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Body mass index (BMI; weight (kg)/height (m)2) is commonly used to measure general adiposity. However, evidence of its appropriateness for males and females remains inconsistent. We aimed to identify the most appropriate sex-specific power value that height should be raised to in the formula and the value that would make it achieve height independency and body fatness dependency. We randomly assigned UK Biobank participants recruited in the United Kingdom between 2006 and 2010 (n  = 489,873; mean age = 56.5 years; 94.2% White) to training and testing sets (80%:20%). Using height raised to the power of −50.00 to 50.00, we identified the optimal power value that either minimized correlation with height or maximized correlation with body fat percentage, using age-adjusted correlations. The optimal power values for height were 1.77 for males and 1.39 for females. The new formulas resulted in 4.5% of females and 2.4% of males being reclassified into a different BMI category. The formulas did not show significant improvement (in terms of area under the receiver operating characteristic curve, sensitivity, and specificity) in identifying individuals with excessive body fat percentage or in predicting risk of all-cause mortality. Therefore, the conventional BMI formula is still valuable in research and disease screening for both sexes. [ABSTRACT FROM AUTHOR]

Population-based prospective studies, such as UK Biobank, are valuable for generating and testing hypotheses about the potential causes of human disease. We describe how UK Biobank's study design, data access policies, and approaches to statistical analysis can help to minimize error and improve the interpretability of research findings, with implications for other population-based prospective studies being established worldwide. [ABSTRACT FROM AUTHOR]

Background Evidence on body fat distribution shows opposing effects of waist circumference (WC) and hip circumference (HC) for coronary heart disease (CHD). We aimed to investigate the causality and the shape of such associations. Methods UK Biobank is a prospective cohort study of 0.5 million adults aged 40–69 years recruited between 2006 and 2010. Adjusted hazard ratios (HRs) for the associations of measured and genetically predicted body mass index (BMI), WC, HC and waist-to-hip ratio with incident CHD were obtained from Cox models. Mendelian randomization (MR) was used to assess causality. The analysis included 456 495 participants (26 225 first-ever CHD events) without prior CHD. Results All measures of adiposity demonstrated strong, positive and approximately log-linear associations with CHD risk over a median follow-up of 12.7 years. For HC, however, the association became inverse given the BMI and WC (HR per usual SD 0.95, 95% CI 0.93–0.97). Associations for BMI and WC remained independently positive after adjustment for other adiposity measures and were similar (1.14, 1.13–1.16 and 1.18, 1.15–1.20, respectively), with WC displaying stronger associations among women. Blood pressure, plasma lipids and dysglycaemia accounted for much of the observed excess risk. MR results were generally consistent with the observational, implying causality. Conclusions Body fat distribution measures displayed similar associations with CHD risk as BMI except for HC, which was inversely associated with CHD risk (given WC and BMI). These findings suggest that different measures of body fat distribution likely influence CHD risk through both overlapping and independent mechanisms. [ABSTRACT FROM AUTHOR]

Background: The role of fatty acids in coronary heart disease (CHD) remains uncertain. There is little evidence from large-scale epidemiological studies on the relevance of circulating fatty acids levels to CHD risk. This study aims to examine the independent associations of the major circulating types of fatty acids with CHD risk. Methods: UK Biobank is a prospective study of adults aged 40–69 in 2006–2010; in 2012–2013, a subset of the participants were resurveyed. Analyses were restricted to 89,242 participants with baseline plasma fatty acids (measured using nuclear magnetic resonance spectroscopy) and without prior CHD. Cox proportional hazards models were used to estimate hazard ratios (HRs) for the associations with incidence CHD, defined as the first-ever myocardial infarction, unstable angina pectoris, coronary-related death, or relevant procedure. And the major types of fatty acids were mutually adjusted to examine the independent associations. Hazard ratios were corrected for regression dilution using the correlation of baseline and resurvey fatty acids measures. Results: During a median follow-up of 11.8 years, 3,815 incident cases of CHD occurred. Independently of other fatty acids, CHD risk was positively associated with saturated fatty acids (SFA) and monounsaturated fatty acids (MUFA), inversely associated with omega-3 polyunsaturated fatty acids (PUFA), but there was no strong evidence of an association with omega-6 PUFA: HR per standard deviation higher were 1.14 (95% CI, 1.09–1.20), 1.15 (1.10–1.21), 0.91 (0.87–0.94), and 1.04 (0.99–1.09) respectively. Independently of triglycerides and cholesterol, the inverse association with omega-3 PUFA was not materially changed, but the positive associations with SFA and MUFA attenuated to null after adjusting for triglycerides levels. Conclusions: This large-scale study has quantitated the independent associations of circulating fatty acids with CHD risk. Omega-3 PUFA was inversely related to CHD risk, independently of other fatty acids and major lipid fractions. By contrast, independently of other fatty acids, the positive associations of circulating SFA and MUFA with CHD risk were mostly attributed to their relationship with triglycerides. [ABSTRACT FROM AUTHOR]

