Publications by authors named "Peter Whincup"

338 Publications

Association of Childhood Fat Mass and Weight With Adult-Onset Type 2 Diabetes in Denmark.

JAMA Netw Open 2021 Apr 1;4(4):e218524. Epub 2021 Apr 1.

Population Health Research Institute, St George's, University of London, Cranmer Terrace, London, United Kingdom.

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.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.8524DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087954PMC
April 2021

Excessive Orthostatic Changes in Blood Pressure Are Associated With Incident Heart Failure in Older Men: A Prospective Analysis From the BRHS.

Hypertension 2021 May 15;77(5):1481-1489. Epub 2021 Mar 15.

University College London Research Department of Primary Care and Population Health, Royal Free Hospital, United Kingdom (A.G., O.P., L.T.L., S.G.W.).

[Figure: see text].
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.15817DOI Listing
May 2021

Inflammatory markers and incident heart failure in older men: the role of NT-proBNP.

Biomark Med 2021 Apr 12;15(6):413-425. Epub 2021 Mar 12.

Department of Primary Care & Population Health, University College London, London, UK.

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. 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). NP activity is associated with pro-inflammatory biomarkers and may explain the link between inflammation and incident HF.
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http://dx.doi.org/10.2217/bmm-2020-0669DOI Listing
April 2021

Genome-wide association study of circulating interleukin 6 levels identifies novel loci.

Hum Mol Genet 2021 Apr;30(5):393-409

Institute of Cardiovascular Science, University College London, London WC1E 6BT, UK.

Interleukin 6 (IL-6) is a multifunctional cytokine with both pro- and anti-inflammatory properties with a heritability estimate of up to 61%. The circulating levels of IL-6 in blood have been associated with an increased risk of complex disease pathogenesis. We conducted a two-staged, discovery and replication meta genome-wide association study (GWAS) of circulating serum IL-6 levels comprising up to 67 428 (ndiscovery = 52 654 and nreplication = 14 774) individuals of European ancestry. The inverse variance fixed effects based discovery meta-analysis, followed by replication led to the identification of two independent loci, IL1F10/IL1RN rs6734238 on chromosome (Chr) 2q14, (Pcombined = 1.8 × 10-11), HLA-DRB1/DRB5 rs660895 on Chr6p21 (Pcombined = 1.5 × 10-10) in the combined meta-analyses of all samples. We also replicated the IL6R rs4537545 locus on Chr1q21 (Pcombined = 1.2 × 10-122). Our study identifies novel loci for circulating IL-6 levels uncovering new immunological and inflammatory pathways that may influence IL-6 pathobiology.
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http://dx.doi.org/10.1093/hmg/ddab023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8098112PMC
April 2021

Poor oral health and the association with diet quality and intake in older people in two studies in the UK and USA.

Br J Nutr 2021 Jan 20:1-13. Epub 2021 Jan 20.

Population Health Sciences Institute, Newcastle University, The Baddiley-Clark Building, Richardson Road, Newcastle Upon TyneNE2 4AX, UK.

We aimed to investigate the associations of poor oral health cross-sectionally with diet quality and intake in older people. We also examined whether change in diet quality is associated with oral health problems. Data from the British Regional Heart Study (BRHS) comprising British males aged 71-92 years and the Health, Aging and Body Composition (HABC) Study comprising American males and females aged 71-80 years were used. Dental data included tooth loss, periodontal disease, dry mouth and self-rated oral health. Dietary data included diet quality (based on Elderly Dietary Index (BRHS) and Healthy Eating Score (HABC Study)) and several nutrients. In the BRHS, change in diet quality over 10 years (1998-2000 to 2010-2012) was also assessed. In the BRHS, tooth loss, fair/poor self-rated oral health and accumulation of oral health problems were associated with poor diet quality, after adjustment. Similar associations were reported for high intake of processed meat. Poor oral health was associated with the top quartile of percentage of energy content from saturated fat (self-rated oral health, OR 1·34, 95 % CI 1·02, 1·77). In the HABC Study, no significant associations were observed for diet quality after adjustment. Periodontal disease was associated with the top quartile of percentage of energy content from saturated fat (OR 1·48, 95 % CI 1·09, 2·01). In the BRHS, persistent low diet quality was associated with higher risk of tooth loss and accumulation of oral health problems. Older individuals with oral health problems had poorer diets and consumed fewer nutrient-rich foods. Persistent poor diet quality was associated with oral health problems later in life.
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http://dx.doi.org/10.1017/S0007114521000180DOI Listing
January 2021

Evaluating an Intervention to Increase Cereal Fiber Intake in Children: A Randomized Controlled Feasibility Trial.

