Urinary Sodium Excretion, Blood Pressure, and Risk of Future Cardiovascular Disease and Mortality in Subjects Without Prior Cardiovascular Disease.

Hypertension is a risk factor for cardiovascular disease. Increased urinary sodium excretion, representing dietary sodium intake, is associated with hypertension. Low sodium intake has been associated with increased mortality in observational studies. Further studies should assess whether confounding relationships explain associations between sodium intake and outcomes. We studied UK Biobank participants (n=457 484; mean age, 56.3 years; 44.7% men) with urinary electrolytes and blood pressure data. Estimated daily urinary sodium excretion was calculated using Kawasaki formulae. We analyzed associations between sodium excretion and blood pressure in subjects without cardiovascular disease, treated hypertension, or diabetes mellitus at baseline (n=322 624). We tested relationships between sodium excretion, incidence of fatal and nonfatal cardiovascular disease, heart failure, and mortality. Subjects in higher quintiles of sodium excretion were younger, with more men and higher body mass index. There was a linear relationship between increasing urinary sodium excretion and blood pressure. During median follow-up of 6.99 years, there were 11 932 deaths (1125 cardiovascular deaths) with 10 717 nonfatal cardiovascular events. There was no relationship between quintile of sodium excretion and outcomes. These relationships were unchanged after adjustment for comorbidity or excluding subjects with events during the first 2 years follow-up. No differing risk of incident heart failure (1174 events) existed across sodium excretion quintiles. Urinary sodium excretion correlates with elevated blood pressure in subjects at low cardiovascular risk. No pattern of increased cardiovascular disease, heart failure, or mortality risk was demonstrated with either high or low sodium intake.

The association between driving time and unhealthy lifestyles: a cross-sectional, general population study of 386 493 UK Biobank participants.

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.

Associations of dietary protein intake with bone mineral density: An observational study in 70,215 UK Biobank participants.

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 (ß-coefficient 0.010 [95% CI 0.005; 0.015, p < 0.0001]) and men (ß-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.

Systematic comparative validation of self-report measures of sedentary time against an objective measure of postural sitting (activPAL).

BACKGROUND: Sedentary behaviour is a public health concern that requires surveillance and epidemiological research. For such large scale studies, self-report tools are a pragmatic measurement solution. A large number of self-report tools are currently in use, but few have been validated against an objective measure of sedentary time and there is no comparative information between tools to guide choice or to enable comparison between studies. The aim of this study was to provide a systematic comparison, generalisable to all tools, of the validity of self-report measures of sedentary time against a gold standard sedentary time objective monitor. METHODS: Cross sectional data from three cohorts (N = 700) were used in this validation study. Eighteen self-report measures of sedentary time, based on the TAxonomy of Self-report SB Tools (TASST) framework, were compared against an objective measure of postural sitting (activPAL) to provide information, generalizable to all existing tools, on agreement and precision using Bland-Altman statistics, on criterion validity using Pearson correlation, and on data loss. RESULTS: All self-report measures showed poor accuracy compared with the objective measure of sedentary time, with very wide limits of agreement and poor precision (random error > 2.5 h). Most tools under-reported total sedentary time and demonstrated low correlations with objective data. The type of assessment used by the tool, whether direct, proxy, or a composite measure, influenced the measurement characteristics. Proxy measures (TV time) and single item direct measures using a visual analogue scale to assess the proportion of the day spent sitting, showed the best combination of precision and data loss. The recall period (e.g. previous week) had little influence on measurement characteristics. CONCLUSION: Self-report measures of sedentary time result in large bias, poor precision and low correlation with an objective measure of sedentary time. Choice of tool depends on the research context, design and question. Choice can be guided by this systematic comparative validation and, in the case of population surveillance, it recommends to use a visual analog scale and a 7 day recall period. Comparison between studies and improving population estimates of average sedentary time, is possible with the comparative correction factors provided.

Tobacco exposure and sleep disturbance in 498 208 UK Biobank participants.

