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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.

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.

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.

The mechanisms underlying the association between orthostatic hypotension (OH) and cardiovascular disease are unclear. We investigated whether OH is associated with circulating cardiovascular risk markers. This was a cross-sectional analysis of 3857 older, community-dwelling men. “Consensus OH” was defined as a sitting-tostanding decrease in systolic blood pressure ≥20 mm Hg and/or diastolic blood pressure ≥10 mm Hg that occurred within three minutes of standing. Multiple generalized linear regression and logistic models were used to examine the association between cardiovascular risk markers and OH. Consensus OH was present in 20.2%, consisting of isolated systolic OH in 12.6%, isolated diastolic OH in 4.6%, and combined systolic and diastolic OH in 3.0%. Concentration of von Willebrand factor, a marker of endothelial dysfunction, was positively associated with isolated systolic OH (OR 1.35, 95% CI 1.05-1.73) and combined systolic and diastolic OH (OR 2.27, 95% CI 1.35-3.83); high circulating phosphate concentration, which may reflect vascular calcification, was associated with isolated diastolic OH (OR 1.53, 95% CI 1.04-2.25) and combined systolic and diastolic OH (OR 2.12, 95% CI 1.31-3.44), high-sensitivity troponin T, a marker of myocardial injury, was positively associated with isolated diastolic OH (OR 1.69, 95% CI 1.07-2.65) and N-terminal pro-brain natriuretic peptide, a marker of cardiac stress, was positively associated with combined systolic and diastolic OH (OR 2.14, 95% CI 1.14-4.03). In conclusion, OH is associated with some cardiovascular risk markers implicated in endothelial dysfunction, vascular calcification, myocardial injury, and cardiac stress. Clinicians should consider assessing cardiovascular risk in patients with OH.

The aim of this study was to assess whether adiposity or body composition relates to microvascular characteristics of the retina, indicative of cardiometabolic function. A fully automated QUARTZ software processed retinal images from 68,550 UK Biobank participants (aged 40-69 years). Differences in retinal vessel diameter and tortuosity with body composition measures from the Tanita analyzer were obtained by using multilevel regression analyses adjusted for age, sex, ethnicity, clinic, smoking, and Townsend deprivation index. Venular tortuosity and diameter increased by approximately 2% (P

BACKGROUND: Although 10 000 steps per day is widely promoted to have health benefits, there is little evidence to support this recommendation. We aimed to determine the association between number of steps per day and stepping rate with all-cause mortality. METHODS: In this meta-analysis, we identified studies investigating the effect of daily step count on all-cause mortality in adults (aged ≥18 years), via a previously published systematic review and expert knowledge of the field. We asked participating study investigators to process their participant-level data following a standardised protocol. The primary outcome was all-cause mortality collected from death certificates and country registries. We analysed the dose-response association of steps per day and stepping rate with all-cause mortality. We did Cox proportional hazards regression analyses using study-specific quartiles of steps per day and calculated hazard ratios (HRs) with inverse-variance weighted random effects models. FINDINGS: We identified 15 studies, of which seven were published and eight were unpublished, with study start dates between 1999 and 2018. The total sample included 47 471 adults, among whom there were 3013 deaths (10·1 per 1000 participant-years) over a median follow-up of 7·1 years ([IQR 4·3-9·9]; total sum of follow-up across studies was 297 837 person-years). Quartile median steps per day were 3553 for quartile 1, 5801 for quartile 2, 7842 for quartile 3, and 10 901 for quartile 4. Compared with the lowest quartile, the adjusted HR for all-cause mortality was 0·60 (95% CI 0·51-0·71) for quartile 2, 0·55 (0·49-0·62) for quartile 3, and 0·47 (0·39-0·57) for quartile 4. Restricted cubic splines showed progressively decreasing risk of mortality among adults aged 60 years and older with increasing number of steps per day until 6000-8000 steps per day and among adults younger than 60 years until 8000-10 000 steps per day. Adjusting for number of steps per day, comparing quartile 1 with quartile 4, the association between higher stepping rates and mortality was attenuated but remained significant for a peak of 30 min (HR 0·67 [95% CI 0·56-0·83]) and a peak of 60 min (0·67 [0·50-0·90]), but not significant for time (min per day) spent walking at 40 steps per min or faster (1·12 [0·96-1·32]) and 100 steps per min or faster (0·86 [0·58-1·28]). INTERPRETATION: Taking more steps per day was associated with a progressively lower risk of all-cause mortality, up to a level that varied by age. The findings from this meta-analysis can be used to inform step guidelines for public health promotion of physical activity. FUNDING: US Centers for Disease Control and Prevention.

IntroductionIt is well established that physical activity (PA) protects against mortality and morbidity, but how long-term patterns of PA are associated with mortality and cardiovascular disease (CVD) remains unclear.Methods3231 men recruited to the British Regional Heart Study, a prospective cohort study, reported usual PA levels at baseline in 1978–1980 (aged 40–59 years) and at 12-year, 16-year and 20-year follow ups. Twenty-year trajectories of PA, spanning from 1978/1980 to 2000, were identified using group-based trajectory modelling. Men were subsequently followed up until 30 June 2016 for mortality through National Health Service central registers and for non-fatal CVD events through primary and secondary care records. Data analyses were conducted in 2019.ResultsThree PA trajectories were identified: low/decreasing (22.7%), light/stable (51.0%) and moderate/increasing (26.3%). Over a median follow-up of 16.4 years, there were 1735 deaths. Compared with the low/decreasing group, membership of the light/stable (HR 0.83, 95% CI 0.74 to 0.94) and moderate/increasing (HR 0.76, 95% CI 0.66 to 0.88) groups was associated with a lower risk of all-cause mortality. Similar associations were observed for CVD mortality, major coronary heart disease and all CVD events. Associations were only partially explained by a range of confounders. Sensitivity analyses suggested that survival benefits were largely driven by most recent/current PA.ConclusionsA dose-response relationship was observed, with higher levels of PA from midlife to old age associated with additional benefits. However, even fairly modest and sustained PA was protective and may be more achievable for the most inactive.

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.

