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Background: Components of social connection are associated with mortality, but research examining their independent and combined effects in the same dataset is lacking. This study aimed to examine the independent and combined associations between functional and structural components of social connection and mortality., Methods: Analysis of 458,146 participants with full data from the UK Biobank cohort linked to mortality registers. Social connection was assessed using two functional (frequency of ability to confide in someone close and often feeling lonely) and three structural (frequency of friends/family visits, weekly group activities, and living alone) component measures. Cox proportional hazard models were used to examine the associations with all-cause and cardiovascular disease (CVD) mortality., Results: Over a median of 12.6 years (IQR 11.9-13.3) follow-up, 33,135 (7.2%) participants died, including 5112 (1.1%) CVD deaths. All social connection measures were independently associated with both outcomes. Friends/family visit frequencies < monthly were associated with a higher risk of mortality indicating a threshold effect. There were interactions between living alone and friends/family visits and between living alone and weekly group activity. For example, compared with daily friends/family visits-not living alone, there was higher all-cause mortality for daily visits-living alone (HR 1.19 [95% CI 1.12-1.26]), for never having visits-not living alone (1.33 [1.22-1.46]), and for never having visits-living alone (1.77 [1.61-1.95]). Never having friends/family visits whilst living alone potentially counteracted benefits from other components as mortality risks were highest for those reporting both never having visits and living alone regardless of weekly group activity or functional components. When all measures were combined into overall functional and structural components, there was an interaction between components: compared with participants defined as not isolated by both components, those considered isolated by both components had higher CVD mortality (HR 1.63 [1.51-1.76]) than each component alone (functional isolation 1.17 [1.06-1.29]; structural isolation 1.27 [1.18-1.36])., Conclusions: This work suggests (1) a potential threshold effect for friends/family visits, (2) that those who live alone with additional concurrent markers of structural isolation may represent a high-risk population, (3) that beneficial associations for some types of social connection might not be felt when other types of social connection are absent, and (4) considering both functional and structural components of social connection may help to identify the most isolated in society., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Aims: To investigate the combined association of adiposity and walking pace with incident type 2 diabetes., Methods: We undertook a prospective cohort study in 194 304 White-European participants (mean age 56.5 years, 55.9% women). Participants' walking pace was self-reported as brisk, average or slow. Adiposity measures included body mass index (BMI), waist circumference (WC) and body fat percentage (BF%). Associations were investigated using Cox proportional hazard models, with a 2-year landmark analysis. A four-way decomposition analysis was used for mediation and additive interaction., Results: The median (interquartile range) follow-up was 5.4 (4.8-6.3) years. During the follow-up period, 4564 participants developed type 2 diabetes. Compared to brisk-walking participants with normal BMI, those with obesity who walked briskly were at an approximately 10- to 12-fold higher risk of type 2 diabetes (hazard ratio [HR] 9.64, 95% confidence interval [CI] 7.24-12.84, in women; HR 11.91, 95% CI 8.80-16.12, in men), whereas those with obesity and walked slowly had an approximately 12- to 15-fold higher risk (HR 12.68, 95% CI 9.62-16.71, in women; HR 15.41, 95% CI 11.27-21.06, in men). There was evidence of an additive interaction between WC and BF% and walking pace among women, explaining 17.8% and 47.9% excess risk respectively. Obesity mediated the association in women and men, accounting for 60.1% and 44.9%, respectively., Conclusions: Slow walking pace is a risk factor for type 2 diabetes independent of adiposity. Promoting brisk walking as well as weight management might be an effective type 2 diabetes prevention strategy given their synergistic effects., (© 2023 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Background: Coffee is among the most consumed beverages worldwide. Coffee consumption has been associated with lower risk of type 2 diabetes mellitus (T2D), but underlying mechanisms are not well understood. We aimed to study the role of classic and novel-T2D biomarkers with anti- or pro-inflammatory activity in the association between habitual coffee intake and T2D risk. Furthermore, we studied differences by coffee types and smoking status in this association., Methods: Using two large population-based cohorts, the UK-Biobank (UKB; n = 145,368) and the Rotterdam Study (RS; n = 7111), we investigated associations of habitual coffee consumption with incident T2D and repeated measures of insulin resistance (HOMA-IR), using Cox proportional hazards and mixed effect models, respectively. Additionally, we studied associations between coffee and subclinical inflammation biomarkers including C-reactive protein (CRP) and IL-13, and adipokines, such as adiponectin and leptin, using linear regression models. Next, we performed formal causal mediation analyses to investigate the role of coffee-associated biomarkers in the association of coffee with T2D. Finally, we evaluated effect modification by coffee type and smoking. All models were adjusted for sociodemographic, lifestyle and health-related factors., Results: During a median follow-up of 13.9 (RS) and 7.4 (UKB) years, 843 and 2290 incident T2D cases occurred, respectively. A 1 cup/day increase in coffee consumption was associated with 4% lower T2D risk (RS, HR = 0.96 [95%CI 0.92; 0.99], p = 0.045; UKB, HR = 0.96 [0.94; 0.98], p < 0.001), with lower HOMA-IR (RS, log-transformed β = -0.017 [-0.024;-0.010], p < 0.001), and with lower CRP (RS, log-transformed β = -0.014 [-0.022;-0.005], p = 0.002; UKB, β = -0.011 [-0.012;-0.009], p < 0.001). We also observed associations of higher coffee consumption with higher serum adiponectin and IL-13 concentrations, and with lower leptin concentrations. Coffee-related CRP levels partially mediated the inverse association of coffee intake with T2D incidence (average mediation effect RS β = 0.105 (0.014; 0.240), p = 0.016; UKB β = 6.484 (4.265; 9.339), p < 0.001), with a proportion mediated by CRP from 3.7% [-0.012%; 24.4%] (RS) to 9.8% [5,7%; 25.8%] (UKB). No mediation effect was observed for the other biomarkers. Coffee-T2D and coffee-CRP associations were generally stronger among consumers of ground (filtered or espresso) coffee and among never and former smokers., Conclusions: Lower subclinical inflammation may partially mediate the beneficial association between coffee consumption and lower T2D risk. Consumers of ground coffee and non-smokers may benefit the most. KEYWORDS (MESH TERMS): coffee consumptions; diabetes mellitus, type 2; inflammation; adipokines; biomarkers; mediation analysis; follow-up studies., Competing Interests: Conflict of Interest The authors declare no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Diet, the most important modulator of inflammatory and immune responses, may affect COVID-19 incidence and disease severity. Data from 196,154 members of the UK biobank had at least one 24 h dietary recall. COVID-19 outcomes were based on PCR testing, hospital admissions, and death certificates. Adjusted Poisson regression analyses were performed to estimate the risk ratios (RR) and their 95% confidence intervals (CI) for dietary inflammatory index (DII)/energy-adjusted DII (E-DII) scores. Models were adjusted for sociodemographic factors, comorbidities, smoking status, physical activity, and sleep duration. Between January 2020 and March 2021, there were 11,288 incident COVID-19 cases, 1270 COVID-19-related hospitalizations, and 315 COVID-19-related deaths. The fully adjusted model showed that participants in the highest (vs. lowest) DII/E-DII quintile were at 10-17% increased risk of COVID-19 (DII: RR Q5 vs . Q1 = 1.10, 95% CI 1.04-1.17, P trend < 0.001; E-DII: RR Q5 vs . Q1 = 1.17, 95% CI 1.10-1.24, P trend < 0.001) and ≈40% higher risk was observed for disease severity (DII: RR Q5 vs . Q1 = 1.40, 95% CI 1.18-1.67, P trend < 0.001; E-DII: RR Q5 vs . Q1 = 1.39, 95% CI 1.16-1.66, P trend < 0.001). There was a 43% increased risk of COVID-19-related death in the highest DII quintile (RR Q5 vs . Q1 = 1.43, 95% CI 1.01-2.01, P trend = 0.04). About one-quarter of the observed positive associations between DII and COVID-19-related outcomes were mediated by body mass index (25.8% for incidence, 21.6% for severity, and 19.8% for death). Diet-associated inflammation increased the risk of COVID-19 infection, severe disease, and death.

