Sex differences in the association between short sleep duration and obesity: A systematic-review and meta-analysis.

AIMS: Obesity is a leading contributor to global morbidity and mortality. Short sleep duration is significantly associated with the incidence of obesity, however, it remains unclear whether this relationship is influenced by sex. The purpose of this meta-analysis was to systematically evaluate the evidence of whether the association between short sleep duration and obesity differs between males and females. DATA SYNTHESIS: The protocol was registered with PROSPERO (CRD42023374205). From inception through June 2023, Medline, Embase and Web of Science databases were searched for longitudinal cohort studies with minimum 12 months of observation. The quality of studies was assessed using the Newcastle-Ottawa Quality Assessment for Cohort Studies. Results were pooled using a random effects model. Results are expressed as ratio of odds ratios (ROR) with 95% confidence interval (CI). ROR directly estimates the relative strength of the association of interest (measured as odds ratio [OR] between females and males). Sensitivity analysis was performed and inconsistency between studies was assessed using I2 statistics. A total of 4582 articles were retrieved with the search strategy, of which 6 were included. The meta-analysis indicated that the association between short sleep duration and obesity incidence was statistically significant in both men [OR 1.26 (95% CI 1.13-1.40)] and women [OR 1.36 (95% CI 1.16-1.59)]. However, it did not differ significantly between sexes ROR (women/men) 1.04 (95%CI 0.79-1.36; I2 20.1%). CONCLUSIONS: This meta-analysis indicates that women and men who subjectively report short sleep duration have similarly increased risks of incident obesity.

Exploring educational inequalities in hypertension control, salt knowledge and awareness, and patient advice: insights from the WHO STEPS surveys of adults from nine Eastern European and Central Asian countries.

OBJECTIVE: To inform strategies aimed at improving blood pressure (BP) control and reducing salt intake, we assessed educational inequalities in high blood pressure (HBP) awareness, treatment and control; physician's advice on salt reduction; and salt knowledge, perceptions and consumption behaviours in Eastern Europe and Central Asia. DESIGN: Data were collected in cross-sectional, population-based nationally representative surveys, using a multi-stage clustered sampling design. Five HBP awareness, treatment and control categories were created from measured BP and hypertension medication use. Education and other variables were self-reported. Weighted multinomial mixed-effects regression models, adjusted for confounders, were used to assess differences across education categories. SETTINGS: Nine Eastern European and Central Asian countries (Armenia, Azerbaijan, Belarus, Georgia, Kyrgyzstan, Republic of Moldova, Tajikistan, Turkey and Uzbekistan). PARTICIPANTS: Nationally representative samples of 30 455 adults aged 25-65 years. RESULTS: HBP awareness, treatment and control varied substantially by education. The coverage of physician's advice on salt was less frequent among participants with lower education, and those with untreated HBP or unaware of their HBP. The education gradient was evident in salt knowledge and perceptions of salt intake but not in salt consumption behaviours. Improved salt knowledge and perceptions were more prevalent among participants who received physician's advice on salt reduction. CONCLUSIONS: There is a strong education gradient in HBP awareness, treatment and control as well as salt knowledge and perceived intake. Enhancements in public and patient knowledge and awareness of HBP and its risk factors targeting socio-economically disadvantaged groups are urgently needed to alleviate the growing HBP burden in low- and middle-income countries.

Comment on Hogas et al. Salt, Not Always a Cardiovascular Enemy? A Mini-Review and Modern Perspective. Medicina 2022, 58, 1175.

Hogas et al. recently published their perspective on dietary salt in a mini review [...].

Short duration of sleep and incidence of overweight or obesity in Chinese children and adolescents: A systematic review and meta-analysis of prospective studies.

