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Background Tumour necrosis factor alpha (TNFα) is a pro-inflammatory cytokine implicated in atherosclerotic plaque formation. We investigated whether circulating TNFα is prospectively associated with myocardial infarction (MI) or stroke in the older general population, independently of established cardiovascular risk factors and other inflammatory markers related to CHD risk. Methods We measured baseline TNFα concentrations in stored serum samples of 362 incident MI and 299 incident stroke cases and controls (2 per case, frequency matched by age, gender and town) who were ‘nested’ in parallel prospective studies of 4252 men and 4286 women aged 60–79 years assessed in general practices in 24 British towns in 1998–2000 and followed up for an average 7 years for fatal and non-fatal MI and stroke. Results TNFα levels were 11.4% (95% CI 9.5, 13.3%) higher among MI cases than controls; geometric mean 1.84 pg/mL compared to 1.63 pg/mL, p (difference)

Objective Although obesity beginning early in life is becoming more common, its implications for coronary heart disease (CHD) risk in later life remain uncertain. We examined the relationship of body mass index (BMI) before 30 years of age to CHD risk in later life. Design Systematic review of published studies relating BMI between age 2-30 years to later CHD risk. Studies were identified using Medline (1950 onwards), Embase (1980 onwards) and Web of Science (1970 onwards) databases (to November 2007). Measurements Relative risks (RR) of CHD associated with a 1 standard deviation (SD) increase in BMI (most based on a narrow age-range at measurement) were extracted by 2 authors independently, and combined using random-effect models. Results Fifteen studies provided seventeen estimates (731,337 participants, 23,894 CHD events) of the association of early BMI to later CHD outcome. BMI in early childhood (2 to 6 years, 3 estimates) showed a weak inverse association with CHD risk (RR 0.94, 95% CI 0.82-1.07). BMI in later childhood (7 to

Background: The extent to which chronic exposure to outdoor air pollutants influences lung function in adults is unclear. The aim of this study was to measure the association between chronic exposure to outdoor air pollutants and adult lung function. Methods: The relationship between measures of lung function (forced expiratory volume in 1 s (FEV1) and FEV1 as a percentage of forced vital capacity (FVC)) and average exposure to particulate matter

The 2004 UK Quality and Outcomes Framework (QOF) remunerates general practitioners for achieving a target blood pressure (BP) ofor=150/90 mm Hg for patients with ischaemic heart disease, stroke and hypertension. Using the DIN-LINK GP database, we investigated whether introducing the target altered BP recording. We extracted 3 164 189 BP measurements from 236 467 patients, with the above diagnoses from 2000 to 2005. Treatment was assessed by Read codes indicating prescriptions for antihypertensive drugs. Over this period, recorded systolic BP (SBP) fell: 36% had an SBP150 mm Hg in 2000-2001, and only 19% in 2004-2005. However, there was a trend towards recording systolic values just below, rather than just above the 150 cut-off. In 2000-2001, 2.3% of patients had 148-149 recorded and 1.8% had 151-152. In 2004-2005, the figures were 4.2 and 1.3%, respectively. By smoothing the distribution we estimate that the true percentage of patients with SBP150 mm Hg in 2004-2005 was 23%, rather than the 19% recorded. Moreover, patients with a recorded SBP=148-149 were more likely to have a recorded diastolic BPor=90 (93%) than patients with SBP=151-152 (78%). However, patients just below the 150 mm Hg cut-off received more antihypertensive treatment than those just above it (odds ratio=1.20, 95% confidence interval 1.01-1.41). We conclude that blood pressure levels in UK primary care have continued to fall through the introduction of QOF, offering significant public health benefits in the future. This fall has been exaggerated due to values being clustered just below the QOF target, but there is no evidence of adverse effects of this on clinical management.

Background: It is unclear whether it is possible to accurately estimate physical activity energy expenditure (PAEE) by self-report in youth. Objective: We assessed the validity and reliability of 4 self-reports to assess PAEE and time spent at moderate and vigorous intensity physical activity (MVPA) over the previous week in British young people between 4 and 17 y of age. Design: PAEE and MVPA were derived from the Children’s Physical Activity Questionnaire, Youth Physical Activity Questionnaire, and Swedish Adolescent Physical Activity Questionnaire; a lifestyle score indicative of habitual activity was derived from the Child Heart and Health Study in England Questionnaire. These data were compared with criterion methods, PAEE, and MVPA derived from simultaneous measurements by doubly labeled water and accelerometry in 3 age groups: 4–5 y (n ¼ 27), 12–13 y (n ¼ 25), and 16– 17 y (n ¼ 24). Validity was assessed by using Spearman correlations and the Bland-Altman method, and reliability was assessed by using intraclass correlation coefficients. Results: The strength of association between questionnaire and criterion methods varied (r ¼ 0.09 to r ¼ 0.46). Some questionnaires were able to accurately assess group-level PAEE and MVPA for some age groups, but the error was large for individual-level estimates throughout. Reliability of the Youth Physical Activity Questionnaire and Child Heart and Health Study in England Questionnaire was good (intraclass correlation coefficient: 0.64–0.92). Conclusions: Absolute PAEE and MVPA estimated from these selfreports were not valid on an individual level in young people, although some questionnaires appeared to rank individuals accurately. Age (the outcome of interest) and whether individual or group-level estimates are necessary will influence the best choice of self-report method when assessing physical activity in youth. Am J Clin Nutr 2009;89:862– 70.

Objectives: This study sought to better determine the link between leptin and coronary heart disease (CHD).Background: Circulating leptin is considered a risk factor for CHD but larger studies are ...

Purpose\ud Little is known about social inequalities in disability in the elderly. We examined the extent and determinants of socioeconomic inequalities in disability and functional limitation in elderly men in Britain.\ud \ud Methods\ud Disability was ascertained as problems with activities of daily living (ADLs) and instrumental ADL in a socioeconomically representative sample of 3981 men from 24 British towns who were between 63 to 82 years of age in 2003. We also examined functional limitation. Measures of socioeconomic position were social class, age at leaving full-time education, and car and house ownership.\ud \ud Results\ud Men in lower social classes had greater risks of both ADL and instrumental ADL disability and functional limitation compared with higher social classes; odds ratios (95% CI) for social class V compared with I were 3.13 (1.64–5.97), 2.87 (1.49–5.51), and 2.65 (1.31–5.35), respectively. Behavioral risk factors (smoking, body mass index, physical activity) and particularly co-morbidity attenuated these differences; together, they reduced relative risks to 1.11 (0.49–2.51), 1.01 (0.45–2.25), and 1.05 (0.46–2.42). Age at leaving full-time education had no relation to functional limitations after taking social class into account. Men who were not house or car owners had greater odds of functional limitation and ADL disability compared with house or car owners, independent of behavioural risk factors, comorbidities and social class.\ud \ud Conclusion\ud Strong socioeconomic inequalities in disability exist in the elderly, which were considerably explained by behavioral factors and comorbidity. Policy efforts are needed to reduce the social disparities in disability in the elderly.

To examine trends and demographic factors affecting persistence with ocular hypotensive therapy, from a period before prostaglandins were available to when they were the most common therapy.Computerised patient records from 94 general practices across the United Kingdom, identified 5670 registered patients newly prescribed an ocular hypotensive drug (1993-2005). Persistence was defined as continuing therapy without a 90-day gap in prescription for (i) any ocular hypotensive and (ii) initial monotherapy. Time to failure with the treatment was compared using proportional hazard analyses, adjusted for age, gender, practice, year of initial treatment, and a sociodemographic indicator. Study findings were set in the context of a review of the literature.Percentage persistent at 1-year rose after 1997 when prostaglandins were introduced; from 61% in 1994-1996 to 70% in 2002-2004. Persistence with any treatment did not differ between those initiated on beta-blockers compared to prostaglandins (1.05, 95% CI 0.93-1.17). However, 20% of subjects initiated on beta-blockers received a prostaglandin by 1 year. Conversely, 8% of those initiated on prostaglandins received a beta-blocker. When failure with initial therapy was considered, beta-blockers appeared worse (1.35, 95% CI 1.21-1.50); this was consistent with findings from six studies in the review (1.40, 95% CI 1.34-1.46). Neither gender nor social factors were associated with persistence, but younger subjects (35-64 years) were significantly more likely to fail as were those over 85 years.Introduction of prostaglandins may explain an improvement in persistence over a decade. However, whether the higher cost of initiating patients on prostaglandins is justified remains questionable unless clinically indicated.

