Health Prospective Cohort Study Research Articles

Prenatal oxidative stress and rapid infant weight gain.

Infant weight patterns predict subsequent weight outcomes. Rapid infant weight gain, defined as a >0.67 increase in weight-for-age z-score (WAZ) between two time points in infancy, increases obesity risk. Higher oxidative stress, an imbalance between antioxidants and reactive oxygen species, has been associated with low birthweight and paradoxically also with later obesity. We hypothesized that prenatal oxidative stress may also be associated with rapid infant weight gain, an early weight pattern associated with future obesity. Within the NYU Children's Health and Environment Study prospective pregnancy cohort, we analyzed associations between prenatal lipid, protein, and DNA urinary oxidative stress biomarkers and infant weight data. Primary outcome was rapid infant weight gain (>0.67 increase in WAZ) between birth and later infancy at the 8 or 12 month visit. Secondary outcomes included: very rapid weight gain (>1.34 increase in WAZ), low (<2500 g) or high (≥4000 g) birthweight, and low (< -1 WAZ) or high (>1 WAZ) 12 month weight. Pregnant participants consented to the postnatal study (n = 541); 425 participants had weight data both at birth and in later infancy. In an adjusted binary model, prenatal 8-iso-PGF2α, a lipid oxidative stress biomarker, was associated with rapid infant weight gain (aOR 1.44; 95% CI: 1.16, 1.78, p = 0.001). In a multinomial model using ≤0.67 change in WAZ as a reference group, 8-iso-PGF2α was associated with rapid infant weight gain (defined as >0.67 but ≤1.34 WAZ; aOR 1.57, 95% CI: 1.19, 2.05, p = 0.001) and very rapid infant weight gain (defined as >1.34 WAZ; aOR 1.33; 95% CI: 1.02, 1.72, p < 0.05) Secondary analyses detected associations between 8-iso-PGF2α and low birthweight outcomes. We found an association between 8-iso-PGF2α, a lipid prenatal oxidative stress biomarker, and rapid infant weight gain, expanding our understanding of the developmental origins of obesity and cardiometabolic disease.

Infant Nasopharyngeal Microbiota Subphenotypes and Early Childhood Lung Function: Evidence from a Rural Ghanaian Pregnancy Cohort.

Early life respiratory microbiota may increase risk for future pulmonary disease. Associations between respiratory microbiota and lung health in children from low- and middle-income countries are not well-described. Leveraging the Ghana Randomized Air Pollution and Health Study (GRAPHS) prospective pregnancy cohort in Kintampo, Ghana, we collected nasopharyngeal swabs in 112 asymptomatic children aged median 4.3 months (interquartile range (IQR) 2.9, 7.1) and analyzed 22 common bacterial and viral pathogens with MassTag polymerase chain reaction (PCR). We prospectively followed the cohort and measured lung function at age four years by impulse oscillometry. First, we employed latent class analysis (LCA) to identify nasopharyngeal microbiota (NPM) subphenotypes. Then, we used linear regression to analyze associations between subphenotype assignment and lung function. LCA suggest that a two-class model best described the infant NPM. We identified a higher diversity subphenotype (N = 38, 34%) with more pathogens (median 4; IQR 3.25, 4.75) and a lower diversity subphenotype (N = 74, 66%) with fewer pathogens (median 1; IQR 1, 2). In multivariable linear regression models, the less diverse NPM subphenotype had higher small airway resistance (R5-R20 = 17.9%, 95% CI 35.6, 0.23; p = 0.047) compared with the more diverse subphenotype. Further studies are required to understand the role of the microbiota in future lung health.

Magnesium intake is associated with a reduced risk of incident liver cancer, based on an analysis of the NIH-American Association of Retired Persons (NIH-AARP) Diet and Health Study prospective cohort

