Women's reproductive health factors and body adiposity: findings from the UK Biobank.

OBJECTIVE: To conduct a comprehensive examination of the association between women's reproductive health factors and measures of body adiposity in a contemporary Western population. METHODS: A cross-sectional analysis of 502 664 individuals from the UK Biobank was conducted. Multivariable linear regression models were used to examine the association of age at menarche, age at first birth, parity and age at menopause with measures of general and central body adiposity, adjusted for age, smoking and socioeconomic status. The association between number of children and body adiposity in men was also assessed. RESULTS: Age at menarche was inversely associated with body mass index (BMI); adjusted mean BMI was 29.0 kg m(-2) in women with menarche before the age of 12 years, compared with 26.5 kg m(-2) in those who had menarche after 14 years of age. Age at first birth was linearly and inversely associated with BMI: 0.16 kg m(-2) lower BMI per year increase in age of first birth. Each additional live birth or child fathered was associated with a 0.22 kg m(-2) higher BMI in women and a 0.14 kg m(-2) higher BMI in men. There was no evidence for an association between age at menopause and BMI. Corresponding associations for other markers of general or abdominal adiposity were similar to those for BMI. Findings were broadly similar in analyses stratified by age, smoking status, socioeconomic status, ethnic background, and history of diabetes or cardiovascular disease. CONCLUSIONS: In women from a contemporary Western population, earlier age at menarche and age at first birth, and higher number of total live births were associated with higher levels of body adiposity. Prospective evaluations of the association between reproductive health factors, adiposity and the onset of cardiometabolic diseases are needed to assess causality, and to explore the mechanisms involved.

Associations of diabetes mellitus with site-specific cancer mortality in the Asia-Pacific region.

BACKGROUND: Owing to the increasing prevalence of obesity and diabetes in Asia, and the paucity of studies, we examined the influence of raised blood glucose and diabetes on cancer mortality risk. MATERIALS AND METHODS: Thirty-six cohort Asian and Australasian studies provided 367, 361 participants (74% from Asia); 6% had diabetes at baseline. Associations between diabetes and site-specific cancer mortality were estimated using time-dependent Cox models, stratified by study and sex, and adjusted for age. RESULTS: During a median follow-up of 4.0 years, there were 5992 deaths due to cancer (74% Asian; 41% female). Participants with diabetes had 23% greater risk of mortality from all-cause cancer compared with those without: hazard ratio (HR) 1.23 [95% confidence interval (CI) 1.12, 1.35]. Diabetes was associated with mortality due to cancer of the liver (HR 1.51; 95% CI 1.19, 1.91), pancreas (HR 1.78; 95% CI 1.20, 2.65), and, less strongly, colorectum (HR 1.32; 95% CI 0.98, 1.78). There was no evidence of sex- or region-specific differences in these associations. The population attributable fractions for cancer mortality due to diabetes were generally higher for Asia compared with non-Asian populations. CONCLUSION: Diabetes is associated with increased mortality from selected cancers in Asian and non-Asian populations.

Associations between gender, age and waist circumference.

In December 2008, the World Health Organization (WHO) convened a consultation to discuss cut-points for waist circumference (WC). As part of that effort, this paper examines the impact of gender and age on WC. As WC is influenced by body weight, body composition and fat distribution, their associations with gender and age were reviewed. We also noted the relationships with sex hormones, parity and menopause. We then summarized data on gender, age and WC. This presentation is not intended to be comprehensive, but to provide an overview of the available research. There are large differences in body composition in men and women, with women having more body fat. Fat distribution also differs with gender, with men having a relatively more central distribution of fat. These differences begin early in life and become more apparent in puberty due to changes in sex hormone levels. In both, men and women, waist and waist-to-hip ratio increase with age. A large portion of this increase is driven by gains in body weight, but the increases observed are larger than those that would be predicted from increases in the body mass index alone, and increases in WC are seen with aging in the absence of weight gain. The current practice of using seperate waist cut-points by gender is appropriate. Although WC increases with age, so does the risk of many chronic diseases. An evaluation of the need for age-specific waist cut-points in adults would need to consider disease risk.