PURPOSE: To examine the prospective relation of social engagement with cardiovascular disease (CVD) mortality, taking into account behavioral factors (smoking, physical activity, body weight, and alcohol consumption), socioeconomic factors, and presence of comorbidity and disability.METHODS: A socioeconomically representative cohort of 5925 men aged 52-74 years from 24 British towns was followed up from 1992-2006. A scale from 0-9 was used based on questions reflecting the frequency and extent of social engagement in 1992.RESULTS: CVD mortality risk decreased with increasing social engagement score-age-adjusted hazard ratio (HR) for those with the highest social engagement score of 8-9 was 0.42 (95% confidence interval [95%CI], 0.32-0.53) compared to those with the lowest scores of 0-3 (p for trend

OBJECTIVE—The objective of this study was to assess the relationship between putative markers of endothelial dysfunction (tissue plasminogen activator [t-PA] antigen and von Willebrand factor [vWF] antigen) and development of type 2 diabetes, as well as the role of inflammation, adipokines, hepatic function, and insulin resistance in modifying these relationships. RESEARCH DESIGN AND METHODS—This was a prospective study of 3,562 nondiabetic men aged 60–79 years followed up for an average of 7 years during which there were 162 incident cases of type 2 diabetes. RESULTS—Elevated t-PA (top third) was associated with a near threefold increase in risk of diabetes compared with the risk in those in the bottom third after adjustment for lifestyle factors and waist circumference (relative risk [RR] 2.98 [95%CI 1.79–5.00]; Ptrend < 0.0001); weaker but significant (marginal) associations were seen with vWF (1.24 [0.83–1.85]; P = 0.05 for trend). Both biomarkers of endothelial dysfunction correlated significantly with markers of inflammation (interleukin-6 [IL-6] and C-reactive protein [CRP]), hepatic function (γ-glutamyl transferase [GGT]), and insulin resistance, with t-PA showing stronger associations with adiposity, hepatic function, and insulin resistance than vWF. t-PA was also significantly and inversely associated with adiponectin. Adjustment for IL-6, adiponectin, and GGT attenuated the association of incident diabetes with vWF (1.06 [0.71–1.60]), but the relationship seen with t-PA remained significant (adjusted RR 2.19 [1.29–3.70]). Subsequent adjustment for insulin attenuated the association further, but t-PA was still associated with a significant increase in risk (1.66 [0.96–2.85]; Ptrend = 0.02). CONCLUSION—t-PA antigen, but not vWF antigen, is independently associated with risk of type 2 diabetes.

Background— The incidence of myocardial infarction (MI) in Britain has fallen markedly in recent years. Few studies have investigated the extent to which this decline can be explained by concurrent changes in major cardiovascular risk factors. Methods and Results— The British Regional Heart Study examined changes in cardiovascular risk factors and MI incidence over 25 years from 1978 in a cohort of 7735 men. During this time, the age-adjusted hazard of MI decreased by 3.8% (95% confidence interval 2.6% to 5.0%) per annum, which corresponds to a 62% decline over the 25 years. At the same time, after adjustment for age, cigarette smoking prevalence, mean systolic blood pressure, and mean non–high-density lipoprotein (HDL) cholesterol decreased, whereas mean HDL cholesterol, mean body mass index, and physical activity levels rose. No significant change occurred in alcohol consumption. The fall in cigarette smoking explained the greatest part of the decline in MI incidence (23%), followed by changes in blood pressure (13%), HDL cholesterol (12%), and non-HDL cholesterol (10%). In combination, 46% (approximate 95% confidence interval 23% to 164%) of the decline in MI could be explained by these risk factor changes. Physical activity and alcohol consumption had little influence, whereas the increase in body mass index would have produced a rise in MI risk. Conclusions— Modest favorable changes in the major cardiovascular risk factors appear to have contributed to considerable reductions in MI incidence. This highlights the potential value of population-wide measures to reduce exposure to these risk factors in the prevention of coronary heart disease.

Previous studies examining the relationship between physical activity levels and broad-based measures of psychological wellbeing in adolescents have been limited by not controlling for potentially confounding variables. The present study examined the relationship between adolescents' self-reported physical activity level, sedentary behaviour and psychological wellbeing; while controlling for a broad range of sociodemographic, health and developmental factors.The study entailed a cross-sectional school-based survey in ten British towns. Two thousand six hundred and twenty three adolescents (aged 13-16 years) reported physical activity levels, patterns of sedentary behaviour (TV/computer/video usage) and completed the strengths and difficulties questionnaire (SDQ).Lower levels of self-reported physical activity and higher levels of sedentary behaviour showed graded associations with higher SDQ total difficulties scores, both for boys (P0.001) and girls (P0.02) after adjustment for age and town. Additional adjustment for social class, number of parents, predicted school examination results, body mass index, ethnicity, alcohol intake and smoking status had little effect on these findings.Low levels of self-reported physical activity are independently associated with diminished psychological wellbeing among adolescents. Longitudinal studies may provide further insights into the relationship between wellbeing and activity levels in this population. Ultimately, randomised controlled trials are needed to evaluate the effects of increasing physical activity on psychological wellbeing among adolescents.

Infancy may be a sensitive period regarding effects of sodium intake on future blood pressure (BP). This has only been demonstrated in one randomized trial of low sodium formulae with follow-up in adolescence in one-third of participants.To prospectively assess associations between sodium intake in infancy and BP at 7 years in the Avon Longitudinal Study of Parents and Children (ALSPAC).A total of 533 children with sodium data at 4 months and 710 children with sodium at 8 months.0.4% of participants at 4 months and 73.0% at 8 months exceeded recommended levels for infant sodium intake. After minimal adjustment (child age, sex, energy), sodium intake at 4 months was positively associated with systolic blood pressure (SBP) at 7 years (beta=0.54 mm Hg/mmol; 95% CI: 0.09, 0.98 mm Hg; P=0.02). This changed little following adjustment for confounders but attenuated after adjusting for breastfeeding. This association was not mediated by sodium intake at 7 years. Due to high sodium-potassium correlations, effects of sodium independent of potassium could not be estimated with reasonable precision. Sodium intake neither at 8 months nor at 7 years was associated with SBP at 7 years.The association between sodium intake at 4 months and future SBP requires replication in studies that can control for effects of potassium before we can conclude that early infancy is a sensitive period with respect to effects of sodium on future BP. The majority of infants exceeded recommended levels of sodium intake at 8 months, and interventions to reduce sodium in infants' diets should be considered.

Background The independent influence of childhood social circumstances on health in later life remains uncertain. We examined the extent to which childhood socioeconomic circumstances are related to the risk of coronary heart disease (CHD) in older British men, taking account of adult social class and behavioural risk factors.Methods A socio-economically representative sample of 5552 British men (52-74 years) with retrospective assessment of childhood socio-economic circumstances (father's occupation and childhood household amenities) who were followed up for CHD (fatal and non-fatal) for 12 years.Results Men whose childhood social class was manual had an increased hazard ratio (HR) 1.34 (95% CI 1.11-1.63)-this effect was diminished when adjusted for adult social class and adult behavioural risk factors (cigarette smoking, alcohol, physical activity and body weight) (HR 1.19; 95% CI 0.97-1.46). Men whose family did not own a car in their childhood were at increased CHD risk even after adjustments for adult social class and behaviours (HR 1.35, 95% CI 1.04-1.75). Men with combined exposure to both childhood and adult manual social class had the highest risk of CHD (HR 1.51; 95% CI 1.19-1.91); this was substantially reduced by adjustment for adult behavioural risk factors (adjusted HR 1.28; 95% CI 0.99-1.65).Conclusions Less affluent socio-economic conditions in childhood may have a modest persisting influence on risk of CHD in later life.

Adiponectin is considered by many to be part of the ‘common soil’ linking type 2 diabetes and coronary heart disease (CHD). We examined the relationship between adiponectin and insulin resistance, metabolic, inflammatory and haemostatic risk factors and hepatic function. The study was carried out in 3640 non-diabetic men aged 60–79 years drawn from general practices in 24 British towns and who were not on warfarin. Adiponectin was associated with waist circumference (inversely), alcohol intake (positively) and physical activity (nonlinearly); no association was seen with cigarette smoking, prevalent CHD or stroke. After adjustment for these factors, adiponectin was significantly inversely associated with insulin resistance, triglyceride, C-reactive protein (but not interleukin 6), tissue plasminogen activator and alanine aminotransferase and positively associated with high-density lipoprotein cholesterol (HDL-cholesterol) and Factor VIII, factors associated with diabetes. No association was seen with cholesterol, smoking, systolic blood pressure or coagulation factors. Risk of the metabolic syndrome decreased significantly with increasing adiponectin. Adiponectin is inversely associated with factors strongly associated with the development of diabetes. Limited associations with the established major risk factors for CHD suggest adiponectin may be a stronger marker of risk for diabetes than for CHD.

