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The association between bone mineral density (BMD) and cardiovascular disease (CVD) is not fully understood. We evaluated BMD as a risk factor for cardiovascular disease and specifically atrial fibrillation (AF), acute myocardial infarction (AMI), ischemic (IS) and hemorrhagic stroke (HS) and heart failure (HF) in men and women. This prospective population cohort utilized data on 22 857 adults from the second and third surveys of the HUNT Study in Norway free from CVD at baseline. BMD was measured using single and dual-energy X-ray absorptiometry in the non-dominant distal forearm and T-score was calculated. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated from adjusted cox proportional hazards models. The analyses were sex-stratified, and models were adjusted for age, age-squared, BMI, physical activity, smoking status, alcohol use, and education level. Additionally, in women, we adjusted for estrogen use and postmenopause. During a mean follow-up of 13.6 ± 5.7 years, 2 928 individuals (12.8%) developed fatal or non-fatal CVD, 1 020 AF (4.5%), 1 172 AMI (5.1%), 1 389 IS (6.1%), 264 HS (1.1%), and 464 HF (2.0%). For every 1 unit decrease in BMD T-score the HR for any CVD was 1.01 (95% CI 0.98 to 1.04) in women and 0.99 (95% CI 0.94 to 1.03) in men. Point estimates for the four cardiovascular outcomes ranged from slightly protective (HR 0.95 for AF in men) to slightly deleterious (HR 1.12 for HS in men). We found no evidence of association of lower distal forearm BMD with CVD, AF, AMI, IS, HS, and HF. Supplementary Information The online version contains supplementary material available at 10.1007/s10654-021-00803-y.

Background and Purpose: Obesity is one of the most prevalent modifiable risk factors of ischemic stroke. However, it is still unclear whether obesity itself or the metabolic abnormalities due to obesity increase the risk of ischemic stroke. We therefore investigated the association between metabolic health, weight, and risk of ischemic stroke in a large prospective cohort study. Methods: In the Norwegian HUNT study (Trøndelag Health Study), we included 35 105 participants with complete information on metabolic risk factors and relevant covariates. Metabolically unhealthy state was defined as sex specific increased waist circumference in addition to 2 or more of the following criteria: hypertension, increased blood pressure, decreased high-density lipoprotein, triglycerides or glucose, or self-reported diagnosis of diabetes. We then applied Cox proportional hazard models to estimate the risk for ischemic stroke among overweight and obese metabolically healthy and unhealthy participants compared with metabolically healthy, normal weight participants. Results: A total of 1161 ischemic stroke cases occurred after an average observation time of 11.9 years. In general, metabolically unhealthy participants were at increased risk of ischemic stroke (for obese participants: hazard ratio, 1.30 [95% CI, 1.09–1.56] compared with metabolically healthy participants with a normal body mass index). Hypertension appeared to be the most important metabolic risk factor. Metabolically healthy participants with overweight or obesity were at similar risk of ischemic stroke compared with normal weight participants (hazard ratio, 1.02 [95% CI, 0.81–1.28] for participants with obesity). Obesity and overweight even over an extended period of time seems to be benign about ischemic stroke, as long as it was not associated with metabolic abnormalities. Conclusions: Obesity was not an independent ischemic stroke risk factor in this cohort, and the risk depended more on the metabolic consequences of obesity.

OBJECTIVE Atrial fibrillation (AF) is the most common arrhythmia and has been described as a global epidemic. Although AF is associated with both obesity and its metabolic consequences, little is known about the association between metabolically healthy obesity and AF. METHODS In a population-based study, 47,870 adults were followed for incident AF from 2006 to 2008 until 2015. Participants were classified according to BMI and metabolic status (using waist circumference, triglycerides, high-density lipoprotein cholesterol, blood pressure, and glucose) at baseline. RESULTS During a median follow-up of 8.1 years, 1,758 participants developed AF. Compared with metabolically healthy individuals with BMI

We examined the short-term risk of stroke associated with drugs prescribed in Norway or Sweden in a comprehensive, hypothesis-free manner using comprehensive nation-wide data. We identified 27,680 and 92,561 cases with a first ischemic stroke via the patient- and the cause-of-death registers in Norway (2004–2014) and Sweden (2005–2014), respectively, and linked these data to prescription databases. A case-crossover design was used that compares the drugs dispensed within 1 to 14 days before the date of ischemic stroke occurrence with those dispensed 29 to 42 days before the index event. A Bolasso approach, a version of the Lasso regression algorithm, was used to select drugs that acutely either increase or decrease the apparent risk of ischemic stroke. Application of the Bolasso regression algorithm selected 19 drugs which were associated with increased risk for ischemic stroke and 11 drugs with decreased risk in both countries. Morphine in combination with antispasmodics was associated with a particularly high risk of stroke (odds ratio 7.09, 95% confidence intervals 4.81–10.47). Several potentially intriguing associations, both within and across pharmacological classes, merit further investigation in focused, follow-up studies.

Asthma, a chronic inflammatory airway disease, shares several common pathophysiological mechanisms with acute myocardial infarction (AMI). Our aim was to assess the prospective associations between asthma, levels of asthma control and risk of AMI. We followed 57,104 adults without previous history of AMI at baseline from Nord-Trøndelag health study (HUNT) in Norway. Self-reported asthma was categorised as active asthma (i.e., using asthma medication) and non-active asthma (i.e., not using asthma medication). Levels of asthma control were defined as controlled, partly controlled, and uncontrolled based on the Global Initiative for Asthma guidelines. AMI was ascertained by linking HUNT data with hospital records. A total of 2868 AMI events (5.0%) occurred during a mean (SD) follow-up of 17.2 (5.4) years. Adults with active asthma had an estimated 29% higher risk of developing AMI [adjusted hazard ratio (HR) 1.29, 95% CI 1.08–1.54] compared with adults without asthma. There was a significant dose–response association between asthma control and AMI risk, with highest risk in adults with uncontrolled asthma (adjusted HR 1.73, 95% CI 1.13–2.66) compared to adults with controlled asthma (p for trend < 0.05). The associations were not explained by smoking status, physical activity and C-reactive protein levels. Our study suggests that active asthma and poor asthma control are associated with moderately increased risk of AMI. Further studies are needed to evaluate causal relationship and the underlying mechanisms and to clarify the role of asthma medications in the risk of AMI.

