Comprehensive analyses of circulating cardiometabolic proteins and objective measures of fat mass.

BACKGROUND: The underlying molecular pathways for the effect of excess fat mass on cardiometabolic diseases is not well understood. Since body mass index is a suboptimal measure of body fat content, we investigated the relationship of fat mass measured by dual-energy X-ray absorptiometry with circulating cardiometabolic proteins. METHODS: We used data from a population-based cohort of 4950 Swedish women (55-85 years), divided into discovery and replication samples; 276 proteins were assessed with three Olink Proseek Multiplex panels. We used random forest to identify the most relevant biomarker candidates related to fat mass index (FMI), multivariable linear regression to further investigate the associations between FMI characteristics and circulating proteins adjusted for potential confounders, and principal component analysis (PCA) for the detection of common covariance patterns among the proteins. RESULTS: Total FMI was associated with 66 proteins following adjustment for multiple testing in discovery and replication multivariable analyses. Five proteins not previously associated with body size were associated with either lower FMI (calsyntenin-2 (CLSTN2), kallikrein-10 (KLK10)), or higher FMI (scavenger receptor cysteine-rich domain-containing group B protein (SSC4D), trem-like transcript 2 protein (TLT-2), and interleukin-6 receptor subunit alpha (IL-6RA)). PCA provided an efficient summary of the main variation in FMI-related circulating proteins involved in glucose and lipid metabolism, appetite regulation, adipocyte differentiation, immune response and inflammation. Similar patterns were observed for regional fat mass measures. CONCLUSIONS: This is the first large study showing associations between fat mass and circulating cardiometabolic proteins. Proteins not previously linked to body size are implicated in modulation of postsynaptic signals, inflammation, and carcinogenesis.

The Effects of Statins on Cognitive Performance Are Mediated by Low-Density Lipoprotein, C-Reactive Protein, and Blood Glucose Concentrations.

Statins are widely used for cardiovascular disease prevention but their effects on cognition remain unclear. Statins reduce cholesterol concentration and have been suggested to provide both beneficial and detrimental effects. Our aim was to investigate the cross-sectional and longitudinal association between statin use and cognitive performance, and whether blood low-density lipoprotein, high-density lipoprotein, triglycerides, glucose, C-reactive protein, and vitamin D biomarkers mediated this association. We used participants from the UK biobank aged 40-69 without neurological and psychiatric disorders (n = 147 502 and n = 24 355, respectively). We performed linear regression to evaluate the association between statin use and cognitive performance and, mediation analysis to quantify the total, direct, indirect effects and the proportion meditated by blood biomarkers. Statin use was associated with lower cognitive performance at baseline (ß = -0.40 [-0.53, -0.28], p = <.0001), and this association was mediated by low-density lipoprotein (proportion mediated = 51.4%, p = .002), C-reactive protein (proportion mediated = -11%, p = .006) and blood glucose (proportion mediated = 2.6%, p = .018) concentrations. However, statin use was not associated with cognitive performance, measured 8 years later (ß = -0.003 [-0.11, 0.10], p = .96). Our findings suggest that statins are associated with lower short-term cognitive performance by lowering low-density lipoprotein and raising blood glucose concentrations, and better performance by lowering C-reactive protein concentrations. In contrast, statins have no effect on long-term cognition and remain beneficial in reducing cardiovascular risk factors.

Circulating proteins and peripheral artery disease risk: observational and Mendelian randomization analyses.

