International Journal of Epidemiology

IntroductionCircadian misalignment is an emerging risk factor for poor cardiovascular health, and chronotype may reflect underlying circadian processes. While previous conventional observational studies have reported adverse associations between evening chronotype and individual cardiovascular risk factors, Mendelian randomization (MR) may provide further insights into the role of chronotype in overall cardiovascular health, as measured by the American Heart Associations Lifes Essential 8 (LE8; ...

Medication use is common in large-scale population cohorts, and can modify phenotypic traits of interest. This can potentially bias effect estimates in genome-wide association studies (GWAS) and impact downstream analyses such as mendelian randomization (MR). The best approach to account for medication use in GWAS is unclear. In this study, we compared seven different methods of adjusting for antihypertensive use in a systolic blood pressure (SBP) GWAS of 407,960 White British individuals in the...

The doubly-ranked non-linear Mendelian randomization method can yield biased estimates when instrument strength varies across individuals due to gene-environment (GxE) interactions. We propose a simple strategy to mitigate this bias by modelling GxE interactions and removing the fitted GxE component from the exposure before stratification by the doubly-ranked method. In simulations, the proposed GxE correction strategy eliminated GxE-induced bias with null, linear and non-linear exposure-outcome...

BackgroundDeath certificates record both an underlying cause and contributing conditions, yet mortality statistics predominantly report only the underlying cause. We quantify this "hidden burden" across all ICD-10 conditions in Australian mortality data using the multiple-to-underlying ratio (MUR): total death certificate mentions divided by underlying cause deaths. MethodsWe analysed Australian Bureau of Statistics Causes of Death 2023 data (N = 187,268 registered deaths) to compute the ratio ...

BackgroundEvidence on how leisure-time physical activity (LTPA) improves lifetime body mass index (BMI) remains fragmented and prone to confounding. MethodsWe pooled 14,993 adults (30-90 y; 52.7% women; cohorts: REGICOR-ACRISC, ILERVAS, ARTPER) with baseline estimated LTPA (moderate-to-vigorous LTPA [MVLTPA] in REGICOR-ACRISC), genotype, and repeated BMI values from electronic health records (1990-2024, 36,157 measures). LTPA was categorized into cohort-specific quartiles; MVLTPA in 0, <100, <2...

BackgroundHigher childhood (pre-morbid) cognitive function (IQ) appears to confer a lower risk of cardiovascular disease (CVD) episodes in adulthood, however, the underpinning mechanisms are uncertain. We tested the association between childhood cognitive ability and later CVD risk factors that may underpin this gradient. MethodsWe used data from two well-characterized prospective birth cohort studies initiated in the United Kingdom in 1958 (N=10870) and 1970 (N=9278). Cognitive function was qu...

BackgroundVisceral adiposity is widely regarded as the pathogenic component of central obesity in cardiometabolic disease. However, emerging evidence suggests that abdominal subcutaneous adiposity may also confer metabolic risk in South Asian populations, although data in young, lean individuals are scarce. We investigated associations of MRI-measured abdominal subcutaneous adipose tissue (ASAT) and visceral adipose tissue (VAT) with cardiometabolic risk markers in young rural Indian adults. Me...

BackgroundMendelian randomization (MR) is increasingly used for causal inference in nutritional epidemiology; however, dietary MR studies often rely on instruments statistically selected from genome-wide association studies of self-reported intake, which are vulnerable to pleiotropy and reverse causation and may violate core MR assumptions. We aimed to develop and evaluate a biologically informed framework for selecting valid genetic instruments for dietary exposures, based on genes encoding tas...

Mendelian randomization is currently mainly implemented through the use of genetic variants as instrumental variables to investigate the causal effect of an exposure on an outcome of interest. Mendelian randomization studies are robust to confounding bias and reverse causation, but they remain susceptible to selection bias; for example, this can happen if the exposure or outcome are associated with selection into the study sample. Negative controls are sometimes used to detect biases (typically ...

ObjectivesAn update to the NICE Type 2 diabetes (T2DM) guideline in February 2022 recommended an SGLT2 inhibitor be offered to people with heart failure (HF) or cardiovascular disease (CVD) as comorbidities and considered for people at high CVD risk. We report uptake of this guideline in England by September 2023. DesignObservational cohort study. SettingGeneral practices contributing to the Clinical Practice Research Data Link, linked to hospital admission records. Participants587,826 people...