Liver cancer incidence and mortality are escalating globally. Magnesium intake has been studied extensively in nonmalignant liver pathology, but the association between dietary intake of magnesium and primary liver malignancy has not been previously evaluated. We aimed to determine the association between total magnesium intake and primary liver cancer risk. Using the NIH-American Association of Retired Persons (NIH-AARP) Diet and Health Study prospective cohort, we estimated the association between magnesium intake and the risk of incident primary liver cancer using Cox proportional hazard modeling adjusted for relevant confounders. Comprehensive stratified and sensitivity analyses were performed. During 6.4 million person-years of follow-up time, 1067 primary liver cancers occurred in 536,359 participants. Higher magnesium intake was independently associated with a lower risk of liver cancer (P-trend=0.005), with intakes in the highest compared with lowest quartile associated with 35% lower risk (HR: 0.65; 95% CI: 0.48, 0.87). The dose-related inverse association was more pronounced in moderate and heavy alcohol users (HR: 0.54; 95% CI: 0.35, 0.82; P-trend=0.006), and this interaction was statistically significant (P-interaction=0.04). Based on a prospective cohort analysis, we demonstrated that magnesium intake is associated with a lower risk of primary liver cancer, which was more pronounced among moderate and heavy alcohol users. Robust experimental and mechanistic data provide a biological basis to support these findings.

Associations between calcium and magnesium intake and the risk of incident oesophageal cancer: an analysis of the\xa0NIH-AARP Diet and Health Study\xa0prospective cohort

BackgroundRisk reduction through dietary modifications is an adjunct strategy for prevention of oesophageal cancer, a leading cause of cancer-related mortality and morbidity worldwide. We aimed to estimate the association between calcium and magnesium intakes and incident oesophageal cancer (OC).MethodsWe conducted a retrospective analysis of the NIH-AARP Diet and Health Study prospective cohort. We used multivariable Cox proportional hazard modeling to estimate the association between total intakes and incident OC overall and by histology (oesophageal squamous cell carcinoma (OSCC) and adenocarcinoma (OAC)). Sensitivity and stratified analyses were performed.ResultsAmong 536,359 included respondents, 1414 incident OCs occurred over 6.5 million person-years follow-up time. Increasing dietary calcium intake was associated with an adjusted 32–41% lower risk of OSCC compared to the lowest quartile (p-trend 0.01). There was a positive association between increasing magnesium intake and OAC risk, but only among participants with low calcium:magnesium intake ratios (p-trend 0.04). There was a significant interaction with smoking status.ConclusionsBased on a retrospective analysis of the NIH-AARP Diet and Health Study prospective cohort, dietary intakes of calcium and magnesium were significantly associated with risk of OSCC and, among certain participants, OAC, respectively. If validated, these findings could inform dietary modifications among at-risk individuals. Mechanistic investigations would provide additional insight.

Circulating Branched-Chain Amino Acids and Incident Cardiovascular Disease in a Prospective Cohort of US Women.

Circulating branched-chain amino acids (BCAAs; isoleucine, leucine, and valine) are strong predictors of type 2 diabetes mellitus (T2D), but their association with cardiovascular disease (CVD) is uncertain. We hypothesized that plasma BCAAs are positively associated with CVD risk and evaluated whether this was dependent on an intermediate diagnosis of T2D. Participants in the Women's Health Study prospective cohort were eligible if free of CVD at baseline blood collection (n=27 041). Plasma metabolites were measured via nuclear magnetic resonance spectroscopy. Multivariable Cox regression models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for BCAAs with incident CVD (myocardial infarction, stroke, and coronary revascularization). We confirmed 2207 CVD events over a mean 18.6 years of follow-up. Adjusting for age, body mass index, and other established CVD risk factors, total BCAAs were positively associated with CVD (per SD: HR, 1.13; 95% CI, 1.08-1.18), comparable to LDL-C (low-density lipoprotein cholesterol) with CVD (per SD: HR, 1.12; 95% CI, 1.07-1.17). BCAAs were associated with coronary events (myocardial infarction: HR, 1.16; 95% CI, 1.06-1.26; revascularization: HR, 1.17; 95% CI, 1.11-1.25), and borderline significant association with stroke (HR, 1.07; 95% CI, 0.99-1.15). The BCAA-CVD association was greater (P interaction=0.036) among women who developed T2D before CVD (HR, 1.20; 95% CI, 1.08-1.32) versus women without T2D (HR, 1.08; 95% CI, 1.03-1.14). Adjusting for LDL-C, an established CVD risk factor, did not attenuate these findings; however, adjusting for HbA1c and insulin resistance eliminated the associations of BCAAs with CVD. Circulating plasma BCAAs were positively associated with incident CVD in women. Impaired BCAA metabolism may capture the long-term risk of the common cause underlying T2D and CVD.