Key Points Question Is childhood fat mass (FM) more strongly associated with long-term type 2 diabetes (T2D) risk than childhood weight, independent of height? Findings In a population-based cohort study including more than 260 000 schoolchildren in Denmark, there were stronger associations (per kilogram increase) between childhood FM and adult T2D risk, independent of childhood height, than those observed for childhood weight. Meaning Results suggest that weight-based measures, currently used as the basis for childhood obesity assessment in the form of body mass index, were less strongly associated with adult T2D risk than childhood FM., This cohort study uses data from Copenhagen School Health Records Register to investigate the association of childhood fat mass and weight with adult-onset type 2 diabetes., Importance Childhood obesity, defined by cutoffs based on the weight-based marker of body mass index, is associated with adult type 2 diabetes (T2D) risk. Whether childhood fat mass (FM) is the driver of these associations is currently unknown. Objective To quantify and compare height-independent associations between childhood FM and weight with adult T2D risk in a historic Danish cohort. Design, Setting, and Participants This population-based retrospective cohort study included schoolchildren from The Copenhagen School Health Records Register born between January 1930 and December 1985 with follow-up to adulthood through December 31, 2015. Analyses were based on 269 913 schoolchildren aged 10 years with 21 896 established adult T2D cases and 261 192 children aged 13 years with 21 530 established adult T2D cases for whom childhood height and weight measurements, as well as predicted FM, were available. Statistical analyses were performed between April 2019 to August 2020. Exposures Childhood FM and weight at ages 10 and 13 years. Main Outcomes and Measures Diagnoses of T2D were established by linkage to national disease registers for adults aged at least 30 years. Sex-specific Cox regression quantified associations, adjusted for childhood height, which were evaluated within 5 birth-cohort groups. Group-specific results were pooled using random-effects meta-analyses accounting for heterogeneity across group-specific associations. Results This cohort study analyzed data from 269 913 children aged 10 years (135 940 boys [50.4%]) with 21 896 established adult T2D cases and 261 192 children aged 13 years (131 025 boys [50.2%]) with 21 530 established adult T2D cases. After adjusting for childhood height, increases in FM and weight (per kilogram) among boys aged 10 years were associated with elevated T2D risks at age 50 years of 12% (hazard ratio [HR], 1.12; 95% CI, 1.10-1.14) and 7% (HR, 1.07; 95% CI, 1.05-1.09), respectively, and among girls aged 10 years of 15% (HR, 1.15; 95% CI, 1.13-1.17) and 10% (HR, 1.10; 95% CI, 1.08-1.11), respectively. Among children aged 13 years, increases in FM and weight (per kilogram) were associated with increased T2D risks at age 50 years of 10% (HR, 1.10; 95% CI, 1.09-1.10) and 6% (HR, 1.06; 95% CI, 1.05-1.07) for boys, respectively, and of 10% (HR, 1.10; 95% CI, 1.10-1.11) and 7% (HR, 1.07; 95% CI, 1.06-1.08), respectively, for girls. Conclusions and Relevance This cohort study found that a 1-kg increase in childhood FM was more strongly associated with increased adult T2D risk than a 1-kg increase in weight, independent of childhood height. Information on FM, rather than weight-based measures, focuses on a modifiable component of weight that may be associated with adult T2D risk. These findings support the assessment of childhood FM in adiposity surveillance initiatives in an effort to reduce long-term T2D risk.

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 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 Previous research has reported associations between features of the residential built environment and physical activity but these studies have mainly been cross-sectional, limiting inference. This paper examines whether changes in a range of residential built environment features are associated with changes in measures of physical activity in adults. It also explores whether observed effects are moderated by socio-economic status. Methods Data from the Examining Neighbourhood Activity in Built Living Environments in London (ENABLE London) study were used. 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 2 years. Accelerometer-derived steps (primary outcome), and GIS-derived measures of residential walkability, park proximity and public transport accessibility were obtained both at baseline and follow-up. 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 changes in neighbourhood walkability, park proximity and public transport accessibility were associated with changes in daily steps. We also explored whether observed effects were moderated by housing tenure as a marker of socio-economic status. Results Between baseline and follow-up, participants experienced a 1.4 unit (95%CI 1.2,1.6) increase in neighbourhood walkability; a 270 m (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). Conclusion 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.

BackgroundNeighbourhood characteristics may affect mental health and well-being, but longitudinal evidence is limited. We examined the effect of relocating to East Village (the former London 2012 Olympic Athletes’ Village), repurposed to encourage healthy active living, on mental health and well-being.Methods1278 adults seeking different housing tenures in East village were recruited and examined during 2013–2015. 877 (69%) were followed-up after 2 years; 50% had moved to East Village. Analysis examined change in objective measures of the built environment, neighbourhood perceptions (scored from low to high; quality −12 to 12, safety −10 to 10 units), self-reported mental health (depression and anxiety) and well-being (life satisfaction, life being worthwhile and happiness) among East Village participants compared with controls who did not move to East Village. Follow-up measures were regressed on baseline for each outcome with group status as a binary variable, adjusted for age, sex, ethnicity, housing tenure and household clustering (random effect).ResultsParticipants who moved to East Village lived closer to their nearest park (528 m, 95% CI 482 to 575 m), in more walkable areas, and had better access to public transport, compared with controls. Living in East Village was associated with marked improvements in neighbourhood perceptions (quality 5.0, 95% CI 4.5 to 5.4 units; safety 3.4, 95% CI 2.9 to 3.9 units), but there was no overall effect on mental health and well-being outcomes.ConclusionDespite large improvements in the built environment, there was no evidence that moving to East Village improved mental health and well-being. Changes in the built environment alone are insufficient to improve mental health and well-being.

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.

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.

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.

Supplemental Digital Content is available in the text., To examine the baseline associations of retinal vessel morphometry with blood pressure (BP) and arterial stiffness in United Kingdom Biobank. The United Kingdom Biobank included 68 550 participants aged 40 to 69 years who underwent nonmydriatic retinal imaging, BP, and arterial stiffness index assessment. A fully automated image analysis program (QUARTZ [Quantitative Analysis of Retinal Vessel Topology and Size]) provided measures of retinal vessel diameter and tortuosity. The associations between retinal vessel morphology and cardiovascular disease risk factors/outcomes were examined using multilevel linear regression to provide absolute differences in vessel diameter and percentage differences in tortuosity (allowing within person clustering), adjusted for age, sex, ethnicity, clinic, body mass index, smoking, and deprivation index. Greater arteriolar tortuosity was associated with higher systolic BP (relative increase, 1.2%; 95% CI, 0.9; 1.4% per 10 mmHg), higher mean arterial pressure, 1.3%; 0.9, 1.7% per 10 mmHg, and higher pulse pressure (PP, 1.8%; 1.4; 2.2% per 10 mmHg). Narrower arterioles were associated with higher systolic BP (−0.9 µm; −0.94, −0.87 µm per 10 mmHg), mean arterial pressure (−1.5 µm; −1.5, −1.5 µm per 10 mmHg), PP (−0.7 µm; −0.8, −0.7 µm per 10 mmHg), and arterial stiffness index (−0.12 µm; −0.14, −0.09 µm per ms/m2). Associations were in the same direction but marginally weaker for venular tortuosity and diameter. This study assessing the retinal microvasculature at scale has shown clear associations between retinal vessel morphometry, BP, and arterial stiffness index. These observations further our understanding of the preclinical disease processes and interplay between microvascular and macrovascular disease.

Summary Background The built environment can affect health behaviours, but longitudinal evidence is limited. We aimed to examine the effect of moving into East Village, the former London 2012 Olympic and Paralympic Games Athletes' Village that was repurposed on active design principles, on adult physical activity and adiposity. Methods In this cohort study, we recruited adults seeking new accommodation in East Village and compared physical activity and built environment measures with these data in control participants who had not moved to East Village. At baseline and after 2 years, we objectively measured physical activity with accelerometry and adiposity with body-mass index and bioimpedance, and we assessed objective measures of and participants' perceptions of change in their built environment. We examined the change in physical activity and adiposity between the East Village and control groups, after adjusting for sex, age group, ethnicity, housing tenure, and household (as a random effect). Findings We recruited participants for baseline assessment between Jan 24, 2013, and Jan 7, 2016, and we followed up the cohort after 2 years, between Feb 24, 2015, and Oct 24, 2017. At baseline, 1819 households (one adult per household) consented to initial contact by the study team. 1278 adults (16 years and older) from 1006 (55%) households participated at baseline; of these participants, 877 (69%) adults from 710 (71%) households were assessed after 2 years, of whom 441 (50%) participants from 343 (48%) households had moved to East Village. We found no effect associated with moving to East Village on daily steps, the time spent doing moderate-to-vigorous physical activity (either in total or in 10-min bouts or more), daily sedentary time, body-mass index, or fat mass percentage between participants who had moved to East Village and those in the control group, despite sizeable improvements in walkability and neighbourhood perceptions of crime and quality among the East Village group relative to their original neighbourhood at baseline. Interpretation Despite large improvements in neighbourhood perceptions and walkability, we found no clear evidence that moving to East Village was associated with increased physical activity. Improving the built environment on its own might be insufficient to increase physical activity. Funding National Institute for Health Research and National Prevention Research Initiative.