Background: The prevalence of sleep disturbance is high and increasing. The study investigated whether active, former and passive smoking were associated with sleep disturbance. Methods: This cross-sectional study used data from the UK Biobank: a cohort study of 502 655 participants, of whom 498 208 provided self-reported data on smoking and sleep characteristics. Multivariable multinomial and logistic regression models were used to examine the associations between smoking and sleep disturbance. Results: Long-sleep duration (>9 h) was more common among current smokers [odds ratio (OR): 1.47; 95% confidence interval (CI): 1.17-1.85; probability value (P) = 0.001] than never smokers, especially heavy (>20/day) smokers (OR: 2.85; 95% CI: 1.66-4.89; P < 0.001). Former heavy (>20/day) smokers were also more likely to report short (<6 h) sleep duration (OR: 1.41; 95% CI: 1.25-1.60; P < 0.001), long-sleep duration (OR: 1.99; 95% CI: 1.47-2.71; P < 0.001) and sleeplessness (OR: 1.47; 95% CI: 1.38-1.57; P < 0.001) than never smokers. Among never smokers, those who lived with more than one smoker had higher odds of long-sleep duration than those not cohabitating with a smoker (OR: 2.71; 95% CI: 1.26-5.82; P = 0.011). Conclusions: Active and passive exposure to high levels of tobacco smoke are associated with sleep disturbance. Existing global tobacco control interventions need to be enforced.

Men across a range of ethnicities have a higher prevalence of diabetes: findings from a cross-sectional study of 500 000 UK Biobank participants.

AIMS: Studies show that white men have a higher prevalence of Type 2 diabetes mellitus than women at a given age and BMI, but equivalent standardized data for other ethnic groups in the UK are sparse. METHODS: This cross-sectional study analysed UK Biobank data from 489 079 participants to compare the prevalence of diabetes mellitus across four major ethnic groups including: 471 700 (96.4%) white, 7871 (1.6%) South Asian, 7974 (1.6%) black and 1534 (0.3%) Chinese participants, before and after standardizing for age, socio-economic status (SES), BMI and lifestyle factors including physical activity, TV viewing, fruit and vegetable intake, processed meat, red meat, oily fish, alcohol intake and smoking. A subgroup analysis of South Asians was also undertaken. RESULTS: Crude diabetes prevalence was higher in men across all four ethnicities. After standardizing for age, SES, BMI and lifestyle factors, a significant sex difference in diabetes prevalence persisted in white (men 6.0% vs. women 3.6%), South Asian (21.0% vs. 13.8%) and black individuals (13.3% vs. 9.7%) (P < 0.0001); there was a non-significant difference between Chinese men and women (7.1% vs. 5.5%) (P = 0.211). Sex differences persisted across South Asian subgroups. CONCLUSIONS: Men across a range of major ethnic groups including white, South Asian and black, have a higher prevalence of diabetes compared with women of similar age, BMI, SES and lifestyle in the UK.

Dietary fat and total energy intake modifies the association of genetic profile risk score on obesity: evidence from 48 170 UK Biobank participants.

