Long-chain n -3 polyunsaturated fatty acids for the management of age- and disease-related declines in skeletal muscle mass, strength and physical function.

PURPOSE OF REVIEW: This review uses the hierarchy of evidence as a framework to critically evaluate the effect of long chain n -3 polyunsaturated fatty acid (LC n -3 PUFA) ingestion alone, or as an adjunctive intervention to resistance training, on muscle health-related outcomes in healthy and clinical older adult populations. RECENT FINDINGS: Systematic reviews and meta-analyses of randomized controlled trials consistently report small, but clinically-relevant, effects of LC n -3 PUFA ingestion on strength outcomes, whereas mixed findings have been reported regarding changes in muscle mass and physical function. Cohort studies indicate an association between higher dietary LC n -3 PUFA intake and reduced likelihood of a sarcopenia diagnosis. Acute metabolic studies provide limited evidence for an effect of LC n -3 PUFA ingestion alone, or in combination with resistance training, on free-living integrated rates of MPS, static markers of muscle protein breakdown, or satellite cell activation in healthy older adults. SUMMARY: Recent data supports the efficacy of LCn-3 PUFA ingestion to facilitate small, but clinically relevant, improvements in muscle strength in healthy and clinical older adult populations. The mechanism(s) that underpin the action of LC n -3 PUFA in promoting strength outcomes remain unknown, but likely relate to neuromuscular function.

In people with type 2 diabetes, sarcopenia is associated with the incidence of cardiovascular disease: A prospective cohort study from the UK Biobank.

AIM: To investigate the association of sarcopenia with cardiovascular disease (CVD) incidence in people with type 2 diabetes. MATERIALS AND METHODS: A prospective cohort study with 11 974 White European UK Biobank participants with type 2 diabetes, aged 40-70 years, included. Sarcopenia was defined based on the European Working Group on Sarcopenia in Older People as either non-sarcopenic or sarcopenic. Outcomes included CVD, stroke, heart failure (HF) and myocardial infarction (MI). The association between sarcopenia and the incidence of outcomes was investigated using Cox proportional hazard models adjusted for sociodemographic and lifestyle factors. The rate advancement period was used to estimate the time period by which CVD is advanced because of sarcopenia. RESULTS: Over a median follow-up of 10.7 years, 1957 participants developed CVDs: 373 had a stroke, 307 had an MI and 742 developed HF. Compared with non-sarcopenia, those with sarcopenia had higher risks of CVD (HR 1.89 [95% CI 1.61; 2.21]), HF (HR 2.59 [95% CI 2.12; 3.18]), stroke (HR 1.90 [95% CI 1.38; 2.63]), and MI (HR 1.56 [95% CI 1.04; 2.33]) after adjustment for all covariates. Those with sarcopenia had CVD incidence rates equivalent to those without sarcopenia who were 14.5 years older. Similar results were found for stroke, HF and MI. CONCLUSIONS: In people with type 2 diabetes, sarcopenia increased the risk of developing CVD, which might occur earlier than in those without sarcopenia. Therefore, sarcopenia screening and prevention in patients with type 2 diabetes may be useful to prevent the complications of CVD.

Association Between Device-Measured Physical Activity and Incident Heart Failure: A Prospective Cohort Study of 94 739 UK Biobank Participants.