UK Biobank is an intensively characterised prospective cohort of 500,000 adults aged 40-69 years when recruited between 2006 and 2010. The study was established to enable researchersworldwide to undertake health-related research in the public interest. The existence of such a large, detailed prospective cohort with a high degree of participant engagement enabled its rapid repurposing for coronavirus disease-2019 (COVID-19) research. In response to the pandemic, the frequency of updates on hospitalisations and deaths among participants was immediately increased, and new data linkages were established to national severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) testing and primary care health records to facilitate research into the determinants of severe COVID-19. UK Biobank also instigated several sub-studies on COVID-19. In 2020, monthly blood samples were collected from approximately 20,000 individuals to investigate the distribution and determinants of SARS-CoV-2 infection, and to assess the persistence of antibodies following infection with another blood sample collected after 12 months. UK Biobank also performed repeat imaging of approximately 2,000 participants (half of whom had evidence of previous SARS-CoV-2 infection and half did not) to investigate the impact of the virus on changes in measures of internal organ structure and function. In addition, approximately 200,000 UK Biobank participants took part in a self-test SARS-CoV-2 antibody sub-study (between February and November 2021) to collect objective data on previous SARS-CoV-2 infection. These studies are enabling unique research into the genetic, lifestyle and environmental determinants of SARSCoV-2 infection and severe COVID-19, as well as their long-term health effects. UK Biobank's contribution to the national and international response to the pandemic represents a case study for its broader value, now and in the future, to precision medicine research. [ABSTRACT FROM AUTHOR]

Data on patients discharged following COVID-19 hospitalization is scarce. We conducted an electronic health records study of community-acquired COVID-19 patients discharged between 15 March and 14 July 2020 from hospitals in Oxfordshire, UK. Of 403 discharged patients, 114 (28%) were readmitted or died within 60 days (incidence rate 18/100 person-months). Rates of readmission or death were twice as high among those ≥ 65 years as those < 65 years [standardized rate ratio: 2.21 (95% CI: 1.45–3.56)] and among women than men [2.25 (1.05–4.18)]. These findings suggest important sex differences in 60-day outcomes following COVID-19 hospitalization that have not previously been well described. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to quantify the associations of regional fat mass and fat-free mass with systolic blood pressure.Methods: This analysis combined individual participant data from two large-scale imaging studies: UK Biobank and Oxford BioBank. In both studies, participants were interviewed and measured, and they underwent dual-energy x-ray absorptiometry imaging. Linear regression was used to relate systolic blood pressure to anthropometric measures of adiposity (BMI, waist circumference, and waist to hip ratio) and dual-energy x-ray absorptiometry-derived measures of body composition (visceral android fat, subcutaneous android fat, subcutaneous gynoid fat, and fat-free mass).Results: Among 10,260 participants (mean age 49; 96% white), systolic blood pressure was positively associated with visceral android fat (3.2 mmHg/SD in men; 2.8 mmHg/SD in women) and fat-free mass (1.92 mmHg/SD in men; 1.64 mmHg/SD in women), but there was no evidence of an association with subcutaneous android or gynoid fat. Associations of systolic blood pressure with BMI were slightly steeper than those with waist circumference or waist to hip ratio; these associations remained unchanged following adjustment for fat-free mass, but adjustment for visceral android fat eliminated associations with waist circumference and waist to hip ratio and more than halved associations with BMI.Conclusions: This analysis indicates that visceral fat is the primary etiological component of excess adiposity underlying the development of adiposity-related hypertension. [ABSTRACT FROM AUTHOR]