Adult height and cancer mortality in Asia: the Asia Pacific Cohort Studies Collaboration.

BACKGROUND: The observation that taller people experience an increased risk of selected cancers is largely restricted to Caucasian cohorts. These associations may plausibly differ in Asian populations. For the first time, we make direct comparison in the same analyses of the associations between height and a series of malignancies in Australasian (Caucasian) and Asian populations. METHODS: Analyses were based on the Asia Pacific Cohort Studies Collaboration of 506 648 study participants (408 381 Asia, 98 267 Australasia) drawn from 38 population-based cohort studies. Cox proportional hazards regression was used to estimate the relationship between height and cancer rates. RESULTS: A total of 3 272 600 person-years of follow-up gave rise to 7497 cancer deaths (4415 in Asia; 3082 in Australasia). After multiple adjustments and left censoring, taller individuals experienced increased rates of carcinoma of the intestine (men and women); all cancers, liver, lung, breast, 'other' malignancies (all women); and cancers of the prostate and bladder (men). No consistent regional (Asia versus Australasia) or sex differences were observed. CONCLUSIONS: In the present study, taller men and women had an elevated risk of selected malignancies. These associations did not differ appreciably between Asian and Caucasian populations.

Efficacy of weight loss drugs on obesity and cardiovascular risk factors in obese adolescents: a meta-analysis of randomized controlled trials.

Weight loss drugs have been developed to reduce the comorbidities associated with excess weight. We conducted a meta-analysis of the efficacy of orlistat and sibutramine on weight, body mass index, waist circumference and cardiovascular risk factors in overweight adolescents. MEDLINE and the Cochrane Library were searched for relevant articles using MESH terms and keywords. Studies were included if they had reported quantitative estimates and standard deviations of the association between each weight loss drug and weight, with information on at least one cardiovascular risk factor. A total of eight trials (three orlistat and five sibutramine) with information on 1391 individuals was included in the present analysis. The mean decrease in weight between the intervention and control groups was 5.25 kg (95% confidence interval: 3.03-7.48) after a minimum follow-up of 6 months. There was evidence of statistical heterogeneity between the studies (I(2) = 76%) that was no longer apparent after exclusion of trials of orlistat (mean weight decrease = 5.32 kg; I(2) = 38%). There was little evidence that treatment was associated with adverse effects on cardiovascular risk factors but this requires verification from future large trials with longer study follow-up.

A systematic review of school-based intervention studies for the prevention or reduction of excess weight among Chinese children and adolescents.

The aim of this paper was to conduct a systematic review of intervention studies in China aimed at the prevention or control of excess weight gain among children and adolescents. Two Chinese databases (The China Full Text Database and Wanfang Database) and two English databases (Medline and Meditext) were searched with keywords for intervention studies published between 1990 and 2006. Data were extracted on aspects of study quality, methodology and effectiveness of interventions. Quality assessment was conducted using a previously established assessment tool. Twenty-two studies were included, of which 17 were conducted among overweight and/or obese children and/or adolescents. Interventions strategies varied across studies but the majority focused on improving the level of knowledge, physical activity levels and/or diet of overweight children and adolescents. Most studies reported a beneficial effect of the intervention with one or more of the study outcomes, but all of the studies had serious, or moderate, methodological weaknesses. None of the trials identified by this systematic review demonstrated convincing evidence of the efficacy of any single intervention for the prevention of overweight and obesity in children and adolescents from Mainland China. Future intervention trials should address the methodological weaknesses identified in this review.

Comparison of the risk of fatal coronary heart disease in treated xanthomatous and non-xanthomatous heterozygous familial hypercholesterolaemia: a prospective registry study.

