Systematic review Short and long sleep durations are both associated with increased risk of stroke: a meta-analysis of observational studies Beihai Ge1,2 and Xiaomei Guo1* Background There is uncertainty about the relationship between sleep duration and stroke risk. Aim We aimed to clarify the relationship between sleep duration and risk of stroke by using epidemiological evidence. Methods We searched MEDLINE and EMBASE to identify all studies that might be looking at the association between sleep duration and stroke, including both cohort and cross-sectional studies. Pooled hazard ratios (HRs) and odds ratios (ORs) were calculated through a random-effects model. Results Our study included a total of 12 cohort studies and 6 cross-sectional studies. Pooled results from the cohort studies showed that short sleep duration was associated with a higher risk for stroke [HR, 1·13; 95% confidence interval (CI) 1·02– 1·25], and that long sleep duration also increases the risk of having a stroke (HR, 1·40; 95% CI, 1·16–1·64). Results from cross-sectional studies confirmed the relationship between stroke and inappropriate sleep duration, either too little sleep or too much. For short sleep duration, the OR was 1·71 (1·39– 2·02); for long sleep duration, the OR was 2·12 (1·51–2·73). Conclusion Both short and long sleep durations have a significant association with higher risk of stroke. Key words: long sleep duration, meta-analysis, observational studies, short sleep duration, stroke
Introduction Stroke is one of the leading causes of morbidity and mortality worldwide. It has been estimated by the World Health Organization (WHO) that in 2002 over 15 million strokes occurred throughout the world; more than a third of these (5·5 million) resulted in death. Since there were about 57 million deaths worldwide in 2002, stroke accounted for nearly 10% of all deaths (1). Therefore, it is important to identify the risk factors for stroke, especially those that can be modified, to improve the prevention and control of this serious medical condition. Sleep plays an important role in our lives. Indeed, it takes up more of our time in a 24-h period than any other activity. It has Correspondence: Xiaomei Guo*, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. E-mail: [email protected] 1 Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China 2 Department of Internal Medicine, People’s Hospital of Chibi City, Chibi, China Received: 16 May 2014; Accepted: 25 August 2014; Published online 3 November 2014 Conflict of interest: None declared. Funding: This work was supported by National Nature Science Foundation of China (30971244, 81270353) (URL: http://isisn.nsfc.gov.cn/ egrantweb/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. DOI: 10.1111/ijs.12398 © 2014 World Stroke Organization
been demonstrated that lack of sleep has harmful effects on several systems, with detectable changes in metabolic, endocrine and immune pathways (2). Furthermore, there is growing evidence of a link between suboptimal sleep duration and adverse health outcomes, including type 2 diabetes, obesity, hypertension, coronary artery disease and total mortality (3–7). It is important to note that several epidemiological studies have been conducted to investigate the association between sleep duration and stroke (8). Some have demonstrated an association between suboptimal sleep duration and stroke (9,10), but others failed to detect any significant associations between this exposure and stroke outcome (11,12). Therefore, the purpose of this report is to provide a systematic review of epidemiological evidence regarding the association between sleep duration and stroke risk or mortality, both qualitatively and quantitatively.
