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Insomnia symptoms and the risk of all-cause mortality among stroke survivors

樱花视频 volume听24, Article听number:听3376 (2024) Cite this article

Abstract

Background

Insomnia is more frequently reported in stroke survivors but its independent role in mortality in stroke survivors is unknown. The purpose of this study was to investigate the association of insomnia symptoms with all-cause mortality among stroke survivors.

Methods

The Health and Retirement Study, a survey of Americans older than 50 years and their spouses of any age from 2002 to 2018 was used. Only participants with a history of stroke were included. The exposure variable of interest was insomnia symptoms including difficulty initiating sleep, difficulty maintaining sleep, waking up too early, and nonrestorative sleep. The outcome was all-cause mortality. Cox proportional hazards regression models were employed to investigate the association between insomnia symptoms and all-cause mortality.

Results

A total of 3,501 stroke survivors were included of which 55% were females. Over a mean follow-up of 6 years, 1,782 deaths occurred. Difficulty initiating sleep (HR鈥�=鈥�1.87, 95% CI: 1.07, 3.25) and difficulty maintaining sleep (1.89, 95% CI: 1.09, 3.29) were associated with all-cause mortality only among male stroke survivors younger than 65 years old while nonrestorative sleep (HR鈥�=鈥�1.31, 95% CI: 1.05, 1.62) was associated with all-cause mortality only among male stroke survivors aged 65 years and older. Furthermore, male stroke survivors younger than 65 years of age and older than 65 with insomnia symptom scores ranging from 5 to 8 (mean鈥�=鈥�6.2) had a higher but statistically nonsignificant risk of all-cause mortality (HR鈥�=鈥�1.56, 95% CI: 0.81, 3.01 and HR鈥�=鈥�1.08 95% CI: 0.85, 1.38, respectively) compared to their counterparts without insomnia symptoms. There was no association between insomnia symptoms and all-cause mortality among female stroke survivors.

Conclusion

Insomnia symptoms were associated with an increased risk of death especially in male stroke survivors younger than 65 years of age. Future studies should explore the benefit of insomnia symptom management in stroke survivors.

Peer Review reports

Introduction

Sleep is essential for human health and its disruption could lead to adverse health outcomes. In a recent study, being diagnosed with a sleep disorder (i.e., sleep apnea, insomnia, restless leg syndrome) was associated with a 50% increased all-cause mortality over 5 years compared to no diagnosis of sleep disorder [1]. Insomnia is a sleep disorder defined as a persistent difficulty with sleep initiation, duration, consolidation, or quality that occurs despite adequate opportunity and circumstances for sleep, and results in some form of daytime impairment [2]. A systematic review reported a higher risk of mortality in patients with insomnia disorder when compared to those without insomnia (HR鈥�=鈥�1.66, 95% CI: 1.25鈥�2.19) [3]. Another study found more specifically, that difficulty initiating sleep and non-restorative sleep were associated with an increased risk of all-cause mortality [4]. Several other studies have linked insomnia to long-term mortality in the general population [5,6,7,8].

Previous studies have noticed differences by sex in the association between insomnia and death. Difficulty initiating sleep was found to be associated with increased mortality in males (HR鈥�=鈥�1.25, 95% CI: 1.04鈥�1.50), but not in females (HR鈥�=鈥�0.89, 95% CI: 0.79, 1.00)(9). However, being an 鈥渆arly waker鈥� was not associated with increase mortality in both males (HR鈥�=鈥�1.04, 95% CI: 0.88鈥�1.22) and females (HR鈥�=鈥�0.81, 95% CI: 0.75, 0.91) (9鈥�10). Furthermore, in the Atherosclerosis Risk in Communities Study, insomnia was not associated with an increased risk for death (OR 1.01, CI: 0.85鈥�1.21) in both sexes [11].

Insomnia has been linked to multiple dysfunctions such as increased inflammation, glucose intolerance, dysregulation of the hypothalamic-pituitary axis, and increased sympathetic nervous system activity [12,13,14,15]. However, studies suggest that these conditions cannot totally explain the observed association between insomnia symptoms and total mortality [9]. The mechanism by which insomnia increases the risk of death may also include daytime impairments, such as depressed mood, anxiety, fatigue, and ill health [3].

