Cohort Profile: Better Health in Late Life.

Purpose: Humans are living longer and may develop multiple chronic diseases in later life. The Better Health in Late Life cohort study aims to improve our understanding of the risks and outcomes of multimorbidity in the Danish population. Methods: A randomly-selected sample of Danish residents who were 50-65 years of age received a questionnaire and an invitation to participate in this study. Respondents completed an online survey between October 2021 and January 2022 which addressed topics that included self-assessed health, mental health, sleep, specific medical conditions, use of painkillers, diet, alcohol consumption, smoking, physical activity, and body composition. This information was linked to the Danish health and social registries (some established in 1943 and onwards) that maintain data on filled prescriptions, hospital records, socioeconomic status, and health care utilization. Results: Responses were received from 115,431 of the 301,244 residents invited to participate (38%). We excluded respondents who answered none of the questions as well as those who provided no information on sex or indicated an age other than 50-65 years. Of the 114,283 eligible respondents, 54.8% were female, 30.3% were overweight, and 16.7% were obese. Most participants reported a weekly alcohol consumption of less than seven units and 13.3% were current smokers; 5.2% had a history of hospitalization for solid cancer, and 3.0%, 2.3%, 2.0%, and 0.9% reported chronic pulmonary disease, diabetes, stroke, and myocardial infarction, respectively. The most frequently filled prescriptions were for medications used to treat the nervous system and cardiovascular diseases (38.1% and 37.4%, respectively).

Birth weight, childhood body mass index, and risk of diverticular disease in adulthood.

OBJECTIVE: Adult overweight is associated with increased risk of diverticular disease (DD). We investigated associations between birthweight and childhood body mass index (BMI) and DD. METHODS: Cohort study of 346,586 persons born during 1930-1996 with records in the Copenhagen School Health Records Register. Data included birthweight, and height and weight from ages 7 through 13. We used Cox proportional hazard regression to examine associations between birthweight and BMI z-scores and DD registered in the Danish National Patient Registry. Due to non-proportionality, we followed participants from age 18-49 and from age 50. RESULTS: During follow-up, 5459 (3.2%) women and 4429 (2.5%) men had DD. For low and high BMI in childhood, we observed a higher risk of DD before age 50. Among women with z-scores <0 at age 13, the hazard ratio (HR) was 1.16 [95% confidence interval (CI): 0.98-1.39] per one-point lower z-score. For z-scores ≥0 at age 13, the HR was 1.30 (95% CI: 1.11-1.51) per one-point higher z-score. Among men with z-scores <0 at age 13, the HR was 1.02 (95% CI: 0.85-1.22). For z-scores ≥0 at age 13, the HR was 1.54 (95% CI: 1.34-1.78). Z-scores ≥0 were not associated with DD after age 50. Among women only, birthweight was inversely associated with DD before age 50 [HR = 0.90 (95% CI: 0.83-0.99) per 500 g higher birthweight]. CONCLUSION: BMI z-scores below and above zero in childhood were associated with higher risk of DD before age 50. In addition, we observed lower risk of DD among women, the higher their birthweight.

Perceived stress and semen quality.

