Showing papers by "Debbie A Lawlor published in 2004"

Associations of parental, birth, and early life characteristics with systolic blood pressure at 5 years of age. Findings from the Mater-University Study of Pregnancy and its Outcomes

Abstract: Background— We examined the associations of a range of parental and early life characteristics with systolic blood pressure at 5 years of age. Methods and Results— Information from 3864 children who were followed up prospectively from their mother’s first antenatal clinic assessment was used. Maternal age, body mass index, and smoking during pregnancy were all positively associated with offspring systolic blood pressure at 5 years of age. The systolic blood pressure of children whose mothers had smoked throughout pregnancy was on average 0.92 mm Hg (95% CI 0.17 to 1.68) greater than that of children whose mothers had never smoked, after full adjustment. Children who had been breast fed until at least 6 months had lower systolic blood pressure than those who were breast fed for a shorter duration. Paternal body mass index and child’s weight, height, and body mass index were all positively associated with blood pressure at age 5. Conclusions— Because childhood blood pressure tracks into adulthood, intervent...

Associations of measures of lung function with insulin resistance and Type 2 diabetes: findings from the British Women’s Heart and Health Study

Abstract: The aim of this study was to assess the associations of lung function with insulin resistance and Type 2 diabetes. We did a cross-sectional study of 3911 women who were 60 to 79 years old from 23 British towns, assessing the association of measures of lung function with insulin resistance (based on fasting insulin and glucose concentrations) and Type 2 diabetes (World Health Organisation diagnostic criteria). Forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were inversely associated with insulin resistance and prevalence of Type 2 diabetes. In age-adjusted analyses, the homeostasis model assessment (HOMA) score (insulin resistance) decreased by 5% (95% CI: 2–7%) for a one standard deviation increase in log FEV1 and by 8% (95% CI: 6–10%) for a one standard deviation increase in log FVC. With additional adjustment for height, smoking, BMI, waist-to-hip ratio, physical activity, white cell count, adult social class, childhood social class and respiratory medication, these associations attenuated to 3% (95% CI: 1 to 5%) and 5% (95% CI: 3 to 8%). The fully adjusted odds ratio for diabetes prevalence was 0.85 (95% CI: 0.74–0.98) for a one standard deviation increase in log FEV1 and 0.80 (95% CI: 0.70–0.92) for a one standard deviation increase in log FVC. Forced expiratory flow in the central period of FVC was not associated with insulin resistance or diabetes. Lung function measures which predominantly reflect lung volume are inversely associated with insulin resistance and Type 2 diabetes. These associations could reflect childhood exposures which affect lung growth and also programme insulin resistance.

Exercise interventions for cancer patients: systematic review of controlled trials

Abstract: Objective: To systematically review controlled trials investigating the effects of exercise interventions in cancer patients. Methods: Studies were located through searching seven electronic databases (Medline, Embase, Cochrane Library, CancerLit, PsycInfo, Cinahl, SportDiscus), scanning reference lists of relevant articles, contacting experts (n = 20), and checking the contents lists of journals available through ZETOC (Electronic Table of Contents). To be included, trials had to be prospective, controlled, involve participants diagnosed with cancer and test an exercise intervention. Types of outcome were not restricted. Two reviewers independently applied the selection criteria. ResultsThirty-three controlled trials (including 25 randomized trials) were included in the review. There was some evidence that physical function was increased among those who exercised. Furthermore, symptoms of fatigue did not appear to be increased and there were few adverse effects reported. There was insufficient evidence to determine effects on other outcomes, such as quality of life, with results hampered by the heterogeneity between studies as well as poor methodological quality. Data were also lacking on the long term effects of exercise relating to cancer recurrence or survival. Conclusions There is preliminary evidence that exercise interventions for cancer patients can lead to moderate increases in physical function and are not associated with increased symptoms of fatigue. However, it is impossible from current evidence to determine whether exercise has long term beneficial effects on survival or quality of life.

