Showing papers by "Debbie A Lawlor published in 2007"

A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity

Abstract: Obesity is a serious international health problem that increases the risk of several common diseases. The genetic factors predisposing to obesity are poorly understood. A genome-wide search for type 2 diabetes-susceptibility genes identified a common variant in the FTO (fat mass and obesity associated) gene that predisposes to diabetes through an effect on body mass index (BMI). An additive association of the variant with BMI was replicated in 13 cohorts with 38,759 participants. The 16% of adults who are homozygous for the risk allele weighed about 3 kilograms more and had 1.67-fold increased odds of obesity when compared with those not inheriting a risk allele. This association was observed from age 7 years upward and reflects a specific increase in fat mass.

Clustered environments and randomized genes: a fundamental distinction between conventional and genetic epidemiology.

Abstract: 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 (a ¼ 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 ¼ 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.

A systematic review of the association between circulating concentrations of C reactive protein and cancer

Abstract: The objective of this study was to review and summarise the published evidence for an association between circulating concentrations of C reactive protein (CRP) and cancer through a systematic review. 90 discrete studies were identified. 81 (90%) were prevalent case-control or cross-sectional studies, and only 9 studies had a prospective design. In most prevalent studies, CRP concentrations were found to be higher in patients with cancer than in healthy controls or controls with benign conditions. Of the nine large prospective studies identified in this review, four reported no relationship between circulating CRP levels and breast, prostate or colorectal cancers, and five studies found that CRP was associated with colorectal or lung cancers. Most of the studies evaluating CRP as a diagnostic marker of cancer did not present relevant statistical analyses. Furthermore, any association reported in the prevalent studies might reflect reverse causation, survival bias or confounding. The prospective studies provided no strong evidence for a causal role of CRP in cancer. Instead of further prevalent studies, more large prospective studies and CRP gene-cancer association studies would be valuable in investigating the role of CRP in cancer.

Socioeconomic inequalities in health

Abstract: Socioeconomic differences in health have been described since the 16th and 17th centuries,1 2 but only recently has reducing them been central to public health policy in many Western countries3 Over the past three decades, epidemiological studies have confirmed the existence of socioeconomic inequalities in a range of health outcomes, including premature mortality, cardiovascular disease, obesity, diabetes, self reported ill health, and smoking related cancers, and have explored potential mechanisms linking lower socioeconomic position to poorer health4 The Whitehall cohort studies have made important contributions to this literature5 Several studies,6 7 8 9 including a publication from Whitehall II,10 have found that poorer socioeconomic position is associated with worse morbidity, mortality, and self reported health in older people In this week's BMJ, a new analysis of data from Whitehall II by Chandola and colleagues examines the extent to which socioeconomic inequalities in self reported physical and mental health continue into older age11 The paper adds to the literature by using repeated measures of socioeconomic position and self reported health, both of which may change with age The paper demonstrates one of the strengths of prospective cohort studies—the ability to examine changing relations between health related characteristics over time Three key messages emerge: firstly, self reported physical health declines with age in all groups (women and men, people who are retired and those who continue work, and people in all employment grades); secondly, in contrast, self reported mental health increases in all groups; and thirdly the rate of decline in physical health with age is greater in those from lower employment grades than those from higher employment grades, which results in a widening of health inequalities with age11 The authors focus specifically on socioeconomic inequalities But their repeated measurements and detailed analyses allow other inequalities to be explored Figure 2 in their paper shows the trajectories of health change with age by occupational grade for the final phase (2002-4) of the study However, the authors do not highlight that the interactions of age with time period included in their statistical model suggest that these trajectories changed over time We calculated the trajectories of physical and mental health for each time period that the study covered using data from the full results of model I, presented in the appendix to the paper (figs 1​1 and 2​2)11 We found that in the first period (1991-3) physical health did not decline with increasing age, and during the rest of the 1990s the decline in self reported physical health with age was much less pronounced than that seen since 2000 (fig 1​1)) With respect to self reported mental health, in the early 1990s the increase with age was more noticeably linear—continuing to increase into later older age—than in more recent years, where at older age the improvement in mental health flattens off (fig 2​2)) The differing impressions given by trajectories in the different periods are a reminder of how difficult it can be to summarise the results of complex statistical models in a transparent way Fig 1 Trajectories of age related short form 36 (SF-36) physical health in Whitehall II cohort, predicted from model I of Chandola and colleagues11 Fig 2 Trajectories of age related mental health component in Whitehall II cohort, predicted from model I of Chandola and colleagues11 These findings suggest that people in recent years perceive a greater decline in their physical health and a smaller improvement in their mental health as they age than people did a decade ago Reasons underlying this cannot be determined from the data presented, but continued reporting in the media of the “burden” of an older population, together with changing roles of the family and society, and changing attitudes in society towards care for older people might be important The results of the statistical model also show that sex is the strongest predictor of physical health; the physical scores of the women in the reference group were, on average, 265 points lower than those for the men in that group This compares to a difference of 160 points between the lowest and highest employment grades in this group Women also reported worse mental health (difference of 196 points on the mental health score) As the authors report no evidence of statistical interaction between sex and age, the results suggest that the sex differences found in the reference age persist as people get older In summary, the full model results suggest that socioeconomic inequalities in self reported health persist and possibly widen with age, that the relation between age and self reported health changes over time, and that women have worse self reported health than men at all ages and time points The implications of the findings for public health are uncertain because the meaning of differences of this size in self reported physical or mental health is unclear A difference of 1 in the short form 36 (SF-36) score probably corresponds to 005-007 of a standard deviation: in previous UK based studies the standard deviation has ranged from 15-20, with similar means to those published in table 1 of the paper11 Quantifying similar trajectories for objective health outcomes (such as blood pressure, fasting and postload glucose, lipid values, incident diabetes, and cardiovascular disease) that have a clearer meaning to clinicians, public health practitioners, and the public, and exploring how these change with socioeconomic position, age, and sex over different time periods, is something that Whitehall II can do and that we look forward to seeing

