In which common chronic conditions can (or cannot) obesity and lifestyle factors explain higher concentrations of C-reactive protein?

AIM: Elevated C-reactive protein (CRP), a marker of inflammation, is common in many chronic conditions. We aimed to examine to what extent elevated CRP in chronic conditions could be explained by concurrent adiposity. MATERIALS AND METHODS: This cross-sectional study analysed UK Biobank data on 10 chronic conditions reported at baseline. Linear regression models explored the extent to which CRP concentrations were elevated in each condition, unadjusted; adjusted for sociodemographic confounders and lifestyle and body mass index (BMI) in a series of models; or adjusted for BMI and waist circumference together or for adiposity alone. RESULTS: After exclusion of participants with a potential acute infection at baseline, we tested the association in 292 772 UK Biobank participants. Linear regression showed that elevated CRP concentration was associated with all included conditions. After adjustment for sociodemographic confounders, lifestyle and BMI, chronic kidney disease, heart failure, liver disease, psoriasis, rheumatoid arthritis and chronic obstructive pulmonary disease were still associated with elevated CRP. In contrast, the association between prevalent diabetes, prior myocardial infarction (MI), hypertension and sleep apnoea and CRP could be mostly explained by adiposity alone. For example, the 42% higher CRP concentrations in diabetes compared to those without diabetes in the unadjusted model (lnCRP ß: 0.35; 95% confidence interval [CI]: 0.32-0.37, p < 0.001) were completely attenuated after adjustment for BMI (lnCRP ß: -0.07; 95% CI: -0.09-0.05, p < 0.001). CONCLUSIONS/INTERPRETATION: In diabetes, MI, hypertension and sleep apnoea and elevated CRP appears to be accounted for by the greater adiposity typically evident in these conditions. However, for the other conditions, systemic inflammation cannot be explained by excess adiposity alone.

Association of meat, vegetarian, pescatarian and fish-poultry diets with risk of 19 cancer sites and all cancer: findings from the UK Biobank prospective cohort study and meta-analysis.

BACKGROUND: The associations of cancer with types of diets, including vegetarian, fish, and poultry-containing diets, remain unclear. The aim of this study was, therefore, to investigate the association of type of diet with all cancers and 19 site-specific incident cancers in a prospective cohort study and then in a meta-analysis of published prospective cohort studies. METHODS: A total of 409,110 participants from the UK Biobank study, recruited between 2006 and 2010, were included. The outcomes were incidence of all cancers combined and 19 cancer sites. Associations between the types of diets and cancer were investigated using Cox proportional hazards models. Previously published prospective cohort studies were identified from four databases, and a meta-analysis was conducted using random-effects models. RESULTS: The mean follow-up period was 10.6 years (IQR 10.0; 11.3). Compared with meat-eaters, vegetarians (hazard ratio (HR) 0.87 [95% CI: 0.79 to 0.96]) and pescatarians (HR 0.93 [95% CI: 0.87 to 1.00]) had lower overall cancer risk. Vegetarians also had a lower risk of colorectal and prostate cancers compared with meat-eaters. In the meta-analysis, vegetarians (Risk Ratio (RR): 0.90 [0.86 to 0.94]) and pescatarians (RR 0.91 [0.86; 0.96]) had lower risk of overall and colorectal cancer. No associations between the types of diets and prostate, breast, or lung cancers were found. CONCLUSIONS: Compared with meat-eaters, vegetarians and pescatarians had a lower risk of overall, colorectal, and prostate cancer. When results were pooled in a meta-analysis, the associations with overall and colorectal cancer persisted, but the results relating to other specific cancer sites were inconclusive.

The association between a lifestyle score, socioeconomic status, and COVID-19 outcomes within the UK Biobank cohort.

