Associations of childhood adiposity with menstrual irregularity and polycystic ovary syndrome in adulthood: the Childhood Determinants of Adult Health Study and the Bogalusa Heart Study.

STUDY QUESTION: Is high adiposity in childhood associated with menstrual irregularity and polycystic ovary syndrome (PCOS) in later life? SUMMARY ANSWER: Overall, greater childhood BMI was associated with menstrual irregularity, and greater childhood BMI and waist/height ratio (WHtR) in white but not black participants were associated with PCOS in adulthood. WHAT IS KNOWN ALREADY: Increased childhood BMI has been associated with irregular menstrual cycles and PCOS symptoms in adulthood in two longitudinal population-based studies, but no study has reported on associations with childhood abdominal obesity. Few studies have investigated whether there are racial differences in the associations of adiposity with PCOS though there has been some suggestion that associations with high BMI may be stronger in white girls than in black girls. STUDY DESIGN, SIZE, DURATION: The study included 1516 participants (aged 26-41 years) from the Australian Childhood Determinants of Adult Health study (CDAH) and 1247 participants (aged 26-57 years) from the biracial USA Babies substudy of the Bogalusa Heart Study (BBS) who were aged 7-15 years at baseline. At follow-up, questions were asked about menstruation (current for CDAH or before age 40 years for BBS), ever having had a diagnosis of PCOS and symptoms of PCOS. PARTICIPANTS/MATERIALS, SETTING, METHODS: In CDAH, a single childhood visit was conducted in 1985. In BBS, multiple childhood visits occurred from 1973 to 2000 and race was reported (59% white; 41% black). In childhood, overweight and obesity were defined by international age-sex-specific standards for BMI and WHtR was considered as an indicator of abdominal obesity. Multilevel mixed-effects Poisson regression estimated relative risks (RRs) adjusting for childhood age, highest parental and own education and age at menarche. MAIN RESULTS AND THE ROLE OF CHANCE: The prevalence of childhood obesity was 1.1% in CDAH and 7.5% in BBS. At follow-up, menstrual irregularity was reported by 16.7% of CDAH and 24.5% of BBS participants. The prevalence of PCOS was 7.4% in CDAH and 8.0% in BBS participants. In CDAH, childhood obesity was associated with menstrual irregularity (RR = 2.84, 95% CI: 1.63-4.96) and PCOS (RR = 4.05, 95% CI: 1.10-14.83) in adulthood. With each 0.01 unit increase in childhood WHtR there was a 6% (95% CI: 1-11%) greater likelihood of PCOS. Overall, in BBS, childhood obesity was associated with increased risk of menstrual irregularity (RR = 1.44, 95% CI: 1.08-1.92) in adulthood. Significant interaction effects between race and childhood adiposity were detected in associations with PCOS. In BBS white participants, childhood obesity was associated with PCOS (RR = 2.93, 95% CI: 1.65-5.22) and a 0.01 unit increase in childhood WHtR was associated with an 11% (95% CI: 5-17%) greater likelihood of PCOS in adulthood. In BBS black participants, no statistically significant associations of childhood adiposity measures with PCOS were observed. LIMITATIONS, REASONS FOR CAUTION: The classification of menstrual irregularity and PCOS was based on self-report by questionnaire, which may have led to misclassification of these outcomes. However, despite the limitations of the study, the prevalence of menstrual irregularity and PCOS in the two cohorts was consistent with the literature. While the study samples at baseline were population-based, loss to follow-up means the generalizability of the findings is uncertain. WIDER IMPLICATIONS OF THE FINDINGS: Greater childhood adiposity indicates a higher risk of menstrual irregularity and PCOS in adulthood. Whether this is causal or an early indicator of underlying hormonal or metabolic disorders needs clarification. The stronger associations of adiposity with PCOS in white than black participants suggest that there are racial differences in childhood adiposity predisposing to the development of PCOS and other environmental or genetic factors are also important. STUDY FUNDING/COMPETING INTEREST(S): The CDAH study was supported by grants from the Australian National Health and Medical Research Council (grants 211316, 544923 and 1128373). The Bogalusa Heart Study is supported by US National Institutes of Health grants R01HD069587, AG16592, HL121230, HD032194 and P50HL015103. No competing interests existed.

