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.

Cause-specific mortality among spouses of Parkinson disease patients.

BACKGROUND: Caring for a chronically ill spouse is stressful, but the health effects of caregiving are not fully understood. We studied the effect on mortality of being married to a person with Parkinson disease. METHODS: All patients in Denmark with a first-time hospitalization for Parkinson disease between 1986 and 2009 were identified, and each case was matched to five population controls. We further identified all spouses of those with Parkinson disease (n = 8,515) and also the spouses of controls (n = 43,432). All spouses were followed in nationwide registries until 2011. RESULTS: Among men, being married to a Parkinson disease patient was associated with a slightly higher risk of all-cause mortality (hazard ratio = 1.06 [95% confidence interval = 1.00-1.11]). Mortality was particularly high for death due to external causes (1.42 [1.09-1.84]) including suicide (1.89 [1.05-3.42]) and death from undefined symptoms/abnormal findings (1.25 [1.07-1.47]). Censoring at the time of death of the patient attenuated the findings for all-cause mortality in husbands (1.02 [0.95-1.09]), indicating that part of the association is with bereavement. Still, living with a person with Parkinson disease 5 years after first Parkinson hospitalization was associated with higher risk of all-cause mortality for both husbands (1.15 [1.07-1.23]) and wives (1.11 [1.04-1.17]). CONCLUSIONS: Caring for a spouse with a serious chronic illness is associated with a slight but consistent elevation in mortality risk.

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.

Education and risk of coronary heart disease: assessment of mediation by behavioral risk factors using the additive hazards model.

Educational-related gradients in coronary heart disease (CHD) and mediation by behavioral risk factors are plausible given previous research; however this has not been comprehensively addressed in absolute measures. Questionnaire data on health behavior of 69,513 participants, 52 % women, from seven Danish cohort studies were linked to registry data on education and incidence of CHD. Mediation by smoking, low physical activity, and body mass index (BMI) on the association between education and CHD were estimated by applying newly proposed methods for mediation based on the additive hazards model, and compared with results from the Cox proportional hazards model. Short (vs. long) education was associated with 277 (95 % CI: 219, 336) additional cases of CHD per 100,000 person-years at risk among women, and 461 (95 % CI: 368, 555) additional cases among men. Of these additional cases 17 (95 % CI: 12, 22) for women and 37 (95 % CI: 28, 46) for men could be ascribed to the pathway through smoking. Further, 39 (95 % CI: 30, 49) cases for women and 94 (95 % CI: 79, 110) cases for men could be ascribed to the pathway through BMI. The effects of low physical activity were negligible. Using contemporary methods, the additive hazards model, for mediation we indicated the absolute numbers of CHD cases prevented when modifying smoking and BMI. This study confirms previous claims based on the Cox proportional hazards model that behavioral risk factors partially mediates the effect of education on CHD, and the results seems not to be particularly model dependent.

Supermarket and fast-food outlet exposure in Copenhagen: associations with socio-economic and demographic characteristics.

OBJECTIVE: To investigate whether exposure to fast-food outlets and supermarkets is socio-economically patterned in the city of Copenhagen. DESIGN: The study was based on a cross-sectional multivariate approach to examine the association between the number of fast-food outlets and supermarkets and neighbourhood-level socio-economic indicators. Food business addresses were obtained from commercial and public business locators and geocoded using a geographic information system for all neighbourhoods in the city of Copenhagen (n 400). The regression of counts of fast-food outlets and supermarkets v. indicators of socio-economic status (percentage of recent immigrants, percentage without a high-school diploma, percentage of the population under 35 years of age and average household income in Euros) was performed using negative binomial analysis. SETTING: Copenhagen, Denmark. SUBJECTS: The unit of analysis was neighbourhood (n 400). RESULTS: In the fully adjusted models, income was not a significant predictor for supermarket exposure. However, neighbourhoods with low and mid-low income were associated with significantly fewer fast-food outlets. Using backwise deletion from the fully adjusted models, low income remained significantly associated with fast-food outlet exposure (rate ratio = 0·66-0·80) in the final model. CONCLUSIONS: In the city of Copenhagen, there was no evidence of spatial patterning of supermarkets by income. However, we detected a trend in the exposure to fast-food outlets, such that neighbourhoods in the lowest income quartile had fewer fast-food outlets than higher-income neighbourhoods. These findings have similarities with studies conducted in the UK, but not in the USA. The results suggest there may be socio-economic factors other than income associated with food exposure in Europe.

A Real-World, Prospective, Non-interventional Study of Adults with T2D Switching to IDegAsp from Glargine U100 or U300 in Japan.

INTRODUCTION: This real-world study investigated glycaemic control and quality of life (QoL) in insulin-experienced Japanese patients with type 2 diabetes (T2D) who switched to insulin degludec/insulin aspart (IDegAsp). METHODS: This was a prospective, non-interventional, open-label, single-arm study. Eligible patients were adults (aged ≥ 20 years) with T2D, previously treated with insulin glargine 100 or 300 units/mL (glargine U100/U300) with or without prandial insulin, who switched to IDegAsp as part of routine practice. Change from baseline to end of study (EOS; 26 weeks after initiation or IDegAsp discontinuation) in the following endpoints was assessed by adjusted mixed models for repeated measures: glycated haemoglobin (HbA1c; primary endpoint), fasting plasma glucose (FPG), insulin dose and total Diabetes Therapy-Related Quality of Life (DTR-QoL) score. Non-severe hypoglycaemia was assessed in the 4-week period prior to initiating IDegAsp and in the 4-week period before EOS or discontinuation using negative binomial regression. RESULTS: The full analysis set included 236 patients from 29 centres in Japan with mean (± SD) age 63.2 years (± 12.3), HbA1c 7.7% (± 1.0) and diabetes duration 14.9 (± 9.3) years. After 26 weeks with IDegAsp, HbA1c (estimated change - 0.1% [- 0.2; 0.0]95% confidence interval (CI), p = 0.3036) and FPG (- 7.5 mg/dL [- 23.5; 8.5]95% CI, p = 0.3477) were maintained; there were significant reductions in basal and total insulin dose: estimated change of - 3.4 units/day [- 3.8; - 3.0]95% CI and - 1.0 units/day [- 1.9; - 0.1]95% CI, respectively (both p < 0.05). Non-severe hypoglycaemia rates were similar in the periods before and after initiating IDegAsp, while there was a significant improvement in total DTR-QoL score after 26 weeks with IDegAsp (p = 0.0012). CONCLUSION: These real-world data suggest that switching to IDegAsp from glargine U100 or U300 was well tolerated in a Japanese population with T2D, with no new safety or tolerability signals, and associated with maintenance of glycaemic control and improved QoL. TRIAL REGISTRATION: This study is registered at ClinicalTrials.gov: NCT03745157.