BACKGROUND: Studies of objectively measured physical activity (PA) have investigated acute cardiovascular outcomes but not heart failure (HF), an emerging chronic condition. This study aimed to investigate the dose-response relationship between device-measured PA and HF by intensity of PA. METHODS: This was a prospective cohort study of 94 739 UK Biobank participants who had device-measured PA in 2013 to 2015 and were free from myocardial infarction and HF. PA was measured with a wrist-worn accelerometer, and time spent on light-, moderate-, and vigorous-intensity PA was extracted. Incident HF was ascertained from linked hospital and death records. Cox proportional hazard models with cubic penalized splines were used to study the associations, which were adjusted for sociodemographic and lifestyle factors. Competing risk was handled with cause-specific hazard ratios. RESULTS: The overall incidence of HF was 98.5 per 10 000 person-years over a median 6.1 years of follow-up. Compared with participants who undertook no moderate- to vigorous-intensity PA, those who performed 150 to 300 min/wk of moderate-intensity PA (hazard ratio, 0.37 [95% CI, 0.34-0.41]) and 75 to 150 min/wk of vigorous-intensity PA (hazard ratio, 0.34 [95% CI, 0.25-0.46]) were at lower HF risk. The association between vigorous-intensity PA and HF was reverse-J shaped with a potentially lower risk reduction above 150 min/wk. CONCLUSIONS: Device-measured PA, especially moderate-intensity PA, was associated with a lower risk of HF. Current vigorous-intensity PA recommendations should be encouraged but not increased. In contrast, increasing moderate-intensity PA may be beneficial even among those meeting current recommendations.

Dose-response relationship between device-measured physical activity and incident type 2 diabetes: findings from the UK Biobank prospective cohort study.

BACKGROUND: Most studies investigating the association between physical activity (PA) and the risk of type 2 diabetes are derived from self-reported questionnaires, with limited evidence using device-based measurements. Therefore, this study aimed to investigate the dose-response relationship between device-measured PA and incident type 2 diabetes. METHODS: This prospective cohort study included 40,431 participants of the UK Biobank. Wrist-worn accelerometers were used to estimate total, light, moderate, vigorous and moderate-to-vigorous PA. The associations between PA and incident type 2 diabetes were analysed using Cox-proportional hazard models. The mediating role of body mass index (BMI) was tested under a causal counterfactual framework. RESULTS: The median follow-up period was 6.3 years (IQR: 5.7-6.8), with 591 participants developing type 2 diabetes. Compared to those achieving < 150 min/week of moderate PA, people achieving 150-300, 300-600 and > 600 min/week were at 49% (95% CI 62-32%), 62% (95% CI 71-50%) and 71% (95% CI 80-59%) lower risk of type 2 diabetes, respectively. For vigorous PA, compared to those achieving < 25 min/week, individuals achieving 25-50, 50-75 and > 75 min/week were at 38% (95% CI 48-33%), 48% (95% CI 64-23%) and 64% (95% CI 78-42%) lower type 2 diabetes risk, respectively. Twelve per cent and 20% of the associations between vigorous and moderate PA and type 2 diabetes were mediated by lower BMI, respectively. CONCLUSIONS: PA has clear dose-response relationship with a lower risk of type 2 diabetes. Our findings support the current aerobic PA recommendations but suggest that additional PA beyond the recommendations is associated with even greater risk reduction. TRIAL REGISTRATION: The UK Biobank study was approved by the North West Multi-Centre Research Ethics Committee (Ref 11/NW/0382 on June 17, 2011).

Cost-effectiveness of cognitive behavioural and personalized exercise interventions for reducing fatigue in inflammatory rheumatic diseases.

OBJECTIVES: To estimate the cost-effectiveness of a cognitive behavioural approach (CBA) or a personalized exercise programme (PEP), alongside usual care (UC), in patients with inflammatory rheumatic diseases who report chronic, moderate to severe fatigue. METHODS: A within-trial cost-utility analysis was conducted using individual patient data collected within a multicentre, three-arm randomized controlled trial over a 56-week period. The primary economic analysis was conducted from the UK National Health Service (NHS) perspective. Uncertainty was explored using cost-effectiveness acceptability curves and sensitivity analysis. RESULTS: Complete-case analysis showed that, compared with UC, both PEP and CBA were more expensive [adjusted mean cost difference: PEP £569 (95% CI: £464, £665); CBA £845 (95% CI: £717, £993)] and, in the case of PEP, significantly more effective [adjusted mean quality-adjusted life year (QALY) difference: PEP 0.043 (95% CI: 0.019, 0.068); CBA 0.001 (95% CI: -0.022, 0.022)]. These led to an incremental cost-effectiveness ratio (ICER) of £13 159 for PEP vs UC, and £793 777 for CBA vs UC. Non-parametric bootstrapping showed that, at a threshold value of £20 000 per QALY gained, PEP had a probability of 88% of being cost-effective. In multiple imputation analysis, PEP was associated with significant incremental costs of £428 (95% CI: £324, £511) and a non-significant QALY gain of 0.016 (95% CI: -0.003, 0.035), leading to an ICER of £26 822 vs UC. The estimates from sensitivity analyses were consistent with these results. CONCLUSION: The addition of a PEP alongside UC is likely to provide a cost-effective use of health care resources.

