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Background: The associations between height, socioeconomic position (SEP) and coronary heart disease (CHD) incidence are well established, but the contribution of genetic factors to these associations is still poorly understood. We used a polygenic score (PGS) for height to shed light on these associations., Methods: Finnish population-based health surveys in 1992-2011 (response rates 65-93%) were linked to population registers providing information on SEP and CHD incidence up to 2019. The participants (N=29 996; 54% women) were aged 25-75 at baseline, and there were 1767 CHD incident cases (32% in women) during 472 973 person years of follow-up. PGS-height was calculated based on 33 938 single-nucleotide polymorphisms, and residual height was defined as the residual of height after adjusting for PGS-height in a linear regression model. HRs of CHD incidence were calculated using Cox regression., Results: PGS-height and residual height showed clear gradients for education, social class and income, with a larger association for residual height. Residual height also showed larger associations with CHD incidence (HRs per 1 SD 0.94 in men and 0.87 in women) than PGS-height (HRs per 1 SD 0.99 and 0.97, respectively). Only a small proportion of the associations between SEP and CHD incidence was statistically explained by the height indicators (6% or less)., Conclusions: Residual height associations with SEP and CHD incidence were larger than for PGS-height. This supports the role of material and social living conditions in childhood as contributing factors to the association of height with both SEP and CHD risk., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Depression is a risk factor for coronary heart disease (CHD), but less is known whether genetic susceptibility to CHD or regional-level social indicators modify this association., Methods: Risk factors of CHD including a Polygenic Risk Score (PRS) were measured for 19 999 individuals residing in Finland in 1997, 2002, 2007 and 2012 (response rates 60%-75%). During the register-based follow-up until 2015, there were 1381 fatal and non-fatal incident CHD events. Unemployment rate, degree of urbanisation and crime rate of the municipality of residence were used as regional level social indicators. HRs were calculated using register-based antidepressant purchases as a non-reversible time-dependent covariate., Results: Those having depression and in the highest quartile of PRS had somewhat higher CHD risk than predicted only by the main effects of depression and PRS (HR for interaction 1.53, 95% CI 0.95 to 2.45). Depression was moderately associated with CHD in high crime (HR 1.51, 95% CI 1.20 to 1.90) and weakly in low crime regions (HR 1.07, 95% CI 0.86 to 1.33; p value of interaction=0.087). Otherwise, we did not found evidence for interactions., Conclusions: Those having both depression and high genetic susceptibility need a special attention in healthcare for CHD., Competing Interests: Competing interests: VS reports personal fees from Novo Nordisk and Sanofi for consulting and grants from Bayer outside this work., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Numerous observational studies have highlighted structural inequalities in COVID-19 mortality in the UK. Such studies often fail to consider the hierarchical, spatial nature of such inequalities in their analysis, leading to the potential for bias and an inability to reach conclusions about the most appropriate structural levels for policy intervention., Methods: We use publicly available population data on COVID-19-related mortality and all-cause mortality between March and July 2020 in England and Wales to investigate the spatial scale of such inequalities. We propose a multiscale approach to simultaneously consider three spatial scales at which processes driving inequality may act and apportion inequality between these., Results: Adjusting for population age structure and number of local care homes we find highest regional inequality in March and June/July. We find finer grained within region inequality increased steadily from March until July. The importance of spatial context increases over the study period. No analogous pattern is visible for non-COVID-19 mortality. Higher relative deprivation is associated with increased COVID-19 mortality at all stages of the pandemic but does not explain structural inequalities., Conclusions: Results support initial stochastic viral introduction in the South, with initially high inequality decreasing before the establishment of regional trends by June and July, prior to reported regionality of the 'second-wave'. We outline how this framework can help identify structural factors driving such processes, and offer suggestions for a long-term, locally targeted model of pandemic relief in tandem with regional support to buffer the social context of the area., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Background: Genetic vulnerability to coronary heart disease (CHD) is well established, but little is known whether these effects are mediated or modified by equally well-established social determinants of CHD. We estimate the joint associations of the polygenetic risk score (PRS) for CHD and education on CHD events., Methods: The data are from the 1992, 1997, 2002, 2007 and 2012 surveys of the population-based FINRISK Study including measures of social, behavioural and metabolic factors and genome-wide genotypes (N=26 203). Follow-up of fatal and non-fatal incident CHD events (N=2063) was based on nationwide registers., Results: Allowing for age, sex, study year, region of residence, study batch and principal components, those in the highest quartile of PRS for CHD had strongly increased risk of CHD events compared with the lowest quartile (HR=2.26; 95% CI: 1.97 to 2.59); associations were also observed for low education (HR=1.58; 95% CI: 1.32 to 1.89). These effects were largely independent of each other. Adjustment for baseline smoking, alcohol use, body mass index, igh-density lipoprotein (HDL) and total cholesterol, blood pressure and diabetes attenuated the PRS associations by 10% and the education associations by 50%. We do not find strong evidence of interactions between PRS and education., Conclusions: PRS and education predict CHD events, and these associations are independent of each other. Both can improve CHD prediction beyond behavioural risks. The results imply that observational studies that do not have information on genetic risk factors for CHD do not provide confounded estimates for the association between education and CHD., Competing Interests: Competing interests: VS reports personal fees and non-financial support from Novo Nordisk, personal fees from Sanofi and grants from Bayer, outside the scope of the submitted work. All the other authors have nothing further to declare., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: A strict high legal age limit for alcohol purchases decreases adolescents' access to alcohol, but little is known about long-term health effects. The aim was to estimate the effect of increased alcohol availability during adolescence on alcohol-related morbidity and mortality., Methods: A nationwide register-based study using data from a natural experiment setting. In two regions of Sweden, strong beer (4.5%-5.6% alcohol by volume) became temporarily available for purchase in grocery stores for individuals 16 years or older (instead of 21) in 1967/1968. The intervention group was defined as all individuals living in the intervention area when they were 14-20 years old (n=72 110). The remaining Swedish counties excluding bordering counties, without the policy change, were used as the control group (n=456 224). The outcomes of alcohol-related morbidity and mortality were collected from the Hospital Discharge Register and Cause of Death Register, in which average follow-up times were 38 years and 41 years, respectively. HRs with 95% CIs were obtained by Cox regression analysis., Results: In the fully adjusted model, no clear evidence of an association between increased alcohol availability during adolescence and alcohol-related morbidity (HR: 0.99, 95% CI 0.96 to 1.02) or mortality (HR: 1.02, 95% CI 0.95 to 1.10) was found., Conclusion: The initial elevated risk of alcohol-related morbidity and mortality later in life among adolescents exposed to increased access to strong beer in Sweden vanished when a regional measure population density of locality was included in the model, which is important to consider in future research., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Marital relationship quality has been suggested to have independent effects on cardiovascular health outcomes. This study investigates the association between changes in marital relationship quality and cardiovascular disease (CVD) risk factors in men., Methods: We used data from The Avon Longitudinal Study of Parents and Children, a prospective birth cohort study (Bristol, UK). Our baseline sample was restricted to married study fathers with baseline relationship and covariate data (n=2496). We restricted final analysis (n=620) to those with complete outcome, exposure and covariate data, who were married and confirmed the study child's father at 6.4 years and 18.8 years after baseline. Relationship quality was measured at baseline and 6.4 years and operationalised as consistently good, improving, deteriorating or consistently poor relationship. We measured CVD risk factors of blood pressure, resting heart rate, body mass index, lipid profile and fasting glucose at 18.8 years after baseline., Results: Improving relationships were associated with lower levels of low-density lipoprotein (-0.25 mmol/L, 95% CI -0.46 to -0.03) and relative reduction of body mass index (-1.07 kg/m 2 , 95% CI -1.73 to -0.42) compared with consistently good relationships, adjusting for confounders. Weaker associations were found between improving relationships and total cholesterol (-0.24 mmol/L, 95% CI -0.48 to 0.00) and diastolic blood pressure (-2.24 mm Hg, 95% CI -4.59 to +0.11). Deteriorating relationships were associated with worsening diastolic blood pressure (+2.74 mm Hg, 95% CI 0.50 to 4.98)., Conclusions: Improvement and deterioration of longitudinal relationship quality appears associated with respectively positive and negative associations with a range of CVD risk factors., Competing Interests: Competing interests: This publication is the work of the authors andIB-B willserve as guarantor for the contents of this paper., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Rationale and Objectives: Self-reported smoking underestimates disease risk. Smoking affects DNA methylation, in particular the cg05575921 site in the aryl hydrocarbon receptor repressor (AHRR ) gene. We tested the hypothesis that AHRR cg05575921 hypomethylation is associated with risk of smoking-related morbidity and mortality., Methods: From the Copenhagen City Heart Study representing the Danish general population, we studied 9234 individuals. Using bisulphite treated leucocyte DNA, AHRR (cg05575921) methylation was measured. Rs1051730 ( CHRN3A ) genotype was used to evaluate smoking heaviness. Participants were followed for up to 22 years for exacerbations of COPD, event of lung cancer and all-cause mortality. Six-year lung cancer risk was calculated according to the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO M2012 )., Measurements and Main Results: AHRR (cg05575921) hypomethylation was associated with former and current smoking status, high daily and cumulative smoking, short time since smoking cessation (all p values <7×10 -31 ), and the smoking-related CHRN3A genotype (-0.48% per T-allele, p=0.002). The multifactorially adjusted HRs for the lowest versus highest methylation quintiles were 4.58 (95% CI 2.83 to 7.42) for COPD exacerbations, 4.87 (2.31 to 10.3) for lung cancer and 1.67 (1.48 to 1.88) for all-cause mortality. Finally, among 2576 high-risk smokers eligible for lung cancer screening by CT, observed cumulative incidences of lung cancer after 6 years for individuals in the lowest and highest methylation quintiles were 3.7% and 0.0% (p=2×10 -7 ), whereas predicted PLCO M2012 6-year risks were similar (4.3% and 4.4%, p=0.77)., Conclusion: AHRR (cg05575921) hypomethylation, a marker of smoking behaviour, provides potentially clinical relevant predictions of future smoking-related morbidity and mortality., Competing Interests: Competing interests: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background: Supplemental periconceptional folic acid is recommended to reduce the risk of fetal neural tube defects. A previous report indicated an elevated risk of breast cancer and all cancer deaths in later life among women randomised by alternate allocation to high-dose (5 mg/day) folic acid in pregnancy compared with placebo; however, findings were based on small numbers of cases. Our aim was to extend the previous analysis by including data from an additional 10 years of follow-up., Methods: Records of participants in a large (n=2928) trial of folate supplementation (5 or 0.2 mg folic acid, or placebo) in pregnancy in the 1960s were linked to central registries in Scotland. Unadjusted and adjusted HRs were calculated for all-cause, cardiovascular, all cancer and breast cancer mortality, and all cancer and breast cancer morbidity. Analyses were done using (1) data from the time of the previous linkage (2002) to March 2013; and (2) data from 1980 to March 2013., Results: There was no evidence to suggest an excess risk of morbidity or mortality in either supplementation group compared with placebo for 2002-2013 and no associations were seen for the full time period (1980-2013)., Conclusions: Findings from this extended follow-up do not support our previous observation of an elevated risk of mortality from breast cancer or all cancers in later life among women who had taken 5 mg folic acid/day during pregnancy. Furthermore, there were no associations with risk of mortality from all-causes, all cancers or cardiovascular disease., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: Taller adults have a reduced risk of cardiovascular disease, and there is some evidence that pre-adolescent exposures, indexed by leg length, underlie this association. Associations with other aspects of skeletal size in childhood have not previously been investigated., Methods: We have examined associations of cardiovascular mortality and morbidity with childhood height, shoulder breadth, leg, trunk and foot length using a cohort of children whose families participated in a 1937-9 survey of diet and health followed up for 59 years., Results: Altogether 2642 traced participants had at least one anthropometric measurement; a subsample (n=1043), completed the Rose angina questionnaire and provided information about doctor-diagnosed ischaemic heart disease (IHD) in 1997-8. Childhood stature was weakly inversely associated with cardiovascular mortality, and leg length was the component with the strongest associations. There was evidence from secondary analyses that childhood anthropometric measurements were inversely related to early (age <65 years) rather than late cardiovascular mortality. Childhood stature was inversely associated with self-reported IHD and associations with leg length were strongest. Associations were somewhat attenuated in models including terms for having been breastfed and socioeconomic position., Conclusion: Pre-adult exposures are more strongly associated with cardiovascular morbidity than mortality, and they affect premature cardiovascular mortality more than later mortality.