Aims: We conducted observational and Mendelian randomization (MR) analyses to explore the associations between blood proteins and risk of peripheral artery disease (PAD). Methods and results: The observational cohort analyses included data on 257 proteins estimated in fasting blood samples from 12 136 Swedish adults aged 55-94 years who were followed up for incident PAD via the Swedish Patient Register. Mendelian randomization analyses were undertaken using cis-genetic variants strongly associated with the proteins as instrumental variables and genetic association summary statistic data for PAD from the FinnGen study (11 924 cases and 288 638 controls) and the Million Veteran Program (31 307 cases and 211 753 controls). The observational analysis, including 86 individuals diagnosed with incident PAD during a median follow-up of 6.6-year, identified 13 proteins [trefoil factor two, matrix metalloproteinase-12 (MMP-12), growth differentiation factor 15, V-set and immunoglobulin domain-containing protein two, N-terminal prohormone brain natriuretic peptide, renin, natriuretic peptides B, phosphoprotein associated with glycosphingolipid-enriched microdomains one, C-C motif chemokine 15, P-selectin, urokinase plasminogen activator surface receptor, angiopoietin-2, and C-type lectin domain family five member A] associated with the risk of PAD after multiple testing correction. Mendelian randomization analysis found associations of T-cell surface glycoprotein CD4, MMP-12, secretoglobin family 3A member 2, and ADM with PAD risk. The observational and MR associations for T-cell surface glycoprotein CD4 and MMP-12 were in opposite directions. Conclusion: This study identified many circulating proteins in relation to the development of incident PAD. Future studies are needed to verify our findings and assess the predictive and therapeutic values of these proteins in PAD.

Sleep duration, daytime napping, and risk of peripheral artery disease: multinational cohort and Mendelian randomization studies.

Aims: Sleep duration has been associated with cardiovascular disease, however the effect of sleep on peripheral artery disease (PAD) specifically remains unestablished. We conducted observational and Mendelian randomization (MR) analyses to assess the associations of sleep duration and daytime napping with PAD risk. Methods and results: Sleep traits were assessed for associations with incident PAD using cohort analysis among 53 416 Swedish adults. Replicated was sought in a case-control study of 28 123 PAD cases and 128 459 controls from the veterans affairs Million Veteran Program (MVP) and a cohort study of 452 028 individuals from the UK Biobank study (UKB). Two-sample Mendelian randomization (MR) was used for casual inference-based analyses of sleep-related traits and PAD (31 307 PAD cases 211 753 controls). Observational analyses demonstrated a U-shaped association between sleep duration and PAD risk. In Swedish adults, incident PAD risk was higher in those with short sleep [<5 h; hazard ratio (HR) 1.74; 95% confidence interval (CI) 1.31-2.31] or long sleep (≥8 h; HR 1.24; 95% CI 1.08-1.43), compared to individuals with a sleep duration of 7 to <8 h/night. This finding was supported by the analyses in MVP and UKB. Observational analysis also revealed positive associations between daytime napping (HR 1.32, 95% CI 1.18-1.49) with PAD. MR analysis supported an inverse association between sleep duration [odds ratio (OR) per hour increase: 0.79, 95% CI, 0.55, 0.89] and PAD and an association between short sleep and increased PAD (OR 1.20, 95% CI, 1.04-1.38). Conclusion: Short sleep duration was associated with an increased risk of PAD.

Swedish Snuff (Snus), Cigarette Smoking, and Risk of Type 2 Diabetes.

INTRODUCTION: Cigarette smoking is a known risk factor for Type 2 diabetes, but evidence regarding former smoking and moist snuff (snus) use and Type 2 diabetes risk is inconclusive. This study investigated the relationships of cigarette smoking and Swedish snus use with the risk of Type 2 diabetes in a cohort of middle-aged and elderly participants. METHODS: Participants (N=36,742; age range=56-95 years) were followed for incident Type 2 diabetes and death between 2009 and 2017 through linkage to the Swedish National Patient, Prescribed Drug and Death Registers. Cox proportional hazards regression was used to obtain hazard ratios and 95% CIs adjusted for potential confounders, including physical activity, education, BMI, and alcohol intake. Analyses were conducted in 2021‒2022. RESULTS: Former and current smoking was associated with an increased risk of Type 2 diabetes (hazard ratios [95% CI]=1.17 [1.07, 1.29] and 1.57 [1.36, 1.81], respectively). In those who stopped smoking, Type 2 diabetes risk remained elevated up to approximately 15 years after cessation. In participants who have never smoked, snus use was linked to a higher risk of Type 2 diabetes in the model adjusted for age and sex (hazard ratio [95% CI]=1.49 [1.04, 2.15]), but this was attenuated after multivariable adjustment (hazard ratio [95% Cl]=1.29 [0.89, 1.86]). CONCLUSIONS: This study indicates that current and former smoking are associated with an increased risk of Type 2 diabetes in middle-aged and older individuals. There was less evidence of an association of snus use with the risk of Type 2 diabetes, suggesting that compounds other than nicotine may underlie the detrimental association of smoking with the risk of Type 2 diabetes.