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.

© 2019 Harris et al. Background: Data are lacking from physical activity (PA) trials with long-term follow-up of both objectively measured PA levels and robust health outcomes. Two primary care 12-week pedometer-based walking interventions in adults and older adults (PACE-UP and PACE-Lift) found sustained objectively measured PA increases at 3 and 4 years, respectively. We aimed to evaluate trial intervention effects on long-term health outcomes relevant to walking interventions, using routine primary care data. Methods and Findings: Randomisation was from October 2012-November 2013 for PACE-UP participants from seven general (family) practices and October 2011-October 2012 for PACE-Lift participants from three practices. We downloaded primary care data, masked to intervention or control status, for 1001 PACE-UP participants age 45-75 years, 36% (361) male and 296 PACE-Lift participants, age 60-75 years, 46% (138) male, who gave written informed consent, for 4-year periods following randomisation. The following new events were counted for all participants, including those with pre-existing diseases (apart from diabetes, where existing cases were excluded): non-fatal cardiovascular; total cardiovascular (including fatal); incident diabetes; depression; fractures; and falls. Intervention effects on time to first event post-randomisation were modelled using Cox regression for all outcomes, except for falls, which used Negative Binomial regression to allow for multiple events, adjusting for age, sex, and study. Absolute risk reductions (ARRs) and numbers needed to treat (NNT) were estimated. Data were downloaded for 1297 (98%) of 1321 trial participants. Event rates were low (

Background: The relevance of blood lipid concentrations to long-term incidence of cardiovascular disease and the relevance of lipid-lowering therapy for cardiovascular disease outcomes is unclear. We investigated the cardiovascular disease risk associated with the full spectrum of bloodstream non-HDL cholesterol concentrations. We also created an easy-to-use tool to estimate the long-term probabilities for a cardiovascular disease event associated with non-HDL cholesterol and modelled its risk reduction by lipid-lowering treatment. Methods: In this risk-evaluation and risk-modelling study, we used Multinational Cardiovascular Risk Consortium data from 19 countries across Europe, Australia, and North America. Individuals without prevalent cardiovascular disease at baseline and with robust available data on cardiovascular disease outcomes were included. The primary composite endpoint of atherosclerotic cardiovascular disease was defined as the occurrence of the coronary heart disease event or ischaemic stroke. Sex-specific multivariable analyses were computed using non-HDL cholesterol categories according to the European guideline thresholds, adjusted for age, sex, cohort, and classical modifiable cardiovascular risk factors. In a derivation and validation design, we created a tool to estimate the probabilities of a cardiovascular disease event by the age of 75 years, dependent on age, sex, and risk factors, and the associated modelled risk reduction, assuming a 50% reduction of non-HDL cholesterol. Findings: Of the 524 444 individuals in the 44 cohorts in the Consortium database, we identified 398 846 individuals belonging to 38 cohorts (184 055 [48·7%] women; median age 51·0 years [IQR 40·7–59·7]). 199 415 individuals were included in the derivation cohort (91 786 [48·4%] women) and 199 431 (92 269 [49·1%] women) in the validation cohort. During a maximum follow-up of 43·6 years (median 13·5 years, IQR 7·0–20·1), 54 542 cardiovascular endpoints occurred. Incidence curve analyses showed progressively higher 30-year cardiovascular disease event-rates for increasing non-HDL cholesterol categories (from 7·7% for non-HDL cholesterol

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.

The trajectories of physical activity (PA) from midlife into old age and their associations with established and novel cardiovascular disease (CVD) risk factors in later life remain unclear. This study examined associations between 20-year nonoccupational PA trajectories and a range of CVD biomarkers at ages 60–79 years. We used data from a sample of 3,331 men (mean baseline age = 50.2 ± 5.8 years) recruited in 1978–1980, with follow-up after 12, 16, and 20 years, reporting habitual nonoccupational PA at each wave. At the 20-year follow-up, surviving men attended a physical examination and provided a fasting blood sample. Group-based trajectory modeling was used to identify trajectories. Adjusted regression analyses examined the association between trajectory-group membership and several cardiometabolic, cardiac, and inflammatory markers at follow-up. Three distinct 20-year trajectories were identified: low/decreasing (21.3%), light/stable (51.8%), and moderate/increasing (27.0%). Compared with the low/decreasing group, membership in the light/stable and moderate/increasing trajectory groups was associated with a more favorable cardiometabolic profile and lower levels of inflammation and endothelial dysfunction. Although following a moderate-increasing PA trajectory was most favorable, more modest but sustained doses of PA into old age may be sufficient to lower CVD risk.

Purpose Correlates of physical activity (PA) vary according to type. However, predictors of long-term patterns of PA types into old age are unknown. This study aimed to identify 20-yr trajectories of PA types into old age and their predictors. Methods Seven thousand seven hundred thirty-five men (age, 40-59 yr) recruited from UK towns in 1978 to 1980 were followed up after 12, 16, and 20 yr. Men reported participation in sport/exercise, recreational activity and walking, health status, lifestyle behaviors and socio-demographic characteristics. Group-based trajectory modeling identified the trajectories of PA types and associations with time-stable and time-varying covariates. Results Men with ≥3 measures of sport/exercise (n = 5116), recreational activity (n = 5085) and walking (n = 5106) respectively were included in analyses. Three trajectory groups were identified for sport/exercise, four for recreational activity and three for walking. Poor health, obesity and smoking were associated with reduced odds of following a more favorable trajectory for all PA types. A range of socioeconomic, regional and lifestyle factors were also associated with PA trajectories but the magnitude and direction were specific to PA type. For example, men with manual occupations were less likely to follow a favorable sport/exercise trajectory but more likely to follow an increasing walking trajectory compared to men with nonmanual occupations. Retirement was associated with increased PA but this was largely due to increased sport/exercise participation. Conclusions Physical activity trajectories from middle to old age vary by activity type. The predictors of these trajectories and effects of major life events, such as retirement, are also specific to the type of PA.

Background Research evaluating lifestyle interventions for prevention of cardiovascular disease (CVD) may not reach those most at risk. We compared the response rate to a randomised controlled trial (RCT) of a lifestyle intervention by CVD risk, ethnicity and level of deprivation. Methods Primary care patients with a QRisk2 score ≥ 20% were invited to participate in a RCT of an intensive lifestyle intervention versus usual care. This cross-sectional analysis compares anonymised data of responders and non-responders with multiple logistic regression, using adjusted odds ratios (AORs) for QRisk2 score, ethnicity, Index of Multiple Deprivation (IMD 2010) quintile, age and sex. Results From 60 general practices, 8902 patients were invited and 1489 responded. The mean age was 67.3 years and 21.0% were female. Of all patients invited, 69.9% were of white ethnic background, 13.9% ethnic minority backgrounds and 16.2% had no ethnicity data recorded in their medical records. Likelihood of response decreased as QRisk2 score increased (AOR 0.82 per 5 percentage points, 95% CI 0.77–0.88). Black African or Caribbean patients (AOR 0.67; 95% CI 0.45–0.98) and those with missing ethnicity data (AOR 0.55; 95% CI 0.46–0.66) were less likely to respond compared to participants of white ethnicity, but there was no difference in the response rates between south Asian and white ethnicity (AOR 1.08; 95% CI 0.84–1.38). Patients residing in the fourth (AOR 0.70; 95% CI 0.56–0.87) and fifth (AOR 0.52; 95% CI 0.40–0.68) most deprived IMD quintile were less likely to respond compared to the least deprived quintile. Conclusions Evaluations of interventions intended for those at high risk of CVD may fail to reach those at highest risk. Hard to reach patient groups may require different recruitment strategies to maximise participation in future trials. Improvements in primary care ethnicity data recording is required to aid understanding of how successfully study samples represent the target population. Trial registration ISRCTN, ISRCTN84864870. Registered 15 May 2012, 10.1186/ISRCTN84864870. Electronic supplementary material The online version of this article (10.1186/s12889-018-5939-y) contains supplementary material, which is available to authorized users.