Low physical activity (PA) and high levels of sedentary time (ST) are associated with higher cardiovascular disease (CVD) risk among older people. However, their independent contribution and importance of duration of PA and ST bouts remain unclear. We investigated associations between objectively measured PA, ST and non-invasive vascular measures, markers of CVD risk. Cross-sectional study of 1216 men from the British Regional Heart Study, mean age 78.5 years, measured in 2010–2012. Carotid intima thickness (CIMT), distensibility coefficient (DC) and plaque presence were measured using ultrasound; pulse wave velocity (cfPWV) and augmentation index (AIx) using a Vicorder. PA and ST were measured using hip-worn ActiGraph GT3X accelerometers. After adjusting for covariates, each additional 1000 steps per day was associated with a 0.038 m/s lower cfPWV (95% CI = − 0.076, 0.0003), 0.095 10− 3 kPa− 1 higher DC (95% CI = 0.006, 0.185), 0.26% lower AIx (95% CI = − 0.40, − 0.12) and a 0.005 mm lower CIMT (95% CI = − 0.008, − 0.001). Moderate and vigorous PA (MVPA) was associated with lower AIx and CIMT, light PA (LPA) with lower cfPWV and CIMT and ST with higher cfPWV, AIx and CIMT and lower DC. LPA and ST were highly correlated (r = − 0.62). The independence of MVPA and ST or MVPA and LPA was inconsistent across vascular measures. Bout lengths for both PA and ST were not associated with vascular measures. In our cross-sectional study of older men, all PA regardless of intensity or bout duration was beneficially associated with vascular measures, as was lower ST. LPA was particularly relevant for cfPWV and CIMT., Highlights • We examined physical activity, sedentary time and vascular measures in older men. • Higher PA and lower ST were beneficially associated with cfPWV, DC, AIx and CIMT. • More minutes of moderate and vigorous PA were associated with a lower AIx and CIMT. • More light PA was associated with a lower cfPWV and CIMT. • Bout lengths of MVPA, LPA and ST were not associated with vascular measures.

Background There is widespread concern about the possible health effects of traffic-related air pollution. Nitrogen dioxide (NO2) is a convenient marker of primary pollution. We investigated the associations between lung function and current residential exposure to a range of air pollutants (particularly NO2, NO, NOx and particulate matter) in London children. Moreover, we placed the results for NO2 in context with a meta-analysis of published estimates of the association. Methods and Findings Associations between primary traffic pollutants and lung function were investigated in 4884 children aged 9-10 years who participated in the Child Heart and Health Study in England (CHASE). A systematic literature search identified 13 studies eligible for inclusion in a meta-analysis. We combined results from the meta-analysis with the distribution of the values of FEV1 in CHASE to estimate the prevalence of children with abnormal lung function (FEV12 exposure. In CHASE, there were non-significant inverse associations between all pollutants except ozone and both FEV1 and FVC. In the meta-analysis, a 10 μg/m3 increase in NO2 was associated with an 8 ml lower FEV1 (95% CI: -14 to -1 ml; p: 0.016). The observed effect was not modified by a reported asthma diagnosis. On the basis of these results, a 10 μg/m3 increase in NO2 level would translate into a 7% (95% CI: 4% to 12%) increase of the prevalence of children with abnormal lung function. Conclusions Exposure to traffic pollution may cause a small overall reduction in lung function and increase the prevalence of children with clinically relevant declines in lung function.

Aim To examine whether low circulating vitamin C concentrations and low fruit and vegetable intakes were associated with insulin resistance and other Type 2 diabetes risk markers in childhood. Methods We conducted a cross‐sectional, school‐based study in 2025 UK children aged 9–10 years, predominantly of white European, South‐Asian and black African origin. A 24‐h dietary recall was used to assess fruit, vegetable and vitamin C intakes. Height, weight and fat mass were measured and a fasting blood sample collected to measure plasma vitamin C concentrations and Type 2 diabetes risk markers. Results In analyses adjusting for confounding variables (including socio‐economic status), a one interquartile range higher plasma vitamin C concentration (30.9 μmol/l) was associated with a 9.6% (95% CI 6.5, 12.6%) lower homeostatic model assessment of insulin resistance value, 0.8% (95% CI 0.4, 1.2%) lower fasting glucose, 4.5% (95% CI 3.2, 5.9%) lower urate and 2.2% (95% CI 0.9, 3.4%) higher HDL cholesterol. HbA1c concentration was 0.6% (95% CI 0.2, 1.0%) higher. Dietary fruit, vegetable and total vitamin C intakes were not associated with any Type 2 diabetes risk markers. Lower plasma vitamin C concentrations in South‐Asian and black African‐Caribbean children could partly explain their higher insulin resistance. Conclusions Lower plasma vitamin C concentrations are associated with insulin resistance and could partly explain ethnic differences in insulin resistance. Experimental studies are needed to establish whether increasing plasma vitamin C can help prevent Type 2 diabetes at an early stage., What's new? We examined the cross‐sectional associations between intakes of fruit, vegetables and vitamin C, circulating vitamin C concentrations and insulin resistance in UK children.Circulating vitamin C concentration was inversely associated with insulin resistance, while intakes of fruit, vegetable and vitamin C were unrelated to insulin resistance.Low levels of circulating vitamin C concentrations in UK South‐Asian children could contribute to their higher insulin resistance.Further studies (including trials) are needed to examine the association of vitamin C with insulin resistance and its potential implications for Type 2 diabetes prevention.

Background Older adults have low physical activity(PA) and high sedentary behaviour(SB) levels. We investigate how total volume and specific patterns of moderate to vigorous PA(MVPA), light PA(LPA) and SB are related to adiposity and metabolic syndrome (MS). Then, with reference to physical activity guidelines which encourage MVPA in bouts > =10 min and avoiding “long” sedentary bouts, we investigate whether accumulating PA and SB in bouts of different defined durations are differently associated with these outcomes. Methods Cross-sectional study of men (71–91 years) recruited in UK primary care centres. Nurses made physical measures (weight, height, bio-impedance, blood pressure) and took fasting blood samples. 1528/3137 (49 %) surviving men had ≥3 valid days (≥600 min) accelerometer data. 450 men with pre-existing chronic disease were excluded. 1009/1078 (93.6 %) had complete covariate data. Results Men (n = 1009, mean age 78.5(SD 4.7) years) spent 612(SD 83), 202(SD 64) and 42(SD 33) minutes in SB, LIPA and MVPA respectively. Each additional 30 min/day of SB and MVPA were associated with 0.32 (95 % CI 0.23, 0.40)Kg/m2 higher Body Mass Index (BMI) and −0.72(−0.93, −0.51) lower BMI Kg/m2 respectively. Patterns for waist circumference (WC), fat mass index (FMI), fasting insulin and MS were similar. MVPA in bouts lasting

Objectives Adiposity in middle age is an established risk factor for cardiovascular disease and type 2 diabetes; less is known about the impact of adiposity from early adult life. We examined the effects of high body mass index (BMI) in early and middle adulthood on myocardial infarction (MI), stroke and diabetes risks. Design A prospective cohort study. Participants 7735 men with BMI measured in middle age (40–59 years) and BMI ascertained at 21 years from military records or participant recall. Primary and secondary outcome measures 30-year follow-up data for type 2 diabetes, MI and stroke incidence; Cox proportional hazards models were used to examine the effect of BMI at both ages on these outcomes, adjusted for age and smoking status. Results Among 4846 (63%) men (with complete data), a 1 kg/m2 higher BMI at 21 years was associated with a 6% (95% CI 4% to 9%) higher type 2 diabetes risk, compared with a 21% (95% CI 18% to 24%) higher diabetes risk for a 1 kg/m2 higher BMI in middle age (hazard ratio (HR) 1.21, 95% CI 1.18 to 1.24). Higher BMI in middle age was associated with a 6% (95% CI 4% to 8%) increase in MI and a 4% (95% CI 1% to 7%) increase in stroke; BMI at 21 years showed no associations with MI or stroke risk. Conclusions Higher BMI at 21 years of age is associated with later diabetes incidence but not MI or stroke, while higher BMI in middle age is strongly associated with all outcomes. Early obesity prevention may reduce later type 2 diabetes risk, more than MI and stroke.

The characteristics of the retinal vascular network have been prospectively associated with many systemic and vascular diseases. QUARTZ is a fully automated software that has been developed to localize and quantify the morphological characteristics of blood vessels in retinal images for use in epidemiological studies. This software was used to analyse a dataset containing 16,000 retinal images from the EPIC-Norfolk cohort study. The objective of this paper is to both assess the suitability of this dataset for computational analysis and to further evaluate the QUARTZ software.