Establishing a three-generation prospective study: Bogalusa daughters.

OBJECTIVE: The Developmental Origins of Disease hypothesis has spurred increased interest in how prenatal exposures affect lifelong health, while mechanisms such as epigenetics may explain the multigenerational influences on health. Such factors are not well captured within conventional epidemiologic study designs. We explored the feasibility of collecting information on the offspring and grand-offspring of participants in a long-running study. DESIGN: The Bogalusa Heart Study is a study, begun in 1973, of life-course cardiovascular health in a semirural population (65% white and 35% black). MAIN MEASURES: Female participants who had previously provided information on their pregnancies were contacted to obtain contact information for their daughters aged 12 and older. Daughters were then contacted to obtain reproductive histories, and invited for a clinic or lab visit to measure cardiovascular risk factors. RESULTS: Two hundred seventy-four daughters of 208 mothers were recruited; 81% (223) had a full clinic visit and 19% (51) a phone interview only. Forty-five percent of the daughters were black, and 55% white. Mean and median age at interview was 27, with 15% under the age of 18. The strongest predictors of participation were black race, recent maternal participation in the parent study, and living in or near Bogalusa. Simple correlations for cardiovascular risk factors across generations were between r = 0.19 (systolic blood pressure) and r = 0.39 (BMI, LDL). CONCLUSION: It is feasible to contact the children of study participants even when participants are adults, and initial information on the grandchildren can also be determined in this manner.

Childhood adiposity and fertility difficulties: the Bogalusa Heart Study.

BACKGROUND: Adult obesity is associated with infertility; however, childhood obesity has received little consideration. OBJECTIVES: The present study sought to evaluate the impact of childhood adiposity on fertility. METHODS: Associations between childhood adiposity and self-reported fertility difficulties were estimated among women participating in a long-term study of cardiovascular risks and reproductive health (n = 1061). RESULTS: Participants with obesity between ages 9 and 12 were more likely to report fertility difficulties (adjusted relative risk [aRR], 1.82, 95% CI 1.17-2.82) and inability to become pregnant when trying (aRR = 1.94, 95% CI 1.22-3.08) as were those with obesity prior to age 9 (aRR = 1.76, 95% CI 1.04-2.97). Similar associations were seen among those ever overweight or obese in childhood. High subscapular skinfold thickness (age < 12) increased risk of receiving help becoming pregnant (aRR = 2.16, 95% CI 1.15-4.06), inability to become pregnant (aRR = 1.46, 95% CI 1.05-2.04) and any fertility difficulties (aRR = 1.56, 95% CI 1.13-2.14); associations for triceps skinfold were attenuated. Participants with increased adiposity also had fewer pregnancies and live births. Effects persisted, excluding women with polycystic ovarian syndrome. CONCLUSIONS: This study supports an association between childhood adiposity and infertility, not solely driven by polycystic ovarian syndrome.

Maternal apolipoprotein E genotype as a potential risk factor for poor birth outcomes: The Bogalusa Heart Study.

