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OBJECTIVE People living with type 2 diabetes (T2D) are at higher infection risk, but it is unknown how this risk varies by ethnicity or whether the risk is similarly observed in people with nondiabetic hyperglycemia (“prediabetes”). RESEARCH DESIGN AND METHODS We included 527,151 patients in England with T2D and 273,216 with prediabetes, aged 18–90, and alive on 1 January 2015 on the Clinical Practice Research Datalink. Each was matched to two patients without diabetes or prediabetes on age, sex, and ethnic group. Infections during 2015–2019 were collated from primary care and linked hospitalization records. Infection incidence rate ratios (IRRs) for those with prediabetes or T2D were estimated, unadjusted and adjusted for confounders. RESULTS People with T2D had increased risk for infections presenting in primary care (IRR 1.51, 95% CI 1.51–1.52) and hospitalizations (IRR 1.91, 1.90–1.93). This was broadly consistent overall within each ethnic group, although younger White T2D patients (age CONCLUSIONS The elevated infection risk for people with T2D appears similar for different ethnic groups and is also seen in people with prediabetes. Infections are a substantial cause of ill-health and health service use for people with prediabetes and T2D. This has public health implications with rising prediabetes and diabetes prevalence.

Aims/hypothesis The aim of the study was to examine the association of retinal vessel morphometry with BP, body composition and biochemistry, and to determine whether these associations differ by diabetes status. Methods The UK Biobank ocular assessment included 68,550 participants aged 40-70 years who underwent non-mydriatic retinal photography, BP and body composition measurements, and haematological analysis. A fully automated image analysis program provided measurements of retinal vessel diameter and tortuosity. The associations between retinal vessel morphology and cardiometabolic risk factors by diabetes status were examined using multilevel linear regression, to provide absolute differences in vessel diameter and percentage differences in tortuosity (allowing for within-person clustering). Results A total of 50,233 participants (a reduction from 68,550) were included in these analyses. Overall, those with diabetes had significantly more tortuous venules and wider arteriolar diameters compared with those without. Associations between venular tortuosity and cardiometabolic risk factors differed according to diabetes status (p interaction 1c, C-reactive protein, white cell count and granulocyte count. For example, a unit rise in white cell count was associated with a 0.18% increase (95% CI 0.05, 0.32%) in venular tortuosity for those without diabetes and a 1.48% increase (95% CI 0.90, 2.07%) among those with diabetes. For arteriolar diameter, significant interactions were evident for systolic BP, diastolic BP, mean arterial pressure (MAP) and LDL-cholesterol. For example, a 10 mmHg rise in systolic BP was associated with a −0.92 μm difference (95% CI −0.96 to −0.88 μm) in arteriolar diameter for those without diabetes, and a −0.58 μm difference (95% CI −0.76 to −0.41 μm) among those with diabetes. No interactions were observed for arteriolar tortuosity or venular diameters. Conclusions/interpretation We provide clear evidence of the modifying effect of diabetes on cardiometabolic risk factor associations with retinal microvascular architecture. These observations suggest the occurrence of preclinical disease processes, and may be a sign of impaired autoregulation due to hyperglycaemia, which has been suggested to play a pivotal role in the development of diabetes-related microvascular complications. Data Availability The data supporting the results reported here are available through the UK Biobank (https://www.ukbiobank.ac.uk/enable-your-research/apply-for-access). Graphical abstract

Background: Taking fewer than the widely promoted “10 000 steps per day” has recently been associated with lower risk of all-cause mortality. The relationship of steps and cardiovascular disease (CVD) risk remains poorly described. A meta-analysis examining the dose–response relationship between steps per day and CVD can help inform clinical and public health guidelines. Methods: Eight prospective studies (20 152 adults [ie, ≥18 years of age]) were included with device-measured steps and participants followed for CVD events. Studies quantified steps per day and CVD events were defined as fatal and nonfatal coronary heart disease, stroke, and heart failure. Cox proportional hazards regression analyses were completed using study-specific quartiles and hazard ratios (HR) and 95% CI were meta-analyzed with inverse-variance–weighted random effects models. Results: The mean age of participants was 63.2±12.4 years and 52% were women. The mean follow-up was 6.2 years (123 209 person-years), with a total of 1523 CVD events (12.4 per 1000 participant-years) reported. There was a significant difference in the association of steps per day and CVD between older (ie, ≥60 years of age) and younger adults (ie, Conclusions: For older adults, taking more daily steps was associated with a progressively decreased risk of CVD. Monitoring and promoting steps per day is a simple metric for clinician–patient communication and population health to reduce the risk of CVD.

BackgroundThe joint associations of total and intensity-specific physical activity with obesity in relation to all-cause mortality risk are unclear.MethodsWe included 34 492 adults (72% women, median age 62.1 years, 2034 deaths during follow-up) in a harmonised meta-analysis of eight population-based prospective cohort studies with mean follow-up ranging from 6.0 to 14.5 years. Standard body mass index categories were cross-classified with sample tertiles of device-measured total, light-to-vigorous and moderate-to-vigorous physical activity and sedentary time. In five cohorts with waist circumference available, high and low waist circumference was combined with tertiles of moderate-to-vigorous physical activity.ResultsThere was an inverse dose–response relationship between higher levels of total and intensity-specific physical activity and mortality risk in those who were normal weight and overweight. In individuals with obesity, the inverse dose–response relationship was only observed for total physical activity. Similarly, lower levels of sedentary time were associated with lower mortality risk in normal weight and overweight individuals but there was no association between sedentary time and risk of mortality in those who were obese. Compared with the obese-low total physical activity reference, the HRs were 0.59 (95% CI 0.44 to 0.79) for normal weight-high total activity and 0.67 (95% CI 0.48 to 0.94) for obese-high total activity. In contrast, normal weight-low total physical activity was associated with a higher risk of mortality compared with the obese-low total physical activity reference (1.28; 95% CI 0.99 to 1.67).ConclusionsHigher levels of physical activity were associated with lower risk of mortality irrespective of weight status. Compared with obesity-low physical activity, there was no survival benefit of being normal weight if physical activity levels were low.

Poor oral health could be associated with changes in musculoskeletal health over time. This aim of this study was to investigate the longitudinal relationship between oral health and decline in physical function in later life.We did a prospective analysis of two cohorts of older adults (aged 70 years or older) including men from the British Regional Heart Study (BRHS; n=612), and men and women from the Health, Aging and Body Composition (Health ABC) Study (n=1572), followed up for about 8 years. Data were available for clinical or self-reported oral health measures, muscle (grip) strength, and physical performance (chair stand and gait speed). ANCOVA models were used to assess the association between oral health and follow-up physical function scores. Multivariate logistic regression models were used to examine the associations between oral health and decline in physical function over the follow-up period. In the BRHS, changes in oral health and physical function were also assessed. All models were adjusted for relevant sociodemographic, behavioural, and health-related factors.In the BRHS, complete tooth loss and difficulty eating were associated with weaker grip strength at follow-up, and periodontal status was associated with decline in gait speed. In the Health ABC Study, complete tooth loss, poor self-rated oral health, and the presence of one oral health problem were associated with slower gait speed at follow-up. In both studies, dry mouth was associated with declines in physical function. In the BRHS, deterioration of dentition (tooth loss) over the follow-up period was associated with decline in chair stand speed (adjusted odds ratio 2·34 [95% CI 1·20-4·46]), as was deterioration in difficulty eating (2·41 [1·04-5·60]).Oral health problems are associated with poorer physical function and greater decline in physical function in older adults, and could be an indicator of individuals at risk of reduced physical capacity and subsequent frailty and disability in later life.The Dunhill Medical Trust and the US National Institutes of Health-National Institute of Dental and Craniofacial Research.

Aim: To determine the relationship between baseline inflammation (CRP and IL-6) with natriuretic peptide (NP) activity (measured by NT-proBNP) and incident heart failure (HF) in older men. Methods & results: In the British Regional Heart Study, 3569 men without prevalent myocardial infarction or HF were followed for mean 16.3 years; 327 developed HF. Baseline CRP and IL-6 were significantly and positively associated with NT-proBNP. Those in the highest CRP and IL-6 quartiles had an elevated risk of HF after age and BMI adjustment (HR = 1.42 [1.01–1.98] and 1.71 [1.24–2.37], respectively), which markedly attenuated after NT-proBNP adjustment (HR = 1.15 [0.81–1.63] and 1.25 [0.89–1.75], respectively). Conclusion: NP activity is associated with pro-inflammatory biomarkers and may explain the link between inflammation and incident HF., Lay abstract Inflammation describes the body’s natural response to infections, injuries and toxins. Inflammation is a helpful response in the short term, but it is thought that long-lasting inflammation – for example, due to illnesses such as diabetes or obesity – may have harmful effects. Previous studies have found that people with higher levels of inflammatory molecules in the blood seem to be more likely to develop heart failure (HF) later on. The amount of fluid in the body is controlled, in part, by molecules in the blood known as ‘natriuretic peptides' (NPs). People with HF have much higher levels of NPs in their blood, and these are used to help diagnose HF. There are suggestions that inflammation and natriuretic peptides are linked to one another. Using a sample of men aged 60–79 years, who did not have HF, we compared blood markers of inflammation and NPs at a baseline examination. Men with higher blood inflammatory markers tended to have higher blood NP levels. We then followed these men up for an average of 16.3 years. Men with higher blood inflammatory markers at baseline were more likely to develop HF, as expected, even after accounting for differences in age and BMI. However, when we accounted for NP levels at baseline, the increased risk of HF with inflammation disappeared. This suggests that NP activity is important in the relationship between inflammation and the risk of HF. Future studies should account for this when examining the link. It is possible that NPs or, more likely, whatever is driving their release, may explain why people with inflammation are more likely to get HF.

