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Aims: To develop and externally validate the LIFE‐T1D model for the estimation of lifetime and 10‐year risk of cardiovascular disease (CVD) in individuals with type 1 diabetes. Materials and Methods: A sex‐specific competing risk‐adjusted Cox proportional hazards model was derived in individuals with type 1 diabetes without prior CVD from the Swedish National Diabetes Register (NDR), using age as the time axis. Predictors included age at diabetes onset, smoking status, body mass index, systolic blood pressure, glycated haemoglobin level, estimated glomerular filtration rate, non‐high‐density lipoprotein cholesterol, albuminuria and retinopathy. The model was externally validated in the Danish Funen Diabetes Database (FDDB) and the UK Biobank. Results: During a median follow‐up of 11.8 years (interquartile interval 6.1–17.1 years), 4608 CVD events and 1316 non‐CVD deaths were observed in the NDR (n = 39 756). The internal validation c‐statistic was 0.85 (95% confidence interval [CI] 0.84–0.85) and the external validation c‐statistics were 0.77 (95% CI 0.74–0.81) for the FDDB (n = 2709) and 0.73 (95% CI 0.70–0.77) for the UK Biobank (n = 1022). Predicted risks were consistent with the observed incidence in the derivation and both validation cohorts. Conclusions: The LIFE‐T1D model can estimate lifetime risk of CVD and CVD‐free life expectancy in individuals with type 1 diabetes without previous CVD. This model can facilitate individualized CVD prevention among individuals with type 1 diabetes. Validation in additional cohorts will improve future clinical implementation. [ABSTRACT FROM AUTHOR]

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]

Background: Women with peripheral artery disease (PAD) often have atypical symptoms, late hospital presentations, and worse prognosis. Risk factor identification and management are important. We assessed sex differences in associations of risk factors with PAD. Methods: 500,207 UK Biobank participants (54.5% women, mean age 56.5 years) without prior hospitalisation of PAD at baseline were included. Examined risk factors included blood pressure, smoking, diabetes, lipids, adiposity, history of stroke or myocardial infarction (MI), socioeconomic status, kidney function, C-reactive protein, and alcohol consumption. Poisson and Cox regressions were used to estimate sex-specific incidence of PAD hospitalisation or death, hazard ratios (HRs), and women-to-men ratios of HRs (RHR) with confidence intervals (CIs). Results: Over a median of 12.6 years, 2658 women and 5002 men had a documented PAD. Age-adjusted incidence rates were higher in men. Most risk factors were associated with a higher risk of PAD in both sexes. Compared with men, women who were smokers or had a history of stroke or MI had a greater excess risk of PAD (relative to those who never smoked or had no history of stroke or MI): RHR 1.18 (95%CI 1.04, 1.34), 1.26 (1.02, 1.55), and 1.50 (1.25, 1.81), respectively. Higher high-density lipoprotein cholesterol (HDL-C) was more strongly associated with a lower risk of PAD in women than men, RHR 0.81 (0.68, 0.96). Compared to HDL-C at 40 to 60 mg/dL, the lowest level of HDL-C (≤40 mg/dL) was related to greater excess risk in women, RHR 1.20 (1.02, 1.41), whereas the highest level of HDL-C (>80 mg/dL) was associated with lower risk of PAD in women, but higher risk in men, RHR 0.50 (0.38, 0.65). Conclusions: While the incidence of PAD was higher in men, smoking and a history of stroke or MI were more strongly associated with a higher risk of PAD in women than men. HDL-C was more strongly associated with a lower risk of PAD in women than men. [ABSTRACT FROM AUTHOR]

Objectives: There is conflicting evidence around the role of sex hormones with cardiovascular outcomes. The aim of this study was to examine the association of sex hormones with the risk of myocardial infarction (MI) in pre- and post-menopausal women, and men in the UK Biobank. Methods: The UK Biobank is a prospective population-based cohort study, that recruited over 500,000 (aged 40–69 years) women and men between 2006 and 2010. Sex specific cox regression models, estimating hazard ratios (HRs) and women to men ratio of HRs (RHR) with respective 95% confidence intervals (CI), were used to model the association of sex hormones [oestrogen, testosterone, oestrogen: testosterone (O/T) ratio, sex hormone–binding globulin (SHBG) and the free androgen index (FAI)], measured at study baseline, with incident MI for women and men. Results: Data were from 479,797 participants [264,282 (55.1%) women] without a history of MI at study baseline. Over 12.5 years of follow-up, there were 4,908 MI events in women and 10,517 in men. Neither oestrogen nor testosterone were associated with MI in women and men after multiple adjustment. For men, but not women, a unit higher log-transformed O/T ratio was associated with a lower risk of MI 0.79 (0.65, 0.95) after adjustment for traditional CVD risk factors. The corresponding women to men RHR (95% CI) was 1.24 (0.99, 1.56). Higher SHBG (per unit) was also associated with a lower risk of MI in men 0.94 (0.89, 0.99), and not in women 1.02 (0.95, 1.09) after multiple adjustment, the corresponding women to men RHR (95% CI) was 1.09 (1.00, 1.18). Higher FAI was associated with a higher risk of MI in men 1.09 (1.02, 1.15), though not in women 0.97 (0.92, 1.02), the corresponding women to men RHR was 0.89 (0.82, 0.97). Finally, there were differential effects in the association of SHBG and FAI between pre- and post-menopausal women. Conclusions: A higher O/T ratio was associated with a lower risk of MI, and a higher FAI with a higher risk of MI after adjustment for CVD risk factors in men, but not in women. Thus, hormone ratios, rather than each alone, may play an important role in modulating the effect of MI. Plain Language Summary: There are conflicting findings surrounding the association of sex hormones and myocardial infarction (MI) (heart disease). In particular, high oestradiol levels in women are often thought to be protective and explain why the rates of heart disease are lower in women than men. For men, those with low levels of testosterone are often thought to be more prone to develop heart disease in their lifetimes. Our study presents a comprehensive analysis of the association of sex hormones (in isolation and also together via their ratios), in women and men using the large-scale UK Biobank. We found that neither oestrogen nor testosterone alone were associated with heart disease in women and men after accounting for cardiovascular risk factors, but the ratio of testosterone and oestrogen was associated with a lower risk of heart disease in men, though not in women. We also saw the association of sex hormone–binding globulin (SHBG), and free androgen index (FAI) (calculated by the ratio of total testosterone level to SHBG) with heart disease was different between women and men, and between pre- and post-menopausal women. This paper highlights the complex interplay between sex hormones with heart disease in the presence of age and cardiovascular risk factors. In particular the balance (ratio) of sex hormones maybe more important, rather than each in isolation, when exploring their association with heart disease. Highlights: Neither oestrogen nor testosterone were associated with MI in women and men after multiple adjustment. For men, but not women, higher oestrogen/testosterone ratio was associated with a lower risk of MI after adjustment for traditional CVD risk factors. Higher SHBG was associated with a lower risk of MI in men, but not women overall. Higher FAI was associated with a higher risk of MI in men but not women overall. There were differential effects in SHBG and FAI between pre- and post-menopausal women. [ABSTRACT FROM AUTHOR]