J Nutr 2021 02;151(2):379-386

Population Health Research Institute, St George's, University of London, London, United Kingdom.

Background: Observational studies have shown that higher cereal fiber intake is associated with reduced type 2 diabetes risk. However, it remains uncertain whether this association is causal.

Objective: This study evaluated the feasibility of an intervention to increase cereal fiber intake in children using breakfast cereals.

Methods: The study was a 2-arm parallel group randomized controlled trial in 9-10-y-old children, who received free supplies of high-fiber breakfast cereals (>3.5 g/portion) or low-fiber breakfast cereals (<1.0 g/portion) to eat daily for 1 mo with behavioral support to promote adherence. Children provided baseline and 1-mo fasting blood samples, physical measurements, and 24-h dietary recalls. The primary outcome was the group difference in change in plasma total alkylresorcinol (AR) concentration; secondary outcomes were group differences in nutrient intakes and adiposity indices. Analyses (complete case and multiple imputation) were conducted by regressing the final AR concentration on baseline AR in models adjusted for sex, ethnicity, age, and school (random effect).

Results: Two-hundred seventy-two children were randomly assigned (137 receiving a low-fiber and 135 a high-fiber diet) and 193 (71%) provided fasting blood samples at baseline and follow-up. Among randomized participants, median (IQR) of baseline AR was 43.1 (24.6-85.5) nmol/L and of cereal fiber intake was 4.5 (2.7-6.4) g; 87% of participants reported consuming the cereal on most or all days. Compared with changes in the low-fiber group, the high-fiber group had greater increases in AR (40.7 nmol/L; 95% CI: 21.7, 59.8 nmol/L, P < 0.0001) and in reported cereal fiber intake (2.9g/d; 95% CI: 2.0, 3.7 g; P < 0.0001). There were no appreciable differences in other secondary outcomes.

Conclusions: We have developed a simple and acceptable nutritional intervention that increases markers of daily cereal fiber intake in children. This intervention could be used to test whether increases in cereal fiber intake in children might reduce insulin resistance. This trial was registered at www.isrctn.com as ISRCTN33260236.
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http://dx.doi.org/10.1093/jn/nxaa347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7849987PMC
February 2021

Joint associations of accelero-meter measured physical activity and sedentary time with all-cause mortality: a harmonised meta-analysis in more than 44 000 middle-aged and older individuals.

Br J Sports Med 2020 Dec;54(24):1499-1506

Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.

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.
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http://dx.doi.org/10.1136/bjsports-2020-103270DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719907PMC
December 2020

Associations of the systolic and diastolic components of orthostatic hypotension with markers of cardiovascular risk in older men: A cross-sectional analysis from The British Regional Heart Study.

J Clin Hypertens (Greenwich) 2020 10 16;22(10):1892-1901. Epub 2020 Aug 16.

Research Department of Primary Care & Population Health, Royal Free Campus, University College London, London, UK.

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-to-standing 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.
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http://dx.doi.org/10.1111/jch.13996DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8029713PMC
October 2020

Associations of cord leptin and cord insulin with adiposity and blood pressure in White British and Pakistani children aged 4/5 years.

Wellcome Open Res 2019 15;4:157. Epub 2019 Oct 15.

Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, BS8 2BN, UK.

Cord leptin and cord insulin concentrations may be important biomarkers of child adiposity and cardiovascular health, especially in populations with an increased long-term risk of type 2 diabetes and cardiovascular diseases. We aimed to determine whether cord leptin and insulin are associated with adiposity and early cardiovascular health at age 4/5, and whether any associations differ between White British and Pakistani children. Using bi-ethnic cohort data from 6060 mother-offspring pairs (2717 (44.8%) White British, 3343 (55.2%) Pakistani), we examined associations of cord leptin and insulin with adiposity (BMI, skinfold thickness) and systolic and diastolic blood pressure at age 4/5. Cord leptin and insulin were higher in Pakistani compared to White British children (7.4 ng/ml versus 6.7 ng/ml and 4.1 mU/L versus 3.63 mU/L respectively). Associations with adiposity measurements were similar in both groups and close to the null value. For example, each 10 ng/ml higher cord leptin was associated with a difference in mean childhood BMI of 0.10 kg/m (95% CI 0.01, 0.19) in White British, 0.01 kg/m (95% CI -0.08, 0.10) in Pakistani and 0.04 kg/m (95% CI -0.02, 0.11) in both groups combined.  Associations with systolic and diastolic blood pressure were also close to the null and consistent in both groups. We found no evidence that cord leptin or insulin were likely to be valuable biomarkers for predicting later adiposity and blood pressure in White British or Pakistani children. For now, other factors such as family history and social-economic status may be more useful markers of risk.
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http://dx.doi.org/10.12688/wellcomeopenres.15433.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7475957PMC
October 2019

Establishing reference intervals for triglyceride-containing lipoprotein subfraction metabolites measured using nuclear magnetic resonance spectroscopy in a UK population.

