Association of sleep-disordered breathing, sleep apnea, and hypertension in a large community-based study. Sleep Heart Health Study.

CONTEXT: Sleep-disordered breathing (SDB) and sleep apnea have been linked to hypertension in previous studies, but most of these studies used surrogate information to define SDB (eg, snoring) and were based on small clinic populations, or both. OBJECTIVE: To assess the association between SDB and hypertension in a large cohort of middle-aged and older persons. DESIGN AND SETTING: Cross-sectional analyses of participants in the Sleep Heart Health Study, a community-based multicenter study conducted between November 1995 and January 1998. PARTICIPANTS: A total of 6132 subjects recruited from ongoing population-based studies (aged > or = 40 years; 52.8% female). MAIN OUTCOME MEASURES: Apnea-hypopnea index (AHI, the average number of apneas plus hypopneas per hour of sleep, with apnea defined as a cessation of airflow and hypopnea defined as a > or = 30% reduction in airflow or thoracoabdominal excursion both of which are accompanied by a > or = 4% drop in oxyhemoglobin saturation) [corrected], obtained by unattended home polysomnography. Other measures include arousal index; percentage of sleep time below 90% oxygen saturation; history of snoring; and presence of hypertension, defined as resting blood pressure of at least 140/90 mm Hg or use of antihypertensive medication. RESULTS: Mean systolic and diastolic blood pressure and prevalence of hypertension increased significantly with increasing SDB measures, although some of this association was explained by body mass index (BMI). After adjusting for demographics and anthropometric variables (including BMI, neck circumference, and waist-to-hip ratio), as well as for alcohol intake and smoking, the odds ratio for hypertension, comparing the highest category of AHI (> or = 30 per hour) with the lowest category (< 1.5 per hour), was 1.37 (95% confidence interval [CI], 1.03-1.83; P for trend = .005). The corresponding estimate comparing the highest and lowest categories of percentage of sleep time below 90% oxygen saturation (> or = 12% vs < 0.05%) was 1.46 (95% CI, 1.12-1.88; P for trend <.001). In stratified analyses, associations of hypertension with either measure of SDB were seen in both sexes, older and younger ages, all ethnic groups, and among normal-weight and overweight individuals. Weaker and nonsignificant associations were observed for the arousal index or self-reported history of habitual snoring. CONCLUSION: Our findings from the largest cross-sectional study to date indicate that SDB is associated with systemic hypertension in middle-aged and older individuals of different sexes and ethnic backgrounds.

Gender differences in response to nicotine replacement therapy: objective and subjective indexes of tobacco withdrawal.

K. A. Perkins (1996) recently proposed that nicotine reinforcement controls smoking to a greater degree among men than women and that consequently, nicotine replacement therapy (NRT) during smoking cessation should benefit men more than women. The authors tested this hypothesis. Polysomnographic measures of sleep and self-report indexes of tobacco withdrawal were collected pre- and postcessation from an active nicotine patch group and a placebo patch group in a randomized, double-blind clinical trial (N = 34). Objective sleep parameters supported Perkins's hypothesis and indicated that among women, NRT may be less effective at suppressing certain withdrawal responses compared with men and may produce some iatrogenic effects. Valid and reliable self-report measures of withdrawal did not reveal gender differences in response to NRT.

Blood pressure perturbations caused by subclinical sleep-disordered breathing.

