Naja Hulvej Rod

Perceived stress as a risk factor for changes in health behaviour and cardiac risk profile: a longitudinal study

Objective.  The aim of this study was to evaluate the long‐term effects of stress on changes in health behaviour and cardiac risk profile in men and women.

The joint effect of sleep duration and disturbed sleep on cause-specific mortality: Results from the Whitehall II cohort study

Background Both sleep duration and sleep quality are related to future health, but their combined effects on mortality are unsettled. We aimed to examine the individual and joint effects of sleep duration and sleep disturbances on cause-specific mortality in a large prospective cohort study. Methods We included 9,098 men and women free of pre-existing disease from the Whitehall II study, UK. Sleep measures were self-reported at baseline (1985–1988). Participants were followed until 2010 in a nationwide death register for total and cause-specific (cardiovascular disease, cancer and other) mortality. Results There were 804 deaths over a mean 22 year follow-up period. In men, short sleep (≤6 hrs/night) and disturbed sleep were not independently associated with CVD mortality, but there was an indication of higher risk among men who experienced both (HR = 1.57; 95% CI: 0.96–2.58). In women, short sleep and disturbed sleep were independently associated with CVD mortality, and women with both short and disturbed sleep experienced a much higher risk of CVD mortality (3.19; 1.52–6.72) compared to those who slept 7–8 hours with no sleep disturbances; equivalent to approximately 90 additional deaths per 100,000 person years. Sleep was not associated with death due to cancer or other causes. Conclusion Both short sleep and disturbed sleep are independent risk factors for CVD mortality in women and future studies on sleep may benefit from assessing disturbed sleep in addition to sleep duration in order to capture health-relevant features of inadequate sleep.

Education and cause-specific mortality: the mediating role of differential exposure and vulnerability to behavioral risk factors.

Background: Differential exposures to behavioral risk factors have been shown to play an important mediating role on the education–mortality relation. However, little is known about the extent to which educational attainment interacts with health behavior, possibly through differential vulnerability. Methods: In a cohort study of 76,294 participants 30 to 70 years of age, we estimated educational differences in cause-specific mortality from 1980 through 2009 and the mediating role of behavioral risk factors (smoking, alcohol intake, physical activity, and body mass index). With the use of marginal structural models and three-way effect decomposition, we simultaneously regarded the behavioral risk factors as intermediates and clarified the role of their interaction with educational exposure. Results: Rate differences in mortality comparing participants with low to high education were 1,277 (95% confidence interval = 1,062 to 1,492) per 100,000 person-years for men and 746 (598 to 894) per 100,000 person-years for women. Smoking was the strongest mediator for cardiovascular disease, cancer, and respiratory disease mortality when conditioning on sex, age, and cohort. The proportion mediated through smoking was most pronounced in cancer mortality as a combination of the pure indirect effect, owing to differential exposure (men, 42% [25% to 75%]; women, 36% [17% to 74%]) and the mediated interactive effect, owing to differential vulnerability (men, 18% [2% to 35%], women, 26% [8% to 50%]). The mediating effects through body mass index, alcohol intake, or physical activity were partial and varied for the causes of deaths. Conclusion: Differential exposure and vulnerability should be addressed simultaneously, as these mechanisms are not mutually exclusive and may operate at the same time.

Additive interaction in survival analysis: use of the additive hazards model.

It is a widely held belief in public health and clinical decision-making that interventions or preventive strategies should be aimed at patients or population subgroups where most cases could potentially be prevented. To identify such subgroups, deviation from additivity of absolute effects is the relevant measure of interest. Multiplicative survival models, such as the Cox proportional hazards model, are often used to estimate the association between exposure and risk of disease in prospective studies. In Cox models, deviations from additivity have usually been assessed by surrogate measures of additive interaction derived from multiplicative models—an approach that is both counter-intuitive and sometimes invalid. This paper presents a straightforward and intuitive way of assessing deviation from additivity of effects in survival analysis by use of the additive hazards model. The model directly estimates the absolute size of the deviation from additivity and provides confidence intervals. In addition, the model can accommodate both continuous and categorical exposures and models both exposures and potential confounders on the same underlying scale. To illustrate the approach, we present an empirical example of interaction between education and smoking on risk of lung cancer. We argue that deviations from additivity of effects are important for public health interventions and clinical decision-making, and such estimations should be encouraged in prospective studies on health. A detailed implementation guide of the additive hazards model is provided in the appendix.

