On the use of the healthy lifestyle index to investigate specific disease outcomes.

The healthy lifestyle index (HLI), defined as the unweighted sum of individual lifestyle components, was used to investigate the combined role of lifestyle factors on health-related outcomes. We introduced weighted outcome-specific versions of the HLI, where individual lifestyle components were weighted according to their associations with disease outcomes. Within the European Prospective Investigation into Cancer and Nutrition (EPIC), we examined the association between the standard and the outcome-specific HLIs and the risk of T2D, CVD, cancer, and all-cause premature mortality. Estimates of the hazard ratios (HRs), the Harrell's C-index and the population attributable fractions (PAFs) were compared. For T2D, the HR for 1-SD increase of the standard and T2D-specific HLI were 0.66 (95% CI: 0.64, 0.67) and 0.43 (0.42, 0.44), respectively, and the C-index were 0.63 (0.62, 0.64) and 0.72 (0.72, 0.73). Similar, yet less pronounced differences in HR and C-index were observed for standard and outcome-specific estimates for cancer, CVD and all-cause mortality. PAF estimates for mortality before age 80 were 57% (55%, 58%) and 33% (32%, 34%) for standard and mortality-specific HLI, respectively. The use of outcome-specific HLI could improve the assessment of the role of lifestyle factors on disease outcomes, thus enhancing the definition of public health recommendations.

Plant Omega-3 Fatty Acids May Lower Risk of Atrial Fibrillation in Individuals with a Low Intake of Marine Omega-3 Fatty Acids.

BACKGROUND: Omega-3 fatty acids derived from seafood acids may influence cardiac arrhythmogenesis, whereas the role of the major plant-derived omega-3 fatty acid, alpha-linolenic acid (ALA), on atrial fibrillation (AF) is largely unknown. OBJECTIVES: We aimed to investigate the association between ALA intake and risk of incident AF overall and in subjects with a low intake of marine omega-3 fatty acids. METHODS: We followed a total of 54,260 middle-aged men and women enrolled into the Danish Diet, Cancer, and Health cohort for development of AF using nationwide registries. Intake of ALA was assessed using a validated food frequency questionnaire and modeled as a restricted cubic spline. Statistical analyses were conducted using Cox proportional hazards regression. RESULTS: We identified a total of 4902 incident AF events during a median of 16.9 y of follow-up. In multivariable analyses, we observed indications of a statistically nonsignificant inverse association between ALA intake and risk of AF up to an ALA intake of 2.5 g/d, whereas no appreciable association was found for higher intakes of ALA. A statistically significant dose-dependent negative association was found between ALA intake and risk of AF in individuals consuming < 250 mg marine omega-3 fatty acids daily, whereas no association was found in those with a higher intake of marine omega-3 fatty acids. CONCLUSIONS: Intake of ALA was associated with a lower risk of AF in individuals consuming a low intake of marine omega-3 fatty acids. This finding is novel and warrants further investigation.

Role of dietary fibres in cardiometabolic diseases.

PURPOSE OF REVIEW: This review highlights recent developments in understanding the role of dietary fibre and specific fibre types on risk and management of cardiometabolic disease with a focus on the causal pathways leading to cardiometabolic diseases, namely weight management, glycaemic control, and lipid levels, as well as the latest findings for cardiovascular disease outcomes such as coronary heart disease, stroke, and mortality. Evidence for mechanisms through gut microbiota are also briefly reviewed. RECENT FINDINGS: Dietary fibre intake is associated with improved weight management, the extent of which may depend on the subtype of dietary fibre. Overall dietary fibre intake reduces blood glucose and HbA1c, however soluble fibres may be particularly effective in reducing HbA1c, fasting blood glucose and blood lipids. Individual meta-analyses and umbrella reviews of observational studies on dietary fibre, as well as major fibre types, observed inverse associations with incident coronary heart disease, stroke, and mortality due to cardiovascular disease. As different types of fibres exerted different health benefits, fibre diversity (i.e. combinations of fibres) should be further investigated. SUMMARY: Dietary fibres improve both short-term and long-term cardiometabolic disease risk factors and outcomes, and thus should be on every menu.