Gamma-Glutamyltransferase Is Associated With Incident Vascular Events Independently of Alcohol Intake: Analysis of the British Women’s Heart and Health Study and Meta-Analysis

Abstract: Objective—To investigate the association of -glutamyltransferase (GGT) with incident CHD and stroke. GGT is a marker of alcohol intake but may also reflect oxidative stress and nonalcoholic fatty liver disease. Alanine aminotransferase (ALT) is the enzyme most closely associated with liver fat content. Methods and Results—Associations of GGT and ALT with incident CHD, stroke, and a combined outcome of CHD or stroke were examined in the British Women’s Heart and Health study (n2961), and a meta-analysis of population based studies examining these associations was performed. In pooled analyses of fully adjusted results of 10 prospective studies, a change of 1 U/L of GGT was associated with a HR1.20 (95% CI: 1.02, 1.40) for CHD; a HR1.54 (95% CI: 1.20, 2.00) for stroke; and HR1.34 (95% CI: 1.22, 1.48) for CHD or stroke. Heterogeneity was substantially decreased when 2 studies in Asian populations were excluded. In a subgroup of nondrinkers results were similar to the main analysis. Meta analyses of the only 2 studies that examined the association of ALT with incident cardiovascular events found a HR1.18 (95% CI: 0.99, 1.41) for CHD and a HR1.10 (95% CI: 0.89, 1.36) for CHD or stroke (combined). Conclusion—GGT is associated with incident vascular events independently of alcohol intake. The mechanisms underlying this association remain unclear and require future study. (Arterioscler Thromb Vasc Biol. 2007;27:2729-2735.)

Socioeconomic Position, Co-Occurrence of Behavior-Related Risk Factors, and Coronary Heart Disease: the Finnish Public Sector Study

Abstract: 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 39 255 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 ...

The Emerging Risk Factors Collaboration: analysis of individual data on lipid, inflammatory and other markers in over 1.1 million participants in 104 prospective studies of cardiovascular diseases.

Abstract: Many long-term prospective studies have reported on associations of cardiovascular diseases with circulating lipid markers and/or inflammatory markers. Studies have not, however, generally been designed to provide reliable estimates under different circumstances and to correct for within-person variability. The Emerging Risk Factors Collaboration has established a central database on over 1.1 million participants from 104 prospective population-based studies, in which subsets have information on lipid and inflammatory markers, other characteristics, as well as major cardiovascular morbidity and cause-specific mortality. Information on repeat measurements on relevant characteristics has been collected in approximately 340,000 participants to enable estimation of and correction for within-person variability. Re-analysis of individual data will yield up to approximately 69,000 incident fatal or nonfatal first ever major cardiovascular outcomes recorded during about 11.7 million person years at risk. The primary analyses will involve age-specific regression models in people without known baseline cardiovascular disease in relation to fatal or nonfatal first ever coronary heart disease outcomes. This initiative will characterize more precisely and in greater detail than has previously been possible the shape and strength of the age- and sex-specific associations of several lipid and inflammatory markers with incident coronary heart disease outcomes (and, secondarily, with other incident cardiovascular outcomes) under a wide range of circumstances. It will, therefore, help to determine to what extent such associations are independent from possible confounding factors and to what extent such markers (separately and in combination) provide incremental predictive value.