To investigate the prospective associations between oral health and progression of physical frailty in older adults.Prospective analysis.Data are from the British Regional Heart Study (BRHS) comprising 2137 men aged 71 to 92 years from 24 British towns and the Health, Aging, and Body Composition (HABC) Study of 3075 men and women aged 70 to 79 years.Oral health markers included denture use, tooth count, periodontal disease, self-rated oral health, dry mouth, and perceived difficulty eating. Physical frailty progression after ∼8 years follow-up was determined based on 2 scoring tools: the Fried frailty phenotype (for physical frailty) and the Gill index (for severe frailty). Logistic regression models were conducted to examine the associations between oral health markers and progression to frailty and severe frailty, adjusted for sociodemographic, behavioral, and health-related factors.After full adjustment, progression to frailty was associated with dentition (per each additional tooth, odds ratio [OR] 0.97; 95% CI: 0.95-1.00),21 teeth with (OR 1.71; 95% CI: 1.01-2.88) or without denture use (OR 2.32; 95% CI 1.12-4.81), and symptoms of dry mouth (OR ≥1.8; 95% CI ≥ 1.06-3.10) in the BRHS cohort. In the HABC Study, progression to frailty was associated with dry mouth (OR 3.87; 95% CI 1.68-8.93) and ≥2 cumulative oral health problems (OR 2.54; 95% CI 1.27-5.10) and progression to severe frailty was associated with periodontal disease (pocket depth; OR 4.11; 95% CI 1.13-14.92) after full adjustment.These findings indicate that oral health problems, particularly tooth loss and dry mouth, in older adults are associated with progression to frailty in later life. Additional research is needed to determine if interventions aimed at maintaining (or improving) oral health can contribute to reducing the risk, and worsening, of physical frailty in older adults.

Background Observational studies have shown that higher cereal fiber intake is associated with reduced type 2 diabetes risk. However, it remains uncertain whether this association is causal. Objective This study evaluated the feasibility of an intervention to increase cereal fiber intake in children using breakfast cereals. Methods The study was a 2-arm parallel group randomized controlled trial in 9–10-y-old children, who received free supplies of high-fiber breakfast cereals (g3.5 g/portion) or low-fiber breakfast cereals (l1.0 g/portion) to eat daily for 1 mo with behavioral support to promote adherence. Children provided baseline and 1-mo fasting blood samples, physical measurements, and 24-h dietary recalls. The primary outcome was the group difference in change in plasma total alkylresorcinol (AR) concentration; secondary outcomes were group differences in nutrient intakes and adiposity indices. Analyses (complete case and multiple imputation) were conducted by regressing the final AR concentration on baseline AR in models adjusted for sex, ethnicity, age, and school (random effect). Results Two-hundred seventy-two children were randomly assigned (137 receiving a low-fiber and 135 a high-fiber diet) and 193 (71%) provided fasting blood samples at baseline and follow-up. Among randomized participants, median (IQR) of baseline AR was 43.1 (24.6–85.5) nmol/L and of cereal fiber intake was 4.5 (2.7–6.4) g; 87% of participants reported consuming the cereal on most or all days. Compared with changes in the low-fiber group, the high-fiber group had greater increases in AR (40.7 nmol/L; 95% CI: 21.7, 59.8 nmol/L, P l 0.0001) and in reported cereal fiber intake (2.9g/d; 95% CI: 2.0, 3.7 g; P l 0.0001). There were no appreciable differences in other secondary outcomes. Conclusions We have developed a simple and acceptable nutritional intervention that increases markers of daily cereal fiber intake in children. This intervention could be used to test whether increases in cereal fiber intake in children might reduce insulin resistance. This trial was registered at www.isrctn.com as ISRCTN33260236.

AimsWe examine whether inclusion of Artificial Intelligence (AI)-enabled retinal vasculometry (RV) improves existing risk algorithms for incident stroke, myocardial infarction (MI) and circulatory mortality.MethodsAI-enabled retinal vessel image analysis processed images from 88,052 UK Biobank (UKB) participants (aged 40-69 years at image capture) and 7,411 EPIC-Norfolk participants (aged 48-92). Retinal arteriolar and venular width, tortuosity and area were extracted. Prediction models were developed in UKB using multivariable Cox proportional hazards regression for circulatory mortality, incident stroke and MI, and externally validated in EPIC-Norfolk. Model performance was assessed using optimism adjusted calibration, C- and R2 statistics. Performance of Framingham risk scores (FRS) for incident stroke and incident MI, with addition of RV to FRS, were compared with a simpler model based on RV, age, smoking status and medical history (antihypertensive/cholesterol lowering medication, diabetes, prevalent stroke/MI).ResultsUKB prognostic models were developed on 65,144 participants (mean age 56.8; median follow-up 7.7 years) and validated in 5,862 EPIC-Norfolk participants (67.6, 9.1 years respectively). Prediction models for circulatory mortality in men and women had optimism adjusted C- and R2 statistics between 0.75-0.77 and 0.33-0.44 respectively. For incident stroke and MI, addition of RV to FRS did not improve model performance in either cohort. However, the simpler RV model performed equally or better than FRS.ConclusionRV offers an alternative predictive biomarker to traditional risk-scores for vascular health, without the need for blood sampling or blood pressure measurement. Further work is needed to examine RV in population screening to triage individuals at high-risk. (250 words)HIGHLIGHTSWhat is already known on this topicPopulation screening for MI and stroke using risk prediction tools exist but have limited uptake; risk scores for circulator mortality do not exist.What this study addsRisk models developed in UK Biobank (validated in EPIC-Norfolk) using Artificial Intelligence (AI)-enabled retinal vasculometry (RV), age, history of cardiovascular disease, use of hypertensive medication and smoking yielded high predictive test performance for circulatory mortality.Risk scores for MI and stroke performed similarly to established risk scores.How this study might affect research, practice or policyAI-enabled RV extraction offers a non-invasive prognostic biomarker of vascular health that does not require blood sampling or blood pressure measurement, and potentially has greater community reach to identify individuals at medium-high risk requiring further clinical assessment.SYNOPSIS/PRECISRisk models developed in UK Biobank (validated in EPIC-Norfolk) using Artificial Intelligence enabled retinal vasculometry indices, age, history of cardiovascular disease, use of hypertensive medication and smoking yielded high predictive test performance for circulatory mortality. Risk scores for MI and stroke performed similarly to established risk scores.

We examined the associations between haematological and inflammatory variables with future venous thromboembolism (VTE), in 3494 men aged 60-79 years, with no previous history of VTE or myocardial infarction, who were not receiving oral anticoagulants. After a mean follow-up period of 18 years, there were 149 confirmed cases of fatal or non-fatal VTE (deep vein thrombosis and/or pulmonary embolism). Among classical cardiovascular risk factors, only obesity and cigarette smoking were associated with VTE risk. After adjustment for age, obesity and smoking, VTE risk was associated with coagulation factor VIII, factor IX, von Willebrand factor (VWF), activated partial thromboplastin time (APTT), and fibrin D-dimer. Hazard ratios (95% CI) for top to bottom quarters (bottom to top for APTT), were respectively 2.17 (1.37, 3.44), 2.15 (1.30, 3.53), 2.02 (1.27, 3.22), 2.43 (1.47, 4.02) and 3.62 (2.18, 6.08). The 11% of men with both the shortest APTT and highest D-dimer combined had a 5.02 (2.37, 10.62) higher risk of VTE. VTE risk was not associated with fibrinogen, factor VII or activated protein C resistance; full blood count variables or with inflammatory markers, plasma viscosity, C-reactive protein or interleukin-6. The combination of D-dimer and APTT merits evaluation as an adjunct to VTE risk prediction scores.

Funder: National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care East Midlands, Funder: National Institute on Aging, Funder: Stockholms Läns Landsting; FundRef: http://dx.doi.org/10.13039/501100004348, Funder: Norwegian Directorate for Public Health, Funder: Centrum for Idrottsforskning; FundRef: http://dx.doi.org/10.13039/501100005350, Funder: The Coca-Cola Company, Objectives: To examine the joint associations of accelerometer-measured physical activity and sedentary time with all-cause mortality. Methods: We conducted a harmonised meta-analysis including nine prospective cohort studies from four countries. 44 370 men and women were followed for 4.0 to 14.5 years during which 3451 participants died (7.8% mortality rate). Associations between different combinations of moderate-to-vigorous intensity physical activity (MVPA) and sedentary time were analysed at study level using Cox proportional hazards regression analysis and summarised using random effects meta-analysis. Results: Across cohorts, the average time spent sedentary ranged from 8.5 hours/day to 10.5 hours/day and 8 min/day to 35 min/day for MVPA. Compared with the referent group (highest physical activity/lowest sedentary time), the risk of death increased with lower levels of MVPA and greater amounts of sedentary time. Among those in the highest third of MVPA, the risk of death was not statistically different from the referent for those in the middle (16%; 95% CI 0.87% to 1.54%) and highest (40%; 95% CI 0.87% to 2.26%) thirds of sedentary time. Those in the lowest third of MVPA had a greater risk of death in all combinations with sedentary time; 65% (95% CI 1.25% to 2.19%), 65% (95% CI 1.24% to 2.21%) and 263% (95% CI 1.93% to 3.57%), respectively. Conclusion: Higher sedentary time is associated with higher mortality in less active individuals when measured by accelerometry. About 30–40 min of MVPA per day attenuate the association between sedentary time and risk of death, which is lower than previous estimates from self-reported data.