Background: Modifiable behavioural risk factors--including exercise, obesity and smoking--have been causally associated with colorectal cancer mortality. However, results have been inconsistent and undiagnosed cancers may affect baseline risk factors, distorting the temporal relationship that is observed between them., Objective: To determine whether risk factors for colorectal cancers available in the Whitehall I study were predictive of colonic or rectal cancer mortality., Methods: Prospective cohort study over 40 years on Whitehall I men aged 40-69 on entry between 1967 and 1970. Associations between baseline risk factors and cause-specific mortality were tested with Cox proportional hazards models. Events within the first 10 years of follow-up were excluded to minimise 'reverse causality.', Results: 329 colon and 121 rectal cancer deaths occurred among 17,949 men followed up for a total of 472,523 person-years. Age and smoking were associated with increased mortality from colorectal cancers. Compared with never-smokers, current smoking was associated with age-adjusted HRs for colon and rectal cancers of 1.45 (95% CI 1.03 to 2.03) and 1.97 (95% CI 1.02 to 3.80), respectively. A significant effect of current smoking on rectal cancer mortality was only apparent after events in the first 10&emsp14;years of follow-up were excluded. No convincing evidence was found that body mass index, diabetes mellitus, blood pressure or physical activity were associated with colorectal cancer mortality., Conclusion: Smoking significantly increases mortality from colorectal cancer and its decreasing prevalence in the UK may partly explain falling mortality from the disease. Changes in health behaviours in response to early cancer symptoms may result in differential misclassification or 'reverse causality' unless early events are excluded. Although many individual cohort studies have not shown significant relationships between behavioural risk factors and colorectal cancer mortality, their contribution to meta-analyses remains important.