BACKGROUND: Infection with SARS-CoV-2 virus (COVID-19) impacts disadvantaged groups most. Lifestyle factors are also associated with adverse COVID-19 outcomes. To inform COVID-19 policy and interventions, we explored effect modification of socioeconomic-status (SES) on associations between lifestyle and COVID-19 outcomes. METHODS: Using data from UK-Biobank, a large prospective cohort of 502,536 participants aged 37-73 years recruited between 2006 and 2010, we assigned participants a lifestyle score comprising nine factors. Poisson regression models with penalised splines were used to analyse associations between lifestyle score, deprivation (Townsend), and COVID-19 mortality and severe COVID-19. Associations between each exposure and outcome were examined independently before participants were dichotomised by deprivation to examine exposures jointly. Models were adjusted for sociodemographic/health factors. RESULTS: Of 343,850 participants (mean age > 60 years) with complete data, 707 (0.21%) died from COVID-19 and 2506 (0.76%) had severe COVID-19. There was evidence of a nonlinear association between lifestyle score and COVID-19 mortality but limited evidence for nonlinearity between lifestyle score and severe COVID-19 and between deprivation and COVID-19 outcomes. Compared with low deprivation, participants in the high deprivation group had higher risk of COVID-19 outcomes across the lifestyle score. There was evidence for an additive interaction between lifestyle score and deprivation. Compared with participants with the healthiest lifestyle score in the low deprivation group, COVID-19 mortality risk ratios (95% CIs) for those with less healthy scores in low versus high deprivation groups were 5.09 (1.39-25.20) and 9.60 (4.70-21.44), respectively. Equivalent figures for severe COVID-19 were 5.17 (2.46-12.01) and 6.02 (4.72-7.71). Alternative SES measures produced similar results. CONCLUSIONS: Unhealthy lifestyles are associated with higher risk of adverse COVID-19, but risks are highest in the most disadvantaged, suggesting an additive influence between SES and lifestyle. COVID-19 policy and interventions should consider both lifestyle and SES. The greatest public health benefit from lifestyle focussed COVID-19 policy and interventions is likely to be seen when greatest support for healthy living is provided to the most disadvantaged groups.

Vegetarians, fish, poultry, and meat-eaters: who has higher risk of cardiovascular disease incidence and mortality? A prospective study from UK Biobank.

AIMS: To compare the incidence and mortality risk for cardiovascular diseases (CVD) [CVD and also ischaemic heart disease (IHD), myocardial infarction (MI), stroke, and heart failure (HF)] among people with different types of diets-including vegetarians, fish eaters, fish and poultry eaters, and meat-eaters-using data from UK Biobank. METHODS AND RESULTS: A total of 422 791 participants (55.4% women) were included in this prospective analysis. Using data from a food frequency questionnaire, four types of diets were derived. Associations between types of diets and health outcomes were investigated using Cox proportional hazard models. Meat-eaters comprised 94.7% of the cohort and were more likely to be obese than other diet groups. After a median follow-up of 8.5 years, fish eaters, compared with meat-eaters, had lower risks of incident CVD {hazard ratios (HR): 0.93 [95% confidence intervals (CI): 0.88-0.97]}, IHD [HR: 0.79 (95% CI: 0.70-0.88)], MI [HR: 0.70 (95% CI: 0.56-0.88)], stroke [HR: 0.79 (95% CI: 0.63-0.98)] and HF [HR: 0.78 (95% CI: 0.63-0.97)], after adjusting for confounders. Vegetarians had lower risk of CVD incidence [HR: 0.91 (95% CI: 0.86-0.96)] relative to meat-eaters. In contrast, the risk of adverse outcomes was not different in fish and poultry eaters compared with meat-eaters. No associations were identified between types of diets and CVD mortality. CONCLUSION: Eating fish rather than meat or poultry was associated with a lower risk of a range of adverse cardiovascular outcomes. Vegetarianism was only associated with a lower risk of CVD incidence.

Comparison of Conventional Lipoprotein Tests and Apolipoproteins in the Prediction of Cardiovascular Disease.

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.

Association Between Walking Pace and Stroke Incidence: Findings From the UK Biobank Prospective Cohort Study.

Background and Purpose- Stroke incidence in younger and middle-aged people is growing. Despite this, its associations in this subset of the stroke population are unknown, and prevention strategies are not tailored to meet their needs. This study examined the association between self-reported walking pace and incident stroke. Methods- Data from the UK Biobank were used in a prospective population-based study. Three hundred and sixty-three thousand, one hundred and thirty-seven participants aged 37 to 73 years (52% women) were recruited. The associations of self-reported walking pace with stroke incidence over follow-up were investigated using Cox proportional-hazard models. Results- Among 363,137 participants, 2705 (0.7%) participants developed a fatal or nonfatal stroke event over the mean follow-up period of 6.1 years (interquartile range, 5.4-6.7). Slow walking pace was associated with a higher hazard for stroke incidence (hazard ratio [HR], 1.45 [95% CI, 1.26-1.66]; P<0.0001). Stroke incidence was not associated with walking pace among people <65 years of age. However, slow walking pace was associated with a higher risk of stroke among participants aged ≥65 years (HR, 1.42 [95% CI, 1.17-1.72]; P<0.0001). A higher risk for stroke was observed on those with middle (HR, 1.28 [95% CI, 1.01-1.63]; P=0.039) and higher (HR, 1.29 [95% CI, 1.05-1.69]; P=0.012) deprivation levels but not in the least deprived individuals. Similarly, overweight (HR, 1.30 [95% CI, 1.04-1.63]; P=0.019) and obese (HR, 1.33 [95% CI, 1.09-1.63]; P=0.004) but not normal-weight individuals had a higher risk of stroke incidence. Conclusions- Slow walking pace was associated with a higher risk of stroke among participants over 64 years of age in this population-based cohort study. The addition of the measurement of self-reported walking pace to primary care or public health clinical consultations may be a useful screening tool for stroke risk.