BACKGROUND: Psychological stress is prevalent among reproductive-aged men. Assessment of semen quality for epidemiological studies is challenging as data collection is expensive and cumbersome, and studies evaluating the effect of perceived stress on semen quality are inconsistent. OBJECTIVE: To examine the association between perceived stress and semen quality. MATERIAL AND METHODS: We analyzed baseline data on 644 men (1,159 semen samples) from two prospective preconception cohort studies during 2015-2021: 592 in Pregnancy Study Online (PRESTO) and 52 in SnartForaeldre.dk (SF). At study entry, men aged ≥21 years (PRESTO) and ≥18 years (SF) trying to conceive without fertility treatment completed a questionnaire on reproductive and medical history, socio-demographics, lifestyle, and the 10-item version of the Perceived Stress Scale (PSS; interquartile range [IQR] of scores: 0-40). After enrollment (median weeks: 2.1, IQR: 1.3-3.7), men were invited to perform in-home semen testing, twice with 7-10 days between tests, using the Trak Male Fertility Testing System. Semen quality was characterized by semen volume, sperm concentration, and total sperm count. We fit generalized estimating equation linear regression models to estimate the percent difference in mean log-transformed semen parameters by four PSS groups (<10, 10-14, 15-19, ≥20), adjusting for potential confounders. RESULTS: The median PSS score and IQR was 15 (10-19), and 136 men (21.1%) had a PSS score ≥20. Comparing men with PSS scores ≥20 with <10, the adjusted percent difference was -2.7 (95% CI: -9.8; 5.0) for semen volume, 6.8 (95% CI: -10.9; 28.1) for sperm concentration, and 4.3 (95% CI: -13.8; 26.2) for total sperm count. CONCLUSION: Our findings indicate that perceived stress is not materially associated with semen volume, sperm concentration, or total sperm count.

Theoretical substitutions between dairy products and all-cause and cause-specific mortality. Results from the Danish diet, cancer and health cohort.

A daily intake of dairy products is recommended in many countries in order to maintain optimal health throughout life. However, evidence regarding the association between intake of individual dairy products and mortality is limited. We therfore, explored associations between intake of different dairy products and all-cause and cause-specific mortality using specified theoretical substitution analyses. We analysed data from 55 775 Danish men and women aged 50-64 years between 1993 and 1997. Information about dairy product intake at baseline was collected using a validated food frequency questionnaire. Information about vital status and causes of death was obtained through national registers. Measures of associations were calculated using Cox proportional hazards regression. During a median follow-up of 19·0 years, 11 586 participants died. For all-cause mortality, we observed that the intake of low-fat milk, whole-fat milk or low-fat yogurt products in place of cheese was associated with a higher rate of death (hazard ratios between 1·03 and 1·12 per serving/d substituted). The same pattern was present for CVD mortality. For cancer mortality, whole-fat milk and low-fat yogurt products in place of cheese were also associated with a higher rate of death for men while for women, whole-fat milk in place of buttermilk was associated with a higher cancer mortality rate. The results appeared robust in several sensitivity analyses. Our results suggest that intake of low-fat milk, whole-fat milk or low-fat yogurt products in place of cheese is associated with a higher rate of all-cause and cause-specific mortality.

Air pollution and fecundability: Results from a Danish preconception cohort study.

BACKGROUND: Animal and epidemiologic studies indicate that air pollution may adversely affect fertility. Epidemiologic studies have been restricted largely to couples undergoing fertility treatment or have retrospectively ascertained time-to-pregnancy among pregnant women. OBJECTIVES: We examined the association between residential ambient air pollution and fecundability, the per-cycle probability of conception, in a large preconception cohort of Danish pregnancy planners. METHODS: During 2007-2018, we used the Internet to recruit and follow women who were trying to conceive without the use of fertility treatment. Participants completed an online baseline questionnaire eliciting socio-demographic characteristics, lifestyle factors, and medical and reproductive histories and follow-up questionnaires every 8 weeks to ascertain pregnancy status. We determined concentrations of ambient nitrogen oxides (NOx ), nitrogen dioxide (NO2 ), carbon monoxide (CO), ozone (O3 ), particulate matter <2.5 µm (PM2.5 ) and <10 µm (PM10 ), and sulphur dioxide (SO2 ) at each participant's residential address. We calculated average exposure during the year before baseline, during each menstrual cycle over follow-up and during the entire pregnancy attempt time. We used proportional probabilities regression models to estimate fecundability ratios (FRs) and 95% confidence intervals (CIs), adjusting for potential confounders and co-pollutants. The analysis was restricted to the 10,183 participants who were trying to conceive for <12 cycles at study entry whose addresses could be geocoded. RESULTS: During 12 months of follow-up, 73% of participants conceived. Higher concentrations of PM2.5 and PM10 were associated with small reductions in fecundability. For example, the FRs for a one interquartile range (IQR) increase in PM2.5 (IQR = 3.2 µg/m3 ) and PM10 (IQR = 5.3 µg/m3 ) during each menstrual cycle were 0.93 (95% CI: 0.87, 0.99) and 0.91 (95% CI: 0.84, 0.99), respectively. Other air pollutants were not appreciably associated with fecundability. CONCLUSIONS: In this preconception cohort study of Danish women, residential exposures to PM2.5 and PM10 were associated with reduced fecundability.

