Search

The gene-centric Human CVD BeadChip (Illumina) approach is employed to determine and identify different association signals that are shown to be linked with lipids and apoliproteins. The individual differences observed in the potential of blood lipids to assess CVD risk are shown to be highly related to the multiple common alleles.

Objectives. We examined the association between health behaviors and socioeconomic status (SES) in childhood and adult life. Methods. Self-reported diet, smoking, and physical activity were determined among 3523 women aged 60 to 79 years recruited from general practices in 23 British towns from 1999 through 2001. Results. The most affluent women reported eating more fruit, vegetables, chicken, and fish and less red or processed meat than did less affluent women. Affluent women were less likely to smoke and more likely to exercise. Life course SES did not influence the types of fat, bread, and milk consumed. Adult SES predicted consumption of all foods considered and predicted smoking and physical activity habits independently of childhood SES. Childhood SES predicted fruit and vegetable consumption independently of adult SES and, to a lesser extent, predicted physical activity. Downward social mobility over the life course was associated with poorer diets and reduced physical activity. Conclusions. Among older women, healthful eating and physical activity were associated with both current and childhood SES. Interventions designed to improve social inequalities in health behaviors should be applied during both childhood and adult life. (Am J Public Health. 2009;99:320-327. doi:10.2105/ AJPH.2007.129288)

The study attempts to evaluate published evidence to try and establish a relationship between lower birth weight and the increased risk of type 2 diabetes. The results conclude that birth weight is inversely related to the risk of type 2 diabetes.

Background Raised C-reactive protein (CRP) is a risk factor for type 2 diabetes. According to the Mendelian randomization method, the association is likely to be causal if genetic variants that affect CRP level are associated with markers of diabetes development and diabetes. Our objective was to examine the nature of the association between CRP phenotype and diabetes development using CRP haplotypes as instrumental variables. Methods and Findings We genotyped three tagging SNPs (CRP+2302G > A; CRP+1444T > C; CRP+4899T > G) in the CRP gene and measured serum CRP in 5,274 men and women at mean ages 49 and 61 y (Whitehall II Study). Homeostasis model assessment-insulin resistance (HOMA-IR) and hemoglobin A1c (HbA1c) were measured at age 61 y. Diabetes was ascertained by glucose tolerance test and self-report. Common major haplotypes were strongly associated with serum CRP levels, but unrelated to obesity, blood pressure, and socioeconomic position, which may confound the association between CRP and diabetes risk. Serum CRP was associated with these potential confounding factors. After adjustment for age and sex, baseline serum CRP was associated with incident diabetes (hazard ratio = 1.39 [95% confidence interval 1.29-1.51], HOMA-IR, and HbA1c, but the associations were considerably attenuated on adjustment for potential confounding factors. In contrast, CRP haplotypes were not associated with HOMA-IR or HbA1c (p=0.52-0.92). The associations of CRP with HOMA-IR and HbA1c were all null when examined using instrumental variables analysis, with genetic variants as the instrument for serum CRP. Instrumental variables estimates differed from the directly observed associations (p = 0.007-0.11). Pooled analysis of CRP haplotypes and diabetes in Whitehall II and Northwick Park Heart Study II produced null findings (p = 0.25-0.88). Analyses based on the Wellcome Trust Case Control Consortium (1,923 diabetes cases, 2,932 controls) using three SNPs in tight linkage disequilibrium with our tagging SNPs also demonstrated null associations. Conclusions Observed associations between serum CRP and insulin resistance, glycemia, and diabetes are likely to be noncausal. Inflammation may play a causal role via upstream effectors rather than the downstream marker CRP. The Editors' Summary of this article follows the references., Introduction C-reactive protein (CRP) is a nonspecific marker of systemic inflammation that predicts incident type 2 diabetes. Chronic low-grade inflammation may induce insulin resistance and is a candidate pathway leading [...]