Background We examined associations of objectively measured physical activity ( PA ) and sedentary time with cardiovascular disease biomarkers at age 60 to 64 years. This included investigation of sex differences and the extent to which associations may be mediated by adiposity. Methods and Results Participants were 795 men and 827 women aged 60 to 64 years from the Medical Research Council National Survey of Health and Development. Combined heart rate and movement sensors worn for 5 consecutive days were used to derive overall PA energy expenditure, kJ /kg per day) and time spent sedentary (PA (>3 metabolic equivalent of tasks). Linear regression models were used to relate each PA parameter to inflammatory (C‐reactive protein, interleukin‐6), endothelial (tissue‐plasminogen activator, E‐selectin) and adipokine (leptin, adiponectin) markers extracted from fasting blood samples. Greater time in light PA and moderate‐to‐vigorous intensity PA and less sedentary time were associated with more favorable biomarker levels. For C‐reactive protein, interleukin‐6, and leptin, these differences were greater among women than men. For example, % differences (95% confidence intervals) in leptin for men and women per SD increases in sedentary time: 7.9 (2.7, 13.0) and 20.6 (15.3, 25.8); light intensity PA : −3.8 (−8.9, 12.7) and −17.7 (−23.1, −12.4), moderate‐to‐vigorous intensity PA : −12.9 (−17.9, −8.0) and −18.3 (−23.4, −13.1). Fat mass mediated a greater proportion of these associations in women than men. Conclusions Greater light PA and moderate‐to‐vigorous intensity PA and less sedentary time in early old age were associated with more favorable cardiovascular biomarker profiles. Fat mass partially mediated these associations but more strongly in women than men, which explained sex differences.

ObjectivesThe neighbourhood environment is increasingly shown to be an important correlate of health. We assessed associations between housing tenure, neighbourhood perceptions, sociodemographic factors and levels of physical activity (PA) and adiposity among adults seeking housing in East Village (formerly London 2012 Olympic/Paralympic Games Athletes’ Village).SettingCross-sectional analysis of adults seeking social, intermediate and market-rent housing in East Village.Participants1278 participants took part in the study (58% female). Complete data on adiposity (body mass index (BMI) and fat mass %) were available for 1240 participants (97%); of these, a subset of 1107 participants (89%) met the inclusion criteria for analyses of accelerometer-based measurements of PA. We examined associations between housing sector sought, neighbourhood perceptions (covariates) and PA and adiposity (dependent variables) adjusted for household clustering, sex, age group, ethnic group and limiting long-standing illness.ResultsParticipants seeking social housing had the fewest daily steps (8304, 95% CI 7959 to 8648) and highest BMI (26.0 kg/m2, 95% CI 25.5kg/m2to 26.5 kg/m2) compared with those seeking intermediate (daily steps 9417, 95% CI 9106 to 9731; BMI 24.8 kg/m2, 95% CI 24.4 kg/m2to 25.2 kg/m2) or market-rent housing (daily steps 9313, 95% CI 8858 to 9768; BMI 24.6 kg/m2, 95% CI 24.0 kg/m2to 25.2 kg/m2). Those seeking social housing had lower levels of PA (by 19%–42%) at weekends versus weekdays, compared with other housing groups. Positive perceptions of neighbourhood quality were associated with higher steps and lower BMI, with differences between social and intermediate groups reduced by ~10% following adjustment, equivalent to a reduction of 111 for steps and 0.5 kg/m2for BMI.ConclusionsThe social housing group undertook less PA than other housing sectors, with weekend PA offering the greatest scope for increasing PA and tackling adiposity in this group. Perceptions of neighbourhood quality were associated with PA and adiposity and reduced differences in steps and BMI between housing sectors. Interventions to encourage PA at weekends and improve neighbourhood quality, especially among the most disadvantaged, may provide scope to reduce inequalities in health behaviour.

Background Guidelines recommend walking to increase moderate to vigorous physical activity (MVPA) for health benefits. Objectives To assess the effectiveness, cost-effectiveness and acceptability of a pedometer-based walking intervention in inactive adults, delivered postally or through dedicated practice nurse physical activity (PA) consultations. Design Parallel three-arm trial, cluster randomised by household. Setting Seven London-based general practices. Participants A total of 11,015 people without PA contraindications, aged 45–75 years, randomly selected from practices, were invited. A total of 6399 people were non-responders, and 548 people self-reporting achieving PA guidelines were excluded. A total of 1023 people from 922 households were randomised to usual care (n = 338), postal intervention (n = 339) or nurse support (n = 346). The recruitment rate was 10% (1023/10,467). A total of 956 participants (93%) provided outcome data. Interventions Intervention groups received pedometers, 12-week walking programmes advising participants to gradually add ‘3000 steps in 30 minutes’ most days weekly and PA diaries. The nurse group was offered three dedicated PA consultations. Main outcome measures The primary and main secondary outcomes were changes from baseline to 12 months in average daily step counts and time in MVPA (in ≥ 10-minute bouts), respectively, from 7-day accelerometry. Individual resource-use data informed the within-trial economic evaluation and the Markov model for simulating long-term cost-effectiveness. Qualitative evaluations assessed nurse and participant views. A 3-year follow-up was conducted. Results Baseline average daily step count was 7479 [standard deviation (SD) 2671], average minutes per week in MVPA bouts was 94 minutes (SD 102 minutes) for those randomised. PA increased significantly at 12 months in both intervention groups compared with the control group, with no difference between interventions; additional steps per day were 642 steps [95% confidence interval (CI) 329 to 955 steps] for the postal group and 677 steps (95% CI 365 to 989 steps) for nurse support, and additional MVPA in bouts (minutes per week) was 33 minutes per week (95% CI 17 to 49 minutes per week) for the postal group and 35 minutes per week (95% CI 19 to 51 minutes per week) for nurse support. Intervention groups showed no increase in adverse events. Incremental cost per step was 19p and £3.61 per minute in a ≥ 10-minute MVPA bout for nurse support, whereas the postal group took more steps and cost less than the control group. The postal group had a 50% chance of being cost-effective at a £20,000 per quality-adjusted life-year (QALY) threshold within 1 year and had both lower costs [–£11M (95% CI –£12M to –£10M) per 100,000 population] and more QALYs [759 QALYs gained (95% CI 400 to 1247 QALYs)] than the nurse support and control groups in the long term. Participants and nurses found the interventions acceptable and enjoyable. Three-year follow-up data showed persistent intervention effects (nurse support plus postal vs. control) on steps per day [648 steps (95% CI 272 to 1024 steps)] and MVPA bouts [26 minutes per week (95% CI 8 to 44 minutes per week)]. Limitations The 10% recruitment level, with lower levels in Asian and socioeconomically deprived participants, limits the generalisability of the findings. Assessors were unmasked to the group. Conclusions A primary care pedometer-based walking intervention in 45- to 75-year-olds increased 12-month step counts by around one-tenth, and time in MVPA bouts by around one-third, with similar effects for the nurse support and postal groups, and persistent 3-year effects. The postal intervention provides cost-effective, long-term quality-of-life benefits. A primary care pedometer intervention delivered by post could help address the public health physical inactivity challenge. Future work Exploring different recruitment strategies to increase uptake. Integrating the Pedometer And Consultation Evaluation-UP (PACE-UP) trial with evolving PA monitoring technologies. Trial registration Current Controlled Trials ISRCTN98538934. 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. 22, No. 37. See the NIHR Journals Library website for further project information.