Objective: To investigate the association between self-reported walking pace and type 2 diabetes (T2D) incidence and whether it differed by physical activity levels and walking time., Methods: There were 162,155 participants (mean age, 57.1 years; 54.9% women) from the UK Biobank prospective study, recruited between 2006 and 2010, included in the study. Walking pace was self-reported and classified as brisk, average, or slow. Total physical activity and walking time were self-reported using the International Physical Activity Questionnaire. Association between walking pace and T2D incidence and the potential moderating role of physical activity and walking time were investigated using Cox proportional hazards models., Results: The median follow-up was 7.4 (interquartile range, 6.7 to 8.2) years. There were 4442 participants in whom T2D developed during the follow-up period. In the fully adjusted model (sociodemographic factors, diet, body mass index, and physical activity), average walking pace (hazard ratio [HR], 1.28; 95% CI, 1.14 to 1.44) and slow walking pace (HR, 1.91; 95% CI, 1.62 to 2.24) were associated with a higher T2D risk compared with brisk walking among women. Among men, average walking pace (HR, 1.28; 95% CI, 1.17 to 1.40) and slow walking pace (HR, 1.73; 95% CI, 1.50 to 1.99) were also associated with higher T2D risk. Compared with slow walkers, brisk walkers have the same diabetes incidence rate 18.6 and 16.0 years later, for women and men, respectively., Conclusion: Average and slow walking pace was associated with a higher risk of incident T2D in both men and women, independent of major confounding factors. The associations were consistent across different physical activity levels and walking time., (Copyright © 2022 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Introduction: The aim of this study was to determine risk of being SARS-CoV-2 positive and severe infection (associated with hospitalization/mortality) in those with family history of diabetes., Methods: We used UK Biobank, an observational cohort recruited between 2006 and 2010. We compared the risk of being SARS-CoV-2 positive and severe infection for those with family history of diabetes (mother/father/sibling) against those without., Results: Of 401,268 participants in total, 13,331 tested positive for SARS-CoV-2 and 2282 had severe infection by end of January 2021. In unadjusted models, participants with ≥2 family members with diabetes were more likely to be SARS-CoV-2 positive (risk ratio-RR 1.35; 95% confidence interval-CI 1.24-1.47) and severe infection (RR 1.30; 95% CI 1.04-1.59), compared to those without. The excess risk of being tested positive for SARS-CoV-2 was attenuated but significant after adjusting for demographics, lifestyle factors, multimorbidity and presence of cardiometabolic conditions. The excess risk for severe infection was no longer significant after adjusting for demographics, lifestyle factors, multimorbidity and presence of cardiometabolic conditions, and was absent when excluding incident diabetes., Conclusion: The totality of the results suggests that good lifestyle and not developing incident diabetes may lessen risks of severe infections in people with a strong family of diabetes., (© 2021 The Authors. Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd.)

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.

Background: To investigate whether the excess risk of adverse health outcomes associated with a lower physical capability in adulthood differs by deprivation levels., Methods: 279,030 participants from the UK Biobank were included. Handgrip strength and walking pace were the exposures. All-cause mortality, CVD mortality and incidence were the outcomes. Townsend deprivation index was treated as a potential effect modifier. The associations were investigated using Cox-regression models with years of follow-up as the time-varying covariate., Results: A significant interaction between deprivation and handgrip strength was found for all-cause mortality (p = 0.024), CVD mortality (p = 0.006) and CVD incidence (p = 0.001). The hazard ratio for all-cause mortality was 1.18 [1.09; 1.29] per 1-tertile higher level of grip strength in the least deprived group, whereas it was 1.30 [1.18; 1.43] in the most deprived individuals. Similar results were found for CVD mortality and incidence per tertile increment in handgrip strength in the least and most deprived quintiles, respectively. No significant interactions between deprivation and walking pace were found for any of the outcomes., Conclusion: Low handgrip strength is a stronger predictor of morbidity and mortality in individuals living in more deprived areas.

Objectives: We aimed to investigate demographic, lifestyle, socioeconomic and clinical risk factors for COVID-19, and compared them to risk factors for pneumonia and influenza in UK Biobank., Design: Cohort study., Setting: UK Biobank., Participants: 49-83 year olds (in 2020) from a general population study., Main Outcome Measures: Confirmed COVID-19 infection (positive SARS-CoV-2 test). Incident influenza and pneumonia were obtained from primary care data. Poisson regression was used to study the association of exposure variables with outcomes., Results: Among 235 928 participants, 397 had confirmed COVID-19. After multivariable adjustment, modifiable risk factors were higher body mass index and higher glycated haemoglobin (HbA1C) (RR 1.28 and RR 1.14 per SD increase, respectively), smoking (RR 1.39), slow walking pace as a proxy for physical fitness (RR 1.53), and use of blood pressure medications as a proxy for hypertension (RR 1.33). Higher forced expiratory volume in 1 s (FEV1) and high-density lipoprotein (HDL) cholesterol were both associated with lower risk (RR 0.84 and RR 0.83 per SD increase, respectively). Non-modifiable risk factors included male sex (RR 1.72), black ethnicity (RR 2.00), socioeconomic deprivation (RR 1.17 per SD increase in Townsend Index), and high cystatin C (RR 1.13 per SD increase). The risk factors overlapped with pneumonia somewhat, less so for influenza. The associations with modifiable risk factors were generally stronger for COVID-19, than pneumonia or influenza., Conclusion: These findings suggest that modification of lifestyle may help to reduce the risk of COVID-19 and could be a useful adjunct to other interventions, such as social distancing and shielding of high risk., Competing Interests: Competing interests: PW has received research grants from Roche Diagnostics, AstraZeneca and Boehringer Ingelheim outside the submitted work, and NS has received grant and personal fees from Boehringer Ingelheim, and personal fees from Amgen, AstraZeneca, Eli Lilly, Novo Nordisk, Pfizer, and Sanofi outside the submitted work. All authors declare no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Introduction: Older people have been reported to be at higher risk of COVID-19 mortality. This study explored the factors mediating this association and whether older age was associated with increased mortality risk in the absence of other risk factors., Methods: In UK Biobank, a population cohort study, baseline data were linked to COVID-19 deaths. Poisson regression was used to study the association between current age and COVID-19 mortality., Results: Among eligible participants, 438 (0.09%) died of COVID-19. Current age was associated exponentially with COVID-19 mortality. Overall, participants aged ≥75 years were at 13-fold (95% CI 9.13-17.85) mortality risk compared with those <65 years. Low forced expiratory volume in 1 second, high systolic blood pressure, low handgrip strength, and multiple long-term conditions were significant mediators, and collectively explained 39.3% of their excess risk. The associations between these risk factors and COVID-19 mortality were stronger among older participants. Participants aged ≥75 without additional risk factors were at 4-fold risk (95% CI 1.57-9.96, P = 0.004) compared with all participants aged <65 years., Conclusions: Higher COVID-19 mortality among older adults was partially explained by other risk factors. 'Healthy' older adults were at much lower risk. Nonetheless, older age was an independent risk factor for COVID-19 mortality., Competing Interests: The authors have declared that no competing interests exist.