Background The developmental overnutrition hypothesis suggests that greater maternal obesity during pregnancy results in increased offspring adiposity in later life. If true, this would result in the obesity epidemic progressing across generations irrespective of environmental or genetic changes. It is therefore important to robustly test this hypothesis. Methods and Findings We explored this hypothesis by comparing the associations of maternal and paternal prepregnancy body mass index (BMI) with offspring dual energy X-ray absorptiometry (DXA)-determined fat mass measured at 9 to 11 y (4,091 parent-offspring trios) and by using maternal FTO genotype, controlling for offspring FTO genotype, as an instrument for maternal adiposity. Both maternal and paternal BMI were positively associated with offspring fat mass, but the maternal association effect size was larger than that in the paternal association in all models: mean difference in offspring sex- and age-standardised fat mass z-score per 1 standard deviation BMI 0.24 (95% confidence interval [CI]: 0.22 to 0.26) for maternal BMI versus 0.13 (95% CI: 0.11, 0.15) for paternal BMI; p-value for difference in effect < 0.001. The stronger maternal association was robust to sensitivity analyses assuming levels of non-paternity up to 20%. When maternal FTO, controlling for offspring FTO, was used as an instrument for the effect of maternal adiposity, the mean difference in offspring fat mass z-score per 1 standard deviation maternal BMI was -0.08 (95% CI: -0.56 to 0.41), with no strong statistical evidence that this differed from the observational ordinary least squares analyses (p = 0.17). Conclusions Neither our parental comparisons nor the use of FTO genotype as an instrumental variable, suggest that greater maternal BMI during offspring development has a marked effect on offspring fat mass at age 9-11 y. Developmental overnutrition related to greater maternal BMI is unlikely to have driven the recent obesity epidemic. doi:10.1371/journal.pmed.0050033, Introduction According to the developmental overnutrition hypothesis, high maternal glucose and high free fatty acid and amino acid plasma concentrations result in permanent changes in appetite control, neuroendocrine functioning, or [...]

Background A high proportion of women start pregnancy overweight or obese. According to the developmental overnutrition hypothesis, this could lead offspring to have metabolic disruption throughout their lives and thus perpetuate the obesity epidemic across generations. Concerns about this hypothesis are influencing antenatal care. However, it is unknown whether maternal pregnancy adiposity is associated with long-term risk of adverse metabolic profiles in offspring, and if so, whether this association is causal, via intrauterine mechanisms, or explained by shared familial (genetic, lifestyle, socioeconomic) characteristics. We aimed to determine if associations between maternal body mass index (BMI) and offspring systemic cardio-metabolic profile are causal, via intrauterine mechanisms, or due to shared familial factors. Methods and findings We used 1- and 2-stage individual participant data (IPD) meta-analysis, and a negative-control (paternal BMI) to examine the association between maternal pre-pregnancy BMI and offspring serum metabolome from 3 European birth cohorts (offspring age at blood collection: 16, 17, and 31 years). Circulating metabolic traits were quantified by high-throughput nuclear magnetic resonance metabolomics. Results from 1-stage IPD meta-analysis (N = 5327 to 5377 mother-father-offspring trios) showed that increasing maternal and paternal BMI was associated with an adverse cardio-metabolic profile in offspring. We observed strong positive associations with very-low-density lipoprotein (VLDL)-lipoproteins, VLDL-cholesterol (C), VLDL-triglycerides, VLDL-diameter, branched/aromatic amino acids, glycoprotein acetyls, and triglycerides, and strong negative associations with high-density lipoprotein (HDL), HDL-diameter, HDL-C, HDL.sub.2 -C, and HDL.sub.3 -C (all P 0.003, equivalent to P > 0.05 after accounting for multiple testing). Results were similar in each individual cohort, and in the 2-stage analysis. Offspring BMI showed similar patterns of cross-sectional association with metabolic profile as for parental pre-pregnancy BMI associations but with greater magnitudes. Adjustment of parental BMI-offspring metabolic traits associations for offspring BMI suggested the parental associations were largely due to the association of parental BMI with offspring BMI. Limitations of this study are that inferences cannot be drawn about the role of circulating maternal fetal fuels (i.e., glucose, lipids, fatty acids, and amino acids) on later offspring metabolic profile. In addition, BMI may not reflect potential effects of maternal pregnancy fat distribution. Conclusion Our findings suggest that maternal BMI-offspring metabolome associations are likely to be largely due to shared genetic or familial lifestyle confounding rather than to intrauterine mechanisms., Author(s): Diana L. Santos Ferreira 1,2, Dylan M. Williams 3,4, Antti J. Kangas 5,6, Pasi Soininen 5,6,7, Mika Ala-Korpela 1,2,5,6,7, George Davey Smith 1,2, Marjo-Riitta Jarvelin 3,6,8,9, Debbie A. Lawlor [...]