An increasing number of people are now living with cardiovascular disease (CVD), with concomitant CVD-related hospitalizations, operations, and prescriptions. To ultimately deliver optimal cardiovascular care, access to population-based biobanks with data on multiomics, phenotypes, and lifestyle risk factors are crucial. UK Biobank is a cohort study that incorporated data between 2006 and 2010 from over half a million individuals (40 to 69 years of age) at recruitment from across the United Kingdom. As one of the most accessible, largest, and in-depth cohort studies in the world, UK Biobank continues to enhance the resource with the addition of data from various omics platforms (eg, genomics, metabolomics, proteomics), multimodal imaging, self-reported risk factors and health outcomes, and linkage to electronic health records. The vision of UK Biobank is to allow as many researchers as possible to apply their expertise and imagination to undertake research to prevent, diagnose, and treat a wide range of chronic conditions, including CVD. [ABSTRACT FROM AUTHOR]

Background and Aims: The independent role of body fat distribution and fat-free mass in heart failure (HF) risk is unclear. We investigated the role of different body composition compartments in risk of HF., Methods: Present analyses include 428 087 participants (mean age 55.9 years, 44% male) from the UK Biobank. Associations of long-term average levels of body composition measures with incident HF were determined using adjusted Cox proportional hazards regression models., Results: Over a median follow-up of 13.8 years, there were 10 455 first-ever incident HF events. Overall, HF risk was more strongly associated with central adiposity (waist circumference (WC) adjusted for body mass index (BMI); HR 1.38, 95% CI 1.32 to 1.45) than general adiposity (BMI adjusted for WC; HR 1.22, 95% CI 1.16 to 1.27). Although dual X-ray absorptiometry-derived body fat remained positively related to HF after adjustment for fat-free mass (HR 1.37, 95% CI 1.18 to 1.59), the association of fat-free mass with HF was substantially attenuated by fat mass (HR 1.12, 95% CI 1.01 to 1.26) while visceral fat (VAT) remained associated with HF independent of subcutaneous fat (HR 1.20, 95% CI 1.09 to 1.33). In analyses of HF subtypes, HF with preserved ejection fraction was independently associated with all fat measures (eg, VAT: HR 1.23, 95% CI 1.12 to 1.35; body fat: HR 1.36, 95% CI 1.17 to 1.57) while HF with reduced ejection fraction was not independently associated with fat measures (eg, VAT: HR 1.29, 95% CI 0.98 to 1.68; body fat: HR 1.29, 95% CI 0.80 to 2.07)., Conclusions: This large-scale study shows that excess adiposity and fat mass are associated with higher HF risk while the association of fat-free mass with HF could be explained largely by its correlation with fat mass. The study also describes the independent relevance of body fat distribution to HF subtypes, suggesting different mechanisms may be driving their aetiopathogenesis., Competing Interests: Competing interests: SL reports grants from the Medical Research Council (MRC) and research funding from the US Centers for Disease Control and Prevention Foundation (with support from Amgen) during the conduct of the study., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: The independent effect of waist-to-height ratio (WHtR) and body fat percentage (BF%) on ischemic cardiovascular disease (CVD) remains uncertain., Objectives: This study aimed to investigate the independent associations of WHtR and BF% with ischemic CVD., Methods: This prospective cohort study used data from the UK Biobank. BF% was calculated as fat mass divided by body weight, measured by bioimpedance. Cox models estimated hazard ratios (HRs) with 95% confidence intervals (CIs) for overall and sex-specific associations of BF% and WHtR with risks of ischemic CVD and its main subtypes [myocardial infarction (MI) and ischemic stroke (IS)], adjusted for a range of potential confounders, including mutual adjustment for BF% and WHtR., Results: In total, 468,333 participants without existing CVD were included in the analysis. During 12 y of follow-up, 20,151 ischemic CVD events, 13,604 MIs, and 6681 ISs were recorded. WHtR was linearly associated with ischemic CVD, MI, and IS, with an HR per 5% increase of 1.23 (95% CI: 1.20, 1.25), 1.24 (95% CI: 1.21, 1.27), and 1.22 (95% CI: 1.18, 1.26), respectively, independent of BF%. A stronger association between WHtR and MI was seen in females than in males. The association of BF% with these outcomes was substantially attenuated in both sexes after adjustment for WHtR. For example, in females, the HR (highest compared with lowest fifth) was reduced from 1.94 (95% CI: 1.76, 2.15) to 1.04 (95% CI: 0.90, 1.01) for ischemic CVD, from 2.04 (95% CI: 1.79, 2.32) to 0.97 (95% CI: 0.81, 1.16) for MI, and from 1.81 (95% CI: 1.54, 2.13) to 1.07 (95% CI: 0.85, 1.33) for IS., Conclusions: WHtR, when used as a proxy measure for central obesity, is linearly associated with ischemic CVD in both sexes, which is independent of BF%. In contrast, the relationship of BF% with these health outcomes is predominantly driven by its correlation with WHtR., Competing Interests: Conflict of interest MW does consultancy for Amgen and Freeline outside the submitted work; no support from any organization for the submitted work; no other relationships or activities that could appear to have influenced the submitted work. All other authors report no conflicts of interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background Associations of coronary heart disease (CHD) with plasma lipids are well described, but the associations with characteristics of lipoproteins (which transport lipids) remain unclear. Methods and Results UK Biobank is a prospective study of 0.5 million adults. Analyses were restricted to 89 422 participants with plasma lipoprotein and apolipoprotein measures from Nightingale nuclear magnetic resonance spectroscopy and without CHD at baseline. CHD risk was positively associated with concentrations of very-low-density lipoproteins, intermediate-density lipoproteins, and low-density lipoproteins (LDL), and inversely associated with high-density lipoproteins. Hazard ratios (99% CIs) per SD were 1.22 (1.17-1.28), 1.16 (1.11-1.21), 1.20 (1.15-1.25), and 0.90 (0.86-0.95), respectively. Larger subclasses of very-low-density lipoproteins were less strongly associated with CHD risk, but associations did not materially vary by size of LDL or high-density lipoprotein. Given lipoprotein particle concentrations, lipid composition (including cholesterol) was not strongly related to CHD risk, except for triglyceride in LDL particles. Apolipoprotein B was highly correlated with LDL concentration ( r =0.99), but after adjustment for apolipoprotein B, concentrations of very-low-density lipoprotein and high-density lipoprotein particles remained strongly related to CHD risk. Conclusions This large-scale study reliably quantifies the associations of nuclear magnetic resonance-defined lipoprotein characteristics with CHD risk. CHD risk was most strongly related to particle concentrations, and separate measurements of lipoprotein concentrations may be of greater value than the measurement by apolipoprotein B, which was largely determined by LDL concentration alone. Furthermore, there was strong evidence of positive association with mean triglyceride molecules per LDL particle but little evidence of associations with total triglycerides or other lipid and lipoprotein fractions after accounting for lipoprotein concentrations.