Hyperinsulinaemia and Increased Risk of Breast Cancer: Findings From the British Women's Heart and Health Study

Abstract: Objective: To assess the association between fasting insulin levels and breast cancer. Design: Cross sectional study. Participants: 3868 women aged 60-79 years. Main outcome measure: Prevalent breast cancer (151 cases). Results: Insulin levels were positively associated with breast cancer. The age adjusted odds ratio (95% confidence interval) for a one unit increase in log(e) insulin levels among women without diabetes was 1.34 (1.02, 1.77). This association was not substantively altered by adjustment for potential confounding factors (age of menopause, hysterectomy/oophorectomy, hormone replacement use, oral contraceptive use, parity, adult social class and smoking) or potential mediating factors (body mass index, waist to hip ratio, leg length, age at menarche and childhood social class). Women with both long legs and higher insulin levels were at particularly increased risk, with breast cancer prevalence being 5.7% among women in the highest thirds of both insulin levels and leg-length compared to 1.8% among those in the lowest thirds of both. Positive associations between insulin levels and breast cancer were found for both pre- and post-menopausal breast cancers. Fasting glucose levels, HOMA score, diabetes and a history of gestational glycosuria or diabetes were also positively associated with breast cancer. Conclusions: Hyperinsulinaemia is positively associated with breast cancer in this cohort of older women. This effect may be mediated via a number of hormonal pathways acting at different stages of the life course.

Mis)use of Factor Analysis in the Study of Insulin Resistance Syndrome

Abstract: Over the last decade, factor analysis has been used increasingly to describe patterns of simultaneous occurrence of the central components of the insulin resistance syndrome. In this paper, the authors describe factor analysis, review studies that have used factor analysis to examine the insulin resistance syndrome, and explore how factor analysis might be used to increase our understanding of this syndrome. Most studies that they reviewed gave vague reasons for using factor analysis and did not demonstrate an understanding of the use and limitations of this statistical method. Confirmatory factor analysis based on sound theoretical concepts and a clear understanding of the statistical methods may provide some insights into the pathophysiology of the syndrome. However, to date none of the studies has adopted this approach, and other statistical approaches and study designs are likely to provide greater understanding of the syndrome.

Associations of components of adult height with coronary heart disease in postmenopausal women: the British women’s heart and health study

Abstract: Objective: To assess the associations between components of adult height and coronary heart disease (CHD) in postmenopausal women. Methods: Cross sectional analysis of 4286 women randomly selected from 23 British towns. The association of components of adult height with prevalent CHD (n = 694) were assessed. Results: Shorter stature, shorter leg length, and trunk length were all associated with CHD in age adjusted analyses. The association between trunk length and CHD was attenuated to the null with adjustment for smoking. The leg length–CHD association was independent of smoking, socioeconomic position in childhood and adulthood, birth weight, and other potential confounders. Insulin resistance did not appear to be an important mediating factor in the association between leg length and CHD. After full adjustment for all potential confounding factors the odds ratio (95% confidence interval) of CHD for a 1 SD (4.3 cm) increase in leg length was 0.84 (0.77 to 0.93) and the odds ratio for a 1 SD (0.05) increase in the leg to trunk ratio was 0.85 (0.79 to 0.95). Conclusions: The specific association between leg length and CHD suggests that early life environmental exposures that influence skeletal growth also influence CHD risk in later life.

Commentary: The hormone replacement–coronary heart disease conundrum: is this the death of observational epidemiology?