BACKGROUND AND AIMS: Overweight and obesity in children have become a global public health problem. Epidemiological studies suggest that sleep duration may contribute to the incidence of overweight and obesity in all stages of life. China has an increasing prevalence of overweight and obesity, and sleep deprivation is common among Chinese children. The aim of this study was to assess the prospective relationship between short sleep duration and overweight or obesity in Chinese children and to gain an estimate of the risk. METHODS AND RESULTS: A systematic search was performed on 28/04/2020 by using Medline, PubMed and Web of Science. The exposure was the duration of sleep, and the outcome measure the incidence of overweight or obesity. The odds ratios (OR) and hazard ratios (HR) and 95% confidence intervals (C.I.) were extracted to calculate the pooled relative risk (RR) by a random effect model. Heterogeneity and publication bias of the studies were checked by sensitivity analysis. Seven studies fulfilled the criteria for a systematic review, and 5 studies for a meta-analysis. The total of 33,206 participants included boys and girls, aged 6-17 years old. In Chinese children the pooled RR for short sleep duration and overweight or obesity combined was 1.47 (95% C.I. 1.26, 1.71, p < 0.00001, n = 32,607), and for obesity alone 1.40 (95% C.I. 1.01, 1.95, p = 0.04, n = 17,038). There was no significant heterogeneity or publication bias between studies. CONCLUSION: Short sleep duration is associated with the development of overweight and obesity in Chinese children.

May Measurement Month 2019: an analysis of blood pressure screening results from the United Kingdom and Republic of Ireland.

In the UK, heart and circulatory diseases account for 29% of all deaths (14% through coronary heart disease and 8% through stroke). In 2015, the prevalence of hypertension was 20% in the UK and 23% in the Republic of Ireland. In 2019, 14% of people registered with a UK general practice had hypertension and yet it was the attributable risk factor for around half of all deaths from coronary heart disease or stroke. We participated in May Measurement Month 2019 to increase awareness of blood pressure (BP) measurement, and to identify the proportion of undiagnosed hypertension and degree of uncontrolled hypertension in the community. The 2019 campaign set up screening sites within the community at places of worship, supermarkets, GP surgeries, workplaces, charity events, community pharmacies, gyms, and various other public places. We screened 10194 participants (mean age 51 ± 18 years, 60% women) and found that 1013 (9.9%) were on antihypertensive treatment, while 3408 (33.4%) had hypertension. Of the 3408 participants with hypertension, only 33.5% were aware of their condition despite 98.8% having previous BP measurements. In those on antihypertensive medication, only 38.2% had controlled BP (<140 and <90 mmHg). Our UK and Republic of Ireland data demonstrate concerning levels of undiagnosed hypertension and sub-optimal BP control in many individuals with a diagnosis. This evidence supports a critical need for better systematic community and primary care screening initiatives.

Covid-19 and cardiovascular risk: Susceptibility to infection to SARS-CoV-2, severity and prognosis of Covid-19 and blockade of the renin-angiotensin-aldosterone system. An evidence-based viewpoint.

The presence of cardiovascular co-morbidities and the known effects of coronaviruses on the cardiovascular system have called attention to the potential implications for patients with cardiovascular risk factors. This evidence-based viewpoint will address two questions: (a) are individuals with underlying cardiovascular risk factors (e.g. high blood pressure or diabetes) or overt disease (e.g. coronary heart disease, heart failure, kidney disease) more likely to develop severe Covid-19 and to die than those without underlying conditions? (b) does the regular use of angiotensin-converting enzyme inhibitors (ACE-i) or angiotensin-receptor blockers (ARB) make patients more likely to get infected and to die of Covid-19? With a necessary cautionary note that the evidence around the links between Covid-19 and cardiovascular disease is accruing at a fast pace, to date we can conclude that: (a) the greater susceptibility of individuals with underlying cardiovascular conditions to develop more severe Covid-19 with higher mortality rate is likely to be confounded, in part, by age and the type of co-morbidities. Patients with heart failure or chronic kidney disease might show an excess risk; (b) neither ACE-i nor ARB are associated with greater risk of SARS-Cov2 infection, or severity or risk of death in patients with Covid-19. Patients on these drugs should not stop them, unless under strict medical supervision and with the addition of a suitable replacement medicine.