Insomnia is highly prevalent, affecting approximately 32 to 41% of stroke survivors [16]. Both insomnia and insomnia symptoms are higher in stroke survivors compared to the general population [17]. Insomnia could negatively affect stroke rehabilitation including post-stroke depression, recurrent stroke, and death but the independent role of insomnia in mortality is less studied in this vulnerable group [18]. Most of the previous studies were conducted in the general population (3, 4, 9鈥�10). The objective of this study was to determine the independent role of insomnia in mortality within community-dwelling stroke survivors and whether this association is modified by age and sex.

Methods

Data source and study population

This study used data from the Health and Retirement Study (HRS), which is an ongoing national longitudinal study of Americans older than 50 years and their spouses of any age, conducted by the University of Michigan and sponsored by the National Institute on Aging (NIA U01AG009740) [19]. The HRS sample was assembled in several waves of enrollment and data collection and consisted of persons older than 50 years and their spouses of any age. To keep the sample fully representative of the USA population over age 50, the HRS cohort is replenished every 6 years with younger cohorts not previously represented [19]. Once a participant is recruited, they complete a survey every two years, and every 4 years biomarkers and physical measures are collected. Variables used in this study were derived from the self or proxy reported and the exit surveys. Self-reported health measures used in HRS have been previously assessed showing substantial agreement with surveys and medical records [20, 21]. Further details about the survey can be found on the HRS website [22].

Study inclusion and design

The sleep questions of interest were introduced in 2002. Therefore, the present study included participants starting in 2002 and followed until death, loss to follow-up, or censored on December 31, 2018. Only participants who self-reported a history of stroke and completed the sleep questions were included. Stroke survivors were determined by self-report of a physician鈥檚 diagnosis of stroke. The validity of self-reported stroke as an accurate estimate of stroke has been well documented [21, 23, 24]. Studies reported substantial agreement between self-reported strokes and hospital records, and that self-reported stroke had a positive predictive value of 79% with an estimated sensitivity of 80% and specificity of >鈥�99% [21, 23]. In addition, a previous study compared the HRS self-reported stroke data with medically verified stroke studies and concluded that the HRS provides valuable data for stroke prevalence and incidence [24]. If a participant reported multiple strokes, only the first stroke was considered. Respondents with Transient Ischemic Attack (TIA) and unknown stroke status were excluded. This study was restricted to stroke survivors due to the high prevalence of insomnia in stroke survivors and the association between sleep disturbances and stroke [16, 25]. Among those interviewed in 2002, 1,222 met the inclusion criteria. In the subsequent years, as repeated surveys were conducted, new eligible participants who were not in the 2002 interview or developed a stroke later and became eligible were added resulting in a final sample of 3,501 (Fig.听1). Insomnia symptoms were measured after stroke occurrence. Likewise, all baseline characteristics were measured after stroke occurrence.

Fig. 1
figure 1

Flowchart of stroke survivors鈥� inclusion process. a Transient ischemic attack (TIA), unknown stroke status (don鈥檛 know, refuse), have never been told that they had a stroke. b New eligible are participants who were not in the initial interview of 2002 or participants who developed a stroke later and became eligible. Baseline characteristics including insomnia symptoms were assessed after stroke diagnosis

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Exposure: insomnia symptoms

Self-reported insomnia symptoms were assessed using the Adapted Brief Insomnia Questionnaire (BIQ), a validated screening tool that measures self-reported sleep complaints rather than diagnosed insomnia [26, 27]. Participants answered four questions about how often they had trouble falling asleep, trouble with waking up during the night, trouble with waking up too early and not being able to return to sleep, and how often they felt rested in the morning (Additional file 1). The possible response options were 鈥渕ost of the time鈥�, 鈥渟ometimes鈥� or 鈥渞arely or never鈥�. Those reporting 鈥渕ost of the time鈥� to the first 3 questions were given a score of 2, 鈥渟ometimes鈥� a score of 1, and 鈥渞arely or never鈥� a score of 0. Reverse-coding was applied to the last question resulting in a total insomnia symptoms severity score that ranges between 鈥�0鈥�=鈥塶o insomnia鈥� and 鈥�8鈥�=鈥塻evere insomnia symptoms鈥� [28].

Outcome: all-cause mortality

Mortality events that occurred during the follow-up were obtained by either the exit survey or the core interview of their spouse/partner. An Exit Interview was conducted with a 鈥減roxy informant鈥� for the study participant who had died. The proxy is often a widow, widower, or some other family member who is knowledgeable about the health of the deceased. The HRS death was compared to the National Death Index and found to be reliable to establish death [29].