Background: Hearing and vision problems are common in older adults. We investigated the association of self-reported sensory impairment with lifestyle factors, chronic conditions, physical functioning, quality of life and social interaction. / Methods: A population-based cross-sectional study of participants of the British Regional Heart Study aged 63–85 years. / Results: A total of 3981 men (82% response rate) provided data. Twenty-seven per cent (n = 1074) reported hearing impairment including being able to hear with aid (n = 482), being unable to hear (no aid) (n = 424) and being unable to hear despite aid (n = 168). Three per cent (n = 124) reported vision impairment. Not being able to hear, irrespective of use of hearing aid, was associated with poor quality of life, poor social interaction and poor physical functioning. Men who could not hear despite hearing aid were more likely to report coronary heart disease (CHD) [age-adjusted odds ratios (ORs) 1.89 (95% confidence interval 1.36–2.63)]. Vision impairment was associated with symptoms of CHD including breathlessness [OR 2.06 (1.38–3.06)] and chest pain [OR 1.58 (1.07–2.35)]. Vision impairment was also associated with poor quality of life, poor social interaction and poor physical functioning. / Conclusions: Sensory impairment is associated with poor physical functioning, poor health and poor social interaction in older men. Further research is warranted on pathways underlying these associations.

Socio-economic gradients in diet quality are well established. However, the influence of material socio-economic conditions particularly in childhood, and the use of multiple disaggregated socio-economic measures on diet quality have been little studied in the elderly. In the present study, we examined childhood and adult socio-economic measures, and social relationships, as determinants of diet quality cross-sectionally in 4252 older British men (aged 60–79 years). A FFQ provided data on daily fruit and vegetable consumption and the Elderly Dietary Index (EDI), with higher scores indicating better diet quality. Adult and childhood socio-economic measures included occupation/father's occupation, education and household amenities, which combined to create composite scores. Social relationships included social contact, living arrangements and marital status. Both childhood and adult socio-economic factors were independently associated with diet quality. Compared with non-manual social class, men of childhood manual social class were less likely to consume fruit and vegetables daily (OR 0·80, 95 % CI 0·66, 0·97), as were men of adult manual social class (OR 0·65, 95 % CI 0·54, 0·79), and less likely to be in the top EDI quartile (OR 0·73, 95 % CI 0·61, 0·88), similar to men of adult manual social class (OR 0·66, 95 % CI 0·55, 0·79). Diet quality decreased with increasing adverse adult socio-economic scores; however, the association with adverse childhood socio-economic scores diminished with adult social class adjustment. A combined adverse childhood and adulthood socio-economic score was associated with poor diet quality. Diet quality was most favourable in married men and those not living alone, but was not associated with social contact. Diet quality in older men is influenced by childhood and adulthood socio-economic factors, marital status and living arrangements.

Aims Light-to-moderate drinking has been associated with reduced risk of heart failure (HF). We have examined the association between alcohol consumption and incident HF in older British men. Methods and results Prospective study of 3530 men aged 60–79 years with no diagnosed HF or myocardial infarction (MI) at baseline and followed up for a mean period of 11 years, in whom there were 198 incident HF cases. Men were divided into 6 categories of alcohol consumption: none

Background: Diet quality is a major risk factor for morbidity and mortality, but few studies have examined the relationship between dietary patterns and the risk of cardiovascular disease (CVD) and mortality in older adults. We examined prospective associations between dietary patterns defined using principal component analysis and the risk of CVD and all-cause mortality in older British men. Methods: 3226 men aged 60-79 years from the British Regional Heart Study, free from CVD at baseline, were followed-up for 11 years. Baseline food frequency questionnaire data were used to generate dietary intake data on 34 food groups. Principal component analysis identified dietary patterns which were then categorised according to quartiles of adherence. Cox proportional hazards regression examined associations between dietary patterns and risk of all-cause mortality, CVD mortality, CVD events and coronary heart disease (CHD) events, adjusting for confounders. Results: Principal component analysis identified three interpretable dietary patterns, which explained 20.8% of the total variance. An ‘unhealthy’ dietary pattern explained the greatest single proportion of the variance (7.9%) and was characterised by consumption of red meat, meat products, white bread, fried potato and eggs. A ‘healthy’ dietary pattern was characterised by consumption of poultry, fish, fruit, vegetables, legumes, pasta, rice, wholemeal bread, eggs and olive oil and explained 7.1% of the variance. Finally, a ‘sweet’ dietary pattern was characterised by consumption of biscuits, puddings, chocolate, sweets, sweet spreads and breakfast cereal and explained 5.8% of the variance. There were 899 deaths, 316 CVD deaths, 569 CVD events and 301 CHD events during follow-up. An ‘unhealthy’ dietary pattern was associated with a graded increase in risk of all-cause mortality, after adjustment for sociodemographic, behavioural and cardiovascular risk factors (highest vs. lowest quartile; HR: 1.44, 95% CI: 1.13-1.84, p-trend = 0.007). No significant associations were seen between the risk of all-cause mortality and the ‘healthy’ diet (highest vs. lowest quartile; HR: 0.83, 95% CI: 0.66-1.04, p-trend = 0.28) or the ‘sweet’ diet (highest vs. lowest quartile; HR: 1.00, 95% CI: 0.77-1.29, p-trend = 0.71). None of the dietary patterns were significantly associated with cardiovascular outcomes (CVD mortality, CVD events or CHD events). Conclusions: Dietary patterns are an important risk factor for all-cause mortality in the elderly. Older adults should avoid a high consumption of components of an ‘unhealthy’ dietary pattern to reduce the risk of all-cause mortality.

Background— Smoking is an important cardiovascular disease risk factor, but the mechanisms linking smoking to blood pressure are poorly understood. Methods and Results— Data on 141 317 participants (62 666 never, 40 669 former, 37 982 current smokers) from 23 population-based studies were included in observational and Mendelian randomization meta-analyses of the associations of smoking status and smoking heaviness with systolic and diastolic blood pressure, hypertension, and resting heart rate. For the Mendelian randomization analyses, a genetic variant rs16969968/rs1051730 was used as a proxy for smoking heaviness in current smokers. In observational analyses, current as compared with never smoking was associated with lower systolic blood pressure and diastolic blood pressure and lower hypertension risk, but with higher resting heart rate. In observational analyses among current smokers, 1 cigarette/day higher level of smoking heaviness was associated with higher (0.21 bpm; 95% confidence interval 0.19; 0.24) resting heart rate and slightly higher diastolic blood pressure (0.05 mm Hg; 95% confidence interval 0.02; 0.08) and systolic blood pressure (0.08 mm Hg; 95% confidence interval 0.03; 0.13). However, in Mendelian randomization analyses among current smokers, although each smoking increasing allele of rs16969968/rs1051730 was associated with higher resting heart rate (0.36 bpm/allele; 95% confidence interval 0.18; 0.54), there was no strong association with diastolic blood pressure, systolic blood pressure, or hypertension. This would suggest a 7 bpm higher heart rate in those who smoke 20 cigarettes/day. Conclusions— This Mendelian randomization meta-analysis supports a causal association of smoking heaviness with higher level of resting heart rate, but not with blood pressure. These findings suggest that part of the cardiovascular risk of smoking may operate through increasing resting heart rate.

