International Journal of Epidemiology

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...

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...

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...

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...

BackgroundWhile multi-omics approaches, incorporating polygenic risk scores (PRS), metabolomics, and proteomics have shown promise in predicting major adverse cardiovascular events (MACE), their added value beyond cardiovascular disease (CVD) risk factors remains underexplored. We aimed to assess whether integrating multi-omics biomarkers into the SCORE2 model improves the prediction of MACE in apparently healthy individuals. MethodsThis study included 24,042 UK Biobank participants without CVD...

BackgroundSmoking, unhealthy nutrition, alcohol consumption, and physical inactivity (SNAP behaviours) are major risk factors for multimorbidity but are often studied in isolation. Using longitudinal data, Suhag et al. identified clusters of older adults (aged [&ge;]50) with common SNAP behaviour patterns and distinct sociodemographic profiles and multimorbidity prevalence; whether and how these patterns generalise across adulthood remains unclear. AimTo conceptually replicate Suhag et al. acro...

BackgroundLow mitochondrial DNA (mtDNA) abundance in blood cells has been associated with various diseases and major causes of mortality. However, the causal link and molecular mechanisms involved remain unclear, and previous studies have had limited follow-up durations. To address these gaps, we examined the relationship of blood mtDNA abundance with all-cause and cause-specific mortality over three decades, and integrated blood transcriptomic profiling to explore underlying molecular mechanism...

BackgroundConcern about long-term health effects of repetitive head impacts in football has increased, but it remains unclear whether position-specific exposure patterns were associated with differential long-term all-cause mortality among elite players across the 20th century. MethodsWe conducted two retrospective cohort studies of elite male professional football players. The World Cup cohort included all players on the team rosters from FIFA World Cup tournaments (1930-1990), and the UEFA Eu...

Drug repurposing offers the opportunity to identify promising drug targets efficiently using existing data, but there are currently limitations to these efforts; there is a particular need for versatile, but rigorous high-throughput approaches. As such, we developed a flexible, high-throughput, Mendelian randomization (MR)-based drug repurposing pipeline with three stages: 1) MR-based identification, 2) MR-based validation and prioritization, and 3) application. This pipeline can be applied to a...

Background and AimsThe glucagon-like peptide-1 receptor agonist (GLP-1 RA) semaglutide has demonstrated efficacy for the secondary prevention of cardiovascular disease among patients with overweight/obesity without diabetes mellitus. However, the comparative effectiveness of GLP-1 RA versus other antiobesity medications (e.g. phentermine-topiramate) not been evaluated. MethodsThis was a retrospective, observational, cohort study using target trial emulation methodology using the Truveta electro...

IntroductionUnderstanding the links between metabolism, ageing and age-related phenotypes may clarify the role of ageing in disease onset and improve risk prediction. MethodsWe conducted a cross-cohort assessment of biological age using broad-spectrum LC-MS metabolomics in 2,295 participants, aged 20-89, from the UK Airwave study (N=960) and The Irish Longitudinal Study of Ageing (N=1,335). ResultsN2,N2-dimethylguanosine, C-glycosyltryptophan, bile acid glucuronides, and zeta-carotene were ass...

Biological ageing begins before birth, with early-life exposures shaping late-life health. These exposures drive health inequities early, yet specific exposures and the composition of the ageing exposome remain largely undefined. This gap may persist as the field lacks agnostic investigations accounting for non-linearity, interactions and subtle signals. We aimed to identify exposures predictive of epigenetic ageing accumulated during childhood and adolescence and explore the composition of the...

COVID-19 has been shown to cause a range of harmful long-term effects on nearly every organ system1-3. These findings are based on retrospective studies comparing COVID-19 patients to patients with similar medical histories and demographics but no COVID-19 diagnosis4-16. However, concerns have emerged that these comparisons may be biased if COVID-19 patients had unrelated health conditions or other factors not recorded in their medical records17-21. Here, using a massive dataset of 14.4 billion ...

IntroductionDysglycemia is a well-established risk factor for cardiovascular disease (CVD); yet traditional glycemic traits, including fasting plasma glucose (FPG) and HbA1c, do not capture dynamic glucose fluctuations that may inform CVD risk. We cross-sectionally investigated the association of continuous glucose monitor (CGM)-derived metrics and 2-h post-prandial glucose (2-h PPG) with estimated 10-year CVD risk among individuals without diabetes. MethodsWe included 1,360 Framingham Heart St...

BackgroundObstructive sleep apnea (OSA), as measured by the Apnea Hypopnea Index (AHI), is associated with adverse outcomes. Measures that characterize the temporal variability in events may provide information over and beyond a simple summary of event frequency as measured by the AHI. Research QuestionTo assess whether temporal variability in the occurrence of obstructive apnea/hypopneas during the night is associated with all-cause mortality or incident cardiovascular disease (CVD). Study De...

BackgroundThe Global Youth Tobacco Survey (GYTS) is widely used to monitor tobacco use among adolescents worldwide. However, inconsistent analytical approaches particularly in handling complex survey designs and predictor selection limit comparability across countries, survey waves, and software platforms. Although much of the GYTS literature relies on proprietary tools such as SAS and SPSS, practical and transparent guidance on implementing reproducible, theory-informed analyses remains limited...

ObjectiveTo evaluate risk of early-onset dementia (EOD) after diagnosis of cancer among Medicaid beneficiaries. DesignLongitudinal observational study of Medicaid enrollment, inpatient, and outpatient claims data from 26 states and Washington, DC, 2001-2019. MethodsBeneficiaries aged 18-64 with [&ge;]6 months of enrollment were matched 1:1 on cancer status (lung, colon, breast, prostate) by age, sex, race, year and state. We estimated the weighted cumulative incidence functions of EOD at 1, 2,...

BackgroundThe long preclinical phase of dementia can bias estimated effects of baseline exposures on dementia incidence. We demonstrate simulations informed by reverse Mendelian randomization (MR) findings to quantify the age-specific magnitude of reverse causation bias in analyses in observational studies of the effects of body mass index (BMI) on dementia. MethodsWe simulated longitudinal trajectories of BMI and dementia risk from ages 45 to 90 years, calibrating to published evidence on age-...