Abstract 048: Circulating Branched-Chain Amino Acids and Incident Cardiovascular Disease in a Prospective Cohort of US Women

Introduction: Recent metabolomics studies have identified circulating levels of branched-chain amino acids (BCAAs; isoleucine, leucine, valine) as strong predictors of type 2 diabetes (T2D). Whether BCAAs are implicated in cardiovascular disease (CVD) risk has not been established. Hypothesis: We hypothesized that higher baseline levels of plasma BCAAs are associated with an elevated risk of incident CVD events, and evaluated whether this relationship was dependent on an intermediate diagnosis of T2D. Methods: Participants enrolled in the Women’s Health Study prospective cohort were eligible if they did not report CVD or cancer prior to baseline blood collection (N=27,172, mean baseline age=54.7 years). Plasma BCAA metabolites were measured via proton NMR spectroscopy, ln-transformed, and standardized for analysis. We used multivariable Cox proportional regression models to estimate hazard ratios (HR) and 95% confidence intervals (CI) per standard deviation (SD) of total and individual BCAAs with incident CVD (myocardial infarction [MI], stroke, coronary revascularization). Results: 1,917 confirmed CVD events occurred over follow-up (mean 18.6 years). In models adjusted for age, body mass index, smoking status, diet quality, physical activity, and other established CVD risk factors, total BCAAs were positively associated with CVD (per SD, HR=1.13, CI=1.08 to 1.19), comparable in magnitude to the association of LDL cholesterol with CVD (per SD, HR=1.15, CI=1.09 to 1.21). In particular, BCAAs were associated with coronary events (MI: HR=1.21, CI=1.10 to 1.33; revascularization: HR=1.15, CI=1.07 to 1.23), but not with stroke (HR=1.07, CI=0.98 to 1.15). The BCAA-CVD relationship was notably greater (p-interaction=0.008) among participants who developed T2D prior to a CVD event (HR=1.25, CI=1.13 to 1.39), vs. women without T2D (HR=1.07, CI=1.01 to 1.13). Isoleucine, leucine, and valine were each associated with CVD (p&lt;0.05). Further adjusting for biomarkers of potential intermediates, HbA1c, lipids, and a lipoprotein-based insulin resistance score entirely eliminated the associations of BCAAs with CVD. Conclusions: Circulating plasma BCAAs were positively associated with long-term incident CVD in a cohort of US women, in particular among women who developed T2D prior to a CVD event. Impaired BCAA metabolism may represent a shared pathway of insulin resistance that links the risks of T2D and CVD.

Psychological symptoms and subsequent healthy lifestyle after a colorectal cancer diagnosis.

Although medical professionals recommend lifestyle changes following a colorectal cancer (CRC) diagnosis to improve outcomes, such changes are not consistently implemented. This study examines whether higher distress is associated with lower likelihood of engaging in favorable behaviors after CRC diagnosis. Women from the Nurses' Health Study prospective cohort who completed anxiety (n = 145) and depression (n = 227) symptom scales within 4 years after receiving a CRC diagnosis were included. Measures of lifestyle (diet, physical activity, alcohol, smoking, body mass index [BMI]) were queried prediagnosis, when psychological symptoms were assessed (1988 and 1992, respectively), and then every 4 years thereafter until 2010. Women were categorized according to initial psychological symptoms levels and followed through 2010 or until last follow-up completed. Higher versus lower anxiety symptoms were significantly related to unhealthier lifestyle scores throughout follow-up (β = -0.25, CI [-0.44, -0.05]); however, the rate of change over time was similar across groups (pinteraction effect = 0.41). Stratified analyses hinted that higher anxiety and depression symptoms were related to increased odds of reporting a future unhealthy lifestyle within 10-years postdiagnosis. Beyond 10 years, anxiety became statistically unrelated with future lifestyle, and higher depressive symptoms were associated with lower odds of subsequently having an unhealthy lifestyle, albeit nonstatistically significant (OR = 0.35, 95% CI [0.10, 1.24], p = 0.10). Among women with CRC, higher anxiety and depression symptoms were associated with subsequent unhealthier lifestyle in the 10 years following diagnosis. With replication, such findings may suggest that treating psychological symptoms early in the cancer trajectory may not solely reduce psychological distress but also promote healthier lifestyle. (PsycINFO Database Record

Exposure to Greenness and Mortality in a Nationwide Prospective Cohort Study of Women.