Background Brisk walking in older people can increase step-counts and moderate to vigorous intensity physical activity (MVPA) in ≥10-minute bouts, as advised in World Health Organization guidelines. Previous interventions have reported step-count increases, but not change in objectively measured MVPA in older people. We assessed whether a primary care nurse-delivered complex intervention increased objectively measured step-counts and MVPA. Methods and Findings A total of 988 60–75 year olds, able to increase walking and randomly selected from three UK family practices, were invited to participate in a parallel two-arm cluster randomised trial; randomisation was by household. Two-hundred-ninety-eight people from 250 households were randomised between 2011 and 2012; 150 individuals to the intervention group, 148 to the usual care control group. Intervention participants received four primary care nurse physical activity (PA) consultations over 3 months, incorporating behaviour change techniques, pedometer step-count and accelerometer PA intensity feedback, and an individual PA diary and plan. Assessors were not blinded to group status, but statistical analyses were conducted blind. The primary outcome was change in accelerometry assessed average daily step-counts between baseline and 3 months, with change at 12 months a secondary outcome. Other secondary outcomes were change from baseline in time in MVPA weekly in ≥10-minute bouts, accelerometer counts, and counts/minute at 3 months and 12 months. Other outcomes were adverse events, anthropometric measures, mood, and pain. Qualitative evaluations of intervention participants and practice nurses assessed the intervention’s acceptability. At 3 months, eight participants had withdrawn or were lost to follow-up, 280 (94%) individuals provided primary outcome data. At 3 months changes in both average daily step-counts and weekly MVPA in ≥10-minute bouts were significantly higher in the intervention than control group: by 1,037 (95% CI 513–1,560) steps/day and 63 (95% CI 40–87) minutes/week, respectively. At 12 months corresponding differences were 609 (95% CI 104–1,115) steps/day and 40 (95% CI 17–63) minutes/week. Counts and counts/minute showed similar effects to steps and MVPA. Adverse events, anthropometry, mood, and pain were similar in the two groups. Participants and practice nurses found the intervention acceptable and enjoyable. Conclusions The PACE-Lift trial increased both step-counts and objectively measured MVPA in ≥10-minute bouts in 60–75 year olds at 3 and 12 months, with no effect on adverse events. To our knowledge, this is the first trial in this age group to demonstrate objective MVPA increases and highlights the value of individualised support incorporating objective PA assessment in a primary care setting. Trial Registration Controlled-Trials.com ISRCTN42122561, In this cluster randomized controlled trial, Tess Harris and colleagues investigate whether a program delivered by primary care nurses to older adults can increase bouts of moderate to vigorous physical activity., Editors’ Summary Background Worldwide, people are becoming increasingly sedentary. They are sitting at desks instead of doing manual labor; they are driving to work instead of walking; and they are participating in fewer leisure time physical activities. But the human body needs regular exercise to stay healthy. Physical activity helps to maintain a healthy weight and prevents or delays heart disease, type 2 diabetes, and some cancers. Moreover, physically active people feel better and live longer than physically inactive people. The World Health Organization recommends that adults should be active daily and should do at least 150 minutes of moderate- to vigorous-intensity physical activity (MVPA) every week in bouts that each last at least 10 minutes. Moderate-intensity physical activities (for example, brisk walking) require a moderate amount of effort and noticeably increase the heart rate; vigorous-intensity physical activities (for example, running) require a large amount of effort and cause rapid breathing and a substantial heart rate increase. Why Was This Study Done? When physical activity is objectively measured using an accelerometer (a movement monitor that is usually worn on the waist; unlike pedometers, which simply count the number of steps a person takes, accelerometers record both step-counts and the intensity of physical activity), fewer than 5% of older people achieve the recommended weekly levels of MVPA. These levels could be reached by taking regular brisk walks but how can older people be persuaded to make such walks part of their daily lives? In this cluster randomized controlled trial—the PACE (Pedometer Accelerometer Consultation Evaluation)-Lift trial—the researchers assess whether an intervention to increase walking comprising pedometer and accelerometer feedback combined with physical activity consultations provided by practice nurses can lead to sustained increases in physical activity in 60–75 year olds. Cluster randomized trials compare outcomes in groups of people (here, husbands and wives living in one household) assigned through the play of chance to receive a test or a control intervention. What Did the Researchers Do and Find? The researchers assigned 298 people from 250 households to receive the intervention or usual care and determined the participants’ physical activity at baseline, 3 months, and 12 months by asking them to wear an accelerometer for 7 days. Intervention group participants received four physical activity consultations with a primary care nurse over 3 months. At the first consultation, the nurse gave each participant a pedometer to measure step-counts, a physical activity diary in which to record their goals and progress, and the PACE-Lift patient handbook. At each consultation, the nurse used behavior change techniques (for example, goal setting) to encourage the participant to walk regularly, gave the participant visual feedback from their accelerometer readings, and devised a personal walking plan. Control group participants received normal care only from the practice. At 3 months and 12 months, both the average daily step-count and the weekly MVPA level had decreased from baseline in the control group but increased in the intervention group. At 3 months, compared to the control group, the average step-count in the intervention group was 1,037 steps/day higher and the MVPA in bouts of more than 10 minutes in the intervention group was 63 minutes/week higher. At 12 months, the corresponding differences were 609 steps/day and 40 minutes/week. There were no significant differences in adverse events (for example, pain), body fat, or other measured health-related outcomes between the groups. What Do These Findings Mean? These findings show that the complex intervention tested in the PACE-Lift trial increased both step-counts and objectively measured MPVA among 60–75 year olds for at least 12 months. Importantly, all the participants and practice nurses were positive and enthusiastic about the intervention. Moreover, the observed increase in physical activity is estimated to reduce the participants’ risk of heart disease and type 2 diabetes by an estimated 5.5% and 9.1%, respectively. Further trials are needed to determine which aspects of the intervention were responsible for increasing physical activity, to determine whether the intervention’s effects will persist for longer than 12 months, and to test the intervention in socio-economically diverse populations (all the PACE-Lift participants came from an affluent, non-ethnically diverse area). However, these findings highlight the value of family practices providing older individuals with individualized support that incorporates objective assessment of physical activity to help them become more physically active. Additional Information Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001783. The US Centers for Disease Control and Prevention provides information on all aspects of healthy living; its Physical Activity for Everyone web pages include guidelines for older people, instructional videos, and personal success stories (some information in English and Spanish) The World Health Organization provides information about physical activity and health (in several languages); its Global Recommendations on Physical Activity for Health are available in several languages The UK National Health Service information source Choices explains the benefits of regular physical activity, provides recommendations for older people, and includes tips for exercising and some personal stories MedlinePlus has links to other resources about exercise and physical fitness (in English and Spanish) More information about the PACE-Lift trial protocol is available

OBJECTIVES: To examine the influence of lifestyle factors and changes in these factors on risk of the metabolic syndrome in elderly men. DESIGN: Cross-sectional and longitudinal analyses of cohort study. SETTING: General practices in 24 British towns. PARTICIPANTS: Three thousand fifty-one men aged 60 to 79 with no diabetes mellitus or diagnosis of coronary heart disease. MEASUREMENTS: Lifestyle factors (smoking, physical activity, alcohol intake, body weight, dietary fat and carbohydrate intake) including recent changes in the previous 3 years (physical activity and body weight); metabolic syndrome. RESULTS: After adjustment for each of the other modifiable lifestyle factors, overweight/obesity and physical inactivity were associated with a significantly higher risk of the metabolic syndrome, as were cigarette smoking and a high-carbohydrate diet (>57% of energy). Alcohol intake and dietary fat intake were not related to the metabolic syndrome. Long-term ex-smokers showed similar risk to never smokers. Taking up physical activity and losing weight in the previous 3 years were associated with a reduction in risk of the metabolic syndrome. CONCLUSION: Overweight/obesity, physical inactivity, a high-carbohydrate diet, and cigarette smoking are associated with higher risk of the metabolic syndrome in elderly men. Modification of lifestyle factors, even later in life, has considerable potential for primary prevention of the metabolic syndrome.

Although body build is related to disability and mortality in older people, the independent contributions of adiposity and lean mass are not fully defined. The authors examined the relations of body composition (fat mass index, fat-free mass index) and adiposity (body mass index, waist circumference) to ill health and physical disability in a cross-sectional study of 4,252 British men aged 60-79 years in 1998-2000. Increased body mass index, waist circumference, and fat mass index were associated with increased prevalence of cardiovascular disease, overall ill health, and disability. Adjusted odds ratios of cardiovascular disease (top vs. bottom fifth) were 1.58 (95% confidence interval (CI): 1.23, 2.03) for fat mass index, 1.45 (95% CI: 1.14, 1.86) for body mass index, and 1.27 (95% CI: 0.99, 1.62) for waist circumference. For overall "poor/fair" health, the corresponding odds ratios were 1.71 (95% CI: 1.33, 2.21), 1.49 (95% CI: 1.17, 1.90), and 1.64 (95% CI: 1.28, 2.09) and, for mobility limitation, they were 1.56 (95% CI: 1.17, 2.06), 1.96 (95% CI: 1.48, 2.56), and 1.88 (95% CI: 1.42, 2.49). A high fat-free mass index was associated with only a decreased prevalence of respiratory problems and cancer (odds ratios=0.45 (95% CI: 0.33, 0.62) and 0.62 (95% CI: 0.42, 0.94), respectively). Body fatness, not fat-free mass, is associated with cardiovascular disease and disability in older men. Simple measures of overweight, such as body mass index and waist circumference, are good indicators of the likelihood of morbidity in older men. Prevention of weight gain with increasing age is likely to reduce morbidity and disability among older men.

Aims: To study trends in the prevalence of being treated for glaucoma and ocular hypertension from 1994 to 2003, and to examine factors determining treatment in 2002. Methods: Computerised data (the DIN-LINK database) from 131 general practices across the United Kingdom, in which half a million patients aged 40 years or more were registered annually, were used. On average 10 000 patients were treated for glaucoma and ocular hypertension annually. Results: Prevalence of being treated for glaucoma and ocular hypertension increased from 1.7% in 1994 to 2.3% in 2003. Those aged 85 years or more were 13 times (95% CI 12.2 to 13.8) more likely to be treated than those aged 40–64 years. Men were more likely to be treated than women (OR 1.24, 95% CI 1.19 to 1.28). Subjects “hard pressed” were less likely to be treated than “wealthy achievers” (OR 0.92, 95% CI 0.86 to 0.99). While use of topical β blocker only medications has declined since 1995, use of topical prostaglandins and combination therapies has increased. In 2003, use of prostaglandins overtook β blocker only medications. Conclusion: Prevalence of being treated for glaucoma has increased over time, and rises with age. Differences in treatment by sex and social status could be explained by use of or access to health care or by underlying prevalence of disease. Trends in treated glaucoma emphasise the shift from use of topical β blockers to newer therapies.