Plasma protein and venous thromboembolism: prospective cohort and mendelian randomisation analyses.

We conducted cohort and Mendelian randomisation (MR) analyses to examine the associations of circulating proteins with risk of venous thromboembolism (VTE) to provide evidence basis for disease prevention and drug development. Cohort analysis was performed in 11 803 participants without baseline VTE. Cox regression was used to estimate the associations between 257 proteins and VTE risk. A machine-learning model was constructed to compare the importance of identified proteins and traditional risk factors. Genetic association data on VTE were obtained from a genome-wide meta-analysis (26 066 cases and 624 053 controls) and FinnGen (14 454 cases and 294 700 controls). The cohort analysis, including 353 incident VTE cases diagnosed during a 6.6-year follow-up, identified 21 proteins associated with VTE risk after false discovery rate correction. The machine-learning model indicated that body mass index and von Willebrand factor (vWF) made the same as well as most of the contributions to the overall model prediction. MR analysis found that genetically predicted levels of vWF, SERPINE1 (plasminogen activator inhibitor 1, known as PAI-1), EPHB4 (ephrin type-B receptor 4), TYRO3 (tyrosine-protein kinase receptor TYRO3), TNFRSF11A (tumour necrosis factor receptor superfamily member 11A), and BOC (brother of CDO) were causally associated with VTE risk.

Morning chronotype and digestive tract cancers: Mendelian randomization study.

Morning chronotype has been associated with a reduced risk of prostate and breast cancer. However, few studies have examined whether chronotype is associated with digestive tract cancer risk. We conducted a Mendelian randomization (MR) study to assess the associations of chronotype with major digestive tract cancers. A total of 317 independent genetic variants associated with chronotype at the genome-wide significance level (P < 5 × 10-8 ) were used as instrumental variables from a genome-wide meta-analysis of 449 734 individuals. Summary-level data on overall and six digestive tract cancers, including esophageal, stomach, liver, biliary tract, pancreatic and colorectal cancers, were obtained from the UK Biobank (11 952 cases) and FinnGen (7638 cases) study. Genetic liability to morning chronotype was associated with reduced risk of overall digestive tract cancer and cancers of stomach, biliary tract and colorectum in UK Biobank. The associations for the overall digestive tract, stomach and colorectal cancers were directionally replicated in FinnGen. In the meta-analysis of the two sources, genetic liability to morning chronotype was associated with a decreased risk of overall digestive tract cancer (odds ratio [OR] 0.94, 95% confidence interval [CI]: 0.90-0.98), stomach cancer (OR 0.84, 95% CI: 0.73-0.97) and colorectal cancer (OR 0.92, 95% CI: 0.87-0.98), but not with the other studied cancers. The associations were consistent in multivariable MR analysis with adjustment for genetically predicted sleep duration, short sleep, insomnia and body mass index. The study provided MR evidence of inverse associations of morning chronotype with digestive tract cancer, particularly stomach and colorectal cancers.

Anger frequency and risk of cardiovascular morbidity and mortality.

Aims: Anger may increase the risk of cardiovascular diseases (CVDs) but previous findings are inconclusive and large prospective studies are needed. We investigated whether frequency of strong anger is associated with the incidence of specific CVDs and CVD mortality, and if sex, age, and cardiometabolic risk factors modify these associations. Methods and results: We used data from a population-based cohort of 47 077 Swedish adults (56-94 years of age) who completed questionnaires regarding their experience of anger, lifestyle habits, and health characteristics. Participants were followed for incident cardiovascular outcomes and death up to 9 years through linkage to the Swedish National Patient and Death Registers. Hazard ratios and confidence intervals adjusted for potential confounders were assessed.In multivariable analyses, frequent episodes of strong anger were associated with an increased risk of heart failure, atrial fibrillation, and CVD mortality [hazard ratios (95% confidence intervals) = 1.19 (1.04-1.37), 1.16 (1.06-1.28), and 1.23 (1.09-1.40), respectively]. The link between anger frequency and heart failure was more pronounced in men and participants with a history of diabetes. No evidence of an independent association of anger frequency with risk of myocardial infarction, aortic valve stenosis, and abdominal aortic aneurysm was found. Conclusion: Our findings indicate that anger may contribute to the development of specific CVDs and CVD mortality, especially heart failure in men and in those with diabetes.