A systematic evaluation of seven different scores representing the EAT-Lancet reference diet and mortality, stroke, and greenhouse gas emissions in three cohorts.

Different approaches have been used for translation of the EAT-Lancet reference diet into dietary scores that can be used to assess health and environmental impact. Our aim was to compare the different EAT-Lancet diet scores, and to estimate their associations with all-cause mortality, stroke incidence, and greenhouse gas emissions. We did a systematic review (PROSPERO, CRD42021286597) to identify different scores representing adherence to the EAT-Lancet reference diet. We then qualitatively compared the diet adherence scores, including their ability to group individuals according the EAT-Lancet reference diet recommendations, and quantitatively assessed the associations of the diet scores with health and environmental outcome data in three diverse cohorts: the Danish Diet, Cancer and Health Cohort (DCH; n=52 452), the Swedish Malmö Diet and Cancer Cohort (MDC; n=20 973), and the Mexican Teachers' Cohort (MTC; n=30 151). The DCH and MTC used food frequency questionnaires and the MDC used a modified diet history method to assess dietary intake, which we used to compute EAT-Lancet diet scores and evaluate the associations of scores with hazard of all-cause mortality and stroke. In the MDC, dietary greenhouse gas emission values were summarised for every participant, which we used to predict greenhouse gas emissions associated with varying diet adherence scores on each scoring system. In our review, seven diet scores were identified (Knuppel et al, 2019; Trijsburg et al, 2020; Cacau et al, 2021; Hanley-Cook et al, 2021; Kesse-Guyot et al, 2021; Stubbendorff et al, 2022; and Colizzi et al, 2023). Two of the seven scores (Stubbendorff and Colizzi) were among the most consistent in grouping participants according to the EAT-Lancet reference diet recommendations across cohorts, and higher scores (greater diet adherence) were associated with decreased risk of mortality (in the DCH and MDC), decreased risk of incident stroke (in the DCH and MDC for the Stubbendorff score; and in the DCH for the Colizzi score), and decreased predicted greenhouse gas emissions in the MDC. We conclude that the seven different scores representing the EAT-Lancet reference diet had differences in construction, interpretation, and relation to disease and climate-related outcomes. Two scores generally performed well in our evaluation. Future studies should carefully consider which diet score to use and preferably use multiple scores to assess the robustness of estimations, given that public health and environmental policy rely on these estimates.

Hepatic steatosis, metabolic dysfunction and risk of mortality: findings from a multinational prospective cohort study.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS) are implicated in the aetiology of non-communicable diseases. Our study aimed to evaluate associations between NAFLD and MetS with overall and cause-specific mortality. METHODS: We used dietary, lifestyle, anthropometric and metabolic biomarker data from a random subsample of 15,784 EPIC cohort participants. NAFLD was assessed using the fatty liver index (FLI) and MetS using the revised definition. Indices for metabolic dysfunction-associated fatty liver disease (MAFLD) were calculated. The individual associations of these indices with overall and cause-specific mortality were assessed using multivariable Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (95%CIs). As a subobjective, risk associations with adaptations of new classifications of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic and alcohol-related liver disease (MetALD) were also assessed. RESULTS: Among the 15,784 sub-cohort participants, a total of 1997 deaths occurred (835 due to cancer, 520 to CVD, 642 to other causes) over a median 15.6 (IQR, 12.3-17.1) years of follow-up. Compared to an FLI < 30, FLI ≥ 60 was associated with increased risks of overall mortality (HR = 1.44, 95%CI = 1.27-1.63), and deaths from cancer (HR = 1.32, 95%CI = 1.09-1.60), CVD (HR = 2.06, 95% CI = 1.61-2.63) or other causes (HR = 1.21, 95%CI = 0.97-1.51). Mortality risk associations were also elevated for individuals with MAFLD compared to those without. Individuals with MetS were at increased risk of all mortality endpoints, except cancer-specific mortality. MASLD and MetALD were associated with higher risk of overall mortality. CONCLUSIONS: Our findings based on a prospective cohort suggest that individuals with hepatic steatosis or metabolic dysfunction have a higher overall and cause-specific mortality risk.

Source-specific nitrate intake and all-cause mortality in the Danish Diet, Cancer, and Health Study.