Social inequalities in antidepressant treatment and mortality: a longitudinal register study

Abstract: Background. Despite an increased prevalence of depression among people of low socio-economic position, it remains unclear whether their treatment with antidepressants appropriately matches their increased need compared with people from more affluent backgrounds. This study examined socio-economic differences in antidepressant prescriptions and mortality related to depressive dis- orders. Method. A longitudinal register study of 17 947 male and 47 458 female local government employees with linked information on socio-economic indicators (education and occupational status) and data on antidepressant use and mortality associated with depressive disorder (suicide, alcohol-related deaths) during the years 1994 to 2000. Results. In men, antidepressant treatment was less common among low educational groups than among high educational groups (OR 0 . 87, 95 % CI 0 . 76-0 . 99) and a corresponding difference was seen between occupational statuses (OR for manual v. upper non-manual 0 . 72, 95 % CI 0 . 62-0 . 84). In women, socio-economic position was not associated with antidepressant use. However, both among the men and women, employees with low socio-economic position had increased risk for mental-health-related mortality, as indicated by suicides, deaths from alcohol-related causes, and all-cause mortality. Conclusions. These data suggest a mismatch in the treatment of depression relative to apparent clinical need, with the lowest levels of treatment concentrated in the lower socio-economic groups, despite evidence of their increased prevalence of depression and suicide.

Intrauterine Growth Retardation, Insulin Resistance, and Nonalcoholic Fatty Liver Disease in Children: Response to Nobili et al.

Abstract: We read with interest the article by Nobili et al. (1), who reported results of a case-control study that demonstrated an association between intrauterine growth retardation (defined as small for gestational age [SGA]) and pediatric nonalcoholic streatohepatitis (nonalcoholic fatty liver disease [NAFLD]). Nobili et al. (1) compared children with NAFLD with hospital control subjects. The choice of control subjects may result in an underestimate of the association between SGA and NAFLD if hospitalized children …

Offspring Birth Weight and Parental Mortality: Prospective Observational Study and Meta-Analysis

Abstract: The authors have investigated associations between offspring size at birth and parental cardiovascular disease mortality among 12,086 mothers and 6,936 fathers of participants in the British 1958 birth cohort. Birth weight was inversely associated with all-cause mortality and cardiovascular mortality in both mothers and fathers. The adjusted hazard ratio of cardiovascular disease mortality for a 1-standard deviation increase in offspring birth weight in mothers was 0.87 (95% confidence interval (CI): 0.82, 0.93) and in fathers was 0.94 (95% CI: 0.89, 0.99). The association was not specific for cardiovascular disease. In fathers, similar weak associations with violent and accidental deaths, stomach cancer, and alcohol- and smoking-related outcomes were found. Weak associations for these outcomes were also found for mothers, but the magnitude of the association with cardiovascular disease was greater than with any other outcomes. In a meta-analysis pooling results from this study with six others, the adjusted hazard ratio of cardiovascular disease mortality among mothers was 0.75 (95% CI: 0.67, 0.84) and that among fathers was 0.93 (95% CI: 0.91, 0.95), with evidence that the difference in effect between mothers and fathers was not due to chance (p < 0.001). The weak association of offspring birth weight with cardiovascular disease in fathers may be due to residual confounding by factors such as socioeconomic position and smoking that they share with the offspring's mother and that would therefore be associated with low offspring birth weight as well as adverse outcomes in the father. The stronger association in mothers is consistent with intergenerational effects on intrauterine growth and with the fetal origins hypothesis.