Self-Reported Psychosomatic Complaints and Conduct Problems in Swedish Adolescents.

Physical conditions in children and adolescents are often under reported during mainstream school years and may underlie mental health disorders. Additionally, comparisons between younger and older schoolchildren may shed light on developmental differences regarding the way in which physical conditions translate into conduct problems. The aim of the current study was to examine the incidence of psychosomatic complaints (PSC) in young and older adolescent boys and girls who also report conduct problems. A total of 3132 Swedish adolescents (age range 15-18 years, 47% boys) completed the Uppsala Life and Health Cross-Sectional Survey (LHS) at school. The LHS question scores were categorised by two researchers who independently identified questions that aligned with DSM-5 conduct disorder (CD) criteria and PSC. MANOVA assessed the effects of PSC, age, and gender on scores that aligned with the DSM criteria for CD. The main effects of gender, age, and PSC on the conduct problem scores were observed. Adolescents with higher PSC scores had higher conduct problem scores. Boys had higher serious violation of rules scores than girls, particularly older boys with higher PSC scores. Psychosomatic complaints could be a useful objective identifier for children and adolescents at risk of developing conduct disorders. This may be especially relevant when a reliance on a child's self-reporting of their behavior may not help to prevent a long-term disturbance to their quality of life.

Swedish snuff (snus) dipping, cigarette smoking, and risk of peripheral artery disease: a prospective cohort study.

Tobacco smoking is an important risk factor for peripheral artery disease (PAD), but it remains unknown whether smokeless tobacco, such as Swedish snuff (snus), is also associated with this disease. We used data from the Cohort of Swedish Men including 24,085 men. Individuals were grouped into never, past, and current snus dippers as well as never, past quitting ≥ 10 years, past, quitting < 10 years, and current smokers. Incident PAD cases were defined by linkage of the cohort with the Swedish National Patient Register. Cox proportional hazards regression was used to analyze the data. Over a mean follow-up period of 9.1 years (from July 1, 2009 to December 31, 2019), 655 incident PAD cases were ascertained. Cigarette smoking but not Swedish snus dipping was associated with an increased risk of PAD. Compared with never snus dippers, the hazard ratio of PAD was 0.95 (95% confidence interval [CI] 0.73-1.24) for past snus dippers and 0.88 (95% CI 0.66-1.17) for current snus dippers. Compared to never smokers, the hazard ratio of PAD was 1.38 (95% CI 1.14-1.68) for past smoker who stopped smoking for ≥ 10 years, 2.61 (95% CI 1.89-3.61) for past smoker who stopped smoking for < 10 years, and 4.01 (95% CI 3.17, 5.08) for current smoker. In conclusion, cigarette smoking but not Swedish snus dipping increases the risk of PAD.

Self-reported symptoms of sleep-disordered breathing and risk of cardiovascular diseases: Observational and Mendelian randomization findings.

Sleep-disordered breathing may increase the risk of cardiovascular diseases, but observational findings are inconclusive. We investigated whether sleep-disordered breathing-related symptoms are associated with risk of several cardiovascular diseases using data from a cohort study and by performing Mendelian randomization analyses. The cohort study included 43,624 adults (56-94 years old) who completed questionnaires regarding symptoms of snoring and cessation of breathing, lifestyle habits and health characteristics. Participants were followed up for incident cardiovascular diseases and death over 8 years through linkage to the Swedish National Patient and Death Registers. The Mendelian randomization analyses were conducted using single-nucleotide polymorphisms robustly associated with sleep apnea in a recent genome-wide association study and summary-level data for major cardiovascular diseases from large-scale consortia. In the cohort study, an increased risk of atrial fibrillation was observed in participants who reported both snoring and cessation of breathing (hazard ratio [95% confidence interval] = 1.16 [1.03-1.30]) compared with those without sleep-disordered breathing symptoms. There was no association between sleep-disordered breathing symptoms and risk of myocardial infarction, heart failure, aortic valve stenosis or abdominal aortic aneurysm in multivariable analyses. Mendelian randomization analyses showed no association of genetic liability to sleep apnea with myocardial infarction, heart failure or atrial fibrillation, but revealed a suggestive association with coronary artery disease (odds ratio [95% confidence interval] = 1.24 [1.02-1.52]).