INTRODUCTION: Nitrate and nitrite are naturally occurring in both plant- and animal-sourced foods, are used as additives in the processing of meat, and are found in water. There is growing evidence that they exhibit a spectrum of health effects, depending on the dietary source. The aim of the study was to examine source-dependent associations between dietary intakes of nitrate/nitrite and both all-cause and cause-specific mortality. METHODS: In 52,247 participants of the Danish Diet, Cancer and Health Study, associations between source-dependent nitrate and nitrite intakes--calculated using comprehensive food composition and national drinking water quality monitoring databases--and all-cause, cardiovascular disease (CVD)-related, and cancer-related mortality over 27 years were examined using restricted cubic splines within Cox proportional hazards models adjusting for demographic, lifestyle, and dietary confounders. Analyses were stratified by factors hypothesised to influence the formation of carcinogenic N-nitroso compounds (namely, smoking and dietary intakes of vitamin C, vitamin E, folate, and polyphenols). RESULTS: Plant-sourced nitrate intake was inversely associated with all-cause mortality [HRQ5vsQ1: 0.83 (0.80, 0.87)] while higher risks of all-cause mortality were seen for higher intakes of naturally occurring animal-sourced nitrate [1.09 (1.04, 1.14)], additive permitted meat-sourced nitrate [1.19 (1.14, 1.25)], and tap water-sourced nitrate [1.19 (1.14, 1.25)]. Similar source-dependent associations were seen for nitrite and for CVD-related and cancer-related mortality except that naturally occurring animal-sourced nitrate and tap water-sourced nitrate were not associated with cancer-related mortality and additive permitted meat-sourced nitrate was not associated with CVD-related mortality. No clear patterns emerged in stratified analyses. CONCLUSION: Nitrate/nitrite from plant sources are inversely associated while those from naturally occurring animal-sources, additive-permitted meat sources, and tap water-sources are positively associated with mortality.

Bidirectional Association Between Atrial Fibrillation and Myocardial Infarction, and Relation to Mortality in the Framingham Heart Study.

BACKGROUND: Individuals with both atrial fibrillation (AF) and myocardial infarction (MI) have higher mortality compared with individuals with only 1 condition. Whether mortality differs according to the temporal order of AF and MI is unclear. METHODS AND RESULTS: We included participants from the FHS (Framingham Heart Study) from 1960 and onwards. We assessed the hazard ratio (HR) of new-onset AF and MI, and mortality according to MI and AF status (prevalent and interim) using multivariable-adjusted Cox proportional hazards models. Interim diseases were modeled as time-varying variables. For the analysis of new-onset AF, 10 923 participants (55% women; mean±SD age, 54±8 years) were included. For new-onset MI, 10 804 participants (55% women; mean±SD age, 54±8 years) were included. Compared with no MI, the hazard of new-onset AF was higher in participants with prevalent (HR, 1.60 [95% CI, 1.32-1.94]) and interim MI (HR, 3.96 [95% CI, 3.18-4.91]). Both ST-segment-elevation MI and non-ST-segment-elevation MI were associated with new-onset AF. Interim AF, not prevalent AF, was associated with higher hazard rate of new-onset MI (HR, 2.21 [95% CI, 1.67-2.92]). Interim AF was associated with both ST-segment-elevation MI and non-ST-segment-elevation MI. Mortality was significantly greater among participants with AF and MI compared with participants with 1 of the 2, regardless of temporal order. CONCLUSIONS: We report a bidirectional association between AF and MI, which was observed for both non-ST-segment-elevation MI and ST-segment-elevation MI. Participants with both AF and MI had considerably higher mortality compared with participants with only 1 of the 2 conditions, regardless of order.

Dietary intake of plant- and animal-derived protein and incident cardiovascular diseases: the pan-European EPIC-CVD case-cohort study.