We studied the acute effects of apneas and hypopneas on blood pressure in a nonclinic population of middle-aged adults. Arterial pressure was measured noninvasively (photoelectric plethysmography) during an overnight, in-laboratory polysomnographic study in 72 men and 23 women enrolled in the Wisconsin Sleep Cohort Study, a population-based study of sleep-disordered breathing. Sleep-disordered breathing events (272 apneas and 1469 hypopneas) were observed in 92% of subjects. The across-subject mean decreases in arterial O2 saturation were 9+/-8% (SD) for apneas (17+/-8 seconds duration) and 4+/-3% for hypopneas (21+/-6 seconds duration; 41+/-17% of baseline ventilation). In both apneas and hypopneas, even those with only 1% to 3% O2 desaturations, blood pressure decreased during the event, followed by an abrupt increase in the postevent recovery period. Mean values for peak changes in blood pressure (difference between the maximum during the recovery period and the minimum during the event) were 23+/-10 mm Hg for systolic and 13+/-6 mm Hg for diastolic pressure. The strongest predictors of the pressor responses to apneas and hypopneas were (in order of importance): magnitude of the ventilatory overshoot, length of the event, magnitude of changes in heart rate and arterial O2 saturation, and presence or absence of electroencephalographic arousal. We speculate that these fluctuations may play a role in the pathogenesis of hypertension in individuals with subclinical sleep-disordered breathing.

Automated detection and classification of sleep-disordered breathing from conventional polysomnography data.

Efficient automated detection of sleep-disordered breathing (SDB) from routine polysomnography (PSG) data is made difficult by the availability of only indirect measurements of breathing. The approach we used to overcome this limitation was to incorporate pulse oximetry into the definitions of apnea and hypopnea. In our algorithm, 1) we begin with the detection of desaturation as a fall in oxyhemoglobin saturation level of 2% or greater once a rate of descent greater than 0.1% per second (but less than 4% per second) has been achieved and then ask if an apnea or hypopnea was responsible; 2) an apnea is detected if there is a period of no breathing, as indicated by sum respiratory inductive plethysmography (RIP), lasting at least 10 seconds and coincident with the desaturation event; and 3) if there is breathing, a hypopnea is defined as a minimum of three breaths showing at least 20% reduction in sum RIP magnitude from the immediately preceding breath followed by a return to at least 90% of that "baseline" breath. Our evaluation of this algorithm using 10 PSG records containing 1,938 SDB events showed strong event-by-event agreement with manual scoring by an experienced polysomnographer. On the basis of manually verified computer desaturations, detection sensitivity and specificity percentages were, respectively, 73.6 and 90.8% for apneas and 84.1 and 86.1% for hypopneas. Overall, 93.1% of the manually detected events were detected by the algorithm. We have designed an efficient algorithm for detecting and classifying SDB events that emulates manual scoring with high accuracy.

Tobacco withdrawal and nicotine replacement influence objective measures of sleep.

Research has not adequately characterized the impact of tobacco withdrawal on objectively assessed sleep parameters despite the recent inclusion of insomnia as a nicotine withdrawal sign in the Diagnostic and Statistical Manual of Mental Disorders (4th ed.; American Psychiatric Association, 1994). Moreover, whether 24-hr nicotine replacement aids or interferes with sleep during withdrawal is unknown. In a double-masked, randomized clinical trial, 34 cigarette smokers who were motivated to quit received either active nicotine patches or placebo patches while quitting. Sleep was polysomnographically monitored for 2 precessation nights and 3 postcessation nights. The study demonstrates that among dependent smokers (a) tobacco withdrawal increases objectively assessed sleep disturbance (sleep fragmentation) and (b) nicotine replacement results in postcessation improvements in important polysomnographic measures of sleep quality (sleep fragmentation, Stage 3 and Stage 4 sleep).

Hematuria home screening: repeat testing results.

To determine at what interval screening should be repeated to detect bladder cancer before it becomes muscle invasive 856 men who had 14 negative daily home tests for hematuria with a chemical reagent strip 9 months previously performed repeat tests. Of these men 50 (5.8%) had at least 1 positive test during the second 14-day screening period and 38 were evaluated, 15 of whom (39.5%) had significant urological pathological conditions, including 8 with malignancies. Bladder cancer was noted in 7 men, with no tumor invading the muscularis propria. The finding of 7 bladder cancers in 856 men (0.82%) who had a negative test 9 months previously indicates that bladder cancer has a brief preclinical duration and that testing must be repeated at least annually for screening to detect bladder cancer consistently before invasion occurs.

Comparison of bladder cancer outcome in men undergoing hematuria home screening versus those with standard clinical presentations.