Ann Clin Biochem 2021 01 21;58(1):47-53. Epub 2020 Oct 21.

Institute of Cardiovascular Science, Faculty of Population Health, University College London, London, UK.

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 (<55, 55-65, >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.
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http://dx.doi.org/10.1177/0004563220961753DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791273PMC
January 2021

Cardiovascular Health and Stroke in Older British Men: Prospective Findings From the British Regional Heart Study.

Stroke 2020 11 11;51(11):3286-3294. Epub 2020 Sep 11.

Department of Primary Care and Population Health (A.A., L.L., O.P., G.W.), University College London.

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.
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http://dx.doi.org/10.1161/STROKEAHA.120.030546DOI Listing
November 2020

Vitamin D deficiency is associated with orthostatic hypotension in older men: a cross-sectional analysis from the British Regional Heart Study.

Age Ageing 2021 01;50(1):198-204

Research Department of Primary Care and Population Health, University College London, Royal Free Campus, London NW3 2PF, UK.

Background: orthostatic hypotension (OH) that occurs within, or at, 1 minute of standing is associated with higher risk of falls, myocardial infarction, syncope and mortality, compared to OH that occurs after 1 minute of standing. Whether vitamin D deficiency increases the risk of OH is controversial.

Methods: this was a cross-sectional analysis of 3,620 older, community-dwelling men. Multinomial, multiple logistic regression models were used to calculate the risk of OH across categories of vitamin D status (deficient [<25 nmol/l], insufficient [≥25-<50 nmol/l] and sufficient [≥50 nmol/l]) and parathyroid hormone quintile.

Results: men with vitamin D deficiency were more likely to have OH that occurred within 1 minute of standing in univariate logistic regression (OR 1.88, 95% CI 1.40-2.53) and multinomial, multiple logistic regression (OR 1.51, 95% CI 1.06-2.15), compared to men with sufficient levels of vitamin D. Vitamin D insufficiency was not associated with the risk of OH. Elevated parathyroid hormone was not associated with risk of OH.

Conclusion: the absence of an association between vitamin D insufficiency and risk of OH and the presence of an association between vitamin D deficiency and risk of OH suggest that there may be a threshold effect; it is only below a particular level of vitamin D that risk of OH is increased. In this cohort, the threshold was <25 nmol/l. Future work should investigate whether treating vitamin D deficiency can improve postural blood pressure or if preventing vitamin D deficiency reduces the incidence of OH.
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http://dx.doi.org/10.1093/ageing/afaa146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793603PMC
January 2021

Weekend and weekday associations between the residential built environment and physical activity: Findings from the ENABLE London study.

PLoS One 2020 2;15(9):e0237323. Epub 2020 Sep 2.

Department of Public Health, Environments and Society, London School of Hygiene and Tropical Medicine, London, United Kingdom.

Background: We assessed whether the residential built environment was associated with physical activity (PA) differently on weekdays and weekends, and contributed to socio-economic differences in PA.

Methods: Measures of PA and walkability, park proximity and public transport accessibility were derived for baseline participants (n = 1,064) of the Examining Neighbourhood Activities in Built Living Environments in London (ENABLE London) Study. Multilevel-linear-regressions examined associations between weekend and weekday steps and Moderate to Vigorous PA (MVPA), residential built environment factors, and housing tenure status as a proxy for socio-economic position.

Results: A one-unit decrease in walkability was associated with 135 (95% CI [28; 242]) fewer steps and 1.2 (95% CI [0.3; 2.1]) fewer minutes of MVPA on weekend days, compared with little difference in steps and minutes of MVPA observed on weekdays. A 1km-increase in distance to the nearest local park was associated with 597 (95% CI [161; 1032]) more steps and 4.7 (95% CI [1.2; 8.2]) more minutes of MVPA on weekend days; 84 fewer steps (95% CI [-253;420]) and 0.3 fewer minutes of MVPA (95%CI [-2.3, 3.0]) on weekdays. Lower public transport accessibility was associated with increased steps on a weekday (767 steps, 95%CI [-13,1546]) compared with fewer steps on weekend days (608 fewer steps, 95% CI [-44, 1658]). None of the associations between built environment factors and PA on either weekend or weekdays were modified by socio-economic status. However, socio-economic differences in PA related moderately to socio-economic disparities in PA-promoting features of the residential neighbourhood.