Background Both positive and negative associations between higher body mass index (BMI) and Parkinson disease (PD) have been reported in observational studies, but it has been difficult to establish causality because of the possibility of residual confounding or reverse causation. To our knowledge, Mendelian randomisation (MR)-the use of genetic instrumental variables (IVs) to explore causal effects-has not previously been used to test the effect of BMI on PD. Methods and findings Two-sample MR was undertaken using genome-wide association (GWA) study data. The associations between the genetic instruments and BMI were obtained from the GIANT consortium and consisted of the per-allele difference in mean BMI for 77 independent variants that reached genome-wide significance. The per-allele difference in log-odds of PD for each of these variants was estimated from a recent meta-analysis, which included 13,708 cases of PD and 95,282 controls. The inverse-variance weighted method was used to estimate a pooled odds ratio (OR) for the effect of a 5-kg/m.sup.2 higher BMI on PD. Evidence of directional pleiotropy averaged across all variants was sought using MR-Egger regression. Frailty simulations were used to assess whether causal associations were affected by mortality selection. A combined genetic IV expected to confer a lifetime exposure of 5-kg/m.sup.2 higher BMI was associated with a lower risk of PD (OR 0.82, 95% CI 0.69-0.98). MR-Egger regression gave similar results, suggesting that directional pleiotropy was unlikely to be biasing the result (intercept 0.002; p = 0.654). However, the apparent protective influence of higher BMI could be at least partially induced by survival bias in the PD GWA study, as demonstrated by frailty simulations. Other important limitations of this application of MR include the inability to analyse non-linear associations, to undertake subgroup analyses, and to gain mechanistic insights. Conclusions In this large study using two-sample MR, we found that variants known to influence BMI had effects on PD in a manner consistent with higher BMI leading to lower risk of PD. The mechanism underlying this apparent protective effect warrants further study., Author(s): Alastair J. Noyce 1,2, Demis A. Kia 1, Gibran Hemani 3,4, Aude Nicolas 5, T. Ryan Price 5, Eduardo De Pablo-Fernandez 1, Philip C. Haycock 3,4, Patrick A. Lewis [...]

