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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: 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., (© The Author(s) 2023. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Significance Statement: Kidney stone disease is a common disorder with poorly understood pathophysiology. Observational and genetic studies indicate that adiposity is associated with an increased risk of kidney stone disease. However, the relative contribution of general and central adipose depots and the mechanisms by which effects of adiposity on kidney stone disease are mediated have not been defined. Using conventional and genetic epidemiological techniques, we demonstrate that general and central adiposity are independently associated with kidney stone disease. In addition, one mechanism by which central adiposity increases risk of kidney stone disease is by increasing serum calcium concentration. Therapies targeting adipose depots may affect calcium homeostasis and help to prevent kidney stone disease., Background: Kidney stone disease affects approximately 10% of individuals in their lifetime and is frequently recurrent. The disease is linked to obesity, but the mechanisms mediating this association are uncertain., Methods: Associations of adiposity and incident kidney stone disease were assessed in the UK Biobank over a mean of 11.6 years/person. Genome-wide association studies and Mendelian randomization (MR) analyses were undertaken in the UK Biobank, FinnGen, and in meta-analyzed cohorts to identify factors that affect kidney stone disease risk., Results: Observational analyses on UK Biobank data demonstrated that increasing central and general adiposity is independently associated with incident kidney stone formation. Multivariable MR, using meta-analyzed UK Biobank and FinnGen data, established that risk of kidney stone disease increases by approximately 21% per one standard deviation increase in body mass index (BMI, a marker of general adiposity) independent of waist-to-hip ratio (WHR, a marker of central adiposity) and approximately 24% per one standard deviation increase of WHR independent of BMI. Genetic analyses indicate that higher WHR, but not higher BMI, increases risk of kidney stone disease by elevating adjusted serum calcium concentrations (β=0.12 mmol/L); WHR mediates 12%-15% of its effect on kidney stone risk in this way., Conclusions: Our study indicates that visceral adipose depots elevate serum calcium concentrations, resulting in increased risk of kidney stone disease. These findings highlight the importance of weight loss in individuals with recurrent kidney stones and suggest that therapies targeting adipose depots may affect calcium homeostasis and contribute to prevention of kidney stone disease., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Nephrology.)

Background: Atrial fibrillation (AF) has a higher prevalence in men than in women and is associated with measures of adiposity and lean mass (LM). However, it remains uncertain whether the risks of AF associated with these measures vary by sex., Methods: Among 477 904 UK Biobank participants aged 40-69 without prior AF, 23 134 incident AF cases were identified (14 400 men, 8734 women; median follow-up 11.1 years). Cox proportional hazards models were used to estimate the covariate adjusted hazard ratios (HRs) describing the association of AF with weight, measures of adiposity [fat mass (FM), waist circumference (WC)] and LM, and their independent relevance, by sex., Results: Weight and WC were independently associated with risk of AF [HR: 1.25 (1.23-1.27) per 10 kg, HR: 1.11 (1.09-1.14) per 10 cm, respectively], with comparable effects in both sexes. The association with weight was principally driven by LM, which, per 5 kg, conferred double the risk of AF compared with FM when mutually adjusted [HR: 1.20 (1.19-1.21), HR: 1.10 (1.09-1.11), respectively]; however, the effect of LM was weaker in men than in women (p-interaction = 4.3 x 10-9). Comparing the relative effects of LM, FM and WC identified different patterns within each sex; LM was the strongest predictor for both, whereas WC was stronger than FM in men but not in women., Conclusions: LM and FM (as constituents of weight) and WC are risk factors for AF. However, the independent relevance of general adiposity for AF was more limited in men than in women. The relevance of both WC and LM suggests a potentially important role for visceral adiposity and muscle mass in AF development., (© The Author(s) 2021. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Background: China has high stroke rates despite the population being relatively lean. Uncertainty persists about the relevance of adiposity to risk of stroke types. We aimed to assess the associations of adiposity with incidence of stroke types and effect mediation by blood pressure in Chinese men and women., Methods: The China Kadoorie Biobank enrolled 512 891 adults aged 30-79 years from ten areas (five urban and five rural) during 2004-08. During a median 9 years (IQR 8-10) of follow-up, 32 448 strokes (about 90% confirmed by neuroimaging) were recorded among 489 301 participants without previous cardiovascular disease. Cox regression analysis was used to produce adjusted hazard ratios (HRs) for ischaemic stroke (n=25 210) and intracerebral haemorrhage (n=5380) associated with adiposity., Findings: Mean baseline body-mass index (BMI) was 23·6 kg/m 2 (SD 3·2), and 331 723 (67·8%) participants had a BMI of less than 25 kg/m 2 . Throughout the range examined (mean 17·1 kg/m 2 [SD 0·9] to 31·7 kg/m 2 [2·0]), each 5 kg/m 2 higher BMI was associated with 8·3 mm Hg (SE 0·04) higher systolic blood pressure. BMI was positively associated with ischaemic stroke, with an HR of 1·30 (95% CI 1·28-1·33 per 5 kg/m 2 higher BMI), which was generally consistent with that predicted by equivalent differences in systolic blood pressure (1·25 [1·24-1·26]). The HR for intracerebral haemorrhage (1·11 [1·07-1·16] per 5 kg/m 2 higher BMI) was less extreme, and much weaker than that predicted by the corresponding difference in systolic blood pressure (1·48 [1·46-1·50]). Other adiposity measures showed similar associations with stroke types. After adjustment for usual systolic blood pressure, the positive associations with ischaemic stroke were attenuated (1·05 [1·03-1·07] per 5 kg/m 2 higher BMI); for intracerebral haemorrhage, they were reversed (0·73 [0·70-0·77]). High adiposity (BMI >23 kg/m 2 ) accounted for 14·7% of total stroke (16·5% of ischaemic stroke and 6·7% of intracerebral haemorrhage)., Interpretation: In Chinese adults, adiposity was strongly positively associated with ischaemic stroke, chiefly through its effect on blood pressure. For intracerebral haemorrhage, leanness, either per se or through some other factor (or factors), might increase risk, offsetting the protective effects of lower blood pressure., Funding: UK Wellcome Trust, UK Medical Research Council, British Heart Foundation, Cancer Research UK, Kadoorie Charitable Foundation, Chinese Ministry of Science and Technology, Chinese National Natural Science Foundation., (Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

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]