Objective: To inform potential guideline development, we investigated nonlinear associations between television viewing time (TV time) and adverse health outcomes., Methods: From 2006 to 2010, 490,966 UK Biobank participants, aged 37 to 73 years, were recruited. They were followed from 2006 to 2018. Nonlinear associations between self-reported TV time (hours per day) and outcomes explored using penalized cubic splines in Cox proportional hazards adjusted for demographics and lifestyle. Population-attributable and potential impact fractions were calculated to contextualize population-level health outcomes associated with different TV time levels. Nonlinear isotemporal substitution analyses were used to investigate substituting TV time with alternative activities. Primary outcomes were mortality: all-cause, cardiovascular disease (CVD) and cancer; incidence: CVD and cancer; secondary outcomes were incident myocardial infarction, stroke, and heart failure and colon, lung, breast, and prostate cancer., Results: Those with noncommunicable disease (109,867 [22.4%]), CVD (32,243 [6.6%]), and cancer (37,81 [7.7%]) at baseline were excluded from all-cause mortality, CVD, and cancer analyses, respectively. After 7.0 years (mortality) and 6.2 years (disease incidence) mean follow-up, there were 10,306 (2.7%) deaths, 24,388 (5.3%) CVD events, and 39,121 (8.7%) cancer events. Associations between TV time and all-cause and CVD mortality were curvilinear (P non-linear ≤.003), with lowest risk observed <2 hours per day. Theoretically, 8.64% (95% confidence interval [CI], 6.60-10.73) of CVD mortality is attributable to TV time. Limiting TV time to 2 hours per day might have prevented, or at least delayed, 7.97% (95% CI, 5.54-10.70) of CVD deaths. Substituting TV time with sleeping, walking, or moderate or vigorous physical activity was associated with reduced risk for all outcomes when baseline levels of substitute activities were low., Conclusion: TV time is associated with numerous adverse health outcomes. Future guidelines could suggest limiting TV time to less than 2 hours per day to reduce most of the associated adverse health events., (Copyright © 2020. Published by Elsevier Inc.)

Aims: We examined the link between BMI and risk of a positive test for SARS-CoV-2 and risk of COVID-19-related death among UK Biobank participants., Methods: Among 4855 participants tested for SARS-CoV-2 in hospital, 839 were positive and of these 189 died from COVID-19. Poisson models with penalised thin plate splines were run relating exposures of interest to test positivity and case-fatality, adjusting for confounding factors., Results: BMI was associated strongly with positive test, and risk of death related to COVID-19. The gradient of risk in relation to BMI was steeper in those under 70, compared with those aged 70 years or older for COVID-19 related death (P interaction  = 0.03). BMI was more strongly related to test positivity (P interaction  = 0.010) and death (P interaction  = 0.002) in non-whites (predominantly South Asians and Afro-Caribbeans), compared with whites., Conclusions: These data add support for adiposity being more strongly linked to COVID-19-related deaths in younger people and non-white ethnicities. If future studies confirm causality, lifestyle interventions to improve adiposity status may be important to reduce the risk of COVID-19 in all, but perhaps particularly, non-white communities., Competing Interests: Declaration of competing interest NS reports personal fees from Amgen, AstraZeneca, Eli Lilly, Novo Nordisk, Pfizer, and Sanofi, and grants and personal fees from Boehringer Ingelheim, outside the submitted work. PW reports grant from Boehringer Ingelheim outside submitted work. All other authors declare no competing interests., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: It is unclear what combinations of physical capability markers used to define sarcopenia have the strongest associations with health outcomes., Aim: To compare the associations between different combinations of physical capability markers of sarcopenia with cardiovascular and respiratory outcomes and all-cause mortality., Study Design: 469,830 UK Biobank participants were included in this prospective study. Four groups were derived based on combinations of three physical capability markers used to define sarcopenia or severe sarcopenia: gait speed, grip strength and muscle mass. Outcomes studied were all-cause mortality, as well as incidence and mortality from cardiovascular disease (CVD), respiratory disease and chronic obstructive pulmonary disease (COPD)., Results: All combinations of physical capability markers used to define sarcopenia or severe sarcopenia identified individuals at increased risk of respiratory disease and all-cause mortality. However, the definition most strongly associated with a wide range of adverse health outcomes was the combination of slow gait speed plus low muscle mass, followed by severe sarcopenia, and the combination of slow gait speed plus low grip strength. The current definition of sarcopenia (low grip strength plus low muscle mass) had the weakest associations with all-cause (HR: 1.35 [95% CI: 1.07 to 1.71]) and respiratory mortality (HR: 1.88 [95% CI: 1.15 to 3.10]), as well as respiratory disease (HR: 1.38 [95% CI: 1.11 to 1.73]) and COPD incidence (HR: 2.08 [95% CI: 1.14 to 3.79])., Conclusions: Associations of sarcopenia with adverse outcomes were strongest when sarcopenia was defined as slow gait speed plus low muscle mass, followed by severe sarcopenia, suggesting that this combination of physical capability markers should be still considered in the diagnosis of sarcopenia., Competing Interests: Conflict of intereset The authors declare that they have no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background and Aims: COVID-19 and low levels of vitamin D appear to disproportionately affect black and minority ethnic individuals. We aimed to establish whether blood 25-hydroxyvitamin D (25(OH)D) concentration was associated with COVID-19 risk, and whether it explained the higher incidence of COVID-19 in black and South Asian people., Methods: UK Biobank recruited 502,624 participants aged 37-73 years between 2006 and 2010. Baseline exposure data, including 25(OH)D concentration and ethnicity, were linked to COVID-19 test results. Univariable and multivariable logistic regression analyses were performed for the association between 25(OH)D and confirmed COVID-19, and the association between ethnicity and both 25(OH)D and COVID-19., Results: Complete data were available for 348,598 UK Biobank participants. Of these, 449 had confirmed COVID-19 infection. Vitamin D was associated with COVID-19 infection univariably (OR = 0.99; 95% CI 0.99-0.999; p = 0.013), but not after adjustment for confounders (OR = 1.00; 95% CI = 0.998-1.01; p = 0.208). Ethnicity was associated with COVID-19 infection univariably (blacks versus whites OR = 5.32, 95% CI = 3.68-7.70, p-value<0.001; South Asians versus whites OR = 2.65, 95% CI = 1.65-4.25, p-value<0.001). Adjustment for 25(OH)D concentration made little difference to the magnitude of the association., Conclusions: Our findings do not support a potential link between vitamin D concentrations and risk of COVID-19 infection, nor that vitamin D concentration may explain ethnic differences in COVID-19 infection., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