BACKGROUND: Obesity is a multifactorial condition influenced by both genetics and lifestyle. The aim of this study was to investigate whether the association between a validated genetic profile risk score for obesity (GPRS-obesity) and body mass index (BMI) or waist circumference (WC) was modified by macronutrient intake in a large general population study. METHODS: This study included cross-sectional data from 48 170 white European adults, aged 37-73 years, participating in the UK Biobank. Interactions between GPRS-obesity and macronutrient intake (including total energy, protein, fat, carbohydrate and dietary fibre intake) and its effects on BMI and WC were investigated. RESULTS: The 93-single-nucleotide polymorphism (SNP) GPRS was associated with a higher BMI (ß: 0.57 kg m-2 per s.d. increase in GPRS (95% confidence interval: 0.53-0.60); P=1.9 × 10-183) independent of major confounding factors. There was a significant interaction between GPRS and total fat intake (P(interaction)=0.007). Among high-fat-intake individuals, BMI was higher by 0.60 (0.52, 0.67) kg m-2 per s.d. increase in GPRS-obesity; the change in BMI with GPRS was lower among low-fat-intake individuals (ß: 0.50 (0.44, 0.57) kg m-2). Significant interactions with similar patterns were observed for saturated fat intake (high ß: 0.66 (0.59, 0.73) versus low ß: 0.49 (0.42, 0.55) kg m-2, P(interaction)=2 × 10-4) and for total energy intake (high ß: 0.58 (0.51, 0.64) versus low ß: 0.49 (0.42, 0.56) kg m-2, P(interaction)=0.019), but not for protein intake, carbohydrate intake and fibre intake (P(interaction) >0.05). The findings were broadly similar using WC as the outcome. CONCLUSIONS: These data suggest that the benefits of reducing the intake of fats and total energy intake may be more important in individuals with high genetic risk for obesity.

Association between grip strength and diabetes prevalence in black, South-Asian, and white European ethnic groups: a cross-sectional analysis of 418 656 participants in the UK Biobank study.

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.

Ethnic differences in microvascular function in apparently healthy South African men and women.

Microvascular dysfunction precedes the clinical manifestations of cardiovascular disease. Given the ethnic disparities in cardiovascular disease, we aimed to investigate ethnic differences in microvascular endothelial function in a group of young (18-33 years old), apparently healthy individuals (n = 33, nine Black African, 12 mixed ancestry and 12 Caucasian). Microvascular endothelium-dependent and -independent function was assessed by laser Doppler imagery and iontophoresis of ACh and sodium nitroprusside (SNP), respectively, adjusting for skin resistance. Microvascular reactivity was expressed as maximum absolute perfusion, percentage change from baseline and area under the curve (AUC). Skin resistance was significantly lower in the Caucasian group in response to ACh (Caucasian, mean 0.16 ± 0.03 Ω versus Black, 0.21 ± 0.04 Ω and mixed ancestry, 0.20 ± 0.02 Ω, P < 0.01) and SNP (Caucasian, 0.08 ± 0.01 Ω versus Black, 0.11 ± 0.02 Ω and mixed ancestry, 0.12 ± 0.01 Ω, P < 0.01). Microvascular function in response to ACh was significantly higher in the Caucasian group compared with the other two groups; however, after adjusting for skin resistance these differences were no longer significant. Conversely, the microvascular SNP response remained significantly higher in the Caucasian group, even after adjusting for skin resistance (P < 0.01). Diastolic blood pressure was inversely associated with the AUC of ACh (r = -0.4) and all SNP responses (r = -0.3 to -0.6). Skin resistance was inversely associated with AUC and maximum absolute ACh response (r = -0.59 and -0.64, respectively) and all SNP responses (r = -0.37 to -0.79). Ethnic differences in endothelium-independent microvascular function may contribute to ethnic disparities in cardiovascular disease. Moreover, skin resistance plays a significant role in the interpretation of the microvascular response to outcomes of iontophoresis in a multiethnic group.

Oxygen cost of walking, physical activity, and sedentary behaviours in rheumatoid arthritis.

OBJECTIVES: To evaluate the oxygen cost of gait and measure physical activity profiles, including time spent sedentary, in people with rheumatoid arthritis (RA) and matched controls. METHOD: We recruited 19 people with RA and 19 controls matched for age, sex, and body mass index (BMI). Demographic details and clinical characteristics of the RA population were recorded. Oxygen uptake per metre walked (oxygen cost) was measured in the laboratory using a portable gas analyser. Activity profiles including the number of steps per day, time spent sedentary (sitting or lying down), and intensity of walking were recorded over 5 days using an activity monitor, from which physical activity was classified by intensity categories. Levels of pain, fatigue, anxiety, and depression were recorded. RESULTS: People with RA walked with a slower self-selected gait speed (p < 0.001) than controls but there was no difference in the oxygen cost of walking (p = 0.992) between the groups. People with RA took fewer steps (p < 0.001), had increased sedentary time (p = 0.029) and lower time walking at cadences commensurate with moderate to vigorous physical activity (MVPA) compared to controls (p < 0.001). Pain, fatigue, and depression were higher in the RA group (all p < 0.001). CONCLUSIONS: The oxygen cost of walking in this cohort of people with RA was similar to that of matched controls but there was an increase in time spent sedentary and a reduction in time spent at cadences commensurate with MVPA. Clinical symptoms such as depression, pain, and fatigue may explain the changes in activity/sedentary behaviours in people with RA and require further investigation.