Background Nuclear magnetic resonance (NMR) spectroscopy allows triglycerides to be subclassified into 14 different classes based on particle size and lipid content. We recently showed that these subfractions have differential associations with cardiovascular disease events. Here we report the distributions and define reference interval ranges for 14 triglyceride-containing lipoprotein subfraction metabolites. Methods Lipoprotein subfractions using the Nightingale NMR platform were measured in 9073 participants from four cohort studies contributing to the UCL-Edinburgh-Bristol consortium. The distribution of each metabolite was assessed, and reference interval ranges were calculated for a disease-free population, by sex and age group (65 years), and in a subgroup population of participants with cardiovascular disease or type 2 diabetes. We also determined the distribution across body mass index and smoking status. Results The largest reference interval range was observed in the medium very-low density lipoprotein subclass (2.5th 97.5th percentile; 0.08 to 0.68 mmol/L). The reference intervals were comparable among male and female participants, with the exception of triglyceride in high-density lipoprotein. Triglyceride subfraction concentrations in very-low density lipoprotein, intermediate-density lipoprotein, low-density lipoprotein and high-density lipoprotein subclasses increased with increasing age and increasing body mass index. Triglyceride subfraction concentrations were significantly higher in ever smokers compared to never smokers, among those with clinical chemistry measured total triglyceride greater than 1.7 mmol/L, and in those with cardiovascular disease, and type 2 diabetes as compared to disease-free subjects. Conclusion This is the first study to establish reference interval ranges for 14 triglyceride-containing lipoprotein subfractions in samples from the general population measured using the nuclear magnetic resonance platform. The utility of nuclear magnetic resonance lipid measures may lead to greater insights for the role of triglyceride in cardiovascular disease, emphasizing the importance of appropriate reference interval ranges for future clinical decision making.

Accurate assessment of childhood adiposity is important both for individuals and populations. We compared fat mass (FM) predictions from a novel prediction model based on height, weight and demographic factors (height–weight equation) with FM from bioelectrical impedance (BIA) and dual-energy X-ray absorptiometry (DXA), using the deuterium dilution method as a reference standard. FM data from all four methods were available for 174 ALSPAC Study participants, seen 2002–2003, aged 11–12-years. FM predictions from the three approaches were compared to the reference standard using; R2, calibration (slope and intercept) and root mean square error (RMSE). R2 values were high from ‘height–weight equation’ (90%) but lower than from DXA (95%) and BIA (91%). Whilst calibration intercepts from all three approaches were close to the ideal of 0, the calibration slope from the ‘height–weight equation’ (slope = 1.02) was closer to the ideal of 1 than DXA (slope = 0.88) and BIA (slope = 0.87) assessments. The ‘height–weight equation’ provided more accurate individual predictions with a smaller RMSE value (2.6 kg) than BIA (3.1 kg) or DXA (3.4 kg). Predictions from the ‘height–weight equation’ were at least as accurate as DXA and BIA and were based on simpler measurements and open-source equation, emphasising its potential for both individual and population-level FM assessments.

Background BMI underestimates and overestimates body fat in children from South Asian and Black ethnic groups, respectively. Methods We used cross-sectional NCMP data (2015–17) for 38 270 children in three inner-London local authorities: City & Hackney, Newham and Tower Hamlets (41% South Asian, 18.8% Black): 20 439 4–5 year-olds (48.9% girls) and 17 831 10–11 year-olds (49.1% girls). We estimated the proportion of parents who would have received different information about their child’s weight status, and the area-level prevalence of obesity—defined as ≥98th centile—had ethnic-specific BMI adjustments been employed in the English National Child Measurement Programme (NCMP). Results Had ethnic-specific adjustment been employed, 19.7% (3112/15 830) of parents of children from South Asian backgrounds would have been informed that their child was in a heavier weight category, and 19.1% (1381/7217) of parents of children from Black backgrounds would have been informed that their child was in a lighter weight category. Ethnic-specific adjustment increased obesity prevalence from 7.9% (95% CI: 7.6, 8.3) to 9.1% (8.7, 9.5) amongst 4–5 year-olds and from 17.5% (16.9, 18.1) to 18.8% (18.2, 19.4) amongst 10–11 year-olds. Conclusions Ethnic-specific adjustment in the NCMP would ensure equitable categorization of weight status, provide correct information to parents and support local service provision for families.

Preventing oral health problems can be crucial for maintaining physical independence in older adults. We aimed to examine the associations of a range of oral health problems with incidence of disability in older adults.We used prospective data from the British Regional Health Study (BRHS) (N = 2147, 71-92 years), and the Health, Aging and Body Composition (HABC) study (USA) (N = 3075, 71-80 years). Oral health measures included tooth loss, periodontal disease, self-rated oral health, and self-reported dry mouth. Participants were followed for onset of disability over a follow-up period of 3 years. Onset of disability was assessed through new cases of mobility limitations, activities of daily living (ADL), and instrumental activities of daily living (IADL). Logistic regression was performed to calculate the odds of incident disability.In the BRHS, tooth loss was associated with greater odds of mobility limitations and ADL difficulties. Periodontal disease was associated with greater incidence of mobility limitations. Self-report of ≥3 dry mouth symptoms was associated with increased odds of incident mobility limitations and ADL difficulties (OR = 2.08, 95% CI 1.27-3.42; OR = 1.73, 95% CI 1.03-2.90). Fair/poor self-rated oral health was associated with greater incidence of IADL difficulties. In the HABC study, complete tooth loss was associated with greater incidence of mobility limitations (OR = 1.86, 95% CI 1.13-3.06), and fair/poor self-rated oral health was associated with increased odds of incident ADL difficulties (OR = 1.42, 95% CI 1.04-1.94).Oral health problems in older adults, particularly tooth loss, self-reported dry mouth and self-rated oral health were associated with greater incidence of disability. Poor oral health plays a potentially important role in the development of disability in older populations, which in turn is an essential part of quality of life and healthy aging.

Peer reviewed: True, Acknowledgements: We thank John Reilly for his advice on data sources and data access; Cara L Eckhardt, Josephine Avila, Igor Y Kon, and Jinzhong Wang from the Eckhardt et al study23; and all staff involved in recruitment and data collection from the included studies. Data gathered from South Africa was supported by South Africa Medical Research Council and National Research Foundation., Objective To evaluate the performance of a UK based prediction model for estimating fat-free mass (and indirectly fat mass) in children and adolescents in non-UK settings. Design Individual participant data meta-analysis. Setting 19 countries. Participants 5693 children and adolescents (49.7% boys) aged 4 to 15 years with complete data on the predictors included in the UK based model (weight, height, age, sex, and ethnicity) and on the independently assessed outcome measure (fat-free mass determined by deuterium dilution assessment). Main outcome measures The outcome of the UK based prediction model was natural log transformed fat-free mass (lnFFM). Predictive performance statistics of R2 , calibration slope, calibration-in-the-large, and root mean square error were assessed in each of the 19 countries and then pooled through random effects meta-analysis. Calibration plots were also derived for each country, including flexible calibration curves. Results The model showed good predictive ability in non-UK populations of children and adolescents, providing R2 values of >75% in all countries and >90% in 11 of the 19 countries, and with good calibration (ie, agreement) of observed and predicted values. Root mean square error values (on fat-free mass scale) were

Preventing deterioration of oral health in older age can be crucial for survival. We aimed to examine associations of oral health problems with all-cause, cardiovascular disease (CVD), and respiratory mortality in older people. We used cohort data from the British Regional Health Study (BRHS) (N = 2147, 71–92 years), and the Health, Aging and Body Composition (HABC) Study (USA) (N = 3075, 71–80 years). Follow-up was 9 years (BRHS) and 15 years (HABC Study). Oral health comprised tooth loss, periodontal disease, dry mouth, and self-rated oral health. Cox regression was performed for all-cause mortality, competing risks for CVD mortality, and accelerated failure time models for respiratory mortality. In the BRHS, tooth loss was associated with all-cause mortality (hazard ratio (HR) = 1.59, 95% CI 1.09, 2.31). In the HABC Study, tooth loss, dry mouth, and having ≥ 3 oral problems were associated with all-cause mortality; periodontal disease was associated with increased CVD mortality (subdistribution hazard ratio (SHR) = 1.49, 95% CI 1.01, 2.20); tooth loss, and accumulation of oral problems were associated with high respiratory mortality (tooth loss, time ratio (TR) = 0.73, 95% CI 0.54, 0.98). Findings suggest that poor oral health is associated with mortality. Results highlight the importance of improving oral health to lengthen survival in older age.

BACKGROUND: increasing numbers of older adults are living with frailty and its adverse consequences. We investigated relationships between diet quality or patterns and incident physical frailty in older British men and whether any associations were influenced by inflammation. METHODS: prospective study of 945 men from the British Regional Heart Study aged 70–92 years with no prevalent frailty. Incident frailty was assessed by questionnaire after 3 years of follow-up. Frailty was defined as having at least three of: low grip strength, low physical activity, slow walking speed, unintentional weight loss and feeling of low energy, all based on self-report. The Healthy Diet Indicator (HDI) based on WHO dietary guidelines and the Elderly Dietary Index (EDI) based on a Mediterranean-style dietary intake were computed from questionnaire data and three dietary patterns were identified using principal components analysis: prudent, high fat/low fibre and high sugar. RESULTS: men in the highest EDI category and those who followed a prudent diet were less likely to become frail [top vs bottom category odds ratio (OR) (95% CI) 0.49 (0.30, 0.82) and 0.53 (0.30, 0.92) respectively] after adjustment for potential confounders including BMI and prevalent cardiovascular disease. No significant association was seen for the HDI. By contrast those who had a high fat low fibre diet pattern were more likely to become frail [OR (95% CI) 2.54 (1.46, 4.40)]. These associations were not mediated by C-reactive protein (marker of inflammation). CONCLUSIONS: the findings suggest adherence to a Mediterranean–style diet is associated with reduced risk of developing frailty in older people.