May Measurement Month 2017: an analysis of blood pressure screening results from the United Kingdom and the Republic of Ireland-Europe.

Elevated blood pressure (BP), or hypertension, is a growing burden worldwide, leading to over 10 million deaths each year. May Measurement Month (MMM) is a global initiative aimed at raising awareness of high BP and acting as a stimulus to improving screening programmes worldwide. In the United Kingdom (UK) nearly 1 in 5 people, and in the Republic of Ireland (RoI) 3 out of 10, have hypertension, of which a large proportion remains undiagnosed. An opportunistic cross-sectional survey of volunteers aged ≥18 years was carried out in May 2017. Blood pressure measurement, the definition of hypertension and statistical analysis followed a standardized protocol. Screenings sites in hospitals, universities, shopping centres, workplaces, sports clubs, community centres, GP practices, and pharmacies were set up across the UK and RoI as part of this initiative. Seven thousand seven hundred and fourteen individuals were screened during MMM17. After multiple imputation, 3099 (40.3%) had hypertension. Of individuals not receiving antihypertensive medication, 1406 (23.4%) were hypertensive. Of individuals receiving antihypertensive medication, 682 (40.5%) had uncontrolled BP. MMM17 was the largest BP screening campaign ever undertaken in the UK and RoI. These data prove for the first time that a relatively inexpensive, volunteer based, convenience sampling of screening BP in the community identified two out of five individuals as hypertensive, with one in four not receiving treatment. Of major concern is that these data demonstrate that of those individuals receiving treatment, two out of five still did not have controlled BP.

Sleep and Cardio-Metabolic Disease.

PURPOSE OF REVIEW: This review summarises and discusses the epidemiological evidence suggesting a causal relationship between sleep duration and cardio-metabolic risk and outcomes in population. RECENT FINDINGS: Sleep duration is affected by a variety of cultural, social, psychological, behavioural, pathophysiological and environmental influences. Changes in modern society-like longer working hours, more shift-work, 24/7 availability of commodities and 24-h global connectivity-have been associated with a gradual reduction in sleep duration and sleeping patterns across westernised populations. We review the evidence of an association between sleep disturbances and the development of cardio-metabolic risk and disease and discuss the implications for causality of these associations. Prolonged curtailment of sleep duration is a risk factor for the development of obesity, diabetes, hypertension, heart disease and stroke and may contribute, in the long-term, to premature death.

Pro: Reducing salt intake at population level: is it really a public health priority?

A reduction in salt intake reduces blood pressure, stroke and other cardiovascular events, including chronic kidney disease, by as much as 23% (i.e. 1.25 million deaths worldwide). It is effective in both genders, any age, ethnic group, and in high-, medium- and low-income countries. Population salt reduction programmes are both feasible and effective (preventive imperative). Salt reduction programmes are cost-saving in all settings (high-, middle- and low-income countries) (economic imperative). Public health policies are powerful, rapid, equitable and cost-saving (political imperative). The important shift in public health has not occurred without obstinate opposition from organizations concerned primarily with the profits deriving from population high salt intake and less with public health benefits. A key component of the denial strategy is misinformation (with 'pseudo' controversies). In general, poor science has been used to create uncertainty and to support inaction. This paper summarizes the evidence in favour of a global salt reduction strategy and analyses the peddling of well-worn myths behind the false controversies.

Systematic review of studies evaluating urinary iodine concentration as a predictor of 24-hour urinary iodine excretion for estimating population iodine intake.