The aim of the current study was to investigate the association between diet and handgrip strength. The current study included 68,002 participants (age 63.8 ± 2.7 years, 50.3% women, 49.7% men) from UK Biobank. Diet and nutritional data (carotene, retinol, potassium, vitamin C, foliate, vitamin B12, vitamin B6, iron, vitamin E, calcium, magnesium, carbohydrates, protein, polyunsaturated fat, fat, starch and saturated fat) were collected and handgrip strength measured. Associations were compared, stratified by sex, using regression analyses, after adjustment for age, sex, month of assessment, ethnicity, deprivation index, height, comorbidities and total energy intake. The current data revealed negative associations between carbohydrate intake and handgrip strength as well as positive associations between oily fish, retinol and magnesium intake and grip strength in both sexes. In women, positive associations were observed between intake of red meat, fruit and vegetables, vitamin E, iron, vitamin B12, folate and vitamin C and hand grip strength. In men only negative associations were seen between bread and processed meat with grip strength. We have shown associations of several nutrients and food items with muscle strength and appropriately designed trials are needed to investigate whether these nutrients/food items may be beneficial in the maintenance of muscle during ageing., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: To identify predictors of favorable changes to postprandial insulin and glucose levels in response to interrupting prolonged sitting time with standing or light-intensity physical activity., Methods: Data were combined from four similarly designed randomized acute cross-over trials (n = 129; body mass index [BMI] range, 19.6-44.6 kg·m; South Asian = 31.0%; dysglycemia = 27.1%). Treatments included: prolonged sitting (6.5 h) or prolonged sitting broken-up with either standing or light-intensity physical activity (5 min every 30 min). Time-averaged postprandial responses for insulin and glucose were calculated for each treatment (mean ± 95% confidence interval). Mutually adjusted interaction terms were used to examine whether anthropometric (BMI), demographic (age, sex, ethnicity [white European vs South Asian]) and a cardiometabolic variable (Homeostatic Model Assessment of Insulin Resistance)-modified responses., Results: Postprandial insulin and glucose were reduced when individuals interrupted prolonged sitting with bouts of light physical activity, but not with standing. Reductions in time-averaged postprandial insulin were more pronounced if individuals were South Asian compared with white European (-18.9 mU·L [-23.5%] vs -8.2 mU·L [-9.3%]), female compared with male (-15.0 mU·L [-21.2%] vs -12.1 mU·L [-17.6%]) or had a BMI ≥27.2 kg·m (-20.9 mU·L [-22.9%] vs -8.7 mU·L [-18.2%]). Similarly, being female (-0.4 mmol·L [-0.6 mmol·L, -0.2 mmol·L], -6.8% vs -0.1 mmol·L [-0.3 mmol·L, 1 mmol·L], -1.7%) or having a BMI ≥27.2 kg·m (-0.4 mmol·L [-0.6 mmol·L, -0.2 mmol·L], -6.7% vs -0.2 mmol·L [-0.4 mmol·L, 0.0 mmol·L], -3.4%) modified the postprandial glucose response. No significant interactions were found for Homeostatic Model Assessment of Insulin Resistance or age., Conclusions: Being female, South Asian, or having a higher BMI, all predicted greater reductions in postprandial insulin, whereas being female and having a higher BMI predicted greater reductions in postprandial glucose when sitting was interrupted with light physical activity. These results could help to guide personalized interventions in high-risk participants for whom breaking prolonged sitting time with light activity may yield the greatest therapeutic potential.

Objective: To investigate whether the addition of grip strength and/or self-reported walking pace to established cardiovascular disease (CVD) risk scores improves their predictive abilities., Patients and Methods: A total of 406,834 participants from the UK Biobank, with baseline measurements between March 13, 2006, and October 1, 2010, without CVD at baseline were included in this study. Associations of grip strength and walking pace with CVD outcomes were investigated using Cox models adjusting for classical risk factors (as included in established risk scores), and predictive utility was determined by changes in C-index and categorical net reclassification index., Results: Over a median of 8.87 years of follow-up (interquartile range 3, 8.25-9.47 years), there were 7274 composite fatal/nonfatal events (on the basis of the American College of Cardiology/American Heart Association [ACC/AHA] outcome) and 1955 fatal events (on the basis of the Systematic Coronary Risk Evaluation [SCORE] risk score). Both grip strength and walking pace were inversely associated with CVD outcomes after adjusting for classical risk factors. Addition of grip strength (change in C-index: ACC/AHA, +0.0017; SCORE, +0.0047), usual walking pace (ACC/AHA, +0.0031; SCORE, +0.0130), and both combined (ACC/AHA, +0.0041; SCORE, +0.0148) improved the C-index and also improved the net reclassification index (grip, +0.55%; walking pace, +0.53%; combined, 1.12%)., Conclusion: The present study has found that the addition of grip strength or usual walking pace to existing risk scores results in improved CVD risk prediction, with an additive effect when both are added. As both these measures are cheap and easy to administer, these tools could provide an important addition to CVD risk screening, although further external validation is required., (Copyright © 2020 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Background: Recent efforts to address the obesity epidemic have focused on sugar consumption, especially sugar-sweetened beverages. However, sugar takes many forms, is only one contributor to overall energy consumption and is correlated with other health-related lifestyle factors. The objective was to investigate the associations with all-cause mortality of sugar- and artificially sweetened beverages and naturally sweet juices., Methods: Setting: UK Biobank, UK. Participants joined the UK Biobank study from 2006 to 2010 and were followed up until 2016; 198,285 men and women aged 40-69 years were eligible for this study (40% of the UK Biobank), of whom 3166 (1.6%) died over a mean of 7 years follow-up., Design: prospective population-based cohort study. Exposure variables: dietary consumption of sugar-sweetened beverages, artificially sweetened beverages, naturally sweet juices (100% fruit/vegetable juices) and total sugar intake, self-reported via 24-h dietary assessment tool completed between 2009 and 2012., Main Outcome: all-cause mortality. Cox regression analyses were used to study the association between the daily intake of the above beverages and all-cause mortality. Models were adjusted for sociodemographic, economic, lifestyle and dietary confounders., Results: Total energy intake, total sugar intake and percentage of energy derived from sugar were comparable among participants who consumed > 2/day sugar-sweetened beverages and > 2/day fruit/vegetable juices (10,221 kJ/day versus 10,381 kJ/day; 183 g versus 190 g; 30.6% versus 31.0%). All-cause mortality was associated with total sugar intake (highest quintile adj. HR 1.28, 95% CI 1.06-1.55) and intake of sugar-sweetened beverages (> 2/day adj. HR 1.84, 95% CI 1.42-2.37) and remained so in sensitivity analyses. An association between artificially sweetened beverage intake and mortality did not persist after excluding deaths in the first 2 years of follow-up (landmark analysis) nor after excluding participants with recent weight loss. Furthermore, the inverse association between fruit/vegetable juice intake and mortality did not persist after additional adjustment for a diet quality score., Conclusions: Higher mortality is associated with sugar-sweetened beverages specifically. The lack of an adverse association with fruit/vegetable juices suggests that source of sugar may be important and the association with artificially sweetened beverage may reflect reverse causation.