Objective: To improve classification of movement behaviours in free-living accelerometer data using machine-learning methods, and to investigate the association between machine-learned movement behaviours and risk of incident cardiovascular disease (CVD) in adults.Methods: Using free-living data from 152 participants, we developed a machine-learning model to classify movement behaviours (moderate-to-vigorous physical activity behaviours (MVPA), light physical activity behaviours, sedentary behaviour, sleep) in wrist-worn accelerometer data. Participants in UK Biobank, a prospective cohort, were asked to wear an accelerometer for 7 days, and we applied our machine-learning model to classify their movement behaviours. Using compositional data analysis Cox regression, we investigated how reallocating time between movement behaviours was associated with CVD incidence.Results: In leave-one-participant-out analysis, our machine-learning method classified free-living movement behaviours with mean accuracy 88% (95% CI 87% to 89%) and Cohen's kappa 0.80 (95% CI 0.79 to 0.82). Among 87 498 UK Biobank participants, there were 4105 incident CVD events. Reallocating time from any behaviour to MVPA, or reallocating time from sedentary behaviour to any behaviour, was associated with lower CVD risk. For an average individual, reallocating 20 min/day to MVPA from all other behaviours proportionally was associated with 9% (95% CI 7% to 10%) lower risk, while reallocating 1 hour/day to sedentary behaviour from all other behaviours proportionally was associated with 5% (95% CI 3% to 7%) higher risk.Conclusion: Machine-learning methods classified movement behaviours accurately in free-living accelerometer data. Reallocating time from other behaviours to MVPA, and from sedentary behaviour to other behaviours, was associated with lower risk of incident CVD, and should be promoted by interventions and guidelines. [ABSTRACT FROM AUTHOR]

Background: Increased total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and decreased high-density lipoprotein cholesterol (HDL-C) concentrations, are established risk factors for cardiovascular morbidity and mortality; but their impact on the risk of advanced chronic kidney disease (CKD) is unclear. This study evaluates the association between the different lipid profiles and the onset of advanced CKD using a general population sample.Methods: This observational study used records of 911,360 individuals from the English Clinical Practice Research Datalink (from 2000 to 2014), linked to coded hospital discharges and mortality registrations. Cox models were used to examine the independent association between the equal quarters of TC, TG, LDL-C, and HDL-C and the risk of advanced CKD, after adjustment for sex and age, and potential effect mediators.Results: During a median follow-up of 7.5 years, 11,825 individuals developed CKD stages 4-5. After adjustment for sex and age, the hazard ratios (HRs) and confidence intervals (CIs) for CKD stages 4-5 comparing the 4th vs. 1st quarters of TG and 1st vs. 4th quarters of HDL-C were 2.69 (95% CI, 2.49-2.90) and 2.61 (95% CI, 2.42-2.80), respectively. Additional adjustment for potential effect mediators reduced the HRs to 1.28 (95% CI, 1.15-1.43), and 1.27 (95% CI, 1.14-1.41), respectively. There was no evidence of fully adjusted associations with CKD stages 4-5 for levels of either TC or LDL-C.Conclusions: Elevated TG and reduced HDL-C levels are independently associated with the onset of advanced CKD. Future studies, such as in basic science and randomized trials, are needed to understand whether associations between TG and HDL-C and the development of CKD are causal. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the association between individual and combinations of macronutrients with premature death, CVD and dementia. Sex differences were investigated. Data were utilised from a prospective cohort of 120 963 individuals (57 % women) within the UK Biobank, who completed ≥ two 24-h diet recalls. The associations of macronutrients, as percentages of total energy intake, with outcomes were investigated. Combinations of macronutrients were defined using k-means cluster analysis, with clusters explored in association with outcomes. There was a higher risk of death with high carbohydrate intake (hazard ratios (HR), 95 % CI upper v. lowest third 1·13 (1·03, 1·23)), yet a lower risk with higher intakes of protein (upper v. lowest third 0·82 (0·76, 0·89)). There was a lower risk of CVD with moderate intakes (middle v. lowest third) of energy and protein (sub distribution HR (SHR), 0·87 (0·79, 0·97) and 0·87 (0·79, 0·96), respectively). There was a lower risk of dementia with moderate energy intake (SHR 0·71 (0·52, 0·96)). Sex differences were identified. The dietary cluster characterised by low carbohydrate, low fat and high protein was associated with a lower risk of death (HR 0·84 (0·76, 0·93)) compared with the reference cluster and a lower risk of CVD for men (SHR 0·83 (0·71, 0·97)). Given that associations were evident, both as single macronutrients and for combinations with other macronutrients for death, and for CVD in men, we suggest that the biggest benefit from diet-related policy and interventions will be when combinations of macronutrients are targeted. [ABSTRACT FROM AUTHOR]

Background: Women's reproductive factors have been associated with the risk of dementia; however, these findings remain uncertain. This study aimed to examine the risk of incident all-cause dementia associated with reproductive factors in women and the number of children in both sexes and whether the associations vary by age, socioeconomic status (SES), smoking status, and body mass index (BMI) in the UK Biobank.Methods and Findings: A total of 273,240 women and 228,957 men without prevalent dementia from the UK Biobank were included in the analyses. Cox proportional hazard regressions estimated hazard ratios (HRs) for reproductive factors with incident all-cause dementia. Multiple adjusted models included age at study entry, SES, ethnicity, smoking status, systolic blood pressure, BMI, history of diabetes mellitus, total cholesterol, antihypertensive drugs, and lipid-lowering drugs. Over a median of 11.8 years follow-up, 1,866 dementia cases were recorded in women and 2,202 in men. Multiple adjusted HRs ((95% confidence intervals (CIs)), p-value) for dementia were 1.20 (1.08, 1.34) (p = 0.016) for menarche <12 years and 1.19 (1.07, 1.34) (p = 0.024) for menarche >14 years compared to 13 years; 0.85 (0.74, 0.98) (p = 0.026) for ever been pregnant; 1.43 (1.26, 1.62) (p < 0.001) for age at first live birth <21 compared to 25 to 26 years; 0.82 (0.71, 0.94) (p = 0.006) for each abortion; 1.32 (1.15, 1.51) (p = 0.008) for natural menopause at <47 compared to 50 years; 1.12 (1.01, 1.25) (p = 0.039) for hysterectomy; 2.35 (1.06, 5.23) (p = 0.037) for hysterectomy with previous oophorectomy; and 0.80 (0.72, 0.88) (p < 0.001) for oral contraceptive pills use. The U-shaped associations between the number of children and the risk of dementia were similar for both sexes: Compared with those with 2 children, for those without children, the multiple adjusted HR ((95% CIs), p-value) was 1.18 (1.04, 1.33) (p = 0.027) for women and 1.10 (0.98, 1.23) (p = 0.164) for men, and the women-to-men ratio of HRs was 1.09 (0.92, 1.28) (p = 0.403); for those with 4 or more children, the HR was 1.14 (0.98, 1.33) (p = 0.132) for women and 1.26 (1.10, 1.45) (p = 0.003) for men, and the women-to-men ratio of HRs was 0.93 (0.76, 1.14) (p = 0.530). There was evidence that hysterectomy (HR, 1.31 (1.09, 1.59), p = 0.013) and oophorectomy (HR, 1.39 (1.08, 1.78), p = 0.002) were associated with a higher risk of dementia among women of relatively lower SES only. Limitations of the study include potential residual confounding and self-reported measures of reproductive factors, as well as the limited representativeness of the UK Biobank population.Conclusions: In this study, we observed that some reproductive events related to shorter cumulative endogenous estrogen exposure in women were associated with higher dementia risk, and there was a similar association between the number of children and dementia risk between women and men. [ABSTRACT FROM AUTHOR]