Purpose To examine associations between retinal vessel morphometry and cardiometabolic risk factors in older British men and women. Design Retinal imaging examination as part of the European Prospective Investigation into Cancer—Norfolk Eye Study. Participants Retinal imaging and clinical assessments were carried out in 7411 participants. Retinal images were analyzed using a fully automated validated computerized system that provides novel measures of vessel morphometry. Methods Associations between cardiometabolic risk factors, chronic disease, and retinal markers were analyzed using multilevel linear regression, adjusted for age, gender, and within-person clustering, to provide percentage differences in tortuosity and absolute differences in width. Main Outcomes Measures Retinal arteriolar and venular tortuosity and width. Results In all, 279 802 arterioles and 285 791 venules from 5947 participants (mean age, 67.6 years; standard deviation [SD], 7.6 years; 57% female) were analyzed. Increased venular tortuosity was associated with higher body mass index (BMI; 2.5%; 95% confidence interval [CI], 1.7%–3.3% per 5 kg/m 2 ), hemoglobin A1c (HbA1c) level (2.2%; 95% CI, 1.0%–3.5% per 1%), and prevalent type 2 diabetes (6.5%; 95% CI, 2.8%–10.4%); wider venules were associated with older age (2.6 μm; 95% CI, 2.2–2.9 μm per decade), higher triglyceride levels (0.6 μm; 95% CI, 0.3–0.9 μm per 1 mmol/l), BMI (0.7 μm; 95% CI, 0.4–1.0 per 5 kg/m 2 ), HbA1c level (0.4 μm; 95% CI, –0.1 to 0.9 per 1%), and being a current smoker (3.0 μm; 95% CI, 1.7–4.3 μm); smoking also was associated with wider arterioles (2.1 μm; 95% CI, 1.3–2.9 μm). Thinner venules were associated with high-density lipoprotein (HDL) (1.4 μm; 95% CI, 0.7–2.2 per 1 mmol/l). Arteriolar tortuosity increased with age (5.4%; 95% CI, 3.8%–7.1% per decade), higher systolic blood pressure (1.2%; 95% CI, 0.5%–1.9% per 10 mmHg), in females (3.8%; 95% CI, 1.4%–6.4%), and in those with prevalent stroke (8.3%; 95% CI, –0.6% to 18%); no association was observed with prevalent myocardial infarction. Narrower arterioles were associated with age (0.8 μm; 95% CI, 0.6–1.0 μm per decade), higher systolic blood pressure (0.5 μm; 95% CI, 0.4–0.6 μm per 10 mmHg), total cholesterol level (0.2 μm; 95% CI, 0.0–0.3 μm per 1 mmol/l), and HDL (1.2 μm; 95% CI, 0.7–1.6 μm per 1 mmol/l). Conclusions Metabolic risk factors showed a graded association with both tortuosity and width of retinal venules, even among people without clinical diabetes, whereas atherosclerotic risk factors correlated more closely with arteriolar width, even excluding those with hypertension and cardiovascular disease. These noninvasive microvasculature measures should be evaluated further as predictors of future cardiometabolic disease.

We aimed to investigate the associations of poor oral health cross-sectionally with diet quality and intake in older people. We also examined whether change in diet quality is associated with oral health problems. Data from the British Regional Heart Study (BRHS) comprising British males aged 71–92 years and the Health, Aging and Body Composition (HABC) Study comprising American males and females aged 71–80 years were used. Dental data included tooth loss, periodontal disease, dry mouth and self-rated oral health. Dietary data included diet quality (based on Elderly Dietary Index (BRHS) and Healthy Eating Score (HABC Study)) and several nutrients. In the BRHS, change in diet quality over 10 years (1998–2000 to 2010–2012) was also assessed. In the BRHS, tooth loss, fair/poor self-rated oral health and accumulation of oral health problems were associated with poor diet quality, after adjustment. Similar associations were reported for high intake of processed meat. Poor oral health was associated with the top quartile of percentage of energy content from saturated fat (self-rated oral health, OR 1·34, 95 % CI 1·02, 1·77). In the HABC Study, no significant associations were observed for diet quality after adjustment. Periodontal disease was associated with the top quartile of percentage of energy content from saturated fat (OR 1·48, 95 % CI 1·09, 2·01). In the BRHS, persistent low diet quality was associated with higher risk of tooth loss and accumulation of oral health problems. Older individuals with oral health problems had poorer diets and consumed fewer nutrient-rich foods. Persistent poor diet quality was associated with oral health problems later in life.

We aimed to investigate the associations of poor oral health cross-sectionally with diet quality and intake in older people. We also examined whether change in diet quality is associated with oral health problems. Data from the British Regional Heart Study (BRHS) comprising British males aged 71–92 years and the Health, Aging and Body Composition (HABC) Study comprising American males and females aged 71–80 years were used. Dental data included tooth loss, periodontal disease, dry mouth and self-rated oral health. Dietary data included diet quality (based on Elderly Dietary Index (BRHS) and Healthy Eating Score (HABC Study)) and several nutrients. In the BRHS, change in diet quality over 10 years (1998–2000 to 2010–2012) was also assessed. In the BRHS, tooth loss, fair/poor self-rated oral health and accumulation of oral health problems were associated with poor diet quality, after adjustment. Similar associations were reported for high intake of processed meat. Poor oral health was associated with the top quartile of percentage of energy content from saturated fat (self-rated oral health, OR 1·34, 95 % CI 1·02, 1·77). In the HABC Study, no significant associations were observed for diet quality after adjustment. Periodontal disease was associated with the top quartile of percentage of energy content from saturated fat (OR 1·48, 95 % CI 1·09, 2·01). In the BRHS, persistent low diet quality was associated with higher risk of tooth loss and accumulation of oral health problems. Older individuals with oral health problems had poorer diets and consumed fewer nutrient-rich foods. Persistent poor diet quality was associated with oral health problems later in life.

ObjectiveFrailty and heart failure (HF) are cross-sectionally associated. Published longitudinal data are very limited. We sought to investigate associations between frailty and incident HF.MethodsProspective study of 1722 men, examined at age 72–91 years. Scores based on the Fried phenotype, Gill index and a novel frailty score, based on the Health Ageing and Body Composition Battery, incorporating slow walking speed, low chair-stand time and subjective difficulty with balance, were calculated. Associations between these scores and incident HF were analysed with Cox proportional hazard modelling.Results1445 men with frailty data and without prevalent HF were included. 99 developed HF (mean follow-up 6.1 years). Men scoring 3/3 on our novel frailty score had elevated risk of incident HF (HR 2.77, 95% CI 1.25 to 6.15), which persisted after adjustment for established risk factors and interleukin-6 (HR 3.14, 95% CI 1.35 to 7.31). This risk remained increased, although attenuated, after excluding HF events within 2 years of baseline (HR 2.05, 95% CI 0.61 to 6.92). The frailty phenotype showed a non-significant association with HF (age-adjusted HR 1.92, 95% CI 0.99 to 3.73), which was further attenuated after adjustment for prevalent coronary heart disease and Body mass index (HR 1.60, 95% CI 0.81 to 3.15). Gill-type scores were weakly associated with HF risk after these adjustments (HR 1.31, 95% CI 0.47 to 3.70).ConclusionIn these older men, the combination of slow walk speed, low sit-stand time and balance problems were associated with high risk of incident HF, independent of established risk factors and inflammatory markers. However, undiagnosed HF at baseline may still be a confounder. There is a differential association between aspects of the frailty phenotype and incident HF.

BACKGROUND/OBJECTIVES: Subclinical cardiovascular disease (CVD) is cross-sectionally associated with frailty, but the relationship between subclinical CVD and incident frailty has not been reported. We aimed to assess this prospective association. DESIGN: Longitudinal analysis of data from the British Regional Heart Study, a prospective cohort study. PARTICIPANTS: 1057 men, aged 71-92 years, robust or pre-frail at baseline, and without a clinical diagnosis of CVD. MEASUREMENTS: Participants underwent baseline measurement of carotid-femoral pulse wave velocity (cfPWV), carotid intima-media thickness (CIMT), carotid distensibility coefficient (DC), and ankle-brachial pressure index (ABPI), and had questionnaire-based frailty assessment after three years. Frailty status was based on the Fried phenotype. Multivariate logistic regressions examined associations between incident frailty and tertile of cfPWV, CIMT, DC, and ABPI group (

We have assessed the association between excessive orthostatic changes in blood pressure and risk of incident heart failure (HF) in older, community-dwelling men. This was a prospective cohort study of 3505 men (mean age, 68.5 years), who did not have prevalent HF, myocardial infarction, or stroke. Excessive orthostatic change in blood pressure was defined continuously and categorically as orthostatic hypotension (sitting-to-standing decrease in systolic blood pressure ≥20 mm Hg or diastolic blood pressure ≥10 mm Hg), systolic orthostatic hypertension (increase in systolic blood pressure ≥20 mm Hg, diastolic orthostatic hypertension as diastolic blood pressure ≥10 mm Hg), and orthostatic normotension (neither orthostatic hypotension nor orthostatic hypertension). There was a U-shaped association between orthostatic changes in systolic blood pressure and the risk of incident HF; for diastolic blood pressure, only its fall predicted HF. After adjustment for possible confounders, the hazard ratio (95% CI) for incident HF was 1.65 (1.24–2.18) in men with orthostatic hypotension and 0.90 (0.65–1.24) and 1.88 (1.30–2.73) in men with diastolic and systolic orthostatic hypertension, respectively. Both components of orthostatic hypotension were associated with increased risk, although the systolic component was more predictive than the diastolic component. Both orthostatic hypotension and orthostatic hypertension are associated with risk of incident HF in older men. Our findings suggest that orthostatic hypertension is defined by a rise beyond threshold in systolic blood pressure only. Further prospective studies in diverse cohorts are needed to confirm our findings.