Background There is limited evidence to support the use of customised centile charts to identify those at risk of stillbirth and infant death at term. We sought to determine birth weight thresholds at which mortality and morbidity increased and the predictive ability of noncustomised (accounting for gestational age and sex) and partially customised centiles (additionally accounting for maternal height and parity) to identify fetuses at risk. Methods This is a population-based linkage study of 979,912 term singleton pregnancies in Scotland, United Kingdom, between 1992 and 2010. The main exposures were noncustomised and partially customised birth weight centiles. The primary outcomes were infant death, stillbirth, overall mortality (infant and stillbirth), Apgar score Findings Birth weight [less than or equal to]25th centile was associated with higher risk for all mortality and morbidity outcomes. For stillbirth, low Apgar score, and neonatal unit admission, risk also increased from the 85th centile. Similar patterns and magnitude of associations were observed for both non- and partially customised birth weight centiles. Partially customised birth weight centiles did not improve the discrimination of mortality (AUROC 0.61 [95%CI 0.60, 0.62]) compared with noncustomised birth weight centiles (AUROC 0.62 [95%CI 0.60, 0.63]) and slightly underperformed in reclassifying pregnancies to different risk categories for both fatal and non-fatal adverse outcomes (NRI -0.027 [95% CI -0.039, -0.016], p < 0.001). We were unable to fully customise centile charts because we lacked data on maternal weight and ethnicity. Additional analyses in an independent UK cohort (n = 10,515) suggested that lack of data on ethnicity in this population (in which national statistics show 98% are white British) and maternal weight would have misclassified ~15% of the large-for-gestation fetuses. Conclusions At term, birth weight remains strongly associated with the risk of stillbirth and infant death and neonatal morbidity. Partial customisation does not improve prediction performance. Consideration of early term delivery or closer surveillance for those with a predicted birth weight [less than or equal to]25th or [greater than or equal to]85th centile may reduce adverse outcomes. Replication of the analysis with fully customised centiles accounting for ethnicity is warranted., Author(s): Stamatina Iliodromiti 1,*, Daniel F. Mackay 2, Gordon C. S. Smith 3,4, Jill P. Pell 2, Naveed Sattar 5, Debbie A. Lawlor 6, Scott M. Nelson 1 Introduction Infants [...]

Background It has been suggested that greater maternal adiposity during pregnancy affects lifelong risk of offspring fatness via intrauterine mechanisms. Our aim was to use Mendelian randomisation (MR) to investigate the causal effect of intrauterine exposure to greater maternal body mass index (BMI) on offspring BMI and fat mass from childhood to early adulthood. Methods and Findings We used maternal genetic variants as instrumental variables (IVs) to test the causal effect of maternal BMI in pregnancy on offspring fatness (BMI and dual-energy X-ray absorptiometry [DXA] determined fat mass index [FMI]) in a MR approach. This was investigated, with repeat measurements, from ages 7 to 18 in the Avon Longitudinal Study of Parents and Children (ALSPAC; n = 2,521 to 3,720 for different ages). We then sought to replicate findings with results for BMI at age 6 in Generation R (n = 2,337 for replication sample; n = 6,057 for total pooled sample). In confounder-adjusted multivariable regression in ALSPAC, a 1 standard deviation (SD, equivalent of 3.7 kg/m2) increase in maternal BMI was associated with a 0.25 SD (95% CI 0.21-0.29) increase in offspring BMI at age 7, with similar results at later ages and when FMI was used as the outcome. A weighted genetic risk score was generated from 32 genetic variants robustly associated with BMI (minimum F-statistic = 45 in ALSPAC). The MR results using this genetic risk score as an IV in ALSPAC were close to the null at all ages (e.g., 0.04 SD (95% CI -0.21-0.30) at age 7 and 0.03 SD (95% CI -0.26-0.32) at age 18 per SD increase in maternal BMI), which was similar when a 97 variant generic risk score was used in ALSPAC. When findings from age 7 in ALSPAC were meta-analysed with those from age 6 in Generation R, the pooled confounder-adjusted multivariable regression association was 0.22 SD (95% CI 0.19-0.25) per SD increase in maternal BMI and the pooled MR effect (pooling the 97 variant score results from ALSPAC with the 32 variant score results from Generation R) was 0.05 SD (95%CI -0.11-0.21) per SD increase in maternal BMI (p-value for difference between the two results = 0.05). A number of sensitivity analyses exploring violation of the MR results supported our main findings. However, power was limited for some of the sensitivity tests and further studies with relevant data on maternal, offspring, and paternal genotype are required to obtain more precise (and unbiased) causal estimates. Conclusions Our findings provide little evidence to support a strong causal intrauterine effect of incrementally greater maternal BMI resulting in greater offspring adiposity., Author(s): Rebecca C. Richmond 1,2,*, Nicholas J. Timpson 1,2, Janine F. Felix 3,4,5, Tom Palmer 6, Romy Gaillard 3,4,5, George McMahon 2, George Davey Smith 1,2, Vincent W. Jaddoe 3,4,5, [...]