Does Childhood Sexual Abuse Predict Young Adult's BMI? A Birth Cohort Study

Abstract: OBJECTIVE: The objective was to identify the extent to which childhood sexual abuse (CSA) is associated with BMI and overweight status in young adulthood and to examine whether any associations differ by gender. RESEARCH METHODS AND PROCEDURES: The Mater-University of Queensland Study of Pregnancy is a prospective birth cohort from a population-based sample involving 7223 singletons whose mothers were enrolled in the 1980s at the first antenatal visit. The present cohort consisted of a subgroup of 2461 young adults who had both self-reported CSA data and measured BMI at 21 years. RESULTS: Of 1273 men, 10.5% reported non-penetrative and 7.5% reported penetrative CSA before age 16 years. Of 1305 women, 20.6% reported non-penetrative and 7.9% reported penetrative CSA by age 16 years. We found young women's BMI and the prevalence of overweight at age 21 were greater in those who experienced penetrative CSA. This association was robust to adjustment for a variety of potential confounders. However, there was no association between non-penetrative CSA and BMI in women and no association between either category of CSA and BMI in men. There was statistical evidence for a gender difference in the association of CSA with mean BMI at age 21 (p value for statistical interaction Language: en

Do Childhood Sleeping Problems Predict Obesity in Young Adulthood? Evidence from a Prospective Birth Cohort Study

Abstract: It has been suggested that sleeping problems are causally associated with obesity in early life, but most studies examining this association have been cross-sectional. The authors used a population-based birth cohort of 2,494 children who were born between 1981 and 1983 in Brisbane, Australia, to examine the prospective association between early-life sleeping problems (at ages 6 months and 2-4 years) and obesity at age 21 years. The authors compared mean body mass indices (BMIs; weight (kg)/height (m)2) and persons in the categories of overweight (BMI 25.0-29.9) and obesity (BMI > or =30) among offspring at age 21 years according to maternally reported childhood sleeping problems. They found that young adult BMI and the prevalence of obesity were greater in offspring who had had sleeping problems at ages 2-4 years than in with those who had not had sleeping problems. These associations were robust to adjustment for a variety of potential confounders, including offspring sex, maternal mental health, and BMI, and several mediators, including adolescent dietary patterns and television-watching. These findings provide some evidence for a long-term impact of childhood sleeping problems on the later development of obesity.

Physical Activity and Common Mental Disorder: Results from the Caerphilly Study

Abstract: The authors examined associations between leisure-time and occupational physical activity and common mental disorder (CMD), defined as anxiety and depression, using data from a cohort of middle-aged men in Caerphilly, South Wales, United Kingdom, who were followed for 5 years (1989-1993) and 10 years (1993-1997). CMD was measured using the General Health Questionnaire. Total leisure-time activity and percentage of time spent in heavy-intensity activity were estimated from self-reports (Minnesota Leisure Time Physical Activity Questionnaire). Men were classified into four classes of occupational activity. Among 1,158 men with complete data, those who participated in any heavy-intensity leisure-time activity had reduced odds of CMD 5 years later (below median vs. none: adjusted odds ratio (OR(adj)) = 0.61, 95% confidence interval (CI): 0.40, 0.93); median or above vs. none: OR(adj) = 0.54, 95% CI: 0.35, 0.83). Analyses using multiple imputation to deal with missing data found weaker evidence for an association (OR(adj) = 0.79 (95% CI: 0.54, 1.15) and OR(adj) = 0.73 (95% CI: 0.49, 1.09), respectively). There was little evidence that men in the most physically demanding jobs had reduced odds of CMD after 5 years, and there was no association between physical activity and CMD 10 years later. Among these men, heavy-intensity leisure-time physical activity was associated with a small reduction in CMD over 5 years.

Effect of conjugal bereavement on mortality of the bereaved spouse in participants of the Renfrew/Paisley Study

Abstract: Objectives: To investigate how loss of a spouse affects mortality risk in the bereaved partner. Design and setting: Prospective cohort study in Renfrew and Paisley in Scotland. Participants: 4395 married couples aged 45–64 years when the study was carried out between 1972 and 1976. Methods: The date of bereavement for the bereaved spouse was the date of death of his or her spouse. Bereavement could occur at any time during the follow-up period, so it was considered as a time-dependent exposure variable and the Cox proportional hazards model for time-dependent variables was used. The relative rate (RR) of mortality was calculated for bereaved versus non-bereaved spouses and adjusted for confounding variables. Main outcome measures: Causes of death to 31 March 2004. Results: Bereaved participants were at higher risk than non-bereaved participants of dying from any cause (RR 1.27; 95% CI 1.2 to 1.35). These risks remained but were attenuated after adjustment for confounding variables. There were raised RRs for bereaved participants dying of cardiovascular disease, coronary heart disease, stroke, all cancer, lung cancer, smoking-related cancer, and accidents or violence. After adjustment for confounding variables, RRs remained higher for bereaved participants for all these causes except for mortality from lung cancer. There was no strong statistical evidence that the increased risks of death associated with bereavement changed with time after bereavement. Conclusions: Conjugal bereavement, in addition to existing risk factors, is related to mortality risk for major causes of death.