Methods Search strategy We searched MEDLINE and EMBASE to identify all studies that might be looking at the association between sleep duration and stroke. The literature search process was conducted in accordance with the statement of preferred reporting items for systematic reviews and meta-analysis (PRISMA) (1), which can be found in Tables S1 and S2. The key words used for searching were sleep, sleep duration and stroke. The search included all relevant studies published before February 2014, was limited to adult human beings, and used only articles written in English. We also scrutinized references from relevant papers and review articles to identify any additional relevant studies. Study selection and data extraction Studies were included if they met the following criteria: the study had an observational design, including cross-sectional and cohort studies, the exposure of interest was sleep duration, the outcome was stroke incidence or mortality and the result was reported by odds ratio (OR) in cross-sectional studies or by relative risk (RR) or hazard ratio (HR) in cohort studies together with a 95% confidence interval (CI). We excluded reviews, comments and studies that had insufficient data, as well as studies that had not been conducted on humans. Data extraction Using a standardized data extraction form, two of our authors extracted the data independently and in duplicate, and the differences between these were resolved through discussion and consensus with another of our authors. The information that was extracted included the study design, study name, year of publication, country of origin of the population studied, sample size, Vol 10, February 2015, 177–184
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Systematic review participants’ characteristics (age and gender), exposure and outcome ascertainment, sleep duration categories and covariates used in the adjustment. Exposure and outcome Duration of sleep was assessed by self-reported habitual sleep duration using either questionnaires or interviews. Short sleep duration was defined in hours per night, showing the following from the different studies: ≤4 (10), ≤5 (9,12–15) or ≤6 (8,11,16– 22). And long sleep duration was defined as ≥8 (8,12,17,18), ≥9 (11,13,15,16,20–22), or ≥10 h/night (9,10,14,19). The reference categories for sleep duration in the studies, in hours per night, were 7 (9,10,12–15,20), 7–7·9 (11,16,17), 7–8 (12,21), 6–8 (8,18) or 7–9 h/night (19). Statistical analysis Our study used the Newcastle-Ottawa-Scale (NOS) score system to evaluate the quality of the studies included (23). To estimate the quantitative association between short or long sleep duration and stroke, we obtained pooled estimates, based on the adjusted HRs, RRs, or ORs with their corresponding 95% CIs, extracted from each study for the meta-analysis. When several OR estimates for an outcome were reported in a study, we selected the OR that was adjusted for the most covariates. A random-effects model was used in default because this takes into consideration the betweenstudy heterogeneity (24). Between-study heterogeneity was tested by Q statistics and quantified by I2 statistics (25,26), and heterogeneity was then classified as low (I2 < 25%), moderate (I2 < 50%) or high (I2 > 50%). Publication bias was evaluated by Egger’s regression test, Begger’s funnel plot and the trim and fill method, which estimates the number and outcomes of potentially missing studies resulting from publication bias (27,28). The influence of each individual study on the pooled results was examined by omitting one study at a time and recalculating the pooled ORs of the remaining studies. All statistical analyses were performed using stata Version 10·0 (StataCorp, College Station, TX, USA).
Results A flow chart indicating the procedure for identifying the studies is presented in Fig. 1. Eighteen population samples from 15 articles met the inclusion criteria and provided suitable data for
Fig. 1 Flow diagram of study identification.
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B. Ge and X. Guo pooled analyses. These samples included 12 cohort studies (8–13,16,17,22) and 6 cross-sectional studies (14,15,18–21). Of the 12 cohort samples, 5 were conducted in the United States, 5 in Japan and 2 in Europe. The six cross-sectional studies included four that were conducted in the United States, one in Australia and one in Finland. Table 1 summarizes the characteristics of the studies that were included. Short sleep duration and stroke The 12 cohort studies from nine articles reported the relationship between short sleep duration and stroke incidence or mortality. The pooled-HR (Fig. 2) comparing the category for short sleep to the reference category was 1·13 (95% CI: 1·02–1·25; P = 0·003), with no evidence of heterogeneity (I2 = 0·0%, P = 0·457). Begger’s funnel plots (Fig. S1) did not show obvious asymmetry, and Egger’s test did not support the existence of publication bias (t = 1·75, P = 0·111). Sensitivity analysis (Fig. S2) showed that omission of any of the studies changed the pooled-HRs only slightly. The subgroup analyses of the cohort studies are shown in