Lower cardiorespiratory fitness contributes to increased insulin resistance and fasting glycaemia in middle-aged South Asian compared with European men living in the UK.

AIMS/HYPOTHESIS: This study aimed to determine the extent to which increased insulin resistance and fasting glycaemia in South Asian men, compared with white European men, living in the UK, was due to lower cardiorespiratory fitness (maximal oxygen uptake [VO(2max)]) and physical activity. METHODS: One hundred South Asian and 100 age- and BMI-matched European men without diagnosed diabetes, aged 40-70 years, had fasted blood taken for measurement of glucose concentration, HOMA-estimated insulin resistance (HOMA(IR)), plus other risk factors, and underwent assessment of physical activity (using accelerometry), VO(2max), body size and composition, and demographic and other lifestyle factors. For 13 South Asian and one European man, HbA1c levels were >6.5% (>48 mmol/mol), indicating potential undiagnosed diabetes; these men were excluded from the analyses. Linear regression models were used to determine the extent to which body size and composition, fitness and physical activity variables explained differences in HOMA(IR) and fasting glucose between South Asian and European men. RESULTS: HOMA(IR) and fasting glucose were 67% (p < 0.001) and 3% (p < 0.018) higher, respectively, in South Asians than Europeans. Lower VO(2max), lower physical activity and greater total adiposity in South Asians individually explained 68% (95% CI 45%, 91%), 29% (11%, 46%) and 52% (30%, 80%), respectively, and together explained 83% (50%, 119%) (all p < 0.001) of the ethnic difference in HOMA(IR). Lower VO(2max) and greater total adiposity, respectively, explained 61% (9%, 111%) and 39% (9%, 76%) (combined effect 63% [8%, 115%]; all p < 0.05) of the ethnic difference in fasting glucose. CONCLUSIONS/INTERPRETATION: Lower cardiorespiratory fitness is a key factor associated with the excess insulin resistance and fasting glycaemia in middle-aged South Asian, compared with European, men living in the UK.

Levels of physical activity and relationship with markers of diabetes and cardiovascular disease risk in 5474 white European and South Asian adults screened for type 2 diabetes.

OBJECTIVE: Investigate levels of physical activity and their association with health in a white European (WE) and South Asian (SA) population. METHODS: This study reports data from a diabetes screening programme, 2004-2007, Leicester, UK. Physical activity was measured using the International Physical Activity Questionnaire; additional outcomes included fasting and 2-h post-challenge glucose, lipid profile, body mass index (BMI) and waist circumference. RESULTS: 1164 SA (female=48%) and 4310 WE (female=53%) were included. SAs were more likely fall below the minimum physical activity recommendations for health compared to WEs (age-adjusted OR for SA men=2.35; 95% CI=1.89-2.93, age adjusted OR for SA women=2.25; 95% CI=1.81-2.80). There were significant associations between levels of physical activity and BMI (men and women), waist circumference (men and women), 2-h glucose (women), HDL-cholesterol (men) and triglycerides (men) in WEs and waist circumference (women) and HDL-cholesterol (men) in SAs. Significant interactions between ethnicity and physical activity existed in the relationship with BMI and waist circumference in men. CONCLUSIONS: SAs are substantially less physically active than WEs. There may also be differences between SAs and WEs in the health benefits associated with higher physical activity that warrant further investigation.