BACKGROUND: Epidemiological evidence suggests that a potential association between dietary protein intake and cardiovascular disease (CVD) may depend on the protein source, that is, plant- or animal-derived, but past research was limited and inconclusive. OBJECTIVES: To evaluate the association of dietary plant- or animal-derived protein consumption with risk of CVD, and its components ischemic heart disease (IHD) and stroke. METHODS: This analysis in the European Prospective Investigation into Cancer and Nutrition (EPIC)-CVD case-cohort study included 16,244 incident CVD cases (10,784 IHD and 6423 stroke cases) and 15,141 subcohort members from 7 European countries. We investigated the association of estimated dietary protein intake with CVD, IHD, and stroke (total, fatal, and nonfatal) using multivariable-adjusted Prentice-weighted Cox regression. We estimated isocaloric substitutions of replacing fats and carbohydrates with plant- or animal-derived protein and replacing food-specific animal protein with plant protein. Multiplicative interactions between dietary protein and prespecified variables were tested. RESULTS: Neither plant- nor animal-derived protein intake was associated with incident CVD, IHD, or stroke in adjusted analyses without or with macronutrient-specified substitution analyses. Higher plant-derived protein intake was associated with 22% lower total stroke incidence among never smokers [HR 0.78, 95% confidence intervals (CI): 0.62, 0.99], but not among current smokers (HR 1.08, 95% CI: 0.83, 1.40, P-interaction = 0.004). Moreover, higher plant-derived protein (per 3% total energy) when replacing red meat protein (HR 0.52, 95% CI: 0.31, 0.88), processed meat protein (HR 0.39, 95% CI: 0.17, 0.90), and dairy protein (HR 0.54, 95% CI: 0.30, 0.98) was associated with lower incidence of fatal stroke. CONCLUSION: Plant- or animal-derived protein intake was not associated with overall CVD. However, the association of plant-derived protein consumption with lower total stroke incidence among nonsmokers, and with lower incidence of fatal stroke highlights the importance of investigating CVD subtypes and potential interactions. These observations warrant further investigation in diverse populations with varying macronutrient intakes and dietary patterns.

Inflammation and Gut Barrier Function-Related Genes and Colorectal Cancer Risk in Western European Populations.

Gut barrier dysfunction and related inflammation are known to be associated with the development and progression of colorectal cancer (CRC). We investigated associations of 292 single-nucleotide polymorphisms (SNPs) from 27 genes related to endotoxins/lipopolysaccharide (LPS) sensing and tolerance, mucin synthesis, inflammation, and Crohn's disease with colon and rectal cancer risks. Incident CRC cases (N=1,374; colon=871, rectum=503) were matched 1:1 to controls nested within the European Prospective Investigation into Cancer and Nutrition cohort. Previously measured serum concentrations of gut barrier function and inflammation biomarkers (flagellin/LPS-specific immunoglobulins and C-reactive protein [CRP]) were available for a sub-set of participants (Ncases=1,001; Ncontrols=667). Forty-two unique SNPs from 19 different genes were associated with serum biomarkers at Punadjusted≤0.05 among controls. Among SNPs associated with a gut permeability score, 24 SNPs were in genes related to LPS sensing and mucin synthesis. Nine out of 12 SNPs associated with CRP were in genes related to inflammation or Crohn's disease. TLR4 was associated with colon cancer at the SNP level (nine SNPs, all Punadjusted≤0.04) and at the gene level (Punadjusted≤0.01). TLR4 rs10759934 was associated with rectal cancer but not colon cancer. Similarly, IL10 was associated with rectal cancer risk at a SNP and gene level (both Punadjusted ≤ 0.01), but not colon cancer. Genes and SNPs were selected a priori therefore we present unadjusted P-values. However, no association was statistically significant after multiple testing correction. This large and comprehensive study has identified gut barrier function and inflammation-related genes possibly contributing to CRC risk in European populations and is consistent with potential etiological links between host genetic background, gut barrier permeability, microbial endotoxemia and CRC development.

Lifestyle changes in middle age and risk of cancer: evidence from the European Prospective Investigation into Cancer and Nutrition.