Background In conventional epidemiology confounding of the exposure of interest with lifestyle or socioeconomic factors, and reverse causation whereby disease status influences exposure rather than vice versa, may invalidate causal interpretations of observed associations. Conversely, genetic variants should not be related to the confounding factors that distort associations in conventional observational epidemiological studies. Furthermore, disease onset will not influence genotype. Therefore, it has been suggested that genetic variants that are known to be associated with a modifiable (nongenetic) risk factor can be used to help determine the causal effect of this modifiable risk factor on disease outcomes. This approach, mendelian randomization, is increasingly being applied within epidemiological studies. However, there is debate about the underlying premise that associations between genotypes and disease outcomes are not confounded by other risk factors. We examined the extent to which genetic variants, on the one hand, and nongenetic environmental exposures or phenotypic characteristics on the other, tend to be associated with each other, to assess the degree of confounding that would exist in conventional epidemiological studies compared with mendelian randomization studies. Methods and Findings We estimated pairwise correlations between nongenetic baseline variables and genetic variables in a cross-sectional study comparing the number of correlations that were statistically significant at the 5%, 1%, and 0.01% level (α = 0.05, 0.01, and 0.0001, respectively) with the number expected by chance if all variables were in fact uncorrelated, using a two-sided binomial exact test. We demonstrate that behavioural, socioeconomic, and physiological factors are strongly interrelated, with 45% of all possible pairwise associations between 96 nongenetic characteristics (n = 4,560 correlations) being significant at the p < 0.01 level (the ratio of observed to expected significant associations was 45; p-value for difference between observed and expected < 0.000001). Similar findings were observed for other levels of significance. In contrast, genetic variants showed no greater association with each other, or with the 96 behavioural, socioeconomic, and physiological factors, than would be expected by chance. Conclusions These data illustrate why observational studies have produced misleading claims regarding potentially causal factors for disease. The findings demonstrate the potential power of a methodology that utilizes genetic variants as indicators of exposure level when studying environmentally modifiable risk factors., Introduction Observational epidemiology has had notable successes, but also high-profile failures, in that it has identified many modifiable exposures apparently increasing or decreasing disease risk that have been revealed by [...]

ABSTRACT Background Evidence suggests that variations in fasting glucose and insulin amongst those without frank type 2 diabetes mellitus are important determinants of cardiovascular disease. However, the relative importance of [...]

Objectives. We examined the associations between socioeconomic position, co-occurrence of behavior-related risk factors, and the effect of these factors on the relative and absolute socioeconomic gradients in coronary heart disease. Methods. We obtained the socioeconomic position of 9337 men and 39255 women who were local government employees aged 17-65 years from employers' records (the Public Sector Study, Finland). A questionnaire survey in 2000-2002 was used to collect data about smoking, heavy alcohol consumption, physical inactivity, obesity, and prevalence of coronary heart disease (myocardial infarction or angina diagnosed by a doctor). Results. The age-adjusted odds of coronary heart disease were 2.1-2.2 times higher for low-income groups than high-income groups for both men and women, and adjustment for risk factors attenuated these associations by 13%-29%. There was no further attenuation with additional adjustment for the number of co-occurring risk factors, although socioeconomic disadvantage was associated with the co-occurrence of multiple risk factors. The absolute difference in coronary heart disease risk between socioeconomic groups could not be attributed to the measured risk factors. Conclusions. Interventions to reduce adult behavior-related risk factors may not completely remove socioeconomic differences in relative or absolute coronary heart disease risk, although they would lessen these effects.