OBJECTIVE: The objective of this study was to assess the association between apolipoprotein E (apoE) genotype and preterm birth (PTB) and small for gestational age (SGA). STUDY DESIGN: ApoE phenotyping was performed on 680 women linked to 1065 births. Allele frequencies were compared and PTB and SGA risk was estimated using log-binomial regression. RESULTS: The ɛ2 allele was more common in SGA births (P<0.01). SGA risk was increased among ɛ2 carriers compared with genotype ɛ3/ɛ3, though associations were attenuated following adjustment for maternal age, education, race, smoking and prenatal visits. Stronger associations were observed for term SGA (first birth: adjusted relative risk (aRR)=1.78, 95% confidence interval (CI) 1.06 to 2.98; any birth: aRR=1.52, 95% CI 0.96 to 2.40) and among whites specifically (first: aRR=2.88, 95% CI 1.45 to 5.69; any: aRR=2.75, 95% CI 1.46 to 5.22). CONCLUSIONS: Associations between maternal apoE genotype and SGA may represent decreased fetal growth in women with lower circulating cholesterol levels.

Childhood obesity patterns and relation to middle-age sleep apnoea risk: the Bogalusa Heart Study.

BACKGROUND: Obese adults have a higher risk of obstructive sleep apnoea (OSA); however, the relationship between childhood obesity and adult OSA risk is unclear. Objectives This study aimed to examine overweight/obesity (OW) in childhood and risk of OSA in middle age. METHODS: Childhood OW status was classified as never OW, weight cycling, persistent OW and incident OW. After 35 years of follow-up, high risk for OSA was determined by a positive score in ≥2 domains on the Berlin Questionnaire with obesity removed from scoring. RESULTS: At initial assessment, mean (SD) age was 9.9 (2.9) years, and 23.9% were OW. Overall, 25.7% had scores indicating a high risk for OSA. Compared with participants who were never OW, those with persistent OW and incident OW were 1.36 (95%CI: 1.04-1.77) and 1.47 (1.11-1.96) times more likely to be high risk for OSA, after adjustment for multiple risk factors and adult OW status. Participants with an OW duration of 1-4 years, 5-8 years, and 8+ years were 0.96 (0.44-2.09), 1.20 (0.70-2.04) and 1.52 (1.22-1.90) times more likely to be high risk for OSA compared with those who were never OW (P for trend: 0.0002). CONCLUSIONS: These results suggest that childhood OW is associated with a high risk of OSA in middle age.

The low-carbohydrate diet and cardiovascular risk factors: evidence from epidemiologic studies.

AIMS: Obesity is an important public health issue because of its high prevalence and concomitant increase in risk of cardiovascular diseases. Low carbohydrate diets are popular for weight loss and weight management but are not recommended in leading guidelines due to the perception that increases in dietary fat intake may lead to an adverse cardiovascular risk profile. To clarify the effects of a low-carbohydrate diet for weight loss on cardiovascular disease risk factors as compared to a low fat diet for weight loss, we systematically reviewed data from randomized controlled clinical trials and large observational studies. DATA SYNTHESIS: We searched the MEDLINE database (Jan 1966-Nov 2013) to identify studies that examined a low-carbohydrate diet as compared to a low-fat diet for weight loss or the improvement of cardiovascular disease risk factors. CONCLUSIONS: Recent randomized controlled trials document that low-carbohydrate diets not only decrease body weight but also improve cardiovascular risk factors. In light of this evidence from randomized controlled trials, dietary guidelines should be re-visited advocating a healthy low carbohydrate dietary pattern as an alternative dietary strategy for the prevention of obesity and cardiovascular disease risk factors.

Long-term oral mesalazine adherence and the risk of disease flare in ulcerative colitis: nationwide 10-year retrospective cohort from the veterans affairs healthcare system.