Introduction: Asthma, a chronic inflammatory airway disease, shares several common pathophysiological mechanisms with stroke. Research of the association between asthma, asthma control and stroke risk are lacking. Aims and Objectives: To assess the association between asthma, levels of asthma control and stroke risk. Methods: This prospective population cohort utilized data on 58 540 adults from a second and third examinations of “The Nord-Trondelag Health Study” in Norway free from stroke at baseline. Self-reported asthma was categorized as ever asthma and active asthma (i.e., being on asthma medication within 12 months of the baseline). Asthma control was defined according to the Global Initiative for Asthma guidelines and was categorized into controlled, partly-controlled and uncontrolled asthma. Stroke was ascertained by linking HUNT data with Nord-Trondelag hospital records and Norwegian Patient Registry. Results: During a mean follow-up of 17.27 ± 5.33 years, 2 029 participants (3.5%) developed stroke. Active asthma was associated with small borderline increased risk of stroke (adjusted HR 1.20, 95% CI 0.99-1.45). Subgroup analyses revealed stronger association between active asthma and stroke risk among male participants (adjusted HR 1.35, 95% CI 1.06-1.73) and among smokers (adjusted HR 1.35, 95% CI 1.09-1.68). Associations were not explained by C-reactive protein levels and physical activity. There were no significant associations in asthma control groups (p for trend >0.100). Conclusions: Active asthma was associated with modest increased risk of stroke in males and smokers independently of other conventional cardiovascular risk factors.

Background Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. Anxiety and depression may activate the autonomic nervous system which is likely to play an important role in the etiology of AF. However, little is known about the association between symptoms of anxiety and depression and risk of AF. Objective This study aimed to assess the association between symptoms of anxiety and depression and risk of AF. Methods In a population-based study, 37,402 adult residents were followed for incident AF from 2006 to 2008 until 2015. Participants were classified according to data on anxiety and depression symptoms. Cox proportional regression models were used to adjust for common AF risk factors. Results During a median follow-up of 8.1 years, 1433 (3.8%) participants developed AF. In comparisons with no anxiety symptoms, the multivariable-adjusted hazard ratios (HRs) were 1.1 (95% CI: 0.9–1.5) for mild to moderate anxiety symptoms and 1.0 (95% CI: 0.8–1.4) for severe anxiety symptoms. In comparisons with no depression symptoms, the multivariable-adjusted HRs were 1.5 (95% CI: 1.2–1.8) for mild to moderate depression symptoms and 0.9 (95% CI: 0.6–1.3) for severe depression symptoms. Recurrent anxiety/depression symptoms were not associated with increased AF risk. Conclusions In this large, population-based study, we found no evidence of an association between symptoms of anxiety or severe depression and AF risk, even for recurrent anxiety or depression symptoms. An unexpected association of symptoms of mild to moderate depression with increased AF risk requires confirmation in other studies. Our findings add to the sparse literature on symptoms of anxiety and depression and risk of AF. © 2019 The Authors. Published by Elsevier B.V. This is anopen access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Wholesale, unbiased assessment of Scandinavian electronic health-care databases offer a unique opportunity to reveal potentially important undiscovered drug side effects. We examined the short-term risk of acute myocardial infarction (AMI) associated with drugs prescribed in Norway or Sweden. We identified 24,584 and 97,068 AMI patients via the patient- and the cause-of-death registers and linked to prescription databases in Norway (2004–2014) and Sweden (2005–2014), respectively. A case-crossover design was used to compare the drugs dispensed 1–7 days before the date of AMI diagnosis with 15–21 days’ time -window for all the drug individually while controlling the receipt of other drugs. A BOLASSO approach was used to select drugs that acutely either increase or decrease the apparent risk of AMI. We found 48 drugs to be associated with AMI in both countries. Some antithrombotics, antibiotics, opioid analgesics, adrenergics, proton-pump inhibitors, nitroglycerin, diazepam, metoclopramide, acetylcysteine were associated with higher risk for AMI; whereas angiotensin-II-antagonists, calcium-channel blockers, angiotensin-converting-enzyme inhibitors, serotonin-specific reuptake inhibitors, allopurinol, mometasone, metformin, simvastatin, levothyroxine were inversely associated. The results were generally robust in different sensitivity analyses. This study confirms previous findings for certain drugs. Based on the known effects or indications, some other associations could be anticipated. However, inverse associations of hydroxocobalamin, levothyroxine and mometasone were unexpected and needs further investigation. This pharmacopeia-wide association study demonstrates the feasibility of a systematic, unbiased approach to pharmacological triggers of AMI and other diseases with acute, identifiable onsets. © The Author(s) 2019. This article is licensed under a Creative Commons Attribution 4.0 International License.