The effect of home-based resistance exercise training in people with type 2 diabetes: A randomized controlled trial.

AIMS: To evaluate the effects of pragmatic home-based resistance exercise training on glycated haemoglobin (HbA1c) as well as muscle strength and body composition in people with type 2 diabetes. MATERIALS AND METHODS: People with type 2 diabetes were randomized (1:1) to usual care or usual care plus home-based resistance exercise for 32 weeks. The changes in HbA1c, body composition, physical function, quality of life, continuous glucose monitoring and liver fat were compared by randomized group using linear regression. RESULTS: This study recruited 120 participants (female: n = 46 [38%], age 60.2 (9.4) years, BMI 31.1 (5.4) kg.m-2 ), 64 to intervention and 56 to usual care. Intention to treat analysis revealed no effect on HbA1c (difference in difference: -0.4 mmol/mol, 95% confidence interval [CI]: -3.26, 2.47; p = 0.78) but the intervention increased the number of push-ups (3.6 push-ups, 95% CI: 0.8, 6.4), arm lean mass (116 g, 95% CI: 6, 227) and leg lean mass (438 g, 95% CI 65, 810) and decreased liver fat (-1.27%, 95% CI -2.17, -0.38), with no differences in other outcomes. Per-protocol analysis revealed similar results. CONCLUSIONS: Home-based resistance exercise is unlikely to lower HbA1c in people with type 2 diabetes but may be of benefit for maintaining muscle mass and function and reducing liver fat.

Association between walking pace and incident type 2 diabetes by adiposity level: A prospective cohort study from the UK Biobank.

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.

Associations of grip strength and walking pace with mortality in stroke survivors: A prospective study from UK Biobank.

INTRODUCTION: Although stroke is an emerging cause of disability and mortality globally, associations between physical capability markers and mortality in stroke survivors are elusive. This study investigated the individual and combined associations of walking pace and grip strength with all-cause and stroke mortality in stroke survivors. METHODS: Individual and combined associations of walking pace and grip strength with stroke deaths and all-cause mortality were investigated using Cox proportional-hazard models adjusted for sociodemographic, lifestyle, and health-related variables. RESULTS: Seven thousand four hundred eighty-six stroke survivors from the UK Biobank study (aged 40-70 years; 42.4% women) were included in this prospective study. Over a median follow-up of 12.6 (IQR: 11.9-13.3) years, 1490 (19.9%) participants died, of whom 222 (3.0%) died from stroke. After adjusting for confounding factors, and compared to individuals in the average/brisk walking pace category, those who reported a slow walking pace had 2.00 (95% CI: 1.50-2.68) and 1.99 (95% CI: 1.78-2.23) times higher risk of stroke mortality and all-cause mortality, respectively. Similar associations were identified for participants with low grip strength compared with those with normal levels. For combined associations, those with both slow walking pace and low grip strength showed the highest risk of stroke mortality (hazard ratio: 2.86 [95% CI: 1.93-4.22]). Similar results were found for all-cause mortality. CONCLUSIONS: Low grip strength and slow walking pace were associated with a higher risk of stroke and all-cause mortality in stroke survivors. If these associations are causal, improving physical capability among stroke survivors might potentially prolong survival.

Derivation and Validation of a 10-Year Risk Score for Symptomatic Abdominal Aortic Aneurysm: Cohort Study of Nearly 500 000 Individuals.

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.

Associations of muscle mass and grip strength with severe NAFLD: A prospective study of 333,295 UK Biobank participants.