BACKGROUND: Adherence is a major factor in determining disease activity in ulcerative colitis (UC). There are limited data on long-term nationwide adherence levels among patients with UC. AIM: To evaluate the long-term adherence levels to oral mesalazine (mesalamine) in the Veterans Affairs (VA) healthcare system, to determine the impact of non-adherence on the risk of flares, and to evaluate the different pharmacy data-based adherence indicators. METHODS: Nationwide data were obtained from the VA for the period 2001-2011. UC patients who started mesalazine maintenance during the inclusion period were included. Level of adherence was assessed using three different indicators: medication possession ratio (MPR), continuous single-interval medication availability (CSA) and continuous multiple-interval medication gaps (CMG). Cox regression modelling was used to predict disease flares and assess the predictive value of each adherence indicator. RESULTS: We included 13 062 patients into the analysis with median follow-up time of 6.1 years. Percentage of patients with high adherence was 47%, 43%, 31% as identified by CSA, MPR and CMG respectively. Low adherers had a significant increase in the risk of flares compared with high adherers (Hazard ratio: 2.8, 1.7 and 1.8, P < 0.001 for CSA, MPR and CMG, respectively). Compared with other adherence indicators, CSA offered the best trend in predicting disease flares. CONCLUSIONS: Long-term high-adherence level was lower than previously reported. Adherence was a significant factor in predicting disease flares. Pharmacy adherence indicators may be useful to healthcare providers in identifying patients at high risk of exacerbations.

Non-soy legume consumption lowers cholesterol levels: a meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: Studies evaluating the effect of legume consumption on cholesterol have focused on soybeans, however non-soy legumes, such as a variety of beans, peas, and some seeds, are commonly consumed in Western countries. We conducted a meta-analysis of randomized controlled trials evaluating the effects of non-soy legume consumption on blood lipids. METHODS AND RESULTS: Studies were retrieved by searching MEDLINE (from January 1966 through July 2009), EMBASE (from January 1980 to July 2009), and the Cochrane Collaboration's Central Register of Controlled Clinical Trials using the following terms as medical subject headings and keywords: fabaceae not soybeans not isoflavones and diet or dietary fiber and cholesterol or hypercholesterolemia or triglycerides or cardiovascular diseases. Bibliographies of all retrieved articles were also searched. From 140 relevant reports, 10 randomized clinical trials were selected which compared a non-soy legume diet to control, had a minimum duration of 3 weeks, and reported blood lipid changes during intervention and control. Data on sample size, participant characteristics, study design, intervention methods, duration, and treatment results were independently abstracted by 2 investigators using a standardized protocol. Data from 10 trials representing 268 participants were examined using a random-effects model. Pooled mean net change in total cholesterol for those treated with a legume diet compared to control was -11.8 mg/dL (95% confidence interval [CI], -16.1 to -7.5); mean net change in low-density lipoprotein cholesterol was -8.0mg/dL (95% CI, -11.4 to -4.6). CONCLUSION: These results indicate that a diet rich in legumes other than soy decreases total and LDL cholesterol.

Safety and efficacy of glargine compared with NPH insulin for the treatment of Type 2 diabetes: a meta-analysis of randomized controlled trials.

AIMS: We systematically analysed evidence from randomized controlled trials (RCTs) examining the safety and efficacy of neutral protamine Hagedorn (NPH) insulin and glargine in the management of adults with Type 2 diabetes. METHODS: Studies were identified by searching medline (1966-March 2007), embase (1974-2007), American Diabetes Association abstract database and the Cochrane Central Register of Controlled Trials using Medical Subject Headings (MeSH) diabetes mellitus, Type 2, insulin, insulin isophane, hypoglycaemic agents and the keywords glargine and NPH. Data on study design, participants, fasting plasma glucose (FPG), glycated haemoglobin (HbA(1c)), body weight and hypoglycaemia were independently abstracted by two investigators using a standardized protocol. RESULTS: Data from a total of 4385 participants in 12 RCTs were pooled using a random-effects model. The mean net change (95% confidence interval) for FPG, HbA(1c) and body weight for patients treated with NPH insulin as compared with glargine was 0.21 mmol/l (-0.02 to 0.45), 0.08% (-0.04 to 0.21) and -0.33 kg (-0.61 to -0.06), respectively, with negative values favouring NPH and positive values favouring glargine. More participants experienced symptomatic and nocturnal hypoglycaemia on NPH than glargine, but there was no significant difference in confirmed or severe episodes. CONCLUSIONS: We identified no difference in glucose-lowering between insulin glargine and NPH insulin, but less patient-reported hypoglycaemia with glargine and slightly less weight gain with NPH in adults with Type 2 diabetes.