Social inequality in chronic disease outcomes.

Socioeconomic differences in morbidity and mortality, particularly across educational groups, are widening. Differential exposures to behavioural risk factors have been shown to play an important mediating role on the social inequality in chronic diseases such as heart disease, cerebrovascular disease, chronic obstructive pulmonary disease, and lung cancer. However, much less attention has been given to the potential role of interaction, where the same level of exposure to a behavioural risk factor has different effect across socioeconomic groups, creating subgroups that are more vulnerable than others. In this thesis, Paper 1 describes the unique cohort consortium which was established by pooling and harmonising prospective data from existing cohort studies in Denmark. This consortium generated a large study population with long follow-up sufficient to study power demanding questions of mechanisms underlying social inequalities in chronic disease outcomes. In Paper 2 on incidence of coronary heart disease, smoking and body mass index partially mediated the observed educational differences. This result suggested that some of the social inequality in coronary heart disease may be enhanced by differential exposure to behavioural risk factors (i.e. smoking and obesity). In Paper 3 on incidence of stroke, an observed interaction between education and smoking indicated that participants, particularly men, with low level of education may be more vulnerable to the effect of smoking than those with high level of education in terms of ischemic stroke. Finally, Paper 4 revealed that behavioural risk factors, primarily smoking, explained a considerable part of the educational differences in cause-specific mortality. Further, this paper added important knowledge about the considerable part of the mediated effect, which could be due to interaction between education and smoking. In conclusion, the research in this thesis is a practical implementation of contemporary statistical methodology, the additive hazards models, in which the potential role of behavioural risk factors can be regarded not only as mediation but also as interaction with the effect of socioeconomic position on chronic disease outcomes. The results support that two central mechanisms, differential exposure and differential vulnerability to behavioural risk factors, particularly smoking; have contributed substantially to the social inequality in chronic disease outcomes in Denmark. These mechanism are not mutually exclusive and should be regarded simultaneously. However, the findings could be non-causal associations due to, for instance, psychosocial or environmental factors. Nevertheless, research on social inequality in chronic disease outcomes should regard not only that the smoking prevalence is higher in lower socioeconomic groups (differential exposure), but also that health consequences of being a smoker seem to be worse in these subgroups (differential vulnerability).

Cohort profile: the Social Inequality in Cancer (SIC) cohort study.

The Social Inequality in Cancer (SIC) cohort study was established to determine pathways through which socioeconomic position affects morbidity and mortality, in particular common subtypes of cancer. Data from seven well-established cohort studies from Denmark were pooled. Combining these cohorts provided a unique opportunity to generate a large study population with long follow-up and sufficient statistical power to develop and apply new methods for quantification of the two basic mechanisms underlying social inequalities in cancer-mediation and interaction. The SIC cohort included 83 006 participants aged 20-98 years at baseline. A wide range of behavioural and biological risk factors such as smoking, physical inactivity, alcohol intake, hormone replacement therapy, body mass index, blood pressure and serum cholesterol were assessed by self-administered questionnaires, physical examinations and blood samples. All participants were followed up in nationwide demographic and healthcare registries. For those interested in collaboration, further details can be obtained by contacting the Steering Committee at the Department of Public Health, University of Copenhagen, at inan@sund.ku.dk.

Measurement of ethnic background in cross-national school surveys: agreement between students' and parents' responses.

PURPOSE: Indicators such as country of birth and language spoken at home have been used as proxy measures for ethnic background, but the validity of these indicators in surveys among school children remains unclear. This study aimed at comparing item response and student-parent agreement on four questions about country of birth and language spoken at home in three European countries. METHODS: We analyzed data from the Health Behaviour in School-aged Children (HBSC) Child-Parent Validation Study 2005, including 486 matched student-parent pairs from Denmark, Hungary, and Scotland. Selected items from the internationally standardized HBSC questionnaire were completed by 11-year-old students and their parents. We examined item response and student-parent agreement on the four HBSC Ethnic Background Indicators: the student's country of birth, mother's country of birth, father's country of birth, and language usually spoken at home. RESULTS: All item response rates were high for both students (>92%) and parents (>96%). The percent student-parent agreement was high on all four items (>97%). The strength of agreement ranged from good to excellent for all items indicated by the kappa value (between .60 and 1.00). Results were robust across countries. CONCLUSIONS: Our findings suggest that students as young as 11 years are able to provide valid responses to four simple questions about country of birth and language spoken at home. The four HBSC Ethnic Background Indicators can be useful in epidemiologic studies on identification of subgroups that may receive unequal prevention services or in assessment of how risk factors, symptoms, and diseases may differ by ethnic background among school children.