Few trials have compared estimates of change in physical activity (PA) levels using self-reported and objective PA measures when evaluating trial outcomes. The PACE-UP trial offered the opportunity to assess this, using the self-administered International Physical Activity Questionnaire (IPAQ) and waist-worn accelerometry. The PACE-UP trial (N = 1023) compared usual care (n = 338) with two pedometer-based walking interventions, by post (n = 339) or with nurse support (n = 346). Participants wore an accelerometer at baseline and 12 months and completed IPAQ for the same 7-day periods. Main outcomes were weekly minutes, all in ≥10 min bouts as per UK PA guidelines of: i) accelerometer moderate-to-vigorous PA (Acc-MVPA) ii) IPAQ moderate+vigorous PA (IPAQ-MVPA) and iii) IPAQ walking (IPAQ-Walk). For each outcome, 12 month values were regressed on baseline to estimate change. Analyses were restricted to 655 (64%) participants who provided data on all outcomes at baseline and 12 months. Both intervention groups significantly increased their accelerometry MVPA minutes/week compared with control: postal group 42 (95% CI 22, 61), nurse group 43 (95% CI 24, 63). IPAQ-Walk minutes/week also increased: postal 57 (95% CI 2, 112), nurse 43 (95% CI -11, 97) but IPAQ-MVPA minutes/week showed non-significant decreases: postal -11 (95% CI -65, 42), nurse -34 (95% CI -87, 19). Our results demonstrate the necessity of using a questionnaire focussing on the activities being altered, as with IPAQ-Walk questions. Even then, the change in PA was estimated with far less precision than with accelerometry. Accelerometry is preferred to self-report measurement, minimising bias and improving precision when assessing effects of a walking intervention. Trial registration: ISRCTN, ISRCTN98538934 . Registered 2 March 2012.

BackgroundPhysical inactivity is an important cause of noncommunicable diseases. Interventions can increase short-term physical activity (PA), but health benefits require maintenance. Few interventions have evaluated PA objectively beyond 12 months. We followed up two pedometer interventions with positive 12-month effects to examine objective PA levels at 3-4 years.Methods and findingsLong-term follow-up of two completed trials: Pedometer And Consultation Evaluation-UP (PACE-UP) 3-arm (postal, nurse support, control) at 3 years and Pedometer Accelerometer Consultation Evaluation-Lift (PACE-Lift) 2-arm (nurse support, control) at 4 years post-baseline. Randomly selected patients from 10 United Kingdom primary care practices were recruited (PACE-UP: 45-75 years, PACE-Lift: 60-75 years). Intervention arms received 12-week walking programmes (pedometer, handbooks, PA diaries) postally (PACE-UP) or with nurse support (PACE-UP, PACE-Lift). Main outcomes were changes in 7-day accelerometer average daily step counts and weekly time in moderate-to-vigorous PA (MVPA) in ≥10-minute bouts in intervention versus control groups, between baseline and 3 years (PACE-UP) and 4 years (PACE-Lift). PACE-UP 3-year follow-up was 67% (681/1,023) (mean age: 59, 64% female), and PACE-Lift 4-year follow-up was 76% (225/298) (mean age: 67, 53% female). PACE-UP 3-year intervention versus control comparisons were as follows: additional steps/day postal +627 (95% CI: 198-1,056), p = 0.004, nurse +670 (95% CI: 237-1,102), p = 0.002; total weekly MVPA in bouts (minutes/week) postal +28 (95% CI: 7-49), p = 0.009, nurse +24 (95% CI: 3-45), p = 0.03. PACE-Lift 4-year intervention versus control comparisons were: +407 (95% CI: -177-992), p = 0.17 steps/day, and +32 (95% CI: 5-60), p = 0.02 minutes/week MVPA in bouts. Neither trial showed sedentary or wear-time differences. Main study limitation was incomplete follow-up; however, results were robust to missing data sensitivity analyses.ConclusionsIntervention participants followed up from both trials demonstrated higher levels of objectively measured PA at 3-4 years than controls, similar to previously reported 12-month trial effects. Pedometer interventions, delivered by post or with nurse support, can help address the public health physical inactivity challenge.Trial registrationsPACE-UP isrctn.com ISRCTN98538934; PACE-Lift isrctn.com ISRCTN42122561.

Background Evidence largely from animal studies suggests that conjugated linoleic acid ( CLA ) may have cardiovascular health benefits. However, few prospective studies have examined the association between CLA and cardiovascular disease. We have prospectively examined the association between serum CLA and incident coronary heart disease and heart failure ( HF ) in older men. Methods and Results Prospective study of 3806 men, aged 60 to 79 years, without prevalent HF followed up for an average of 13 years, during which there were 295 incident HF cases. A high‐throughput serum nuclear magnetic resonance metabolomics platform was used to measure CLA concentration in serum, expressed as a percentage of total fatty acids ( CLA %). CLA % was adversely associated with cholesterol and high‐density lipoprotein cholesterol but was inversely associated with C‐reactive protein and NT ‐pro BNP (N‐terminal pro‐B‐type natriuretic peptide; a marker of ventricular stress). No association was seen between CLA % and incident coronary heart disease. High CLA % was associated with significantly reduced risk of HF after adjustment for HF risk factors and C‐reactive protein (hazard ratio [95% confidence interval ], 0.64 [0.43–0.96]; quartile 4 versus quartile 1). Elevated CLA % was associated with reduced HF risk only in those with higher dairy fat intake, a major dietary source of CLA (test for interaction P =0.03). The reduced risk of HF was partially explained by NT ‐pro BNP . High dairy fat intake was not associated with incident coronary heart disease but was associated with reduced risk of HF , largely because of the inverse effect of CLA . Conclusions The finding that high CLA % is associated with lower risk of incident HF in older men requires confirmation in larger studies.

Objective We estimated associations of time of day with cardiovascular disease (CVD) risk factors measured in older men. Methods CVD risk factors (markers of inflammation and haemostasis, and cardiac markers) were measured on one occasion between 08:00 and 19:00 hours in 4252 men aged 60–79 years from the British Regional Heart Study. Linear models were used to estimate associations between time of day and risk factors. When an association was found, we examined whether the relationship between risk factors and cardiovascular mortality was affected by the adjustment for time of day using survival analyses. Results N-terminal pro-brain natriuretic peptide (NT-proBNP) levels increased by 3.3% per hour (95% CI 1.9% to 4.8%), interleukin-6 (IL-6) increased by 2.6% per hour (95% CI 1.8% to 3.4%), while tissue plasminogen activator (t-PA) decreased by 3.3% per hour (95% CI 3.7% to 2.9%); these associations were unaffected by adjustment for possible confounding factors. The percentages of variation in these risk factors attributable to time of day were less than 2%. In survival analyses, the association of IL-6, NT-proBNP and t-PA with cardiovascular mortality was not affected by the adjustment for time of day. C reactive protein, fibrinogen, D-dimer, von Willebrand factor and cardiac troponin T showed no associations with time of day. Conclusions In older men, markers of inflammation (IL-6), haemostasis (t-PA) and a cardiac marker (NT-proBNP) varied by time of day. The contribution of time of day to variations in these markers was small and did not appear to be relevant for the CVD risk prediction.