Seasonal variations in sleep duration and sleep complaints: A Swedish cohort study in middle-aged and older individuals.

Subjective sleep reports are widely used research tools in epidemiology. Whether sleep reports can differ between seasons is less clear. Using multivariable binary or multinomial logistic regression analyses, in the present Swedish cross-sectional two-centre cohort study (N = 19,254; mean age 61 years), we found that participants surveyed during the summer (June-August) were more likely to report short sleep duration (defined as ≤ 6 hr) compared with those interviewed during the autumn (odds ratio [95% confidence interval] = 1.14 [1.04-1.25]). Individuals interviewed in the winter (December-February) were less likely to report early awakenings compared with participants surveyed in the autumn (September-November; odds ratio [95% confidence interval] = 0.85 [0.75-0.96]). Complaints of difficulties in falling asleep and disturbed sleep were less common among participants interviewed during spring (March-May) compared with those interviewed during the autumn (odds ratio [95% confidence interval] = 0.86 [0.74-0.99] and 0.88 [0.79-0.98], respectively). No seasonal variations in reports of long sleep, difficulty maintaining sleep, or feeling not rested after sleep were observed. Additional subgroup analysis revealed that summer participants were more likely to report short sleep duration and early morning awakenings than individuals surveyed in winter. In conclusion, this Swedish study indicates that self-reported sleep characteristics may vary across seasons. Further studies are needed to confirm our findings.

Sleep-disordered breathing-related symptoms and risk of stroke: cohort study and Mendelian randomization analysis.

BACKGROUND: Sleep-disordered breathing (SDB) may contribute to development of stroke. However, findings are inconclusive. We investigated whether SDB-related symptoms are associated with incidence of stroke and its types in a general community sample of adult men and women as well as to perform Mendelian randomization (MR) analysis. METHODS: We used data from a cohort of 41,742 Swedish adults (56-94 years of age) who completed questionnaires regarding snoring, cessation of breathing, lifestyle and health characteristics. Participants were followed up for incident stroke and death over 8 years through linkage to the Swedish Registers. Hazard ratios, adjusted for potential confounders, were estimated by Cox proportional hazards regression. MR analyses were performed using single-nucleotide polymorphisms associated with sleep apnea at the genome-wide significance level and summary-level data for stroke and its subtypes from consortia and a meta-analysis of Genome-Wide Association Studies. RESULTS: In the cohort study, symptoms of disturbing snoring and/or cessation of breathing were associated with increased risk of total stroke (hazard ratio 1.12, 95% confidence interval 1.02-1.24) and intracerebral hemorrhage (hazard ratio 1.59, 95% confidence interval 1.23-2.05) but not with ischemic stroke or subarachnoid hemorrhage. MR analyses showed no association of genetic liability to sleep apnea with the risk of overall stroke or any specific types of stroke or ischemic stroke subtypes. CONCLUSIONS: SDB-related symptoms were associated with increased risk of total stroke, specifically intracerebral hemorrhage, in the observational analyses but not in the MR analyses. There was limited evidence of an association of SDB with ischemic stroke and subarachnoid hemorrhage.

Important gender differences in psychosomatic and school-related complaints in relation to adolescent weight status.