Abstract: Under its definition for the word ‘hindsight’ the Oxford English Dictionary includes the following statement ‘hindsight is always better than foresight’ (http://dictionary.oed.com/), and the slogan of a private survey and evaluation company, ingeniously called Hindsight, is ‘remember hindsight is always 20/20!’ (http://www. hndsight.com/). We have the benefit of the ‘hindsight’ from randomized controlled trials (RCT) when we comment on this meta-analysis of observational studies, but whether the conflicting results between the trial and observational evidence on the association between hormone replacement therapy (HRT) use and coronary heart disease (CHD) will lead to 20/20 vision remains to be seen. The disparity between findings from observational studies and RCT of the effects of HRT on CHD,1–4 has created considerable debate among researchers, practitioners and postmenopausal women. The authors of the meta-analysis reprinted in this issue of the International Journal of Epidemiology concluded that the pooled estimate of effect from the best quality observational studies (internally controlled prospective and angiographic studies) inferred a relative reduction of 50% with ever use of HRT and stated that ‘overall, the bulk of the evidence strongly supports a protective effect of estrogens that is unlikely to be explained by confounding factors’.4 By contrast, recent randomized trials among both women with established CHD and healthy women have found HRT to be associated with slightly increased risk of CHD or null effects.1,2 For example, the large Women’s Health Initiative (WHI) randomized trial found that the hazards ratio for CHD associated with being allocated to combined HRT was 1.29 (95% CI: 1.02, 1.63), after 5.2 years of follow-up.1 These marked differences between observational findings and trials are important for two reasons. First, and foremost, is the clinical impact. As another commentator on the same subject remarked: ‘Does HRT decrease or increase the risk of heart disease? At least every woman, every gynecologist and every primary care doctor want to know the “correct” answer.’5 Second, is the broader implication for observational epidemiology. Prior to the publication of the WHI it was suggested that well conducted observational studies produced similar estimates of treatment effects as RCT, and that the notion of a hierarchy of evidence with the RCT on top could not be supported.6,7 The differing results between observational studies and RCT in the association between HRT and CHD throw this idea into question and may signify the death of observational epidemiology.8 It is important, therefore, to determine why the results from the trials and observational studies are so different. A number of explanations have been suggested for these disparities. Whilst some have suggested that the results of the trials were biased because of contamination, and in the case of the WHI, early termination of the arm assessing the effect of combined HRT, the consistency across a number of trials of a null effect make these explanations unlikely. More plausible explanations are that women who participated in the trials were importantly different from those who participated in the observational studies, or that the observational study results were confounded.

Clustering of risk factors and social class in childhood and adulthood in British women's heart and health study: cross sectional analysis.

Abstract: Objective To examine co-occurrence and clustering of risk factors used in the Framingham equation by social class in childhood and adult life. Design Cross sectional study. Setting 23 towns across England, Wales, and Scotland. Participants 2936 women aged 60-79 years. Main outcome measures Prevalence of risk factors (hypertension, obesity, smoking, left ventricular hypertrophy on electrocardiography, diabetes, and low concentration of high density cholesterol); ratios of observed to expected frequencies of clusters of risk factors. Results Risk factors were more common in women from manual social classes in either childhood or adult life, and the co-occurrence of three or four of these risk factors was greater among more disadvantaged groups. Within the four socioeconomic groups, these risk factors occurred together more than would be expected from their individual frequency distributions, indicating that they were clustered. The extent of this clustering was similar in all four social class groups. Conclusions Clustering of risk factors included in the Framingham risk function occurs in all social class groups, but the lack of social patterning makes it unlikely that clustering is an explanation of socioeconomic inequalities in cardiovascular disease. As the proportion of women with co-occurrence of risk factors is greatest in those from manual social class in childhood, this measure of socioeconomic position might prove useful in risk prediction.

Association between self-reported childhood socioeconomic position and adult lung function: findings from the British Women’s Heart and Health Study

Abstract: 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 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.

Missed appointments in primary care: questionnaire and focus group study of health professionals