Objectives. We examined associations between childhood intelligence and hospital admissions for injuries in adulthood. Methods. Data were derived from a cohort study (=11 103) involving individuals born in Aberdeen, Scotland, between 1950 and 1956. Results. Overall, 1043 cohort members had at least 1 hospital admission resulting from an unintentional injury over 231 152 person-years of risk. There were inverse linear associations between childhood intelligence assessed at the ages of 7, 9, and 11 years and having had a hospital admission stemming from an unintentional injury (gender-adjusted hazard ratio [HR] for a 1-standard-deviation increase in intelligence test score at age 7 years=0.75; 95% confidence interval [CI] =0.70, 0.80). These associations were not markedly affected by adjustment for childhood socioeconomic status, maternal age or height, birthweight, or childhood growth. However, they were attenuated after adjustment for educational attainment (HR=0.85; 95% C1=0.78, 0.91). Conclusions. Childhood intelligence is related to hospital admissions for injuries in adulthood, and this relationship is partly explained by educational attainment. The association between childhood intelligence and injury may contribute to the association between childhood intelligence and premature mortality demonstrated in several studies. (Am J Public Health. 2007;97:291-297. doi: 10.2105/AJPH.2005.080168)

The role of variation of glucokinase (GCK) in the determination of fasting glucose and birth weight is examined using a tagging single-nucleotide polymorphism (tSNP) approach. A comprehensive analysis of common variation of the glucokinase gene has indicated that this is the first gene to be reproducibly associated with fasting glucose and fetal growth.

Objectives. We assessed the association of father's social class, recorded at the time of birth, with coronary heart disease and stroke in a British cohort of 11 106 individuals born in the 1950s. Methods. Survival analysis was used to relate social class at birth to the occurrence of either fatal or nonfatal coronary heart disease or stroke. Results. Rates of coronary heart disease and stroke increased across the social class distribution from highest to lowest, and patterns of association were similar for the 2 outcomes. The gender-adjusted hazard ratio of experiencing either coronary heart disease or stroke comparing the manual and nonmanual social class categories was 1.52 (95% confidence interval [CI] = 1.14, 2.02). This ratio fell to 1.41 (95% CI = 1.05, 1.88) after adjustment for indicators of intrauterine and childhood growth. Further adjustment for educational attainment reduced the ratio to 1.28 (95% CI = 0.94, 1.75). Conclusions. We found that social class at birth was associated with risk of fatal and nonfatal cardiovascular disease among individuals born in the 1950s, a period of relative prosperity and after the introduction of the welfare state in Britain. This relation appeared to be mediated in part through educational attainment.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.socscimed.2005.10.007 Byline: Mary Shaw (a), Debbie A. Lawlor (a), Jake M. Najman (b) Keywords: Teenage; Mother; Longitudinal; Australia; Child; Health outcomes; Psychological behaviour Abstract: In many industrialised countries teenage pregnancy and teenage parenthood have in recent years been identified as social and public health problems that need to be tackled. A number of studies have looked at various outcomes for teenage mothers and their offspring, and many report a strong association with poverty for the mother both before and after having a child. Few studies, however, adequately control for socioeconomic circumstances when examining health and related outcomes. Most studies have focused on perinatal outcomes in the offspring with few looking at later health and development. In Australia, where the rate of teenage pregnancy is relatively high compared to other comparable countries, teenage pregnancy is a not prominent policy concern. As such, Australia offers the opportunity to study the outcomes of teenage parenthood in a country where there may be less stigma than in countries that portray teenage parenthood as a major health and/or social problem. This paper reports findings from the Mater-University Study of Pregnancy (MUSP) and its outcomes, a prospective study of women, and their offspring, who received antenatal care at a major public hospital (Mater Misericordiae Hospital) in South Brisbane, Australia, between 1981 and 1984. We have examined the associations of maternal age (a[c]1/218 years (n=460) versus >18 years (n=4800)) at first antenatal visit with offspring psychological, behavioural and health characteristics when the offspring -- the teenage children of teenage mothers -- were aged 14 years. Multiple logistic regression was used to determine the effect of maternal and family characteristics on associations between maternal age and childhood outcomes at age 14. Results show that the 14 year old offspring of mothers who were aged 18 years and younger compared to those who were offspring of older mothers were more likely to have disturbed psychological behaviour, poorer school performance, poorer reading ability, were more likely to have been in contact with the criminal justice system and were more likely to smoke regularly and to consume alcohol. However, maternal age was not associated with health outcomes in their offspring at age 14 years. Indicators of low socioeconomic position and maternal depression were also associated with poorer psychological, cognitive and behavioural outcomes among 14 year olds. In addition children from poorer socioeconomic backgrounds and whose mothers were depressed were more likely to have self-reported poor health, asthma, to have been admitted to hospital twice or more since birth and to be bed-wetters at age 14. The associations between maternal age and psychological distress, school performance, and smoking and alcohol use were all largely explained by socioeconomic factors, maternal depression, family structure and maternal smoking. These findings confirm that not all teenage mothers and their offspring have adverse outcomes, and that many if not the majority have good outcomes. Author Affiliation: (a) University of Bristol, UK (b) University of Queensland, UK