Conclusions: The residential built environment is associated with PA differently at weekends and on weekdays, and contributes moderately to socio-economic differences in PA.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0237323PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7467308PMC
October 2020

Quantifying childhood fat mass: comparison of a novel height-and-weight-based prediction approach with DXA and bioelectrical impedance.

Int J Obes (Lond) 2021 Jan 26;45(1):99-103. Epub 2020 Aug 26.

Population Health Research Institute, St George's, University of London, London, UK.

Accurate assessment of childhood adiposity is important both for individuals and populations. We compared fat mass (FM) predictions from a novel prediction model based on height, weight and demographic factors (height-weight equation) with FM from bioelectrical impedance (BIA) and dual-energy X-ray absorptiometry (DXA), using the deuterium dilution method as a reference standard. FM data from all four methods were available for 174 ALSPAC Study participants, seen 2002-2003, aged 11-12-years. FM predictions from the three approaches were compared to the reference standard using; R, calibration (slope and intercept) and root mean square error (RMSE). R values were high from 'height-weight equation' (90%) but lower than from DXA (95%) and BIA (91%). Whilst calibration intercepts from all three approaches were close to the ideal of 0, the calibration slope from the 'height-weight equation' (slope = 1.02) was closer to the ideal of 1 than DXA (slope = 0.88) and BIA (slope = 0.87) assessments. The 'height-weight equation' provided more accurate individual predictions with a smaller RMSE value (2.6 kg) than BIA (3.1 kg) or DXA (3.4 kg). Predictions from the 'height-weight equation' were at least as accurate as DXA and BIA and were based on simpler measurements and open-source equation, emphasising its potential for both individual and population-level FM assessments.
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http://dx.doi.org/10.1038/s41366-020-00661-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7752759PMC
January 2021

Longitudinal impact of changes in the residential built environment on physical activity: findings from the ENABLE London cohort study.

Int J Behav Nutr Phys Act 2020 08 1;17(1):96. Epub 2020 Aug 1.

Department of Public Health, Environments and Society, London School of Hygiene and Tropical Medicine, London, UK.

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.
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http://dx.doi.org/10.1186/s12966-020-01003-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7395376PMC
August 2020

Retinal Vascular Tortuosity and Diameter Associations with Adiposity and Components of Body Composition.

Obesity (Silver Spring) 2020 09 29;28(9):1750-1760. Epub 2020 Jul 29.

Population Health Research Institute, St George's, University of London, London, UK.

Objective: The aim of this study was to assess whether adiposity or body composition relates to microvascular characteristics of the retina, indicative of cardiometabolic function.

Methods: 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.

Results: Venular tortuosity and diameter increased by approximately 2% (P < 10 ) and 0.6 μm (P < 10 ), respectively, per SD increase in BMI, waist circumference index, waist-hip ratio, total body fat mass index, and fat-free mass index (FFMI). Venular associations with adiposity persisted after adjustment for FFMI, whereas associations with FFMI were weakened by FMI adjustment. Arteriolar diameter (not tortuosity) narrowing with FFMI was independent of adiposity (-0.6 μm; -0.7 to -0.4 μm per SD increment of FFMI), while adiposity associations with arteriolar diameter were largely nonsignificant after adjustment for FFMI.

Conclusions: This demonstrates, on an unprecedented scale, that venular tortuosity and diameter are more strongly associated with adiposity, whereas arteriolar diameter relates more strongly to fat-free mass. Different attributes of the retinal microvasculature may reflect distinct roles of body composition and fatness on the cardiometabolic system.
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http://dx.doi.org/10.1002/oby.22885DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7116641PMC
September 2020

Retinal Vasculometry Associations With Glaucoma: Findings From the European Prospective Investigation of Cancer-Norfolk Eye Study.

Am J Ophthalmol 2020 12 25;220:140-151. Epub 2020 Jul 25.

NIHR Biomedical Research Centre at Moorfields Eye Hospital and UCL Institute of Ophthalmology, London, United Kingdom; Integrative Epidemiology Research Group, UCL Institute of Ophthalmology, London, United Kingdom.

Purpose: To examine retinal vasculometry associations with different glaucomas in older British people.

Design: Cross-sectional study.

Methods: A total of 8,623 European Prospective Investigation into Cancer-Norfolk Eye study participants were examined, who underwent retinal imaging, ocular biometry assessment, and clinical ascertainment of ocular hypertensive or glaucoma status (including glaucoma suspect [GS], high-tension open-angle glaucoma [HTG], and normal-tension glaucoma [NTG]). Automated measures of arteriolar and venular tortuosity, area, and width from retinal images were obtained. MainOutcomeMeasures: Associations between glaucoma and retinal vasculometry outcomes were analyzed using multilevel linear regression, adjusted for age, sex, height, axial length, intraocular and systemic blood pressure, and within-person clustering, to provide absolute differences in width and area, and percentage differences in vessel tortuosity. Presence or absence of within-person-between-eye differences in retinal vasculometry by diagnoses were examined.