Covariates

Based on previous literature [3, 10, 12, 18, 30] the following covariates were considered. First, demographic factors included sex, age, race, and ethnicity (Non-Hispanic White, Non-Hispanic Black, Hispanic, and Non-Hispanic Other), marital status (divorced, widowed, never-married, currently married), and geographic region (Southern or other). Second, socio-economic status (SES) factors included education (less than high school, high school, some college, college graduates, and more), household income and wealth, employment status, and the social deprivation index (SDI). The SDI index was produced by the Robert Graham Center, using 7 key neighborhood factors derived from the 2011鈥�2015 American Community Survey (ACS) including the percent population with <鈥�100% Federal Poverty Level, percent population with less than 12 years of education, percent non-employed, percent population living in renter-occupied housing units, percent population living in crowded housing units, percent single-parent households, and percent population with no car [31]. The index was derived at the level of the census tract, generating values from 0 to 100 that is applied to each participant with a higher score indicating a more deprived area. Third, behavioral risk factors included alcohol consumption, smoking, body mass index, and physical activity. Fourth, comorbidities that did not mediate the association between insomnia symptoms and all-cause mortality were added to the model [32]. They were self-reported diabetes, hypertension, heart disease (i.e., heart attack, coronary heart disease, angina, congestive heart failure, or other heart problems), cancer, and lung disease. Depression showed evidence of mediation and was therefore not included in the model (Additional file 2). Finally, the time since stroke occurrence and activities of daily living were included as a covariate.

The variable activities of daily living consisted of six questions: Because of a health or memory problem, (1) Do you have any difficulty with dressing, including putting on shoes and socks? (2) Do you have any difficulty walking across a room? (3) Do you have any difficulty with bathing or showering? (4) Do you have any difficulty with such as cutting up your food? (5) Do you have any difficulty getting in or out of bed? (6) Do you have any difficulty with using the toilet, including getting up and down? The response option 鈥淵es鈥� was coded as 鈥�1,鈥� and 鈥淣o鈥� was coded as 鈥�0.鈥� The sum score ranged between 0 and 6; a higher score indicates a lower level of independence [33].

Data analysis

Descriptive statistics

Descriptive statistics were generated to assess the distribution of the study characteristics by insomnia symptom scores. All baseline characteristics were summarized using mean and standard deviation for continuous variables and frequencies and percentages for the categorical or ordinal variables. Multicollinearity was tested for the covariates using the variance inflation factor (VIF). A VIF of 10 or greater was used to signify multicollinearity.

Time to event analysis

Cox proportional hazard regression analyses were performed to evaluate the association between insomnia symptoms and all-cause mortality. The proportional hazard assumption was tested graphically and using the Kolmogorov-type supremum test. Time-independent covariates were entered into the model sequentially. Model 1 was adjusted for demographic factors. Model 2 was adjusted for Model 1 variables and socioeconomic factors. Model 3 was adjusted for model 2 variables, behavioral risk factors, and time since stroke diagnosis. Model 4 was adjusted for model 3 variables and comorbidities. Model 5 was adjusted for model 4 variables and activities of daily living.

Predefined stratified analyses were performed to determine whether the association of insomnia symptoms with all-cause mortality was modified by sex (male vs. female), sex and age (male鈥�<鈥�65, male鈥夆墺鈥�65, female鈥�<鈥�65, female鈥夆墺鈥�65 years). The age cut point was chosen based on the higher risk of insomnia in younger adults and the major decline in stroke mortality in past decades observed among people鈥�<鈥�65 years [30, 34] A p-value for interaction was obtained by comparing models with and without multiplicative interaction terms (insomnia symptoms, sex, age) before conducting the stratified analyses. A p-value鈥�<鈥�0.05 was considered statistically significant.