OBJECTIVES: Because repetitive hematuria home screening with a chemical reagent strip can detect early stage bladder cancer (BC) in asymptomatic middle-aged and elderly men, the ability of this screening to effect earlier detection and reduce BC mortality was investigated. METHODS: Grades, stages, and outcomes of BCs detected by hematuria screening in 1575 men were compared with those of all newly diagnosed BCs in men age 50 years or older reported to the Wisconsin cancer registry in 1988. BC grades and stages were assigned by review of all pathology slides/blocks, and causes of deaths were determined from cancer registry records. As an additional control group, outcomes of BC cases diagnosed in men solicited to take part in screening, who declined, were also determined. RESULTS: The proportions of low-grade (grades 1 and 2) superficial (Stages Ta and T1) versus high-grade (grade 3) or invasive (Stage T2 or higher) cancers in cases detected by hematuria screening (screened cases) and those reported to the tumor registry (unscreened cases) were not significantly different (52.4% versus 47.7% in 21 screened and 56.8% versus 43.3% in 511 unscreened cases) (P > 0.20). Of the high-grade or invasive cases, however, the proportion of late stage (T2 or higher) tumors was significantly lower in the screening-detected BCs compared to unscreened ones (P = 0.007). No screened case has died of BC (3- to 9-year follow-up), whereas 16.4% of unscreened cases have within 2 years of diagnosis (P = 0.025). Twenty-three of 1940 (1.2%) men who were solicited but chose not to participate in screening were diagnosed with BC within 18 months after what would have been their last home screening date, compared with 1.3% of participants having BC detected by screening. Thus, screening participants and those who were solicited and declined had similar likelihoods of developing BC. CONCLUSIONS: Hematuria home screening detects high-grade cancers before they become muscle invading and significantly reduces BC mortality.

Smoking as a risk factor for sleep-disordered breathing.

BACKGROUND: Recent evidence indicates that the prevalence of sleep-disordered breathing is remarkably high (24% for men and 9% for women) and that the public health burden attributable to sleep-disordered breathing is substantial. This investigation examines current and former cigarette smoking as potential risk factors for sleep-disordered breathing. METHODS: Data were from 811 adults enrolled in the University of Wisconsin Sleep Cohort Study, Madison. The Sleep Cohort Study is a longitudinal, epidemiologic study that uses nocturnal polysomnography to investigate sleep-disordered breathing and other disorders of sleep. The presence and severity of sleep-disordered breathing was quantified by the frequency of apneas and hypopneas per hour of sleep. RESULTS: Logistic regression analyses were used to control for potential confounding factors. Compared with never smokers, current smokers had a significantly greater risk of snoring (odds ratio, 2.29) and of moderate or worse sleep-disordered breathing (odds ratio, 4.44). Heavy smokers (> or = 40 cigarettes per day) had the greatest risk of mild sleep-disordered breathing (odds ratio, 6.74) and of moderate or worse sleep-disordered breathing (odds ratio, 40.47). Former smoking was unrelated to snoring and sleep-disordered breathing after adjustment for confounders. CONCLUSIONS: Current cigarette smokers are at greater risk for sleep-disordered breathing than are never smokers. Heavy smokers have the greatest risk while former smokers are not at increased risk for sleep-disordered breathing. Thus, smoking cessation should be considered in the treatment and prevention of sleep-disordered breathing.

The relation between cigarette smoking and sleep disturbance.