Abstract: BACKGROUND: The issue of missed appointments in primary care is important for patients and staff. Little is known about how missed appointments, and the people who miss them, are managed in primary care, or about effective strategies for managing missed appointments. AIMS: To understand the perceptions of primary care staff as to why patients miss appointments, to determine how these perceptions influence their management, and to explore the merit of different management strategies. Design of study: A postal questionnaire survey and focus group interviews. SETTING: General practices in Yorkshire. RESULTS: Missed appointments were regarded as an important problem. Patient factors rather than practice factors were perceived as most important in causing missed appointments. Intervention strategies appeared to be driven by perceptions of why patients miss appointments. Negative attitudes, embodied in terms such as "offenders" to refer to those who missed appointments were prevalent, and favoured intervention strategies included punishing the patient in some way. Receptionists believed that general practitioners should address the issue of the missed appointment with the patient. General practitioners felt guarded about addressing missed appointments with their patients in case it affected the doctor-patient relationship. CONCLUSION: People who miss appointments were viewed negatively by primary care staff, and most of the reasons for missed appointments were focused on patients. These beliefs underpinned intervention strategies aimed mainly at punishment. Since there is no evidence base concerning interventions that are effective in reducing missed appointments, these negative attitudes may not be beneficial to staff or their patients.

The association of the PON1 Q192R polymorphism with coronary heart disease: findings from the British Women's Heart and Health cohort study and a meta-analysis

Abstract: There have been inconsistent results from case-control studies assessing the association of the PON1 Q192R polymorphism with coronary heart disease (CHD). Most studies have included predominantly men and the association in women is unclear. Since lipid levels vary between the sexes the antioxidant effect of PON1 and any genes associated with it may also vary by sex. We have examined the association of the PON1 Q192R polymorphism with CHD in a large cohort of British women and combined the results from our cohort study with those from all other published studies. The distribution of genotypes was the same among women with CHD and those without disease. The odds ratio (95% confidence interval) of having CHD comparing those with either the QR or RR genotype to those with QQ genotype (dominant model of association) was 1.03 (0.89, 1.21) and the per allele odds ratio was 0.98 (0.95, 1.01). In a meta-analysis of this and 38 other published studies (10,738 cases and 17,068 controls) the pooled odds ratio for the dominant effect was 1.14 (1.08, 1.20) and for the per allele effect was 1.10 (1.06, 1.13). There was evidence of small study bias in the meta-analyses and the dominant effect among those studies with 500 or more cases was 1.05 (0.96, 1.15). Ethnicity and reporting of whether the genotyping was done blind to the participants clinical status also contributed to heterogeneity between studies, but there was no difference in effect between studies with 50% or more women compared to those with fewer women and no difference between studies of healthy populations compared to those at high risk (with diabetes, renal disease of familial hypercholesterolaemia). There is no robust evidence that the PON1 Q192R polymorphism is associated with CHD risk in Caucasian women or men.

Association Between Childhood Socioeconomic Status and Coronary Heart Disease Risk Among Postmenopausal Women: Findings From the British Women's Heart and Health Study

Abstract: 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

Socioeconomic position and hormone replacement therapy use: explaining the discrepancy in evidence from observational and randomized controlled trials.

Abstract: 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.

Birth weight is inversely associated with coronary heart disease in post-menopausal women: findings from the British women's heart and health study

Abstract: 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.

Blood pressure, haemorrhagic stroke, and ischaemic stroke: the Korean national prospective occupational cohort study

Abstract: Deaths from haemorrhagic stroke declined consistently through the 20th century, but deaths from ischaemic stroke showed a rise and fall, mirroring the coronary heart disease epidemic.1 Blood pressure has also declined,2 and if blood pressure is more strongly associated with haemorrhagic stroke than with ischaemic stroke, this might contribute to the divergent trends. Previous meta-analyses have shown contradictory findings; one showed similar associations for both stroke subtypes,3 and another, of Asian studies, showed a stronger association with haemorrhagic stroke than with ischaemic stroke.4 To resolve this uncertainty, we examined the association of blood pressure with subtype of stroke in a large cohort of Korean civil servants. The Korean National Health System for public servants and teachers provides medical expenses and biennial multiphasic health examinations at which blood pressure is measured in the seated position by trained staff using a standard mercury sphygmomanometer …

Teenage pregnancy rates: high compared with where and when?