Background and ObjectivesRecent large-scale studies have consistently linked healthy dietary patterns to improved cardiometabolic health; however, the underlying biological pathways remain largely unclear, especially in non-European populations. In this study, we leverage data from four population-based cohorts (UK Biobank, NEO study, GNHS, and 10K) to investigate both common and cohort-specific biological pathways linking healthy dietary patterns to cardiometabolic disease through multi-omics p...

The ageing society and worldwide rise of chronic disease make adequate early identification of at-risk individuals and preventive intervention highly relevant to public health. Molecular indicators of global health have been developed, such as metabolomics-based MetaboHealth. A shortcoming of molecular biomarkers may be their lack of integration of lifestyle and environmental factors relevant for health span. Hence, we explored the MetaboHealth biomarker and a range of health- and lifestyle fact...

BackgroundFinancial strain has been linked to adverse cardiovascular outcomes, yet whether this association persists beyond objective socioeconomic resources remains unclear. We examined associations of financial strain with incident heart disease and all-cause mortality among US adults aged 50 years or older. MethodsProspective cohort study using the Health and Retirement Study (2006-2022). Among 7219 participants completing the Psychosocial Leave-Behind Questionnaire, the exposure was ongoing...

1.Disease-specific Polygenic Risk Scores (PRS) are usually evaluated against the incidence of diseases they were derived for. Individuals may be more interested in how these PRS influence their probable cause of death. Using UK Biobank data, we examined the top 10 causes of death among individuals in the highest quintile of disease-specific PRS for Alzheimers disease, bowel cancer, cardiovascular disease, coronary artery disease, ischaemic stroke, breast cancer, epithelial ovarian cancer, and pr...

IntroductionCardiovascular diseases (CVDs) are the leading cause of death globally, with rising burdens in Africa due to ageing populations, lifestyle changes, and poor risk factor control. Conventional risk scores developed in high-income settings often perform poorly in African populations. Machine-learning (ML) approaches offer potential to improve prediction by capturing complex, non-linear interactions among demographic, behavioural, and biological factors. This study applies ML models to W...

BACKGROUNDVisceral adipose tissue (VAT) has been associated with cardiovascular disease (CVD) mortality. However, the comparative performance of VAT-related clinical surrogates remains poorly characterized. OBJECTIVESTo evaluate the performance of seven VAT-related clinical surrogates for predicting CVD and cause-specific CVD mortality. METHODSWe analyzed data from the Mexico City Prospective Cohort, a population-based prospective cohort study, with baseline recruitmetn between 1998 - 2004 and...

BackgroundThe 2023 AHA PREVENT (Predicting Risk of Cardiovascular Disease Events) equations were expected to replace the 2013 ACC/AHA Pooled Cohort Equations (PCE) for estimating atherosclerotic cardiovascular disease (ASCVD) risk. The real-world implications of this transition on statin eligibility and disparity are unknown. ObjectivesTo evaluate how transitioning from PCE to AHA PREVENT alters statin eligibility across risk thresholds and racial and ethnic subgroups. Design, Setting, and Par...

ImportanceThe association between high-density lipoprotein cholesterol (HDL-C) and coronary artery calcium (CAC) burden remains unclear, and the potential modifying effects of lifestyle and genetic factors are not well characterized. ObjectiveTo clarify the relationship between HDL-C and CAC scores in older adults and examine whether alcohol consumption and the ALDH2 rs671 genetic variant modify this association. Design, Setting, and ParticipantsRetrospective analysis of 819 community-dwelling...

Health metrics and modelling capacity have expanded to address present burden and burden attributable to risk factors in the past. There remains a gap in accessible tools that estimate avoidable burden; --that is, the future health and economic impacts of preventive and treatment interventions. This paper describes and demonstrates the Health Interventions Impact Calculator (HIIC), a free web-based analysis and visualisation tool that allows for rapid estimation of the future health and economi...

ObjectiveTo examine how habitual ultraviolet (UV) exposure relates to cause-specific mortality and incidence, to quantify trade-offs between non-skin disease and skin cancer, and to explore potential circulating mediators. DesignA population-based prospective cohort study with epidemiological and proteomic mediation analyses. SettingUK Biobank, recruited from 22 assessment centres across England, Scotland, and Wales. Participants419 007 adults of White European ancestry with data on habitual ...