Underweight or overweight in adolescence is linked to several adverse health outcomes. Less evidence exists about the association between weight status and school-related psychosocial characteristics in high income countries. We sought to investigate the relationship between weight status and psychosomatic and school-related complaints with a focus on gender differences. The study is a cohort of 18,462 adolescents (12-19 years; 51% girls) conducted in Sweden. The associations between weight status and psychosomatic and school-related complaints were estimated by binary logistic regression adjusted for several potential confounders. After correction for multiple testing, being underweight or overweight/obese was adversely associated with several psychosomatic and school-related complaints with significant differences between boys and girls. Specifically, underweight boys had higher odds to have psychosomatic complaints than normal-weight boys, while no such associations were observed among underweight girls. Overweight/obese (vs. normal-weight) boys had higher odds to complain about headache, pain in the back/hips, and feeling low. Overweight/obese (vs. normal-weight) girls were more likely to complain about feeling low, anxious/worried and having difficulty in falling asleep (P ≤ 0.01). In relation to school-related complaints (e.g., being bullied at school and academic failure), greater associations were observed for overweight/obese girls and boys than for underweight adolescents compared with normal-weight peers.

Swedish snuff (snus) and risk of cardiovascular disease and mortality: prospective cohort study of middle-aged and older individuals.

BACKGROUND: Cigarette smoking is a well-known risk factor for cardiovascular disease (CVD), but whether smokeless tobacco such as snuff is associated with the risk of CVD is still unclear. We investigated the association of the use of Swedish oral moist snuff (snus) with a broad range of CVDs and CVD mortality. METHODS: We used data from a population-based cohort of 41,162 Swedish adults with a mean baseline age of 70 (56-94) years who completed questionnaires regarding snus use and other lifestyle habits and health characteristics. Participants were followed up for incident cardiovascular outcomes and death over 8 years through linkage to the Swedish National Patient and Death Registers. Hazard ratios (HR) were estimated by Cox proportional hazards regression. We conducted analyses among all subjects as well as among never smokers to reduce residual confounding from smoking. RESULTS: After adjustment for smoking and other confounders, snus use was not associated with myocardial infarction, heart failure, atrial fibrillation, aortic valve stenosis, abdominal aortic aneurysm, stroke, or CVD mortality. However, in never smokers, snus use was associated with a statistically significant increased risk of total and ischemic stroke (HRs [95% confidence intervals] = 1.52 [1.01-2.30] and 1.63 [1.05-2.54], respectively) and non-significantly positively associated with some other CVDs. CONCLUSIONS: In this middle-aged and elderly Swedish population, current Swedish snus use was not associated with the risk of major heart and valvular diseases, abdominal aortic aneurysm, or CVD mortality in the entire study population, but was linked to an increased risk of stroke in never smokers.

Association between pet ownership and sleep in the Swedish CArdioPulmonary bioImage Study (SCAPIS).

Preliminary findings suggest that pets may impact the owner's sleep. By using data from the Swedish CArdioPulmonary bIoimage Study (SCAPIS) cohort, we aimed to investigate the association of pet ownership with the following self-reported sleep outcomes in 3788 to 4574 participants: (i) achieving the recommended daily sleep duration for adults (i.e., at least 7 h per day); (ii) sleep quality as measured by the Pittsburgh Sleep Quality Index (a score of > 5 indicating poor sleep quality); and (iii) difficulty falling or staying asleep. Sleep metrics were not associated with pet ownership, dog ownership, and dog walking when controlling the logistic regression for possible confounders (e.g., shift work, lack of social interaction, and chronic stress). In contrast, cat ownership was associated with a higher odds ratio of failing to achieve the recommended duration of 7 h of sleep per day (adjusted odds ratio [95% CI]:1.18 [1.02, 1.37] versus non-cat owners). Our findings suggest that certain pet groups might have a more significant impact on the owner's sleep than others. As the observed association between cat ownership and short sleep duration might be a chance finding, this observation should be seen as hypothesis-generating only.

Sleep duration and risk of overall and 22 site-specific cancers: A Mendelian randomization study.