Aims Although obesity has been associated with risk of atrial fibrillation (AF), the associations of long-term obesity, recent obesity, and weight change with AF risk throughout adulthood are uncertain. Methods and results An ambispective cohort study was conducted which included 15 214 individuals. The cohort was created from 2006 to 2008 (the baseline) and was followed for incident AF until 2015. Weight and height were directly measured at baseline. Data on previous weight and height were retrieved retrospectively from measurements conducted 10, 20, and 40 years prior to baseline. Average body mass index (BMI) over time and weight change was calculated. During follow-up, 1149 participants developed AF. The multivariable-adjusted hazard ratios were 1.2 (95% confidence interval 1.0–1.4) for average BMI 25.0–29.9 kg/m2 and 1.6 (1.2–2.0) for average BMI ≥30 kg/m2 when compared with normal weight. The association of average BMI with AF risk was only slightly attenuated after adjustment for most recent BMI. In contrast, current BMI was not strongly associated with the risk of AF after adjustment for average BMI earlier in life. Compared with stable BMI, both loss and gain in BMI were associated with increased AF risk. After adjustment for most recent BMI, the association of BMI gain with AF risk was largely unchanged, while the association of BMI loss with AF risk was weakened. Conclusion Long-term obesity and BMI change are associated with AF risk. Obesity earlier in life and weight gain over time exert cumulative effects on AF development even after accounting for most recent BMI.

Excessive daytime sleepiness (EDS) affects 10–20% of the population and is associated with substantial functional deficits. Here, we identify 42 loci for self-reported daytime sleepiness in GWAS of 452,071 individuals from the UK Biobank, with enrichment for genes expressed in brain tissues and in neuronal transmission pathways. We confirm the aggregate effect of a genetic risk score of 42 SNPs on daytime sleepiness in independent Scandinavian cohorts and on other sleep disorders (restless legs syndrome, insomnia) and sleep traits (duration, chronotype, accelerometer-derived sleep efficiency and daytime naps or inactivity). However, individual daytime sleepiness signals vary in their associations with objective short vs long sleep, and with markers of sleep continuity. The 42 sleepiness variants primarily cluster into two predominant composite biological subtypes - sleep propensity and sleep fragmentation. Shared genetic links are also seen with obesity, coronary heart disease, psychiatric diseases, cognitive traits and reproductive ageing., A main symptom of chronic insufficient sleep is excessive daytime sleepiness. Here, Wang et al. report 42 genome-wide significant loci for self-reported daytime sleepiness in 452,071 individuals from the UK Biobank that cluster into two biological subtypes of either sleep propensity or sleep fragmentation.

Background: Asthma, a chronic inflammatory airway disease, shares common pathophysiological mechanisms with ischemic stroke. The aim of the study is to assess the association between asthma, levels of asthma control and ischemic stroke risk in men and women and by smoking habits. Methods: This prospective population-based cohort study utilized data on 58 712 adults from HUNT Study in Norway free from stroke. Self-reported asthma was categorized as ever asthma, non-active asthma and active asthma (i.e., being on asthma medication within 12 months of the baseline). Asthma control was defined ac-cording to the Global Initiative for Asthma questionnaire and was categorized into controlled and not controlled asthma. Stroke was ascertained by linking HUNT data with Nord-Trøndelag hospital records and the Norwegian Patient Registry. Results: During a mean follow-up of 17.3 �5.3 years, 2619 participants (4.5%) had a first stroke. Not controlled asthma was associated with a modest increased risk of stroke (adjusted HR 1.34, 95%CI 1.03–1.73). Subgroup analyses revealed that the respective association was stronger among those with history of smoking (HR 1.48, 95%CI 1.10–2.00) and males (HR 1.55, 95%CI 1.12–2.16) while absent in non-smokers (HR 1.02, 95%CI 0.61–1.70) and females (HR 1.05, 95%CI 0.69–1.60). Likewise, active asthma was associated with similar increased stroke risk among smokers and males and absent in non-smokers and females. Conclusions: Symptomatic and active asthma was associated with a modest increased relative risk for ischemic stroke in smokers and males. Future studies should clarify the difference in risks and mechanisms between different phenotypes of asthma. © 2019 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license

Background Most previous studies on sleep duration and coronary heart disease (CHD) have been small and have inadequately controlled for cardiovascular risk factors and chronic diseases. Therefore, our aim was to prospectively examine the associations of sleep duration with CHD while accounting for these factors. Methods Prospective cohort study of 392 164 adults at age 20years or older who attended a health check-up program from 1994 to 2011 in Taiwan and who have information on sleep duration, sleep medications and potential confounders. Participants answered the question: "How long do you sleep for?"—there were four response categories: (a) 0–4h; (b) 4–6h; (c) 6–8h and (d) >8h. The participants were then followed for CHD mortality from the Taiwanese cause-of-death register. Results When compared to those who slept 6–8h per night, the risk of dying from CHD was increased by 34% (HR 1.34, 95% Confidence Interval [CI] 0.87–2.07) and 35% (HR 1.35, 95% CI 1.11–1.65) in those who slept less than 4h per night and more than 8h per night, respectively. When stratifying by sex and age, we found some evidence for a stronger U-shaped association in females than in males and in older adults than in younger adults (p for interaction=0.01 and 0.13, respectively). Conclusions Adequate sleep duration should be considered an important component of a healthy lifestyle. Further studies are needed to better elucidate the underlying mechanisms.