Background orthostatic hypotension (OH) that occurs within, or at, 1 minute of standing is associated with higher risk of falls, myocardial infarction, syncope and mortality, compared to OH that occurs after 1 minute of standing. Whether vitamin D deficiency increases the risk of OH is controversial. Methods this was a cross-sectional analysis of 3,620 older, community-dwelling men. Multinomial, multiple logistic regression models were used to calculate the risk of OH across categories of vitamin D status (deficient [ Results men with vitamin D deficiency were more likely to have OH that occurred within 1 minute of standing in univariate logistic regression (OR 1.88, 95% CI 1.40–2.53) and multinomial, multiple logistic regression (OR 1.51, 95% CI 1.06–2.15), compared to men with sufficient levels of vitamin D. Vitamin D insufficiency was not associated with the risk of OH. Elevated parathyroid hormone was not associated with risk of OH. Conclusion the absence of an association between vitamin D insufficiency and risk of OH and the presence of an association between vitamin D deficiency and risk of OH suggest that there may be a threshold effect; it is only below a particular level of vitamin D that risk of OH is increased. In this cohort, the threshold was

Background and Purpose: Research exploring the utility of cardiovascular health (CVH) and its Life’s Simple 7 (LS7) components (body mass index, blood pressure [BP], glucose, cholesterol, physical activity, smoking, and diet) for prevention of stroke in older adults is limited. In the British Regional Heart Study, we explored (1) prospective associations of LS7 metrics and composite CVH scores with, and their impact on, stroke in middle and older age; and (2) if change in CVH was associated with subsequent stroke. Methods: Men without cardiovascular disease were followed from baseline recruitment (1978–1980), and again from re-examination 20 years later, for stroke over a median period of 20 years and 16 years, respectively. LS7 were measured at each time point except baseline diet. Cox models estimated hazard ratios (95% CI) of stroke for (1) ideal and intermediate versus poor levels of LS7; (2) composite CVH scores; and (3) 4 CVH trajectory groups (low-low, low-high, high-low, high-high) derived by dichotomising CVH scores from each time point across the median value. Population attributable fractions measured impact of LS7. Results: At baseline (n=7274, mean age 50 years), healthier levels of BP, physical activity, and smoking were associated with reduced stroke risk. At 20-year follow-up (n=3798, mean age 69 years) only BP displayed an association. Hazard ratios for intermediate and ideal (versus poor) levels of BP 0.65 (0.52–0.81) and 0.40 (0.24–0.65) at baseline; and 0.84 (0.67–1.05) and 0.57 (0.36–0.90) at 20-year follow-up. With reference to low-low trajectory, the low-high trajectory was associated with 40% reduced risk, hazard ratio 0.60 (0.44–0.83). Associations of CVH scores weakened, and population attributable fractions of LS7 reduced, from middle to old age; population attributable fraction of nonideal BP from 53% to 39%. Conclusions: Except for BP, CVH is weakly associated with stroke at older ages. Prevention strategies for older adults should prioritize BP control but also enhance focus beyond traditional risk factors.

Background The American Heart Association’s model of ideal cardiovascular health (CVH), based on 7 well-known and modifiable health factors (body mass index, blood pressure (BP), glucose, cholesterol, physical activity, smoking and diet - Life’s Simple 7 or LS7) was developed to promote primordial prevention of cardiovascular disease (CVD), including stroke. Stroke burden rises sharply with age. However most research exploring CVH has been conducted in middle-aged participants. In the British Regional Heart Study (BRHS), we prospectively explored associations of each LS7 factor and composite CVH scores with stroke in middle and older age; and associations between CVH trajectories and stroke incidence in later life. Methods The BRHS is a prospective study of men recruited in 1978–1980 (aged 40–59y, baseline) and followed up for CVD events. The men were re-examined at 20 years (Q20). All components of LS7 were measured at both time points except baseline diet. Men without pre-existing CVD were followed from baseline (mean age 50y, n=6612) and again from Q20 (mean age 69y, n=3798) for a median period of 20y and 16y respectively. Cox models estimated risk of stroke as adjusted hazard ratios (HRs) for ideal and intermediate vs poor levels of LS7 factors; for composite CVH scores; and for 4 CVH trajectory groups based on transitions in CVH status (low/high) from baseline to Q20 - Low-Low, Low-High, High-Low and High-High. Results Stroke event rates for baseline and Q20 cohorts were 3.1 and 8.4 per 1000 person years respectively. At baseline, healthier levels of three LS7 - BP, physical activity and smoking were associated with reduced risk of stroke. HRs [95% Confidence Intervals] for intermediate and ideal (vs poor) were 0.62 [0.49, 0.79] and 0.41 [0.24, 0.69] for BP; 0.68 [0.49, 0.95] and 0.55 [0.39, 0.79] for physical activity; and 0.68 [0.54, 0.86] and 0.57 [0.43, 0.77] for smoking. For exposures measured at Q20, only BP maintained a protective association (HRs 0.84 [0.66, 1.06] and 0.50 [0.30, 0.84] for intermediate and ideal levels respectively). Protection from each unit increase in overall CVH scores also weakened with age. With reference to the Low-Low trajectory, all trajectories were generally associated with reduced risk. The HRs were Low-High 0.57 (0.41, 0.79); High-Low 0.85 (0.61, 1.19) and High-High 0.77 (0.58, 1.03) respectively. Conclusion Not all components of CVH individually influence stroke. While the association between CVH and stroke weakens with age, improving overall CVH may bring some benefit even in later life.

Background We investigated the associations of poor oral health with dietary quality and intake in older people. We also examined whether changes in dietary quality can influence the risk of oral health problems. Methods Data come from the British Regional Heart Study (BRHS) and the Health, Aging and Body Composition (HABC) Study. The BRHS included older men from 24 British towns aged 71–92 years in 2010–12 (n=2,147). The HABC Study, included 3,075 American men and women aged 71–80. In both studies, measures of oral health included tooth loss, periodontal disease, dry mouth, and self-rated oral health. Dietary data included dietary quality (Elderly Dietary Index in the BRHS, and Healthy Eating Score in the HABC Study) and intake (processed meat, calories from fat, protein and fruits and vegetables). Additionally in the BRHS, change in dietary quality was assessed over 10 years from 1998–2000 (age 60–79 years) to 2010–2012 (71–92 years). Results In the BRHS, tooth loss, fair/poor self-rated oral health and accumulation of oral health problems were associated with poor dietary quality, after adjustment for age, social class, smoking, alcohol, history of cardiovascular disease (CVD) and diabetes, body mass index (BMI) and energy intake. Similar associations were observed for high intake of processed meat. Accumulation of oral health problems and self-rated oral health were associated with being in the top quartile of percentage of calories from saturated fat (fair/poor self-rated oral health, odds ratio (OR)=1.34, 95% CI 1.02–1.77) after adjustment for confounders. In the HABC study, no significant associations were observed between poor oral health and dietary quality after full adjustment. In the fully-adjusted model (age, gender, race, education, smoking, alcohol, history of CVD and diabetes, BMI and energy intake), periodontal disease was associated with the top quartile of percentage of calories from saturated fat (OR=1.48, 95%CI 1.09–2.01). In the BRHS, persistent low dietary quality over 10 years (from age 60–79 to 71–92 years), was associated with higher risk of tooth loss and accumulation of oral health problems at 71–92 years. Conclusion Older individuals with oral health problems had poorer diets and consumed fewer nutrient-rich foods. Moreover, persistent poor dietary quality in older ages was associated with oral health problems later in life, suggesting bi-directional associations between oral health and dietary intake in older age. Improved management of nutrition and oral health are both important aspects of the health of older populations.

BackgroundThere is growing interest in the role of vitamin D in extra-skeletal health, including postural hypotension. Postural hypotension is found in 1 in 5 community-dwelling adults aged 60 years and above. It increases risk of falls, fractures, cardiovascular disease and all-cause mortality. Better understanding of the aetiology of postural hypotension may help yield more effective treatment options than those that are currently available.AimThe aim of this study was to investigate the association between circulating vitamin D, parathyroid hormone and postural hypotension.MethodThis was a cross-sectional analysis of 3620 community-dwelling men living in the UK (mean age 68.6 years; standard deviation 5.5 years). Vitamin D status (nmol/L) was categorised as sufficient (≥50), insufficient (≥25 – ResultsCompared to sufficient levels of vitamin D, vitamin D deficiency increased risk of postural hypotension that specifically occurred within one minute of standing (OR 1.51, 95% CI = 1.06 to 2.15) in multinomial, multiple logistic regression. Neither vitamin D insufficiency, nor elevated parathyroid hormone, were associated with postural hypotension.ConclusionIn this study, vitamin D deficiency was associated with increased risk of postural hypotension. Further research may help clarify whether treating vitamin D deficiency can reduce the degree of postural hypotension, or if preventing the progression to vitamin D deficiency can reduce the incidence of postural hypotension.