BACKGROUND & AIMS: Cross-sectional studies have reported that lower muscle mass and strength are risk factors for non-alcoholic fatty liver disease (NAFLD). However, the evidence from prospective studies is limited. This study examined both the strength and pattern of the associations between these 2 physical capability markers and severe NAFLD using data from the UK Biobank study. METHODS: A total of 333,295 participants were included in this prospective study. Grip strength was measured using a Jamar J00105 hydraulic hand dynamometer, and the Janssen equation was used to estimate skeletal muscle mass by bioelectrical impedance. Muscle mass was adjusted for body weight and all exposures were sex-standardised. Associations of muscle mass and strength with severe NAFLD (defined as hospital admission or death) were first investigated by tertile of each exposure using Cox proportional hazard models. Non-linear associations were investigated using penalised cubic splines fitted in the Cox proportional hazard models. RESULTS: After a median follow-up of 10 years (IQR 9.3 to 10.7 years), 3,311 individuals had severe NAFLD (3,277 hospitalisations and 34 deaths). Compared with the lowest tertile of muscle mass, the risk of severe NAFLD was lower in the middle (hazard ratio 0.76; 95% CI 0.70-0.83) and the highest tertile (hazard ratio 0.46; 95% CI 0.40-0.52). Tertiles of grip strength showed a similar pattern. Non-linearity was only identified for muscle mass (p <0.001). Being on the lower tertile of grip strength and muscle mass accounted for 17.7% and 33.1% of severe NAFLD cases, respectively. CONCLUSIONS: Lower muscle mass and grip strength were associated with higher risk of developing severe NAFLD. Interventions to improve physical capability may be protective, but this needs to be investigated in appropriately designed trials. LAY SUMMARY: Lower muscle mass - both quantity and quality - were associated with a higher risk of severe non-alcoholic fatty liver disease. Therefore, improving muscle mass might be a protective factor against this increasing public health problem.

Ethnic differences in cardiovascular risk: examining differential exposure and susceptibility to risk factors.

BACKGROUND: Ethnic differences in cardiovascular disease (CVD) risk have been known for decades, but a systematic exploration of how exposure and susceptibility to risk factors may contribute is lacking. This study aimed to investigate the potential impact of differential exposure and susceptibility between South Asian, Black, and White individuals. METHODS: This is a population-based prospective cohort study of UK Biobank participants with a median follow-up of 11.3 years. The association between ethnic group and CVD risk was studied. Additional risk factors were then adjusted to examine mediations. Moderation analysis was conducted to identify whether risk factors had a stronger association in the ethnic minority groups. Population attributable fractions were also calculated to quantify the relative contributions of risk factors for each ethnic group. RESULTS: When adjusted for only age and sex, there was a higher risk of CVD among South Asian (n=8815; HR [95% CI] 1.69 [1.59-1.79]) and Black (n=7526; HR [95% CI] 1.12 [1.03-1.22]) compared with White participants (n=434,809). The excess risk of Black participants was completely attenuated following adjustment for deprivation. Compared with White participants, the associations of BMI, triglycerides, and HbA1c with CVD were stronger in South Asians. Adiposity was attributable to the highest proportion of CVD regardless of ethnicity. Smoking had the second largest contribution to CVD among White and Black participants, and HbA1c among South Asian participants. CONCLUSIONS: Adiposity is an important risk factor for CVD regardless of ethnicity. Ethnic inequalities in CVD incidence may be best tackled by targeting interventions according to ethnic differences in risk profiles.

Device-measured physical activity and incident affective disorders.