Background: Sex differences in cardiometabolic disease risk are commonly observed across the life course but are poorly understood and may be due to different associations of adiposity with cardiometabolic risk in females and males. We examined whether adiposity is differently associated with cardiometabolic trait levels in females and males at 3 different life stages.Methods and Findings: Data were from 2 generations (offspring, Generation 1 [G1] born in 1991/1992 and their parents, Generation 0 [G0]) of a United Kingdom population-based birth cohort study, the Avon Longitudinal Study of Parents and Children (ALSPAC). Follow-up continues on the cohort; data up to 25 y after recruitment to the study are included in this analysis. Body mass index (BMI) and total fat mass from dual-energy X-ray absorptiometry (DXA) were measured at mean age 9 y, 15 y, and 18 y in G1. Waist circumference was measured at 9 y and 15 y in G1. Concentrations of 148 cardiometabolic traits quantified using nuclear magnetic resonance spectroscopy were measured at 15 y, 18 y, and 25 y in G1. In G0, all 3 adiposity measures and the same 148 traits were available at 50 y. Using linear regression models, sex-specific associations of adiposity measures at each time point (9 y, 15 y, and 18 y) with cardiometabolic traits 3 to 6 y later were examined in G1. In G0, sex-specific associations of adiposity measures and cardiometabolic traits were examined cross-sectionally at 50 y. A total of 3,081 G1 and 4,887 G0 participants contributed to analyses. BMI was more strongly associated with key atherogenic traits in males compared with females at younger ages (15 y to 25 y), and associations were more similar between the sexes or stronger in females at 50 y, particularly for apolipoprotein B-containing lipoprotein particles and lipid concentrations. For example, a 1 standard deviation (SD) (3.8 kg/m2) higher BMI at 18 y was associated with 0.36 SD (95% confidence interval [CI] = 0.20, 0.52) higher concentrations of extremely large very-low-density lipoprotein (VLDL) particles at 25 y in males compared with 0.15 SD (95% CI = 0.09, 0.21) in females, P value for sex difference = 0.02. By contrast, at 50 y, a 1 SD (4.8 kg/m2) higher BMI was associated with 0.33 SD (95% CI = 0.25, 0.42) and 0.30 SD (95% CI = 0.26, 0.33) higher concentrations of extremely large VLDL particles in males and females, respectively, P value for sex difference = 0.42. Sex-specific associations of DXA-measured fat mass and waist circumference with cardiometabolic traits were similar to findings for BMI and cardiometabolic traits at each age. The main limitation of this work is its observational nature, and replication in independent cohorts using methods that can infer causality is required.Conclusions: The results of this study suggest that associations of adiposity with adverse cardiometabolic risk begin earlier in the life course among males compared with females and are stronger until midlife, particularly for key atherogenic lipids. Adolescent and young adult males may therefore be high priority targets for obesity prevention efforts. [ABSTRACT FROM AUTHOR]

Background: It is commonly assumed that high oestradiol levels in women are cardioprotective. We assessed the association between oestradiol and the risk of incident myocardial infarction (MI) in women.Methods: We used data from 263 295 female UK Biobank participants [mean age 56.2; standard deviation (SD) 8.0 years] without previous cardiovascular disease (CVD). Associations of oestradiol with age and other cardiovascular risk factors were assessed. Cox proportional hazards models estimated crude, ag- and multiple-adjusted hazard ratios (HR) for MI associated with oestradiol levels.Results: After a mean follow-up of 9 years, 2206 incident cases of MI had been recorded, including 230 events among the 57 204 women (mean age 48) with detectable oestradiol levels. In the unadjusted analyses, a unit higher in log-transformed oestradiol was associated with an HR [95% confidence interval (CI) for MI of 0.73 (0.58; 0.92)]. After adjusting for age, this HR became 0.94 (0.75; 1.17), and after further adjusting for classical CVD risk factors, it was 1.05 (0.83; 1.31. Results were similar in subgroup analyses defined by age, menopausal status, socioeconomic status, contraceptive pill use and the use of hormone replacement therapy. The multivariable-adjusted HR for the 171 431 women (mean age 59) with undetectable levels of oestradiol, compared with those with detectable levels, was 0.97 (0.92; 1.02).Conclusions: Higher levels of oestradiol were not associated with a decreased risk of MI. The presumed cardioprotective effects of oestradiol seem to be largely confounded by age and further confounded by other cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

Background: Sex differences in major cardiovascular risk factors for incident (fatal or non-fatal) all-cause dementia were assessed in the UK Biobank. The effects of these risk factors on all-cause dementia were explored by age and socioeconomic status (SES).Methods: Cox proportional hazards models were used to estimate hazard ratios (HRs) and women-to-men ratio of HRs (RHR) with 95% confidence intervals (CIs) for systolic blood pressure (SBP) and diastolic blood pressure (DBP), smoking, diabetes, adiposity, stroke, SES and lipids with dementia. Poisson regression was used to estimate the sex-specific incidence rate of dementia for these risk factors.Results: 502,226 individuals in midlife (54.4% women, mean age 56.5 years) with no prevalent dementia were included in the analyses. Over 11.8 years (median), 4068 participants (45.9% women) developed dementia. The crude incidence rates were 5.88 [95% CI 5.62-6.16] for women and 8.42 [8.07-8.78] for men, per 10,000 person-years. Sex was associated with the risk of dementia, where the risk was lower in women than men (HR = 0.83 [0.77-0.89]). Current smoking, diabetes, high adiposity, prior stroke and low SES were associated with a greater risk of dementia, similarly in women and men. The relationship between blood pressure (BP) and dementia was U-shaped in men but had a dose-response relationship in women: the HR for SBP per 20 mmHg was 1.08 [1.02-1.13] in women and 0.98 [0.93-1.03] in men. This sex difference was not affected by the use of antihypertensive medication at baseline. The sex difference in the effect of raised BP was consistent for dementia subtypes (vascular dementia and Alzheimer's disease).Conclusions: Several mid-life cardiovascular risk factors were associated with dementia similarly in women and men, but not raised BP. Future bespoke BP-lowering trials are necessary to understand its role in restricting cognitive decline and to clarify any sex difference. [ABSTRACT FROM AUTHOR]