Abstract: In the past decade teenage pregnancy has become a key policy area in several industrialized countries. During the 1990s, both Britain and the USA identified teenage pregnancy as a national public health issue, alongside cardiovascular disease, cancer and mental health, requiring targeted interventions.1,2 A reason for this concern was that rates of teenage pregnancy were perceived to be higher than those in other developed countries2,3—a notion that has been taken up and inflated by the media. For example: `Britain... has a sky-high level of teenage pregnancies.' [Daily Mail, 8 March 2001] `The sexual behaviour of our children and teenagers has now reached such unprecedented levels of recklessness and damage that it is becoming a horror story running out of control.' [Daily Mail 28 June 2002] In our opinion, such claims are based on selective comparisons. Here we argue that, contrary to the way in which it is frequently presented, the teenage pregnancy rate in Britain is neither high nor dramatically increasing.

Birthweight of offspring and paternal insulin resistance and paternal diabetes in late adulthood: cross sectional survey

Abstract: Aims/hypothesis It has been proposed that genetic factors involved in insulin action could explain part of the link between low birthweight and risk of cardiovascular disease and diabetes in adulthood. To confirm this we examined the association between offspring birthweight and paternal insulin resistance and diabetes in late adulthood.

Chronic diseases, locomotor activity limitation and social participation in older women: cross sectional survey of British Women’s Heart and Health Study

Abstract: OBJECTIVES: to examine the association of chronic degenerative diseases with locomotor activity limitation and social participation among older British women. METHODS: cross-sectional survey of 4,286 women aged 60–79 years from 23 towns in England, Scotland and Wales. RESULTS: the prevalence of locomotor activity limitation was 37.2% and 33.5% of women had difficulty with some aspect of social participation. This prevalence of locomotor activity limitation and difficulties with social participation increased with increasing age and with increasing number of chronic diseases. All chronic diseases assessed were independently (of each other and confounding factors) associated with locomotor activity limitation. Associations were particularly strong for stroke (OR 5.44, 95% CI 3.38–8.75), arthritis (OR 3.95, 95% CI 3.25–4.81) and coronary heart disease (OR 2.26, 95% CI 1.77–2.88). The population attributable fraction for locomotor activity limitation was greatest for arthritis: 37.8% (95% CI 32.0–43.1) and coronary heart disease: 6.7% (95% CI 4.8–8.8). Locomotor activity limitation was strongly associated with social participation. Most chronic diseases of ageing were independently (of locomotor activity limitation, other chronic diseases and confounding factors) associated with reduced social participation. CONCLUSIONS: locomotor activity limitation and difficulties in social participation are common. Arthritis and coronary heart disease contribute importantly to locomotor activity limitation and difficulties with social participation. Effective strategies to prevent or limit the disabling impact of these conditions are essential to improving the quality of life of older women.

The metabolic syndrome and coronary heart disease in older women: findings from the British Women's Heart and Health Study.

Abstract: AIMS: To compare two proposed definitions of the metabolic syndrome and to determine the clinical importance of the syndrome with respect to its association with coronary heart disease (CHD). METHODS: Cross-sectional study of 3770 women aged 60-79 years randomly selected from 23 British towns. RESULTS: The prevalence of the metabolic syndrome was high in this population and similar with both definitions: 28.2% (95% confidence interval 26.8, 29.7%) of the women had metabolic syndrome according to a modified version of the WHO definition, and 29.2% (27.7, 30.7%) had the ATP III-defined syndrome. There was reasonable agreement between the two definitions, with 79% of the participants being similarly classified by both definitions. The syndrome was associated with prevalent CHD, with the magnitude of the association with CHD being similar for both definitions. The odds ratio (95% confidence interval) for the age, smoking, physical activity, adult and childhood social class adjusted association of the WHO defined syndrome with prevalent CHD was 1.45 (1.19, 1.75) and for the ATP III-defined syndrome was 1.53 (1.27, 1.85). Insulin resistance alone, hypertension alone and dyslipidaemia alone were all associated with CHD, with the magnitudes of these associations being similar to those for the WHO and ATP III-defined syndrome with CHD. CONCLUSIONS: The prevalence of the metabolic syndrome is high in older British women and is associated with CHD. There is reasonable agreement between a modified version of the WHO definition and the ATP III definition of the syndrome, and both are similarly associated with CHD. Single components of the syndrome are associated with CHD to a similar magnitude as the syndrome.