BACKGROUND: Studies on physical activity (PA) and mental health are largely limited to self-reported PA. This study aims to use prospective cohort data to investigate the association between device-measured PA and affective disorders. METHODS: A total of 37,327 participants from UK Biobank who had not had any prior affective disorder diagnoses were included in this prospective cohort study. Wrist-worn accelerometers were used to measure total, light (LPA), moderate (MPA), and vigorous (VPA) PA. Associations between PA domains and affective disorders were analysed using penalised splines in Cox proportional hazard models. Analyses were adjusted for other intensity-specific PA and sociodemographic and lifestyle factors. Sensitivity analyses were conducted adjusting for body mass index and longstanding illnesses as well as excluding events in the first 2 years of follow-up. Preventable fractions for the population were estimated for MPA and VPA. RESULTS: Over a median follow-up of 6.8 years, 1262 (3.4%) individuals were diagnosed with affective disorders. Replacing 30 min of sedentary behaviour in a week with MPA (HR 0.95, 95% CI 0.94-0.97) or VPA (HR 0.91, 95% CI 0.85-0.98) was associated with lower risk of affective behaviours, up to 500 and 120 min of MPA and VPA. Assuming causality, 5.14% and 18.88% of affective disorders could have been prevented if MPA ≥150 min/week and VPA ≥75 min/week were achieved, respectively, across the study population. CONCLUSIONS: Device-measured MPA and VPA were associated with lower risk of affective disorders. The potential mental health benefits of MPA continue to accrue above the current World Health Organization recommendation.

Types of diet, obesity, and incident type 2 diabetes: Findings from the UK Biobank prospective cohort study.

AIM: To investigate the associations between types of diet and incident type 2 diabetes and whether adiposity mediated these associations. MATERIALS AND METHODS: In total, 203 790 participants from UK Biobank (mean age 55.2 years; 55.8% women) without diabetes at baseline were included in this prospective study. Using the dietary intake data self-reported at baseline, participants were categorized as vegetarians (n = 3237), fish eaters (n = 4405), fish and poultry eaters (n = 2217), meat eaters (n = 178 004) and varied diet (n = 15 927). The association between type of diet and incident type 2 diabetes was investigated using Cox-proportional hazards models with a 2-year landmark analysis. The mediation role of adiposity was tested under a counterfactual framework. RESULTS: After excluding the first 2 years of follow-up, the median follow-up was 5.4 (IQR: 4.8-6.3) years, during which 5067 (2.5%) participants were diagnosed with type 2 diabetes. After adjusting for lifestyle factors, fish eaters (HR 0.52 [95% CI: 0.39-0.69]) and fish and poultry eaters (HR 0.62 [95% CI: 0.45-0.88]) had a lower risk of incident type 2 diabetes compared with meat eaters. The association for vegetarians was not significant. Varied diet had a higher risk of type 2 diabetes. Obesity partially mediated the association of fish (30.6%), fish and poultry (49.8%) and varied (55.2%) diets. CONCLUSIONS: Fish eaters, as well as fish and poultry eaters, were at a lower risk of incident type 2 diabetes than meat eaters, partially attributable to lower obesity risk.

Combined association of walking pace and grip strength with incident type 2 diabetes.

The current study aims to investigate the combined association of walking pace and grip strength with incident type 2 diabetes (T2D). A total of 205 738 participants (mean age 56.6 ± 8.1 years, 115 139 [56.0%] women) without diagnosed or unknown diabetes at baseline from the UK Biobank study were included in this prospective study. Walking pace was self-reported as slow, average, or brisk. Grip strength was measured using a dynamometer and classified as weak, average, and strong. The combined association of walking pace and grip strength with incident T2D was investigated using Cox-proportional hazards models with a 2-year landmark analysis. The additive interaction was conducted by estimating relative excess risk due to interaction (RERI). After the median follow-up period of 5.4 years (interquartile range: 4.8-6.5), 5082 (2.5%) participants were diagnosed with T2D. Compared to brisk-strong individuals (reference group), people who were slow-weak had a higher risk of T2D (hazard ratio: 1.64 [95% CI, 1.42-1.89]) after adjusting for all covariates. There were dose-response gradients across both walking pace and grip strength variables. There was a modest amount of negative additive interaction (RERI; -0.06 [95% CI, -0.16; -0.01]. To conclude, slower pace and weaker grip strength were associated with a higher risk of developing T2D, independent of sociodemographics, lifestyle, and adiposity. Combining walking pace and grip strength might be a practical approach to screening people who are at increased risk of developing T2D.

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.