Increasing body mass index from age 5 to 14 years predicts asthma among adolescents: evidence from a birth cohort study.

Abstract: Background: Obesity and asthma are common disorders, and the prevalence of both has increased in recent decades. It has been suggested that increases in the prevalence of obesity might in part explain the increase in asthma prevalence. This study aims to examine the prospective association between change in body mass index (BMI) z-score between ages 5 and 14 years and asthma symptoms at 14 years. Methods: Data was taken from the Mater University Study of Pregnancy and its outcomes (MUSP), a birth cohort of 7223 mothers and children started in Brisbane (Australia) in 1981. BMI was measured at age 5 and 14 years. Asthma was assessed from maternal reports of symptoms at age 5 and 14 years. In this study analyses were conducted on 2911 participants who had information on BMI and asthma at both ages. Results: BMI z-score at age 14 and the change in BMI z-score from age 5 to 14-years were positively associated with asthma symptoms at age 14 years, whereas BMI z-score at age 5 was not associated with asthma at age 14. Adjustment for a range of early-life exposures did not substantially alter these findings. The association between change in BMI z-score with asthma symptoms at 14 years appeared stronger for male subjects compared with female subjects but there was no statistical evidence for a sex difference (P=0.36). Conclusions: Increase in BMI z-score between age 5 and 14 years is associated with increased risk of asthma symptoms in adolescence.

Independent associations of fasting insulin, glucose, and glycated haemoglobin with stroke and coronary heart disease in older women

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 variations in fasting insulin, glucose, and glycated haemoglobin as risk factors for cardiovascular disease in women without diabetes is unclear. Our aim was to determine the independent associations of fasting insulin, glucose, and glycated haemoglobin with coronary heart disease and stroke in older women. METHODS AND FINDINGS: We undertook a prospective cohort study of 3,246 British women aged 60-79 y, all of whom were free of baseline coronary heart disease, stroke, and diabetes, and all of whom had fasting glucose levels below 7 mmol/l. Fasting insulin and homeostasis model assessment for insulin sensitivity (HOMA-S) were linearly associated with a combined outcome of coronary heart disease or stroke (n = 219 events), but there was no association of fasting glucose or glycated haemoglobin with these outcomes. Results were similar for coronary heart disease and stroke as separate outcomes. The age, life-course socioeconomic position, smoking, and physical activity adjusted hazard ratio for a combined outcome of incident coronary heart disease or stroke per one standard deviation of fasting insulin was 1.14 (95% CI 1.02-1.33). Additional adjustment for other components of metabolic syndrome, low-density lipoprotein cholesterol, fasting glucose, and glycated haemoglobin had little effect on this result. CONCLUSIONS: Our findings suggest that in women in the 60-79 y age range, insulin resistance, rather than insulin secretion or chronic hyperglycaemia, is a more important risk factor for coronary heart disease and stroke. Below currently used thresholds of fasting glucose for defining diabetes, neither fasting glucose nor glycated haemoglobin are associated with cardiovascular disease.

Prevalence and functionality of paucimorphic and private MC4R mutations in a large, unselected European British population, scanned by meltMADGE.

Abstract: Identification of unknown mutations has remained laborious, expensive, and only viable for studies of selected cases. Population-based "reference ranges" of rarer sequence diversity are not available. However, the research and diagnostic interpretation of sequence variants depends on such information. Additionally, this is the only way to determine prevalence of severe, moderate, and silent mutations and is also relevant to the development of screening programs. We previously described a system, meltMADGE, suitable for mutation scanning at the population level. Here we describe its application to a population-based study of MC4R (melanocortin 4 receptor) mutations, which are associated with obesity. We developed nine assays representing MC4R and examined a population sample of 1,100 subjects. Two "paucimorphisms" were identified (c.307G>A/p.Val103Ile in 27 subjects and c.-178A>C in 22 subjects). Neither exhibited any anthropometric effects, whereas there would have been >90% power to detect a body mass index (BMI) effect of 0.5 kg/m(2) at P=0.01. Two "private" variants were also identified. c.335C>T/p.Thr112Met has been previously described and appears to be silent. A novel variant, c.260C>A/p.Ala87Asp, was observed in a subject with a BMI of 31.5 kg/m(2) (i.e., clinically obese) but not on direct assay of a further 3,525 subjects. This mutation was predicted to be deleterious and analysis using a cyclic AMP (cAMP) responsive luciferase reporter assay showed substantial loss of function of the mutant receptor. This population-based mutation scan of MC4R suggests that there is no severe MC4R mutation with high prevalence in the United Kingdom, but that obesity-causing MC4R mutation at 1 in 1,100 might represent one of the commonest autosomal dominant disorders in man.

