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The Mediterranean diet (MedDiet) has been linked with better cognitive function and brain integrity. To examine the association of modified Mediterranean diet (mMedDiet) scores from early through middle adulthood in relation to volumetric and microstructural midlife MRI brain measures. Assess the association of mMedDiet and brain measures with four cognitive domains. If variables are correlated, determine if brain measures mediate the relationship between mMedDiet and cognition. 618 participants (mean age 25.4±3.5 at year 0) of the Coronary Artery Risk Development in Young Adults (CARDIA) study were included. Cumulative average mMedDiet scores were calculated by averaging scores from years 0, 7, and 20. MRI scans were obtained at years 25 and 30. General linear models were used to examine the association between mMedDiet and brain measures. Higher cumulative average mMedDiet scores were associated with better microstructural white matter (WM) integrity measured by fractional anisotropy (FA) at years 25 and 30 (all ptrend <0.05). Higher mMedDiet scores at year 7 were associated with higher WM FA at year 25 (β= 0.003, ptrend = 0.03). Higher mMedDiet scores at year 20 associated with higher WM FA at years 25 (β= 0.0005, ptrend = 0.002) and 30 (β= 0.0003, ptrend = 0.02). mMedDiet scores were not associated with brain volumes. Higher mMedDiet scores and WM FA were both correlated with better executive function, processing speed, and global cognition (all ptrend <0.05). WM FA did not mediate the association between mMedDiet scores and cognition. mMedDiet scores may be associated with microstructural WM integrity at midlife. [ABSTRACT FROM AUTHOR]

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Background: Cancer, its treatment, and associated adverse effects may accelerate the functional aging of cancer survivors. In the current study, the authors used geriatric assessment (GA) to compare the functional age of long-term cancer survivors with that of similarly aged women without a cancer history, and to examine whether functional age influences all-cause mortality differently between these 2 groups.Methods: Participants included 1723 cancer survivors and 11,145 age-matched, cancer-free women enrolled in the Iowa Women's Health Study in 1986 who completed the 2004 questionnaire (at ages 73-88 years). GA domain deficits included ≥2 physical function limitations, ≥2 comorbidities, poor general health, poor mental health, and underweight. The risk of all-cause mortality was estimated for deficits in each GA domain between 4 groups based on the cross-classification of the presence and/or absence of cancer history and GA domain deficit (the referent group was cancer-free women without a GA deficit).Results: Both cancer history and GA domain deficits significantly predicted 10-year mortality for all GA domains. Cancer survivors without deficits had a 1.3-fold to 1.4-fold risk of mortality, similar to the 1.1-fold to 1.7-fold risk noted among cancer-free women with deficits (all P < .05). Cancer survivors with deficits were found to have the highest mortality risk for 4 of 5 domains (hazard ratio range, 1.6-2.0). Mortality risk increased with the increasing number of GA deficits, which was greater in cancer survivors compared with cancer-free women.Conclusions: Even without GA deficits, cancer survivors appear to have an excess risk of death compared with women without cancer, and these deficits add to mortality risk. Interventions are needed to maintain or improve functional/physiological capacity as women age, especially in cancer survivors. [ABSTRACT FROM AUTHOR]

Background Joint British Societies have developed a tool that utilizes information on cardiovascular disease (CVD) risk factors to estimate an individual's 'heart age'. We studied if using heart age as an add-on to conventional risk communication could enhance the motivation for adapting to a healthier lifestyle resulting in improved whole-blood cholesterol and omega-3 status after 4 weeks. Methods A total of 48 community pharmacies were cluster-randomized to use heart age+conventional risk communication (intervention) or only conventional risk communication (control) in 378 subjects after CVD risk-factor assessment. Dried blood spots were obtained with a 4-week interval to assay whole-blood cholesterol and omega-3 fatty acids. We also explored pharmacy-staff's (n =27) perceived utility of the heart age tool. Results Subjects in the intervention pharmacies (n =137) had mean heart age 64 years and chorological age 60 years. In these, cholesterol decreased by median (interquartile range) −0.10 (−0.40, 0.35) mmol/l. Cholesterol decreased by −0.20 (−0.70, 0.30) mmol/l (P difference =0.24) in subjects in the control pharmacies (n =120) with mean chronological age 60 years. We observed increased concentrations of omega-3 fatty acids after 4 weeks, non-differentially between groups. Pharmacy-staff (n =27) agreed that heart age was a good way to communicate CVD risk, and most (n =25) agreed that it appeared to motivate individuals to reduce elevated CVD risk factors. Conclusions The heart age tool was considered a convenient and motivating communication tool by pharmacy-staff. Nevertheless, communicating CVD risk as heart age was not more effective than conventional risk communication alone in reducing whole-blood cholesterol levels and improving omega-3 status. [ABSTRACT FROM AUTHOR]