Symptoms of sleep disordered breathing and risk of cancer: a prospective cohort study.

STUDY OBJECTIVES Sleep disordered breathing (SDB) has been associated with oxidative stress, inflammation, and altered hormonal levels, all of which could affect the risk of cancer. The aim of the study is to examine if symptoms of SDB including snoring, breathing cessations, and daytime sleepiness affect the incidence of total cancer and subtypes of cancer. DESIGN Prospective cohort study. SETTING The third wave (1991-1993) of the Copenhagen City Heart Study. PARTICIPANTS There were 8,783 men and women in whom cancer had not been previously diagnosed. MEASUREMENTS AND RESULTS Participants answered questions about snoring and breathing cessations in 1991-1993, whereas information about daytime sleepiness based on the Epworth Sleepiness Scale was collected in a subset of the participants (n = 5,894) in 1998. First-time incidence of cancer was followed until December 2009 in a nationwide cancer register. We found no overall association between symptoms of SDB and incident cancer. Yet, in the small group with high daytime sleepiness, we observed a surprisingly higher cancer incidence (hazard ratio = 4.09; 95% CI 1.58-10.55) in persons younger than 50 years. We also found a higher risk of virus/immune-related cancers (2.73; 1.27-5.91) and alcohol-related cancers (4.92; 1.45-16.76) among persons with daytime sleepiness. More SDB symptoms were associated with a higher risk of smoking-related cancers (Ptrend: 0.04). Apart from these findings there were no clear associations between symptoms of sleep disordered breathing and cancer subtypes. CONCLUSION We found very limited evidence of relationship between symptoms of sleep disordered breathing and incidence of cancer.

Quantifying mediating effects of endogenous estrogen and insulin in the relation between obesity, alcohol consumption and breast cancer

Background: Increased exposure to endogenous estrogen and/or insulin may partly explain the relationship of obesity, physical inactivity, and alcohol consumption and postmenopausal breast cancer. However, these potential mediating effects have not been formally quantified in a survival analysis setting. Methods: We combined data from two case–cohort studies based in the Womens Health Initiative-Observational Study with serum estradiol levels, one of which also had insulin levels. A total of 1,601 women (601 cases) aged 50 to 79 years who were not using hormone therapy at enrollment were included. Mediating effects were estimated by applying a new method based on the additive hazard model. Results: A five-unit increase in body mass index (BMI) was associated with 50.0 [95% confidence interval (CI), 23.2–76.6] extra cases per 100,000 women at-risk per year. Of these, 23.8% (95% CI, 2.9–68.4) could be attributed to estradiol and 65.8% (95% CI, 13.6–273.3) through insulin pathways. The mediating effect of estradiol was greater (48.8%; 95% CI, 18.8–161.1) for BMI when restricted to estrogen receptor positive (ER+) cases. Consuming 7+ drinks/wk compared with abstinence was associated with 164.9 (95% CI, 45.8–284.9) breast cancer cases per 100,000, but no significant contribution from estradiol was found. The effect of alcohol on breast cancer was restricted to ER+ breast cancers. Conclusions: The relation of BMI with breast cancer was partly mediated through estradiol and, to a greater extent, through insulin. Impact: The findings provide support for evaluation of interventions to lower insulin and estrogen levels in overweight and obese postmenopausal women to reduce breast cancer risk. Cancer Epidemiol Biomarkers Prev; 21(7); 1203–12. ©2012 AACR.

Occurrence of delayed-onset post-traumatic stress disorder: a systematic review and meta-analysis of prospective studies

OBJECTIVE Post-traumatic stress disorder (PTSD) develops according to consensus criteria within the first 1-6 months after a horrifying traumatic event, but it is alleged that PTSD may develop later. The objective was to review the evidence addressing occurrence of PTSD with onset >6 months after a traumatic event (delayed-onset PTSD). METHODS Through a systematic search in PubMed, EMBASE, and PsycINFO, we identified 39 studies with prospective ascertainment of PTSD. A meta-analysis was performed in order to obtain a weighted estimate of the average proportion of delayed-onset PTSD cases, and meta-regression was used to examine effects of several characteristics RESULTS Delayed-onset PTSD was reported in all studies except one, and the average prevalence across all follow-up time was 5.6% [95% confidence interval (95% CI) 4.3-7.3%]. The proportion with delayed-onset PTSD relative to all cases of PTSD was on average 24.5% (95% CI 19.5-30.3%) with large variation across studies. In six studies with sub-threshold symptom data, delayed-onset PTSD seemed most likely an aggravation of early symptoms. The proportion with delayed-onset PTSD was almost twice as high among veterans and other professional groups compared to non-professional victims. CONCLUSION Descriptive follow-up data suggest that PTSD may manifest itself >6 months after a traumatic event, delayed-onset PTSD most often, if not always, is preceded by sub-threshold PTSD symptoms, and a higher proportion of PTSD cases are delayed among professional groups. Contextual factors and biased recall may inflate reporting of PTSD and a cautious interpretation of prevalence rates seems prudent.