Changes in intake of dairy product subgroups and risk of type 2 diabetes: modelling specified food substitutions in the Danish Diet, Cancer and Health cohort.

PURPOSE: We investigated the association between an increased intake of one dairy product subgroup at the expense of another within a 5-year period and the subsequent 10-year risk of type 2 diabetes. METHODS: The cohort included 39,393 adults with two measurements of diet assessed using food frequency questionnaires (FFQ) administered in 1993-1997 and 1999-2003. Dairy products were milk (skimmed, semi-skimmed, whole fat), buttermilk, low-fat yogurt, whole-fat yogurt, cheese and butter. Type 2 diabetes cases were ascertained from the Danish National Diabetes Register. The pseudo-observation method was used to calculate risk differences (RD) with 95% confidence intervals (CI). The data were analysed in age strata to fulfil the assumption of independent entry. RESULTS: Among participants aged 56-59 years at completion of the follow-up FFQ, increased intake of whole-fat yogurt in place of skimmed, semi-skimmed or whole-fat milk was associated with a reduced risk (RD% [95% CI]: - 0.8% [- 1.3, - 0.2]; - 0.6% [- 1,1, - 0.1]; - 0.7 [- 1.2, - 0.1]; per 50 g/d, respectively). Among participants aged 60-64 and 65-72, substitution of skimmed milk for semi-skimmed milk was associated with an increased risk of type 2 diabetes (0.5% [0.2, 0.7]; 0.4% [0.1, 0.7]; per 50 g/d, respectively). Similar patterns of associations were found after adjustment for potential mediators. CONCLUSION: Our results suggest that substitution of whole-fat yogurt for milk among those aged 56-59 decreases risk of type 2 diabetes and substitution of skimmed milk for semi-skimmed milk may increase the risk among those aged 60-64 and 65-72.

Food substitution models for nutritional epidemiology.

The advantage of using specified substitution analysis in nutritional epidemiology has been clearly demonstrated in studies of macronutrient intake and disease risk. However, the method has not been widely applied in studies of food intake. The aim of this article is to describe and compare the interpretation and application of different food substitution models in epidemiologic studies on diet and disease development. Both theoretically and in the context of a specific example, we discuss methodologic issues to be considered, including modeling of food substitutions using diet at a single time point or at multiple time points (focusing on dietary changes), choice of substitution unit, adjustment for total energy intake, and adjustment for confounding. We argue that specified food substitution analyses can be used to identify optimal food composition of the diet and that these analyses are thus highly relevant to inform public health policy decision makers.

Substitutions between dairy products and risk of stroke: results from the European Investigation into Cancer and Nutrition-Netherlands (EPIC-NL) cohort.