Associations of Circulating C-Reactive Protein and Interleukin-6 with Survival in Women with and without Cancer: Findings from the British Women's Heart and Health Study

Abstract: Background: Inflammation is associated with worse prognosis and survival in many cancers. Our aim was to investigate the associations of circulating C-reactive protein (CRP) and interleukin-6 (IL-6) concentrations with all-cause mortality in cancer patients and to determine whether any associations were specific to malignancy. Method: We used data from the British Women9s Heart and Health Study, a cohort of 4,286 women aged 60 to 79 years. We investigated the associations between CRP, IL-6, and survival in women with and without cancer using Cox regression and assessed the interaction between cancer status and these inflammatory markers to determine whether these associations differed according to cancer status. Results: Elevated CRP and IL-6 were associated with decreased survival in women with cancer [unadjusted hazard ratio per doubling of CRP, 1.22, 95% confidence interval (95% CI), 1.03, 1.46; and per doubling of IL-6, 1.52, 95% CI, 1.25, 1.86] and in women without cancer [CRP: 1.24 (1.12, 1.37); IL-6: 1.53 (1.35, 1.75)]. Adjustment for age, body mass index, physical activity level, socioeconomic position, HRT use, and tobacco smoking did not change these associations. After mutual adjustment, IL-6 but not CRP was independently associated with survival. We found no strong evidence that these associations differed between cancer patients and cancer-free women. Conclusions: Elevated CRP and IL-6 concentrations were similarly associated with an increased risk of death in elderly women with and without cancer. Thus, in this group, these markers are likely to be indicators of non-cancer comorbidities rather than related to the malignancy itself. (Cancer Epidemiol Biomarkers Prev 2007;16(6):1155–9)

Associations of Gestational Age and Intrauterine Growth With Systolic Blood Pressure in a Family-Based Study of 386 485 Men in 331 089 Families

Abstract: Background— We conducted a family-based study to explore mechanisms underlying the associations of birth weight and gestational age with systolic blood pressure measured at 17 to 19 years of age. Methods and Results— A record linkage study of 386 485 singleton-born men from 331 089 families was undertaken. Birth weight was inversely associated with systolic blood pressure within siblings, with a mean difference (adjusted for age at examination, examination center, and year of examination) within siblings per 1-SD difference in birth weight of −0.21 mm Hg (95% CI, −0.33 to −0.08) and between nonsiblings of −0.12 (95% CI, −0.16 to −0.08). Gestational age was inversely associated with systolic blood pressure within siblings (−0.18 mm Hg; 95% CI, −0.25 to −0.11, per week of gestational age) and between nonsiblings (−0.26 mm Hg; 95% CI, −0.29 to −0.24). Adjustment for socioeconomic position and maternal characteristics did not alter these within- or between-family associations. Furthermore, the associations we...

The associations between birthweight and adult markers of liver damage and function.

Abstract: Evidence suggesting an effect of fetal growth on liver development and function stems from both animal and human studies. The association of birthweight with adult markers of liver damage and function was examined in a random sample of 2101 British women aged 60-79 years. Age-adjusted natural logged levels of alanine aminotransferase (ALT) and gamma glutamyltransferase (GGT) decreased linearly across increasing thirds of birthweight. Alkaline phosphatase (ALP) levels were higher in women of the lowest third of the birthweight distribution compared with other women. No evidence was found for associations of birthweight with aspartate aminotransferase (AST), total bilirubin and albumin. After full adjustment for social class, physical activity, smoking and alcohol consumption, an increase in one standard deviation of birthweight (691 g) was associated with a 2% ([95% CI 0%, 4%], P = 0.021) decrease in the geometric mean of ALT, a 4% decrease in GGT ([95% CI 1%, 6%], P = 0.008) and a 2% decrease in ALP ([95% CI 0%, 3%], P = 0.001). Associations of birthweight with ALT and GGT, but not with ALP, were attenuated when adjusting for components of the metabolic syndrome. These findings suggest that factors affecting intrauterine growth may increase the propensity for adult liver damage. The attenuation of associations with adjustment for components of the metabolic syndrome is in line with non-alcoholic fatty liver disease, indicated by elevated ALT and GGT, being the hepatic manifestation of the metabolic syndrome, and of the influence of perinatal factors on this syndrome.