Objective: HbA 1c levels are increasingly measured in screening for diabetes; we investigated whether HbA 1c may simultaneously improve cardiovascular disease (CVD) risk assessment, using QRISK3, American College of Cardiology/American Heart Association (ACC/AHA), and Systematic COronary Risk Evaluation (SCORE) scoring systems., Research Design and Methods: UK Biobank participants without baseline CVD or known diabetes ( n = 357,833) were included. Associations of HbA1c with CVD was assessed using Cox models adjusting for classical risk factors. Predictive utility was determined by the C-index and net reclassification index (NRI). A separate analysis was conducted in 16,596 participants with known baseline diabetes., Results: Incident fatal or nonfatal CVD, as defined in the QRISK3 prediction model, occurred in 12,877 participants over 8.9 years. Of participants, 3.3% ( n = 11,665) had prediabetes (42.0-47.9 mmol/mol [6.0-6.4%]) and 0.7% ( n = 2,573) had undiagnosed diabetes (≥48.0 mmol/mol [≥6.5%]). In unadjusted models, compared with the reference group (<42.0 mmol/mol [<6.0%]), those with prediabetes and undiagnosed diabetes were at higher CVD risk: hazard ratio (HR) 1.83 (95% CI 1.69-1.97) and 2.26 (95% CI 1.96-2.60), respectively. After adjustment for classical risk factors, these attenuated to HR 1.11 (95% CI 1.03-1.20) and 1.20 (1.04-1.38), respectively. Adding HbA 1c to the QRISK3 CVD risk prediction model (C-index 0.7392) yielded a small improvement in discrimination (C-index increase of 0.0004 [95% CI 0.0001-0.0007]). The NRI showed no improvement. Results were similar for models based on the ACC/AHA and SCORE risk models., Conclusions: The near twofold higher unadjusted risk for CVD in people with prediabetes is driven mainly by abnormal levels of conventional CVD risk factors. While HbA 1c adds minimally to cardiovascular risk prediction, those with prediabetes should have their conventional cardiovascular risk factors appropriately measured and managed., (© 2019 by the American Diabetes Association.)

Objective: To investigate the association of cardiorespiratory fitness with all-cause mortality, and cardiovascular disease (CVD), respiratory disease, chronic obstructive pulmonary disease (COPD) and cancer mortality and incidence., Design: Prospective population-based study., Setting: UK Biobank., Participants: Of the 5 02 628 (5.5% response rate) participants recruited by UK Biobank, we included 73 259 (14.6%) participants with available data in this analysis. Of these, 1374 participants died and 4210 developed circulatory diseases, 1293 respiratory diseases and 4281 cancer, over a median of 5.0 years (IQR 4.3-5.7) follow-up., Main Outcome Measures: All-cause mortality and circulatory disease, respiratory disease, COPD and cancer (such as colorectal, lung, breast and prostate) mortality/incidence. Fitness was estimated using a submaximal cycle ergometer test., Results: The HR for all-cause mortality for each metabolic equivalent of task (MET) higher fitness was 0.96 (95% CI 0.93 to 0.98). Similar results were observed for incident circulatory disease (HR 0.96 [0.95 to 0.97]), respiratory disease (HR 0.96 [0.94 to 0.98]), COPD (HR 0.90 [0.86 to 0.95) and colorectal cancer (HR 0.96 [0.92 to 1.00]). Nonlinear analysis revealed that a high level of fitness (>10METs) was associated with a greater incidence of atrial fibrillation (HR 1.24 [1.07 to 1.44]) and prostate cancer (HR 1.16 [1.02 to 1.32]) compared with average fitness. All results were adjusted for sociodemographic, lifestyle and dietary factors, body composition, and morbidity at baseline and excluded events in the first 2 years of follow-up., Conclusions: Higher cardiorespiratory fitness was associated with lower risk of premature mortality and incidence of CVD, respiratory disease and colorectal cancer., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To investigate the associations of objectively measured cardiorespiratory fitness (CRF) and grip strength (GS) with incident heart failure (HF), a clinical syndrome that results in substantial social and economic burden, using UK Biobank data., Patients and Methods: Of the 502,628 participants recruited into the UK Biobank between April 1, 2007, and December 31, 2010, a total of 374,493 were included in our GS analysis and 57,053 were included in CRF analysis. Associations between CRF and GS and incident HF were investigated using Cox proportional hazard models, with adjustment for known measured confounders., Results: During a mean of 4.1 (range, 2.4-7.1) years, 631 HF events occurred in those with GS data, and 66 HF events occurred in those with CRF data. Higher CRF was associated with 18% lower risk for HF (hazard ratio [HR], 0.82; 95% CI, 0.76-0.88) per 1-metabolic equivalent increment increase and GS was associated with 19% lower incidence of HF risk (HR, 0.81; 95% CI, 0.77-0.86) per 5-kg increment increase. When CRF and GS were standardized, the HR for CRF was 0.50 per 1-SD increment (95% CI, 0.38-0.65), and for GS was 0.65 per 1-SD increment (95% CI, 0.58-0.72)., Conclusion: Our data indicate that objective measurements of physical function (GS and CRF) are strongly and independently associated with lower HF incidence. Future studies targeting improving CRF and muscle strength should include HF as an outcome to assess whether these results are causal., (Copyright © 2019 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Background: Driving is a common type of sedentary behaviour; an independent risk factor for poor health. The study explores whether driving is also associated with other unhealthy lifestyle factors., Methods: In a cross-sectional study of UK Biobank participants, driving time was treated as an ordinal variable and other lifestyle factors dichotomized into low/high risk based on guidelines. The associations were explored using chi-square tests for trend and binary logistic regression., Results: Of the 386 493 participants who drove, 153 717 (39.8%) drove <1 h/day; 140 140 (36.3%) 1 h/day; 60 973 (15.8%) 2 h/day; and 31 663 (8.2%) ≥3 h/day. Following adjustment for potential confounders, driving ≥3 h/day was associated with being overweight/obese (OR = 1.74, 95% CI: 1.64-1.85), smoking (OR = 1.48, 95% CI: 1.37-1.63), insufficient sleep (1.70, 95% CI: 1.61-1.80), low fruit/vegetable intake (OR = 1.26, 95% CI: 1.18-1.35) and low physical activity (OR = 1.05, 95% CI: 1.00-1.11), with dose relationships for the first three, but was not associated with higher alcohol consumption (OR = 0.94, 95% CI: 0.87-1.02)., Conclusions: Sedentary behaviour, such as driving, is known to have an independent association with adverse health outcomes. It may have additional impact mediated through its effect on other aspects of lifestyle. People with long driving times are at higher risk and might benefit from targeted interventions., (© The Author(s) 2018. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: higher grip strength is associated with better health outcomes. The optimal way to report grip strength (i.e. absolute vs. relative) for prediction, however, remains to be established., Methods: in participants (aged 37-73 at baseline) from the UK Biobank, we examined the associations of grip strength, expressed in absolute terms (kilograms) and relative to anthropometric variables, with mortality and disease incidence, after exclusion of the first 2 years of follow-up, and compared risk predictions scores of handgrip strength when differentially expressed., Results: of the 356 721 participants included in the analysis 6,234 died (1.7%) and 4,523 developed CVD (1.3%) over a mean follow-up of 5.0 years (ranging from 3.3 to 7.8) for mortality and 4.1 years (ranging from 2.4 to 7.0) for disease incidence data. As expected, baseline higher grip strength was associated with lower risk of all-cause and cause specific mortality and incidence. These associations did not meaningfully differ when grip-strength was expressed in absolute terms, vs. relative to height, weight, fat-free mass, BMI, fat-free mass index and fat-free mass, or as z-scores. Similarly the different ways of expressing grip strength had little effect on the ability of grip strength to improve risk prediction, based on C-index change, of an office-based risk score., Conclusions: the ability of grip strength to predict mortality is not altered by changing how it is expressed., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Total cholesterol and high-density lipoprotein cholesterol (HDL-C) measurements are central to cardiovascular disease (CVD) risk assessment, but there is continuing debate around the utility of other lipids for risk prediction., Methods: Participants from UK Biobank without baseline CVD and not taking statins, with relevant lipid measurements (n=346 686), were included in the primary analysis. An incident fatal or nonfatal CVD event occurred in 6216 participants (1656 fatal) over a median of 8.9 years. Associations of nonfasting lipid measurements (total cholesterol, HDL-C, non-HDL-C, direct and calculated low-density lipoprotein cholesterol [LDL-C], and apolipoproteins [Apo] A1 and B) with CVD were compared using Cox models adjusting for classical risk factors, and predictive utility was determined by the C-index and net reclassification index. Prediction was also tested in 68 649 participants taking a statin with or without baseline CVD (3515 CVD events)., Results: ApoB, LDL-C, and non-HDL-C were highly correlated (r>0.90), while HDL-C was strongly correlated with ApoA1 (r=0.92). After adjustment for classical risk factors, 1 SD increase in ApoB, direct LDL-C, and non-HDL-C had similar associations with composite fatal/nonfatal CVD events (hazard ratio, 1.23, 1.20, 1.21, respectively). Associations for 1 SD increase in HDL-C and ApoA1 were also similar (hazard ratios, 0.81 [both]). Adding either total cholesterol and HDL-C, or ApoB and ApoA, to a CVD risk prediction model (C-index, 0.7378) yielded similar improvement in discrimination (C-index change, 0.0084; 95% CI, 0.0065, 0.0104, and 0.0089; 95% CI, 0.0069, 0.0109, respectively). Once total and HDL-C were in the model, no further substantive improvement was achieved with the addition of ApoB (C-index change, 0.0004; 95% CI, 0.0000, 0.0008) or any measure of LDL-C. Results for predictive utility were similar for a fatal CVD outcome, and in a discordance analysis. In participants taking a statin, classical risk factors (C-index, 0.7118) were improved by non-HDL-C (C-index change, 0.0030; 95% CI, 0.0012, 0.0048) or ApoB (C-index change, 0.0030; 95% CI, 0.0011, 0.0048). However, adding ApoB or LDL-C to a model already containing non-HDL-C did not further improve discrimination., Conclusions: Measurement of total cholesterol and HDL-C in the nonfasted state is sufficient to capture the lipid-associated risk in CVD prediction, with no meaningful improvement from addition of apolipoproteins, direct or calculated LDL-C.