Systolic and diastolic blood pressures provide information about cardiovascular disease (CVD) but are only extremes of the pressure waveform during the cardiac cycle. We developed summaries of the pressure decay, called PTC1 and PTC2, that are related to arterial compliance and to an existing proprietary summary that has been shown to predict CVD. We derived the summaries from a Windkessel model (consisting of a decaying exponential plus a dampened cosine, with an intercept so they are independent of calibration with blood pressure, unlike the proprietary measures), and we estimated them using nonlinear least squares with standard, free software. Among 6,228 adults from the Multi-Ethnic Study of Atherosclerosis, initially free of CVD in 2000–2002, mean PTC2 was 94 (standard deviation, 46) milliseconds. During median 15-year follow-up, there were 911 CVD events (including 609 incidents of coronary heart disease and 270 strokes). One-standard-deviation higher PTC2 was associated with 17% (95% confidence interval: 10, 24) lower CVD risk, after adjustment for traditional risk factors. Results were similar for PTC1. PTC1 and PTC2 are relatively straightforward to compute and add information beyond traditional risk factors for prediction of CVD. Our work enables others to replicate and extend our results with waveforms from any suitable device. [ABSTRACT FROM AUTHOR]

Intentional weight loss can increase health risk in the long‐term, despite short‐term benefits, because human adipose tissue is widely contaminated with various lipophilic environmental contaminants, especially persistent organic pollutants (POPs). Recently, chronic exposure to low POPs has emerged as a new risk factor for common metabolic diseases and cardiovascular diseases. The amount of POPs released from adipocytes to the circulation increases during weight loss, thereby increasing POPs exposure of other critical organs. Possible harmful effects due to release of POPs during weight loss are opposite to those usually expected from losing weight. It is speculated that this tradeoff can explain recent puzzling findings on intensive weight loss. The presence of POPs in adipose tissue adds a challenge to weight management and an optimal strategy of weight management needs to consider both fat mass and dynamics of POPs. [ABSTRACT FROM AUTHOR]

Background: Problematic relationship to eating and food (PREF) captures a broad range of unhealthy eating behaviors. We previously reported that higher BMI is associated with PREF and graded by the number of PREF endorsed. In this study, we prospectively examined the association between PREF and metabolic syndrome and diabetes. Method: Eight PREF behaviors were assessed and summed to form the PREF score in 3800 black and white adults (age 27–41 years) in the Coronary Artery Risk Development in Young Adults Study. Diagnoses of incident metabolic syndrome and diabetes were made through 15 years of follow‐up. Logistic regression estimated the association with metabolic syndrome. Proportional hazards regression estimated the association with diabetes. Results: The odds ratio of metabolic syndrome was 1.25 per PREF point through 5 years of follow‐up (95% CI: 1.17–1.34) and 1.17 per point from 5 to 10 years of follow‐up (95% CI: 1.08–1.27). Hazard of diabetes was 1.20 per PREF point through 15 years of follow‐up (95% CI: 1.12–1.28). Both associations attenuated after adjustment for BMI. Discussion: Among participants with PREF, higher scores associate with metabolic syndrome and diabetes, with partial attenuation after adjustment for BMI. Early identification of PREF in middle‐aged adults may reduce the burden of metabolic health outcomes. [ABSTRACT FROM AUTHOR]