Background: Although several plausible biological mechanisms have been advanced for the association between greater physical stature and lower coronary heart disease (CHD) risk in prospective cohort studies, the importance of one of the principal artefactual explanations--reverse causality due to shrinkage--remains unresolved. To explore this issue, studies with repeat measurements of height are required, but, to date, such data have been lacking., Objective: To examine the possible relationship between height loss and future CHD., Methods: Data were analysed from the Whitehall II prospective cohort study of 3802 men and 1615 women who participated in a physical examination in 1985-8, had their height re-measured in 1997-9, and were then followed up for fatal and non-fatal CHD., Results: A mean follow-up of 7.4 years after the second height measurement gave rise to 69 CHD events in men and 18 in women. After adjustment for baseline CHD risk factors, greater loss of physical stature between survey and resurvey was associated with an increased risk of CHD in men (HR; 95% CI for a one SD increase: 1.24; 1.00 to 1.53) but not women (0.93; 0.58 to 1.50)., Conclusions: Reverse causality due to shrinkage may contribute to the inverse association between a single measurement of height and later CHD in other studies.

Background: It has been hypothesised that dehydration in infancy could permanently increase sodium retention, raising blood pressure in later life. In this study, the association between gastrointestinal tract infection in infancy, a clinically relevant exposure often accompanied by dehydration, and raised blood pressure in childhood was investigated., Methods: Data from a cohort study nested within a cluster-randomised trial of breastfeeding promotion in the Republic of Belarus were analysed. 17 046 healthy breastfed infants were enrolled from 31 maternity hospitals. 13 889 (81.5%) children were followed-up at 6.5 years. Exposure measures were any gastrointestinal infection in infancy (to 1 year) and hospitalisations for gastrointestinal infection in infancy and in childhood (1-6.5 years). The outcomes were systolic and diastolic blood pressure at age 6.5 years., Results: The prevalence of any gastrointestinal infection in infancy, and of hospitalisation for gastrointestinal infection in infancy or childhood, was 11.4%, 3.2% and 6.0%, respectively. No associations were observed between systolic blood pressure and any gastrointestinal infection (mean difference in those with minus those without infection -0.04 mm Hg; 95% CI -0.52 to 0.43) or hospitalisation for gastrointestinal infection (difference=-0.22 mm Hg; -1.07 to 0.64) in infancy. Nor were associations observed between diastolic blood pressure and any gastrointestinal infection during infancy or hospitalisation for gastrointestinal infection during infancy or childhood., Conclusion: No evidence was found to prove that hospitalisation for gastrointestinal infection in infancy or childhood leads to raised blood pressure at age 6.5 years in a developed country setting.

Background: Overconsumption of alcohol affects health. Data from men from the West of Scotland Collaborative study were analysed to see how reported alcohol was related to acute and mental health hospital admissions., Methods: Men (N = 5772) from a prospective cohort study located in 27 workplaces in West and Central Scotland were screened when aged 35-64 in 1970-3. The number of acute and mental health admissions and bed-days were calculated by alcohol category (none, 1-7, 8-14, 15-21, 22-34 and 35 or more units per week) to the end of 2005. Specific causes were coronary heart disease (CHD), stroke, respiratory diseases and alcohol-related., Results: Men who consumed 22 or more units per week had a 20% higher rate of acute admissions than non-drinkers. The number of bed-days were higher for men drinking eight or more units and increased with consumption, with the highest category having a 58% higher rate of bed-days than non-drinkers. Non-drinkers had the highest admissions for CHD. For stroke, drinkers of 15 or more units had higher admissions and higher number of bed-days and these increased with increasing consumption. Respiratory admissions were higher for drinkers of 22 or more units and bed-days were higher for drinkers of 15 or more units. Alcohol-related admissions and number of bed-days generally increased with consumption. Mental health admissions and number of bed-days were raised for drinkers of 22 or more units with a suggestion of a J-shaped relationship., Conclusion: Alcohol consumption has a substantial effect on acute and mental health admissions and bed-days.