Legume consumption and risk of coronary heart disease in US men and women: NHANES I Epidemiologic Follow-up Study.

BACKGROUND: Soybean protein and dietary fiber supplementation reduce serum cholesterol in randomized controlled trials. Consumption of legumes, which are high in bean protein and water-soluble fiber, may be associated with a reduced risk of coronary heart disease (CHD). METHODS: A total of 9632 men and women who participated in the First National Health and Nutrition Examination Survey Epidemiologic Follow-up Study (NHEFS) and were free of cardiovascular disease (CVD) at their baseline examination were included in this prospective cohort study. Frequency of legume intake was estimated using a 3-month food frequency questionnaire, and incidence of CHD and CVD was obtained from medical records and death certificates. RESULTS: Over an average of 19 years of follow-up, 1802 incident cases of CHD and 3680 incident cases of CVD were documented. Legume consumption was significantly and inversely associated with risk of CHD (P =.002 for trend) and CVD (P =.02 for trend) after adjustment for established CVD risk factors. Legume consumption 4 times or more per week compared with less than once a week was associated with a 22% lower risk of CHD (relative risk, 0.78; 95% confidence interval, 0.68-0.90) and an 11% lower risk of CVD (relative risk, 0.89; 95% confidence interval, 0.80-0.98). CONCLUSIONS: Our study indicates a significant inverse relationship between legume intake and risk of CHD and suggests that increasing legume intake may be an important part of a dietary approach to the primary prevention of CHD in the general population.

Dietary potassium intake and risk of stroke in US men and women: National Health and Nutrition Examination Survey I epidemiologic follow-up study.

BACKGROUND AND PURPOSE: The few prospective studies that have explored the association between dietary intake of potassium and risk of stroke have reported inconsistent findings. This study examines the relationship between dietary potassium intake and the risk of stroke in a representative sample of the US general population. METHODS: Study participants included 9805 US men and women who participated in the first National Health and Nutrition Examination Survey (NHANES I) Epidemiologic Follow-Up Study. Dietary potassium and total energy intake were estimated at baseline by using a 24-hour dietary recall. Incidence data for stroke and coronary heart disease were obtained from medical records and death certificates. RESULTS: Over an average of 19 years of follow up, 927 stroke events and 1847 coronary heart disease events were documented. Overall, stroke hazard was significantly different among quartiles of potassium intake (likelihood ratio P=0.03); however, a test of linear trend across quartiles did not reach a customary level of statistical significance (P=0.14). Participants consuming a low potassium diet at baseline (<34.6 mmol potassium per day) experienced a 28% higher hazard of stroke (hazard ratio 1.28, 95% CI 1.11 to 1.47; P<0.001) than other participants, after adjustment for established cardiovascular disease risk factors. CONCLUSIONS: These findings suggest that low dietary potassium intake is associated with an increased risk of stroke. However, the possibility that the association is due to residual confounding cannot be entirely ruled out in this observational study.

Risk factors for congestive heart failure in US men and women: NHANES I epidemiologic follow-up study.