Results: A total of 565,593 vessel segments from 5,947 participants (mean age 67.6 years, SD 7.6 years, 57% women) were included; numbers with HTG, NTG, and GS in at least 1 eye were 87, 82, and 439, respectively. Thinner arterioles (-3.2 μm; 95% confidence interval [CI] -4.4 μm, -1.9 μm) and venules (-2.7 μm; 95% CI -4.9 μm, -0.5 μm) were associated with HTG. Reduced venular area was associated with HTG (-0.2 mm; 95% CI -0.3 mm, -0.1 mm) and NTG (-0.2 mm; 95% CI -0.3 mm, -0.0 mm). Less tortuous retinal arterioles and venules were associated with all glaucomas, but only significantly for GS (-3.9%; 95% CI -7.7%, -0.1% and -4.8%; 95% CI -7.4%, -2.1%, respectively). There was no evidence of within-person-between-eye differences in retinal vasculometry associations by diagnoses.

Conclusions: Retinal vessel width associations with glaucoma and novel associations with vessel area and tortuosity, together with no evidence of within-person-between-eye differences in retinal vasculometry, suggest a vascular cause of glaucoma.
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http://dx.doi.org/10.1016/j.ajo.2020.07.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7706353PMC
December 2020

Vitamin D deficiency is associated with increased risk of postural hypotension in older men: a cross-sectional analysis from The British Regional Heart Study.

Br J Gen Pract 2020 Jun;70(suppl 1)

University College London Research Department of Primary Care & Population Health.

Background: There is growing interest in the role of vitamin D in extra-skeletal health, including postural hypotension. Postural hypotension is found in 1 in 5 community-dwelling adults aged 60 years and above. It increases risk of falls, fractures, cardiovascular disease and all-cause mortality. Better understanding of the aetiology of postural hypotension may help yield more effective treatment options than those that are currently available.

Aim: The aim of this study was to investigate the association between circulating vitamin D, parathyroid hormone and postural hypotension.

Method: This was a cross-sectional analysis of 3620 community-dwelling men living in the UK (mean age 68.6 years; standard deviation 5.5 years). Vitamin D status (nmol/L) was categorised as sufficient (≥50), insufficient (≥25 - <50), or deficient (<25). Parathyroid hormone levels were categorised by quintiles. Postural hypotension was defined by consensus criteria as a decrease in systolic blood pressure ≥20 mmHg and/or diastolic blood pressure ≥10 mmHg that occurred within three minutes of standing.

Results: Compared to sufficient levels of vitamin D, vitamin D deficiency increased risk of postural hypotension that specifically occurred within one minute of standing (OR 1.51, 95% CI = 1.06 to 2.15) in multinomial, multiple logistic regression. Neither vitamin D insufficiency, nor elevated parathyroid hormone, were associated with postural hypotension.

Conclusion: In this study, vitamin D deficiency was associated with increased risk of postural hypotension. Further research may help clarify whether treating vitamin D deficiency can reduce the degree of postural hypotension, or if preventing the progression to vitamin D deficiency can reduce the incidence of postural hypotension.
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http://dx.doi.org/10.3399/bjgp20X711209DOI Listing
June 2020

Use of Static Cutoffs of Hypertension to Determine High cIMT in Children and Adolescents: An International Collaboration Study.

Can J Cardiol 2020 09 4;36(9):1467-1473. Epub 2020 Mar 4.

Department of Epidemiology, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, China. Electronic address:

Background: Pediatric hypertension is typically defined as blood pressure ≥ sex-, age-, and height-specific 95th percentile (high) cutoffs. Given the number of strata, there are hundreds of cutoffs for defining elevated and high blood pressure that make it cumbersome to use in clinical practice. This study aimed to evaluate the utility of the static cutoffs for pediatric hypertension (120/80 mm Hg for children and 130/80 mm Hg for adolescents) in determining high carotid intimamedia thickness (cIMT) in children and adolescents.

Methods: Data were from 6 population-based cross-sectional studies in Brazil, China, Greece, Italy, Spain, and the United Kingdom. A total of 4280 children and adolescents, aged 6 to 17 years, were included. High cIMT was defined as cIMT ≥ sex-, age- and cohort-specific 90th percentile cutoffs.

Results: Compared with normal blood pressure, hypertension defined using the percentile-based cutoffs from 2017 American Academy of Pediatrics guideline, and the static cutoffs were associated with similar higher odds for high cIMT (percentile-based cutoffs: odds ratio [OR], 1.46, 95% confidence interval [CI], 1.15-1.86; static cutoffs: OR, 1.65, 95% CI, 1.25-2.17), after adjustment for sex, age, race/ethnicity, body mass index, high-density lipoprotein-cholesterol, triglyceride, and fasting blood glucose. The similar utility of 2 definitions in determining high cIMT was further confirmed by area under the receiver operating characteristic curve and net reclassification improvement methods (P for difference > 0.05).

Conclusion: Static cutoffs (120/80 mm Hg for children, 130/80 mm Hg for adolescents) performed similarly compared with percentile-based cutoffs in determining high cIMT, supporting the use of static cutoffs in identifying pediatric hypertension in clinical practice.
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http://dx.doi.org/10.1016/j.cjca.2020.02.093DOI Listing
September 2020

Evaluating the effect of change in the built environment on mental health and subjective well-being: a natural experiment.

J Epidemiol Community Health 2020 08 24;74(8):631-638. Epub 2020 Apr 24.

Population Health Research Institute, St George's, University of London, London, UK.

Background: Neighbourhood 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.

Methods: 1278 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).

Results: Participants 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.

Conclusion: Despite 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.
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http://dx.doi.org/10.1136/jech-2019-213591DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7320742PMC
August 2020

Poor Oral Health and Inflammatory, Hemostatic, and Cardiac Biomarkers in Older Age: Results From Two Studies in the UK and USA.

J Gerontol A Biol Sci Med Sci 2021 Jan;76(2):346-351

Population Health Sciences Institute, Newcastle University, Newcastle Upon Tyne, UK.

Background: We examined the association of objective and subjective oral health markers with inflammatory, hemostatic, and cardiac biomarkers in older age.

Methods: Cross-sectional analyses were based on the British Regional Heart Study (BRHS) comprising British men aged 71-92 years (n = 2,147), and the Health, Aging and Body Composition (HABC) Study comprising American men and women aged 71-80 years (n = 3,075). Oral health markers included periodontal disease, tooth count, dry mouth. Inflammatory biomarkers included C-reactive protein (CRP), interleukin-6 (IL-6) in both studies, and tissue plasminogen activator (t-PA), von Willebrand Factor (vWF), fibrin D-dimer, high-sensitivity Troponin T (hsTnT), and N-terminal pro-brain natriuretic peptide (NTproBNP) only in the BRHS.

Results: In both studies, tooth loss, was associated with the top tertile of CRP-odds ratios (ORs) (95% confidence interval [CI]) are 1.31 (1.02-1.68) in BRHS; and 1.40 (1.13-1.75) in the HABC Study, after adjusting for confounders. In the HABC Study, cumulative (≥3) oral health problems were associated with higher levels of CRP (OR [95% CI] =1.42 [1.01-1.99]). In the BRHS, complete and partial tooth loss was associated with hemostatic factors, in particular with the top tertile of fibrin D-dimer (OR [95% CI] = 1.64 [1.16-2.30] and 1.37 [1.05-1.77], respectively). Tooth loss and periodontal disease were associated with increased levels of hsTnT.

Conclusions: Poor oral health in older age, particularly tooth loss, was consistently associated with some inflammatory, hemostatic, and cardiac biomarkers. Prospective studies and intervention trials could help understand better if poor oral health is causally linked to inflammatory, hemostatic, and cardiac biomarkers.
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http://dx.doi.org/10.1093/gerona/glaa096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812424PMC
January 2021

The effect of moving to East Village, the former London 2012 Olympic and Paralympic Games Athletes' Village, on mode of travel (ENABLE London study, a natural experiment).

Int J Behav Nutr Phys Act 2020 02 10;17(1):15. Epub 2020 Feb 10.

Population Health Research Institute, St George's, University of London, London, UK.

Background: Interventions to encourage active modes of travel (walking, cycling) may improve physical activity levels, but longitudinal evidence is limited and major change in the built environment / travel infrastructure may be needed. East Village (the former London 2012 Olympic Games Athletes Village) has been repurposed on active design principles with improved walkability, open space and public transport and restrictions on residential car parking. We examined the effect of moving to East Village on adult travel patterns.

Methods: One thousand two hundred seventy-eight adults (16+ years) seeking to move into social, intermediate, and market-rent East Village accommodation were recruited in 2013-2015, and followed up after 2 years. Individual objective measures of physical activity using accelerometry (ActiGraph GT3X+) and geographic location using GPS travel recorders (QStarz) were time-matched and a validated algorithm assigned four travel modes (walking, cycling, motorised vehicle, train). We examined change in time spent in different travel modes, using multilevel linear regresssion models adjusting for sex, age group, ethnicity, housing group (fixed effects) and household (random effect), comparing those who had moved to East Village at follow-up with those who did not.