Temperature at birth, coronary heart disease, and insulin resistance: cross sectional analyses of the British women's heart and health study

Abstract: Objective: To assess the association of mean outdoor temperature around the time of birth with insulin resistance and coronary heart disease in later life. Design: Cross sectional study. Setting: 23 British towns. Participants: 4286 women aged 60–79 years. Main outcome measures: Coronary heart disease and insulin resistance. Results: Coronary heart disease prevalence was greatest among women born during the coldest months: the age adjusted odds ratio comparing women born in the coldest quarter of monthly outdoor birth temperatures with the remaining three quarters was 1.24 (95% confidence interval (CI) 1.03 to 1.50). Cold outdoor temperature at birth was also associated with increased insulin resistance, increased triglyceride concentrations, and poorer lung function. The link between cold outdoor temperature at birth and coronary heart disease was only partly explained by known coronary disease risk factors: fully adjusted (for all measured potential explanatory and confounding factors) odds ratio 1.19 (95% CI 0.95 to 1.48). The association between cold temperature at birth and coronary heart disease was most pronounced among those whose fathers were either unemployed or in manual social classes when the participants were children, and was non-existent in those from non-manual social classes in childhood. Conclusions: Cold outdoor temperature at birth is associated with increased coronary heart disease, insulin resistance, dyslipidaemia, and poor lung function. Further research is needed to determine whether this finding reflects events occurring late in the third trimester of intrauterine growth or early in the postnatal period.

Sex differences in body fat distribution and carotid intima media thickness: cross sectional survey using data from the British regional heart study

Abstract: 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.

Smoking before the birth of a first child is not associated with increased risk of breast cancer: findings from the British Women's Heart and Health Cohort Study and a meta-analysis.

Abstract: It has been suggested that the period between puberty and first birth is a time when the breast is particularly susceptible to carcinogenic effects. In a cohort of 3047 women aged 60-79 years (N=139 breast cancer cases), we found no association between smoking before the birth of a first child and breast cancer risk: fully adjusted (for age, number of children, age at birth of first child, age at menarche, age at menopausal, hysterectomy and/or oophorectomy, ever use of oral contraception, use of hormone replacement therapy, alcohol consumption, body mass index, childhood and adulthood social class) odds ratio 1.06 (95% confidence interval: 0.72, 1.56). The pooled estimate from a meta-analysis of our study and 11 previously published studies (N=6528 cases) was 1.07 (0.94, 1.22). We conclude that smoking prior to the birth of a first child is not associated with increased risk of breast cancer.

The relation between birth weight and intima-media thickness in middle-aged adults

Abstract: BACKGROUND Birth weight has been found to be inversely associated with the risk of coronary heart disease and stroke, although the mechanisms for this association remain unclear. Here, we investigate the relation between reported birth weight and atherosclerosis in middle age. METHODS We included the 9817 participants (age 44-65) in the Atherosclerosis Risk in Communities (ARIC) study who were neither a twin nor born prematurely. Carotid atherosclerosis was assessed as intima-media thickness measured by B-mode ultrasound. We studied the association with recalled exact birth weight, and for those unable to recall exact birth weight, with recalled birth weight category. RESULTS Mean intima-media thickness (+/- standard deviation) was 0.73 +/- 0.17 mm. Mean birth weight for the 4635 participants recalling exact birth weight was 3.49 +/- 0.71 kg. A further 4946 participants recalled birth weight category, with 4730 (96%) reporting "medium" birth weight. In univariate analysis, birth weight and intima-media thickness were positively related. However, adjustment for confounding factors reduced the association to only a 0.004 mm higher intima-media thickness (95% CI = - 0.003 to 0.011) mm per 1 kg of birth weight. The same pattern of univariate positive relationship and attenuation with adjustment was seen for birth weight category and intima-media thickness. There was no evidence of interaction between adult body mass index (BMI) and birth weight, or of interaction between category of adult BMI and birth weight category. An inverse relation between birth weight category and intima-media thickness was seen only for those in the lowest category of adult BMI (BMI <25 kg/m). CONCLUSIONS We found no evidence of a clinically significant relation between birth weight and carotid atherosclerosis.

