTIVE To investigate the prevalence of and risk factors for age-related maculopathy (ARM) in three racial/ethnic groups: non-Hispanic whites, non-Hispanic blacks, and Mexican-Americans. DESIGN A nationally representative population-based, cross-sectional study. PARTICIPANTS A total of 8270 persons 40 years of age or older, a sample of the Third National Health and Nutrition Examination Survey. MAIN OUTCOME MEASURES Age-related maculopathy was determined by the grading of fundus photographs using a standardized protocol. RESULTS The prevalence of any ARM in the civilian noninstitutionalized United States population including those 40 years of age or older was 9.4% (95% confidence interval [CI], 8.2, 10.6) as estimated from the sample. After adjusting for age, there was no difference in the prevalence of early ARM (defined largely by the presence of soft drusen) by ethnic/racial group. However, for the less frequent component lesions of early ARM (increased retinal pigment and retinal pigment epithelial depigmentation), the odds ratios (95% CIs) comparing non-Hispanic blacks to non-Hispanic whites were 0.47 (0.31, 0.74) and 0.59 (0.33, 1.04), respectively, and for comparing Mexican-Americans to non-Hispanic whites, they were 0.41 (0.21, 0.81) and 0.72 (0.44, 1.19), respectively. For late ARM, the odds ratio (95% CI) for non-Hispanic blacks compared to non-Hispanic whites was 0.34 (0.10, 1.18) and for Mexican-Americans compared to non-Hispanic whites, it was 0.25 (0.07, 0.90). Other than age, none of the personal, medical, or physiologic variables studied were statistically significantly associated with any of the ARM endpoints in any of the three races/ethnic groups. CONCLUSION Overall, rates of any ARM (including all early and late lesions) are not significantly different among non-Hispanic blacks, Mexican-Americans, and non-Hispanic whites. However, the rates of individual lesions suggest that non-Hispanic whites and Mexican-Americans may be protected against retinal pigment abnormalities and lesions associated with late ARM. There appears to be little influence of personal, medical, and environmental factors studied on these results. Further studies in larger populations of older persons in these ethnic groups would likely clarify these relations.

Multivariate assessment of traditional risk factors for chronic lung disease in very low birth weight neonates

All neonates (n = 581) with birth weights less than 1501 gm admitted to seven neonatal intensive care units in Wisconsin and Iowa were candidates for a study aimed at the multivariate assessment of risk factors for chronic lung disease while controlling for baseline severity of respiratory disease. Data from 361 neonates were analyzed for all risk factors except fluids; only neonates weighing less than 1200 gm were included (n = 220). Information on traditional risk factors for chronic lung disease was abstracted. A total of 110 (30%) of the analyzed neonates were oxygen dependent on day 30 of life. The following baseline factors were associated with increased risk of oxygen dependence in a joint multivariate model: lower birth weight (odds ratio 1.4/100 gm), higher baseline severity score (odds ratio 2.7/doubling at 32 weeks gestational age), lower gestational age (odds ratio 2.4/week at severity 0), Apgar score at 1 minute (odds ratio 1.6/2 points), male gender (odds ratio 1.9), and nonblack race (odds ratio 2.2). After adjustment for all baseline factors, patent ductus arteriosus, ventilator pressure at 96 hours, oxygen at 96 hours, and fluid intake were associated with oxygen dependence. Neonates with a low baseline severity score who remained oxygen dependent had a higher intake of fluid relative to output, whereas neonates with a higher baseline severity score had higher fluid intake and output. Lack of weight loss was associated with increased severity but not with oxygen dependence. The results of this study generally confirm the significance of previously reported risk factors for chronic lung disease in a multivariate setting but show that risk factors may not have the same impact in neonates with different baseline severity.

Retinal vascular abnormalities in persons with type 1 diabetes: The Wisconsin Epidemiologic Study of Diabetic Retinopathy: XVIII☆

PURPOSE To describe the distribution of retinal vascular characteristics and their correlates in people with type 1 diabetes. DESIGN Population-based study with baseline cross-sectional findings. PARTICIPANTS Nine hundred ninety-six persons who were diagnosed with diabetes before 30 years of age and who were taking insulin in an 11-county area in south-central Wisconsin participated in the baseline examination from 1980 to 1982. In addition, 225 persons without diabetes participated. METHODS Retinal photographs of 7 standard fields were taken; lightbox grading was performed to determine arteriovenous (A/V) nicking and focal retinal arteriolar narrowing. Computer-assisted grading was performed from a digitized image of field 1 to determine central retinal arteriolar equivalent (CRAE), central retinal venular equivalent (CRVE), and the arteriole-to-venule ratio (AVR). MAIN OUTCOME MEASURES Frequency and distribution of A/V nicking, CRAE, CRVE, AVR, and focal retinal arteriolar narrowing. RESULTS In multivariate analyses, retinopathy severity, mean arterial blood pressure, presence of gross proteinuria, glycosylated hemoglobin, and history of cardiovascular disease were associated with CRAE. Retinopathy severity, age, mean arterial blood pressure, duration of diabetes, glycosylated hemoglobin level, and body mass index were associated with CRVE. With the exception of glycosylated hemoglobin, similar factors were associated with AVR. Age (odds ratio [OR] per 10 years, 2.43 and 2.02) and retinopathy severity (OR per level, 1.14 and 1.21) were associated with focal retinal arteriolar narrowing and A/V nicking, respectively. In persons >/=18 years of age, smoking was associated with CRAE, CRVE, and A/V nicking (OR, 2.67), but not with AVR or focal arteriolar narrowing. CONCLUSIONS This study documented the frequency and distribution of retinal vascular characteristics and their relationships to various factors in persons with type 1 diabetes.

Gender differences in health-related quality-of-life are partly explained by sociodemographic and socioeconomic variation between adult men and women in the US: evidence from four US nationally representative data sets

PurposeThe purpose of this study was to describe gender differences in self-reported health-related quality-of-life (HRQoL) and to examine whether differences are explained by sociodemographic and socioeconomic status (SES) differentials between men and women.MethodsData were from four US nationally representative surveys: US Valuation of the EuroQol EQ-5D Health States Survey (USVEQ), Medical Expenditure Panel Survey (MEPS), National Health Measurement Study (NHMS) and Joint Canada/US Survey of Health (JCUSH). Gender differences were estimated with and without adjustment for sociodemographic and SES indicators using regression within and across data sets with SF-6D, EQ-5D, HUI2, HUI3 and QWB-SA scores as outcomes.ResultsWomen have lower HRQoL scores than men on all indexes prior to adjustment. Adjusting for age, race, marital status, education and income reduced but did not remove the gender differences, except with HUI3. Adjusting for marital status or income had the largest impact on estimated gender differences.ConclusionsThere are clear gender differences in HRQoL in the United States. These differences are partly explained by sociodemographic and SES differentials.