Results

Descriptive statistics

The study participants鈥� mean age was 71 years (SD鈥�=鈥�12.1), 66.7% were older than 65 years, 55% were female, and 64.6% were Non-Hispanic White (Table听1). The mean of the insomnia symptom scores ranging from 1 to 4 and 5鈥�8 were 2.5 (standard deviation鈥�=鈥�1.1) and 6.2 (standard deviation鈥�=鈥�1.1) respectively. Insomnia symptom scores decreased with increasing age and income. Insomnia symptom scores were higher in females, current smokers, those who were unemployed/disabled, those with low education, low physical activity, obesity, comorbidities, and living in a socially deprived neighborhood. Over a mean of 6 years of follow-up (SD鈥�=鈥�4.4) of 3,501 stroke survivors; 1,782 (50.9%) deaths were recorded. More females (54%) than males (46%) died. The leading causes of death were cardiovascular disease (39%), cancer (14%), allergies, and infectious disease (11.5%) (Additional file 3).

Table 1 Baseline characteristics of stroke survivors by insomnia symptom scores
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Association of Insomnia symptoms with all-cause mortality

The analysis based on individual insomnia symptoms showed that difficulty initiating sleep and difficulty maintaining sleep were associated with all-cause mortality only among male stroke survivors younger than 65 years old (HR鈥�=鈥�1.87, 95% CI: 1.07, 3.25, and HR鈥�=鈥�1.89, 95% CI: 1.09, 3.29, Table听2, Additional File 4), respectively comparing those reporting the symptom most of the time to those without symptom. Similarly, nonrestorative sleep was associated with all-cause mortality only among male stroke survivors aged 65 years and older (HR鈥�=鈥�1.31, 95% CI: 1.05, 1.62) comparing those reporting the symptom most of the time to those without symptoms.

Table 2 Association of individual insomnia symptom with all-cause mortality among stroke survivors stratified by age and sex
Full size table

The analysis based on insomnia symptom scores showed an association between high insomnia symptom scores and all-cause mortality (Additional file 5), especially in male stroke survivors (HR鈥�=鈥�1.18, 95% CI: 1.01, 1.52) but not in female stroke survivors (HR鈥�=鈥�0.90, 95% CI: 0.71, 1.14) in the model adjusted for socioeconomic, behavioral risk factors, comorbidities, and time since stroke diagnosis (Table听3). However, after further adjusting for activities of daily living, the statistical significance was no longer reached for males (HR鈥�=鈥�1.06, 95% CI: 0.81, 1.38). Further differences were noticed by sex and age. The association between insomnia symptom scores 5鈥�8 and all-cause mortality was stronger in male stroke survivors aged鈥�<鈥�65 years than male stroke survivors aged鈥夆墺鈥�65 years (HR鈥�=鈥�1.91, 95% CI: 0.90, 4.04 and HR鈥�=鈥�0.98, 95% CI: 0.72, 1.32, Table听4), respectively. Similar non-statistically significant trends were observed comparing male stroke survivors aged鈥�<鈥�65 years and male stroke survivors aged鈥夆墺鈥�65 years with insomnia symptom scores ranging from 1 to 4 to male stroke survivors with no insomnia symptoms, (HR鈥�=鈥�1.56, 95% CI: 0.81, 3.01, and HR鈥�=鈥�1.08, 95% CI: 0.85, 1.38 respectively).

Table 3 Association of Insomnia symptom scores with all-cause mortality among stroke survivors by sex
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Table 4 Association of Insomnia symptom scores with all-cause mortality among stroke survivors by age and sex
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Discussion

In this study, insomnia symptoms were associated with an increased risk of all-cause mortality among male stroke survivors, especially those who are younger than 65 years of age. The relationship between insomnia symptoms and mortality among stroke survivors has received little attention in the past. Recent improvements in acute stroke management have contributed to a decrease in stroke-related mortality [34]. The prevalence of stroke survivors is increasing and improving post-stroke life expectancy has become a public health priority [35].

The association between insomnia symptoms and all-cause mortality among stroke survivors differed by sex and age. There were some significant associations in males but not in females. The association was stronger in younger male adults (age鈥�<鈥�65) than older male adults (age鈥夆墺鈥�65). In previous studies, insomnia symptoms such as difficulty falling asleep were found to be associated with increased mortality in males (HR鈥�=鈥�1.25, 95% CI: 1.04鈥�1.50), but not in females (HR鈥�=鈥�0.89, 95% CI: 0.79, 1.00) in the general population from the USA and Australia, respectively [9, 10]. In a study from China, restricted to stroke patients at the early stage of recovery, insomnia symptoms were associated with death but the study did not report a separate analysis by age and sex [18]. The difference by age could be due to the higher risk of death at an older age and the competing causes of death as age increases [30]. The underlying reasons for the sex differences in the association between insomnia symptoms and risk of death in stroke survivors required further investigation. However, some hypotheses can be drawn from previous studies suggesting that females have a better quantity (total sleep time) and quality (Slow Wave Sleep and Rapid Eye Movement sleep) of sleep than males [36]. Furthermore, females may cope better with sleep loss in terms of inflammation makers which in part may contribute to females鈥� lower risk of death in association with insomnia symptoms [37]. The mediation analysis found that depression is in the causal path of the association between insomnia symptoms and all-cause mortality. The high prevalence of depression in stroke survivors suggests that depression management may help reduce mortality in this population of stroke survivors [38].