BACKGROUND: There is little epidemiological or clinical information on the relation between smoking and sleep disturbance, despite evidence suggestive of a relationship. The present study tested the hypothesis that cigarette smoking is associated with sleep disturbance. METHODS: Survey data from 3,516 adults were collected as part of a longitudinal, epidemiologic study of sleep-disordered breathing. Symptoms of insomnia, hypersomnia, and parasomnia were assessed using diagnostic criteria from the Diagnostic and Statistical Manual of Mental Disorders (3rd ed., revised). RESULTS: Among both males and females, smoking was associated with difficulty initiating sleep, and difficulty waking up. Excessive daytime sleepiness was related to smoking only for females while nightmares and disturbing dreams were related to smoking only among males. CONCLUSIONS: Smoking was associated with difficulty initiating sleep and with a constellation of symptoms suggestive of sleep fragmentation. Sleep disturbance may be more prevalent among smokers due to the stimulant effects of nicotine, nightly withdrawal, an increased prevalence of sleep disordered breathing relative to nonsmokers, and/or an association with psychological disturbance. These results have important clinical and public health implications for reduction of the disease and disability associated with smoking and sleep disturbance.

Sleep apnea and hypertension. A population-based study.

OBJECTIVE: To measure the independent association of sleep-disordered breathing (sleep apnea and habitual snoring) and hypertension in a healthy adult population. DESIGN: A cross-sectional study of blood pressure during wakefulness and sleep among participants with and without sleep-disordered breathing. SETTING: Community-based study. PARTICIPANTS: 147 men and women, aged 30 to 60 years, selected from Wisconsin State employees enrolled in the Wisconsin Sleep Cohort Study, an ongoing, prospective, epidemiologic study of sleep-disordered breathing. MEASUREMENTS: Sleep and medical history interview, nocturnal polysomnography, and 24-hour ambulatory blood pressure monitoring in all participants. RESULTS: Mean blood pressures were significantly higher among participants with sleep apnea (> or = 5 apneas or hypopneas per hour of sleep) compared with those without (131/80 +/- 1.7/1.1 mm Hg compared with 122/75 +/- 1.9/1.2 mm Hg during wakefulness and 113/66 +/- 1.8/1.1 mm Hg compared with 104/62 +/- 2/1.3 mm Hg during sleep, respectively; P < 0.05). The variability of the blood pressure during sleep was significantly greater in participants with sleep apnea or a history of snoring compared with those without (P < 0.05). After controlling for obesity, age, and sex, sleep apnea was significantly associated with hypertension in a dose-response fashion, with odds ratios ranging from 2.0 for 5 apneic or hypopneic episodes per hour of sleep to 5.0 for 25 apneic or hypopneic episodes. CONCLUSIONS: Our data indicate an association between hypertension and sleep apnea independent of obesity, age, and sex in a nonselected, community-based adult population.

Correlates of malnutrition among children under 2 years of age admitted to hospital in Yaoundé, Cameroon.

A survey of health status, biodemographics, and use of health care services of all children under 2 years of age, consecutively admitted to the Baudeloque ward of the Central Hospital of Yaoundé, Cameroon, was conducted over a 12-month period (1984). During the admission procedure, each child's mother or surrogate mother was interviewed and the child was weighted according to study protocol; additional data were collected by review of hospital records. A total of 669 children were recruited into the study sample; there were no refusals. Nutritional status was estimated by categories based on weight for age. Overall, 43 per cent of the sample were of normal weight-for-age, and 6 per cent, 19 per cent, and 32 per cent were categorized as having severe, moderate, and mild malnutrition, respectively. Multinomial logit modelling was used to identify independent correlates of mild, moderate, and severe PEM simultaneously. The study findings underscore the broad health benefits of immunizations. Furthermore, any prior contact of mother or child with the health care system appears to be associated with better nutritional status on hospital admission. Children with mothers employed outside the home may benefit particularly from health services outreach programmes.

Home screening for hematuria: results of a multiclinic study.

The majority of urinary tract tumors cause bleeding in the urine. A program designed to detect hematuria before it is grossly apparent may contribute to earlier detection and more successful treatment of these malignancies. To test this hypothesis a hematuria home screening study was conducted. A total of 1,340 healthy men 50 years old or older used chemical reagent strips for 14 consecutive days to test the urine. Of the men 283 (21.1%) had at least 1 episode of hematuria. Of the 192 hematuria positive men who received a complete urological evaluation 16 (8.3%) had urological cancers and 47 (24.5%) had other hematuria-causing diseases that required immediate treatment. The quantity and frequency of hematuria were not related to disease severity. A hematuria home screening regimen is feasible and economical, and may promote the early detection of urinary tract cancers and other diseases in men more than 50 years old.