Background Motivational interviewing (MI) enhanced with behaviour change techniques (BCTs) and deployed by health trainers targeting multiple risk factors for cardiovascular disease (CVD) may be more effective than interventions targeting a single risk factor. Objectives The clinical effectiveness and cost-effectiveness of an enhanced lifestyle motivational interviewing intervention for patients at high risk of CVD in group settings versus individual settings and usual care (UC) in reducing weight and increasing physical activity (PA) were tested. Design This was a three-arm, single-blind, parallel randomised controlled trial. Setting A total of 135 general practices across all 12 South London Clinical Commissioning Groups were recruited. Participants A total of 1742 participants aged 40–74 years with a ≥ 20.0% risk of a CVD event in the following 10 years were randomised. Interventions The intervention was designed to integrate MI and cognitive–behavioural therapy (CBT), delivered by trained healthy lifestyle facilitators in 10 sessions over 1 year, in group or individual format. The control group received UC. Randomisation Simple randomisation was used with computer-generated randomisation blocks. In each block, 10 participants were randomised to the group, individual or UC arm in a 4 : 3 : 3 ratio. Researchers were blind to the allocation. Main outcome measures The primary outcomes are change in weight (kg) from baseline and change in PA (average number of steps per day over 1 week) from baseline at the 24-month follow-up, with an interim follow-up at 12 months. An economic evaluation estimates the relative cost-effectiveness of each intervention. Secondary outcomes include changes in low-density lipoprotein cholesterol and CVD risk score. Results The mean age of participants was 69.75 years (standard deviation 4.11 years), 85.5% were male and 89.4% were white. At the 24-month follow-up, the group and individual intervention arms were not more effective than UC in increasing PA [mean 70.05 steps, 95% confidence interval (CI) –288 to 147.9 steps, and mean 7.24 steps, 95% CI –224.01 to 238.5 steps, respectively] or in reducing weight (mean –0.03 kg, 95% CI –0.49 to 0.44 kg, and mean –0.42 kg, 95% CI –0.93 to 0.09 kg, respectively). At the 12-month follow-up, the group and individual intervention arms were not more effective than UC in increasing PA (mean 131.1 steps, 95% CI –85.28 to 347.48 steps, and mean 210.22 steps, 95% CI –19.46 to 439.91 steps, respectively), but there were reductions in weight for the group and individual intervention arms compared with UC (mean –0.52 kg, 95% CI –0.90 to –0.13 kg, and mean –0.55 kg, 95% CI –0.95 to –0.14 kg, respectively). The group intervention arm was not more effective than the individual intervention arm in improving outcomes at either follow-up point. The group and individual interventions were not cost-effective. Conclusions Enhanced MI, in group or individual formats, targeted at members of the general population with high CVD risk is not effective in reducing weight or increasing PA compared with UC. Future work should focus on ensuring objective evidence of high competency in BCTs, identifying those with modifiable factors for CVD risk and improving engagement of patients and primary care. Trial registration Current Controlled Trials ISRCTN84864870. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 69. See the NIHR Journals Library website for further project information. This research was part-funded by the NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London.

Purpose To investigate associations between diet quality, dietary patterns and mobility limitation 15 years later in a population-based sample of older British men. Methods We used longitudinal data from 1234 men from the British Regional Heart Study, mean age 66 years at baseline. Mobility limitation was defined as difficulty going up- or downstairs or walking 400 yards as a result of a long-term health problem. Dietary intake was measured using a food frequency questionnaire data from which the Healthy Diet Indicator (HDI), the Elderly Dietary Index (EDI), and three a posteriori dietary patterns were derived. The a posteriori dietary patterns were identified using principal components analysis: (1) high fat/low fibre, (2) prudent and (3) high sugar. Results Men with greater adherence to the EDI or HDI were less likely to have mobility limitation at follow-up, top vs bottom category odds ratio for the EDI OR 0.50, 95% CI 0.34, 0.75, and for the HDI OR 0.55, 95% CI 0.35, 0.85, after adjusting for age, social class, region of residence, smoking, alcohol consumption and energy intake. Men with a higher score for the high-fat/low-fibre pattern at baseline were more likely to have mobility limitation at follow-up, top vs bottom quartile odds ratio OR 3.28 95% CI 2.05, 5.24. These associations were little changed by adjusting for BMI and physical activity. Conclusion Our study provides evidence that healthier eating patterns could contribute to prevention or delay of mobility limitation in older British men. Electronic supplementary material The online version of this article (10.1007/s00394-018-1786-y) contains supplementary material, which is available to authorized users.

Background: The influence of life-course socioeconomic disadvantage on oral health at older ages is not well-established. We examined the influence of socioeconomic factors in childhood, middle-age and older age on oral health at older ages, and tested conceptual life-course models (sensitive period, accumulation of risk, social mobility) to determine which best described observed associations. / Methods: A representative cohort of British men aged 71–92 in 2010–12 included socioeconomic factors in childhood, middle-age and older age. Oral health assessment at 71–92 years (n = 1622) included tooth count, periodontal disease and self-rated oral health (excellent/good, fair/poor) (n = 2147). Life-course models (adjusted for age and town of residence) were compared with a saturated model using Likelihood-ratio tests. / Results: Socioeconomic disadvantage in childhood, middle-age and older age was associated with complete tooth loss at 71–92 years—age and town adjusted odds ratios (95% CI) were 1.39 (1.02–1.90), 2.26 (1.70–3.01), 1.83 (1.35–2.49), respectively. Socioeconomic disadvantage in childhood and middle-age was associated with poor self-rated oral health; adjusted odds ratios (95% CI) were 1.48 (1.19–1.85) and 1.45 (1.18–1.78), respectively. A sensitive period for socioeconomic disadvantage in middle-age provided the best model fit for tooth loss, while accumulation of risk model was the strongest for poor self-rated oral health. None of the life-course models were significant for periodontal disease measures. / Conclusion: Socioeconomic disadvantage in middle-age has a particularly strong influence on tooth loss in older age. Poor self-rated oral health in older age is influenced by socioeconomic disadvantage across the life-course. Addressing socioeconomic factors in middle and older ages are likely to be important for better oral health in later life.

To examine the association between serum magnesium and incident heart failure (HF) in older men and investigate potential pathways including cardiac function, inflammation and lung function. Prospective study of 3523 men aged 60-79 years with no prevalent HF or myocardial infarction followed up for a mean period of 15 years, during which 268 incident HF cases were ascertained. Serum magnesium was inversely associated with many CVD risk factors including prevalent atrial fibrillation, lung function (FEV1) and markers of inflammation (IL-6), endothelial dysfunction (vWF) and cardiac dysfunction [NT-proBNP and cardiac troponin T (cTnT)]. Serum magnesium was inversely related to risk of incident HF after adjustment for conventional CVD risk factors and incident MI. The adjusted hazard ratios (HRs) for HF in the 5 quintiles of magnesium groups were 1.00, 0.72 (0.50, 1.05), 0.85 (0.59, 1.26), 0.76 (0.52, 1.11) and 0.56 (0.36, 0.86) respectively [p (trend) = 0.04]. Further adjustment for atrial fibrillation, IL-6, vWF and FEV1 attenuated the association but risk remained significantly reduced in the top quintile (≥ 0.87 mmol/l) compared with the lowest quintile [HR 0.62 (0.40, 0.97)]. Adjustment for NT-proBNP and cTnT attenuated the association further [HR 0.70 (0.44, 1.10)]. The benefit of high serum magnesium on HF risk was most evident in men with ECG evidence of ischaemia [HR 0.29 (0.13, 0.68)]. The potential beneficial effect of high serum magnesium was partially explained by its favourable association with CVD risk factors. Further studies are needed to investigate whether serum magnesium supplementation in older adults may protect from the development of HF.

Aims: Taller stature has been associated with increased risk of atrial fibrillation (AF). AF and heart failure (HF) often co-occur but the association between height and risk of HF in older adults has not been well studied. We have examined the association between height and incident AF and incident HF in older adults. Methods: Prospective study of 3346 men aged 60-79 years with no diagnosed HF, myocardial infarction or stroke at baseline (1998-2000) followed up for a mean period of 16 years, in whom there were 294 incident HF cases and 456 incident AF. Men were divided into 5 height groups: 183.0 cms based on the 25th, 50th, 75th and 95th centiles distribution of height. Results: CVD risk factors tended to decrease with increasing height but a positive association was seen between height and electrocardiographic QRS duration and incident AF. Both short stature (183.0 cm) was associated with significantly increased risk of HF in age-adjusted analysis compared to those in the second height quartile [HR (95 %CI) = 1.62 (1.15, 2.26) and 2.04 (1.23, 3.39) respectively]. In short men the increased risk remained after adjustment for adverse CVD risk factors; in tall men the association was largely associated with AF and QRS duration. Conclusion: Tall stature is associated with significantly increased risk of AF leading to increased risk of HF. Short stature was associated with increased HF risk which was not explained by known adverse CVD risk factors.