Objectives. We assessed the associations of childhood socioeconomic position with cardiovascular disease risk factors (smoking, binge alcohol drinking, and being overweight) and examined the roles of educational attainment and cognitive functioning in these associations. Methods. Data were derived from a cohort study involving 7184 individuals who were born in Aberdeen, Scotland, between 1950 and 1956; had detailed records on perinatal characteristics, childhood anthropometry, and cognitive functioning; and responded to a mailed questionnaire when they were aged 45 to 52 years. Results. Strong graded associations existed between social class at birth and smoking, binge drinking, and being overweight. Adjustment for educational attainment completely attenuated these associations. However, after control for adult social class, adult income and other potential confounding or mediating factors, some association remained. Conclusions. Educational attainment is an important mediating factor in the relation between socioeconomic adversity in childhood and smoking, binge drinking, and being overweight in adulthood. doi:10.2105/AJPH.2004.041129)

Objectives. We sought to determine whether residential area deprivation, over and above the effect of life-course socioeconomic status or position (SEP), is associated with coronary heart disease. Methods. We conducted a cross-sectional analysis of 4286 women aged 60 to 79 years from 457 British electoral wards. Results. After adjustment for age and 10 indicators of individual life-course SEP, the odds of coronary heart disease was 27% greater among those living in wards with a deprivation score above the median compared with those living in a ward with a deprivation score equal to or below the median (odds ratio= 1.27; 95% confidence interval = 1.02, 1.57). Conclusions. Adverse area-level socioeconomic characteristics, over and above individual life-course SEP, are associated with increased coronary heart disease.

Objectives. We assessed the association between life-course socioeconomic status or position (SEP) and hormone replacement therapy (HRT). Methods. We conducted a cross-sectional analysis of 4286 women aged 60 to 79 years. Results. Women experiencing adverse socioeconomic circumstances across the life course were less likely to have used HRT. The associations of childhood socioeconomic measures with HRT use were independent of adult SEP, behavioral risk factors, and physiological risk factors for heart disease. Conclusions. SEP from across the life course is associated with HRT use. Because the association between early life SEP and HRT is not fully explained by adult risk factors, residual confounding (which is not captured by adjustment for adult variables only) may explain some of the disparity between observational studies and randomized controlled trials in this area.

Objectives. We assessed the association between childhood socioeconomic status (SES) and coronary heart disease among postmenopausal women. Methods. We conducted a cross-sectional analysis of 3444 women aged 60 to 79 years. Results. There was an independent linear association between childhood and adult SES and coronary heart disease. The association between childhood SES and coronary heart disease was attenuated when we adjusted for insulin resistance syndrome, adult smoking, physical activity, biomarkers of childhood nutrition, and passive smoking. Conclusions. The association between adverse childhood SES and coronary heart disease is in part mediated through insulin resistance, which may be influenced by poor childhood nutrition, and in part through the association between childhood SES and adult behavioral risk factors.