The Examining Neighbourhood Activities in Built Living Environments in London (ENABLE London) study provides a unique opportunity to examine differences in mental health and well-being amongst adults seeking social, intermediate (affordable rent), and market-rent housing in a purpose built neighbourhood (East Village, the former London 2012 Olympic Athletes’ Village), specifically designed to encourage positive health behaviours. Multi-level logistic regression models examined baseline differences in levels of depression, anxiety and well-being across the housing groups. Compared with the intermediate group, those seeking social housing were more likely to be depressed, anxious and had poorer well-being after adjustment for demographic and health status variables. Further adjustments for neighbourhood perceptions suggest that compared with the intermediate group, perceived neighbourhood characteristics may be an important determinant of depression amongst those seeking social housing, and lower levels of happiness the previous day amongst those seeking market-rent housing. These findings add to the extensive literature on inequalities in health, and provide a strong basis for future longitudinal work that will examine change in depression, anxiety and well-being after moving into East Village, where those seeking social housing potentially have the most to gain., Highlights • A natural experiment examining baseline mental health and well-being in adults seeking three housing tenures in East Village. • Those seeking social housing are more likely to report depressive symptoms and low life satisfaction at baseline. • Differences in well-being outcomes across the housing groups can be partially explained by neighbourhood perceptions. • Those seeking social housing appear to have the most to gain by moving to East Village.

Background Most mid-life and older adults are not achieving recommended physical activity (PA) targets and effective interventions are needed to increase and maintain PA long-term for health benefits. The Pedometer And Consultation Evaluation (PACE-UP) trial, a three-armed primary care pedometer-based walking intervention in those aged 45–75 years, demonstrated increased PA levels at 12 months. A three-year follow-up was conducted to evaluate long-term PA maintenance, including a qualitative component. Aim To examine facilitators and barriers to PA maintenance in mid-life and older adults previously involved in a PA trial. Method Semi-structured telephone interviews were conducted with 60 PACE-UP participants across all study arms. Interviews were audio-recorded, transcribed verbatim and coded independently by researchers, prior to thematic analysis. Findings Two-thirds of participants felt since the PACE-UP trial they had an awareness of PA, with the pedometer reported as ‘kick-starting’ regular activity, and then helped them to maintain regular activity. PA facilitators included: maintaining good health, self-motivation, social support and good weather. Lack of time was the most frequently cited barrier. Other barriers were often the inverse of the facilitators; for example, poor health and bad weather. Participants described the type of ‘top-up’ intervention they would find beneficial to aid PA maintenance (eg, text messages, online resources and walking groups). Conclusion A challenge for future PA interventions is to transform barriers into facilitators; for example, educating trial participants about the value of PA for many chronic health conditions to change this from inhibiting to promoting PA. Participants provided ideas for encouraging PA maintenance which could be incorporated into future interventions.

ObjectivesThis study aims to examine the tracking and predictability of physical activity in old age from overall physical activity and participation in sport, recreational activity and walking in mid-life.DesignProspective population-based cohort study.SettingBritish Regional Heart Study participants recruited from primary care centres in the UK in 1978–1980.Participants and outcome measuresMen (n=3413) self-reported their physical activity at baseline, 12, 16 and 20-year follow-ups and were categorised as inactive or active and having high or low participation in sport, walking and recreational activities. Tracking was assessed using kappa statistics and random effects models. Logistic regression estimated the odds of being active at 20-year follow-up according to physical activity participation in mid-life.ResultsAmong 3413 men (mean age at baseline 48.6±5.4 years) with complete data, tracking of overall physical activity was moderate (kappa: 0.23–0.26). Tracking was higher for sports participation (kappa: 0.35–0.38) compared with recreational activity (kappa: 0.16–0.24) and walking (kappa: 0.11–0.15). Intraclass correlation coefficients demonstrated similar levels of stability and only marginally weakened after controlling for covariates. Compared with inactive men, being active at baseline was associated with greater odds of being active at 20-year follow-up (OR 2.7, 95% CI 2.4 to 3.2) after adjusting for sociodemographic, health and lifestyle variables. Playing sport in mid-life was more strongly associated with being active at 20-year follow-up than other domains, particularly when sport participation began earlier in life.ConclusionBeing physically active in mid-life increases the odds of being active in old age. Promoting physical activity in later life might be best achieved by promoting sport participation earlier in the life course.

Background Maintenance of physical activity (PA) during later life is associated with optimal health; however, the long-term trajectories of PA into old age and their predictors have not been extensively researched using latent class methods. This study aimed to identify trajectories of self-reported PA and their predictors in men transitioning from midlife to old age. Methods 7735 men (aged 40–59 years) recruited in 1978–80 were followed up after 12, 16 and 20 years, reporting PA, health status, lifestyle behaviours and socio-demographic characteristics. Group-based trajectory modelling identified the trajectories of PA and associations with time-stable and time-varying covariates. We considered a range of sociodemographic and health and lifestyle factors as potential covariates. Results 4952 men (mean baseline age 49.1 ± 5.6 years) providing PA data at ≥3 time points were included in analyses. Three distinct 20-year trajectories were identified: low decreasing (24.6%, n = 1218), light stable (51.1%, n = 2530) and moderate increasing (24.3%, n = 1204). Being older, having a manual occupation, having never married or had children, residing in the midlands or North of England, suffering from a range of health conditions, being a smoker/ex-smoker and never consuming breakfast cereal or alcohol were independently associated with reduced odds of belonging to the moderate increasing trajectory group compared to the low decreasing group. Of the time-varying covariates considered, leaving employment was associated with a decrease in PA in the low decreasing group (β −0.306, p

Background Epidemiological evidence proposes the direct involvement of the liver enzymes in atrial fibrillation. These relationships are controversial and mechanistically unclear. As part of the British Regional Heart Study, we investigated whether change in liver enzymes over time associates with atrial fibrillation in men initially free of this heart condition. Materials and Methods We prospectively investigated change (delta) in liver enzymes and new-onset atrial fibrillation in a representative sample of 1428 men aged 60-79 years. Results Mean follow-up was 12.3 years, after which 108 new atrial fibrillation cases were identified. The liver enzymes did not differ at baseline or follow-up, except for gamma-glutamyl transferase which was higher at follow-up in men who developed atrial fibrillation compared to those who did not (P

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain similar to 8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD.