ObjectiveTo examine whether sleep traits have a causal effect on risk of breast cancer.DesignMultivariable regression, one- and two-sample Mendelian randomization.SettingThe UK Biobank prospective cohort study and the Breast Cancer Association Consortium (BCAC) case-control genome-wide association study.Participants156,848 women in the multivariable regression and one-sample Mendelian randomization analysis in UK Biobank (7,784 with a breast cancer diagnosis) and 122,977 breast cancer cases and 105,974 controls from BCAC in the two-sample Mendelian randomization analysis.ExposuresSelf-reported chronotype (morning/evening preference), insomnia symptoms and sleep duration in multivariable regression, and genetic variants robustly associated with these sleep traits.Main outcome measuresBreast cancer (prevalent and incident cases in UK Biobank, prevalent cases only in BCAC).ResultsIn multivariable regression analysis using data on breast cancer incidence in UK Biobank, morning preference was inversely associated with breast cancer (HR 0.95, 95% CI 0.93, 0.98 per category increase) while there was little evidence for an association with sleep duration and insomnia symptoms. Using 341 single nucleotide polymorphisms (SNPs) associated with chronotype, 91 SNPs associated sleep duration and 57 SNPs associated with insomnia symptoms, one-sample MR analysis in UK Biobank provided some supportive evidence for a protective effect of morning preference on breast cancer risk (HR 0.85, 95% 0.70, 1.03 per category increase) but imprecise estimates for sleep duration and insomnia symptoms. Two-sample MR using data from BCAC supported findings for a protective effect of morning preference (OR 0.88, 95% CI 0.82, 0.93 per category increase) and adverse effect of increased sleep duration (OR 1.19, 95% CI 1.02, 1.39 per hour increase) on breast cancer (both estrogen receptor positive and negative), while there was inconsistent evidence for insomnia symptoms. Results were largely robust to sensitivity analyses accounting for horizontal pleiotropy.ConclusionsWe found consistent evidence for a protective effect of morning preference and suggestive evidence for an adverse effect of sleep duration on breast cancer risk.

Insomnia is a common disorder linked with adverse long-term medical and psychiatric outcomes. The underlying pathophysiological processes and causal relationships of insomnia with disease are poorly understood. Here we identify 57 loci for self-reported insomnia symptoms in the UK Biobank (n = 453,379) and confirm their impact on self-reported insomnia symptoms in the HUNT study (n = 14,923 cases, 47,610 controls), physician-diagnosed insomnia in Partners Biobank (n = 2,217 cases, 14,240 controls), and accelerometer-derived measures of sleep efficiency and sleep duration in the UK Biobank (n = 83,726). Our results suggest enrichment of genes involved in ubiquitin-mediated proteolysis and of genes expressed in multiple brain regions, skeletal muscle, and adrenal gland. Evidence of shared genetic factors is found between frequent insomnia symptoms and restless legs syndrome, aging, cardio-metabolic, behavioral, psychiatric and reproductive traits. Evidence is found for a possible causal link between insomnia symptoms and coronary artery disease, depressive symptoms and subjective well-being., Editorial summary: Genome-wide association analyses identify 57 loci associated with insomnia symptoms and evidence of shared genetic architecture between insomnia and cardio-metabolic, behavioral, psychiatric and reproductive traits.

Excessive daytime sleepiness (EDS) affects 10-20% of the population and is associated with substantial functional deficits. We identified 42 loci for self-reported EDS in GWAS of 452,071 individuals from the UK Biobank, with enrichment for genes expressed in brain tissues and in neuronal transmission pathways. We confirmed the aggregate effect of a genetic risk score of 42 SNPs on EDS in independent Scandinavian cohorts and on other sleep disorders (restless leg syndrome, insomnia) and sleep traits (duration, chronotype, accelerometer-derived sleep efficiency and daytime naps or inactivity). Strong genetic correlations were also seen with obesity, coronary heart disease, psychiatric diseases, cognitive traits and reproductive ageing. EDS variants clustered into two predominant composite phenotypes - sleep propensity and sleep fragmentation - with the former showing stronger evidence for enriched expression in central nervous system tissues, suggesting two unique mechanistic pathways. Mendelian randomization analysis indicated that higher BMI is causally associated with EDS risk, but EDS does not appear to causally influence BMI.

Objectives To investigate the association between alcohol consumption and left ventricular (LV) function in a population with low average alcohol intake. Design, setting and participants A total of 1296 healthy participants, free from cardiovascular diseases, were randomly selected from the third wave of the Norwegian HUNT study (2006–2008) and underwent echocardiography. After validation of the inclusion criteria, 30 participants were excluded due to arrhythmias or myocardial or valvular pathology. Alcohol consumption, sociodemographic and major cardiovascular risk factors were assessed by questionnaires and clinical examination in the HUNT3. General linear models were used to analyse the cross-sectional associations between alcohol intake and LV indices. Primary and secondary outcome measures LV functional and structural indices were measured with tissue Doppler and speckle tracking echocardiography. Results We observed no associations between alcohol consumption and multivariable-adjusted LV functional indices. Excluding abstainers who reported regular alcohol consumption 10 years prior to the baseline did not change the results. Alcohol consumption was positively associated with LV mass indices (p

Insomnia is a common disorder linked with adverse long-term medical and psychiatric outcomes, but underlying pathophysiological processes and causal relationships with disease are poorly understood. Here we identify 57 loci for self-reported insomnia symptoms in the UK Biobank (n=453,379) and confirm their impact on self-reported insomnia symptoms in the HUNT study (n=14,923 cases, 47,610 controls), physician diagnosed insomnia in Partners Biobank (n=2,217 cases, 14,240 controls), and accelerometer-derived measures of sleep efficiency and sleep duration in the UK Biobank (n=83,726). Our results suggest enrichment of genes involved in ubiquitin-mediated proteolysis, phototransduction and muscle development pathways and of genes expressed in multiple brain regions, skeletal muscle and adrenal gland. Evidence of shared genetic factors is found between frequent insomnia symptoms and restless legs syndrome, aging, cardio-metabolic, behavioral, psychiatric and reproductive traits. Evidence is found for a possible causal link between insomnia symptoms and coronary heart disease, depressive symptoms and subjective well-being.One Sentence SummaryWe identify 57 genomic regions associated with insomnia pointing to the involvement of phototransduction and ubiquitination and potential causal links to CAD and depression.