OBJECTIVE: To examine the usefulness of "spot" urine iodine concentrations (UICs) in predicting 24-hour urine iodine excretion (UIE) for estimating average population iodine intake. METHODS: An electronic literature search was conducted for articles published through 19 May 2013 in MEDLINE (from 1950), EMBASE (from 1980), and the Cochrane Library (from 1993) using the terms "urinary excretion (timed or spot or random) and (24 h or 24 hour), iodine (iodine deficiency), iodine (intake)," and "urine (timed, spot, random, 24-hour)." Full-text articles about studies that examined > 40 healthy human subjects and measured UIE using the 24-hour urine collection method and UIC and/or UIE using one alternative method (spot (random), timed, and "overnight" (first morning urine), fasting or not fasting) were selected and reviewed. RESULTS: The review included data from 1 434 participants across the six studies that met the inclusion criteria. The main statistical methods for comparing data from the 24-hour urine collections with the values obtained from the alternative method(s) were either regression (ß) or correlation (r) coefficients and concordance analysis through Bland-Altman plots. The urine samples collected using the alternative methods were subject to greater intra-individual and inter-individual variability than the 24-hour urine collections. There was a wide range in coefficient values for the comparisons between 24-hour URE measured in 24-hour urine collection and 24-hour UIE estimated using the alternative sampling methods. No alternative sampling method (spot, timed, or "overnight") was appropriate for estimating 24-hour UIE. CONCLUSIONS: The results of this systematic review suggest current data on UICs as a means of predicting 24-hour UIE for estimating population sodium intake are inadequate and highlight the need for further methodological investigations.

Daytime napping and the risk of all-cause and cause-specific mortality: a 13-year follow-up of a British population.

Epidemiologic studies have reported conflicting results on the relationship between daytime napping and mortality risk, and there are few data on the potential association in the British population. We investigated the associations between daytime napping and all-cause or cause-specific mortality in the European Prospective Investigation Into Cancer-Norfolk study, a British population-based cohort study. Among the 16,374 men and women who answered questions on napping habits between 1998 and 2000, a total of 3,251 died during the 13-year follow-up. Daytime napping was associated with an increased risk of all-cause mortality (for napping less than 1 hour per day on average, hazard ratio = 1.14, 95% confidence interval: 1.02, 1.27; for napping 1 hour or longer per day on average, hazard ratio = 1.32, 95% confidence interval: 1.04, 1.68), independent of age, sex, social class, educational level, marital status, employment status, body mass index, physical activity level, smoking status, alcohol intake, depression, self-reported general health, use of hypnotic drugs or other medications, time spent in bed at night, and presence of preexisting health conditions. This association was more pronounced for death from respiratory diseases (for napping less than 1 hour, hazard ratio = 1.40, 95% confidence interval: 0.95, 2.05; for napping 1 hour or more, hazard ratio = 2.56, 95% confidence interval: 1.34, 4.86) and in individuals 65 years of age or younger. Excessive daytime napping might be a useful marker of underlying health risk, particularly of respiratory problems, especially among those 65 years of age or younger. Further research is required to clarify the nature of the observed association.

Current salt reduction policies across gradients of inequality-adjusted human development in the WHO European region: minding the gaps.

OBJECTIVE: To assess current salt reduction policies in countries of the WHO European Region against the backdrop of varying levels of human development adjusted for income, education and health (longevity) inequalities. DESIGN: Population-based, cross-sectional study, with data gathered through systematic review of relevant databases and supplementary information provided by WHO Nutrition Counterparts. SETTING: Member States of the WHO European Region. SUBJECTS: Inequality-adjusted Human Development Index scores were analysed against assessed levels of development and implementation of national nutrition policies and initiatives targeting population-level salt reduction. RESULTS: Within the WHO European Region, Inequality-adjusted Human Development Index values among countries with no existing salt reduction initiatives (mean 0·643 (se 0·022)) were significantly lower than among those with either partially implemented/planned salt initiatives (mean 0·766 (se 0·017), P < 0·001) or fully implemented salt initiatives (mean 0·780 (se 0·021), P < 0·001). CONCLUSIONS: Where salt reduction strategies are implemented as an integral part of national policy, outcomes have been promising. However, low- and middle-income countries may face severe resource constraints that keep them from emulating more comprehensive strategies pursued in high-income countries. Care must be taken to ensure that gaps are not inadvertently widened by monitoring differential policy impacts of salt policies, particularly regarding trade flows.