Background:Green, natural environments may ameliorate adverse environmental exposures (e.g., air pollution, noise, and extreme heat), increase physical activity and social engagement, and lower stress.Objectives:We aimed to examine the prospective association between residential greenness and mortality.Methods:Using data from the U.S.-based Nurses’ Health Study prospective cohort, we defined cumulative average time-varying seasonal greenness surrounding each participant’s address using satellite imagery [Normalized Difference Vegetation Index (NDVI)]. We followed 108,630 women and observed 8,604 deaths between 2000 and 2008.Results:In models adjusted for mortality risk factors (age, race/ethnicity, smoking, and individual- and area-level socioeconomic status), women living in the highest quintile of cumulative average greenness (accounting for changes in residence during follow-up) in the 250-m area around their home had a 12% lower rate of all-cause nonaccidental mortality [95% confidence interval (CI); 0.82, 0.94] than those in the lowest quintile. The results were consistent for the 1,250-m area, although the relationship was slightly attenuated. These associations were strongest for respiratory and cancer mortality. The findings from a mediation analysis suggested that the association between greenness and mortality may be at least partly mediated by physical activity, particulate matter < 2.5 μm, social engagement, and depression.Conclusions:Higher levels of green vegetation were associated with decreased mortality. Policies to increase vegetation may provide opportunities for physical activity, reduce harmful exposures, increase social engagement, and improve mental health. Planting vegetation may mitigate the effects of climate change; in addition, evidence of an association between vegetation and lower mortality rates suggests it also might be used to improve health.Citation:James P, Hart JE, Banay RF, Laden F. 2016. Exposure to greenness and mortality in a nationwide prospective cohort study of women. Environ Health Perspect 124:1344–1352; http://dx.doi.org/10.1289/ehp.1510363

WCRF/AICR recommendation adherence and breast cancer incidence among postmenopausal women with and without non-modifiable risk factors.

Taller height, family history of breast cancer, greater number of years of potential fertility and nulliparity are established non-modifiable risk factors for postmenopausal breast cancer. Greater adherence to the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) diet, physical activity and body weight recommendations has previously been shown to be associated with lower breast cancer risk. However, no prior studies have evaluated whether women with non-modifiable risk factors receive similar benefits from recommendation adherence compared to women without these risk factors. In the Iowa Women's Health Study prospective cohort, we investigated whether associations of WCRF/AICR recommendation adherence differed by the presence/absence of non-modifiable breast cancer risk factors. Baseline (1986) questionnaire data from 36,626 postmenopausal women were used to create adherence scores for the WCRF/AICR recommendations (maximum score = 8.0). Overall and single recommendation adherence in relation to breast cancer risk (n = 3,189 cases) across levels of non-modifiable risk factors were evaluated using proportional hazards regression. Mean adherence score was 5.0 points (range: 0.5-8.0). Higher adherence scores (score ≥ 6.0 vs. ≤ 3.5, HR = 0.76, 95% CI = 0.67-0.87), and adherence to the individual recommendations for body weight and alcohol intake were associated with a lower breast cancer incidence. While not statistically significant among women with more non-modifiable risk factors (score ≥ 6.0 vs. ≤ 3.5, HR = 0.76, 95% CI = 0.36-1.63), hazard ratios were comparable to women with the no non-modifiable risk factors (score ≥ 6.0 vs. ≤ 3.5, HR = 0.74, 95% CI = 0.49-0.93) (p-interaction = 0.57). WCRF/AICR recommendation adherence is associated with lower breast cancer risk, regardless of non-modifiable risk factor status.