The challenge of secondary prevention for coronary heart disease in older patients: findings from the British Women's Heart and Health Study and the British Regional Heart Study

Abstract: BACKGROUND: Secondary prevention of coronary heart disease (CHD) among older individuals is associated with considerable benefit. METHODS: In this study, we have examined the extent of secondary prevention among British women and men aged 60-79 years who were surveyed and examined between 1998 and 2001. RESULTS: Among 483 women (12.1% of the whole sample) and 831 men (19.5%) with CHD, >90% of both sexes had at least one modifiable risk factor, with over two-fifths having high blood pressure and over three-quarters high cholesterol. For total cholesterol and body mass index, mean values in both male and female subjects were above recommended levels, and a large shift in the population distributions would be required for targets to be met. Less than one-quarter of subjects of either sex were on a statin, and whilst the majority of men were taking an antiplatelet medication, only 40% of women were. CONCLUSIONS: Most older women and men in Britain were failing to meet National Service Framework standards for secondary prevention in the period immediately before its implementation. Large shifts in the population distributions of some risk factors would be required in this group to meet these standards.

Commentary: The art and science of epidemiology: governed by the seasons?

Abstract: Epidemiology is the study of ‘the distribution and determinants of health-related events in specified populations, and the application of this study to the control of health problems’.1 Observational epidemiology is bedevilled by problems of uncertainty, bias, and confounding in a world that demands certainty and clear guidance from health scientists.2 The discrepant findings between observational studies and randomized controlled trials of the associations between hormone replacement therapy and coronary heart disease (CHD), and the media and health professional responses to these discrepancies, are a particular example. Two studies3,4 published in this issue of the International Journal of Epidemiology (IJE) are, I think, important since they demonstrate examples of good epidemiological science and the art required in appropriately using epidemiological findings to affect public health policy. In 1999 Moore and colleagues undertook a study, that was published in the IJE, which showed that individuals who were born during the ‘hungry season’ in rural Gambia and who survived to at least 15 years of age had a greatly increased risk of mortality (primarily due to infectious causes) in young adulthood.5 Mortality under the age of 15 years was not affected by season of birth, and when all age groups were combined there was no overall difference in mortality by season of birth.5,6 They explored a number of possible explanations for the association between season of birth and mortality beyond the age of 15 years and excluded ‘chance’ on the basis of the strong effects and small P-values. Explanations relating to maternal or infant infectious or toxin exposures seemed unlikely. There was, however, a link between decreasing maternal weight in the last trimester of pregnancy, lower birthweight infants, and the increased risk of mortality from infectious diseases in young adulthood, all of which were related to the ‘hungry season’. The authors hypothesized that maternal, and hence fetal under-nutrition during critical periods of development, programmed abnormalities in immune function resulting in greater risk to infectious diseases in later life.5 Those findings and the suggested hypothesis were very much in line with the fetal origins of adult disease hypothesis which, until that time, had largely investigated the fetal origins of chronic degenerative adult diseases such as diabetes and cardiovascular disease in the developed world.7 Although a chance finding seemed unlikely, and the suggested explanation for the association was both plausible and backed-up by data demonstrating the associated changes in maternal weight and birthweight, the authors recognized the importance of replicating their findings. Moore and colleagues searched for other suitable datasets and in today’s IJE repeat their analyses in a rural population from Bangladesh.3 At the same time Simondon and colleagues have undertaken similar analyses in a rural population from Senegal.4 Neither study confirms the previous findings, but the fact that Moore et al. in particular recognize the importance of publishing their null findings is an example of good science. Moore and colleagues state (and demonstrate) that: