Daytime sleepiness and risk of stroke and vascular disease: findings from the Northern Manhattan Study (NOMAS).

BACKGROUND: Recent studies have suggested that poor quality and diminished quantity of sleep may be independently linked to vascular events although prospective and multiethnic studies are limited. This study aimed to explore the relationship between daytime sleepiness and the risk of ischemic stroke and vascular events in an elderly, multiethnic prospective cohort. METHODS AND RESULTS: As part of the Northern Manhattan Study, the Epworth Sleepiness Scale was collected during the 2004 annual follow-up. Daytime sleepiness was trichotomized using previously reported cut points of no dozing, some dozing, and significant dozing. Subjects were followed annually for a mean of 5.1 years. Cox proportional hazards models were used to calculate hazard ratios and 95% confidence intervals for stroke, myocardial infarction, and death outcomes. We obtained the Epworth Sleepiness Scale on 2088 community residents. The mean age was 73.5 ± 9.3 years; 64% were women; 17% were white, 20% black, 60% Hispanic, and 3% were other. Over 44% of the cohort reported no daytime dozing, 47% some dozing, and 9% significant daytime dozing. Compared with those reporting no daytime dozing, individuals reporting significant dozing had an increased risk of ischemic stroke (hazard ratio, 2.74 [95% confidence interval, 1.38-5.43]), all stroke (3.00 [1.57-5.73]), the combination of ischemic stroke, myocardial infarction, and vascular death (2.38 [1.50-3.78]), and all vascular events (2.48 [1.57-3.91]), after adjusting for medical comorbidities. CONCLUSIONS: Daytime sleepiness is an independent risk factor for stroke and other vascular events. These findings suggest the importance of screening for sleep problems at the primary care level.

Sleep disturbances and risk of frailty and mortality in older men.

OBJECTIVE: To test the hypothesis that non-frail older men with poorer sleep at baseline are at increased risk of frailty and death at follow-up. METHODS: In this prospective cohort study, subjective (questionnaires) and objective sleep parameters (actigraphy, in-home overnight polysomnography) were measured at baseline in 2505 non-frail men aged ≥67years. Repeat frailty status assessment performed an average of 3.4 years later; vital status assessed every four months. Sleep parameters expressed as dichotomized predictors using clinical cut-points. Status at follow-up exam classified as robust, intermediate (pre-frail) stage, frail, or died in interim. RESULTS: None of the sleep disturbances were associated with the odds of being intermediate/frail/dead (vs. robust) at follow-up. Poor subjective sleep quality (multivariable odds ratio [MOR] 1.26, 95% CI 1.01-1.58), greater nighttime wakefulness (MOR 1.31, 95% CI 1.04-1.66), and greater nocturnal hypoxemia (MOR 1.47, 95% CI 1.02-2.10) were associated with a higher odds of frailty/death at follow-up (vs. robust/intermediate). Excessive daytime sleepiness (MOR 1.60, 95% CI 1.03-2.47), greater nighttime wakefulness (MOR 1.57, 95% CI 1.12-2.20), severe sleep apnea (MOR 1.74, 95% CI 1.04-2.89), and nocturnal hypoxemia (MOR 2.28, 95% CI 1.45-3.58) were associated with higher odds of death (vs. robust/intermediate/frail at follow-up). The association between poor sleep efficiency and mortality nearly reached significance (MOR 1.48, 95% CI 0.99-2.22). Short sleep duration and prolonged sleep latency were not associated with frailty/death or death at follow-up. CONCLUSIONS: Among non-frail older men, poor subjective sleep quality, greater nighttime wakefulness, and greater nocturnal hypoxemia were independently associated with higher odds of frailty or death at follow-up, while excessive daytime sleepiness, greater nighttime wakefulness, severe sleep apnea and greater nocturnal hypoxemia were independently associated with an increased risk of mortality.

Sleep disordered breathing with excessive daytime sleepiness is a risk factor for mortality in older adults.

STUDY OBJECTIVES: Excessive daytime sleepiness (EDS) is associated with increased mortality in older adults, yet sleep disordered breathing (SDB), a common cause of sleepiness, has not been shown to increase mortality in older adults. This study examined the relationship between daytime sleepiness, SDB, self-report sleep parameters, and mortality in older adults. DESIGN: Longitudinal cohort study. SETTING: Clinical and Translational Research Center, at-home testing. PARTICIPANTS: 289 study participants (age >65, no dementia or depression at the time of enrollment) classified as having EDS (n=146) or not (n=143). MEASUREMENTS AND RESULTS: Study participants underwent in-lab polysomnography and multiple sleep latency testing at cohort inception. Survival analysis was conducted, with an average follow-up of 13.8 years. Excessive daytime sleepiness was associated with an unadjusted mortality hazard ratio of 1.5 (95% CI 1.1-2.0). The unadjusted mortality hazard ratio for study participants with both EDS and SDB (apnea-hypopnea index ≥20 events/h) was 2.7, 95% CI: 1.8-4.2. These findings persisted with an adjusted mortality hazard ratio of 2.3, 95% CI: 1.5-3.6 in the final model that included other covariates associated with increased mortality (sleep duration >8.5 h, self-reported angina, male gender, African American race, and age). CONCLUSION: The presence of SDB is an important risk factor for mortality from excessive daytime sleepiness in older adults. In the presence of SDB at an AHI ≥20 events/h, EDS was associated with an increased all-cause mortality risk in older adults, even when adjusting for other significant risk factors, such as prolonged sleep duration. In older patients who had SDB without EDS, or EDS without SDB, there was no increased all-cause mortality rate.

Sleep duration and all-cause mortality: a systematic review and meta-analysis of prospective studies.

BACKGROUND: Increasing evidence suggests an association between both short and long duration of habitual sleep with adverse health outcomes. OBJECTIVES: To assess whether the population longitudinal evidence supports the presence of a relationship between duration of sleep and all-cause mortality, to investigate both short and long sleep duration and to obtain an estimate of the risk. METHODS: We performed a systematic search of publications using MEDLINE (1966-2009), EMBASE (from 1980), the Cochrane Library, and manual searches without language restrictions. We included studies if they were prospective, had follow-up >3 years, had duration of sleep at baseline, and all-cause mortality prospectively. We extracted relative risks (RR) and 95% confidence intervals (CI) and pooled them using a random effect model. We carried out sensitivity analyses and assessed heterogeneity and publication bias. RESULTS: Overall, the 16 studies analyzed provided 27 independent cohort samples. They included 1,382,999 male and female participants (followup range 4 to 25 years), and 112,566 deaths. Sleep duration was assessed by questionnaire and outcome through death certification. In the pooled analysis, short duration of sleep was associated with a greater risk of death (RR: 1.12; 95% CI 1.06 to 1.18; P < 0.01) with no evidence of publication bias (P = 0.74) but heterogeneity between studies (P = 0.02). Long duration of sleep was also associated with a greater risk of death (1.30; [1.22 to 1.38]; P < 0.0001) with no evidence of publication bias (P = 0.18) but significant heterogeneity between studies (P < 0.0001). CONCLUSION: Both short and long duration of sleep are significant predictors of death in prospective population studies.

Habitual sleep duration and insomnia and the risk of cardiovascular events and all-cause death: report from a community-based cohort.