The associations of sugar-sweetened, artificially sweetened and naturally sweet juices with all-cause mortality in 198,285 UK Biobank participants: a prospective cohort study.

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.

Occupation and risk of severe COVID-19: prospective cohort study of 120 075 UK Biobank participants.

OBJECTIVES: To investigate severe COVID-19 risk by occupational group. METHODS: Baseline UK Biobank data (2006-10) for England were linked to SARS-CoV-2 test results from Public Health England (16 March to 26 July 2020). Included participants were employed or self-employed at baseline, alive and aged <65 years in 2020. Poisson regression models were adjusted sequentially for baseline demographic, socioeconomic, work-related, health, and lifestyle-related risk factors to assess risk ratios (RRs) for testing positive in hospital or death due to COVID-19 by three occupational classification schemes (including Standard Occupation Classification (SOC) 2000). RESULTS: Of 120 075 participants, 271 had severe COVID-19. Relative to non-essential workers, healthcare workers (RR 7.43, 95% CI 5.52 to 10.00), social and education workers (RR 1.84, 95% CI 1.21 to 2.82) and other essential workers (RR 1.60, 95% CI 1.05 to 2.45) had a higher risk of severe COVID-19. Using more detailed groupings, medical support staff (RR 8.70, 95% CI 4.87 to 15.55), social care (RR 2.46, 95% CI 1.47 to 4.14) and transport workers (RR 2.20, 95% CI 1.21 to 4.00) had the highest risk within the broader groups. Compared with white non-essential workers, non-white non-essential workers had a higher risk (RR 3.27, 95% CI 1.90 to 5.62) and non-white essential workers had the highest risk (RR 8.34, 95% CI 5.17 to 13.47). Using SOC 2000 major groups, associate professional and technical occupations, personal service occupations and plant and machine operatives had a higher risk, compared with managers and senior officials. CONCLUSIONS: Essential workers have a higher risk of severe COVID-19. These findings underscore the need for national and organisational policies and practices that protect and support workers with an elevated risk of severe COVID-19.

Intranasal ketamine for acute pain management in children: A systematic review and meta-analysis.

STUDY OBJECTIVE: To assess the efficacy and safety of intranasal analgesic-dose ketamine as compared to intranasal fentanyl for pediatric acute pain. METHODS: A systematic review and meta-analysis was performed following the PRISMA guidelines. We searched PubMed, Embase, and Scopus databases for randomized controlled trials from inception to December 2019. We conducted meta-analysis with random-effects models to evaluate pain reduction, rescue analgesia, adverse events and sedation between intranasal ketamine and intranasal fentanyl. Random-effects models were used to estimate weighted mean differences (WMD) and pooled relative risks (RR). RESULTS: A total of 546 studies were screened and 4 trials were included. In the meta-analysis of 4 studies including 276 patients, ketamine had similar reductions in pain scores from baseline to all post-intervention times (10 to 15 min: WMD -1.42, 95% CI -9.95 to 7.10; 30 min: WMD 0.40, 95% CI -6.29 to 7.10; 60 min: WMD -0.64, 95% CI -6.76 to 5.47). Ketamine was associated with similar rates of rescue analgesia (RR 0.74, 95% CI 0.44 to 1.25). Ketamine had a higher risk of non-serious adverse events (RR 2.00, 95% CI 1.43 to 2.79), and no patients receiving ketamine had a serious adverse event. There was one serious adverse event (hypotension) with fentanyl that self-resolved. No patients receiving either IN fentanyl or ketamine had significant sedation. CONCLUSION: Intranasal analgesic-dose ketamine may be considered as an alternative to opioids for acute pain management in children. Its accepted use will depend on the tolerability of non-serious adverse events and the desire to avoid opioids.