Effect of timed dosing of usual antihypertensives according to patient chronotype on cardiovascular outcomes: the Chronotype sub-study cohort of the Treatment in Morning versus Evening (TIME) study.

Background: Timing drug administration to endogenous circadian rhythms may enhance treatment efficacy. In the Chronotype sub-study of the Treatment in Morning versus Evening (TIME) clinical trial we examined whether timing of usual antihypertensive medications according to patient chronotype (a behavioural marker of personal circadian rhythm) may influence clinical cardiovascular outcomes. Methods: This was a cohort sub-study of TIME, a prospective, randomised, open-label, blinded-endpoint, UK clinical trial of morning versus evening dosing of usual antihypertensive medications and cardiovascular outcomes. On August 3rd, 2020, all active TIME participants were invited to complete a validated chronotype questionnaire. Chronotype was quantitatively assessed as the mid sleep time on free days corrected for sleep debt on workdays (MSFsc). We analysed associations between chronotype and antihypertensive dosing time and explored their combined effect on cardiovascular outcomes (a composite endpoint of hospitalisation for non-fatal myocardial infarction (MI) or non-fatal stroke, and single components) using proportional hazard time-to-event models adjusted for baseline covariates. These were used to specifically test for interactions between dosing time and chronotype. Findings: Between August 3, 2020, and March 31, 2021, 5358 TIME participants completed the online questionnaire. 2778 were previously randomised to morning dosing and 2580 to evening dosing of their usual antihypertensives. Chronotype was symmetrically distributed around a median MSFsc of 3:07 am. The composite endpoint increased for later MSFsc (later chronotype) dosed in the morning but not in those dosed in the evening (hazard ratios 1.46 [95% CI 1.14-1.86] and 0.96 [95% CI 0.70-1.30] per hour of MSFsc, respectively; interaction p = 0.036). Later chronotype was associated with increased risk of hospitalisation for non-fatal MI in the morning dosing group, and reduced risk in the evening dosing group (hazard ratios 1.62 [95% CI 1.18-2.22] and 0.66 [95% CI 0.44-1.00] per hour of MSFsc, respectively; interaction p < 0.001). No interaction between chronotype and antihypertensive dosing time was observed for stroke events. Interpretation: Alignment of dosing time of usual antihypertensives with personal chronotype could lower the incidence of non-fatal MI compared to a 'misaligned' dosing time regimen. Future studies are warranted to establish whether synchronizing administration time of antihypertensive therapy with individual chronotype reduces risk of MI. Funding: The TIME study was funded by the British Heart Foundation (CS/14/1/30659) with support from the British and Irish Hypertension Society.

FOUND Trial: randomised controlled trial study protocol for case finding of obstructive sleep apnoea in primary care using a novel device.