Purpose Determine whether a sex difference exists in the association between birth weight and total cholesterol later in life. Methods Meta-analysis of within-study differences in regression coefficients of cholesterol on birth weight. Results A total of 34 regression coefficients from 30 studies were included in the analyses; these provided data on 33,650 males and 23,129 females. There was evidence that the inverse association between birth weight and total cholesterol was stronger in males compared to females. The pooled within-study difference in age-adjusted regression coefficients was −0.03 mmol/l (−0.06, −0.01), p = 0.02 and the pooled within-study difference in age and body mass index adjusted regression coefficients was −0.04 mmol/l (−0.07, −0.02), p = 0.002. There was no evidence of heterogeneity in these meta-analyses (both p values > 0.6). Conclusions These results provide some evidence for a sex difference in the birth weight – total cholesterol association. This is consistent with studies of fetal growth which suggest that birth size reflects different biological processes for females and males. However, other very large studies are required to confirm this finding.

Objective To investigate the association between age at puberty and blood pressure at age 53 years.Design A prospective birth cohort study with regular contacts through childhood and adulthood until the age of 53 years.Participants A total of 1193 men and 1204 women, from a sample of 5362 born in Britain in March 1946.Main outcome measure Blood pressure at age 53 years.Results Regression models indicated that men who had reached puberty latest had a lower mean systolic blood pressure (SBP; P = 0.03) and diastolic blood pressure (DBP; P = 0.01) at 53 years than others. The mean SBP (95% confidence interval) was 6.4 mmHg (1.8,10.9) greater in the earliest puberty group compared with the latest; for DBP the difference was 4.6 mmHg (1.9, 7.4). The associations were not accounted for by current body size, even though later puberty was associated with a decreasing body mass index (BMI) at 53 years. Neither were they accounted for by prepubertal body size, birth weight, or childhood and adult social class. Although women who reached puberty early had a higher BMI and shorter stature at 53 years compared with other women, they did not have higher blood pressure.Conclusions Better health behaviours in men reaching puberty late may explain the association between age at puberty and blood pressure. Alternatively, age at puberty may be a marker of the whole growth trajectory, distinguishing characteristics important in the later development of high blood pressure. The association of early puberty with high adult BMI in both sexes highlights the importance of controlling obesity in those who mature early.

Objectives: Recent studies suggest an association between a microsatellite locus (TH01) located in intron 1 of the tyrosine hydroxylase gene (TH) and nicotine dependence. We aimed here to study whether both TH01 and haplotypes of the wider IGF2-INS-TH region influence initiation of regular smoking in current smokers. Methods: A total of 3637 individuals from three independent studies (two of adults and one of adolescents) were analysed in relation to the age of first regular smoking (AFRS). Haplotypes and genotypes were obtained for the polymorphisms TH01, IGF2 ApaI, INS HphI and DRD4 VNTR (48 bp)n. Association between IGF2-INS-TH haplotypes and AFRS was tested by a regression model. A genotype-based genetic model assuming additivity was followed in order to estimate the effect of individual loci. Results: Overall, no significant associations were found after correcting for multiple tests. However, an IGF2-INS-TH haplotype (*5) was found to be nominally associated with AFRS at younger ages in adult smokers. Analyses of individual loci points to TH01 as a possible candidate influencing initiation of regular smoking. An AFRS-lowering trend nominally associated with allele 9 in a dosage-dependent manner was identified in both adult cohorts. TH01 did not show association or trend with age of initiation (first puff) either in adolescents or in the adolescents smoking regularly at age 18. Conclusion: This study adds to the genetic evaluation of the associations of TH01 with smoking predisposition. Differences between historical and prospective surveys, different biological pathways and possible functional roles of this microsatellite in smoking initiation are discussed.

OBJECTIVE—We have examined the relationship between hepatic enzymes, the metabolic syndrome, insulin resistance, and type 2 diabetes and assessed the potential of hepatic enzyme measurements in determining diabetes risk. RESEARCH DESIGN AND METHODS—We conducted a prospective study of 3,500 nondiabetic men aged 60–79 years who were followed-up for a mean period of 5 years and in whom there were 100 incident type 2 diabetes cases. RESULTS—In cross-sectional analyses, alanine aminotransferase (ALT) and γ-glutamyltransferase (GGT) were strongly associated with obesity, insulin resistance, and the metabolic syndrome. Prospectively, the risk of type 2 diabetes significantly increased with increasing levels of ALT and GGT even after adjustment for confounders including BMI (top versus bottom quarter ALT: relative risk 2.72 [95% CI 1.47–5.02]; GGT: 3.68 [1.68–8.04]). Additional adjustment for insulin resistance attenuated the effects, but the relationships with ALT and GGT remained significant (1.91 [1.01–3.60] and 2.69 [1.21–5.97], respectively). Further adjustment for inflammatory markers (C-reactive protein) made minor differences. Among high-risk subjects (obese men or those with the metabolic syndrome), elevated GGT and ALT enhanced the prediction of diabetes risk. CONCLUSIONS— Elevated levels of ALT and GGT within the normal range are independent predictors of type 2 diabetes in older men and are useful additional measures in identifying those at high risk of diabetes.

Objectives: Smoking is a major cause of death and often initiates in adolescence. Mutations in CYP2A6 slow metabolism of nicotine to cotinine. Haploinsufficiency in adults is associated with lower cigarette consumption, lower cotinine level and higher quit rates. Other genes are also implicated in smoking behaviour. We explored smoking behaviour and cotinine levels in relation to genotypes in adolescents. Methods: 1518 subjects from the Ten Towns Heart Health Study were genotyped for CYP2A6 alleles *1A, *1B, *2, *4, *5, *9 and *12 to classify predicted nicotine metabolism rate. DBH(rs77905), MAOA(rs1801291+VNTR), DRD4(VNTR) and 5HT2A(rs6313) were also studied. Smoking status was established by questionnaire and salivary cotinine measurement at 13-15 and 18 years. Results: No significant associations were identified for DBH, MAOA, DRD4 and 5HT2A markers, with smoking status or cotinine level at either age. At age 18, haploinsufficiency (HI) for CYP2A6 was associated with a higher odds of being a current smoker compared with the *1B carriers (WT1B) (OR=2.23 (1.16, 4.27) for current versus ex); *1A homozygotes (WT1A) were also at slightly higher risk (OR=1.44 (1.01, 2.06)). Partial haploinsufficiency (PHI) was not associated with being a current smoker. There were no significant associations at age 13-15. PHI and HI were associated with higher cotinine levels amongst smokers at both 13-15 and at 18 years compared with WT1B and WT1A groups. Conclusions: CYP2A6 haploinsufficiency increases likelihood of continuing smoking in teenagers. We hypothesize an explanatory 'occupancy' model to explain why haploinsufficiency results in faster progression to nicotine dependence, but lower subsequent consumption.

Background: Most population studies have reported weak or non-significant associations between body mass index (BMI; in kg/m 2 ) and lung function. Objective: This study focused on the distinct effects of fat distributionand body composition on lung function and examined these relations in elderly men. Design: The study was a cross-sectional evaluation of 2744 men aged 60-79 y who were free of cardiovascular disease and cancer and were drawn from general practices in 24 British towns. Anthropometric and body-composition [including fat mass (FM), fat-free mass (FFM), and percentage body fat (%BF) evaluated with bioelectric impedance] measurements were made, and lung function was examined by using spirometry. Results: Height-standardized forced expiratory volume in 1 s (FEV 1 ) was diminished only in lean (BMI < 22.5) and obese (BMI ≥ 30) men, but forced vital capacity (FVC) tended to decrease with increasing BMI (P < 0.01). All other measures of adiposity [ie, waist circumference (WC), waist-hip ratio (WHR), FM, and %BF] were significantly and inversely related to FEV 1 and FVC after adjustment for confounders, including age and cigarette smoking (all: P < 0.05). This was seen both in nonobese (BMI < 30) and obese men. FFM was positively associated with FEV 1 (P = 0.03) and to a lesser extent with FVC. Higher BMI and FFM were both associated with reduced odds of a low FEV 1 -FVC ratio (ie

Background— Atherosclerosis develops from childhood, but the determinants of this preclinical stage remain uncertain. We examined the relations of classic coronary risk factors, adiposity and its associated metabolic disturbances, to arterial distensibility (a marker of early arterial disease) in 13- to 15-year-olds, some of whom had previously been studied at ages 9 to 11 years. Methods and Results— Brachial artery distensibility was measured by a noninvasive ultrasound technique in 471 British children in whom measures of adiposity, blood pressure, fasting blood lipids, and insulin had been made. All adiposity measures showed strong graded inverse relationships with distensibility. Inverse associations with distensibility were also observed for insulin resistance (homeostasis model assessment), diastolic pressure, C-reactive protein, and the number of metabolic syndrome components present, which had a graded relation to distensibility. Total and LDL cholesterol levels were also inversely related to distensibility, but less strongly than adiposity; homocysteine had no relation to distensibility. Although the relations of total and LDL cholesterol and diastolic pressure to distensibility had been present at 9 to 11 years of age, those of adiposity and insulin resistance were only apparent at 13 to 15 years. Conclusions— Adiposity and its metabolic consequences are associated with adverse changes in the arterial wall by the teenage years. The graded relation with increasing adiposity was stronger than that for cholesterol and was seen at body mass index levels well below those considered to represent “obesity.” This emphasizes the importance of population-based strategies to control adiposity and its metabolic consequences in the young.