Table 2. No significant difference was found between the groups for any stratified characteristics such as gender, location, sleep/ stroke assessment and study quality (all P > 0·05). Six cross-sectional studies reported ORs and 95% CIs showing the association between short sleep duration and stroke. All the ORs were in the direction of increased risk and were statistically significant. The pooled-OR (Fig. 3) comparing the category for short sleep to the reference category in each study was 1·71 (95% CI: 1·39–2·02; P < 0·001), with high level between-study heterogeneity (I2 = 77·6%, P < 0·001). However, the funnel plot of these six studies (Fig. S3) suggested the possibility of publication bias (Egger’s test, t = 3·12, P = 0·036). Further evidence of selective publication was suggested by the results of the trim and fill approach, which indicated that three missing studies were required to make the funnel plot symmetrical (Fig. S4). Omitting one study at a time and recalculating the pooled ORs for the remainder of the studies showed that none of the individual studies substantially influenced the pooled OR (Fig. S5). Long sleep duration and stroke Twelve longitudinal cohort studies reported the relationship between long sleep duration and stroke incidence or mortality. The pooled-HR (Fig. 4) comparing the category for short sleep to the reference category in each cohort was 1·40 (95% CI: 1·16– 1·64; P = 0·001), with high level between-study heterogeneity (I2 = 67·7%, P < 0·001). Begger’s funnel plots (Fig. S6) did not show obvious asymmetry, and Egger’s test did not support the existence of publication bias (t = 1·75, P = 0·111). Omitting one study at a time and recalculating the pooled ORs for the remainder of the studies showed that none of the individual studies substantially influenced the pooled HR (Fig. S7). The subgroup analyses of the cohort studies are shown in Table 2. We detected significant differences between the groups for all stratified characteristics including gender, location, sleep/stroke assessment and study quality (all P < 0·05). Six cross-sectional studies reported ORs and 95% CIs showing the association between long sleep duration and stroke. The pooled-OR (Fig. 5) comparing the category for long sleep to the © 2014 World Stroke Organization
© 2014 World Stroke Organization
U.S.
U.S.
U.S.
Europe
MEC
NHEFS
REGARDS
EPICPotsdam
Finland
U.S.
BRFSS 45 and Up Study DILGOM
NHIS
Liu et al., 2013 (19) Magee et al., 2012 (20) Merikanto et al., 2013 (21) Sabanayagam and Shankar, 2010 (15)
Questionnaire
Questionnaire
Questionnaire
Questionnaire
Questionnaire
Combined Questionnaire
Combined Interview
Combined Interview
Combined Questionnaire
Women
Men
Women
Men
Men
Interview
Questionnaire
Questionnaire
Cross-sectional Combined Interview
Cross-sectional Combined Interview
Cross-sectional Combined Questionnaire
Long sleep v Ref. Adjusted covariates
≤5 h v
≤5 h v
≤4 h v
≤4 h v
Introduction Stroke is one of the leading causes of morbidity and mortality worldwide. It has been estimated by the World Health Organization (WHO) that in 2002 over 15 million strokes occurred throughout the world; more than a third of these (5·5 million) resulted in death. Since there were about 57 million deaths worldwide in 2002, stroke accounted for nearly 10% of all deaths (1). Therefore, it is important to identify the risk factors for stroke, especially those that can be modified, to improve the prevention and control of this serious medical condition. Sleep plays an important role in our lives. Indeed, it takes up more of our time in a 24-h period than any other activity. It has Correspondence: Xiaomei Guo*, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. E-mail: [email protected] 1 Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China 2 Department of Internal Medicine, People’s Hospital of Chibi City, Chibi, China Received: 16 May 2014; Accepted: 25 August 2014; Published online 3 November 2014 Conflict of interest: None declared. Funding: This work was supported by National Nature Science Foundation of China (30971244, 81270353) (URL: http://isisn.nsfc.gov.cn/ egrantweb/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. DOI: 10.1111/ijs.12398 © 2014 World Stroke Organization
been demonstrated that lack of sleep has harmful effects on several systems, with detectable changes in metabolic, endocrine and immune pathways (2). Furthermore, there is growing evidence of a link between suboptimal sleep duration and adverse health outcomes, including type 2 diabetes, obesity, hypertension, coronary artery disease and total mortality (3–7). It is important to note that several epidemiological studies have been conducted to investigate the association between sleep duration and stroke (8). Some have demonstrated an association between suboptimal sleep duration and stroke (9,10), but others failed to detect any significant associations between this exposure and stroke outcome (11,12). Therefore, the purpose of this report is to provide a systematic review of epidemiological evidence regarding the association between sleep duration and stroke risk or mortality, both qualitatively and quantitatively.