Risk of depressive disorder following disasters and military deployment: systematic review with meta-analysis.

BACKGROUND Numerous studies describe the occurrence of post-traumatic stress disorder following disasters, but less is known about the risk of major depression. AIMS To review the risk of depressive disorder in people surviving disasters and in soldiers returning from military deployment. METHOD A systematic literature search combined with reference screening identified 23 controlled epidemiological studies. We used random effects models to compute pooled odds ratios (ORs). RESULTS The average OR was significantly elevated following all types of exposures: natural disaster OR = 2.28 (95% CI 1.30-3.98), technological disaster OR = 1.44 (95% CI 1.21-1.70), terrorist acts OR = 1.80 (95% CI 1.38-2.34) and military combat OR = 1.60 (95% CI 1.09-2.35). In a subset of ten high-quality studies OR was 1.41 (95% CI 1.06-1.87). CONCLUSIONS Disasters and combat experience substantially increase the risk of depression. Whether psychological trauma per se or bereavement is on the causal path is unresolved.

The effect of sleep disordered breathing on the outcome of stroke and transient ischemic attack: a systematic review.

STUDY OBJECTIVES The primary objective was to systematically review the literature on how sleep disordered breathing (SDB) affects recurrence and death among stroke or transient ischemic attack (TIA) patients. A secondary objective was to evaluate how treatment of SDB with continuous positive airway pressure (CPAP) affects the risk of recurrence and death in these patients. METHODS Adults (18+) with a stroke or TIA diagnosis were eligible for inclusion. Case groups consisted of patients with a sleep disorder. The outcomes of interest were all-cause mortality, recurrent vascular events, and case fatality. RESULTS Ten articles covering 1,203 stroke and TIA patients were included in the review. The results generally support a dose-response relationship between severity of SDB and risk of recurrent events and all-cause mortality in stroke and TIA patients. Three small-scale articles with substantial risk of bias evaluated the effects of CPAP therapy, and the results are inconclusive. Data on case fatality is too sparse to be conclusive. CONCLUSIONS Existing studies provide sufficient data to establish obstructive SDB as a negative predictor of all-cause mortality and recurrent vascular events following stroke or TIA. The ability of CPAP treatment to lower the risk of serious adverse outcomes after stroke remains controversial because of substantial risk of bias identified in most of the eligible studies addressing this relation. Additional studies are needed.

Combined Effects of Socioeconomic Position, Smoking, and Hypertension on Risk of Ischemic and Hemorrhagic Stroke

Background and Purpose— Combined effects of socioeconomic position and well-established risk factors on stroke incidence have not been formally investigated. Methods— In a pooled cohort study of 68 643 men and women aged 30 to 70 years in Denmark, we examined the combined effect and interaction between socioeconomic position (ie, education), smoking, and hypertension on ischemic and hemorrhagic stroke incidence by the use of the additive hazards model. Results— During 14 years of follow-up, 3613 ischemic strokes and 776 hemorrhagic strokes were observed. Current smoking and hypertension were more prevalent among those with low education. Low versus high education was associated with greater ischemic, but not hemorrhagic, stroke incidence. The combined effect of low education and current smoking was more than expected by the sum of their separate effects on ischemic stroke incidence, particularly among men: 134 (95% confidence interval, 49–219) extra cases per 100 000 person-years because of interaction, adjusted for age, cohort study, and birth cohort. There was no clear evidence of interaction between low education and hypertension. The combined effect of current smoking and hypertension was more than expected by the sum of their separate effects on ischemic and hemorrhagic stroke incidence. This effect was most pronounced for ischemic stroke among women: 178 (95% confidence interval, 103–253) extra cases per 100 000 person-years because of interaction, adjusted for age, cohort study, and birth cohort. Conclusions— Reducing smoking in those with low socioeconomic position and in those with hypertension could potentially reduce social inequality stroke incidence.