Background: Fetal growth is highly socially patterned and is related to health across the life course, but how the social patterns of fetal growth change over time remains understudied. The time trends in maternal social disadvantage in relation to fetal growth were examined in the context of a universal welfare state under changing macroeconomic conditions over a 24-year period., Methods: All births in Denmark from 1981 to 2004 were included, and the association between maternal social disadvantage and birthweight was examined for gestational age z-scores over time using linear regression., Results: All measures of social disadvantage were associated with decreased fetal growth (p<0.001), but with considerable differences in the magnitude of the associations. The association was strongest for non-Western ethnicity (-0.28 z-score), low education (-0.19), teenage motherhood (-0.14), single motherhood (-0.13) and poverty (-0.12) and weakest for unemployment (-0.04). The deficit in fetal growth increased over time for all associations except for unemployment. Also, the measures of social adversity increasingly clustered within individuals over time., Conclusion: Maternal social disadvantage is associated with decreased fetal growth in a welfare state. Social disadvantage is increasingly clustered so that fewer pregnancies are exposed, but those exposed suffer a greater disadvantage in fetal growth. The economic upturn in the last decade did not appear to weaken the association between maternal social disadvantage and decreased fetal growth.

Background: Early life exposure to respiratory diseases is associated with lung impairment in adulthood. The objective of this study was to investigate morbidity, and respiratory and other cause specific mortality, among people who reported a medical history of bronchitis, pneumonia and asthma early in life., Methods: We studied an historical cohort of male students who attended Glasgow University between 1948 and 1968 and for whom long term follow-up and cause specific mortality were available (9544 students, 1553 deaths). A medical history of respiratory diseases, including bronchitis, pneumonia and asthma, along with other disease risk factors and socioeconomic conditions, were collected during university health examinations. A subsample responded to a postal follow-up in adulthood (n = 4044), which included respiratory and other chronic disease questions., Results: A medical history of a respiratory disease (bronchitis, pneumonia and asthma) in early life was associated with a 57% greater risk of overall respiratory disease mortality in adulthood and a more than twofold increase in chronic obstructive pulmonary disease mortality (fully adjusted hazard ratio (HR) 2.37; 95% CI 1.16, 4.83). In addition, students reporting a history of bronchitis had a 38% higher risk of cardiovascular disease mortality (95% CI 1.06, 1.80). Respiratory disease in early life was also associated with a higher risk in adulthood of chronic phlegm, dyspnoea and doctor's diagnosis of asthma, bronchitis and emphysema (adjusted odds ratios ranging from 1.40 to 6.95 for these outcomes)., Conclusion: An early life history of respiratory diseases is associated with higher mortality and morbidity risk in adulthood in men, the associations being seen particularly for respiratory related and cardiovascular deaths among those with a history of bronchitis. All early life respiratory diseases appeared to be negatively associated with later adult respiratory health.

Objective: To examine the socioeconomic patterns and time trends in fetal growth in Denmark, Finland, Norway, and Sweden from 1981 to 2000., Design and Settings: Data on all live-born singleton births was drawn from national population registries in each of the four countries (Denmark n = 1,077,584; Finland n = 400,442; Norway n = 929,458; Sweden n = 1,761,562)., Main Outcome Measure: Slope index of inequality (SII) and mean differences in birthweight for gestational age, SII and risk differences in small-for-gestational-age (SGA) and large-for-gestational-age (LGA) infants., Results: In all countries, gradients in fetal growth by parental education existed. Low parental education was associated with lower birthweight, increased risk of SGA and decreased risk of LGA. Mother's education exerted the strongest influence on outcomes, whereas father's education had a weaker effect. The educational gradients as measured by the SII were generally steepest in Denmark, followed by Norway, Sweden, and Finland. From 1981 to 2000, the educational gradients in birthweight decreased in all countries, except Denmark where it increased. All countries experienced small decreases in the educational gradient in SGA over time., Conclusion: The economic recession in Denmark in the 1980s was concurrent with an increase in disparities in fetal growth, whereas the economic recession in Finland and Sweden in the early 1990s did not substantially increase the socioeconomic inequality in fetal growth. The economic growth in the later part of the 1990s may have diminished the socioeconomic inequality in fetal growth in Finland, Norway, and Sweden.

Study Objective: To examine the separate associations of leg length, a biomarker of prepubertal exposures and growth, and trunk length with adult levels of liver enzymes: alanine aminotransferase (ALT), gamma-glutamyltransferase (GGT), aspartate transaminase (AST) and alkaline phosphatase (ALP)., Methods: A cross-sectional analysis of baseline data from the British Women's Health and Heart Study, a random sample of British women aged 60-79 years., Results: Leg length was inversely associated with age-adjusted levels of ALT, GGT and ALP. These associations remained when controlling for childhood and adulthood social class, physical activity, smoking, alcohol consumption, waist-to-hip ratio and trunk length. Trunk length was positively associated with ALT and inversely associated with ALP and the associations remained when adjusting for covariables., Conclusions: Adult liver function is affected by early life environmental exposures as reflected in leg length, and this may suggest common childhood influences on liver development and adult risk of diabetes and coronary heart disease. Further studies with detailed measures of early life exposures relevant to leg length would be valuable in identifying any specific exposures contributing to adult liver function and cardiovascular disease.

Objectives: To quantify measurement error in the estimation of family diet intakes using 7-day household food inventories and to investigate the effect of measurement-error adjustment on diet-disease associations., Design and Setting: Historical cohort study in 16 districts in England and Scotland, between 1937 and 1939., Subjects: 4999 children from 1352 families in the Carnegie Survey of Diet and Health. 86.6% of these children were traced as adults and form the Boyd Orr cohort. The reproducibility analysis was based on 195 families with two assessments of family diet recorded 3-15 months apart., Methods: Intraclass correlation coefficients (ICCs) were calculated for a variety of nutrients and food groups. Diet-cancer associations reported previously in the Boyd Orr cohort were reassessed using two methods: (a) the ICC and (b) the regression calibration., Main Results: The ICCs for the dietary intakes ranged from 0.44 (beta carotene) to 0.85 (milk and milk products). The crude fully adjusted hazard ratio (HR) for cancer mortality per 1 MJ/day increase in energy intake was 1.15 (95% CI 1.06 to 1.24). After adjustment using the ICC for energy (0.80) the HR (95% CI) increased to 1.19 (1.08 to 1.31), and the estimate from regression calibration was 1.14 (0.98 to 1.32). The crude fully adjusted odds ratio (OR) for cancer incidence per 40 g/day increase in fruit intake was 0.84 (95% CI 0.73 to 0.97). After adjustment using the fruit ICC (0.78) it became 0.81 (0.67 to 0.96) and the OR derived from regression calibration was 0.81 (0.59 to 1.10)., Conclusions: The diet-disease relationships for the dietary intakes with low measurement error were robust to adjustment for measurement error.