Objectives: To estimate the risk of Long COVID by socioeconomic deprivation and to further examine the inequality by sex and occupation., Design: We conducted a retrospective population-based cohort study using data from the ONS COVID-19 Infection Survey between 26 April 2020 and 31 January 2022. This is the largest nationally representative survey of COVID-19 in the UK with longitudinal data on occupation, COVID-19 exposure and Long COVID., Setting: Community-based survey in the UK., Participants: A total of 201,799 participants aged 16 to 64 years and with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection., Main Outcome Measures: The risk of Long COVID at least 4 weeks after SARS-CoV-2 infection by index of multiple deprivation (IMD) and the modifying effects of socioeconomic deprivation by sex and occupation., Results: Nearly 10% ( n  = 19,315) of participants reported having Long COVID. Multivariable logistic regression models, adjusted for a range of variables (demographic, co-morbidity and time), showed that participants in the most deprived decile had a higher risk of Long COVID (11.4% vs. 8.2%; adjusted odds ratio (aOR): 1.46; 95% confidence interval (CI): 1.34, 1.59) compared to the least deprived decile. Significantly higher inequalities (most vs. least deprived decile) in Long COVID existed in healthcare and patient-facing roles (aOR: 1.76; 95% CI: 1.27, 2.44), in the education sector (aOR: 1.68; 95% CI: 1.31, 2.16) and in women (aOR: 1.56; 95% CI: 1.40, 1.73) than men (aOR: 1.32; 95% CI: 1.15, 1.51)., Conclusions: This study provides insights into the heterogeneous degree of inequality in Long COVID by deprivation, sex and occupation. These findings will help inform public health policies and interventions in incorporating a social justice and health inequality lens.