Studies of sleep duration in relation to the risk of site-specific cancers other than breast cancer are scarce. Furthermore, the available results are inconclusive and the causality remains unclear. We aimed to investigate the potential causal associations of sleep duration with overall and site-specific cancers using the Mendelian randomization (MR) design. Single-nucleotide polymorphisms associated with the sleep traits identified from a genome-wide association study were used as instrumental variables to estimate the association with overall cancer and 22 site-specific cancers among 367 586 UK Biobank participants. A replication analysis was performed using data from the FinnGen consortium (up to 121 579 individuals). There was suggestive evidence that genetic liability to short-sleep duration was associated with higher odds of cancers of the stomach (odds ratio [OR], 2.22; 95% confidence interval [CI], 1.15-4.30; P = .018), pancreas (OR, 2.18; 95% CI, 1.32-3.62; P = .002) and colorectum (OR, 1.48; 95% CI, 1.12-1.95; P = .006), but with lower odds of multiple myeloma (OR, 0.47; 95% CI, 0.22-0.99; P = .047). Suggestive evidence of association of genetic liability to long-sleep duration with lower odds of pancreatic cancer (OR, 0.44; 95% CI, 0.25-0.79; P = .005) and kidney cancer (OR, 0.44; 95% CI, 0.21-0.90; P = .025) was observed. However, none of these associations passed the multiple comparison threshold and two-sample MR analysis using FinnGen data did not confirm these findings. In conclusion, this MR study does not provide strong evidence to support causal associations of sleep duration with risk of overall and site-specific cancers. Further MR studies are required.

Important Difference between Occupational Hazard Exposure among Shift Workers and Other Workers; Comparing Workplace before and after 1980.

Improving health and safety at work has been an important issue for the European Union since the 1980s. The existing literature supports that shift work is associated with multiple indicators of poor health but frequently neglects the potential impact of occupational hazards. This study aims at describing and comparing the exposure to different workplace hazards among shift and other workers before and after 1980. Exposure to different workplace hazards (noise, dust, pollutant, and other physical stressors) were analyzed among 119,413 participants from the UK Biobank cohort. After stratifying the analyses before and after 1980, exposure was compared between shift and other workers. Potential confounding variables (sex, age, ethnicity, education level, occupational category, and neuroticism) were adjusted for in the log-binomial regression. Shift workers had a higher prevalence ratio (PR) than other workers of being exposed to almost all identified hazards both before or after 1980. They were also more likely to be exposed to multiple hazards compared to other workers, both before 1980 (PR: 1.25; 95% CI: 1.21-1.30) and after 1980 (PR: 1.34; 95% CI: 1.30-1.38). The prevalence of all measured risk factors was higher after 1980 than before 1980 among shift workers. Of note, the work environment has improved overall for other workers. Our findings suggest that changes at the workplace have benefited other workers more than shift workers as they are still more exposed to all occupational hazards.

Sleep Duration and Stroke: Prospective Cohort Study and Mendelian Randomization Analysis.

BACKGROUND AND PURPOSE: Studies of sleep duration in relation to specific types of stroke are scarce. Moreover, the results are inconclusive and causality remains unclear. Our objective was to investigate whether sleep duration is associated with risk of stroke and its types using observational and Mendelian randomization designs. METHODS: The prospective study included 79 881 women and men (45-79 years of age) who were followed up for incident stroke or death over a mean follow-up of 14.6 years (1 164 646 person-years) through linkage to Swedish Registers. For the Mendelian randomization study, single-nucleotide polymorphisms associated with sleep duration were identified from a genome-wide association study. Summarized data for genetic associations with stroke were obtained from publicly available data of the MEGASTROKE and the International Stroke Genetics Consortia. RESULTS: Compared with normal sleep duration, long sleep (≥9 hours per day) was associated with increased risk of total and ischemic stroke (hazard ratios [95% CI], 1.12 [1.03-1.22] and 1.14 [1.03-1.24], respectively), whereas short sleep (<7 h/d) was linked to higher risk of intracerebral hemorrhage (hazard ratio [95% CI], 1.21 [1.03-1.41]). The 2-sample Mendelian randomization analysis supported no causal association of short or long sleep duration with ischemic stroke as a whole. CONCLUSIONS: In a prospective study, long sleep duration was associated with increased risk of total and ischemic stroke, whereas short sleep was linked to increased risk of intracerebral hemorrhage. However, the Mendelian randomization analysis did not show a significant detrimental effect of short or long sleep duration on the risk of total stroke or stroke types.