Background: The association between the R allele of PON1 Q192R and symptoms reported by sheep dippers and Gulf War veterans has been used to suggest a biological basis for these symptoms. In the absence of such studies in non-occupational populations, these conclusions may not be valid., Objective: To examine the association of paraoxonase (PON1) Q192R with a report of ever being diagnosed with depression among a random sample of 3266 British women, aged 60-79 years., Results: The R allele of PON1 Q192R was associated with depression: per-allele odds ratio 1.22 (95% confidence interval: 1.05 to 1.41) in this population., Conclusions: These findings suggest that the association of PON1 Q192R with symptoms of depression in occupationally exposed groups may be driven by exposure to toxins that everyone in the general population is exposed to rather than exposure to toxins specifically used by sheep dippers or Gulf War veterans, or that other mechanisms underlie the association. This is because the study population in which we have found an association consisted of British women aged 60-79 years, few of whom were sheep dippers or Gulf War veterans. When using genotype-outcome associations to infer causality with respect to an environmental exposure modified by the genotype, it is important to examine these associations in general populations and in those specifically exposed to the putative agent. The possible role of PON1 Q192R in psychiatric morbidity requires further examination.

Average paternal age in the UK is increasing. The public health implications of this trend have not been widely anticipated or debated. This commentary aims to contribute to such a debate. Accumulated chromosomal aberrations and mutations occurring during the maturation of male germ cells are thought to be responsible for the increased risk of certain conditions with older fathers. Growing evidence shows that the offspring of older fathers have reduced fertility and an increased risk of birth defects, some cancers, and schizophrenia. Adverse health outcomes should be weighed up against advantages for children born to older parents, mindful that these societal advantages are likely to change over time.

Background: This study examined whether psychological distress might be a predictor of chronic obstructive pulmonary disease (COPD)., Method: The relation between psychological distress at baseline, measured by the general health questionnaire (GHQ), and chronic bronchitis three years later, as measured by the Medical Research Council (MRC) bronchitis questionnaire and forced expiratory flow in one second (FEV(1)), was examined in 1682 men and 2203 women from the Renfrew and Paisley (MIDSPAN) study. The analyses were run on men and women separately and adjustments were made for age, socioeconomic position, and lung function at baseline (FEV(1)). People with chronic diseases at baseline were then excluded to give a "healthy" baseline cohort. The effect of psychological distress on individual components of the MRC bronchitis questionnaire and FEV(1) was also assessed., Results: In multivariate analyses of the whole cohort baseline psychological distress in women was associated with reduced FEV(1) at follow up (OR 1.31 95% CI 1.0 to 1.73) after adjustment. In women, in the healthy cohort, psychological distress was associated with chronic bronchitis (OR 2.00, 95% CI 1.16 to 3.46), symptoms of bronchial infection (OR 2.14, 95% CI 1.44 to 3.19), symptoms of breathlessness (OR 3.02, 95% CI 1.99 to 4.59), and reduced FEV(1) (OR 1.62, 95% CI 1.13 to 2.32). In men psychological distress predicted symptoms of bronchial infection (OR 2.09, 95% CI 1.28 to 3.42)., Conclusion: This study supports research suggesting that psychological distress is associated with COPD and shows that psychological distress predicts COPD in women. The robustness of the association and the exact mechanism requires further investigation.

Study Objectives: There are contradictory perspectives on the importance of conventional coronary heart disease (CHD) risk factors in explaining population levels and social gradients in CHD. This study examined the contribution of conventional CHD risk factors (smoking, hypertension, dyslipidaemia, and diabetes) to explaining population levels and to absolute and relative social inequalities in CHD. This was investigated in an entire population and by creating a low risk sub-population with no smoking, dyslipidaemia, diabetes, and hypertension to simulate what would happen to relative and social inequalities in CHD if conventional risk factors were removed., Design, Setting, and Participants: Population based study of 2682 eastern Finnish men aged 42, 48, 54, 60 at baseline with 10.5 years average follow up of fatal (ICD9 codes 410-414) and non-fatal (MONICA criteria) CHD events., Main Results: In the whole population, 94.6% of events occurred among men exposed to at least one conventional risk factor, with a PAR of 68%. Adjustment for conventional risk factors reduced relative social inequality by 24%. However, in a low risk population free from conventional risk factors, absolute social inequality reduced by 72%., Conclusions: Conventional risk factors explain the majority of absolute social inequality in CHD because conventional risk factors explain the vast majority of CHD cases in the population. However, the role of conventional risk factors in explaining relative social inequality was modest. This apparent paradox may arise in populations where inequalities in conventional risk factors between social groups are low, relative to the high levels of conventional risk factors within every social group. If the concern is to reduce the overall population health burden of CHD and the disproportionate population health burden associated with the social inequalities in CHD, then reducing conventional risk factors will do the job.

This is the second part of a glossary on indicators of socioeconomic position used in health research (the first part was published in the January issue of the journal).

This glossary presents a comprehensive list of indicators of socioeconomic position used in health research. A description of what they intend to measure is given together with how data are elicited and the advantages and limitation of the indicators. The glossary is divided into two parts for journal publication but the intention is that it should be used as one piece. The second part highlights a life course approach and will be published in the next issue of the journal.