It has been suggested that the effects of alcohol on body weight and fat distribution may be influenced by the quantity and type of drink and may differ according to whether the alcohol is consumed with meals or not.We have examined the cross-sectional association between alcohol intake, patterns of drinking and adiposity (body mass index (BMI), waist-to-hip ratio (WHR), waist circumference (WC) and percentage body fat (%BF)).We studied 3327 men aged 60-79 y with no history of myocardial infarction, stroke or diabetes drawn from general practices in 24 British towns.BMI, WHR, WC and %BF increased significantly with increasing alcohol intake even after adjustment for potential confounders (all P0.0001), although the effects were stronger for WC and WHR (measures of central adiposity). Men who consumedor = 21 units/week showed higher levels of central adiposity (WHR, WC) and general adiposity (BMI, %BF) than nondrinkers and lighter drinkers, irrespective of the predominant type of drink consumed (wine, beer, spirits or mixed). The positive association was most clearly seen in beer and spirit drinkers; positive but weaker associations were seen for wine. Among drinkers, a positive association was seen between alcohol intake and the adiposity variables irrespective of whether the alcohol was drunk with or separately from meals.Higher alcohol consumption (or = 21 units/week) is positively associated with general and to a greater extent with central adiposity, irrespective of the type of drink and whether the alcohol is drunk with meals or not.

Aims: We have examined the cross-sectional relationship between insulin resistance, the metabolic syndrome and haemostatic and inflammatory markers.Methods and results: We carried out the study in 2722 non-diabetic men aged 60-79 years with no history of coronary heart disease or stroke and who were not on warfarin treatment, drawn from general practices in 24 British towns. Insulin resistance (HONIA) was significantly associated with increased inflammatory markers (C-reactive protein (CRP), white cell count), coagulation factors VII-IX, von Willebrand factor (VWF) and tissue plasminogen activator (t-PA) antigens (markers of endothelial dysfunction) and blood viscosity after adjustment for age, smoking, physical activity, alcohol intake and waist circumference. Relationships with fibrinogen and fibrin D-dimer were weak. The relationship between HOMA and CRP was abolished after adjustment for t-PA. The prevalence of the metabolic syndrome was similar using World Health Organization (WHO) and National Cholesterol Education Program definitions (26.7% and 27.0%) but associations between the metabolic syndrome and increased haemostatic markers, particularly for raised factor VIII and VWF were stronger using WHO criteria.Conclusion: Insulin resistance and the metabolic syndrome showed significant associations with markers of haemostasis and inflammation, which may be relevant to their associations with cardiovascular disease. (c) 2005 Elsevier Ireland Ltd. All rights reserved.

Background: Body mass index (BMI; in kg/m(2)) is considered a poor indicator of overall and abdominal obesity in the elderly.Objectives: Our goal was to determine which simple anthropometric measurements [BMI, waist-to-hip ratio (WHR), waist circumference (WC), percentage body fat (%BF), or fat mass (FM)] are most closely associated with metabolic risk factors and insulin resistance in elderly men.Design: This was a cross-sectional study of 2924 men aged 60-79 y with no history of coronary heart disease, stroke, or diabetes who were drawn from general practices in 24 British towns.Results: BMI and WC were the measures most strongly associated with the metabolic syndrome ( 3 of the following: hypertension, low HDL cholesterol, high triacylglycerols, or high blood glucose) and insulin resistance. For a 1-SD increase in BMI, WC, WHR, %BF, and FM, the odds ratios (95% CIs) of having the metabolic syndrome after adjustment for age, socioeconomic status, smoking status, and physical activity were as follows: BMI, 1.61 (1.44,1.79); WC, 1.65 (1.48, 1.81); WHR, 1.49 (1.34, 1.66); %BF, 1.41 (1.25, 1.59); and FM, 1.53 (1.38, 1.70). For insulin resistance, the odds ratios (95 % CIs) were as follows: 2.48 (2.22, 2.77), 2.46 (2.19, 2.65), 1.75 (1.59, 1.93), 1.79 (1.60, 2.00), and 2.10 (1.88, 2.34), respectively. In normal-weight (BMI < 25) and overweight (BMI 25-29.9) men, the presence of the metabolic syndrome and insulin resistance increased with increasing WC; this did not occur in obese men.Conclusions: BMI and WC are the simple measures of adiposity most strongly associated with metabolic abnormalities in elderly men. Our findings suggest that WC can be used as a complementary measurement to identify health risks in normal-weight and overweight elderly persons.

Moderate alcohol consumption is associated with a decreased risk of cardiovascular disease. However, the impact of variation in alcohol intake over time on estimated risk relations has not been adequately addressed. In this study, 6,544 middle-aged British men without previous cardiovascular disease were followed for cardiovascular events and all-cause mortality over 20 years from 1978/1980 to 1998/2000. Alcohol intake was ascertained at regular points throughout the study. A total of 922 men had a major coronary event within 20 years, 352 men had a stroke, and 1,552 men died of all causes. Baseline alcohol intake displayed U-shaped relations with cardiovascular disease and all-cause mortality, with light drinkers having the lowest risks and nondrinkers and heavy drinkers having similarly high risks. However, the nature of these relations changed after adjustment for intake variation; risks associated with nondrinking were lowered, and risks associated with moderate and heavy drinking increased. Regular heavy drinkers had a 74% higher risk of a major coronary event, a 133% higher risk of stroke, and a 127% higher risk of all-cause mortality than did occasional drinkers (these estimates were 8%, 54%, and 44% before adjustment for intake variation). The findings suggest that considerable caution may be needed before any recommendations regarding acceptable limits of alcohol consumption are made.

Objective. To examine the influence of initial infant feeding on obesity in later life.Methods. A systematic review of published studies investigating the association between infant feeding and a measure of obesity was performed with Medline (1966 onward) and Embase (1980 onward) databases, supplemented with manual searches. Data extraction was conducted by 2 authors. Analyses were based on odds ratios of obesity among initially breastfed subjects, compared with formula-fed subjects, pooled with fixed-effects models.Results. Sixty-one studies reported on the relationship of infant feeding to a measure of obesity in later life; of these, 28 (298900 subjects) provided odds ratio estimates. In these studies, breastfeeding was associated with a reduced risk of obesity, compared with formula feeding (odds ratio: 0.87; 95% confidence interval [CI]: 0.85–0.89). The inverse association between breastfeeding and obesity was particularly strong in 11 small studies of Conclusions. Initial breastfeeding protects against obesity in later life. However, a further review including large unpublished studies exploring the effect of confounding factors in more detail is needed.

Aims To examine the associations between cigarette smoking, pipe/cigar smoking, and years since quitting smoking, and inflammatory and haemostatic markers. Methods and results A study in 2920 men aged 60–79 with no history of myocardial infarction, angina, stroke, or diabetes, and who were not on warfarin, from general practices in 24 British towns. After adjustment for other major cardiovascular risk factors, compared with never smokers, current cigarette smokers showed significantly higher levels of C-reactive protein (2.53 vs. 1.35 mg/L), white cell count (7.92 vs. 6.42×109/L), and fibrinogen (3.51 vs. 3.13 g/L). They also showed higher levels of haematocrit, blood and plasma viscosity, tissue plasminogen activator antigen, and fibrin D-dimer, and lower levels of albumin. Primary pipe/cigar smokers showed levels similar to never smokers. Ex-cigarette smokers and secondary pipe/cigar smokers showed intermediate levels although secondary pipe/cigar smokers showed higher odds of having elevated white cell count and fibrinogen than ex-cigarette smokers. Most inflammatory and haemostatic levels improved within 5 years of smoking cessation but took over 20 years to revert to levels of never smokers. Conclusion These findings suggest that activation of inflammation and haemostasis may be potential mechanisms by which cigarette and pipe/cigar smoking increase cardiovascular risk.

During the early 1970s, mortality rates from coronary heart disease (CHD) were exceptionally high in the UK. A twofold regional variation existed with particularly high rates in South Wales, Northern England, Scotland, and Northern Ireland. There was considerable interest in the possibility that ‘soft’ drinking water was a risk factor for CHD and that variations in water hardness/softness across Britain might account for these geographical variations. Professor Gerry Shaper and colleagues submitted a 5-year proposal to the Medical Research Council: to examine the factors responsible for the considerable regional variation in coronary heart disease, hypertension, and stroke in Great Britain, and to determine the causes of these conditions in order to provide a rational basis for recommendations towards their prevention. This proposal embraced the water hardness hypothesis but extended the potential of the data collected to produce a more substantial and wider ranging enquiry into the causes of CHD both at the individual and the regional level: The British Regional Heart Study (BRHS).

We have examined markers of haemostasis and inflammation in men with diabetes, coronary heart disease (CHD) or both, and assessed their associations with insulin resistance in men with Type 2 diabetes.The study was carried out in 4066 British men aged 60 to 79 years who were not on warfarin or insulin, of whom there were 426 men with prevalent Type 2 diabetes and 842 with prevalent CHD.Men with Type 2 diabetes were more likely to have multiple risk factors and higher levels of haemostatic and inflammatory markers than men without, irrespective of CHD status. Compared with men with CHD only, men with diabetes only showed increased levels of tissue plasminogen activator antigen, increased plasma and blood viscosity, and increased levels of coagulation factors VII, VIII and IX. They also had dyslipidaemia. In men with diabetes, increased insulin resistance (homeostasis model assessment, HOMA) was associated with increased levels of haemostatic markers and dyslipidaemia. The prevalence of CHD increased significantly with increasing tertiles of HOMA (adjusted odds ratio 1.32 [95% CI: 0.72-2.42] in the second, and 1.70 [95% CI: 0.92-3.44] in the third tertile; p=0.04 for trend).Increased insulin resistance among men with Type 2 diabetes is associated with increased prevalence of CHD and of activated haemostasis and dyslipidaemia. Reducing insulin resistance in men with diabetes may reduce their tendency to develop thrombosis and hence CHD risk.

It has been proposed that genetic factors involved in insulin action could explain part of the link between low birthweight and risk of cardiovascular disease and diabetes in adulthood. To confirm this we examined the association between offspring birthweight and paternal insulin resistance and diabetes in late adulthood.We did a cross-sectional survey of 4252 men who were 60 to 79 years of age and from 24 British towns. Of these, 2788 men provided details of their offsprings' birthweight and sex.Offspring birthweight was inversely associated with paternal insulin resistance defined by the homeostasis model assessment (HOMA) score and with Type 2 diabetes in late adulthood. Fathers of offspring in the highest quartile of sex-standardised birthweight SD scores had a 34% reduction in odds of having a high HOMA insulin resistance score (OR=0.66, 95% CI: 0.47 to 0.92) compared with fathers of offspring in the lowest quartile after adjustment for potential confounders. A stronger inverse association was seen between offspring birthweight and risk of paternal diabetes (adjusted OR=0.59, 95% CI: 0.39 to 0.88 top quartile vs lowest quartile). For each increase of offspring-birthweight SD score the odds of high HOMA scores decreased by 13% (OR=0.87, 95% CI: 0.78 to 0.98) and the odds for diabetes by 17% (OR=0.83, 95% CI: 0.72 to 0.95), after full adjustment.Offspring birthweight is inversely associated with paternal insulin resistance and diabetes in late adulthood, supporting the hypothesis that genetic factors related to insulin action contribute to the association between birthweight and adult cardiovascular disease and diabetes risk.

Background and Purpose— The geographic variation in CHD and stroke within Great Britain is well known. We aimed to quantify these variations and to determine the contribution of established risk factors. Methods— This prospective study consisted of 7735 men 40 to 59 years of age in 24 British towns who were followed up for 20 years from screening in 1978 to 1980. We compared age-adjusted incidences of major stroke and CHD events in southern England and the rest of Britain before and after adjustment for established cardiovascular risk factors. Results— At least 1 episode of stroke occurred in 467 men (3.54 per 1000 person-years, age standardized) and of CHD in 1299 men (10.05 per 1000 person-years). Event rates varied between towns, from 2.00 to 5.45 per 1000 person-years for stroke and from 6.16 to 12.21 per 1000 person-years for CHD. Incidence for both diseases was highest in Scottish towns and lowest in southern English towns (“north-south gradient”). The hazard ratio for stroke in the rest of Britain compared with southern England was 1.44 (95% confidence interval [CI], 1.16 to 1.78); for CHD, it was 1.32 (95% CI, 1.14 to 1.53). After adjustment for baseline systolic blood pressure, smoking status, physical activity, social class, and height, the hazard ratio was 1.24 (95% CI, 1.00 to 1.54) for stroke and 1.17 (95% CI, 1.02 to 1.35) for CHD. Conclusions— Similar north-south gradients were observed for major stroke and major CHD events. The magnitude of these gradients was considerably diminished when individual risk variables were taken into account.

Objective. To examine the relationship between birth weight and blood total cholesterol (TC) and to compare its strength with that of the relationship between current body mass index and TC.Methods. 1) Cross-sectional study of adolescents, with retrospective ascertainment of birth weight from birth records or parental recall; 2) systematic review of studies examining the relations between birth weight and cholesterol at all ages.Participants. 1) 1532 individuals (92% white, 55% male) in 10 British towns; 2) 28 studies with 32 observations showing the change in TC per 1 kg increase in birth weight—6 in infancy, 14 in adolescents, 12 in adults.Results. In the cross-sectional study, there was a weak inverse relation between birth weight and TC level (−.061 mmol/L fall in TC per kg increase in birth weight, 95% confidence interval −.131 to .008 mmol/L per kg) which was little affected by adjustment for current body size. The difference in TC corresponding to an interquartile range increase in birth weight (−.03 mmol/L) was approximately a quarter of that for an equivalent increase in body mass index (.11 mmol/L). In the systematic review, an inverse association between birth weight and TC of a similar size to that in the cross-sectional study was observed (−.048 mmol/L per kg, 95% confidence interval −.078 to −.018 mmol/L per kg) similar in strength at all ages.Conclusion. The relation of fetal nutrition to TC appears to be weak and is probably of limited public health importance when compared with the effects of childhood obesity.

Background — Physical activity is associated with lower risk of cardiovascular disease, but the mechanisms are uncertain. Hemostatic and inflammatory markers have been linked with risk of cardiovascular disease. We therefore examined the relationship between physical activity and hemostatic and inflammatory variables. Methods and Results — In 1998 to 2000, 20 years after the initial screening of 7735 men 40 to 59 years old from general practices in 24 British towns, 4252 subjects (77% of available survivors, now 60 to 79 old) attended for reexamination. A fasting blood sample was available in 4088 men. All men on warfarin (n=134) and men with incomplete data on physical activity (n=144) were excluded, leaving 3810 men for analysis. Physical activity showed a significant and inverse dose-response relationship with fibrinogen, plasma and blood viscosity, platelet count, coagulation factors VIII and IX, von Willebrand factor, fibrin d -dimer, tissue plasminogen activator antigen, C-reactive protein, and white cell count, even after adjustment for possible confounders. The effects were similar in men with and without prevalent cardiovascular disease. No relationship was seen with activated partial thromboplastin time, activated protein C resistance, hematocrit, or factor VII. An examination of changes in physical activity between baseline and 20 years later showed that inactive men who took up at least light physical activity had levels of blood variables approaching those who remained at least lightly active. Those who became inactive showed levels more similar to those who remained inactive. Conclusions — These data suggest that the benefit of physical activity on cardiovascular disease may be at least partly a result of effects on hemostasis and inflammation.

Physical activity is associated with lower risk of cardiovascular disease, but the mechanisms are uncertain. Hemostatic and inflammatory markers have been linked with risk of cardiovascular disease. We therefore examined the relationship between physical activity and hemostatic and inflammatory variables.In 1998 to 2000, 20 years after the initial screening of 7735 men 40 to 59 years old from general practices in 24 British towns, 4252 subjects (77% of available survivors, now 60 to 79 old) attended for reexamination. A fasting blood sample was available in 4088 men. All men on warfarin (n=134) and men with incomplete data on physical activity (n=144) were excluded, leaving 3810 men for analysis. Physical activity showed a significant and inverse dose-response relationship with fibrinogen, plasma and blood viscosity, platelet count, coagulation factors VIII and IX, von Willebrand factor, fibrin D-dimer, tissue plasminogen activator antigen, C-reactive protein, and white cell count, even after adjustment for possible confounders. The effects were similar in men with and without prevalent cardiovascular disease. No relationship was seen with activated partial thromboplastin time, activated protein C resistance, hematocrit, or factor VII. An examination of changes in physical activity between baseline and 20 years later showed that inactive men who took up at least light physical activity had levels of blood variables approaching those who remained at least lightly active. Those who became inactive showed levels more similar to those who remained inactive.These data suggest that the benefit of physical activity on cardiovascular disease may be at least partly a result of effects on hemostasis and inflammation.