Objective: Observational studies have demonstrated that type 2 diabetes is a stronger risk factor for coronary heart disease (CHD) in women compared with men. However, it is not clear whether this reflects a sex differential in the causal effect of diabetes on CHD risk or results from sex-specific residual confounding.Research Design and Methods: Using 270 single nucleotide polymorphisms (SNPs) for type 2 diabetes identified in a type 2 diabetes genome-wide association study, we performed a sex-stratified Mendelian randomization (MR) study of type 2 diabetes and CHD using individual participant data in UK Biobank (251,420 women and 212,049 men). Weighted median, MR-Egger, MR-pleiotropy residual sum and outlier, and radial MR from summary-level analyses were used for pleiotropy assessment.Results: MR analyses showed that genetic risk of type 2 diabetes increased the odds of CHD for women (odds ratio 1.13 [95% CI 1.08-1.18] per 1-log unit increase in odds of type 2 diabetes) and men (1.21 [1.17-1.26] per 1-log unit increase in odds of type 2 diabetes). Sensitivity analyses showed some evidence of directional pleiotropy; however, results were similar after correction for outlier SNPs.Conclusions: This MR analysis supports a causal effect of genetic liability to type 2 diabetes on risk of CHD that is not stronger for women than men. Assuming a lack of bias, these findings suggest that the prevention and management of type 2 diabetes for CHD risk reduction is of equal priority in both sexes. [ABSTRACT FROM AUTHOR]

Background: Higher levels of physical activity (PA) are associated with a lower risk of cardiovascular disease (CVD). However, uncertainty exists on whether the inverse relationship between PA and incidence of CVD is greater at the highest levels of PA. Past studies have mostly relied on self-reported evidence from questionnaire-based PA, which is crude and cannot capture all PA undertaken. We investigated the association between accelerometer-measured moderate, vigorous, and total PA and incident CVD.Methods and Findings: We obtained accelerometer-measured moderate-intensity and vigorous-intensity physical activities and total volume of PA, over a 7-day period in 2013-2015, for 90,211 participants without prior or concurrent CVD in the UK Biobank cohort. Participants in the lowest category of total PA smoked more, had higher body mass index and C-reactive protein, and were diagnosed with hypertension. PA was associated with 3,617 incident CVD cases during 440,004 person-years of follow-up (median (interquartile range [IQR]): 5.2 (1.2) years) using Cox regression models. We found a linear dose-response relationship for PA, whether measured as moderate-intensity, vigorous-intensity, or as total volume, with risk of incident of CVD. Hazard ratios (HRs) and 95% confidence intervals for increasing quarters of the PA distribution relative to the lowest fourth were for moderate-intensity PA: 0.71 (0.65, 0.77), 0.59 (0.54, 0.65), and 0.46 (0.41, 0.51); for vigorous-intensity PA: 0.70 (0.64, 0.77), 0.54 (0.49,0.59), and 0.41 (0.37,0.46); and for total volume of PA: 0.73 (0.67, 0.79), 0.63 (0.57, 0.69), and 0.47 (0.43, 0.52). We took account of potential confounders but unmeasured confounding remains a possibility, and while removal of early deaths did not affect the estimated HRs, we cannot completely dismiss the likelihood that reverse causality has contributed to the findings. Another possible limitation of this work is the quantification of PA intensity-levels based on methods validated in relatively small studies.Conclusions: In this study, we found no evidence of a threshold for the inverse association between objectively measured moderate, vigorous, and total PA with CVD. Our findings suggest that PA is not only associated with lower risk for of CVD, but the greatest benefit is seen for those who are active at the highest level. [ABSTRACT FROM AUTHOR]

Obesity is associated with severe COVID‐19 outcomes, yet, it is unclear whether the risk of COVID‐19 mortality associated with obesity is similar between the sexes. We used data from the UK Biobank to assess the risk of COVID‐19 mortality associated with various anthropometric measures in women and men. To put these results in context, we also compared these estimates with those for mortality from influenza/pneumonia and coronary heart disease (CHD). The analyses included 502 493 individuals (54% women), of whom 410 (36% women) died from COVID‐19, 549 (36% women) died from influenza/pneumonia and 3355 (19% women) died from CHD. A higher body mass index (BMI), waist circumference, waist‐to‐hip ratio and waist‐to‐height ratio were each associated with a greater risk of death from COVID‐19, influenza/pneumonia and CHD in both sexes, with the exception of the association between higher BMI and the risk of influenza/pneumonia death in men. A higher BMI was associated with a stronger risk of COVID‐19 mortality in women than men; the women‐to‐men ratio of hazard ratios was 1.20 (95% confidence interval 1.00; 1.43). This study demonstrates the role of obesity in COVID‐19 mortality and shows that the relative effects of a higher BMI on COVID‐19 mortality may be stronger in women than men. [ABSTRACT FROM AUTHOR]

Objective: Diabetes has shown to be a stronger risk factor for myocardial infarction (MI) in women than men. Whether sex differences exist across the glycemic spectrum is unknown. We investigated sex differences in the associations of diabetes status and glycated hemoglobin (HbA1c) with the risk of MI.Research Design and Methods: Data were used from 471,399 (56% women) individuals without cardiovascular disease (CVD) included in the UK Biobank. Sex-specific incidence rates were calculated by diabetes status and across levels of HbA1c using Poisson regression. Cox proportional hazards analyses estimated sex-specific hazard ratios (HRs) and women-to-men ratios by diabetes status and HbA1c for MI during a mean follow-up of 9 years.Results: Women had lower incidence rates of MI than men, regardless of diabetes status or HbA1c level. Compared with individuals without diabetes, prediabetes, undiagnosed diabetes, and previously diagnosed diabetes were associated with an increased risk of MI in both sexes. Previously diagnosed diabetes was more strongly associated with MI in women (HR 2.33 [95% CI 1.96; 2.78]) than men (1.81 [1.63; 2.02]), with a women-to-men ratio of HRs of 1.29 (1.05; 1.58). Each 1% higher HbA1c, independent of diabetes status, was associated with an 18% greater risk of MI in both women and men.Conclusions: Although the incidence of MI was higher in men than women, the presence of diabetes is associated with a greater excess relative risk of MI in women. However, each 1% higher HbA1c was associated with an 18% greater risk of MI in both women and men. [ABSTRACT FROM AUTHOR]

Background: Physical inactivity is associated with an increased risk of major chronic diseases, although uncertainty exists about which chronic diseases, themselves, might contribute to physical inactivity. The objective of this study was to compare the physical activity of those with chronic diseases to healthy individuals using an objective measure of physical activity.Methods: We conducted a cross-sectional analysis of data from 96 706 participants aged 40 years or older from the UK Biobank prospective cohort study (2006-10). Diagnoses were identified through ICD 9 and 10 coding within hospital admission records and a cancer registry linked to UK Biobank participants. We extracted summary physical activity information from participants who wore a wrist-worn triaxial accelerometer for 7 days. Statistical analyses included computation of adjusted geometric means and means using general linear models.Results: Participants with chronic disease undertook 9% or 61 minutes (95% confidence interval: 57.8-64.8) less moderate activity and 11% or 3 minutes (95% confidence interval: 2.7-3.3) less vigorous activity per week than individuals without chronic disease. Participants in every chronic-disease subgroup undertook less physical activity than those without chronic disease. Sixty-seven diagnoses within these subgroups were associated with lower moderate activity.Conclusions: The cross-sectional association of physical activity with chronic disease is broad. Given the substantial health benefits of being physically active, clinicians and policymakers should be aware that their patients with any chronic disease are at greater health risk from other diseases than anticipated because of their physical inactivity. [ABSTRACT FROM AUTHOR]