STUDY OBJECTIVES: To investigate the relationship between sleep duration and insomnia severity and the risk of all-cause death and cardiovascular disease (CVD) events. DESIGN: Prospective cohort study. SETTING: Community-based. PARTICIPANTS: A total of 3,430 adults aged 35 years or older. INTERVENTION: None. MEASUREMENTS AND RESULTS: During a median 15.9 year (interquartile range, 13.1 to 16.9) follow-up period, 420 cases developed cardiovascular disease and 901 cases died. A U-shape association between sleep duration and all-cause death was found: the age and gender-adjusted relative risks (95% confidence interval [CI]) of all-cause death (with 7 h of daily sleep being considered for the reference group) for individuals reporting < or = 5 h, 6 h, 8 h, and > or = 9 h were 1.15 (0.91-1.45), 1.02 (0.85-1.25), 1.05 (0.88-1.27), and 1.43 (1.16-1.75); P for trend, 0.019. However, the relationship between sleep duration and risk of CVD were linear. The multivariate-adjusted relative risk (95% CI) for all-cause death (using individuals without insomnia) were 1.02 (0.86-1.20) for occasional insomnia, 1.15 (0.92-1.42) for frequent insomnia, and 1.70 (1.16-2.49) for nearly everyday insomnia (P for trend, 0.028). The multivariate adjusted relative risk (95% CI) was 2.53 (1.71-3.76) for all-cause death and 2.07 (1.11-3.85) for CVD rate in participants sleeping > or = 9 h and for those with frequent insomnia. CONCLUSIONS: Sleep duration and insomnia severity were associated with all-cause death and CVD events among ethnic Chinese in Taiwan. Our data indicate that an optimal sleep duration (7-8 h) predicted fewer deaths.

Sleep duration and mortality: a systematic review and meta-analysis.

Epidemiologic studies have shown that sleep duration is associated with overall mortality. We conducted a systematic review of the associations between sleep duration and all-cause and cause-specific mortality. PubMed was systematically searched up to January, 2008 to identify studies examining the association between sleep duration and mortality (both all-cause and cause-specific) among adults. Data were abstracted serially in a standardized manner by two reviewers and analyzed using random-effects meta-analysis. Twenty-three studies assessing the associations between sleep duration and mortality were identified. All examined sleep duration measured using participant self-report. Among the 16 studies which had similar reference categories and reported sufficient data on short sleep and mortality for meta-analyses, the pooled relative risk (RR) for all-cause mortality for short sleep duration was 1.10 [95% confidence interval (CI): 1.06, 1.15]. For cardiovascular-related and cancer-related mortality, the RRs associated with short sleep were 1.06 (95% CI: 0.94, 1.18) and 0.99 (95% CI: 0.88, 1.13), respectively. Similarly, among the 17 studies reporting data on long sleep duration and mortality, the pooled RRs comparing the long sleepers with medium sleepers were 1.23 (95% CI: 1.17, 1.30) for all-cause mortality, 1.38 (95% CI: 1.13, 1.69) for cardiovascular-related mortality, and 1.21 (95% CI: 1.11, 1.32) for cancer-related mortality. Our findings indicate that both short sleepers and long sleepers are at increased risk of all-cause mortality. Further research using objective measures of sleep duration is needed to fully characterize these associations.

Association of sleep duration with mortality from cardiovascular disease and other causes for Japanese men and women: the JACC study.

STUDY OBJECTIVES: To examine sex-specific associations between sleep duration and mortality from cardiovascular disease and other causes. DESIGN: Cohort study. SETTING: Community-based study. PARTICIPANTS: A total of 98,634 subjects (41,489 men and 57,145 women) aged 40 to 79 years from 1988 to 1990 and were followed until 2003. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: During a median follow-up of 14.3 years, there were 1964 deaths (men and women: 1038 and 926) from stroke, 881 (508 and 373) from coronary heart disease, 4287 (2297 and 1990) from cardiovascular disease, 5465 (3432 and 2033) from cancer, and 14,540 (8548 and 5992) from all causes. Compared with a sleep duration of 7 hours, sleep duration of 4 hours or less was associated with increased mortality from coronary heart disease for women and noncardiovascular disease/noncancer and all causes in both sexes. The respective multivariable hazard ratios were 2.32 (1.19-4.50) for coronary heart disease in women, 1.49 (1.02-2.18) and 1.47 (1.01-2.15) for noncardiovascular disease/noncancer, and 1.29 (1.02-1.64) and 1.28 (1.03-1.60) for all causes in men and women, respectively. Long sleep duration of 10 hours or longer was associated with 1.5- to 2-fold increased mortality from total and ischemic stroke, total cardiovascular disease, noncardiovascular disease/noncancer, and all causes for men and women, compared with 7 hours of sleep in both sexes. There was no association between sleep duration and cancer mortality in either sex. CONCLUSIONS: Both short and long sleep duration were associated with increased mortality from cardiovascular disease, noncardiovascular disease/noncancer, and all causes for both sexes, yielding a U-shaped relationship with total mortality with a nadir at 7 hours of sleep.