Background: Recent epidemiological studies consistently report an inverse association between sibship size and allergic disease, but evidence from individuals born before the 1980s is inconsistent. As information on relative permanence of this finding may offer clues to its biological explanation, the association between sibship size and allergic disease in individuals born between 1918 and 1952 was investigated., Methods: Cross sectional surveys conducted by the Student Health Service at the University of Glasgow (1948-68) provided data on 14 140 men and women aged 16-30 years at the time of examination. The main outcome measures studied were self-reported asthma, eczema-urticaria, and hay fever., Results: A total of 1677 individuals (11.9%) provided a positive history of at least one of the three allergic diseases: 457 (3.2%) asthma, 594 (4.2%) eczema-urticaria, and 885 (6.3%) hay fever. Compared with those without siblings (reference odds ratio = 1), the odds ratios (95% confidence intervals) for having any allergic disease among those with one, two or three siblings were 0.86 (0.75 to 0.99), 0.80 (0.69 to 0.93), and 0.70 (0.60 to 0.83), respectively (p(trend)<0.001). Increasing birth order and low socioeconomic position in childhood were associated with a lower risk of allergy. Adjustment for birth order, year of birth, age, sex, socioeconomic position in childhood, and family history of allergy did not materially alter the results., Conclusions: There is a robust inverse association between sibship size and allergic disease even among people born in the first half of the 20th century. These results favour relatively time-independent explanations for this phenomenon (such as the hygiene hypothesis or parity related changes in the intrauterine environment) over new environmental exposures.

Background: The aim of this study was to examine the associations between birth weight and lung function in a cohort of women aged 60-79 years and to combine these results with those from other published studies in a systematic review and meta-analysis., Methods: The associations of self-reported birth weight with adult lung function (forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and forced expiratory flow rate during mid expiration (FEF(25-75)), all measured using standard procedures, were assessed in a cross sectional study of 2257 British women aged 60-79 years. A detailed literature search was used to identify all published studies of the association, and meta-analysis was used to pool the results from our study and all published studies., Results: There were positive linear associations between birth weight and all three measures of lung function in simple age and examining nurse adjusted regression models. However, with adjustment for height (squared), all three associations attenuated towards the null: adjusted (age, nurse, height2) change in FEV1 per 1 kg birth weight was 0.01 l (95% CI -0.02 to 0.04); in FVC was 0.02 l (95% CI -0.02 to 0.07), and in FEF(25-75) was 0.00 l (95% CI -0.04 to 0.04). Further adjustment for life course socioeconomic position, adult body mass index, and smoking did not alter these associations. The results were similar among life long non-smokers and those who had ever smoked. A meta-analysis of eight studies of adults suggested that there was a positive association between birth weight and FEV1: pooled increase in FEV1 per 1 kg in birth weight 0.048 l (95% CI 0.026 to 0.070) adjusted for age, smoking, and height (or height squared). There was no evidence of small study bias in this meta-analysis., Conclusions: There is a modest positive association between birth weight and lung function which indicates that intrauterine factors might have a role in lung development.

Objective: To examine the associations of childhood and adult measurements of socioeconomic position with coronary heart disease (CHD) risk., Methods: Cross sectional and prospective analysis of a cohort of 4286 British women who were aged 60-79 years at baseline. Among these women there were 694 prevalent cases of CHD and 182 new incident cases among 13 217 person years of follow up of women who were free of CHD at baseline., Results: All measurements of socioeconomic position were associated with increased prevalent and incident CHD in simple age adjusted models. There was a cumulative effect, on prevalent and incident CHD, of socioeconomic position across the lifecourse. This effect was not fully explained by adult CHD risk factors. The adjusted odds ratio of prevalent CHD for each additional adverse (out of 10) lifecourse socioeconomic indicator was 1.11 (95% confidence interval: 1.06, 1.16). The magnitude of the effect of lifecourse socioeconomic position was the same in women who were lifelong non-smokers as in those who had been or were smokers., Conclusion: Adverse socioeconomic position across the lifecourse increases CHD risk cumulatively and this effect is not fully explained by adult risk factors. Specifically in this cohort of women cigarette smoking does not seem to explain the association between adverse lifecourse socioeconomic position and CHD risk.

Study Objective: To examine the association between maternal diet in pregnancy and offspring height, sitting height, and leg length., Design: Cohort study., Setting: South west England., Participants: 6663 singletons (51% male) enrolled in the Avon longitudinal study of parents and children, with information on their mother's diet in late pregnancy (obtained by food frequency questionnaire) and their own height recorded at age 7.5 years., Main Results: Before adjustment, maternal magnesium, iron, and vitamin C were the nutrients most consistently associated with offspring height and its components. However, adjusting for potential confounders weakened all relations considerably. For example, a standard deviation (SD) increase in magnesium intake was associated with a 0.10 (-0.07, 0.14) SD unit increase in height before adjustment, which was reduced to 0.05 (0.01, 0.08) SD units after adjustment, and a SD unit increase in iron intake was associated with 0.08 (0.05, 0.12) and 0.04 (0.01, 0.08) SD unit increases in height before and after adjustment respectively. No other dietary variables were associated with height or its components after adjustment., Conclusions: These findings do not provide evidence that maternal diet in pregnancy has an important influence on offspring height, sitting height, or leg length in well nourished populations, although effects may emerge as offspring become older.

Study Objective: To investigate the association of having been breast fed with cardiovascular disease risk factors, incidence, and mortality., Design: Prospective cohort study., Setting: Caerphilly, South Wales., Participants: All men aged 45-59 years living in and around the study area. Of 2818 eligible men, 2512 (89%) were seen. Altogether 1580 men (63%) obtained details of how they had been fed in infancy (ever breast fed or only bottle fed) from their mother or a close female relative. A subset of 1062 subjects reported on whether bottle fed or the duration of breast feeding if breast fed., Main Results: Breast feeding was not associated with stature, blood pressure, insulin resistance, total cholesterol, or fibrinogen. In fully adjusted models (controlling for age, birth order, and social position in childhood and adulthood), breast feeding was associated with greater body mass index than bottle feeding (difference: 0.41 kg/m(2) (95% CI: 0.01 to 0.81). There was a positive association between breast feeding and coronary heart disease mortality (hazard ratio: 1.73; 1.17 to 2.55) and incidence (1.54; 1.17 to 2.04) (fully adjusted models). There was no evidence of a duration-response effect, which might be expected if an adverse effect of breast feeding was causal., Conclusion: These data provide little evidence of a protective influence of breast feeding on cardiovascular disease risk factors, incidence, or mortality. A possible adverse effect of breast feeding on coronary heart disease incidence was observed but may have a number of explanations, including selection and information bias. In view of these limitations, further long term studies with improved measures of infant feeding are required to confirm or refute these findings.