Reference 1 Weldegiorgis M, Woodward M. Elevated triglycerides and reduced high-density lipoprotein cholesterol are independently associated with the onset of advanced chronic kidney disease: a cohort study of 911,360 individuals from the United Kingdom. B Correction: BMC Nephrol 23, 312 (2022) b B https://doi.org/10.1186/s12882-022-02932-2 b Following publication of the original article [[1]], the authors informed us that the confidence interval is missing in B Table 2, Column 5, row Q2 b . [Extracted from the article]

Aims: Diabetes has been associated with a greater excess risk of cardiovascular disease (CVD) in women than men. We investigated whether there are also sex differences in the association of diabetes duration and the risk of CVD.Methods: Data were used from 18,961 (40% women) individuals with type 2 diabetes, without a history of CVD, in the UK Biobank. Sex-specific incidence rates were calculated by diabetes duration. Cox proportional hazards analyses estimated multiple-adjusted sex-specific hazard ratios (HR) and women-to-men ratio of HRs (RHR).Results: Over a median follow-up of 11 years, 1,506 (29% women) CVD events were documented. Compared with men, women had lower multiple-adjusted incidence rates of CVD per 10,000 person-years for all categories of diabetes duration. Duration of diabetes was associated with an increased risk of CVD in both sexes. A 5-year increase in diabetes duration was associated with an approximately similar excess risk of about 20% for each of the three endpoints, in both sexes.Conclusions/interpretation: The increased risk of CVD associated with longer duration of diabetes is similar in women and men, and thus cannot explain the higher excess risk from diabetes in women in this study population. [ABSTRACT FROM AUTHOR]

In this paper, data obtained between 1984 and 1993 from 11,629 men and women as part of the Scottish Heart Health Study (Scotland, United Kingdom) were used to investigate the relation between antioxidant vitamin and fiber intakes and both incident coronary heart disease (CHD) (649 events) and all-causes mortality (591 deaths). All age-adjusted mean intakes tended to be higher in the group that experiecned no event. For men, increased fiber intake was associated with decreased risk of CHD even after adjustment for a host of other major coronary risk factors; hazard ratios relative to the lowest quarter were 0.68, 0.70, and 0.64 by increasing quarter. This relation was alos observed for mortality (hazard ratios of 0.62, 0.66, and 0.62). Evidence was found that higher intakes of the antioxidants were also beneficial, although the associations were weaker. For women, fiber was the only obviously influential dietary factor, with hazard ratios of 0.94, 0.60, and 0.56 for CHD and 1.25, 0.82, and 0.65 for mortality. These results suggest that the current public health drive to increase the consumption of foods rich in antioxidant vitamins and (particularly) fiber will impact on both CHD risk and the general health of the population. Am J Epidemiol 1999; 150:1073-80. [ABSTRACT FROM PUBLISHER]

Compares risk factors for coronary heart disease from a random sampling of Scottish men and women aged 40-59. Prevalence of the illness among house renters; Hazard from diabetes mellitus in both sexes; Risks of cigarette smoking and physical inactivity at work.

In the article, the author discusses the full eventual hazards of prolonged smoking, as well as the benefits of smoking stoppage in women. They cite the Million Women Study conducted to over one million women in Great Britain., which showed that the annual mortality rate in women smokers was triple that of non-smokers. They compare the study results with that of Richard Doll in the 1900s.

The article discusses research which investigated vascular disease risk in patients with peripheral arterial disease (PAD). Topics explored include the link between raised blood pressure and higher PAD risk, the clinical characteristics of patients that participated in the study such as age, body mass index, and smoking status, and the prevalence of vascular events such as chronic kidney disease and ischaemic heart disease in PAD patients.

Background: Low-risk limits recommended for alcohol consumption vary substantially across different national guidelines. To define thresholds associated with lowest risk for all-cause mortality and cardiovascular disease, we studied individual-participant data from 599 912 current drinkers without previous cardiovascular disease.Methods: We did a combined analysis of individual-participant data from three large-scale data sources in 19 high-income countries (the Emerging Risk Factors Collaboration, EPIC-CVD, and the UK Biobank). We characterised dose-response associations and calculated hazard ratios (HRs) per 100 g per week of alcohol (12·5 units per week) across 83 prospective studies, adjusting at least for study or centre, age, sex, smoking, and diabetes. To be eligible for the analysis, participants had to have information recorded about their alcohol consumption amount and status (ie, non-drinker vs current drinker), plus age, sex, history of diabetes and smoking status, at least 1 year of follow-up after baseline, and no baseline history of cardiovascular disease. The main analyses focused on current drinkers, whose baseline alcohol consumption was categorised into eight predefined groups according to the amount in grams consumed per week. We assessed alcohol consumption in relation to all-cause mortality, total cardiovascular disease, and several cardiovascular disease subtypes. We corrected HRs for estimated long-term variability in alcohol consumption using 152 640 serial alcohol assessments obtained some years apart (median interval 5·6 years [5th-95th percentile 1·04-13·5]) from 71 011 participants from 37 studies.Findings: In the 599 912 current drinkers included in the analysis, we recorded 40 310 deaths and 39 018 incident cardiovascular disease events during 5·4 million person-years of follow-up. For all-cause mortality, we recorded a positive and curvilinear association with the level of alcohol consumption, with the minimum mortality risk around or below 100 g per week. Alcohol consumption was roughly linearly associated with a higher risk of stroke (HR per 100 g per week higher consumption 1·14, 95% CI, 1·10-1·17), coronary disease excluding myocardial infarction (1·06, 1·00-1·11), heart failure (1·09, 1·03-1·15), fatal hypertensive disease (1·24, 1·15-1·33); and fatal aortic aneurysm (1·15, 1·03-1·28). By contrast, increased alcohol consumption was log-linearly associated with a lower risk of myocardial infarction (HR 0·94, 0·91-0·97). In comparison to those who reported drinking >0-≤100 g per week, those who reported drinking >100-≤200 g per week, >200-≤350 g per week, or >350 g per week had lower life expectancy at age 40 years of approximately 6 months, 1-2 years, or 4-5 years, respectively.Interpretation: In current drinkers of alcohol in high-income countries, the threshold for lowest risk of all-cause mortality was about 100 g/week. For cardiovascular disease subtypes other than myocardial infarction, there were no clear risk thresholds below which lower alcohol consumption stopped being associated with lower disease risk. These data support limits for alcohol consumption that are lower than those recommended in most current guidelines.Funding: UK Medical Research Council, British Heart Foundation, National Institute for Health Research, European Union Framework 7, and European Research Council. [ABSTRACT FROM AUTHOR]