BACKGROUND: A clinical diagnosis of familial hypercholesterolaemia (FH) is often made in the absence of tendon xanthomata (TX), which are not usually present before the fourth decade of life. The prognosis of treated non-xanthomatous (TX-) FH is uncertain and the objective of this study was to compare mortality from coronary heart disease (CHD) in patients with treated TX+ (definite) and TX- (possible) heterozygous FH. METHODS: A diagnosis of definite or possible FH was based on raised cholesterol levels (>7.5 mmol/l) and a family history of premature CHD or hypercholesterolaemia. Patients were recruited from 21 outpatient lipid clinics in the UK from 1980 to 1998. The cohort of 1569 patients with TX+ FH were followed for 12754 person years and the cohort of 1302 patients with TX- FH for 10238 person years. The standardised mortality ratio (SMR) was calculated from the ratio of the number of deaths observed to the number expected in the general population of England and Wales (SMR=100 for reference population). FINDINGS AND DISCUSSION: CHD accounted for 64 (63%) of the 102 deaths in the TX+ cohort and 38 (57%) of the 67 deaths in the TX- cohort with the SMR for a fatal coronary event being, respectively, 294 (95% confidence interval 228, 380, P<0.00001) and 205 (95% CI 145, 282, P=0.0001). The similarly elevated CHD mortality risk suggests that, in adulthood, both groups of patients should be treated equally aggressively with HMG Co A reductase inhibitors (statins).

The relation between dietary flavonol intake and coronary heart disease mortality: a meta-analysis of prospective cohort studies.

OBJECTIVE: To assess the association of dietary flavonol intake with the subsequent risk of coronary heart disease (CHD) mortality. DESIGN: Meta-analysis of prospective cohort studies published before September 2001. Studies were identified by MEDLINE and EMBASE searches and by scanning relevant reference lists. The following information was extracted from published reports: size of cohort, mean age, mean duration of follow-up, number of fatal CHD events, mean flavonol intake, main sources of flavonol intake, degree of adjustment for potential confounders, and the relation of CHD mortality to dietary flavonol intake measured at baseline. RESULTS: Seven prospective cohorts of men and women were identified including a total of 2087 fatal CHD events. Comparison of individuals in the top third with those in the bottom third of dietary flavonol intake yielded a combined risk ratio of 0.80 (95% CI 0.69-0.93) after adjustment for known CHD risk factors and other dietary components. CONCLUSION: This overview of prospective cohort studies indicates that high dietary intake of flavonols from a small number of fruits and vegetables, tea and red wine may be associated with a reduced risk from CHD mortality in free-living populations.

Risk of fatal stroke in patients with treated familial hypercholesterolemia: a prospective registry study.

BACKGROUND AND PURPOSE: Although it is recognized that in heterozygous familial hypercholesterolemia, large extracranial carotid vessels are affected by atherosclerosis, the risk of fatal stroke after treatment with cholesterol-lowering therapy remains uncertain. The goal of this study was to determine the risk of fatal stroke in patients with treated familial hypercholesterolemia. METHODS: A cohort of 1405 men and 1466 women with definite or possible heterozygous familial hypercholesterolemia was recruited from 21 outpatient lipid clinics in the United Kingdom. Patients were followed up prospectively from 1980 to 1998 for 22 992 person-years for a median duration of 7.9 years (interquartile range, 4.9 to 12.0 years). The mortality rate was calculated, and the standardized mortality ratio for men and women 20 to 79 years of age was derived from the ratio of the observed deaths to the number expected in the general population of England and Wales (standardized mortality ratio=100 for the standard population). RESULTS: A total of 169 deaths occurred; 9 (5.3%) were a result of stroke. The mortality rate from stroke was 0.39 per 1000 person-years (95% confidence interval, 0.18 to 0.74), and the standardized mortality ratio for fatal stroke was nonsignificantly lower than in the general population (79; 95% CI, 36 to 150). CONCLUSIONS: The results suggest that patients with treated familial hypercholesterolemia are not at increased risk of fatal stroke. However, the possibility cannot be excluded that untreated individuals are at increased risk, which would be consistent with the evidence that familial hypercholesterolemia is a panvascular disease.