Results: Of 877 adults (69%) followed-up, 578 (66%) provided valid accelerometry and GPS data for at least 1 day (≥540 min) at both time points; half had moved to East Village. Despite no overall effects on physical activity levels, sizeable improvements in walkability and access to public transport in East Village resulted in decreased daily vehicle travel (8.3 mins, 95%CI 2.5,14.0), particularly in the intermediate housing group (9.6 mins, 95%CI 2.2,16.9), and increased underground travel (3.9 mins, 95%CI 1.2,6.5), more so in the market-rent group (11.5 mins, 95%CI 4.4,18.6). However, there were no effects on time spent walking or cycling.

Conclusion: Designing walkable neighbourhoods near high quality public transport and restrictions on car usage, may offer a community-wide strategy shift to sustainable transport modes by increasing public transport use, and reducing motor vehicle travel.
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http://dx.doi.org/10.1186/s12966-020-0916-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7011441PMC
February 2020

Is child weight status correctly reported to parents? Cross-sectional analysis of National Child Measurement Programme data using ethnic-specific BMI adjustments.

J Public Health (Oxf) 2020 11;42(4):e541-e550

Centre for Primary Care & Public Health, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AB, UK.

Background: BMI underestimates and overestimates body fat in children from South Asian and Black ethnic groups, respectively.

Methods: We used cross-sectional NCMP data (2015-17) for 38 270 children in three inner-London local authorities: City & Hackney, Newham and Tower Hamlets (41% South Asian, 18.8% Black): 20 439 4-5 year-olds (48.9% girls) and 17 831 10-11 year-olds (49.1% girls). We estimated the proportion of parents who would have received different information about their child's weight status, and the area-level prevalence of obesity-defined as ≥98th centile-had ethnic-specific BMI adjustments been employed in the English National Child Measurement Programme (NCMP).

Results: Had ethnic-specific adjustment been employed, 19.7% (3112/15 830) of parents of children from South Asian backgrounds would have been informed that their child was in a heavier weight category, and 19.1% (1381/7217) of parents of children from Black backgrounds would have been informed that their child was in a lighter weight category. Ethnic-specific adjustment increased obesity prevalence from 7.9% (95% CI: 7.6, 8.3) to 9.1% (8.7, 9.5) amongst 4-5 year-olds and from 17.5% (16.9, 18.1) to 18.8% (18.2, 19.4) amongst 10-11 year-olds.

Conclusions: Ethnic-specific adjustment in the NCMP would ensure equitable categorization of weight status, provide correct information to parents and support local service provision for families.
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http://dx.doi.org/10.1093/pubmed/fdz188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685848PMC
November 2020

Enhanced motivational interviewing for reducing weight and increasing physical activity in adults with high cardiovascular risk: the MOVE IT three-arm RCT.

Health Technol Assess 2019 12;23(69):1-144

Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.

Background: Motivational interviewing (MI) enhanced with behaviour change techniques (BCTs) and deployed by health trainers targeting multiple risk factors for cardiovascular disease (CVD) may be more effective than interventions targeting a single risk factor.

Objectives: The clinical effectiveness and cost-effectiveness of an enhanced lifestyle motivational interviewing intervention for patients at high risk of CVD in group settings versus individual settings and usual care (UC) in reducing weight and increasing physical activity (PA) were tested.

Design: This was a three-arm, single-blind, parallel randomised controlled trial.

Setting: A total of 135 general practices across all 12 South London Clinical Commissioning Groups were recruited.

Participants: A total of 1742 participants aged 40-74 years with a ≥ 20.0% risk of a CVD event in the following 10 years were randomised.

Interventions: The intervention was designed to integrate MI and cognitive-behavioural therapy (CBT), delivered by trained healthy lifestyle facilitators in 10 sessions over 1 year, in group or individual format. The control group received UC.

Randomisation: Simple randomisation was used with computer-generated randomisation blocks. In each block, 10 participants were randomised to the group, individual or UC arm in a 4 : 3 : 3 ratio. Researchers were blind to the allocation.

Main Outcome Measures: The primary outcomes are change in weight (kg) from baseline and change in PA (average number of steps per day over 1 week) from baseline at the 24-month follow-up, with an interim follow-up at 12 months. An economic evaluation estimates the relative cost-effectiveness of each intervention. Secondary outcomes include changes in low-density lipoprotein cholesterol and CVD risk score.