Gastric cancer mortality and nitrate levels in Wisconsin drinking water.

The association between nitrate levels in public and private sources of drinking water and gastric cancer mortality in Wisconsin was investigated in a case-control study. All gastric cancer deaths of Wisconsin residents from 1982 through 1985 were compared with deaths from other causes (controls), and nitrate levels in the home drinking water of these residents were determined. Nitrate measures for public sources were obtained from historic nitrate data from municipal sources that existed in 1970. Nitrate measures for private water sources were obtained by testing the wells individually at the existing residences. Controls were matched individually to gastric cancer cases with respect to sex, year of birth, year of death, Wisconsin birth, and Wisconsin residency at the time of death. Matched-pair analyses were performed on the paired data, and the following levels of nitrate-nitrogen exposure were used as indicators of exposure: 0.5, 2.5, 5.0, and 10.0 mg/l. Matched-pair analysis was also performed for which private water supply constituted exposure. Odds ratios and 95% confidence intervals were, respectively, 0.92 (0.75, 1.12); 0.97 (0.74, 1.35); 0.86 (0.69, 1.08); 1.50 (0.12, 18.25); and 1.09 (0.82, 1.47) for exposure to private well-water sources. These results did not indicate an increased risk of gastric cancer at any level.

Age as a predictor of an aggressive clinical course for superficial bladder cancer in men.

Tumor grade and stage are two of the strongest predictors for indolent versus aggressive clinical course in bladder cancer. To identify age-related trends in tumor aggressiveness the authors investigated the relationships of age with grade and stage. Pathologic specimens were obtained for 89% (527 of 590) of new bladder cancer cases among men older than 50 years of age reported to the state tumor registry in Wisconsin for 1988. Tumors were grouped as low grade (G1, G2) or high grade (G3), and as superficial (Ta) or invasive (greater than or equal to T1), according to the TNM system. This analysis included 485 transitional cell carcinomas (TCC) for which the authors determined stage-stratified and grade-stratified odds ratios for men 50 through 64 years of age and older than 65 years of age. Men older than 65 years of age with superficial TCC were more than three times as likely to have a high-grade malignancy than men 50 through 64 years of age (P = 0.01); the odds ratio was 3.44 (95% CI = 1.28, 9.26). A relationship was not apparent for invasive TCC. Age and stage were weakly associated for low-grade and high-grade TCC that may be due, in part, to the strong correlation of stage with grade as a prognostic indicator. These data suggest that men in older age groups are at increased risk for superficial bladder cancer of high grade, which portends an aggressive clinical course.

Urinary tract cancers found by homescreening with hematuria dipsticks in healthy men over 50 years of age.

In a homescreening study 235 asymptomatic men, 50 years of age and older without known causes of hematuria, tested their urine each week with a chemical reagent strip for the presence of blood for 1 year. Forty-four men had hematuria at least once, and 31 had a full urologic evaluation. Of these, eight were found to have urinary cancers and seven had nonmalignant diseases warranting immediate treatment. In six of these 15 men (only two with cancer) hematuria occurred in over 1/3 of the testings, and in four hematuria was found on microscopic urinalysis at the time of urologic evaluation. The degree of hematuria was unrelated to the seriousness of its cause. We conclude that in this population hematuria occurs intermittently and when found, regardless of quantity or symptoms, serious underlying pathology must be ruled out. Furthermore, regular hematuria home testing offers a promising means of detecting urinary cancers and other diseases that warrant therapy in asymptomatic men 50 years of age and older.

A case-control study of breast cancer and alcohol consumption habits.