UK Biobank is a large-scale prospective study with deep phenotyping and genomic data. Its open-access policy allows researchers worldwide, from academia or industry, to perform health research in the public interest. Between 2006 and 2010, the study recruited 502,000 adults aged 40-69 years from the general population of the United Kingdom. At enrolment, participants provided information on a wide range of factors, physical measurements were taken, and biological samples (blood, urine and saliva) were collected for long-term storage. Participants have now been followed up for over a decade with more than 52,000 incident cancer cases recorded. The study continues to be enhanced with repeat assessments, web-based questionnaires, multi-modal imaging, and conversion of the stored biological samples to genomic and other '-omic' data. The study has already demonstrated its value in enabling research into the determinants of cancer, and future planned enhancements will make the resource even more valuable to cancer researchers. Over 26,000 researchers worldwide are currently using the data, performing a wide range of cancer research. UK Biobank is uniquely placed to transform our understanding of the causes of cancer development and progression, and drive improvements in cancer treatment and prevention over the coming decades., (© 2022. The Author(s).)

Importance: Uncertainty persists regarding the independent association of general and central adiposity with major stroke types., Objective: To determine the independent associations of general and central adiposity with risk of ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage., Design, Setting, and Participants: Between 2006 and 2010, adults without prior stroke at recruitment in England, Scotland, and Wales were recruited into the UK Biobank prospective cohort study and were followed up through linkage with electronic medical records. Data were analyzed from September 2021 to September 2022., Exposures: General adiposity (body mass index [BMI] calculated as weight in kilograms divided by height in meters squared) and central adiposity (waist circumference)., Main Outcomes and Measures: Incident ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage as recorded through record linkage with electronic hospital records. Cox regression estimated adjusted hazard ratios (HRs) by stroke type., Results: Among 490 071 participants, the mean (SD) age was 56.5 (8.1) years, 267 579 (54.6%) were female, and 461 647 (94.2%) were White. During a median (IQR) of 12 (11.2-12.7) years follow-up, 7117 incident ischemic strokes, 1391 intracerebral hemorrhages, and 834 subarachnoid hemorrhages were identified. After mutual adjustment for waist circumference, BMI had no independent association with ischemic stroke (HR per 5-unit higher BMI, 1.04; 95% CI, 0.97-1.11), but was inversely associated with intracerebral hemorrhage (HR, 0.85; 95% CI, 0.74-0.96) and subarachnoid hemorrhage (HR, 0.82; 95% CI, 0.69-0.96). Waist circumference (adjusted for BMI) was positively associated with ischemic stroke (HR per 10-cm higher waist circumference, 1.19; 95% CI, 1.13-1.25) and intracerebral hemorrhage (HR, 1.17; 95% CI, 1.05-1.30), but was not associated with subarachnoid hemorrhage (HR, 1.07; 95% CI, 0.93-1.22)., Conclusions and Relevance: In this large-scale prospective study, the independent and contrasting associations of BMI and waist circumference with stroke types suggests the importance of considering body fat distribution to stroke risk. Waist circumference was positively associated with the risk of ischemic stroke and intracerebral hemorrhage, while BMI was inversely associated with the risk of subarachnoid hemorrhage and intracerebral hemorrhage. This study also suggests that some adverse correlate of low BMI may be associated with an increased risk of intracerebral hemorrhage and subarachnoid hemorrhage, which warrants further investigation.

UK Biobank is an intensively characterized prospective study of 500 000 men and women, aged 40 to 69 years when recruited, between 2006 and 2010, from the general population of the United Kingdom. Established as an open-access resource for researchers worldwide to perform health research that is in the public interest, UK Biobank has collected (and continues to collect) a vast amount of data on genetic, physiological, lifestyle, and environmental factors, with prolonged follow-up of heath conditions through linkage to administrative electronic health records. The study has already demonstrated its unique value in enabling research into the determinants of common endocrine and metabolic diseases. The importance of UK Biobank, heralded as a flagship project for UK health research, will only increase over time as the number of incident disease events accrue, and the study is enhanced with additional data from blood assays (such as whole-genome sequencing, metabolomics, and proteomics), wearable technologies (including physical activity and cardiac monitors), and body imaging (magnetic resonance imaging and dual-energy X-ray absorptiometry). This unique research resource is likely to transform our understanding of the causes, diagnosis, and treatment of many endocrine and metabolic disorders., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.)