The morphometric characteristics of the retinal vasculature are associated with future risk of many systemic and vascular diseases. However, analysis of data from large population based studies is needed to help resolve uncertainties in some of these associations. This requires automated systems that extract quantitative measures of vessel morphology from large numbers of retinal images. Associations between retinal vessel morphology and disease precursors/outcomes may be similar or opposing for arterioles and venules. Therefore, the accurate detection of the vessel type is an important element in such automated systems. This paper presents a deep learning approach for the automatic classification of arterioles and venules across the entire retinal image, including vessels located at the optic disc. This comprises of a convolutional neural network whose architecture contains six learned layers: three convolutional and three fully-connected. Complex patterns are automatically learnt from the data, which avoids the use of hand crafted features. The method is developed and evaluated using 835,914 centreline pixels derived from 100 retinal images selected from the 135,867 retinal images obtained at the UK Biobank (large population-based cohort study of middle aged and older adults) baseline examination. This is a challenging dataset in respect to image quality and hence arteriole/venule classification is required to be highly robust. The method achieves a significant increase in accuracy of 8.1% when compared to the baseline method, resulting in an arteriole/venule classification accuracy of 86.97% (per pixel basis) over the entire retinal image. Morphology of retinal vasculature associated with risk markers of many diseases.Large population based studies help to resolve uncertainties in these associations.Automated system extracts morphometric data from the UK Biobank cohort study.Detection of the vessel type is an important element in such automated systems.Deep learning approach for the automatic classification of arterioles and venules.

BACKGROUND: Frailty is a state of increased vulnerability to disability, falls, and mortality. The Fried frailty phenotype includes assessments of grip strength and gait speed, which are complex or require objective measurements and are challenging in routine primary care practice. In this study, we aimed to develop a simple assessment tool based on self-reported information on the 5 Fried frailty components to identify older people at risk of incident disability, falls, and mortality. METHODS: Analyses are based on a prospective cohort comprising older British men aged 71-92 years in 2010-2012. A follow-up questionnaire was completed in 2014. The discriminatory power for incident disability and falls was compared with the Fried frailty phenotype using receiver operating characteristic-area under the curve (ROC-AUC); for incident falls it was additionally compared with the FRAIL scale (fatigue, resistance, ambulation, illnesses, and loss of weight). Predictive ability for mortality was assessed using age-adjusted Cox proportional hazard models. RESULTS: A model including self-reported measures of slow walking speed, low physical activity, and exhaustion had a significantly increased ROC-AUC [0.68, 95% confidence interval (CI) 0.63-0.72] for incident disability compared with the Fried frailty phenotype (0.63, 95% CI 0.59-0.68; P value of ΔAUC = .003). A second model including self-reported measures of slow walking speed, low physical activity, and weight loss had a higher ROC-AUC (0.64, 95% CI 0.59-0.68) for incident falls compared with the Fried frailty phenotype (0.57, 95% CI 0.53-0.61; P value of ΔAUC

Background Pediatric hypertension is typically defined as blood pressure ≥ sex-, age-, and height-specific 95th percentile (high) cutoffs. Given the number of strata, there are hundreds of cutoffs for defining elevated and high blood pressure that make it cumbersome to use in clinical practice. This study aimed to evaluate the utility of the static cutoffs for pediatric hypertension (120/80 mm Hg for children and 130/80 mm Hg for adolescents) in determining high carotid intimamedia thickness (cIMT) in children and adolescents. Methods Data were from 6 population-based cross-sectional studies in Brazil, China, Greece, Italy, Spain, and the United Kingdom. A total of 4280 children and adolescents, aged 6 to 17 years, were included. High cIMT was defined as cIMT ≥ sex-, age- and cohort-specific 90th percentile cutoffs. Results Compared with normal blood pressure, hypertension defined using the percentile-based cutoffs from 2017 American Academy of Pediatrics guideline, and the static cutoffs were associated with similar higher odds for high cIMT (percentile-based cutoffs: odds ratio [OR], 1.46, 95% confidence interval [CI], 1.15-1.86; static cutoffs: OR, 1.65, 95% CI, 1.25-2.17), after adjustment for sex, age, race/ethnicity, body mass index, high-density lipoprotein-cholesterol, triglyceride, and fasting blood glucose. The similar utility of 2 definitions in determining high cIMT was further confirmed by area under the receiver operating characteristic curve and net reclassification improvement methods (P for difference > 0.05). Conclusion Static cutoffs (120/80 mm Hg for children, 130/80 mm Hg for adolescents) performed similarly compared with percentile-based cutoffs in determining high cIMT, supporting the use of static cutoffs in identifying pediatric hypertension in clinical practice.

Objective Kuwait has one of the highest obesity rates in the world. This study examined the associations between sedentary behaviour (objectively measured and self-reported), adiposity and systolic blood pressure in a sample of adolescents residing in Kuwait. Data was obtained from the Study of Health and Activity among adolescents in Kuwait (2012–2013). The sample included a total of 435 adolescents (201 boys). Outcomes were age- and sex specific body mass index Z-scores and systolic blood pressure. Exposures were total sedentary behaviour measured by accelerometry and time spent in some sedentary behaviours (television viewing, video games, computer use and total screen-time). We used multiple linear regression analyses, adjusted for age, governorate, maternal education and physical activity, to examine associations between sedentary behaviour and adiposity and systolic blood pressure. Results Only 2 statistically significant associations were found between sedentary behaviour and the study outcomes: body mass in boys was directly associated with higher sedentary time [β (95% CIs) 0.003 (0.00 to 0.06)]; body mass index was inversely associated with videogames in both sexes [girls: β (95% CIs) − 0.17 (− 0.48 to − 0.04); boys: − 0.24 (− 0.57 to − 0.12)]. In this sample of Kuwaiti adolescents, sedentary behaviour showed limited deleterious associations with adiposity and systolic blood pressure.

Background Oral health conditions such as tooth loss, periodontal (gum) disease and dryness of mouth are very common health problems in older people, with significant impacts on nutrition, quality of life and well-being of ageing populations. Oral health, particularly periodontal disease, has been linked to systemic inflammation, such as high C-reactive protein (CRP) and interleukin-6 (IL-6). However, very few studies of older people have investigated the associations between oral health and inflammation. We examined whether a range of oral health markers are associated with inflammatory markers in two population-based studies of older people in the UK and USA. Methods Cross-sectional analyses were conducted in the British Regional Heart Study (BRHS) comprising men aged 71–92 (n=2147) from 24 British towns, and the US Health, Aging and Body Composition (HABC) Study comprising men and women aged 71–80 (n=3075). Assessments included oral health (periodontal disease, tooth count, dry mouth) and inflammatory markers such as CRP, IL-6, leptin, tissue plasminogen activator (tPA), von Willebrand Factor (vWF), fibrin D-dimer, high sensitivity Troponin T (hsTnT), N-Terminal prohormone of brain natriuretic peptide (NTproBNP), and proinsulin. Results In the BRHS, having no natural teeth was associated with being in the top tertiles of CRP, and fibrin D-dimer (odds ratio (OR)=1.35, 95%CI: 1.01–1.80; OR=1.38, 95%CI: 1.03–1.85, respectively) after adjustment for age, social class, smoking, history of cardiovascular disease and diabetes, and BMI. Tooth loss ( Conclusion Poor oral health in older people was associated with increased levels of various inflammatory markers including CRP, fibrin D-dimer, hsTnT and NTproBNP. These findings suggest that poor oral health in older age is linked not only to general systemic inflammation but also inflammation associated with metabolic disturbances. These associations could offer insights into mechanistic pathways by which poor oral health could influence age-related conditions.

Background Disability and poor physical function have major impacts on the health and well-being of ageing populations. Poor oral health (tooth loss, periodontal (gum) disease, dryness of mouth) are also very common health problems in older populations, and adversely impact nutrition and quality of life. Studies suggest that poor oral health in older age is associated with disability, however most studies have limited oral health measures. We investigated the association of a range of objectively and subjectively assessed oral health markers with disability and physical function in two population-based studies of older people in the UK and USA. Methods Cross-sectional analyses were conducted in the British Regional Heart Study (BRHS) comprising men aged 71–92 (n=2147) from 24 British towns, and the US Health, Aging and Body Composition (HABC) Study comprising men and women aged 71–80 (n=3075). Assessments included objective measures of oral health (periodontal disease, tooth count), and subjective measures (dry mouth, self-reported oral health, dental service use), and disability [mobility limitations, Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL)], and physical function (grip strength, gait speed, chair stand test). Logistic regression models, adjusted for confounding variables, were used to examine the associations between oral health and disability and physical function. Results In the BRHS, dry mouth, tooth loss, and cumulative oral health problems (≥3 problems) were associated with greater risks of mobility limitations, problems with ADL and IADL; these remained significant after adjustment for confounding variables (for ≥3 dry mouth symptoms, odds ratio (OR)=2.68, 95%CI=1.94–3.69; OR=1.76, 95%CI=1.15–2.69; OR=2.90, 95% CI: 2.01, 4.18, respectively). Similar results were observed in the HABC Study for mobility limitations and ADL (for ≥3 oral health problems, OR=2.19, 95% CI: 1.56–3.07; OR=2.63, 95% CI: 1.81–3.81, respectively), after full-adjustment. In the BRHS, periodontal pocket depth greater >3.5 mm was associated with increased risk of being in the bottom quintile of grip strength (OR=1.59, 95%CI: 1.14–2.20). Moreover, dry mouth was associated with the top quintile of gait speed in the BRHS, and bottom quintile of grip strength in the HABC Study (OR=1.75, 95% CI: 1.22, 2.50; OR=2.43. 95%CI=1.47–4.01, respectively). Conclusion Markers of poor oral health, particularly dry mouth, poor self-rated oral health and having more than one oral health problems were associated with higher risks of disability and impaired physical function in older populations. Investigations to assess these associations prospectively and the underlying pathways are needed.