Background Percutaneous coronary intervention (PCI) is increasingly being performed at centers with offsite surgical support. Strong guideline endorsement of this practice has been lacking, in part because outcome data are limited to modest-size populations with short-term follow-up. Objectives The aim of this study was to compare the outcomes of PCI performed at centers with and without surgical support in the United Kingdom between 2006 and 2012. Methods A retrospective analysis was performed of centrally tracked outcomes from index PCI procedures entered in the British Cardiovascular Intervention Society database between 2006 and 2012, stratified according to whether procedures were performed at centers with onsite or offsite surgical support. The primary endpoint was 30-day all-cause mortality, with secondary endpoints of mortality at 1 and 5 years. Results Outcomes at a median of 3.4 years follow-up were available for 384,013 patients, of whom 31% (n = 119,096) were treated at offsite surgical centers. In an unadjusted analysis, crude mortality rates were lower in patients treated at centers with offsite versus onsite surgical coverage (2.0% vs. 2.2%; p < 0.001). On multivariate adjustment, there were no between-group differences in survival between the naive and imputed populations at 30 days (naive population hazard ratio [HR]: 0.87; 95% confidence interval [CI]: 0.71 to 1.06; p = 0.16; imputed population HR: 0.99; 95% CI: 0.89 to 1.09; p = 0.82), 1 year (naive population HR: 0.92; 95% CI: 0.79 to 1.07; p = 0.26; imputed population HR: 0.99; 95% CI: 0.92 to 1.06; p = 0.78), or 5 years (naive population HR: 0.92; 95% CI: 0.84 to 1.01; p = 0.10; imputed population HR: 0.97; 95% CI: 0.92 to 1.03; p = 0.29). Results were consistent irrespective of procedural indication. No differences in mortality were seen in sensitivity analyses performed using a propensity-matched population of 74,001 patients. Conclusions PCI performed at centers without onsite surgical backup is not associated with any mortality hazard. [ABSTRACT FROM AUTHOR]

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: Abdominal aortic aneurysm (AAA) can occur in patients who are ineligible for routine ultrasound screening. A simple AAA risk score was derived and compared with current guidelines used for ultrasound screening of AAA., Methods: United Kingdom Biobank participants without previous AAA were split into a derivation cohort (n=401 820, 54.6% women, mean age 56.4 years, 95.5% White race) and validation cohort (n=83 816). Incident AAA was defined as first hospital inpatient diagnosis of AAA, death from AAA, or an AAA-related surgical procedure. A multivariable Cox model was developed in the derivation cohort into an AAA risk score that did not require blood biomarkers. To illustrate the sensitivity and specificity of the risk score for AAA, a theoretical threshold to refer patients for ultrasound at 0.25% 10-year risk was modeled. Discrimination of the risk score was compared with a model of US Preventive Services Task Force (USPSTF) AAA screening guidelines., Results: In the derivation cohort, there were 1570 (0.40%) cases of AAA over a median 11.3 years of follow-up. Components of the AAA risk score were age (stratified by smoking status), weight (stratified by smoking status), antihypertensive and cholesterol-lowering medication use, height, diastolic blood pressure, baseline cardiovascular disease, and diabetes. In the validation cohort, over 10 years of follow-up, the C-index for the model of the USPSTF guidelines was 0.705 (95% CI, 0.678-0.733). The C-index of the risk score as a continuous variable was 0.856 (95% CI, 0.837-0.878). In the validation cohort, the USPSTF model yielded sensitivity 63.9% and specificity 71.3%. At the 0.25% 10-year risk threshold, the risk score yielded sensitivity 82.1% and specificity 70.7% while also improving the net reclassification index compared with the USPSTF model +0.176 (95% CI, 0.120-0.232). A combined model, whereby risk scoring was combined with the USPSTF model, also improved prediction compared with USPSTF alone (net reclassification index +0.101 [95% CI, 0.055-0.147])., Conclusions: In an asymptomatic general population, a risk score based on patient age, height, weight, and medical history may improve identification of asymptomatic patients at risk for clinical events from AAA. Further development and validation of risk scores to detect asymptomatic AAA are needed.

Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m 2 /year or more ("Rapid3"; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m 2 at follow-up among those with eGFRcrea 60 mL/min/1.73m 2 or more at baseline ("CKDi25"; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or LARP4B. Individuals at high compared to those at low genetic risk (8-14 vs. 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function., (Copyright © 2020 International Society of Nephrology. All rights reserved.)

Background: The size of any causal contribution of central and general adiposity to CKD risk and the underlying mechanism of mediation are unknown., Methods: Data from 281,228 UK Biobank participants were used to estimate the relevance of waist-to-hip ratio and body mass index (BMI) to CKD prevalence. Conventional approaches used logistic regression. Genetic analyses used Mendelian randomization (MR) and data from 394 waist-to-hip ratio and 773 BMI-associated loci. Models assessed the role of known mediators (diabetes mellitus and BP) by adjusting for measured values (conventional analyses) or genetic associations of the selected loci (multivariable MR)., Results: Evidence of CKD was found in 18,034 (6.4%) participants. Each 0.06 higher measured waist-to-hip ratio and each 5-kg/m 2 increase in BMI were associated with 69% (odds ratio, 1.69; 95% CI, 1.64 to 1.74) and 58% (1.58; 1.55 to 1.62) higher odds of CKD, respectively. In analogous MR analyses, each 0.06-genetically-predicted higher waist-to-hip ratio was associated with a 29% (1.29; 1.20 to 1.38) increased odds of CKD, and each 5-kg/m 2 genetically-predicted higher BMI was associated with a 49% (1.49; 1.39 to 1.59) increased odds. After adjusting for diabetes and measured BP, chi-squared values for associations for waist-to-hip ratio and BMI fell by 56%. In contrast, mediator adjustment using multivariable MR found 83% and 69% reductions in chi-squared values for genetically-predicted waist-to-hip ratio and BMI models, respectively., Conclusions: Genetic analyses suggest that conventional associations between central and general adiposity with CKD are largely causal. However, conventional approaches underestimate mediating roles of diabetes, BP, and their correlates. Genetic approaches suggest these mediators explain most of adiposity-CKD-associated risk., (Copyright © 2021 by the American Society of Nephrology.)