In this study, we aimed to provide novel evidence on the impact of changing lifestyle habits on cancer risk. In the EPIC cohort, 295,865 middle-aged participants returned a lifestyle questionnaire at baseline and during follow-up. At both timepoints, we calculated a healthy lifestyle index (HLI) score based on cigarette smoking, alcohol consumption, body mass index and physical activity. HLI ranged from 0 (most unfavourable) to 16 (most favourable). We estimated the association between HLI change and risk of lifestyle-related cancers-including cancer of the breast, lung, colorectum, stomach, liver, cervix, oesophagus, bladder, and others-using Cox regression models. We reported hazard ratios (HR) with 95% confidence intervals (CI). Median time between the two questionnaires was 5.7 years, median age at follow-up questionnaire was 59 years. After the follow-up questionnaire, we observed 14,933 lifestyle-related cancers over a median follow-up of 7.8 years. Each unit increase in the HLI score was associated with 4% lower risk of lifestyle-related cancers (HR 0.96; 95%CI 0.95-0.97). Among participants in the top HLI third at baseline (HLI > 11), those in the bottom third at follow-up (HLI ≤ 9) had 21% higher risk of lifestyle-related cancers (HR 1.21; 95%CI 1.07-1.37) than those remaining in the top third. Among participants in the bottom HLI third at baseline, those in the top third at follow-up had 25% lower risk of lifestyle-related cancers (HR 0.75; 95%CI 0.65-0.86) than those remaining in the bottom third. These results indicate that lifestyle changes in middle age may have a significant impact on cancer risk.

Body mass index in parents and their adult offspring: A systematic review and meta-analysis.

Obesity may track across generations, due to genetics and shared family environmental factors, or possibly intrauterine programming. However, many studies only assess associations between maternal body mass index (BMI) and offspring BMI in childhood. To determine whether maternal and paternal associations with offspring BMI differ and whether associations persist into adulthood, a systematic review and meta-analysis was done. PubMed, Embase, Web of Science, and Google Scholar (to October 2022) were searched. Observational studies reporting associations between maternal or paternal BMI and adult offspring BMI were included. Offspring BMIs were reported as continuous or categorical measures. Forty-six studies were included in the systematic review. Meta-analyses were conducted using random-effects models. Parental BMI was positively associated with offspring BMI in adulthood. The pooled mother-offspring standardized mean difference (SMD) was 0.23 (95% confidence interval [CI]: 0.20, 0.26), and father-offspring SMD was similar: 0.22 (95% CI: 0.19, 0.25) in adjusted models. Offspring of mothers with overweight or obesity had the same risk of higher BMI as offspring of fathers with overweight or obesity. If these associations are causal, they support interventions targeting all family members, rather than focusing solely on mothers, to obtain a healthy weight development among offspring.

Dietary amino acids and risk of stroke subtypes: a prospective analysis of 356,000 participants in seven European countries.

PURPOSE: Previously reported associations of protein-rich foods with stroke subtypes have prompted interest in the assessment of individual amino acids. We examined the associations of dietary amino acids with risks of ischaemic and haemorrhagic stroke in the EPIC study. METHODS: We analysed data from 356,142 participants from seven European countries. Dietary intakes of 19 individual amino acids were assessed using validated country-specific dietary questionnaires, calibrated using additional 24-h dietary recalls. Multivariable-adjusted Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of ischaemic and haemorrhagic stroke in relation to the intake of each amino acid. The role of blood pressure as a potential mechanism was assessed in 267,642 (75%) participants. RESULTS: After a median follow-up of 12.9 years, 4295 participants had an ischaemic stroke and 1375 participants had a haemorrhagic stroke. After correction for multiple testing, a higher intake of proline (as a percent of total protein) was associated with a 12% lower risk of ischaemic stroke (HR per 1 SD higher intake 0.88; 95% CI 0.82, 0.94). The association persisted after mutual adjustment for all other amino acids, systolic and diastolic blood pressure. The inverse associations of isoleucine, leucine, valine, phenylalanine, threonine, tryptophan, glutamic acid, serine and tyrosine with ischaemic stroke were each attenuated with adjustment for proline intake. For haemorrhagic stroke, no statistically significant associations were observed in the continuous analyses after correcting for multiple testing. CONCLUSION: Higher proline intake may be associated with a lower risk of ischaemic stroke, independent of other dietary amino acids and blood pressure.

Interaction of genetic risk and lifestyle on the incidence of atrial fibrillation.