A population-based case-control study was conducted to investigate the contribution of alcohol consumption during the early adult years (ages 18-35 years) and later adult years (older than age 35) to breast cancer risk. Alcohol consumption histories were obtained by questionnaire from 277 breast cancer cases, 372 population controls, and 433 controls with cancer of sites other than breast. Alcohol exposure during both age periods was significantly greater for breast cancer cases, but risks, estimated by maximum likelihood odds ratios, were highest for alcohol consumption frequency during the early adult period. Age-adjusted odds ratios and 95% confidence intervals (CI) for breast cancer risk and early age drinking (10 versus 0 drinks/week) were 2.2 (95% CI = 1.34, 3.5), relative to the population controls and 2.0 (95% CI = 1.3, 3.1) relative to the cancer controls. Based on later-age drinking of ten versus zero drinks/week, odds ratios were 1.8 (95% CI = 1.3, 2.6) and 1.6 (95% CI = 1.2, 2.2) relative to the population and cancer controls, respectively. The risk estimates were not altered by introduction of the following covariates into the analyses: mother with breast cancer, family status, education, body mass index, smoking, supplemental hormone use, and diet.

A validation study of body fat distribution as determined by self-measurement of waist and hip circumference.

The accuracy of self-measured waist and hip circumferences is investigated in 200 men and women 30-85 years old. Systematic bias is not found in circumferences measured by the men. Female subjects tend to underestimate waist circumference. This error is greatest in women with central fat distribution (characterized by waist:hip ratio). Misclassification of fat distribution pattern may result from this error, which may in turn lead to underestimation of associations between fat pattern and disease risk.

Case-control study of proximal and distal colon cancer and diet in Wisconsin.

The relationship between diet and subsite-specific colon cancer was investigated using dietary histories obtained from a statewide, population-based sample of 152 proximal colon cancer patients, 201 distal colon cancer patients and 618 general population controls. The results do not support hypotheses that (1) dietary fat and cholesterol are more strongly related to proximal colon cancer and (2) vegetables and other dietary sources of fiber are more strongly associated with distal colon cancer. Vegetable consumption over lifetime was consistently protective for both proximal and distal colon cancer. Odds ratios and 95% confidence intervals for the most significant dietary factors (based on high vs. low consumption) for proximal colon cancer were: salad, 0.29 (0.17, 0.48); miscellaneous vegetables, 0.58 (0.35, 0.97); cruciferous vegetables, 0.59 (0.35, 0.97); processed lunchmeat, 2.04 (1.31, 3.17); pan-fried foods, 1.79 (1.15, 2.80); eggs, 1.75 (1.02, 2.99) and for distal colon cancer they were: salad, 0.43 (0.28, 0.67); cruciferous vegetables, 0.44 (0.28, 0.71); cheese, 0.62 (0.40, 0.96); processed lunchmeat, 1.79 (1.17, 2.73); pan-fried foods, 1.55 (1.03, 1.27). The results support recommendations that the "prudent diet" (low-fat, high-vegetable) may reduce colon cancer risk.

Cross-sectional study of recurrent herpes labialis. Prevalence and risk factors.

Consecutive blood donors at 25 sites in southern Wisconsin were interviewed in 1985 to ascertain recurrent herpes labialis histories, other perioral conditions, and status on possible predisposing factors and correlates of lesion recurrence. The prevalence of recurrent herpes labialis was 32.9%. Of the cases, 51.3% reported at least two recurrences per year, 8.6% characterized their condition as severe, and 10% sought medical care. Relations were examined between recurrent herpes labialis and family history of the disease, ethnicity, complexion, hair and eye color, other chronic perioral conditions, solar radiation, exposure to dental procedures, and smoking. The risk of recurrent herpes labialis associated with disease in various first-degree family members, estimated by age-adjusted odds ratios (nominal 95% confidence intervals) were: mother, 3.30 (1.86-5.84); father, 3.80 (1.80-8.12); sister(s), 3.93 (2.25-6.89); and brother(s), 6.81 (3.14-15.04). Ethnicity and phenotypes were not related to disease status. Cases had a higher prevalence of recurrent aphthous ulcers (odds ratio = 3.00, 95% confidence interval = 1.79-5.02) and reported more exposure to solar radiation and more extensive dental histories.