Objective: To determine whether there are sex differences in the association between risk factors and incident stroke, including stroke subtypes., Methods: A total of 471,971 (56% women) UK Biobank participants without a history of cardiovascular disease were included. During 9 years of follow-up, 4,662 (44% women) cases of stroke were recorded. Cox models yielded adjusted hazard ratios (HRs) and women-to-men ratios of HRs (RHRs) for stroke associated with 7 risk factors., Results: The incidence rate per 10,000 person-years was 8.66 (8.29-9.04) in women and 13.96 (13.44-14.50) in men for any stroke, 6.06 (5.75-6.38) in women and 11.35 (10.88; 11.84) in men for ischemic stroke, and 1.56 (1.41-1.73) in women and 2.23 (2.02-2.45) in men for hemorrhagic stroke. The association between increases in blood pressure, body anthropometry, and lipids, diabetes, and atrial fibrillation and any stroke was similar between men and women. Hypertension, smoking, and a low socioeconomic status were associated with a greater HR of any stroke in women than men; the RHRs were 1.36 (1.26-1.47), 1.18 (1.02-1.36), and 1.17 (1.03-1.33), respectively. Diabetes was associated with a higher HR of ischemic stroke in women than men (RHR 1.25 [1.00-1.56]). Atrial fibrillation was associated with a higher HR of hemorrhagic stroke in women than men (RHR 2.80 [1.07-7.36])., Conclusion: Several risk factors are more strongly associated with the risk of any stroke or stroke subtypes in women compared with men. Despite this, the incidence of stroke remains higher among men than women., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Background: Whether measures of central adiposity are more or less strongly associated with risk of albuminuria than body mass index (BMI), and by how much diabetes/levels of glycosylated haemoglobin (HbA1c) explain or modify these associations, is uncertain., Methods: Ordinal logistic regression was used to estimate associations between values of central adiposity (waist-to-hip ratio) and, separately, general adiposity (BMI) with categories of urinary albumin-to-creatinine ratio (uACR) in 408,527 UK Biobank participants. Separate central and general adiposity-based models were initially adjusted for potential confounders and measurement error, then sequentially, models were mutually adjusted (e.g. waist-to-hip ratio adjusted for BMI, and vice versa), and finally they were adjusted for potential mediators., Results: Levels of albuminuria were generally low: 20,425 (5%) had a uACR ≥3 mg/mmol. After adjustment for confounders and measurement error, each 0.06 higher waist-to-hip ratio was associated with a 55% (95%CI 53-57%) increase in the odds of being in a higher uACR category. After adjustment for baseline BMI, this association was reduced to 32% (30-34%). Each 5 kg/m 2 higher BMI was associated with a 47% (46-49%) increase in the odds of being in a higher uACR category. Adjustment for baseline waist-to-hip ratio reduced this association to 35% (33-37%). Those with higher HbA1c were at progressively higher odds of albuminuria, but positive associations between both waist-to-hip ratio and BMI were apparent irrespective of HbA1c. Altogether, about 40% of central adiposity associations appeared to be mediated by diabetes, vascular disease and blood pressure., Conclusions: Conventional epidemiological approaches suggest that higher waist-to-hip ratio and BMI are independently positively associated with albuminuria. Adiposity-albuminuria associations appear strong among people with normal HbA1c, as well as people with pre-diabetes or diabetes.

Objectives: We aimed to investigate whether digital home monitoring with centralised specialist support for remote management of heart failure (HF) is more effective in improving medical therapy and patients' quality of life than digital home monitoring alone., Methods: In a two-armed partially blinded parallel randomised controlled trial, seven sites in the UK recruited a total of 202 high-risk patients with HF (71.3 years SD 11.1; left ventricular ejection fraction 32.9% SD 15.4). Participants in both study arms were given a tablet computer, Bluetooth-enabled blood pressure monitor and weighing scales for health monitoring. Participants randomised to intervention received additional regular feedback to support self-management and their primary care doctors received instructions on blood investigations and pharmacological treatment. The primary outcome was the use of guideline-recommended medical therapy for chronic HF and major comorbidities, measured as a composite opportunity score (total number of recommended treatment given divided by the total number of opportunities the treatment should have been given, with a score 1 indicating 100% adherence to recommendations). Co-primary outcome was change in physical score of Minnesota Living with Heart Failure questionnaire., Results: 101 patients were randomised to 'enhanced self-management' and 101 to 'supported medical management'. At the end of follow-up, the opportunity score was 0.54 (95% CI 0.46 to 0.62) in the control arm and 0.61 (95% CI 0.52 to 0.70) in the intervention arm (p=0.25). Physical well-being of participants also did not differ significantly between the groups (17.4 (12.4) mean (SD) for control arm vs 16.5 (12.1) in treatment arm; p for change=0.84)., Conclusions: Central provision of tailored specialist management in a multi-morbid HF population was feasible. However, there was no strong evidence for improvement in use of evidence-based treatment nor health-related quality of life., Trial Registration Number: ISRCTN86212709., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Several studies have investigated the effect of socioeconomic deprivation on cardiovascular disease (CVD) and diabetes; less is known about its effect on chronic kidney disease (CKD). We aimed to measure the association between deprivation, CKD Stages 4-5 and end-stage renal disease (ESRD) in a general population sample., Methods: This observational study examined 1 405 016 participants from the English Clinical Practice Research Datalink (2000-14), linked to hospital discharge data and death certification. Deprivation was assessed according to the participant's postcode. Cox models were used to estimate hazard ratios (HRs) for CKD Stages 4-5 and ESRD, adjusting for age and sex, and additionally for smoking status, body mass index, diabetes, systolic blood pressure, prior CVD and estimated glomerular filtration rate (eGFR) at baseline., Results: During 7.5 years of median follow-up, 11 490 individuals developed CKD Stages 4-5 and 1068 initiated ESRD. After adjustment for age and sex, the HRs and confidence interval (CI) comparing those in the 20% most deprived of the population to the 20% least deprived were 1.76 (95% CI 1.68-1.84) and 1.82 (95% CI 1.56-2.12) for CKD Stages 4-5 and ESRD, respectively. Further adjustment for known risk factors and eGFR substantially attenuated these HRs. Adding our results to all known cohort studies produced a pooled relative risk of 1.61 (95% CI 1.42-1.83) for ESRD, for comparisons between highest to lowest categories of deprivation., Conclusion: Socioeconomic deprivation is independently associated with an increased hazard of CKD Stages 4-5 and ESRD, but in large part may be mediated by known risk factors., (© The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: Atrial fibrillation (AF) is a stronger risk factor for cardiovascular disease in women than men. We assessed whether there are sex differences in the effects of 43 established and novel risk factors and the risk of incident AF., Methods: Data were used from the Scottish Heart Health Extended Cohort, a prospective cohort study with over 20 years of follow-up for AF incidence. Cox regression models were used to obtain the adjusted sex-specific HRs and 95% CIs, and the women-to-men ratio of HRs (RHRs), of incident AF associated with personal characteristics, smoking, physical measurements, diabetes mellitus, lipid, inflammatory, cardiac, and diet- and renal-related markers., Results: Overall, 15 737 participants (52% women) were included. There were sex differences in the relationship between a 1 SD increase in body mass index (BMI), NT-pro-BNP, uric acid, and cystatin-C and the risk of AF. The HRs were 1.17 (95% CI 1.08 to 1.27) in women and 1.36 (95% CI 1.24 to 1.49) in men for BMI (RHR 0.86, 95% CI 0.77 to 0.97); 1.84 (95% CI 1.62 to 2.09) in women and 1.54 (95% CI 1.40 to 1.68) in men for NT-pro-BNP (RHR 1.22, 95% CI1.05 to 1.42); 1.27 (95% CI 1.14 to 1.41) in women and 1.10 (95% CI 1.00 to 1.20) in men for uric acid (RHR 1.17, 95% CI 1.01 to 1.35); and 1.22 (95% CI 1.13 to 1.32) in women and 1.07 (95% CI 0.96 to 1.18) in men for cystatin-C (RHR 1.16, 95% CI 1.05 to1.27)., Conclusion: Higher BMI is a stronger risk factor for AF in men whereas elevated NT-pro-BNP, uric acid and cystatin-C were more strongly associated with the risk of AF in women., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background/aim: Approximately 20% of undescended testes (UDT) are bilateral. It is unclear whether bilateral orchidopexy (BO) should be undertaken synchronously (SBO) or metachronously (MBO). Our aim was to investigate current UK practice and the complications of SBO vs MBO., Materials & Methods: Following approval of BAPS and BAPU ethics committee, a survey was circulated to UK consultant pediatric surgeons and urologists regarding practice. A departmental retrospective review was additionally carried out for patients undergoing BO between 2005 and 2017., Results: Forty-three consultant surgeons from 20 centres completed the survey. Overall, SBO was preferred by 70% for bilateral palpable UDT versus 30% for bilateral impalpable UDT. When one side was palpable and the other impalpable, 70% preferred SBO. Pediatric urologists were significantly more likely to undertake SBO than pediatric general surgeons. One hundred eighty-eight patients (376 testicular units) were identified who had undergone BO with a median follow up of 9 months. 144/188 (76.6%) underwent SBO, while 44 had MBO. There was no statistical difference in the complication rate between the two groups (7.6% in SBO vs 9.1% in MBO; p = 0.66)., Conclusions: The majority of the responding UK consultants, in particular pediatric urologists, favor SBO. This potentially offers a reduction in cost, more rapid completion of treatment, and is not associated with additional complications by comparison to MBO. We recommend SBO to be standard practice for bilateral UDT whenever possible., Level of Evidence: Level III, Retrospective Comparative Study., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Aims: To test two related hypotheses that elevated blood pressure (BP) is a risk factor for aortic valve stenosis (AS) or regurgitation (AR)., Methods and Results: In this cohort study of 5.4 million UK patients with no known cardiovascular disease or aortic valve disease at baseline, we investigated the relationship between BP and risk of incident AS and AR using multivariable-adjusted Cox regression models. Over a median follow-up of 9.2 years, 20 680 patients (0.38%) were diagnosed with AS and 6440 (0.12%) patients with AR. Systolic BP (SBP) was continuously related to the risk of AS and AR with no evidence of a nadir down to 115 mmHg. Each 20 mmHg increment in SBP was associated with a 41% higher risk of AS (hazard ratio 1.41, 95% confidence interval 1.38-1.45) and a 38% higher risk of AR (1.38, 1.31-1.45). Associations were stronger in younger patients but with no strong evidence for interaction by gender or body mass index. Each 10 mmHg increment in diastolic BP was associated with a 24% higher risk of AS (1.24, 1.19-1.29) but not AR (1.04, 0.97-1.11). Each 15 mmHg increment in pulse pressure was associated with a 46% greater risk of AS (1.46, 1.42-1.50) and a 53% higher risk of AR (1.53, 1.45-1.62)., Conclusion: Long-term exposure to elevated BP across its whole spectrum was associated with increased risk of AS and AR. The possible causal nature of the observed associations warrants further investigation.