Study Objective: The aims of this study are to confirm the association between psychological distress and coronary heart disease (CHD) using an epidemiological community study with hospital admissions data and to examine if any association is explained by existing illness., Design: Prospective cohort study modelling the association between psychological distress, measured using the 30 item general health questionnaire (GHQ), and hospital admissions data for CHD (ICD 410-414), using proportional hazards modelling adjusted for sociodemographic, CHD risk factors, and angina, bronchitis, diabetes, ischaemia, and stroke., Setting: Two suburbs of Glasgow, Renfrew and Paisley, in Scotland., Participants: 6575 men and women aged 45-64 years from Paisley., Main Results: Five year CHD risk in distressed men compared with non-distressed men was 1.78 (95% confidence intervals (CI), 1.15 to 2.75) in age adjusted analysis, 1.78 (95% CI, 1.14 to 2.79) with sociodemographic and CHD risk factor adjustment, and 1.61 (95% CI 1.02 to 2.55) with additional adjustment for existing illness. Psychological distress was unrelated to five year CHD risk in women. In further analysis, compared with healthy, non-distressed men, distressed physically ill men had a greater risk of CHD than non-distressed physically ill men, a relative risk of 4.01 (95% CI 2.42 to 6.66) compared with 2.12 (95% CI 1.35 to 3.32)., Conclusion: The association of psychological distress with an increased risk of five year CHD risk in men could be a function of baseline physical illness but an effect independent of physical illness cannot be ruled out. Its presence among physically ill men greatly increases CHD risk.

Objective: To determine the role of central adiposity in explaining sex differences in carotid intima media thickness (IMT)., Design: Cross sectional survey., Setting: Two British towns., Participants: 800 men and women aged 56-75 years., Main Outcome Measures: Carotid IMT., Results: There was a continuous linear association between waist-hip ratio and IMT in both men and women. The magnitude of the association between waist to hip ratio and IMT was identical in both sexes. In age adjusted analyses IMT was 14% greater in men compared with women (age adjusted male to female ratio of geometric means 1.14; 95% confidence interval 1.07 to 1.21) with adjustment for waist to hip ratio this attenuated to no difference (1.00; 0.92 to 1.09). Adjustment for body mass index and for lifestyle risk factors had very little effect on the sex difference in mean intima media thickness., Conclusions: Sex differences in body fat distribution may explain sex differences in arterial atherosclerosis.

Objective: To examine whether increasing cumulative deprivation has an incremental effect on total as well as cause specific mortality., Design: Census data on housing conditions as indicators of deprivation from 1960, 1970, and 1980 were linked to 1990-98 death registrations. Relative indices of inequalities were computed for housing conditions to measure the cumulative impact of differences in social conditions., Participants: 97 381 (71.1%) 30-49 year old and 70701 (80.0%) 50-69 year old inhabitants of Oslo, Norway, in 1990 with census information on housing conditions and recorded length of education., Main Results: Mortality risk was increased when all censuses' housing conditions were summed in both age groups and sex. The cause specific analysis indicated such an effect particularly for coronary heart disease, chronic obstructive lung disease, and smoking related cancers. Violent deaths were essentially associated with housing conditions closer to the time of death in men in both age groups and in young women., Conclusions: To fully account for socially mediated risk of death, a full life course approach should be adopted. The relative importance of each stage seems to vary by cause of death.

Objective: To examine the association between a history of type 2 diabetes and birth weight of offspring and grandchildren., Design: Prospective observational study. Diabetic status, as reported by mothers (F1 generation) was collected on grandparents (F0) of babies (F2) born to mothers (F1) who participated in a study of maternal and child health. Associations between risk of grandparental diabetes and birth weight in mothers (F1) and grandchildren (F2) were analysed using linear and logistic regression., Setting: Avon: comprising of the city of Bristol and surrounding areas., Participants: 12 076 singleton babies (F2), their parents (F1) and maternal and paternal grandparents (F0)., Results: Women (F1) who had no parents with type 2 diabetes had lower birth weights than women with one or two diabetic parents, after controlling for the age of both parents. There was a U shaped association between maternal birth weight and grandmaternal diabetes, but no evidence of an association with grandpaternal diabetes. The grandchildren of maternal grandparents with type 2 diabetes were more likely to be in the top tertile of birth weight than grandchildren of non-diabetics. There was evidence for an inverted U shaped association between birth weight of grandchildren and diabetes in paternal grandmothers., Conclusions: This is the first study to show intergenerational associations between type 2 diabetes in one generation and birth weight in the subsequent two generations. While the study has limitations mainly because of missing data, the findings nevertheless provide some support for the role of developmental intrauterine effects and genetically determined insulin resistance in impaired insulin mediated growth in the fetus.

Background: A study was undertaken to assess the associations between indicators of early life socioeconomic position and lung function in older adulthood., Methods: The associations of self-reported indicators of childhood socioeconomic position with adult lung function (forced expiratory volume in 1 second (FEV(1)), forced vital capacity (FVC), and forced expiratory flow rate during mid expiration (FEF(25-75)), all measured using standard procedures) were assessed in a cross sectional study of 3641 British women aged 60-79 years., Results: In confounder adjusted analyses, each individual indicator of childhood circumstances was inversely associated with each measure of lung function. In the fully adjusted models (including mutual adjustment for each of the other indicators of childhood socioeconomic circumstances), only childhood occupational social class and access to a car were associated with lung function in adulthood. However, there were strong linear trends of worsening lung function with greater numbers of indicators of childhood poverty (all p values <0.001)., Conclusions: Childhood poverty is associated with poorer lung function in women aged 60-79 years. Adverse childhood circumstances that affect both lung growth and development and cardiovascular disease in later life may explain some of the well known associations between poor lung function and cardiovascular disease, or lung function may be an important mediating factor in this association.