Importance Asthma, a chronic inflammatory airway disease, and atrial fibrillation (AF) share several common pathophysiological mechanisms. Research on the association between asthma and atrial fibrillation is lacking, and to our knowledge, no previous studies have assessed the dose-response association between levels of asthma control and AF. Objective To assess the association between asthma, levels of asthma control, and AF. Design, Setting, and Participants This prospective population cohort analyzed data on adults from a second and third iteration of the survey-based Nord-Trøndelag Health Study (HUNT) in Norway. All included participants were free from AF at baseline. Atrial fibrillation was ascertained by linking HUNT data with hospital records from the 2 hospitals in Nord-Trøndelag County. Data analysis was completed from May 2017 to November 2017. Exposures Self-reported asthma was categorized into 3 groups: those who had ever had asthma, those who self-report being diagnosed with asthma, and those who had active asthma. Asthma control was defined according to Global Initiative for Asthma guidelines and was categorized into controlled, partly controlled, and uncontrolled cases. Main Outcomes and Measures Atrial fibrillation. Results A total of 54 567 adults were included (of whom 28 821 [52.8%] were women). Of these, 5961 participants (10.9%) reported ever having asthma, 3934 participants (7.2%) reported being diagnosed with asthma, and 2485 participants (4.6%) reported having active asthma. During a mean (SD) follow-up of 15.4 (5.8) years, 2071 participants (3.8%) developed AF. Participants with physician-diagnosed asthma had an estimated 38% higher risk of developing AF (adjusted hazard ratio, 1.38 [95% CI, 1.18-1.61]) compared with participants without asthma. There was a dose-response association between levels of asthma control and risk of AF with the highest risk for AF in participants with uncontrolled asthma (adjusted hazard ratio, 1.74 [95% CI, 1.26–2.42]; P for trend

OBJECTIVE We examined the associations of symptoms of sleep-disordered breathing (SDB), which was defined as loud snoring, stopping breathing for a while during sleep, and daytime sleepiness, and insomnia with glucose metabolism and incident type 2 diabetes in older adults. RESEARCH DESIGN AND METHODS Between 1989 and 1993, the Cardiovascular Health Study recruited 5,888 participants ≥65 years of age from four U.S. communities. Participants reported SDB and insomnia symptoms yearly through 1989–1994. In 1989–1990, participants underwent an oral glucose tolerance test, from which insulin secretion and insulin sensitivity were estimated. Fasting glucose levels were measured in 1989–1990 and again in 1992–1993, 1994–1995, 1996–1997, and 1998–1999, and medication use was ascertained yearly. We determined the cross-sectional associations of sleep symptoms with fasting glucose levels, 2-h glucose levels, insulin sensitivity, and insulin secretion using generalized estimated equations and linear regression models. We determined the associations of updated and averaged sleep symptoms with incident diabetes in Cox proportional hazards models. We adjusted for sociodemographics, lifestyle factors, and medical history. RESULTS Observed apnea, snoring, and daytime sleepiness were associated with higher fasting glucose levels, higher 2-h glucose levels, lower insulin sensitivity, and higher insulin secretion. The risk of the development of type 2 diabetes was positively associated with observed apnea (hazard ratio [HR] 1.84 [95% CI 1.19–2.86]), snoring (HR 1.27 [95% CI 0.95–1.71]), and daytime sleepiness (HR 1.54 [95% CI 1.13–2.12]). In contrast, we did not find consistent associations between insomnia symptoms and glucose metabolism or incident type 2 diabetes. CONCLUSIONS Easily collected symptoms of SDB are strongly associated with insulin resistance and the incidence of type 2 diabetes in older adults. Monitoring glucose metabolism in such patients may prove useful in identifying candidates for lifestyle or pharmacological therapy. Further studies are needed to determine whether insomnia symptoms affect the risk of diabetes in younger adults.

Objective: To examine the length of time between receiving funding and publishing the protocol and main paper for randomised controlled trials. Design: An observational study using survival analysis. Setting: Publicly funded health and medical research in Australia. Participants: Randomised controlled trials funded by the National Health and Medical Research Council of Australia between 2008 and 2010. Main outcome measures: Time from funding to the protocol paper and main results paper. Multiple variable survival models examining whether study characteristics predicted publication times. Results: We found 77 studies with a total funding of $A59 million. The median time to publication of the protocol paper was 6.4 years after funding (95% CI 4.1 to 8.1). The proportion with a published protocol paper 8 years after funding was 0.61 (95% CI 0.48 to 0.74). The median time to publication of the main results paper was 7.1 years after funding (95% CI 6.3 to 7.6). The proportion with a published main results paper 8 years after funding was 0.72 (95% CI 0.56 to 0.87). The HRs for how study characteristics might influence timing were generally close to one with narrow CIs, the notable exception was that a longer study length lengthened the time to the main paper (HR=0.62 per extra study year, 95% CI 0.43 to 0.89). Conclusions: Despite the widespread registration of clinical trials, there remain serious concerns of trial results not being published or being published with a long delay. We have found that these same concerns apply to protocol papers, which should be publishable soon after funding. Funding agencies could set a target of publishing the protocol paper within 18 months of funding. © Published by the BMJ Publishing Group Limited.This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.