INTRODUCTION: Obstructive sleep apnoea (OSA) is a common, but underdiagnosed, sleep disorder. If untreated, it leads to poor health outcomes, including Alzheimer's disease, cancer, cardiovascular disease and all-cause mortality. Our aim is to determine the feasibility and cost-effectiveness of moving the testing for OSA into general practice and how general practitioner (GP)-based screening affects overall detection rates. METHODS AND ANALYSIS: Randomised controlled trial of case finding of OSA in general practice using a novel Medicines and Healthcare products Regulatory Agency-registered device (AcuPebble SA100) compared with usual care with internal feasibility phase. A diverse sample of general practices (approximately 40) from across the West Midlands Clinical Research Network will identify participants from their records. Eligible participants will be aged 50-70 years with body mass index >30 kg/m2 and diabetes (type 1 or 2) and/or hypertension (office blood pressure >145/90 mm Hg or on treatment). They will exclude individuals with known OSA or chronic obstructive pulmonary disease, or those they deem unable to take part. After eligibility screening, consent and baseline assessment, participants will be randomised to either the intervention or control group. Participants in the intervention arm will receive by post the AcuPebble sleep test kit. Those in the control arm will continue with usual care. Follow-up questionnaires will be completed at 6 months. The study is powered (90%) to detect a 5% difference and will require 606 patients in each arm (713 will be recruited to each arm to allow for attrition). Due to the nature of the intervention, participants and GPs will not be blinded to the allocation. OUTCOMES: Primary: Detection rate of moderate-to-severe OSA in the intervention group versus control group. Secondary: Time to diagnosis and time to treatment for intervention versus control group for mild, moderate and severe OSA; cost-effectiveness analysis comparing the different testing pathways. ETHICS AND DISSEMINATION: The trial started on 1 November 2022. Ethical approval was granted from the South Central Oxford A Research Ethics Committee on 9 June 2023 (23/SC/0188) (protocol amendment version 1.3; update with amendment and approval to renumber to V2.0 on 29 August 2023). Patient recruitment began on 7 January 2024; initial planned end date will be on 31 April 2025.Results will be uploaded to the ISRCTN register within 12 months of the end of the trial date, presented at conferences, submitted to peer-reviewed journals and distributed via our patient and public involvement networks.The University of Warwick will act as the trial sponsor. The trial will be conducted in accordance with the Sponsor and Primary Care Clinical Trials Unit standard operating procedures. TRIAL REGISTRATION NUMBER: ISRCTN 16982033.

Effect of Potassium Supplementation on Endothelial Function: A Systematic Review and Meta-Analysis of Intervention Studies.

(1) Background: Endothelial dysfunction is an early predictor of cardiovascular diseases. Although a large body of evidence shows an inverse association between potassium intake and cardiovascular risk, the studies on endothelial function provided contrasting results. Thus, we carried out a systematic review and a meta-analysis of the available intervention studies of the potassium supplementation on endothelial function. (2) Methods: A systematic search of the online databases available (up to December 2022) was conducted including the intervention trials that reported flow-mediated dilation (FMD) changes-a non-invasive method of assessing endothelial function-after two different potassium intake regimens. For each study, the mean difference (MD) and 95% confidence intervals were pooled using a random effect model. (3) Results: Five studies met the pre-defined inclusion criteria and provided eight cohorts with 332 participants. In the pooled analysis, potassium supplementation was associated with a significant increase in FMD (MD: 0.74%), with a higher effect for a urinary potassium excretion higher than 90 mmol/day. There was a moderate heterogeneity among studies (I2 = 59%), explained by the different amount of potassium supplementation. (4) Conclusions: The results of our meta-analysis indicate that dietary potassium supplement improves endothelial function. This effect is directly associated with the amount of potassium supplement. The findings support the campaigns in favour of an increase in dietary potassium intake to reduce cardiovascular risk.

Rising arterial stiffness with accumulating comorbidities associates with heart failure with preserved ejection fraction.