Objective: To investigate whether the association between a genetic profile risk score for obesity (GPRS-obesity) (based on 93 SNPs) and body mass index (BMI) was modified by physical activity (PA), cardiorespiratory fitness, commuting mode, walking pace and sedentary behaviours., Methods: For the analyses we used cross-sectional baseline data from 310,652 participants in the UK Biobank study. We investigated interaction effects of GPRS-obesity with objectively measured and self-reported PA, cardiorespiratory fitness, commuting mode, walking pace, TV viewing, playing computer games, PC-screen time and total sedentary behaviour on BMI. Body mass index (BMI) was the main outcome measure., Results: GPRS-obesity was associated with BMI (β:0.54 kg.m -2 per standard deviation (SD) increase in GPRS, [95% CI: 0.53; 0.56]; P = 2.1 × 10 -241 ). There was a significant interaction between GPRS-obesity and objectively measured PA (P [interaction]  = 3.3 × 10 -11 ): among inactive individuals, BMI was higher by 0.58 kg.m -2 per SD increase in GPRS-obesity (p = 1.3 × 10 -70 ) whereas among active individuals the relevant BMI difference was less (β:0.33 kg.m -2 , p = 6.4 × 10 -41 ). We observed similar patterns for fitness (Unfit β:0.72 versus Fit β:0.36 kg.m -2 , P [interaction]  = 1.4 × 10 -11 ), walking pace (Slow β:0.91 versus Brisk β:0.38 kg.m -2 , P [interaction]  = 8.1 × 10 -27 ), discretionary sedentary behaviour (High β:0.64 versus Low β:0.48 kg.m -2 , P [interaction]  = 9.1 × 10 -12 ), TV viewing (High β:0.62 versus Low β:0.47 kg.m -2 , P [interaction]  = 1.7 × 10 -11 ), PC-screen time (High β:0.82 versus Low β:0.54 kg.m -2 , P [interaction]  = 0.0004) and playing computer games (Often β:0.69 versus Low β:0.52 kg.m -2 , P [interaction]  = 8.9 × 10 -10 ). No significant interactions were found for commuting mode (car, public transport, active commuters)., Conclusions: Physical activity, sedentary behaviours and fitness modify the extent to which a set of the most important known adiposity variants affect BMI. This suggests that the adiposity benefits of high PA and low sedentary behaviour may be particularly important in individuals with high genetic risk for obesity.