Methods Search strategy We searched MEDLINE and EMBASE to identify all studies that might be looking at the association between sleep duration and stroke. The literature search process was conducted in accordance with the statement of preferred reporting items for systematic reviews and meta-analysis (PRISMA) (1), which can be found in Tables S1 and S2. The key words used for searching were sleep, sleep duration and stroke. The search included all relevant studies published before February 2014, was limited to adult human beings, and used only articles written in English. We also scrutinized references from relevant papers and review articles to identify any additional relevant studies. Study selection and data extraction Studies were included if they met the following criteria: the study had an observational design, including cross-sectional and cohort studies, the exposure of interest was sleep duration, the outcome was stroke incidence or mortality and the result was reported by odds ratio (OR) in cross-sectional studies or by relative risk (RR) or hazard ratio (HR) in cohort studies together with a 95% confidence interval (CI). We excluded reviews, comments and studies that had insufficient data, as well as studies that had not been conducted on humans. Data extraction Using a standardized data extraction form, two of our authors extracted the data independently and in duplicate, and the differences between these were resolved through discussion and consensus with another of our authors. The information that was extracted included the study design, study name, year of publication, country of origin of the population studied, sample size, Vol 10, February 2015, 177–184
177
Systematic review participants’ characteristics (age and gender), exposure and outcome ascertainment, sleep duration categories and covariates used in the adjustment. Exposure and outcome Duration of sleep was assessed by self-reported habitual sleep duration using either questionnaires or interviews. Short sleep duration was defined in hours per night, showing the following from the different studies: ≤4 (10), ≤5 (9,12–15) or ≤6 (8,11,16– 22). And long sleep duration was defined as ≥8 (8,12,17,18), ≥9 (11,13,15,16,20–22), or ≥10 h/night (9,10,14,19). The reference categories for sleep duration in the studies, in hours per night, were 7 (9,10,12–15,20), 7–7·9 (11,16,17), 7–8 (12,21), 6–8 (8,18) or 7–9 h/night (19). Statistical analysis Our study used the Newcastle-Ottawa-Scale (NOS) score system to evaluate the quality of the studies included (23). To estimate the quantitative association between short or long sleep duration and stroke, we obtained pooled estimates, based on the adjusted HRs, RRs, or ORs with their corresponding 95% CIs, extracted from each study for the meta-analysis. When several OR estimates for an outcome were reported in a study, we selected the OR that was adjusted for the most covariates. A random-effects model was used in default because this takes into consideration the betweenstudy heterogeneity (24). Between-study heterogeneity was tested by Q statistics and quantified by I2 statistics (25,26), and heterogeneity was then classified as low (I2 < 25%), moderate (I2 < 50%) or high (I2 > 50%). Publication bias was evaluated by Egger’s regression test, Begger’s funnel plot and the trim and fill method, which estimates the number and outcomes of potentially missing studies resulting from publication bias (27,28). The influence of each individual study on the pooled results was examined by omitting one study at a time and recalculating the pooled ORs of the remaining studies. All statistical analyses were performed using stata Version 10·0 (StataCorp, College Station, TX, USA).
Results A flow chart indicating the procedure for identifying the studies is presented in Fig. 1. Eighteen population samples from 15 articles met the inclusion criteria and provided suitable data for
Fig. 1 Flow diagram of study identification.