Overall, the association between insomnia symptoms and all-cause mortality seems to be stronger in stroke survivors compared to the general population [9, 30, 39]. Future studies comparing stroke survivors to individuals without a history of stroke are needed.

Strengths and limitations

The current analysis was based on a representative sample of U.S. adults 50 years and older. Strengths of this study include its prospective nature and a relatively large sample of stroke survivors. However, there are several limitations to the present study that should be noted. First, the data was self-reported. Insomnia symptoms and all-cause mortality were self or proxy-reported, which is likely to result in non-differential misclassification (between exposed and unexposed), given that the exposure and the outcome were measured at different times and participants were unaware of the study hypothesis. Therefore, a resulting bias will likely be toward the null hypothesis. Furthermore, there was no information on the type of stroke. Second, insomnia symptoms were further compiled into an unweighted linear symptoms index assuming equal weighting of all symptoms. As mentioned above, insomnia symptoms rather than diagnosed insomnia were assessed in this study. Third, even though this study adjusted for multiple covariates, we cannot rule out the possibility of residual confounding such as other sleep disorders, sleep duration, or the use of sleep medication. In a previous study, we reported that long sleep duration was associated with all-cause mortality among stroke survivors [40].

In summary, insomnia symptoms were associated with an increased risk of death among stroke survivors, especially in males younger than 65 years of age. These findings suggest that increased public awareness and clinical management of insomnia symptoms in stroke survivors may contribute to improving post-stroke life expectancy.

Data availability

No datasets were generated or analysed during the current study.

Abbreviations

BIQ:

Brief Insomnia Questionnaire

HRS:

Health and Retirement Study

SDI:

Social Deprivation Index

SES:

Socio-Economic Status

TIA:

Transient Ischemic Attack

VIF:

Variance Inflation Factor

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Funding

The authors report no funding.

Author information

Authors and Affiliations

  1. Department of Public Health, College of Health and Human Services, Southern Connecticut State University, 501 Crescent St, New Haven, CT, 06514, USA

    Wendemi Sawadogo

  2. Department of Epidemiology, School of Public Health, Virginia Commonwealth University, Richmond, VA, USA

    Wendemi Sawadogo,听Tilahun Adera听&听James Burch

  3. Divisions: Adult Neurology, Sleep Medicine, Vascular and Critical Care Neurology; Department of Neurology, School of Medicine, Virginia Commonwealth University, Richmond, VA, USA

    Maha Alattar

  4. Department of Biostatistics, School of Public Health, Virginia Commonwealth University, Richmond, VA, USA

    Robert Perera

Authors
  1. Wendemi Sawadogo

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  2. Tilahun Adera

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  3. Maha Alattar

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  4. Robert Perera

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  5. James Burch

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Contributions

Conceptualization, W.S, T.A; methodology, W.S., T.A, M.A, R.P, J.B; software, W.S.; formal analysis, W.S, T.A; writing (original draft preparation), W.S; writing (review and editing), W.S., T.A, M.A, J.B. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Wendemi Sawadogo.

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Ethical approval

The Institutional Review Board of the author鈥檚 university approved this study (HM20023839). Participant consent was waived for this secondary data analysis.

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Not applicable.

Competing interests

All authors declare no conflicts of interest or financial interest.

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Cite this article

Sawadogo, W., Adera, T., Alattar, M. et al. Insomnia symptoms and the risk of all-cause mortality among stroke survivors. 樱花视频 24, 3376 (2024). https://doi.org/10.1186/s12889-024-20892-0

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  • DOI: https://doi.org/10.1186/s12889-024-20892-0

Keywords

樱花视频

ISSN: 1471-2458

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