Purpose: Adequate dietary protein intake is important for the maintenance of bone health; however, data in this area is ambiguous with some suggestion that high protein intake can have deleterious effects on bone health. The aim of the current study was to explore the associations of protein intake with bone mineral density (BMD)., Methods: We used baseline data from the UK Biobank (participants aged 40-69 years) to examine the association of protein intake with BMD (measured by ultrasound). These associations were examined, in women (n = 39,066) and men (n = 31,149), after adjustment for socio-demographic and lifestyle confounders and co-morbidities., Results: Protein intake was positively and linearly associated with BMD in women (β-coefficient 0.010 [95% CI 0.005; 0.015, p < 0.0001]) and men (β-coefficient 0.008 [95% CI 0.000; 0.015, p = 0.044]); per 1.0 g/kg/day increment in protein intake, independently of socio-demographics, dietary factors and physical activity., Conclusions: The current data have demonstrated that higher protein intakes are positively associated with BMD in both men and women. This indicates that higher protein intakes may be beneficial for both men and women., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: Walking pace is associated with all-cause and cardiovascular disease (CVD) mortality. Whether this association extends to other health outcomes and whether it is independent of total amount of time walked are currently unknown. Therefore, the aim of this study was to investigate whether usual walking pace is associated with a range of health outcomes., Methods: UK Biobank participants (318,185 [54%] women) age 40 to 69 yr were included. Walking pace and total walking time were self-reported. The outcomes comprised: all-cause mortality as well as incidence and mortality from CVD, respiratory disease and cancer. The associations were investigated using Cox proportional hazard models., Results: Over a mean of 5.0 yr [ranging from 3.3 to 7.8], 5890 participants died, 18,568 developed CVD, 5430 respiratory disease and 19,234 cancer. In a fully adjusted model, compared to slow pace walkers, men and women, respectively, with a brisk pace having lower risk of mortality from all-causes (hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.69-0.90 and HR, 0.73; 95% CI, 0.62-0.85), CVD (HR, 0.62; 95% CI, 0.50-0.76 and HR, 0.80; 95% CI, 0.73-0.88), respiratory disease (HR, 0.58; 95% CI, 0.43-0.78 and HR, 0.66; 95% CI, 0.57-0.77), chronic obstructive pulmonary disease (HR, 0.26; 95% CI, 0.12-0.56 and HR, 0.28; 95% CI, 0.16-0.49). No associations were found for all-cause cancer, colorectal, and breast cancer. However, brisk walking was associated with a higher risk of prostate cancer., Conclusions: Walking pace is associated with lower risk of a wide range of important health conditions, independently of overall time spent walking.

Background: Combinations of lifestyle factors interact to increase mortality. Combinations of traditional factors such as smoking and alcohol are well described, but the additional effects of emerging factors such as television viewing time are not. The effect of socioeconomic deprivation on these extended lifestyle risks also remains unclear. We aimed to examine whether deprivation modifies the association between an extended score of lifestyle-related risk factors and health outcomes., Methods: Data for this prospective analysis were sourced from the UK Biobank, a prospective population-based cohort study. We assigned all participants an extended lifestyle score, with 1 point for each unhealthy lifestyle factor (incorporating sleep duration and high television viewing time, in addition to smoking, excessive alcohol, poor diet [low intake of oily fish or fruits and vegetables, and high intake of red meat or processed meats], and low physical activity), categorised as most healthy (score 0-2), moderately healthy (score 3-5), or least healthy (score 6-9). Cox proportional hazards models were used to examine the association between lifestyle score and health outcomes (all-cause mortality and cardiovascular disease mortality and incidence), and whether this association was modified by deprivation. All analyses were landmark analyses, in which participants were excluded if they had an event (death or cardiovascular disease event) within 2 years of recruitment. Participants with non-communicable diseases (except hypertension) and missing covariate data were excluded from analyses. Participants were also excluded if they reported implausible values for physical activity, sleep duration, and total screen time. All analyses were adjusted for age, sex, ethnicity, month of assessment, history of hypertension, systolic blood pressure, medication for hypercholesterolaemia or hypertension, and body-mass index categories., Findings: 328 594 participants aged 40-69 years were included in the study, with a mean follow-up period of 4·9 years (SD 0·83) after the landmark period for all-cause and cardiovascular disease mortality, and 4·1 years (0·81) for cardiovascular disease incidence. In the least deprived quintile, the adjusted hazard ratio (HR) in the least healthy lifestyle category, compared with the most healthy category, was 1·65 (95% CI 1·25-2·19) for all-cause mortality, 1·93 (1·16-3·20) for cardiovascular disease mortality, and 1·29 (1·10-1·52) for cardiovascular disease incidence. Equivalent HRs in the most deprived quintile were 2·47 (95% CI 2·04-3·00), 3·36 (2·36-4·76), and 1·41 (1·25-1·60), respectively. The HR for trend for one increment change towards least healthy in the least deprived quintile compared with that in the most deprived quintile was 1·25 (95% CI 1·12-1·39) versus 1·55 (1·40-1·70) for all-cause mortality, 1·30 (1·05-1·61) versus 1·83 (1·54-2·18) for cardiovascular disease mortality, and 1·10 (1·04-1·17) versus 1·16 (1·09-1·23) for cardiovascular disease incidence. A significant interaction was found between lifestyle and deprivation for all-cause and cardiovascular disease mortality (both p interaction <0·0001), but not for cardiovascular disease incidence (p interaction =0·11)., Interpretation: Wide combinations of lifestyle factors are associated with disproportionate harm in deprived populations. Social and fiscal policies that reduce poverty are needed alongside public health and individual-level interventions that address a wider range of lifestyle factors in areas of deprivation., Funding: None., (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.)

Introduction: The risk of mortality from cardiovascular disease (CVD) is higher in wintertime throughout the world, but it is not known if this reflects annual changes in diet or lifestyle, or an endogenous photoperiodic mechanism that is sensitive to changes in day length., Methods: Phenotypic data on cardiometabolic and lifestyle factors were collected throughout a 4 year time period from 502,642 middle-aged participants in UK Biobank. To assess the impact of seasonal environmental changes on cardiovascular risk factors, we linked these data to the outdoor temperature and day length at the time of assessment. Self-reported information on physical activity, diet and disease status were used to adjust for confounding factors related to health and lifestyle., Results: Mortality related to CVD was higher in winter, as were risk factors for this condition including blood pressure, markers of inflammation and body mass index (BMI). These seasonal rhythms were significantly related to day length after adjustment for other factors that might affect seasonality including physical activity, diet and outdoor temperature., Conclusions: The risk of CVD may be modulated by day length at temperate latitudes, and the implications of seasonality should be considered in all studies of human cardiometabolic health. Key messages In this cross-sectional study in UK Biobank, we report annual variations in cardiovascular risk factors and mortality that were associated with day length independent of environmental and lifestyle factors. These seasonal changes in day length might contribute to annual patterns in cardiovascular disease and mortality.