ObjectiveThe epidemic of obesity is contributing to the increasing prevalence of people at high risk of cardiovascular disease (CVD), negating the medical advances in reducing CVD mortality. We compared the clinical and cost-effectiveness of an intensive lifestyle intervention consisting of enhanced motivational interviewing in reducing weight and increasing physical activity for patients at high risk of CVD.MethodsA three-arm, single-blind, parallel-group randomised controlled trial was conducted in consenting primary care centres in south London. We recruited patients aged 40–74 years with a QRisk2 score ≥20.0%, which indicates the probability of having a CVD event in the next 10 years. The intervention was enhanced motivational interviewing which included additional behaviour change techniques and was delivered by health trainers in 10 sessions over 1 year, in either group (n=697) or individual (n=523) format. The third arm received usual care (UC; n=522). The primary outcomes were physical activity (mean steps/day) and weight (kg). Secondary outcomes were changes in low-density lipoprotein cholesterol and CVD risk score. We estimated the relative cost-effectiveness of each intervention.ResultsAt 24 months, the group and individual interventions were not more effective than UC in increasing physical activity (mean difference=70.05 steps, 95% CI −288.00 to 147.90 and mean difference=7.24 steps, 95% CI −224.01 to 238.50, respectively), reducing weight (mean difference=−0.03 kg, 95% CI −0.49 to 0.44 and mean difference=−0.42 kg, 95% CI −0.93 to 0.09, respectively) or improving any secondary outcomes. The group and individual interventions were not cost-effective at conventional thresholds.ConclusionsEnhancing motivational interviewing with additional behaviour change techniques was not effective in reducing weight or increasing physical activity in those at high CVD risk.

Background Kuwait is one of the Arab countries with the highest prevalence of overweight or obesity. However, few studies have described the prevalence of obesity in this country. The aim of this study is to describe the prevalence of overweight and obesity among Kuwaiti adolescents; and to examine the association of overweight and obesity status with familial socioeconomic status (SES). Methods Cross-sectional data from 591 adolescent students (47% boys, median age: 16 years) from the Study of Health and Activity among Adolescents in Kuwait in 2012 and 2013. Body weight status was determined using the International Obesity Task Force (IOTF) body mass index standards. SES was based on parental education. Odds ratio for overweight and obesity were calculated using multiple logistic regression. Results In our study, over half of the adolescents were overweight or obese 54.3% (95% CI: 49.9-58.4). The prevalence of overweight (including obesity) was higher in boys (59.8%, 95% CI: 54.3-66.3) than girls (49.2%, 95% CI: 43.5-54.8). No association between parental education and the risk of overweight/obesity was found. Conclusions There is an alarmingly high rate of overweight/obesity among Kuwaiti adolescents, but we did not find evidence of a social gradient in obesity risk. Urgent actions are needed to reverse this epidemic across all social groups.

Background: Studies have found associations between features of the residential built environment and physical activity but these have been mainly cross-sectional. In this paper we explore whether longitudinal changes in environmental exposures are associated with changes in physical activity in adults. Methods: Data from the Examining Neighbourhood Activity in Built Living Environments in London (ENABLE London) study were used. Daily steps at follow-up were regressed on daily steps at baseline, change in built environment exposures and confounding variables using multilevel linear regression to assess if neighbourhood walkability, park proximity and public transport accessibility were associated with changes in accelerometer-derived daily steps. We also explored whether observed effects were moderated by housing tenure as a marker of socio-economic status. Findings: Between baseline and follow-up, participants experienced a 1·4 unit (95%CI 1·2,1·6) increase in neighbourhood walkability; a 270m (95%CI 232,307) decrease in distance to their nearest park; and a 0·7 point (95%CI 0·6,0·9) increase in accessibility to public transport. A 1 s.d. increase in neighbourhood walkability was associated with an increase of 302 (95%CI 110,494) daily steps. A 1 s.d. increase in accessibility to public transport was not associated with any change in steps overall, but was associated with a decrease in daily steps amongst social housing seekers (-295 steps (95%CI -595, 3), and an increase in daily steps for market-rent housing seekers (410 95%CI -191, 1010) (P-value for effect modification=0·03). Interpretation: Targeted changes in the residential built environment may result in increases in physical activity levels. However, the effect of improved accessibility to public transport may not be equitable, showing greater benefit to the more advantaged. Funding Statement: This research is being supported by project grants from the UK National Prevention Research Initiative (MR/J000345/1) and the UK National Institute for Health Research (NIHR; 12/211/69). Diabetes and obesity prevention research at St George’s, University of London is supported by the NIHR Collaboration for Leadership in Applied Health Research and Care, South London. CMN is supported by the Wellcome Trust Institutional Strategic Support Fund (204809/Z/16/Z). BR was supported by a PhD studentship from St George’s, University of London. ARC and ASP are supported by the NIHR Biomedical Research Centre at University Hospitals Bristol National Health Service Foundation Trust and the University of Bristol. AE is funded by the Medical Research Council as part of the Neighbourhoods and Communities Programme (MC_UU_12017–10). BG-C is supported by a National Health and Medical Research Council Principal Research Fellowship (1107672). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: Full ethical approval was obtained from the relevant Multi-Centre Research Ethics Committee (REC Reference 12/LO/1031). All participants provided written informed consent.

Objective: There is considerable interest in whether the built environment influences health behaviours, but longitudinal evidence is limited. We examined the effect of moving into East Village (the former London 2012 Olympic Games Athletes Village, repurposed on active design principles), on levels of physical activity (PA) and adiposity among adults. Design: A natural experiment. Participants: A cohort of 1278 adults seeking to move into social, intermediate, and market-rent East Village accommodation was recruited in 2013-2015, and followed up after two years. Intervention: Moving to East Village. Main outcome: Change in objectively measured daily steps (ActiGraph GT3X+). Methods: Change in environmental exposures associated with physical activity were assessed using Geographic Information System derived measures. Individual objective measures of PA using accelerometry, body mass index (BMI) and bioelectrical impedance (fat mass %) were obtained, as were perceptions of change in the built environment. We examined change in levels of PA and adiposity, using multilevel models adjusting for sex, age group, ethnic group, housing sector (fixed effects) and household (random effect), comparing those who moved to East Village (intervention group) with those who did not (control group). Effects of housing sector as an effect modifier were also examined. Results: 877 adults (69%) were followed-up, of whom 50% had moved to East Village. Moving to East Village was associated with only a small non-significant increase in mean daily steps (154, 95% CI -231, 539), despite sizeable improvements in walkability and neighbourhood perceptions of crime and quality. There were no appreciable effects on time spent in moderate-to-vigorous PA (MVPA) or sedentary time, BMI or percentage fat mass, overall or by housing sector. Conclusion: Despite strong evidence of large improvements in neighbourhood perceptions and walkability there was no clear evidence that moving to East Village was associated with increased physical activity. Improving the physical activity environment on its own may be insufficient to increase population physical activity. Funding: This research is being supported by project grants from the Medical Research Council National Prevention Research Initiative (MR/J000345/1) and National Institute for Health Research (12/211/69). Diabetes and obesity prevention research at St George’s, University of London is supported by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) South London. BR is supported by a St George’s, University of London, PhD Studentship. AE is funded by the UK Medical Research Council as part of the Neighbourhoods and Communities Programme (MC_UU_12017-10). BG-C is supported by an NHMRC Principal Research Fellowship (#1107672). ARC and ASP are supported by NIHR Biomedical Research Centre at University Hospitals Bristol NHS Foundation Trust and the University of Bristol. Declaration of Interest: We declare that we have no competing interests. Ethical Approval: Full ethical approval was obtained from the relevant Multi-Centre Research Ethics Committee (REC Reference 12/LO/1031). All participants provided written informed consent.

AIMS/HYPOTHESIS: This study aimed to examine the association between copeptin (a surrogate marker of arginine vasopressin) and incident stroke, CHD and cardiovascular mortality in older men with and without diabetes. METHODS: We conducted a prospective study of 3536 men aged 60-79 years who were followed for an average of 13 years. During this period, there were 437 major CHD events (fatal and non-fatal myocardial infarction [MI]), 323 stroke events (fatal and non-fatal) and 497 cardiovascular disease (CVD) deaths. Prevalent diabetes was defined on the basis of a history of doctor-diagnosed diabetes or fasting blood glucose ≥7.0 mmol or HbA1c ≥6.5% (48 mmol/mol) (n = 428). RESULTS: No association was seen between copeptin and incident stroke or CVD mortality in men without diabetes after adjustment for conventional cardiovascular risk factors, renal dysfunction, and insulin and N-terminal pro B-type natriuretic peptide levels. In contrast, elevated copeptin levels were associated with an increased risk of stroke and CVD mortality in men with diabetes after these adjustments. Compared with those in the lowest tertile of copeptin, men in the top tertile had adjusted relative HRs for stroke and CVD death of 2.34 (95% CI 1.04, 5.27) and 2.21 (1.12, 4.36), respectively. The risk of stroke and CVD mortality remained increased after the exclusion of men with prevalent stroke or MI. Higher levels of copeptin were associated with increased risk of CHD in the diabetic and non-diabetic groups, but these associations were attenuated after exclusion of individuals with a previous stroke or MI. CONCLUSIONS/INTERPRETATION: Copeptin was independently associated with an increased risk of incident stroke and CVD mortality in men with diabetes, but not in men without diabetes. Targeting the arginine vasopressin system might have beneficial effects on CVD mortality and stroke risk in older men with diabetes.