Objectives: (1) To assess the association between birth weight and coronary heart disease (CHD) risk in a cohort of post-menopausal women, (2) to determine the combined effects of birth weight and adult body mass index on CHD, (3) to assess the role of insulin resistance as a mediating factor in the associations., Design: Cross sectional survey., Setting: 23 British towns., Participants: 1394 women aged 60-79 years., Main Outcome Measures: coronary heart disease (n = 199 cases)., Results: Birth weight was inversely associated with CHD: age and survivor status of participant's mother adjusted odds ratio (95% confidence intervals) per 1 standard deviation (0.80 kg) increase in birth weight was 0.84 (0.72 to 0.97). This association strengthened to 0.80 (0.68 to 0.93) with further adjustment for adult body mass index, but there was no evidence of an interaction between birth weight and adult body mass index (p = 0.61). The association was not confounded by childhood or adulthood socioeconomic position or by adult smoking status of the participant. Adjustment for components of the insulin resistance syndrome attenuated the association to 0.87 (0.72 to 1.03)., Conclusions: Intrauterine exposures that affect fetal growth also affect future adult CHD risk. The inverse association between birth weight and CHD may in part be mediated via insulin resistance.

Objective: To investigate growth trajectories and predictive factors for those with low birth weight and high adult BMI., Design: Birth cohort study., Setting: England, Scotland, and Wales., Participants: All born 3-9 March, 1958., Main Outcome Measures: People at "high risk" of adult disease were defined as having a combination of lower birth weight (in the lowest third of the distribution) and high BMI (in the highest third of the distribution at age 33)., Results: 284 of 3462 men and 338 of 3555 women were identified as "high risk". This group was shorter than other cohort members at age 7, on average by 1.2 cm (boys) and 1.8 cm (girls), with a deficit of about 3 cm in adult height. The "high risk" group had a similar mean weight to other subjects at age 7, but were heavier thereafter through to age 23. BMI was increased at all ages in the "high risk" group. Independent predictors include paternal BMI, maternal height and smoking in pregnancy, and social class. For each SD increase in father's BMI the odds of low birth weight/high BMI increased by about 20%. For maternal height, a 1 cm increase reduced the odds of low birth weight/high BMI by about 5%. Increased ORs for "high risk" were found for those with manual social origins (1.61 for men; 1.49 for women) and for maternal smoking in pregnancy (1.79 and 2.27 respectively)., Conclusions: Maternal short stature, low social class, and smoking during pregnancy influence the development of "high risk" for adult chronic disease. The causes of high risk therefore seem to reside in utero and even earlier, in the mother's lifetime, with adverse conditions having a detrimental affect and favourable conditions protecting against high risk.

Study Objective: To determine the association between a clinician assessment of temperament in early adulthood and cause specific mortality., Design: Prospective observational study., Setting: Glasgow University., Participants: 9239 male former students aged 16-30 (mean 20.5) years who participated in an ongoing health survey from 1948-68. A physician recorded free text assessment of temperament, which seemed to capture aspects of personality (trait) and mental health (state), was coded into: stable, anxious, schizoid, hypomanic, odd, depressed, immature, hypochondriacal, unstable, and obsessive. Associations between temperament and mortality were investigated using Cox proportional hazards models., Main Results: There were 878 deaths. Most students-8342 (90.3%)-were assessed as stable, the remaining 897 (9.7%) having at least one, and 103 (1.1%) having more than one, temperament type. The second most common temperament was anxiety, recorded in 520 (5.6%) students. In multivariable analyses, having at least one temperament type was associated with increased all cause and stroke mortality, hazard ratios (95% confidence intervals): 1.23 (1.01 to 1.50) and 1.95 (1.06 to 3.59) respectively, compared with stable students. Students with more than one temperament type had higher risk of death from: all causes, 2.05 (1.36 to 3.09); stroke, 3.26 (1.01 to 10.56); and cancer, 2.90 (1.62 to 5.20). Anxiety was positively associated with all cause and cancer mortality, respective hazard ratios: 1.36 (1.07 to 1.72) and 1.51 (1.04 to 2.20). Men labelled hypomanic had increased cardiovascular mortality risk, 1.90 (1.05 to 3.44)., Conclusions: Markers of early adult psychological distress are associated with increased mortality. Mechanisms underlying these associations require investigation.

Health impact assessment (HIA) seeks to expand evaluation of policy and programmes in all sectors, both private and public, to include their impact on population health. While the idea that the public's health is affected by a broad array of social and economic policies is not new and dates back well over two centuries, what is new is the notion-increasingly adopted by major health institutions, such as the World Health Organisation (WHO) and the United Kingdom National Health Services (NHS)-that health should be an explicit consideration when evaluating all public policies. In this article, it is argued that while HIA has the potential to enhance recognition of societal determinants of health and of intersectoral responsibility for health, its pitfalls warrant critical attention. Greater clarity is required regarding criteria for initiating, conducting, and completing HIA, including rules pertaining to decision making, enforcement, compliance, plus paying for their conduct. Critical debate over the promise, process, and pitfalls of HIA needs to be informed by multiple disciplines and perspectives from diverse people and regions of the world.

Study Objective: To determine whether measures of income and wealth are associated with poor self rated health and GHQ depression., Design: Whitehall II study of London based civil servants re-interviewed between 1997-1999; 7162 participants., Main Results: A twofold age adjusted difference in morbidity was observed between the top and bottom of the personal income hierarchy for both sexes. For household income and particularly for wealth these associations are stronger. After adjusting for health at baseline the associations between personal income and both health outcomes are reduced by about 40%-60%. For household income the attenuation is somewhat smaller and for wealth is about 30%. Adjusting for other sociodemographic factors leads to further attenuation of the effects., Conclusions: The associations between income, particularly personal income, and morbidity can be largely accounted for by pre-existing health and other measures of social position. The strong independent association between household wealth-a measure of income earned over decades and across generations-and morbidity are likely to be related to a set of early and current material and psychosocial benefits.

Adverse psychosocial exposure or "misery" is associated with physical disease. This association may not be causal. Rather it may reflect issues of reverse causation, reporting bias, and confounding by aspects of the material environment typically associated with misery. A non-causal relation will not form the basis of effective public health interventions. This may be why psychosocial interventions have, so far, showed little effect on objective physical health outcomes. This paper reviews evidence for the "psychosocial hypothesis" and suggests strategies for clarifying these issues. It concludes that, although misery is clearly a bad thing as it erodes people's quality of life, there is little evidence that psychosocial factors cause physical disease. In the absence of better evidence, suggestions that psychosocial interventions are needed to improve population physical health, in both absolute and relative terms, seem premature.