The association between intake of different dairy products and the risk of stroke remains unclear. We therefore investigated substitutions between dairy product subgroups and risk of stroke. We included 36 886 Dutch men and women. Information about dairy product intake was collected through a FFQ. Dairy products were grouped as low-fat milk, whole-fat milk, buttermilk, low-fat yogurt, whole-fat yogurt, cheese and butter. Incident stroke cases were identified in national registers. We used Cox proportional hazards regression to calculate associations for substitutions between dairy products with the rate of stroke. During a median follow-up of 15·2 years we identified 884 stroke cases (503 ischaemic and 244 haemorrhagic). Median intake of total dairy products was four servings/d. Low-fat yogurt substituted for whole-fat yogurt was associated with a higher rate of ischaemic stroke (hazard ratio (HR) = 2·58 (95 % CI 1·11, 5·97)/serving per d). Whole-fat yogurt as a substitution for any other subgroup was associated with a lower rate of ischaemic stroke (HR between 0·33 and 0·36/serving per d). We did not observe any associations for haemorrhagic stroke. In conclusion, whole-fat yogurt as a substitution for low-fat yogurt, cheese, butter, buttermilk or milk, regardless of fat content, was associated with a lower rate of ischaemic stroke.

Body mass index trajectories preceding first report of poor self-rated health: A longitudinal case-control analysis of the English Longitudinal Study of Ageing.

BACKGROUND: Studies have consistently found that obesity is associated with poor self-rated health, but how body mass index (BMI) developed in the lead up to poor self-rated health is unknown. METHODS: We nested a longitudinal case-control study in the English Longitudinal Study of Ageing (1998-2015) to investigate BMI trajectories in the years preceding a first self-report of poor health. Participants rated their health at each data collection; every other collection included a BMI assessment by a nurse. Case status was defined as a first report of poor health during follow-up. Three age- and sex-matched controls were identified per case using density sampling. BMI trajectories were fitted to time backwards prior to first report of poor health using mixed-effects models. Age and sex were potential modifiers. We conducted subgroup analyses of those not reporting certain chronic diseases or smoking. RESULTS: We identified 732 cases and 2195 controls. Age, but not sex, modified the association between BMI and self-rated health. Participants reporting poor health at age 60 had a 1.5 kg/m2 (95%CI: 0.8 to 2.1) higher BMI at the time of reporting than controls, and their BMI had previously increased markedly (1.3 kg/m2 95%CI: 0.9 to 1.8 over ten years). After age 75, cases no longer had higher BMI than controls, and their BMI had decreased sharply prior to reporting poor health (e.g. -2.0 kg/m2 95%CI: -2.6 to -1.5 per decade on average for those reporting poor health at age 90). Age was also an effect modifier among those without diabetes, however BMI trajectories were more similar among the middle-aged. The subgroup analysis of those without cardiovascular disease, cancer and chronic lung disease showed similar results to the main findings. CONCLUSION: Development of BMI was associated with poor self-rated health; however, the nature of the association depended markedly on age.

Substitutions between dairy product subgroups and risk of type 2 diabetes: the Danish Diet, Cancer and Health cohort.

The aim of this study was to investigate the associations for specified substitutions between different subgroups of dairy products and the risk of type 2 diabetes. We used data from the Danish Diet, Cancer and Health cohort including 54 277 men and women aged 50-64 years at baseline. Information regarding intake of dairy products was obtained from a validated FFQ, and cases of type 2 diabetes were identified through the Danish National Diabetes Register. Cox proportional hazards regressions were used to estimate associations. During a median follow-up of 15·3 years, 7137 cases were identified. Low-fat yogurt products in place of whole-fat yogurt products were associated with a higher rate of type 2 diabetes (hazard ratio (HR) 1·17; 95 % CI 1·06, 1·29) per serving/d substituted. Whole-fat yogurt products in place of low-fat milk, whole-fat milk or buttermilk were associated with a lower rate of type 2 diabetes (HR 0·89; 95 % CI 0·83, 0·96; HR 0·89; 95 % CI 0·82, 0·96; HR 0·89; 95 % CI 0·81, 0·97; per serving/d substituted, respectively). The pattern of associations was similar when intake was expressed as kJ/d (kcal/d). These findings suggest that intake of whole-fat yogurt products in place of low-fat yogurt products, low-fat milk, whole-fat milk and buttermilk are associated with a lower rate of type 2 diabetes.