Are people with metabolically healthy obesity really healthy? A prospective cohort study of 381,363 UK Biobank participants.

AIMS/HYPOTHESIS: People with obesity and a normal metabolic profile are sometimes referred to as having 'metabolically healthy obesity' (MHO). However, whether this group of individuals are actually 'healthy' is uncertain. This study aims to examine the associations of MHO with a wide range of obesity-related outcomes. METHODS: This is a population-based prospective cohort study of 381,363 UK Biobank participants with a median follow-up of 11.2 years. MHO was defined as having a BMI ≥ 30 kg/m2 and at least four of the six metabolically healthy criteria. Outcomes included incident diabetes and incident and fatal atherosclerotic CVD (ASCVD), heart failure (HF) and respiratory diseases. RESULTS: Compared with people who were not obese at baseline, those with MHO had higher incident HF (HR 1.60; 95% CI 1.45, 1.75) and respiratory disease (HR 1.20; 95% CI 1.16, 1.25) rates, but not higher ASCVD. The associations of MHO were generally weaker for fatal outcomes and only significant for all-cause (HR 1.12; 95% CI 1.04, 1.21) and HF mortality rates (HR 1.44; 95% CI 1.09, 1.89). However, when compared with people who were metabolically healthy without obesity, participants with MHO had higher rates of incident diabetes (HR 4.32; 95% CI 3.83, 4.89), ASCVD (HR 1.18; 95% CI 1.10, 1.27), HF (HR 1.76; 95% CI 1.61, 1.92), respiratory diseases (HR 1.28; 95% CI 1.24, 1.33) and all-cause mortality (HR 1.22; 95% CI 1.14, 1.31). The results with a 5 year landmark analysis were similar. CONCLUSIONS/INTERPRETATION: Weight management should be recommended to all people with obesity, irrespective of their metabolic status, to lower risk of diabetes, ASCVD, HF and respiratory diseases. The term 'MHO' should be avoided as it is misleading and different strategies for risk stratification should be explored.

Dose-response association between device-measured physical activity and incident dementia: a prospective study from UK Biobank.

BACKGROUND: Previous cohort studies have investigated the relationship between self-reported physical activity (PA) and dementia. Evidence from objective device-measured PA data is lacking. This study aimed to explore the association of device-measured PA with the risk of dementia incidence and common subtypes (Alzheimer's disease [AD] and vascular dementia) using the UK Biobank study. METHODS: 84,854 participants (55.8% women), invited to participate in the device-measured PA between 2013 and 2015, were included in this prospective cohort study. Wrist accelerometers were used to measure light, moderate, vigorous, moderate-to-vigorous PA (MVPA) and total PA intensity and duration (MET/min/week). Incident dementia (fatal and non-fatal) was extracted from hospital episodes records for incidence and death register for mortality. Incidence follow-up was carried out until the end of March 2021in England and Scotland and the end of March 2018 in Wales. Mortality data were available until February 2021. Nonlinear associations were first investigated using penalised cubic splines fitted in the Cox proportional hazard models. In addition, using MVPA, five categories were created. Associations of these categories with the outcomes were investigated using Cox proportional hazard models. Analyses were adjusted for sociodemographic, lifestyle and health-related factors. RESULTS: After a median follow-up of 6.3 years, 678 individuals were diagnosed with dementia. Evidence of nonlinearity was observed for all PA modes and all-cause dementia. For categories of MVPA, there was a significant trend towards a low risk of overall dementia when higher levels of MVPA were achieved (HRtrend 0.66 [95% CI 0.62 to 0.70]. The lowest risk was identified in individuals who performed more than 1200 MET/min/week, those who had 84% (95% CI 0.12 to 0.21) lower risk of incident dementia compared to those who performed < 300 MET/min/week. CONCLUSIONS: Participants with higher PA levels had a lower risk of incident dementia than those less active, independently of sociodemographic, lifestyle factors and comorbidity. Considering that the majority of previous studies have reported this association using self-reported data, our findings highlight the strong inverse association between PA objectively measured and incident dementia.

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.