Do physical activity, commuting mode, cardiorespiratory fitness and sedentary behaviours modify the genetic predisposition to higher BMI? Findings from a UK Biobank study.

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 (ß: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 (ß:0.33 kg.m-2, p = 6.4 × 10-41). We observed similar patterns for fitness (Unfit ß:0.72 versus Fit ß:0.36 kg.m-2, P[interaction] = 1.4 × 10-11), walking pace (Slow ß:0.91 versus Brisk ß:0.38 kg.m-2, P[interaction] = 8.1 × 10-27), discretionary sedentary behaviour (High ß:0.64 versus Low ß:0.48 kg.m-2, P[interaction] = 9.1 × 10-12), TV viewing (High ß:0.62 versus Low ß:0.47 kg.m-2, P[interaction] = 1.7 × 10-11), PC-screen time (High ß:0.82 versus Low ß:0.54 kg.m-2, P[interaction] = 0.0004) and playing computer games (Often ß:0.69 versus Low ß: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.

The association of grip strength with health outcomes does not differ if grip strength is used in absolute or relative terms: a prospective cohort study.

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.

Pediatric emergency medical services in privately insured patients: A 10-year national claims analysis.

OBJECTIVE: To characterize pediatric Emergency Medicine Service (EMS) transports to the Emergency Department (ED) using a national claims database. METHODS: We included children, 18 years and younger, transported by EMS to an ED, from 2007 to 2016 in the OptumLabs Data Warehouse. ICD-9 and ICD-10 diagnosis codes were used to categorize disease system involvement. Interventions performed were extracted using procedure codes. ED visit severity was measured by the Minnesota Algorithm. RESULTS: Over a 10-year period, 239,243 children were transported. Trauma was the most frequent diagnosis category for transport for children ≥5 years of age, 35.1% (age 6-13) and 32.7% (age 14-18). The most common diagnosis category in children <6 years of age was neurologic (29.3%), followed by respiratory (23.1%). Over 10 years, transports for mental disorders represented 15.3% in children age 14 to 18, and had the greatest absolute increase (rate difference + 10.4 per 10,000) across all diagnoses categories. Neurologic transports also significantly increased in children age 14 to 18 (rate difference + 6.9 per 10,000). Trauma rates decreased across all age groups and had its greatest reduction among children age 14 to 18 (rate difference - 6.8 per 10,000). Across all age groups, an intervention was performed in 15.6%. Most children (83.3%) were deemed to have ED care needed type of visit, and 15.8% of the transports resulted in a hospital admission. CONCLUSION: Trauma is the most frequent diagnosis for transport in children older than 5 years of age. Mental health and neurologic transports have markedly increased, while trauma transports have decreased. Most children arriving by ambulance were classified as requiring ED level of care. These changes might have significant implication for EMS personnel and policy makers.

Dose-response associations of cardiorespiratory fitness with all-cause mortality and incidence and mortality of cancer and cardiovascular and respiratory diseases: the UK Biobank cohort study.

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.

The impact of confounding on the associations of different adiposity measures with the incidence of cardiovascular disease: a cohort study of 296 535 adults of white European descent.

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.

Associations of Dietary Protein Intake With Fat-Free Mass and Grip Strength: A Cross-Sectional Study in 146,816 UK Biobank Participants.

Adequate dietary protein intake is important for the maintenance of fat-free mass (FFM) and muscle strength, but optimal requirements remain unknown. Our aim in the current study was to explore the associations of protein intake with FFM and grip strength. We used baseline data from the UK Biobank (a study of 146,816 participants aged 40-69 years with data collected across the United Kingdom in 2007-2010) to examine the associations of protein intake with FFM and grip strength. Protein intake was positively associated with FFM (men: 5.1% (95% confidence interval (CI): 5.0, 5.2); women: 7.7% (95% CI: 7.7, 7.8)) and grip strength (men: 0.076 kg/kg (95% CI: 0.074, 0.078); women: 0.074 kg/kg (95% CI: 0.073, 0.076)) per 0.5-g/kg/day (grams per kg of body mass per day) increment in protein intake. FFM and grip strength were higher with higher intakes across the full range of intakes (i.e., highest in persons who reported consuming ≥2.00 g/kg/day) independently of sociodemographic factors, other dietary measures, physical activity, and comorbidity. FFM and grip strength were lower with age, but this association did not differ by category of protein intake (P > 0.05). The current recommendation for all adults (ages 40-69 years) to maintain a protein intake of 0.8 g/kg/day may need to be increased to optimize FFM and grip strength.