Results: The mean age of participants was 69.75 years (standard deviation 4.11 years), 85.5% were male and 89.4% were white. At the 24-month follow-up, the group and individual intervention arms were not more effective than UC in increasing PA [mean 70.05 steps, 95% confidence interval (CI) -288 to 147.9 steps, and mean 7.24 steps, 95% CI -224.01 to 238.5 steps, respectively] or in reducing weight (mean -0.03 kg, 95% CI -0.49 to 0.44 kg, and mean -0.42 kg, 95% CI -0.93 to 0.09 kg, respectively). At the 12-month follow-up, the group and individual intervention arms were not more effective than UC in increasing PA (mean 131.1 steps, 95% CI -85.28 to 347.48 steps, and mean 210.22 steps, 95% CI -19.46 to 439.91 steps, respectively), but there were reductions in weight for the group and individual intervention arms compared with UC (mean -0.52 kg, 95% CI -0.90 to -0.13 kg, and mean -0.55 kg, 95% CI -0.95 to -0.14 kg, respectively). The group intervention arm was not more effective than the individual intervention arm in improving outcomes at either follow-up point. The group and individual interventions were not cost-effective.

Conclusions: Enhanced MI, in group or individual formats, targeted at members of the general population with high CVD risk is not effective in reducing weight or increasing PA compared with UC. Future work should focus on ensuring objective evidence of high competency in BCTs, identifying those with modifiable factors for CVD risk and improving engagement of patients and primary care.

Trial Registration: Current Controlled Trials ISRCTN84864870.

Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in ; Vol. 23, No. 69. See the NIHR Journals Library website for further project information. This research was part-funded by the NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London.
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http://dx.doi.org/10.3310/hta23690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6943381PMC
December 2019

Reducing weight and increasing physical activity in people at high risk of cardiovascular disease: a randomised controlled trial comparing the effectiveness of enhanced motivational interviewing intervention with usual care.

Heart 2020 03 12;106(6):447-454. Epub 2019 Dec 12.

Department of Biostatistics and Health Informatics, Institute of Psychiatry, King's College London, London, UK.

Objective: The 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.

Methods: A 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.

Results: At 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.

Conclusions: Enhancing motivational interviewing with additional behaviour change techniques was not effective in reducing weight or increasing physical activity in those at high CVD risk.
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http://dx.doi.org/10.1136/heartjnl-2019-315656DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7057797PMC
March 2020

Trajectories of physical activity from midlife to old age and associations with subsequent cardiovascular disease and all-cause mortality.

J Epidemiol Community Health 2020 02 8;74(2):130-136. Epub 2019 Nov 8.

Primary Care and Population Health, University College London, London, UK.

Introduction: It 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.

Methods: 3231 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.

Results: Three 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.

Conclusions: A 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.
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http://dx.doi.org/10.1136/jech-2019-212706DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6993021PMC
February 2020

Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9.

BMC Cardiovasc Disord 2019 10 29;19(1):240. Epub 2019 Oct 29.

Department Primary Care & Population Health, University College London, London, UK.

Background: We characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9.

Methods: Published and individual participant level data (300,000+ participants) were combined to construct a weighted PCSK9 gene-centric score (GS). Seventeen randomized placebo controlled PCSK9 inhibitor trials were included, providing data on 79,578 participants. Results were scaled to a one mmol/L lower LDL-C concentration.

Results: The PCSK9 GS (comprising 4 SNPs) associations with plasma lipid and apolipoprotein levels were consistent in direction with treatment effects. The GS odds ratio (OR) for myocardial infarction (MI) was 0.53 (95% CI 0.42; 0.68), compared to a PCSK9 inhibitor effect of 0.90 (95% CI 0.86; 0.93). For ischemic stroke ORs were 0.84 (95% CI 0.57; 1.22) for the GS, compared to 0.85 (95% CI 0.78; 0.93) in the drug trials. ORs with type 2 diabetes mellitus (T2DM) were 1.29 (95% CI 1.11; 1.50) for the GS, as compared to 1.00 (95% CI 0.96; 1.04) for incident T2DM in PCSK9 inhibitor trials. No genetic associations were observed for cancer, heart failure, atrial fibrillation, chronic obstructive pulmonary disease, or Alzheimer's disease - outcomes for which large-scale trial data were unavailable.

Conclusions: Genetic variation at the PCSK9 locus recapitulates the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and MI. While indicating an increased risk of T2DM, no other possible safety concerns were shown; although precision was moderate.
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http://dx.doi.org/10.1186/s12872-019-1187-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6820948PMC
October 2019

Associations of Retinal Microvascular Diameters and Tortuosity With Blood Pressure and Arterial Stiffness: United Kingdom Biobank.

Hypertension 2019 12 30;74(6):1383-1390. Epub 2019 Oct 30.

From the Population Health Research Institute, St George's University of London, United Kingdom (R.J.T., C.G.O., P.H.W., D.P.S., A.R.R.).

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/m). 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.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.13752DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7069386PMC
December 2019