BACKGROUND: The relationship between combined genetic predisposition and lifestyle and the risk of incident atrial fibrillation (AF) is unclear. Therefore, we aimed to assess a possible interaction between lifestyle and genetics on AF risk. METHODS: We included AF cases and a randomly drawn subcohort of 4040 participants from the Danish Diet, Cancer and Health cohort. Lifestyle risk factors were assessed, a score was calculated, and participants were categorised as having a poor, intermediate, or ideal lifestyle. We calculated a genetic risk score comprising 142 variants, and categorised participants into low (quintile 1), intermediate (quintiles 2-4) or high (quintile 5) genetic risk of AF. RESULTS: 3094 AF cases occurred during a median follow-up of 12.9 years. Regardless of genetic risk, incidence rates per 1000 person-years were gradually higher with worse lifestyle. For participants with high genetic risk, the incidence rates of AF per 1000 person-years were 5.0 (95% CI 3.4 to 7.3) among individuals with ideal lifestyle, 6.6 (95% CI 5.4 to 8.1) among those with intermediate lifestyle and 10.4 (95% CI 9.2 to 11.8) among participants with poor lifestyle. On an additive scale, there was a positive statistically significant interaction between genetic risk and lifestyle (relative excess risk due to interaction=0.86, 95% CI 0.68 to 1.03, p<0.001). CONCLUSIONS: The rates of AF increased gradually with worse lifestyle within each category of genetic risk. We found a positive interaction on an additive scale between genetic risk and lifestyle, suggesting that risk factor modification is especially important in individuals with a high genetic risk of AF.

Large Language Models for Epidemiological Research via Automated Machine Learning: Case Study Using Data From the British National Child Development Study.

Background: Large language models have had a huge impact on natural language processing (NLP) in recent years. However, their application in epidemiological research is still limited to the analysis of electronic health records and social media data. objectives: To demonstrate the potential of NLP beyond these domains, we aimed to develop prediction models based on texts collected from an epidemiological cohort and compare their performance to classical regression methods. Methods: We used data from the British National Child Development Study, where 10,567 children aged 11 years wrote essays about how they imagined themselves as 25-year-olds. Overall, 15% of the data set was set aside as a test set for performance evaluation. Pretrained language models were fine-tuned using AutoTrain (Hugging Face) to predict current reading comprehension score (range: 0-35) and future BMI and physical activity (active vs inactive) at the age of 33 years. We then compared their predictive performance (accuracy or discrimination) with linear and logistic regression models, including demographic and lifestyle factors of the parents and children from birth to the age of 11 years as predictors. Results: NLP clearly outperformed linear regression when predicting reading comprehension scores (root mean square error: 3.89, 95% CI 3.74-4.05 for NLP vs 4.14, 95% CI 3.98-4.30 and 5.41, 95% CI 5.23-5.58 for regression models with and without general ability score as a predictor, respectively). Predictive performance for physical activity was similarly poor for the 2 methods (area under the receiver operating characteristic curve: 0.55, 95% CI 0.52-0.60 for both) but was slightly better than random assignment, whereas linear regression clearly outperformed the NLP approach when predicting BMI (root mean square error: 4.38, 95% CI 4.02-4.74 for NLP vs 3.85, 95% CI 3.54-4.16 for regression). The NLP approach did not perform better than simply assigning the mean BMI from the training set as a predictor. Conclusions: Our study demonstrated the potential of using large language models on text collected from epidemiological studies. The performance of the approach appeared to depend on how directly the topic of the text was related to the outcome. Open-ended questions specifically designed to capture certain health concepts and lived experiences in combination with NLP methods should receive more attention in future epidemiological studies.

Age at Menopause and the Risk of Stroke: Observational and Mendelian Randomization Analysis in 204 244 Postmenopausal Women.