OBJECTIVES: To examine associations between sarcopenia, obesity, and sarcopenic obesity and risk of cardiovascular disease (CVD) and all-cause mortality in older men.\ud \ud DESIGN: Prospective cohort study.\ud \ud SETTING: British Regional Heart Study.\ud \ud PARTICIPANTS: Men aged 60-79 years (n = 4,252).\ud \ud MEASUREMENTS: Baseline waist circumference (WC) and midarm muscle circumference (MAMC) measurements were used to classify participants into four groups: sarcopenic, obese, sarcopenic obese, or optimal WC and MAMC. The cohort was followed for a mean of 11.3 years for CVD and all-cause mortality. Cox regression analyses assessed associations between sarcopenic obesity groups and all-cause mortality, CVD mortality, CVD events, and coronary heart disease (CHD) events.\ud \ud RESULTS: There were 1,314 deaths, 518 CVD deaths, 852 CVD events, and 458 CHD events during follow-up. All-cause mortality risk was significantly greater in sarcopenic (HR = 1.41, 95% CI = 1.22-1.63) and obese (HR = 1.21, 95% CI = 1.03-1.42) men than in the optimal reference group, with the highest risk in sarcopenic obese (HR = 1.72, 95% CI = 1.35-2.18), after adjustment for lifestyle characteristics. Risk of CVD mortality was significantly greater in sarcopenic and obese but not sarcopenic obese men. No association was seen between sarcopenic obesity groups and CHD or CVD events.\ud \ud CONCLUSION: Sarcopenia and central adiposity were associated with greater cardiovascular mortality and all-cause mortality. Sarcopenic obese men had the highest risk of all-cause mortality but not CVD mortality. Efforts to promote healthy aging should focus on preventing obesity and maintaining muscle mass.

Background and Purpose— Older adults have the highest risks of stroke and the lowest physical activity levels. It is important to quantify how walking (the predominant form of physical activity in older age) is associated with stroke. Methods— A total of 4252 men from a UK population-based cohort reported usual physical activity (regular walking, cycling, recreational activity, and sport) in 1998 to 2000. Nurses took fasting blood samples and made anthropometric measurements. Results— Among 3435 ambulatory men free from cardiovascular disease and heart failure in 1998 to 2000, 195 first strokes occurred during 11-year follow-up. Men walked a median of 7 (interquartile range, 3–12) hours/wk; walking more hours was associated with lower heart rate, D-dimer, and higher forced expiratory volume in 1 second. Compared with men walking 0 to 3 hours/wk, men walking 4 to 7, 8 to 14, 15 to 21, and >22 hours had age- and region-adjusted hazard ratios (95% confidence intervals) for stroke of 0.89 (0.60–1.31), 0.63 (0.40–1.00), 0.68 (0.35–1.32), and 0.36 (0.14–0.91), respectively, P (trend)=0.006. Hazard ratios were somewhat attenuated by adjustment for established and novel risk markers (inflammatory and hemostatic markers and cardiac function [N-terminal pro-brain natriuretic peptide]) and walking pace, but linear trends remained. There was little evidence for a dose–response relationship between walking pace and stroke; comparing average pace or faster to a baseline of slow pace, the hazard ratio for stroke was 0.65 (95% confidence interval, 0.44–0.97), which was fully mediated by time spent walking. Conclusions— Time spent walking was associated with reduced risk of onset of stroke in dose–response fashion, independent of walking pace. Walking could form an important part of stroke-prevention strategies in older people.

ObjectiveTo examine the dose-response associations between accelerometer assessed total physical activity, different intensities of physical activity, and sedentary time and all cause mortality.DesignSystematic review and harmonised meta-analysis.Data sourcesPubMed, PsycINFO, Embase, Web of Science, Sport Discus from inception to 31 July 2018.Eligibility criteriaProspective cohort studies assessing physical activity and sedentary time by accelerometry and associations with all cause mortality and reported effect estimates as hazard ratios, odds ratios, or relative risks with 95% confidence intervals.Data extraction and analysisGuidelines for meta-analyses and systematic reviews for observational studies and PRISMA guidelines were followed. Two authors independently screened the titles and abstracts. One author performed a full text review and another extracted the data. Two authors independently assessed the risk of bias. Individual level participant data were harmonised and analysed at study level. Data on physical activity were categorised by quarters at study level, and study specific associations with all cause mortality were analysed using Cox proportional hazards regression analyses. Study specific results were summarised using random effects meta-analysis.Main outcome measureAll cause mortality.Results39 studies were retrieved for full text review; 10 were eligible for inclusion, three were excluded owing to harmonisation challenges (eg, wrist placement of the accelerometer), and one study did not participate. Two additional studies with unpublished mortality data were also included. Thus, individual level data from eight studies (n=36 383; mean age 62.6 years; 72.8% women), with median follow-up of 5.8 years (range 3.0-14.5 years) and 2149 (5.9%) deaths were analysed. Any physical activity, regardless of intensity, was associated with lower risk of mortality, with a non-linear dose-response. Hazards ratios for mortality were 1.00 (referent) in the first quarter (least active), 0.48 (95% confidence interval 0.43 to 0.54) in the second quarter, 0.34 (0.26 to 0.45) in the third quarter, and 0.27 (0.23 to 0.32) in the fourth quarter (most active). Corresponding hazards ratios for light physical activity were 1.00, 0.60 (0.54 to 0.68), 0.44 (0.38 to 0.51), and 0.38 (0.28 to 0.51), and for moderate-to-vigorous physical activity were 1.00, 0.64 (0.55 to 0.74), 0.55 (0.40 to 0.74), and 0.52 (0.43 to 0.61). For sedentary time, hazards ratios were 1.00 (referent; least sedentary), 1.28 (1.09 to 1.51), 1.71 (1.36 to 2.15), and 2.63 (1.94 to 3.56).ConclusionHigher levels of total physical activity, at any intensity, and less time spent sedentary, are associated with substantially reduced risk for premature mortality, with evidence of a non-linear dose-response pattern in middle aged and older adults.Systematic review registrationPROSPERO CRD42018091808.

Low birth weight has been shown to be associated with later renal function, but it is unclear to what extent this is explained by other established kidney disease risk factors. Here we investigate the roles of diabetes, hypertension, and obesity using data from the Medical Research Council National Survey of Health and Development, a socially stratified sample of 5362 children born in March 1946 in England, Scotland, and Wales, and followed since. The birth weight of 2192 study members with complete data was related to three markers of renal function at age 60-64 (estimated glomerular filtration rate (eGFR) calculated using cystatin C (eGFRcys), eGFR calculated using creatinine and cystatin C (eGFRcr-cys), and the urine albumin-creatinine ratio) using linear regression. Each 1 kg lower birth weight was associated with a 2.25 ml/min per 1.73 m(2) (95% confidence interval 0.80-3.71) lower eGFRcys and a 2.13 ml/min per 1.73 m(2) (0.69-3.58) lower eGFRcr-cys. There was no evidence of an association with urine albumin-creatinine ratio. These associations with eGFR were not confounded by socioeconomic position and were not explained by diabetes or hypertension, but there was some evidence that they were stronger in study members who were overweight in adulthood. Thus, our findings highlight the role of lower birth weight in renal disease and suggest that in those born with lower birth weight particular emphasis should be placed on avoiding becoming overweight.