BACKGROUND: The incidence of congestive heart failure (CHF) has been increasing steadily in the United States during the past 2 decades. We studied risk factors for CHF and their corresponding attributable risk in the First National Health and Nutrition Examination Survey Epidemiologic Follow-up Study. PARTICIPANTS AND METHODS: A total of 13 643 men and women without a history of CHF at baseline examination were included in this prospective cohort study. Risk factors were measured using standard methods between 1971 and 1975. Incidence of CHF was assessed using medical records and death certificates obtained between 1982 and 1984 and in 1986, 1987, and 1992. RESULTS: During average follow-up of 19 years, 1382 CHF cases were documented. Incidence of CHF was positively and significantly associated with male sex (relative risk [RR], 1.24; 95% confidence interval [CI], 1.10-1.39; P<.001; population attributable risk [PAR], 8.9%), less than a high school education (RR, 1.22; 95% CI, 1.04-1.42; P =.01; PAR, 8.9%), low physical activity (RR, 1.23; 95% CI, 1.09-1.38; P<.001; PAR, 9.2%), cigarette smoking (RR, 1.59; 95% CI, 1.39-1.83; P<.001; PAR, 17.1%), overweight (RR, 1.30; 95% CI, 1.12-1.52; P =.001; PAR, 8.0%), hypertension (RR, 1.40; 95% CI, 1.24-1.59; P<.001; PAR, 10.1%), diabetes (RR, 1.85; 95% CI, 1.51-2.28; P<.001; PAR, 3.1%), valvular heart disease (RR, 1.46; 95% CI, 1.17-1.82; P =.001; PAR, 2.2%), and coronary heart disease (RR, 8.11; 95% CI, 6.95-9.46; P<.001; PAR, 61.6%). CONCLUSIONS: Male sex, less education, physical inactivity, cigarette smoking, overweight, diabetes, hypertension, valvular heart disease, and coronary heart disease are all independent risk factors for CHF. More than 60% of the CHF that occurs in the US general population might be attributable to coronary heart disease.

Effects of lifestyle modification on treatment and prevention of hypertension.

Recently published observational epidemiologic studies and clinical trials have provided additional evidence that weight loss, dietary sodium reduction, moderation of alcohol consumption, physical activity, and potassium supplementation reduce blood pressure. Lifestyle modification should be recommended for the prevention and treatment of hypertension in the general population.

Dietary sodium intake and subsequent risk of cardiovascular disease in overweight adults.

CONTEXT: Dietary sodium is positively associated with blood pressure, and ecological and animal studies both have suggested that high dietary sodium intake increases stroke mortality. OBJECTIVE: To examine the risk of cardiovascular disease associated with dietary sodium intake in overweight and nonoverweight persons. DESIGN: Prospective cohort study. SETTING: The first National Health and Nutrition Examination Survey Epidemiologic Follow-up Study, conducted in 1982-1984, 1986, 1987, and 1992. PARTICIPANTS: Of those aged 25 to 74 years when the survey was conducted in 1971 -1975 (14407 participants), a total of 2688 overweight and 6797 nonoverweight persons were included in the analysis. MAIN OUTCOME MEASURES: Dietary sodium and energy intake were estimated at baseline using a single 24-hour dietary recall method. Incidence and mortality data for cardiovascular disease were obtained from medical records and death certificates. RESULTS: For overweight and nonoverweight persons, over an average of 19 years of follow-up, the total number of documented cases were as follows: 680 stroke events (210 fatal), 1727 coronary heart disease events (614 fatal), 895 cardiovascular disease deaths, and 2486 deaths from all causes. Among overweight persons with an average energy intake of 7452 kJ, a 100 mmol higher sodium intake was associated with a 32% increase (relative risk [RR], 1.32; 95% confidence interval [CI], 1.07-1.64; P = .01) in stroke incidence, 89% increase (RR, 1.89; 95% CI, 1.31-2.74; P<.001) in stroke mortality, 44% increase (RR, 1.44; 95% CI, 1.14-1.81; P = .002) in coronary heart disease mortality, 61% increase (RR, 1.61; 95% CI, 1.32-1.96; P<.001) in cardiovascular disease mortality, and 39% increase (RR, 1.39; 95% CI, 1.23-1.58; P<.001) in mortality from all causes. Dietary sodium intake was not significantly associated with cardiovascular disease risk in nonoverweight persons. CONCLUSIONS: Our analysis indicates that high sodium intake is strongly and independently associated with an increased risk of cardiovascular disease and all-cause mortality in overweight persons.