Background Observational studies have shown that women with an early menopause are at higher risk of stroke compared with women with a later menopause. However, associations with stroke subtypes are inconsistent, and the causality is unclear. Methods and Results We analyzed data of the UK Biobank and EPIC-CVD (European Prospective Investigation Into Cancer and Nutrition-Cardiovascular Diseases) study. A total of 204 244 postmenopausal women without a history of stroke at baseline were included (7883 from EPIC-CVD [5292 from the subcohort], 196 361 from the UK Biobank). Pooled mean baseline age was 58.9 years (SD, 5.8), and pooled mean age at menopause was 47.8 years (SD, 6.2). Over a median follow-up of 12.6 years (interquartile range, 11.8-13.3), 6770 women experienced a stroke (5155 ischemic strokes, 1615 hemorrhagic strokes, 976 intracerebral hemorrhages, and 639 subarachnoid hemorrhages). In multivariable adjusted observational Cox regression analyses, the pooled hazard ratios per 5 years younger age at menopause were 1.09 (95% CI, 1.07-1.12) for stroke, 1.09 (95% CI, 1.06-1.13) for ischemic stroke, 1.10 (95% CI, 1.04-1.16) for hemorrhagic stroke, 1.14 (95% CI, 1.08-1.20) for intracerebral hemorrhage, and 1.00 (95% CI, 0.84-1.20) for subarachnoid hemorrhage. When using 2-sample Mendelian randomization analysis, we found no statistically significant association between genetically proxied age at menopause and risk of any type of stroke. Conclusions In our study, earlier age at menopause was related to a higher risk of stroke. We found no statistically significant association between genetically proxied age at menopause and risk of stroke, suggesting no causal relationship.

Intravenous thrombolysis for acute ischemic stroke is associated with lower risk of post-stroke dementia: A nationwide cohort study.

INTRODUCTION: Dementia after stroke is common and is a great concern for patients and their caregivers. The objective was to investigate if intravenous thrombolysis (IVT) for acute ischemic stroke (AIS) was associated with lower risk of dementia after stroke. PATIENTS AND METHODS: When IVT was introduced in Denmark, not all eligible patients were treated due to restricted access. We conducted a nationwide register-based cohort study of all patients with AIS in Denmark from 2004 to 2011. IVT-treated patients were propensity score-matched with comparable non-treated patients. Cox proportional hazards regression was used to estimate the hazard ratio (HR) for all-cause and vascular dementia 2, 5, and 10 years after stroke. RESULTS: Of the 5919 patients eligible for the study, 2305 IVT-treated patients were propensity score-matched with 2305 non-treated patients. Mean (SD) age was 66.6 (13.3) and 61.2% were male. Rate of all-cause dementia was lower for the IVT-treated 2 years (8.4/1000 person years (PY) vs 13.6/1000 PY, HR 0.63 (0.40-0.99)) and 5 years after stroke (7.3/1000 PY vs 11.4/1000 PY, HR 0.65 (0.46-0.91)). 10 years after stroke, the rates of all-cause dementia remained in favor of IVT (8.0/1000 PY vs 9.8/1000 PY, HR 0.83 (0.64-1.07)). IVT-treated had lower rates of vascular dementia 2 years (2.4/1000 PY vs 7.4/1000 PY, HR 0.33 (0.15-0.71)), 5 years (2.3/1000 PY vs 6.2/1000 PY, HR 0.38 (0.23-0.65)), and 10 years after stroke (3.0/1000 PY vs 5.4/1000 PY, HR 0.56 (0.38-0.81)). CONCLUSION: IVT treatment was associated with lower long-term risk of both vascular and all-cause dementia after AIS.

Maternal Pre-Pregnancy BMI, Offspring Adiposity in Late Childhood, and Age of Weaning: A Causal Mediation Analysis.

Infant feeding practices have been hypothesized to influence offspring's body mass index (BMI) later in life, and women with overweight or obesity tend to wean their infants earlier than women with healthy BMI. We, therefore, aimed to investigate how much early age of weaning mediated the maternal-offspring adiposity relationship. The study included 4920 mother-child pairs from the Avon Longitudinal Study of Parents and Children birth cohort. G-computation was applied to estimate the natural direct (NDE) and indirect (NIE) effects, via the age of weaning (<3 months, 3 months, >3 months), of maternal pre-pregnancy overweight or obesity on offspring's BMI and fat mass index. The NDE of maternal overweight or obesity on offspring BMI at 17 years old was 2.63 kg/m2 (95% CI: 2.27 to 2.99). The NIE via the age of weaning was 0.02 kg/m2 (95% CI: 0.00 to 0.04), corresponding to 0.8% of the total effect. Similar results were observed for the offspring's fat mass index. The NDE and NIE were similar to the main analyses when we looked at the relationship stratified by breastfeeding status. Our study found a minimal influence of age of weaning on the pathway between maternal and offspring adiposity, indicating the age of weaning may not be a key mediator.