178
Vol 10, February 2015, 177–184
B. Ge and X. Guo pooled analyses. These samples included 12 cohort studies (8–13,16,17,22) and 6 cross-sectional studies (14,15,18–21). Of the 12 cohort samples, 5 were conducted in the United States, 5 in Japan and 2 in Europe. The six cross-sectional studies included four that were conducted in the United States, one in Australia and one in Finland. Table 1 summarizes the characteristics of the studies that were included. Short sleep duration and stroke The 12 cohort studies from nine articles reported the relationship between short sleep duration and stroke incidence or mortality. The pooled-HR (Fig. 2) comparing the category for short sleep to the reference category was 1·13 (95% CI: 1·02–1·25; P = 0·003), with no evidence of heterogeneity (I2 = 0·0%, P = 0·457). Begger’s funnel plots (Fig. S1) did not show obvious asymmetry, and Egger’s test did not support the existence of publication bias (t = 1·75, P = 0·111). Sensitivity analysis (Fig. S2) showed that omission of any of the studies changed the pooled-HRs only slightly. The subgroup analyses of the cohort studies are shown in Table 2. No significant difference was found between the groups for any stratified characteristics such as gender, location, sleep/ stroke assessment and study quality (all P > 0·05). Six cross-sectional studies reported ORs and 95% CIs showing the association between short sleep duration and stroke. All the ORs were in the direction of increased risk and were statistically significant. The pooled-OR (Fig. 3) comparing the category for short sleep to the reference category in each study was 1·71 (95% CI: 1·39–2·02; P < 0·001), with high level between-study heterogeneity (I2 = 77·6%, P < 0·001). However, the funnel plot of these six studies (Fig. S3) suggested the possibility of publication bias (Egger’s test, t = 3·12, P = 0·036). Further evidence of selective publication was suggested by the results of the trim and fill approach, which indicated that three missing studies were required to make the funnel plot symmetrical (Fig. S4). Omitting one study at a time and recalculating the pooled ORs for the remainder of the studies showed that none of the individual studies substantially influenced the pooled OR (Fig. S5). Long sleep duration and stroke Twelve longitudinal cohort studies reported the relationship between long sleep duration and stroke incidence or mortality. The pooled-HR (Fig. 4) comparing the category for short sleep to the reference category in each cohort was 1·40 (95% CI: 1·16– 1·64; P = 0·001), with high level between-study heterogeneity (I2 = 67·7%, P < 0·001). Begger’s funnel plots (Fig. S6) did not show obvious asymmetry, and Egger’s test did not support the existence of publication bias (t = 1·75, P = 0·111). Omitting one study at a time and recalculating the pooled ORs for the remainder of the studies showed that none of the individual studies substantially influenced the pooled HR (Fig. S7). The subgroup analyses of the cohort studies are shown in Table 2. We detected significant differences between the groups for all stratified characteristics including gender, location, sleep/stroke assessment and study quality (all P < 0·05). Six cross-sectional studies reported ORs and 95% CIs showing the association between long sleep duration and stroke. The pooled-OR (Fig. 5) comparing the category for long sleep to the © 2014 World Stroke Organization
© 2014 World Stroke Organization
U.S.
U.S.
U.S.
Europe
MEC
NHEFS
REGARDS
EPICPotsdam
Finland
U.S.
BRFSS 45 and Up Study DILGOM
NHIS
Liu et al., 2013 (19) Magee et al., 2012 (20) Merikanto et al., 2013 (21) Sabanayagam and Shankar, 2010 (15)
Questionnaire
Questionnaire
Questionnaire
Questionnaire
Questionnaire
Combined Questionnaire
Combined Interview
Combined Interview
Combined Questionnaire
Women
Men
Women
Men
Men
Interview
Questionnaire
Questionnaire
Cross-sectional Combined Interview
Cross-sectional Combined Interview
Cross-sectional Combined Questionnaire
Long sleep v Ref. Adjusted covariates
≤5 h v
≤5 h v
≤4 h v
≤4 h v