Nutritional research in World War 2: the Oxford Nutrition Survey and its research potential 50 years later.

To investigate the nutritional status of the population of the UK during the Second World War, nutritional surveys were commissioned in 1941. These included surveys of two groups of pregnant women: the first comprised 120 working-class women who were studied in the spring of 1942, and a second group of 253 women in 1944. Both groups were followed up until after delivery. Detailed biochemical assessments were performed on each subject. Our statistical analysis of the haematological data showed that nearly 25% of women from the 1942 group were deficient in protein, over 60% were deficient in Fe and vitamin A, and over 70% had severe vitamin C deficiency. The findings were reported to the Ministries of Health and Food who instigated a food supplementation policy at the end of 1942 that entitled pregnant women in the UK to extra rations of fruit, dairy produce and to a supply of cod-liver-oil tablets. A second group of 253 pregnant women were studied 15 months later which enabled the effects of this programme to be investigated. Supplementation reduced the proportion of women with vitamin A concentrations below the normal range from 63% to 38%, and vitamin C from 78% to 20%, but protein and Fe concentrations were not increased but actually declined. These findings continued to exert an influence over government food policy for pregnant women until the abolition of rationing in 1954.

The role of size at birth and postnatal catch-up growth in determining systolic blood pressure: a systematic review of the literature.

OBJECTIVE: To conduct a systematic review in order to (i) summarize the relationship between birthweight and blood pressure, following numerous publications in the last 3 years, (ii) assess whether other measures of size at birth are related to blood pressure, and (iii) study the role of postnatal catch-up growth in predicting blood pressure. DATA IDENTIFICATION: All papers published between March 1996 and March 2000 that examined the relationship between birth weight and systolic blood pressure were identified and combined with the papers examined in a previous review. SUBJECTS: More than 444,000 male and female subjects aged 0-84 years of all ages and races. RESULTS: Eighty studies described the relationship of blood pressure with birth weight The majority of the studies in children, adolescents and adults reported that blood pressure fell with increasing birth weight, the size of the effect being approximately 2 mmHg/kg. Head circumference was the only other birth measurement to be most consistently associated with blood pressure, the magnitude of the association being a decrease in blood pressure by approximately 0.5 mmHg/cm. Skeletal and non-skeletal postnatal catch-up growth were positively associated with blood pressure, with the highest blood pressures occurring in individuals of low birth weight but high rates of growth subsequently. CONCLUSIONS: Both birth weight and head circumference at birth are inversely related to systolic blood pressure. The relationship is present in adolescence but attenuated compared to both the pre- and post-adolescence periods. Accelerated postnatal growth is also associated with raised blood pressure.

Nausea and vomiting in early pregnancy: its role in placental development.

Nausea and emesis in early pregnancy is a common phenomenon affecting between 50% and 70% of pregnant women, but little is known about the etiology and possible function of this common and often incapacitating condition. Morning sickness has been reported to have a positive effect on pregnancy outcome and is associated with a decreased risk of miscarriage, preterm birth, low birth weight (LBW), and perinatal death. Both human and animal studies have shown that reduced energy intakes in early pregnancy are associated with increased placental weight. Based on evidence from the literature, a hypothesis is proposed that suggests a functional role for the nausea and emesis of pregnancy in stimulating early placental growth. It is suggested that morning sickness, resulting from secretion of hCG and thyroxine, reduces maternal energy intake. As a result, maternal levels of the anabolic hormones, insulin, and insulin growth factor-1 (IGF-1) are lowered. By suppressing maternal tissue synthesis in early pregnancy, we propose that nausea and vomiting in pregnancy helps ensure that nutrient partitioning favors the developing placenta. Evidence is also presented that suggests there may be a positive relationship between morning sickness and preconceptional body mass index (BMI), such that women who are underweight will experience less severe symptoms of morning sickness compared with women with normal preconceptional BMIs.