Exercise training has greater effects on insulin sensitivity in daughters of patients with type 2 diabetes than in women with no family history of diabetes.

AIMS/HYPOTHESIS: Sedentary offspring of patients with type 2 diabetes are often more insulin-resistant than persons with no family history of diabetes, but when active or fit offspring of type 2 diabetic patients are compared with non-diabetic persons, differences in insulin resistance are less evident. This study aimed to determine the effects of an exercise training intervention on insulin sensitivity in both groups. METHODS: Women offspring (n = 34) of type 2 diabetic patients (offspring age 35.6 +/- 7.0 years, BMI 28.1 +/- 5.1 kg/m(2)) and 36 matched female controls (age 33.6 +/- 6.1 years, BMI 27.3 +/- 4.7 kg/m(2)) participated. Body composition, fitness and metabolic measurements were made at baseline and after a controlled 7 week exercise intervention. RESULTS: At baseline, insulin sensitivity index (ISI) was 22% lower in offspring than controls (p < 0.05), despite similar body fat and maximal oxygen uptake (.VO(2max)) values in the two groups. ISI increased by 23% (p < 0.05) in offspring following the exercise intervention, compared with 7% (NS) in the controls. Increases in .VO(2max) were similar in both groups (controls 12%, offspring 15%, p < 0.05 for both). Plasma leptin concentrations decreased significantly in the offspring (-24%, p < 0.01) but not in controls (0%, NS). Change in ISI correlated significantly with baseline ISI (r = -0.47, p < 0.0005) and change in leptin (r = -0.43, p < 0.0005). The latter relationship was not attenuated by adjustment for changes in body fat. CONCLUSIONS/INTERPRETATION: Offspring, but not controls, significantly increased ISI in response to an exercise intervention, indicating that insulin sensitivity is more highly modulated by physical activity in daughters of patients with type 2 diabetes than in women with no family history of the disease.

Energy replacement attenuates the effects of prior moderate exercise on postprandial metabolism in overweight/obese men.

BACKGROUND: The extent to which exercise-induced changes to postprandial metabolism are dependant on the associated energy deficit is not known. OBJECTIVE: To determine the effects of exercise, with and without energy replacement, on postprandial metabolism. DESIGN: Each subject underwent three 2-day trials in random order. On day 1 of each trial subjects rested (control), walked at 50% maximal oxygen uptake to induce a net energy expenditure of 27 kJ kg(-1) body mass (energy-deficit) or completed the same walk with the net energy expended replaced (energy-replacement). On day 2 subjects completed an 8.5-h metabolic assessment. For 3 days prior to day 2, subjects consumed an isocaloric diet, avoided planned exercise (apart from exercise interventions) and alcohol. SUBJECTS: A total of 13 overweight/obese men (age: 40+/-8 years, body mass index: 31.1+/-3.0 kg m(-2)). MEASUREMENTS: Postprandial triglyceride, insulin, glucose, non-esterified fatty acid and 3-hydroxybutyrate concentrations and substrate utilization rates were determined. RESULTS: Energy-deficit lowered postprandial triglyceride concentrations by 14 and 10% compared with control and energy-replacement (P<0.05 for both). Energy-deficit increased postprandial 3-hydroxybutyrate concentrations by 40 and 19% compared with control and energy-replacement (P<0.05 for both). Postprandial insulin concentrations were 18 and 10% lower for energy-deficit and energy-replacement compared with control and 10% lower for energy-deficit than energy-replacement (P<0.05 for all). Postprandial fat oxidation increased by 30 and 14% for energy-deficit and energy-replacement compared to control and was 12% higher for energy-deficit than energy-replacement (P<0.05 for all). CONCLUSION: Exercise with energy replacement lowered postprandial insulinaemia and increased fat oxidation. However an exercise-induced energy deficit augmented these effects and was necessary to lower postprandial lipaemia.