Associations of discretionary screen time with mortality, cardiovascular disease and cancer are attenuated by strength, fitness and physical activity: findings from the UK Biobank study.

BACKGROUND: Discretionary screen time (time spent viewing a television or computer screen during leisure time) is an important contributor to total sedentary behaviour, which is associated with increased risk of mortality and cardiovascular disease (CVD). The aim of this study was to determine whether the associations of screen time with cardiovascular disease and all-cause mortality were modified by levels of cardiorespiratory fitness, grip strength or physical activity. METHODS: In total, 390,089 participants (54% women) from the UK Biobank were included in this study. All-cause mortality, CVD and cancer incidence and mortality were the main outcomes. Discretionary television (TV) viewing, personal computer (PC) screen time and overall screen time (TV + PC time) were the exposure variables. Grip strength, fitness and physical activity were treated as potential effect modifiers. RESULTS: Altogether, 7420 participants died, and there were 22,210 CVD events, over a median of 5.0 years follow-up (interquartile range 4.3 to 5.7; after exclusion of the first 2 years from baseline in the landmark analysis). All discretionary screen-time exposures were significantly associated with all health outcomes. The associations of overall discretionary screen time with all-cause mortality and incidence of CVD and cancer were strongest amongst participants in the lowest tertile for grip strength (all-cause mortality hazard ratio per 2-h increase in screen time (1.31 [95% confidence interval: 1.22-1.43], p < 0.0001; CVD 1.21 [1.13-1.30], p = 0.0001; cancer incidence 1.14 [1.10-1.19], p < 0.0001) and weakest amongst those in the highest grip-strength tertile (all-cause mortality 1.04 [0.95-1.14], p = 0.198; CVD 1.05 [0.99-1.11], p = 0.070; cancer 0.98 [0.93-1.05], p = 0.771). Similar trends were found for fitness (lowest fitness tertile: all-cause mortality 1.23 [1.13-1.34], p = 0.002 and CVD 1.10 [1.02-1.22], p = 0.010; highest fitness tertile: all-cause mortality 1.12 [0.96-1.28], p = 0.848 and CVD 1.01 [0.96-1.07], p = 0.570). Similar findings were found for physical activity for all-cause mortality and cancer incidence. CONCLUSIONS: The associations between discretionary screen time and adverse health outcomes were strongest in those with low grip strength, fitness and physical activity and markedly attenuated in those with the highest levels of grip strength, fitness and physical activity. Thus, if these associations are causal, the greatest benefits from health promotion interventions to reduce discretionary screen time may be seen in those with low levels of strength, fitness and physical activity.

The association between physical activity and risk of mortality is modulated by grip strength and cardiorespiratory fitness: evidence from 498 135 UK-Biobank participants.

Aims: It is unclear whether the potential benefits of physical activity differ according to level of cardiorespiratory fitness (CRF) or strength. The aim of this study was to determine whether the association between physical activity and mortality is moderated by CRF and grip strength sufficiently to inform health promotion strategies. Methods and Results: 498 135 participants (54.7% women) from the UK Biobank were included (CRF data available in 67 702 participants). Exposure variables were grip strength, CRF, and physical activity. All-cause mortality and cardiovascular disease (CVD) events were the outcomes. 8591 died over median 4.9 years [IQR 4.3­5.5] follow-up. There was a significant interaction between total physical activity and grip strength (P < 0.0001) whereby the higher hazard of mortality associated with lower physical activity was greatest among participants in the lowest tertile for grip strength (hazard ratio, HR:1.11 [95% CI 1.09­1.14]) and lowest among those in the highest grip strength tertile (HR:1.04 [1.01­1.08]). The interaction with CRF did not reach statistical significance but the pattern was similar. The association between physical activity and mortality was larger among those in the lowest tertile of CRF (HR:1.13 [1.02­1.26]) than those in the highest (HR:1.03 [0.91­1.16]). The pattern for CVD events was similar. Conclusions: These data provide novel evidence that strength, and possibly CRF, moderate the association between physical activity and mortality. The association between physical activity and mortality is strongest in those with the lowest strength (which is easily measured), and the lowest CRF, suggesting that these sub-groups could benefit most from interventions to increase physical activity.