Background: Studies have suggested that women's reproductive factors are associated with the risk of cardiovascular disease (CVD); however, findings are mixed. We assessed the relationship between reproductive factors and incident CVD in the UK Biobank., Methods: Between 2006 and 2010, the UK Biobank recruited over 500 000 participants aged 40-69 years across the UK. During 7 years of follow-up, 9054 incident cases of CVD (34% women), 5782 cases of coronary heart disease (CHD) (28% women), and 3489 cases of stroke (43% women) were recorded among 267 440 women and 215 088 men without a history of CVD at baseline. Cox regression models yielded adjusted hazard ratios (HRs) for CVD, CHD and stroke associated with reproductive factors., Results: Adjusted HRs (95% CI) for CVD were 1.10 (1.01 to 1.30) for early menarche (<12 years), 0.97 (0.96 to 0.98) for each year increase in age at first birth, 1.04 (1.00 to 1.09) for each miscarriage, 1.14 (1.02 to 1.28) for each stillbirth, and 1.33 (1.19 to 1.49) for early menopause (<47 years). Hysterectomy without oophorectomy or with previous oophorectomy had adjusted HRs of 1.16 (1.06 to 1.28) and 2.30 (1.20 to 4.43) for CVD. Each additional child was associated with a HR for CVD of 1.03 (1.00 to 1.06) in women and 1.03 (1.02 to 1.05) in men., Conclusions: Early menarche, early menopause, earlier age at first birth, and a history of miscarriage, stillbirth or hysterectomy were each independently associated with a higher risk of CVD in later life. The relationship between the number of children and incident CVD was similar for men and women., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objectives: To characterise sex differences in macronutrient intakes and adherence to dietary recommendations in the UK Biobank population., Design: Cross-sectional population-based study., Setting: UK Biobank Resource., Participants: 210 106 (52.5% women) individuals with data on dietary behaviour., Main Outcome Measures: Women-to-men mean differences in nutrient intake in grams and as a percentage of energy and women-to-men ORs in non-adherence, adjusting for age, socioeconomic status and ethnicity., Results: There were sex differences in energy intake and distribution. Men had greater intakes of energy and were less likely to have energy intakes above the estimated average requirement compared with women. Small, but significant, sex differences were found in the intakes of all macronutrients. For all macronutrients, men had greater absolute intakes while women had greater intakes as a percentage of energy. Women were more likely to have intakes that exceeded recommendations for total fat, saturated fat and total sugar. Men were less likely to achieve the minimum recommended intakes for protein, polyunsaturated fat and total carbohydrate. Over 95% of men and women were non-adherent to fibre recommendations. Sex differences in dietary intakes were moderated by age and to some extent by socioeconomic status., Conclusions: There are significant sex differences in adherence to dietary recommendations, particularly for sugar. However, given the increased focus on food groups and dietary patterns for nutritional policy, these differences alone may not be sufficient for policy and health promotion. Future studies that are able to explore the sex differences in intakes of different food groups that are risk factors for diet-related diseases are warranted to improve the current understanding of the differential impact of diet on health in women and men., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: There are substantial differences in the distribution of adipose tissue between women and men. We assessed the sex-specific relationships and their differences between measures of general and central adiposity and the risk of incident myocardial infarction (MI)., Methods and Results: Between 2006 and 2010, the UK Biobank recruited over 500 000 participants aged 40 to 69 years across the United Kingdom. During 7 years of follow-up, 5710 cases of MI (28% women) were recorded among 265 988 women and 213 622 men without a history of cardiovascular disease at baseline. Cox regression models yielded adjusted hazard ratios for MI associated with body mass index, waist circumference, waist-to-hip ratio, and waist-to-height ratio. There was an approximate log-linear relationship between measures of general and central adiposity and the risk of MI in both sexes. A 1-SD higher in body mass index, waist circumference, waist-to-hip ratio, and waist-to-height ratio, respectively, were associated with hazard ratios (confidence intervals) for MI of 1.22 (1.17; 1.28), 1.35 (1.28; 1.42), 1.49 (1.39; 1.59), and 1.34 (1.27; 1.40) in women and of 1.28 (1.23; 1.32), 1.28 (1.23; 1.33), 1.36 (1.30; 1.43), and 1.33 (1.28; 1.38) in men. The corresponding women-to-men ratios of hazard ratios were 0.96 (0.91; 1.02), 1.07 (1.00; 1.14), 1.15 (1.06; 1.24), and 1.03 (0.97; 1.09)., Conclusions: Although general and central adiposity measures each have profound deleterious effects on the risk of MI in both sexes, a higher waist circumference and waist-to-hip ratio conferred a greater excess risk of MI in women than in men. Waist-to-hip ratio was more strongly associated with the risk of MI than body mass index in both sexes, especially in women., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)