Self-reported and measured anthropometric variables in association with cardiometabolic markers: A Danish cohort study.

General obesity is a recognized risk factor for various metabolically related diseases, including hypertension, dyslipidemia, and pre-diabetes. In epidemiological studies, anthropometric variables such as height and weight are often self-reported. However, misreporting of self-reported data may bias estimates of associations between anthropometry and health outcomes. Further, few validation studies have compared self-reported and measured waist circumference (WC). This study aimed to quantify the agreement between self-reported and measured height, weight, body mass index (BMI), WC, and waist-to-height ratio (WHtR), and to investigate associations of these anthropometric measures with cardiometabolic biomarkers. A total of 39,514 participants aged above 18 years were included into the Diet, Cancer, and Health-Next Generation Cohort in 2015-19. Self-reported and measured anthropometric variables, blood pressure, and cardiometabolic biomarkers (HbA1c, lipid profiles, C-reactive protein and creatinine) were collected by standard procedures. Pearson correlations (r) and Lin's concordance correlations were applied to evaluate misreporting. Misreporting by age, sex and smoking status was investigated in linear regression models. Multivariable regression models and Receiver Operating Characteristic analyses assessed associations of self-reported and measured anthropometry with cardiometabolic biomarkers. Self-reported height was overreported by 1.07 cm, and weight was underreported by 0.32 kg on average. Self-reported BMI and WC were 0.42 kg/m2 and 0.2 cm lower than measured, respectively. Self-reported and measured height, weight, BMI, WC and WtHR were strongly correlated (r = 0.98, 0.99, 0.98, 0.88, 0.86, respectively). Age, sex, smoking, and BMI contributed to misreporting of all anthropometric measures. Associations between self-reported or measured anthropometric measures and cardiometabolic biomarkers were similar in direction and strength. Concordance between self-reported and measured anthropometric measures, including WC, was very high. Self-reported anthropometric measures were reliable when estimating associations with cardiometabolic biomarkers.

A body shape index (ABSI) is associated inversely with post-menopausal progesterone-receptor-negative breast cancer risk in a large European cohort.

BACKGROUND: Associations of body shape with breast cancer risk, independent of body size, are unclear because waist and hip circumferences are correlated strongly positively with body mass index (BMI). METHODS: We evaluated body shape with the allometric "a body shape index" (ABSI) and hip index (HI), which compare waist and hip circumferences, correspondingly, among individuals with the same weight and height. We examined associations of ABSI, HI, and BMI (per one standard deviation increment) with breast cancer overall, and according to menopausal status at baseline, age at diagnosis, and oestrogen and progesterone receptor status (ER+/-PR+/-) in multivariable Cox proportional hazards models using data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. RESULTS: During a mean follow-up of 14.0 years, 9011 incident breast cancers were diagnosed among 218,276 women. Although there was little evidence for association of ABSI with breast cancer overall (hazard ratio HR = 0.984; 95% confidence interval: 0.961-1.007), we found borderline inverse associations for post-menopausal women (HR = 0.971; 0.942-1.000; n = 5268 cases) and breast cancers diagnosed at age ≥ 55 years (HR = 0.976; 0.951-1.002; n = 7043) and clear inverse associations for ER + PR- subtypes (HR = 0.894; 0.822-0.971; n = 726) and ER-PR- subtypes (HR = 0.906; 0.835-0.983 n = 759). There were no material associations with HI. BMI was associated strongly positively with breast cancer overall (HR = 1.074; 1.049-1.098), for post-menopausal women (HR = 1.117; 1.085-1.150), for cancers diagnosed at age ≥ 55 years (HR = 1.104; 1.076-1.132), and for ER + PR + subtypes (HR = 1.122; 1.080-1.165; n = 3101), but not for PR- subtypes. CONCLUSIONS: In the EPIC cohort, abdominal obesity evaluated with ABSI was not associated with breast cancer risk overall but was associated inversely with the risk of post-menopausal PR- breast cancer. Our findings require validation in other cohorts and with a larger number of PR- breast cancer cases.