Excessive daytime sleepiness is an independent risk indicator for cardiovascular mortality in community-dwelling elderly: the three city study.

BACKGROUND AND PURPOSE: Excessive daytime sleepiness, one of the most frequent sleep complaints in the elderly, may affect survival, but inconsistent results have been observed in that population so far. We therefore estimated the risk of mortality for excessive daytime sleepiness (EDS) in community-dwelling elderly participating in the Three City Study. METHODS: The Three City Study is a French population-based multicenter prospective study including 9294 subjects (60% women) aged >or=65 years at recruitment between 1999 to 2001. At baseline, 8269 subjects rated EDS and nocturnal sleep complaints as never, rare, regular, and frequent in response to an administered questionnaire and provided information on medication use for sleep or anxiety. Hazard ratios (HR) of EDS (regular or frequent) for mortality over 6 years were estimated by a Cox proportional hazard model. RESULTS: At baseline, 18.7% of the study participants had regular or frequent EDS. After 6 years of follow-up, 762 subjects had died including 260 from cancer and 196 from cardiovascular disease. EDS was associated with a significant 33% increased risk of mortality (95% CI: 1.13 to 1.61) after adjustment for age, gender, study center, body mass index, previous cardiovascular disease, Mini Mental State Examination score, and cardiovascular risk factors. Further adjustment for current use of medication for sleep and for depressive symptoms slightly diminished the HRs. EDS was equally predictive of mortality in those who snored loudly and in those who did not. EDS was related to cardiovascular mortality but not to mortality attributable to cancer. CONCLUSIONS: EDS might be independently associated with total and cardiovascular mortality in community-dwelling elderly.

Restless legs symptoms with sleepiness in relation to mortality: 20-year follow-up study of a middle-aged Swedish population.

AIM: The aim of the present study was to investigate restless legs symptoms with concomitant daytime sleepiness as a risk factor for mortality in a middle-aged population. METHODS: A cohort of 5102 subjects aged 30-65 years in mid-Sweden who responded to a postal questionnaire in 1983 was followed up. The questionnaire included questions about restless legs symptoms, daytime sleepiness, demographic and lifestyle variables, sleep habits, medical conditions and depression. Mortality data for the period 1983-2003 were collected and death certificates were available for all the 657 responders who died during the follow-up period. RESULTS: Restless legs symptoms with daytime sleepiness was reported by 10.3% and was associated with shorter night sleep time, several health problems and depression. During the follow-up period 379 men (21.6%) and 278 women (15.5%) died. A multivariate model adjusted for age, short night sleep time, lifestyle factors, medical conditions and depression showed that women reporting restless legs symptoms with daytime sleepiness had an excess mortality compared to women without restless legs symptoms and daytime sleepiness (hazard ratios, 1.85; 95% confidence interval, 1.20-2.85; P = 0.005). No influence on mortality risk was found in men reporting restless legs symptoms with daytime sleepiness. CONCLUSIONS: The occurrence of restless legs symptoms with daytime sleepiness in middle-aged women is associated with increased mortality risk.

Sleep duration associated with mortality in elderly, but not middle-aged, adults in a large US sample.