How many cases of Type 2 diabetes mellitus are due to being overweight in middle age? Evidence from the Midspan prospective cohort studies using mention of diabetes mellitus on hospital discharge or death records.

Abstract: Aims To relate body mass index (BMI) in middle age to development of diabetes mellitus. Methods Participants were 6927 men and 8227 women from the Renfrew/Paisley general population study and 3993 men from the Collaborative occupational study. They were aged 45–64 years and did not have reported diabetes mellitus. Cases who developed diabetes mellitus, identified from acute hospital discharge data and from death certificates in the period from screening in 1970–1976 to 31 March 2004, were related to BMI at screening. Results Of Renfrew/Paisley study men 5.4%, 4.8% of women and 5% of Collaborative study men developed diabetes mellitus. Odds ratios for diabetes mellitus were higher in the overweight group (BMI 25 to < 30 kg/m2) than in the normal weight group (BMI 18.5 to < 25 kg/m2) and highest in the obese group (BMI ≥ 30 kg/m2). Compared with the normal weight group, age-adjusted odds ratios for overweight and obese Renfrew/Paisley men were 2.73 [95% confidence interval (CI) 2.05, 3.64] and 7.26 (95% CI 5.26, 10.04), respectively. Further subdividing the normal, overweight and obese groups showed increasing odds ratios with increasing BMI, even at the higher normal level. Assuming a causal relation, around 60% of cases of diabetes could have been prevented if everyone had been of normal weight. Conclusions Overweight and obesity account for a major proportion of diabetes mellitus, as identified from hospital discharge and death records. With recent increases in the prevalence of overweight, the burden of disease related to diabetes mellitus is likely to increase markedly. Primordial prevention of obesity would be a major strategy for reducing the incidence of diabetes mellitus in populations.

Mendelian Randomization Suggests No Causal Association Between C-reactive Protein and Carotid Intima-media Thickness in the Young Finns Study

Abstract: To the Editor: It is unclear whether C-reactive protein (CRP), a nonspecific marker of acute phase inflammatory response, is causally related to arterial intima-media thickness (IMT), a risk factor for coronary heart disease (CHD). Previous evidence from conventional observational studies is inconsistent and suggests that the association may be biased or confounded.1 According to the Mendelian randomization approach, the genetic variants in the CRP gene ( CRP ) may represent good instruments for CRP levels that are largely free from reverse causation bias and confounding.1 If the association between CRP and IMT is causal, then genetic variants in CRP should be related to IMT to the extent predicted by the magnitude of their association with average CRP levels. …

Cognitive function in childhood and early adulthood and injuries later in life: the Metropolit 1953 male birth cohort

Abstract: BACKGROUND: It has been suggested that cognitive function in childhood is a modifiable risk factor for adult injury. This study examines the relationship between cognitive function measured at the age of 12 and 18 years and fatal and non-fatal injuries later in adult life. METHODS: A total of 11 532 males born in Copenhagen, Denmark in 1953 were followed from 1978 until 2001 with outcomes (death from and hospital admission for unintentional injury) obtained from national registers. At the age of 12 years, 7987 of these cohort members had completed a questionnaire, which included information on cognitive performance. In addition, cognitive test scores measured on most (90%) cohort members were retrieved from the conscription board records (18 years). RESULTS: During follow-up, 100 of the men died as a result of and 2123 had been admitted to hospital at least once for injury. Cognitive function measured at both the age of 12 and 18 years was inversely associated with any form of unintentional injury. Adjustment for educational attainment at the age of 18 years attenuated these associations but did not remove them completely. The association was most evident for falls and poisoning, while associations with other injury types were weaker and disappeared after adjustment for educational status. Cognitive function was associated with repeated hospital admissions for injuries as well as length of hospital stay. CONCLUSIONS: We found marked inverse associations between cognitive function measured in ages 12 and 18 years and adult risk of fatal or non-fatal unintentional injury. An overall increase in educational level may result in a reduction in adult injury risk. Language: en