Although elevated heart rate and blood pressure might represent biologically plausible links for the association of insomnia symptoms with increased risk of cardiovascular disease (CVD), few large studies have investigated the associations of insomnia symptoms with these factors. Our aim was to investigate the associations of self-reported insomnia symptoms with systolic and diastolic blood pressure and resting heart rate in a large population-based study.Self-reported information on insomnia symptoms, including sleep initiation problems, frequent awakening and early awakenings during night, and measurements of resting heart rate and blood pressure were collected from a total of 50,806 men and women who participated in the third wave of the Nord-Trøndelag Health Study (HUNT-3) in 2006-2008.In multivariable analyses, we adjusted for sociodemographic factors, lifestyle factors, established CVD risk factors, and snoring or breathing pauses.Compared to participants reporting none of the insomnia symptoms, those having all three insomnia symptoms several times a week had lower diastolic blood pressure (-0.80 [95% CI: -1.47 to -0.14] mmHg, p = 0.02), lower systolic blood (-1.69 [95% CI: -2.76 to -0.63) mmHg, p0.001), and higher resting heart rate (0.83 [95% CI: 0.11 to 1.55] beats/minute, p = 0.02).We found a modest positive association of insomnia symptoms with resting heart rate, and a modest inverse association of insomnia with blood pressure. However, the actual differences were small, and likely of less clinical importance. Prospective studies are needed to establish whether the potential link between insomnia and CVD is mediated through changes in heart rate and/or blood pressure.

Insomnia is highly prevalent among asthmatics; however, few studies have investigated insomnia symptoms and asthma development. We aimed to investigate the association between insomnia and the risk of incident asthma in a population-based cohort.Among 17 927 participants free from asthma at baseline we calculated odds ratios and 95% confidence intervals for the risk of incident asthma among those with insomnia compared to those without. Participants reported sleep initiation problems, sleep maintenance problems and nonrestorative sleep. Chronic insomnia was defined as those reporting one or more insomnia symptom at baseline and 10 years earlier. Incident asthma was defined by questions on asthma at baseline and follow-up (average 11 years).The prevalence of sleep initiation problems, sleep maintenance problems and nonrestorative sleep were 1%, 1% and 5%, respectively. The multi-adjusted odds ratios were 1.18 (95% CI 0.97–1.44), 1.30 (95% CI 1.03–1.64) and 1.70 (95% CI 1.37–2.11) for people with one, two and three insomnia symptoms, respectively, compared with people without symptoms (pInsomnia symptoms were associated with increased risk of incident asthma in this study.

OBJECTIVES: To examine increases in several health outcomes after the July 22, 2011 terrorist attacks in Norway. METHODS: Retrospective analysis of nationwide registers (n = 4,953,000) where incidences of schizophrenia/psychosis hospitalizations, suicides, acute myocardial infarctions, and preterm births after the terrorist attacks were compared with corresponding periods the previous 3 years. RESULTS: Compared with the same period the preceding 3 years, the observed number of hospitalizations from schizophrenia/psychosis was 14% higher during the first 4 weeks after the terrorist attack (incidence ratio [IR] = 1.14, 95% confidence interval [CI] = 1.07-1.21). The corresponding IRs for the first 3 days and the first week were 1.26 (95% CI = 0.99-1.58) and 1.10 (95% CI = 0.96-1.24). The observed number of suicides was increased by 45% the first 4 weeks (IR = 1.45, 95% CI = 1.12-1.86), 163% the first 3 days (IR = 2.63, 95% CI = 1.15-5.20), and 105% the first week (IR = 2.05, 95% CI = 1.14-3.42). For acute myocardial infarction, there was an increase of 5% the first 4 weeks. There were also more births the 4 weeks (IR = 1.04, 95% CI = 1.01-1.07, but this increase was not seen in preterm births of less than 37 weeks of gestation (IR = 0.93, 95% CI = 0.83-1.04). CONCLUSIONS: We observed a general nationwide increase of health outcomes investigated in this study the first 4 weeks after the terrorist attacks. These results may contribute to the growing body of evidence on the adverse health outcomes that may accompany national stressors. Language: en

Objective: Symptoms of anxiety and depression often co-exist with cardiovascular disease (CVD), yet little is known about the association with left ventricular (LV) subclinical dysfunction. We aimed to study the cross-sectional associations of previous, current and repeated depression or anxiety symptoms, with sensitive indices of LV systolic and diastolic function, based on tissue Doppler (TD) and speckle tracking (ST) imaging methods. Methods: A random selection of 1296 individuals free from known CVD, hypertension and diabetes were examined with echocardiography at baseline of the third Nord-Trøndelag Health Study, (HUNT3, 2006–2008). The primary outcomes were LV diastolic function (e′) and LV systolic function (longitudinal global strain). The primary exposures were self-report on the Hospital Anxiety and Depression Scale (HADS). Associations between outcomes and baseline exposures were available for 1034 (80%), and with previous and repeated exposures for 700 participants who also participated in HUNT2 (1995–1997). Results: Previous and repeated depression symptoms, but not current depression, were linearly associated with a reduction in e′. The average sum of two repeated HADS-D scores 10 years apart had the strongest effect on e′ (−8.3%; 95% CI −13.9% to −2.7%) per 5 units. We observed a sex difference between depression symptoms and longitudinal global strain (p for interaction 0.019), where women had a marginal negative effect. Anxiety symptoms, neither previous, current nor repeated were associated with subclinical LV dysfunction. Conclusions: In a healthy sample, confirmed free of CVD, past and repeated depression symptoms were associated with subclinical LV dysfunction. Thus, depression symptoms might represent a modifiable risk factor for future CVD. This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

Objectives. Recently, studies have reported an association of insomnia with incident heart failure but its causal relation is still uncertain. In patients with heart failure, the left ventricular function is impaired and the deterioration may start long before the patient experiences any symptoms. As the first study, we examined the association of insomnia with left ventricular function using state-of-the art echocardiography methods. Design. In the echocardiography study, several indices of left ventricular function were examined in participants free from cardiovascular diseases, hypertension and diabetes. In total 788 participants with information on all relevant covariates were included. We calculated the least square mean of indices of left ventricular function associated with increasing number of insomnia symptoms (i.e. difficulties falling asleep, frequent awakenings and early awakenings), including systolic mitral annular excursion, peak velocities of systolic and diastolic motion of the mitral annulus and systolic deformation of the left ventricle. Results. We found no clear evidence that increasing number of insomnia symptoms is associated with any of the left ventricular function indices. Conclusions. The methods that were used are sensitive to detect preclinical HF, and therefore, our findings do not support a causal relation between insomnia symptoms and HF.

Almost 10% of all births are preterm, and 2.2% are stillbirths. Recent research has suggested that environmental factors may be a contributory cause of these adverse birth outcomes. The authors examined the relation between ambient temperature and preterm birth and stillbirth in Brisbane, Australia, between 2005 and 2009 (n = 101,870). They used a Cox proportional hazards model with livebirth and stillbirth as competing risks. They also examined whether there were periods in pregnancy where exposure to high temperatures had a greater effect. Higher ambient temperatures in the last 4 weeks of the pregnancy increased the risk of stillbirth. The hazard ratio for stillbirth was 0.3 at 12°C relative to the reference temperature of 21°C. The temperature effect was greatest at less than 36 weeks of gestation. There was an association between higher temperature and shorter gestation, as the hazard ratio for livebirth was 0.96 at 15°C and 1.02 at 25°C. This effect was greatest at later gestational ages. These results provide strong evidence of an association between increased temperature and increased risk of stillbirth and shorter gestation.

Seasonal patterns of birth outcomes, such as low birth weight, preterm birth and stillbirth, have been found around the world. As a result, there has been an increasing interest in evaluating short-term exposure to ambient temperature as a determinant of adverse birth outcomes. This paper reviews the epidemiological evidence on seasonality of birth outcomes and the impact of prenatal exposure to ambient temperature on birth outcomes. We identified 20 studies that investigated seasonality of birth outcomes, and reported statistically significant seasonal patterns. Most of the studies found peaks of preterm birth, stillbirth and low birth weight in winter, summer or both, which indicates the extremes of temperature may be an important determinant of poor birth outcomes. We identified 13 studies that investigated the influence of exposure to ambient temperature on birth weight and preterm birth (none examined stillbirth). The evidence for an adverse effect of high temperatures was stronger for birth weight than for preterm birth. More research is needed to clarify whether high temperatures have a causal effect on fetal health.

STUDY OBJECTIVES: To assess the association between insomnia symptoms and risk of fatal unintentional injuries. DESIGN: Population-based prospective cohort study with a mean follow-up of 14 y, linking health survey data with information on insomnia symptoms to the National Cause of Death Registry. SETTING: Nord-Trondelag County, Norway. PARTICIPANTS: A total of 54,399 men and women 20-89 y of age who participated in the Nord-Trondelag Health Study between 1995 and 1997. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: There were 277 unintentional fatal injuries, including 57 fatal motor vehicle injuries during follow-up. There was a dose-dependent association between the number of insomnia symptoms and risk of unintentional fatal injuries (P for trend 0.001) and fatal motor vehicle injuries (P for trend 0.023), respectively. The proportion of unintentional fatal injuries cases that could have been prevented in the absence of difficulties initiating sleep, difficulties maintaining sleep, and having a feeling of nonrestorative sleep were 8%, 9%, and 8%, respectively. The corresponding estimates for motor vehicle injuries were 34%, 11%, and 10%. CONCLUSION: Insomnia is a major contributor to both unintentional fatal injuries in general as well as fatal motor vehicle injuries. Increasing public health awareness about insomnia and identifying persons with insomnia may be important in preventing unintentional fatal injuries. CITATION: Laugsand LE, Strand LB, Vatten LJ, Janszky I, Bjorngaard JH. Insomnia symptoms and risk for unintentional fatal injuries-the HUNT Study. SLEEP 2014;37(11):1777-1786. Language: en

Aims Insomnia is highly prevalent among heart failure patients, but only a few small studies have investigated insomnia symptoms and risk of heart failure. We aimed to assess the prospective association between self-reported insomnia symptoms and the risk of incident heart failure in a large Norwegian cohort. Methods and results Baseline data on insomnia symptoms, including difficulty initiating sleep, difficulty maintaining sleep and having non-restorative sleep, socio-demographic variables, and health status, including established cardiovascular risk factors, were collected from 54 279 men and women 20–89 years of age who participated in the Nord-Trondelag Health study (HUNT) between 1995 and 1997 and were free from known heart failure at baseline. The cohort was followed for incident heart failure from baseline through 2008. We used Cox proportional hazard models to assess the association of baseline insomnia symptoms with the risk of heart failure. A total of 1412 cases of heart failure occurred during a mean follow-up of 11.3 years (SD = 2.9 years), either identified at hospitals or by the National Cause of Death Registry. There was a dose-dependent association between the number of insomnia symptoms and risk of heart failure. The multi-adjusted hazard ratios were 0.96 (0.57–1.61), 1.35 (0.72–2.50), and 4.53 (1.99–10.31) for people with one, two, and three insomnia symptoms, compared with people with none of the symptoms ( P for trend 0.021). Conclusions Insomnia is associated with an increased risk of incident heart failure. If our results are confirmed by others and causation is proved, evaluation of insomnia symptoms might have consequences for cardiovascular prevention.

Study objectives Previous studies have found an inverse association between insomnia and self-reported physical activity, but it is not clear whether insomnia is associated with cardiorespiratory fitness. Our aim was to investigate different insomnia symptoms in relation to the gold standard measure of cardiorespiratory fitness, i.e., peak oxygen uptake (VO(2peak)). Design Cross-sectional population study. Setting Nord-Trondelag County, Norway. Participants The group comprised 3,489 men and women who were free from cardiovascular or pulmonary diseases, cancer, and sarcoidosis and who did not use antihypertensive medication. They were included in the fully adjusted model when assessing all insomnia symptoms simultaneously. Interventions N/A. Measurements and results For insomnia, the participants reported how often they had experienced sleep problems during the past 3 months, including difficulties falling asleep at night, repeated awakenings during the night, early awakenings without being able to go back to sleep, and daytime sleepiness. Response options were "never/almost never," "sometimes" or "several times a wk." To measure cardiorespiratory fitness, the participants were asked to walk or run on a treadmill with increasing speed and/or incline until exhaustion, and VO(2peak) was recorded. We found a modest inverse and graded association of the insomnia symptoms with VO(2peak). The association was independent of self-reported physical activity and was apparent for all insomnia symptoms except for early awakenings. We found a dose-response relation for a cumulative combination of insomnia symptoms and VO(2peak) for experiencing zero, one to two, or three to four symptoms (P for trend Conclusions We found a modest inverse association of insomnia with VO(2peak) independent of the conventional cardiovascular risk factors and self-reported physical activity.

Background Many previous studies have found seasonal patterns in birth outcomes, but with little agreement about which season poses the highest risk. Some of the heterogeneity between studies may be explained by a previously unknown bias. The bias occurs in retrospective cohorts which include all births occurring within a fixed start and end date, which means shorter pregnancies are missed at the start of the study, and longer pregnancies are missed at the end. Our objective was to show the potential size of this bias and how to avoid it. Methods To demonstrate the bias we simulated a retrospective birth cohort with no seasonal pattern in gestation and used a range of cohort end dates. As a real example, we used a cohort of 114,063 singleton births in Brisbane between 1 July 2005 and 30 June 2009 and examined the bias when estimating changes in gestation length associated with season (using month of conception) and a seasonal exposure (temperature). We used survival analyses with temperature as a time-dependent variable. Results We found strong artificial seasonal patterns in gestation length by month of conception, which depended on the end date of the study. The bias was avoided when the day and month of the start date was just before the day and month of the end date (regardless of year), so that the longer gestations at the start of the study were balanced by the shorter gestations at the end. After removing the fixed cohort bias there was a noticeable change in the effect of temperature on gestation length. The adjusted hazard ratios were flatter at the extremes of temperature but steeper between 15 and 25°C. Conclusions Studies using retrospective birth cohorts should account for the fixed cohort bias by removing selected births to get unbiased estimates of seasonal health effects.

Background/Aims: There has been much interest in the association between ambient air pollution and birth outcomes, and different methods have been applied. Proximity to traffic is a proxy for traffic-related exposures and can be estimated using geographic information systems. The aim of this study was to assess birth outcomes in relation to the distance of the mother's home to the nearest road and the number of roads surrounding it. Methods: We investigated the association between traffic exposure and gestational age, birth weight, and birth length of 970 mothers in Logan, Queensland. We used multiple regression models and controlled for mother's age, smoking, parity, and education. We used a spline to control for trends and seasonal patterns. We modeled the effect of distance to road using a nonlinear spine with 3 degrees of freedom to capture the expected exponential-like decay in risk. For the number of roads surrounding the mother's home (main roads, freeways, and highways), we used a parametric approach by fitting either a quadratic or linear model. Results: There was some evidence of shorter gestations for mothers living closer to a major road and a marginal increase in birth weight and birth length with increasing proximity to a highway. We also found evidence of shorter gestations with greater density of main roads and freeways. Only the association between a shorter gestation and greater road density was statistically significant. Living 2 km from a main road increased gestation by an average of 0.4 weeks compared with being adjacent to a main road. Modeling the effects of wind direction had little effect on the results. Conclusion: Exposure to traffic had only a marginal negative influence on gestation length in this study. Future studies should include both temporal and spatial variation in exposure to air pollution when assessing its effects on birth outcomes.

Background There is overwhelming scientific evidence that human activities have changed and will continue to change the climate of the Earth. Eco-environmental health, which refers to the interdependencies between ecological systems and population health and well-being, is likely to be significantly influenced by climate change. The aim of this study was to examine perceptions from government stakeholders and other relevant specialists about the threat of climate change, their capacity to deal with it, and how to develop and implement a framework for assessing vulnerability of eco-environmental health to climate change. Methods Two focus groups were conducted in Brisbane, Australia with representatives from relevant government agencies, non-governmental organisations, and the industry sector (n = 15) involved in the discussions. The participants were specialists on climate change and public health from governmental agencies, industry, and non-governmental organisations in South-East Queensland. Results The specialists perceived climate change to be a threat to eco-environmental health and had substantial knowledge about possible implications and impacts. A range of different methods for assessing vulnerability were suggested by the participants and the complexity of assessment when dealing with multiple hazards was acknowledged. Identified factors influencing vulnerability were perceived to be of a social, physical and/or economic nature. They included population growth, the ageing population with associated declines in general health and changes in the vulnerability of particular geographical areas due to for example, increased coastal development, and financial stress. Education, inter-sectoral collaboration, emergency management (e.g. development of early warning systems), and social networks were all emphasised as a basis for adapting to climate change. To develop a framework, different approaches were discussed for assessing eco-environmental health vulnerability, including literature reviews to examine the components of vulnerability such as natural hazard risk and exposure and to investigate already existing frameworks for assessing vulnerability. Conclusion The study has addressed some important questions in regard to government stakeholders and other specialists' views on the threat of climate change and its potential impacts on eco-environmental health. These findings may have implications in climate change and public health decision-making.