Background: Disruption of sleep and circadian rhythmicity is a core feature of mood disorders and might be associated with increased susceptibility to such disorders. Previous studies in this area have used subjective reports of activity and sleep patterns, but the availability of accelerometer-based data from UK Biobank participants permits the derivation and analysis of new, objectively ascertained circadian rhythmicity parameters. We examined associations between objectively assessed circadian rhythmicity and mental health and wellbeing phenotypes, including lifetime history of mood disorder., Methods: UK residents aged 37-73 years were recruited into the UK Biobank general population cohort from 2006 to 2010. We used data from a subset of participants whose activity levels were recorded by wearing a wrist-worn accelerometer for 7 days. From these data, we derived a circadian relative amplitude variable, which is a measure of the extent to which circadian rhythmicity of rest-activity cycles is disrupted. In the same sample, we examined cross-sectional associations between low relative amplitude and mood disorder, wellbeing, and cognitive variables using a series of regression models. Our final model adjusted for age and season at the time that accelerometry started, sex, ethnic origin, Townsend deprivation score, smoking status, alcohol intake, educational attainment, overall mean acceleration recorded by accelerometry, body-mass index, and a binary measure of childhood trauma., Findings: We included 91 105 participants with accelerometery data collected between 2013 and 2015 in our analyses. A one-quintile reduction in relative amplitude was associated with increased risk of lifetime major depressive disorder (odds ratio [OR] 1·06, 95% CI 1·04-1·08) and lifetime bipolar disorder (1·11, 1·03-1·20), as well as with greater mood instability (1·02, 1·01-1·04), higher neuroticism scores (incident rate ratio 1·01, 1·01-1·02), more subjective loneliness (OR 1·09, 1·07-1·11), lower happiness (0·91, 0·90-0·93), lower health satisfaction (0·90, 0·89-0·91), and slower reaction times (linear regression coefficient 1·75, 1·05-2·45). These associations were independent of demographic, lifestyle, education, and overall activity confounders., Interpretation: Circadian disruption is reliably associated with various adverse mental health and wellbeing outcomes, including major depressive disorder and bipolar disorder. Lower relative amplitude might be linked to increased susceptibility to mood disorders., Funding: Lister Institute of Preventive Medicine., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: Elevated white blood cell count is associated with a higher risk of cardiovascular disease (CVD). We aimed to investigate whether specific leukocyte subpopulations, which may more closely indicate a specific inflammatory pathway, are specifically associated with CVD., Approach and Results: Participants (478 259) from UK Biobank with data for white blood cell count were included. Death because of CVD (n=1377) and non-CVD causes (n=8987) occurred during median follow-up time of 7.0 years (interquartile range, 6.3-7.6). In Cox models, deciles of leukocyte counts (lymphocytes, monocytes, neutrophils, eosinophils, and basophils) were examined using the fifth decile as the referent group. Models were stratified by sex and adjusted for a range of classical risk factors. A sensitivity analysis excluded participants with baseline comorbidites and the first 2 years of follow-up. Men (hazard ratio [HR], 1.59; 95% confidence interval, 1.22-2.08) and women (HR, 2.15; 95% confidence interval, 1.38-3.35) in the highest decile of neutrophil count were at higher risk of CVD mortality and nonfatal CVD (men HR, 1.28; 95% confidence interval, 1.16-1.42 and women HR, 1.21; 95% confidence interval, 1.06-1.38). In the sensitivity analysis, the power to investigate CVD mortality was limited, but for both sexes combined, the linear HRs for a 1×10 9 /L cell count increase in white blood cell count and neutrophils, respectively, was 1.05 (1.03-1.07) and 1.07 (1.04-1.11)., Conclusions: Among circulating leukocyte subpopulations, neutrophil count in men was most consistently associated with fatal and nonfatal CVD. Further studies of interventions that lower circulating neutrophils, such as canakinumab, are required to investigate causality., (© 2018 American Heart Association, Inc.)

Aims: The data regarding the associations of body mass index (BMI) with cardiovascular (CVD) risk, especially for those at the low categories of BMI, are conflicting. The aim of our study was to examine the associations of body composition (assessed by five different measures) with incident CVD outcomes in healthy individuals., Methods and Results: A total of 296 535 participants (57.8% women) of white European descent without CVD at baseline from the UK biobank were included. Exposures were five different measures of adiposity. Fatal and non-fatal CVD events were the primary outcome. Low BMI (≤18.5 kg m-2) was associated with higher incidence of CVD and the lowest CVD risk was exhibited at BMI of 22-23 kg m-2 beyond, which the risk of CVD increased. This J-shaped association attenuated substantially in subgroup analyses, when we excluded participants with comorbidities. In contrast, the associations for the remaining adiposity measures were more linear; 1 SD increase in waist circumference was associated with a hazard ratio of 1.16 [95% confidence interval (CI) 1.13-1.19] for women and 1.10 (95% CI 1.08-1.13) for men with similar magnitude of associations for 1 SD increase in waist-to-hip ratio, waist-to-height ratio, and percentage body fat mass., Conclusion: Increasing adiposity has a detrimental association with CVD health in middle-aged men and women. The association of BMI with CVD appears more susceptible to confounding due to pre-existing comorbidities when compared with other adiposity measures. Any public misconception of a potential 'protective' effect of fat on CVD risk should be challenged. Take home figureThe obesity paradox is mainly due to the effect of confounding on BMI and disappears on other adiposity measures.

Aims: To quantify the extent to which ethnic differences in muscular strength might account for the substantially higher prevalence of diabetes in black and South-Asian compared with white European adults., Methods: This cross-sectional study used baseline data from the UK Biobank study on 418 656 white European, black and South-Asian participants, aged 40-69 years, who had complete data on diabetes status and hand-grip strength. Associations between hand-grip strength and diabetes were assessed using logistic regression and were adjusted for potential confounding factors., Results: Lower grip strength was associated with higher prevalence of diabetes, independent of confounding factors, across all ethnicities in both men and women. Diabetes prevalence was approximately three- to fourfold higher in South-Asian and two- to threefold higher in black participants compared with white European participants across all levels of grip strength, but grip strength in South-Asian men and women was ~ 5-6 kg lower than in the other ethnic groups. Thus, the attributable risk for diabetes associated with low grip strength was substantially higher in South-Asian participants (3.9 and 4.2 cases per 100 men and women, respectively) than in white participants (2.0 and 0.6 cases per 100 men and women, respectively). Attributable risk associated with low grip strength was also high in black men (4.3 cases) but not in black women (0.4 cases)., Conclusions: Low strength is associated with a disproportionately large number of diabetes cases in South-Asian men and women and in black men. Trials are needed to determine whether interventions to improve strength in these groups could help reduce ethnic inequalities in diabetes prevalence., (© 2017 Diabetes UK.)

International public health guidelines recommend that adults undertake at least 150 min.week-1 of moderate-intensity physical activity. However, the underpinning evidence has largely been obtained from studies of populations of white European descent. It is unclear whether these recommendations are appropriate for other ethnic groups, particularly South Asians, who have greater cardio-metabolic risk than white Europeans. The objective of our study was to determine the level of moderate-intensity physical activity required in South Asians adults to confer a similar cardio-metabolic risk profile to that observed in Europeans of similar age and body mass index (BMI) undertaking the currently recommended levels of 150 min.week-1. 148 South Asians and 163 white Europeans aged 18 to 70 years were recruited. Physical activity was measured objectively via vertical axis accelerations from hip-worn accelerometers. Factor analysis was used to summarize the measured risk biomarkers into a single underlying latent "factor" describing overall cardio-metabolic risk. Sex did not modify the association between physical activity and the cardio-metabolic risk factor, so data for both sexes were combined and models adjusted for age, sex, BMI and accelerometer wear time. We estimated that South Asian adults needed to undertake 232 (95% Confidence interval: 200 to 268) min.week-1 in order to obtain the same cardio-metabolic risk factor score as a white European undertaking 150 minutes of moderate-equivalent physical activity per week. The present findings suggest that South Asian men and women need to undertake ~230 minutes of moderate intensity physical activity per week. This equates to South Asians undertaking an extra 10-15 minutes of moderate intensity physical activity per day on top of existing recommendations.