AIMS: Comorbidities play a significant role towards the pathophysiology of heart failure with preserved ejection fraction (HFpEF), characterized by abnormal macrovascular function and altered ventricular-vascular coupling. However, our understanding of the role of comorbidities and arterial stiffness in HFpEF remains incomplete. We hypothesized that HFpEF is preceded by a cumulative rise in arterial stiffness as cardiovascular comorbidities accumulate, beyond that associated with ageing. METHODS AND RESULTS: Arterial stiffness was assessed using pulse wave velocity (PWV) in five groups: Group A, healthy volunteers (n = 21); Group B, patients with hypertension (n = 21); Group C, hypertension and diabetes mellitus (n = 20); Group D, HFpEF (n = 21); and Group E, HF with reduced ejection fraction (HFrEF) (n = 11). All patients were aged 70 and above. Mean PWV increased from Groups A to D (PWV 10.2, 12.2, 13.0, and 13.7 m/s, respectively) as vascular comorbidities accumulated independent of age, renal function, haemoglobin, obesity (body mass index), smoking status, and hypercholesterolaemia. HFpEF exhibited the highest PWV and HFrEF displayed near-normal levels (13.7 vs. 10 m/s, P = 0.003). PWV was inversely related to peak oxygen consumption (r = -0.304, P = 0.03) and positively correlated with left ventricular filling pressures (E/e') on echocardiography (r = -0.307, P = 0.014). CONCLUSIONS: This study adds further support to the concept of HFpEF as a disease of the vasculature, underlined by an increasing arterial stiffness that is driven by vascular ageing and accumulating vascular comorbidities, for example, hypertension and diabetes. Reflecting a pulsatile arterial afterload associated with diastolic dysfunction and exercise capacity, PWV may provide a clinically relevant tool to identify at-risk intermediate phenotypes (e.g. pre-HFpEF) before overt HFpEF occurs.

Pertinence of Salt-Related Knowledge and Reported Behaviour on Salt Intake in Adults: A Cross-Sectional Study.

The association between salt-related knowledge, attitude, behaviour (KAB) and actual salt consumption in Greek adults is uncertain. This study investigates the correlation between salt intake, gauged by 24-h urinary sodium excretion, with salt-related KAB. It further explores how socio-demographic factors influence these behaviors. Salt consumption was evaluated using a 24-h urinary sodium test, and compared to self-reported KAB data. Knowledge and behavior scores related to salt were computed. An overall cohort-adjusted model examined the relationship between daily salt consumption, knowledge and behavior scores, and certain covariates. Through the stratification by the cohort random effect, two models were established (Cohort I Adults; Cohort II Students) examining the same relationships of the overall cohort model. 463 Greek adults participated. The average salt intake was 9.54 g/day, nearly double the WHO recommendation. Significant differences in knowledge scores were noted based on sex, age, education, and BMI. A trend suggesting lower discretionary salt use with increased salt intake was observed (p = 0.06). However, comprehensive analysis revealed no direct correlation between salt intake and either knowledge (p = 0.562) or behavior scores (p = 0.210). The results emphasize the need for food product reforms by industry stakeholders and accelerated efforts towards reducing salt intake.

Sleep duration predicts cardiovascular outcomes: a systematic review and meta-analysis of prospective studies.

Aims To assess the relationship between duration of sleep and morbidity and mortality from coronary heart disease (CHD), stroke, and total cardiovascular disease (CVD). Methods and results We performed a systematic search of publications using MEDLINE (1966-2009), EMBASE (from 1980), the Cochrane Library, and manual searches without language restrictions. Studies were included if they were prospective, follow-up >3 years, had duration of sleep at baseline, and incident cases of CHD, stroke, or CVD. Relative risks (RR) and 95% confidence interval (CI) were pooled using a random-effect model. Overall, 15 studies (24 cohort samples) included 474 684 male and female participants (follow-up 6.9-25 years), and 16 067 events (4169 for CHD, 3478 for stroke, and 8420 for total CVD). Sleep duration was assessed by questionnaire and incident cases through certification and event registers. Short duration of sleep was associated with a greater risk of developing or dying of CHD (RR 1.48, 95% CI 1.22-1.80, P < 0.0001), stroke (1.15, 1.00-1.31, P = 0.047), but not total CVD (1.03, 0.93-1.15, P = 0.52) with no evidence of publication bias (P = 0.95, P = 0.30, and P = 0.46, respectively). Long duration of sleep was also associated with a greater risk of CHD (1.38, 1.15-1.66, P = 0.0005), stroke (1.65, 1.45-1.87, P < 0.0001), and total CVD (1.41, 1.19-1.68, P < 0.0001) with no evidence of publication bias (P = 0.92, P = 0.96, and P = 0.79, respectively). Conclusion Both short and long duration of sleep are predictors, or markers, of cardiovascular outcomes.