Relative Greenness And Cardiovascular Disease Incidence In The Nurses' Health Study

Background: A few studies have linked lower cardiovascular disease (CVD) rates among individuals with higher levels of greenness around their residential address, although evidence is inconsistent. Because greenness varies across regions of the US, we examined how intra-urban relative greenness exposure might affect CVD using data from the US-based Nurses' Health Study prospective cohort. Methods: A total of 92,053 women (mean age 70 years, range 53-91) were followed from 2000-2010. Greenness exposure was measured using the Normalized Difference Vegetation Index (NDVI) based on satellite imagery. The three month time-varying mean NDVI value within a 250 meter buffer was linked to participants' mailing addresses. We created Z-scores of each participant's NDVI value relative to the average NDVI values for the Core Based Statistical Area (urban centers) in which the participant lived. CVD was defined as the first incidence of fatal coronary heart disease, nonfatal myocardial infarction, or stroke confirmed by medical record review. We conducted a survival analysis and incorporated multiple CVD risk factors or exposure predictors taken from biennial questionnaires and spatial data. Results: Over 1,715,019 person-years, we identified 3,503 CVD events. After adjusting for age, calendar year, race, smoking status, pack-years smoked, parental occupation, nursing degree status, marital status, husband's highest education, Census tract median home value, Census tract median income, population density, and region, a one unit increase in the cumulative average Z-score of relative greenness was associated with a 6% reduction in CVD incidence (95% CI 0.90, 0.99). Conclusions: We observed a protective effect of relative greenness on CVD incidence in this cohort of adult women, indicating that higher exposure to greenness within a city may be related to lower CVD risk. Further research is needed to determine the pathway of influence from relative greenness exposure to CVD incidence.

Surrounding Greenness and Mortality in the Nurses’ Health Study

Background: Many studies have demonstrated lower mortality rates among individuals with higher levels of green space around their residential address, although evidence is inconsistent to date. This study aimed to examine the effect of residential greenness on mortality using data from the US-based Nurses’ Health Study prospective cohort. Methods: A total of 108,629 women were followed from 2000 until 2006. Biennial questionnaires were mailed every two years. Residential greenness was measured using the Normalized Difference Vegetation Index (NDVI) based on Landsat satellite imagery, and defined using the six month time-varying mean NDVI value within a 1,250 meter radial buffer of the participants’ mailing addresses. Deaths were usually reported by families or identified by searching the National Death Index. We conducted a survival analysis and incorporated covariates taken from questionnaires and spatial data. Results: Over 7,524,535 person-months, 8,591 deaths were identified. Mean NDVI values were 144...

Diet Patterns and Mortality: Common Threads and Consistent Results

Diet Patterns and Mortality: Common Threads and Consistent Results

Bidirectional associations between insomnia symptoms and unhealthy behaviours

It has been suggested that there are associations among insomnia symptoms and unhealthy behaviours. However, previous studies are sparse and mainly cross-sectional, and have not been focused on several key unhealthy behaviours. The aim of this study was to examine whether the associations are bidirectional, i.e. whether insomnia symptoms are associated with subsequent unhealthy behaviours, and whether unhealthy behaviours are associated with subsequent insomnia symptoms. The data were derived from the Helsinki Health Study prospective cohort study. The baseline data were collected in 2000-02 (n = 8960, response rate 67%) among 40-60-year-old employees of the City Helsinki, Finland. The follow-up data were collected in 2007 (n = 7332, response rate 83%). Logistic regression analysis was used to examine the associations among insomnia symptoms and unhealthy behaviours, including smoking, heavy and binge drinking, physical inactivity and unhealthy food habits. Frequent insomnia symptoms at baseline were associated with subsequent heavy drinking [odds ratio (OR): 1.34; 95% confidence interval (CI): 1.07-1.68] and physical inactivity (OR: 1.27; 95% CI: 1.08-1.48) after full adjustment for gender, age, corresponding unhealthy behaviour at baseline, marital status, occupational class, sleep duration and common mental disorders. Additionally, heavy drinking (OR: 1.48; 95% CI: 1.22-1.80) and binge drinking (OR: 1.26; 95% CI: 1.08-1.46) at baseline were associated with subsequent insomnia symptoms at follow-up after full adjustment. In conclusion, insomnia symptoms were associated with subsequent heavy drinking and physical inactivity, and heavy and binge drinking were also associated with subsequent insomnia symptoms.

A prospective study of periodontal disease and risk of rheumatoid arthritis.