STUDY OBJECTIVES: To explore age differences in the relationship between sleep duration and mortality by conducting analyses stratified by age. Both short and long sleep durations have been found to be associated with mortality. Short sleep duration is associated with negative health outcomes, but there is little evidence that long sleep duration has adverse health effects. No epidemiologic studies have published multivariate analyses stratified by age, even though life expectancy is 75 years and the majority of deaths occur in the elderly. DESIGN: Multivariate longitudinal analyses of the first National Health and Nutrition Examination Survey using Cox proportional hazards models. SETTING: Probability sample (n = 9789) of the civilian noninstitutionalized population of the United States between 1982 and 1992. PARTICIPANTS: Subjects aged 32 to 86 years. MEASUREMENTS AND RESULTS: In multivariate analyses controlling for many covariates, no relationship was found in middle-aged subjects between short sleep of 5 hours or less and mortality (hazards ratio [HR] = 0.67, 95% confidence interval [CI] 0.43-1.05) or long sleep of 9 hours or more and mortality (HR = 1.04, 95% CI 0.66-1.65). A U-shaped relationship was found only in elderly subjects, with both short sleep duration (HR = 1.27, 95% CI 1.06-1.53) and long sleep duration (HR = 1.36, 95% CI 1.15-1.60) having significantly higher HRs. CONCLUSIONS: The relationship between sleep duration and mortality is largely influenced by deaths in elderly subjects and by the measurement of sleep durations closely before death. Long sleep duration is unlikely to contribute toward mortality but, rather, is a consequence of medical conditions and age-related sleep changes.

Excessive daytime sleepiness and the sleep apnoea/hypopnoea syndrome: a major public health problem?

There is unequivocal evidence that the sleep apnoea/hypopnoea syndrome (SAHS) causes daytime sleepiness and a consequential increase in road accidents. There is not, however, good agreement about the magnitude of that increase in risk. Estimates for the increased risk range from 1.3 to at least 6 times that of control populations. These figures can be used to provide estimates suggesting that between 1% and 50% of all road accident deaths are due to SAHS, depending on the prevalence of SAHS and the relative mortality of SAHS related road accidents. There is need for further investigation to increase confidence in these speculative figures, but meantime, in comparison to death rates from other conditions, excessive daytime sleepiness in SAHS is not a proven major public health problem.

Risk of napping: excessive daytime sleepiness and mortality in an older community population.

OBJECTIVE: To describe the demographic and health-related factors related to excessive daytime sleepiness. To estimate the risk of mortality associated with excessive daytime sleepiness independent of nightime sleep problems and other factors that limit survival. DESIGN: Four-year prospective cohort study with annual interviews. SETTING: One urban and four rural counties in north-central North Carolina. PARTICIPANTS: Adults 65 years and older (n = 3962) living in the community. MAIN OUTCOME MEASURES: Excessive daytime sleepiness was measured as, "How often do you get so sleepy during the day or evening that you have to take a nap?" Mortality was based on continuous surveillance of the population by field investigators and abstraction of death certificates. RESULTS: Point prevalence of excessive daytime sleepiness in this population was 25.2%. Frequent daytime nappers were more likely than infrequent nappers to report nighttime sleep complaints and were more likely to be male and urban-dwellers, to report more depressive symptoms, more limited physical activity, and more functional impairment, and were more likely to be overweight. Of the frequent nappers, 23.9% died, compared with 15.4% of infrequent nappers. In an adjusted Cox proportional hazard model, the 4-year mortality rate was accelerated 1.73 times among older people who nap most of the time and make two or more errors on a cognitive status examination. CONCLUSION: Excessive napping is associated with impaired sleep hygiene as well as with a broad range of activity-related health deficits among community-dwelling older adults. Frequent napping was associated with impaired sleep hygiene, male gender, urban-dwelling, depressive symptoms, physical activity deficits, functional impairment, and excess weight. Mortality risk was elevated selectively among the most cognitively impaired subjects.

Identification of some infants at immediate risk of dying unexpectedly and justifying intensive study.

Children who die unexpectedly in infancy often have symptoms of illness before death. Survey data are used to evaluate risks associated with symptoms. There is a 1 in 50 chance of unexpected infant death occurring in the next 9 days when two or more symptoms occur in infants defined to be at high risk by a discriminant score. The score is based on data collected on all infants at birth and by health visitors at 1 month. This system would identify 50% of cot deaths and provides a basis for prospective physiological studies.