Associations between single and multiple cardiometabolic diseases and cognitive abilities in 474 129 UK Biobank participants.

AIMS: Cardiometabolic diseases (hypertension, coronary artery disease [CAD] and diabetes are known to associate with poorer cognitive ability but there are limited data on whether having more than one of these conditions is associated with additive effects. We aimed to quantify the magnitude of their associations with non-demented cognitive abilities and determine the extent to which these associations were additive. METHODS AND RESULTS: We examined cognitive test scores in domains of reasoning, information processing speed and memory, included as part of the baseline UK Biobank cohort assessment (N = 474 129 with relevant data), adjusting for a range of potentially confounding variables. The presence of hypertension, CAD and diabetes generally associated with poorer cognitive scores on all tests, compared with a control group that reported none of these diseases. There was evidence of an additive deleterious dose effect of an increasing number of cardiometabolic diseases, for reasoning scores (unstandardized additive dose beta per disease = -0.052 score points out of 13, 95% CI [confidence intervals] -0.063 to - 0.041, P < 0.001), log reaction time scores (exponentiated beta = 1.005, i.e. 0.5% slower, 95% CI 1.004-1.005, P < 0.001) and log memory errors (exponentiated beta = 1.005 i.e. 0.5% more errors; 95% CI 1.003-1.008). CONCLUSION: Cardiometabolic diseases are associated with worse cognitive abilities, and the potential effect of an increasing number of cardiometabolic conditions appears additive. These results reinforce the notion that preventing or delaying cardiovascular disease or diabetes may delay cognitive decline and possible dementia.

Probing the metabolic network in bloodstream-form Trypanosoma brucei using untargeted metabolomics with stable isotope labelled glucose.

Metabolomics coupled with heavy-atom isotope-labelled glucose has been used to probe the metabolic pathways active in cultured bloodstream form trypomastigotes of Trypanosoma brucei, a parasite responsible for human African trypanosomiasis. Glucose enters many branches of metabolism beyond glycolysis, which has been widely held to be the sole route of glucose metabolism. Whilst pyruvate is the major end-product of glucose catabolism, its transamination product, alanine, is also produced in significant quantities. The oxidative branch of the pentose phosphate pathway is operative, although the non-oxidative branch is not. Ribose 5-phosphate generated through this pathway distributes widely into nucleotide synthesis and other branches of metabolism. Acetate, derived from glucose, is found associated with a range of acetylated amino acids and, to a lesser extent, fatty acids; while labelled glycerol is found in many glycerophospholipids. Glucose also enters inositol and several sugar nucleotides that serve as precursors to macromolecule biosynthesis. Although a Krebs cycle is not operative, malate, fumarate and succinate, primarily labelled in three carbons, were present, indicating an origin from phosphoenolpyruvate via oxaloacetate. Interestingly, the enzyme responsible for conversion of phosphoenolpyruvate to oxaloacetate, phosphoenolpyruvate carboxykinase, was shown to be essential to the bloodstream form trypanosomes, as demonstrated by the lethal phenotype induced by RNAi-mediated downregulation of its expression. In addition, glucose derivatives enter pyrimidine biosynthesis via oxaloacetate as a precursor to aspartate and orotate.

Alzheimer disease genetic risk factor APOE e4 and cognitive abilities in 111,739 UK Biobank participants.

BACKGROUND: the apolipoprotein (APOE) e4 locus is a genetic risk factor for dementia. Carriers of the e4 allele may be more vulnerable to conditions that are independent risk factors for cognitive decline, such as cardiometabolic diseases. OBJECTIVE: we tested whether any association with APOE e4 status on cognitive ability was larger in older ages or in those with cardiometabolic diseases. SUBJECTS: UK Biobank includes over 500,000 middle- and older aged adults who have undergone detailed medical and cognitive phenotypic assessment. Around 150,000 currently have genetic data. We examined 111,739 participants with complete genetic and cognitive data. METHODS: baseline cognitive data relating to information processing speed, memory and reasoning were used. We tested for interactions with age and with the presence versus absence of type 2 diabetes (T2D), coronary artery disease (CAD) and hypertension. RESULTS: in several instances, APOE e4 dosage interacted with older age and disease presence to affect cognitive scores. When adjusted for potentially confounding variables, there was no APOE e4 effect on the outcome variables. CONCLUSIONS: future research in large independent cohorts should continue to investigate this important question, which has potential implications for aetiology related to dementia and cognitive impairment.