To test for an association between periodontal disease (PD) and incident rheumatoid arthritis (RA) in a large prospective cohort. We conducted a prospective analysis of history of periodontal surgery, tooth loss, and risk of RA among 81,132 women in the Nurses' Health Study prospective cohort. Periodontal surgery and tooth loss were used as proxies for history of PD. There were 292 incident RA cases diagnosed from 1992 to 2004. Information on periodontal surgery and tooth loss in the past 2 years was collected by questionnaire in 1992. Cox proportional hazards models were used to assess relationships between periodontal surgery, tooth loss, and risk of RA adjusting for age, smoking, number of natural teeth, body mass index, parity, breastfeeding, postmenopausal status, postmenopausal hormone use, father's occupation, and alcohol intake. Compared with those who reported no history of periodontal surgery or tooth loss, women with periodontal surgery or tooth loss did not have a significantly elevated risk of RA in multivariable-adjusted models (RR 1.24, 95% CI 0.83, 1.83; and RR 1.18, 95% CI 0.47, 2.95, respectively). In analyses stratified by ever and never-smokers, ever-smokers with periodontal surgery had an increased risk that was also nonsignificant. Those with severe PD (both history of periodontal surgery and tooth loss) did not have a significant increased risk. In this large cohort of American women, there was no evidence of an increased risk of later-onset RA among those with a history of periodontal surgery and/or tooth loss.

Sleep problems and major weight gain: a follow-up study

To examine the associations between sleep problems and major weight gain during a 5- to 7-year follow-up among middle-aged women and men. The Helsinki Health Study prospective cohort baseline survey data from 2000 to 2002 (n = 8960, response rate 67%) among 40- to 60-year-old municipal employees and follow-up survey data from 2007 (n = 7332, response rate 83%) were used. Logistic regression analysis was used to examine the association between the four-item Jenkins Sleep Questionnaire and major weight gain of 5 kg or more over a 5- to 7-year follow-up. Half of the participants reported at least occasional sleep problems, whereas 13% of women and 17% of men reported no such problems at baseline. The frequency of sleep problems varied by item. Frequent sleep problems were reported by 20% of women and 17% of men. Major weight gain was reported by 25% of women and 24% of men. Trouble falling asleep (odds ratio (OR) 1.65; 95% confidence interval (CI) 1.22, 2.22), waking up several times per night (OR 1.49; 95% CI 1.22, 1.81) and trouble staying asleep (OR 1.41; 95% CI 1.13, 1.75) were associated with major weight gain during the follow-up in women but not in men. In contrast, waking up tired was unassociated with weight gain. The summary measure of the four items was also associated with weight gain in women. Adjusting for baseline body mass index, physical health, health behaviour, marital status, education, work arrangements and sleep duration had only minor effects on the above associations. Adjusting for common mental disorders at baseline, the associations were attenuated but remained for trouble falling asleep, waking up several times per night and trouble staying asleep. Occasional sleep problems were also associated with weight gain. Sleep problems likely contribute to weight gain. To prevent major weight gain and obesity, sleep problems need to be taken into account.

Postmenopausal Levels of Endogenous Sex Hormones and Risk of Colorectal Cancer

Observational epidemiologic studies and randomized trials have reported a protective effect of oral hormonal replacement therapy on risk of colorectal cancer. Only one previous prospective study, the Women's Health Initiative Observational Study, has reported on the relationship between endogenous hormones and incident colorectal cancer. Contrary to expectation, the investigators found that women with higher circulating estradiol levels were at increased risk of developing colorectal cancer. We conducted a case-control study nested within the New York University Women's Health Study prospective cohort to evaluate the association between endogenous levels of estrone, estradiol, and sex hormone-binding globulin (SHBG) with risk of colorectal cancer. We measured hormones and SHBG in serum samples collected at enrollment from a total of 148 women who subsequently developed colorectal cancer and 293 matched controls. Circulating estrone levels were positively associated with risk of colorectal cancer: The odds ratio for the highest versus lowest quartile of estrone was 1.8 (95% confidence interval, 1.0-3.3). We found a nonsignificant inverse association between SHBG and colorectal cancer, which disappeared after adjusting for body mass index. We did not find an association between estradiol and colorectal cancer risk, but we cannot rule out a potential association because of substantial laboratory error in the measurement. Our results suggest that endogenous estrone is associated with increased risk of colorectal cancer in postmenopausal women.