Aims Socioeconomic position has been linked to incident heart failure (HF), but the underlying mechanisms are unclear. We examined the association of socioeconomic measures with incident HF in older adults and examined possible underlying pathways. Methods and results A socially representative cohort of men aged 60–79 years in 1998–2000 from 24 British towns was followed-up for 10 years for incident HF. Adult socioeconomic position was based on a cumulative score, including occupation, education, housing tenure, pension, and amenities. Childhood socioeconomic measures included father's occupational social class and household amenities. Prevalent myocardial infarction and HF cases were excluded. Among 3836 men, 229 incident cases of HF occurred over 10 years. Heart failure risk increased with an increasing score of adverse adult socioeconomic measures ( P for trend =

There is little information on how the duration of overweight or obesity during life affects the risk for CKD. To investigate whether prolonged exposure to overweight during adult life increases the risk of later CKD in a cumulative manner, we analyzed data from the Medical Research Council National Survey of Health and Development, a socially stratified sample of 5362 singleton children born in 1 week in March 1946 in England, Scotland, and Wales. Multiple imputation expanded the analysis sample from the initial 1794 participants with complete data to 4584. This study collected self-reported body mass index (BMI) at ages 20 and 26 years and measured BMI at ages 36, 43, 53, and 60-64 years. The outcome of interest was CKD at age 60-64 years, suggested by estimated GFR (eGFR)

Background Previous studies demonstrated that lower outdoor temperatures increase the levels of established cardiovascular disease risk factors, such as blood pressure and lipids. Whether or not low temperatures increase novel cardiovascular disease risk factors levels is not well studied. The aim was to investigate associations of outdoor temperature with a comprehensive range of established and novel cardiovascular disease risk factors in two large Northern European studies of older adults, in whom cardiovascular disease risk is increased. Design and methods Data came from the British Regional Heart Study (4252 men aged 60–79 years) and the Prospective Study of Pravastatin in the Elderly at Risk (5804 men and women aged 70–82 years). Associations between outdoor temperature and cardiovascular disease risk factors were quantified in each study and then pooled using a random effects model. Results With a 5℃ lower mean temperature, total cholesterol was 0.04 mmol/l (95% confidence interval (CI) 0.02–0.07) higher, low density lipoprotein cholesterol was 0.02 mmol/l (95% CI 0.01–0.05) higher and SBP was 1.12 mm Hg (95% CI 0.60–1.64) higher. Among novel cardiovascular disease risk factors, C-reactive protein was 3.3% (95% CI 1.0–5.6%) higher, interleukin-6 was 2.7% (95% CI 1.1–4.3%) higher, and vitamin D was 11.2% (95% CI 1.0–20.4%) lower. Conclusions Lower outdoor temperature was associated with adverse effects on cholesterol, blood pressure, circulating inflammatory markers, and vitamin D in two older populations. Public health approaches to protect the elderly against low temperatures could help in reducing the levels of several cardiovascular disease risk factors.

Dietary patterns are a major risk factor for cardiovascular morbidity and mortality; however, few studies have examined this relationship in older adults. We examined prospective associations between dietary patterns and the risk of CVD and all-cause mortality in 3226 older British men, aged 60–79 years and free from CVD at baseline, from the British Regional Heart Study. Baseline FFQ data were used to generate thirty-four food groups. Principal component analysis identified dietary patterns that were categorised into quartiles, with higher quartiles representing higher adherence to the dietary pattern. Cox proportional hazards examined associations between dietary patterns and risk of all-cause mortality and cardiovascular outcomes. We identified three interpretable dietary patterns: ‘high fat/low fibre’ (high in red meat, meat products, white bread, fried potato, eggs), ‘prudent’ (high in poultry, fish, fruits, vegetables, legumes, pasta, rice, wholemeal bread, eggs, olive oil) and ‘high sugar’ (high in biscuits, puddings, chocolates, sweets, sweet spreads, breakfast cereals). During 11 years of follow-up, 899 deaths, 316 CVD-related deaths, 569 CVD events and 301 CHD events occurred. The ‘high-fat/low-fibre’ dietary pattern was associated with an increased risk of all-cause mortality only, after adjustment for confounders (highest v. lowest quartile; hazard ratio 1·44; 95 % CI 1·13, 1·84). Adherence to a ‘high-sugar’ diet was associated with a borderline significant trend for an increased risk of CVD and CHD events. The ‘prudent’ diet did not show a significant trend with cardiovascular outcomes or mortality. Avoiding ‘high-fat/low-fibre’ and ‘high-sugar’ dietary components may reduce the risk of cardiovascular events and all-cause mortality in older adults.

Objective: To assess whether the extent of primary and secondary coronary heart disease (CHD) prevention in older British men and women differs between patients with and without diabetes. Design: Two prospective cardiovascular cohort studies. Setting: 24 British towns. Patients: 4252 men and 4286 women aged 60–79 years examined between 1998 and 2001. Main outcome measures: Use of aspirin, statin, and blood pressure lowering treatment and risk factor control, examined by diabetic status and history of established CHD. Results: About 20% of the men and 12% of the women had established CHD at age 60–79 years and 7% of the men and 5% of the women had diabetes. In primary CHD prevention, patients with diabetes were more likely to receive CHD risk reducing medications than those without diabetes, but the proportions receiving preventive treatments in both groups were low. In secondary prevention, diabetic and non-diabetic patients received similar levels of treatment, with the exception of angiotensin converting enzyme inhibitors and (for women only) blood pressure lowering treatment, which were more widely used among diabetic patients. There were no clear differences in blood pressure control or cigarette smoking by diabetic status in primary or secondary prevention. Mean total cholesterol concentrations were lower in diabetic patients independently of treatment with statins. Conclusions: Despite their exceptionally high CHD risk, many opportunities to reduce CHD risk among patients with diabetes have not been taken.

Summary. Background: Previous studies have suggested that several hemostatic and inflammatory variables, which are risk predictors for arterial or venous thrombosis, increase with age. However, there is a lack of data from large population studies for reliable estimates of reference ranges. Objectives: To establish reliable reference ranges of hemostatic and inflammatory variables for 5-year age groups in older men and their implications for pathogenesis and diagnosis. Patients and methods: A total of 3861 men aged 60–79 years at the 20 years follow-up of the British Regional Heart Study. Results: Several variables increased with age. The greatest median increases between 60–64 and 75–79 years age groups were observed for fibrin D-dimer (91%) and C-reactive protein (CRP) (57%). Significant median increases were also observed for von Willebrand factor antigen (23%), tissue plasminogen activator antigen (11%), factor VIII (10%), and fibrinogen (8%). In contrast, levels of classical cardiovascular risk factors neither decreased nor increased substantially with age, with the exception of systolic blood pressure (median increase 10%). Conclusions: The exponential increases in risk of arterial and venous thrombotic events in men between age 60 and 79 years (when most such events occur) may be related in part to increasing activation of blood coagulation, fibrinolysis, and inflammation; possibly related to the increasing inflammatory burden of both atherosclerotic and non-vascular disease. These increases also have implications for diagnosis of suspected acute venous thromboembolism (D-dimer), and recently proposed screening for prediction of coronary heart disease risk and detection of occult disease (CRP).

AIMS: To estimate the potential effectiveness of different "high-risk" and "population" approaches to the primary prevention of cardiovascular disease (CVD) in middle-aged British men, after correction for regression dilution bias. METHODS AND RESULTS: We used a combination of cohort and randomised controlled trial evidence to estimate the effectiveness of high-risk strategies, based on the identification of high-risk factors or high absolute risk, and strategies based on population-wide reductions in cholesterol and blood pressure. High-risk strategies were potentially effective but would need to be used widely to have a substantial effect on CVD in the population. Aggressive pharmacological treatment (using statins, beta-blockers, ACE-inhibitors and aspirin) in individuals with a 10-year Framingham event risk of >or=30% (6% of population) would have reduced major CVD by at most 11%. This figure increased to 34% at a >or=20% treatment threshold (26% of population). In contrast, modest downwards shifts in the population distributions of serum total cholesterol and systolic blood pressure led to marked expected reductions in major CVD. Taking regression dilution bias into account, 10% reductions in long-term mean blood cholesterol and blood pressure could have reduced major CVD by 45%. CONCLUSIONS: If high-risk strategies are to have a major impact on CVD in the population, they need to be more widely used than previously envisaged. Population-wide reduction of major risk factors is needed if CVD is to be substantially reduced.