BACKGROUND: Although low-density lipoprotein cholesterol (LDL-C) remains the primary cholesterol target in clinical practice in children and adults, non-high-density lipoprotein cholesterol (non-HDL-C) has been suggested as a more accurate measure of atherosclerotic cardiovascular disease (ASCVD) risk. We examined the associations of childhood non-HDL-C and LDL-C levels with adult ASCVD events and determined whether non-HDL-C has better utility than LDL-C in predicting adult ASCVD events. METHODS: This prospective cohort study included 21126 participants from the i3C Consortium (International Childhood Cardiovascular Cohorts). Proportional hazards regressions were used to estimate the risk for incident fatal and fatal/nonfatal ASCVD events associated with childhood non-HDL-C and LDL-C levels (age- and sex-specific z scores; concordant/ discordant categories defined by guideline-recommended cutoffs), adjusted for sex, Black race, cohort, age at and calendar year of child measurement, body mass index, and systolic blood pressure. Predictive utility was determined by the C index. RESULTS: After an average follow-up of 35 years, 153 fatal ASCVD events occurred in 21126 participants (mean age at childhood visits, 11.9 years), and 352 fatal/nonfatal ASCVD events occurred in a subset of 11296 participants who could be evaluated for this outcome. Childhood non-HDL-C and LDL-C levels were each associated with higher risk of fatal and fatal/nonfatal ASCVD events (hazard ratio ranged from 1.27 [95% CI, 1.14-1.41] to 1.35 [95% CI, 1.13-1.60] per unit increase in the risk factor z score). Non-HDL-C had better discriminative utility than LDL-C (difference in C index, 0.0054 [95% CI, 0.0006-0.0102] and 0.0038 [95% CI, 0.0008-0.0068] for fatal and fatal/nonfatal events, respectively). The discordant group with elevated non-HDL-C and normal LDL-C had a higher risk of ASCVD events compared with the concordant group with normal non-HDL-C and LDL-C (fatal events: hazard ratio, 1.90 [95% CI, 0.98-3.70]; fatal/nonfatal events: hazard ratio, 1.94 [95% CI, 1.23-3.06]). CONCLUSIONS: Childhood non-HDL-C and LDL-C levels are associated with ASCVD events in midlife. Non-HDL-C is better than LDL-C in predicting adult ASCVD events, particularly among individuals who had normal LDL-C but elevated non- HDL-C. These findings suggest that both non-HDL-C and LDL-C are useful in identifying children at higher risk of ASCVD events, but non-HDL-C may provide added prognostic information when it is discordantly higher than the corresponding LDL-C and has the practical advantage of being determined without a fasting sample. [ABSTRACT FROM AUTHOR]

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Introduction: There are known racial differences in cardiovascular health behaviors, including smoking, physical activity, and diet quality. A better understanding of these differences may help identify intervention targets for reducing cardiovascular disease disparities. This study examined whether socioeconomic, psychosocial, and neighborhood environmental factors, in isolation or together, mediate racial differences in health behaviors.Methods: Participants were 3,081 men and women from the Coronary Artery Risk Development in Young Adults study who were enrolled in 1985-1986 (Year 0) and completed a follow-up examination in 2015-2016 (Year 30). A health behavior score was created at Years 0, 7, 20, and 30 using smoking, physical activity, and diet assessed that year. The race difference in health behavior score was estimated using linear regression in serial cross-sectional analyses. Mediation analyses computed the proportion of the race and health behavior score association attributable to socioeconomic, psychosocial, and neighborhood factors.Results: Data analysis conducted in 2016-2017 found that blacks had significantly lower health behavior scores than whites across 30 years of follow-up. Individual socioeconomic factors mediated 48.9%-70.1% of the association between race and health behavior score, psychosocial factors 20.3%-30.0%, and neighborhood factors 22.1%-41.4% (p<0.01 for all).Conclusions: Racial differences in health behavior scores appear to be mediated predominately by correspondingly large differences in socioeconomic factors. This study highlights the profound impact of socioeconomic factors, which are mostly not under an individual's control, on health behaviors. Policy action targeting socioeconomic factors may help reduce disparities in health behaviors. [ABSTRACT FROM AUTHOR]

There may be nontraditional pathways of chronic kidney disease (CKD) progression that are complementary to classical pathways. Therefore, we aimed to examine nontraditional risk factors for incident CKD and its progression. We used the generally healthy population (n = 4382) starting at age 27-41 years in the Coronary Artery Risk Development in Young Adults (CARDIA) cohort, which is an observational longitudinal study. Nontraditional risk factors included forced vital capacity, inflammation, serum urate, and serum carotenoids. CKD risk category was classified using the estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (UACR) measured in 1995-1996 and repeated every 5 years for 20 years: No CKD, low risk, moderate risk, high risk, and very high risk. At baseline, 84.8% had no CKD (eGFR ≥60 mL/min/1.73 m2 and UACR <10 mg/g), 10.3% were in the low risk (eGFR ≥60 and UACR 10-29), and 4.9% had CKD (eGFR <60 and/or UACR ≥ 30). Nontraditional risk factors were significantly associated with the progression of CKD to higher categories. Hazard ratios per standard deviation of the predictor for incident CKD and its progression from the No CKD and low and moderate risk into CKD were inverse for forced vital capacity and serum carotenoids and positive for serum urate, GlycA, and C-reactive protein, the first 3 even after adjustment for conventional risk factors. Several nontraditional markers were significantly associated with an increased risk of progression to higher CKD categories in generally healthy young to middle-aged adults. [Display omitted] [ABSTRACT FROM AUTHOR]

This article summarizes background materials and presentations at a symposium that considered the issue of the role of foods and dietary patterns vs. nutrients in relation to chronic disease risk. A model of food synergy is presented as a basis for studying whole foods and dietary patterns. Findings from a series of studies of walnuts were presented and support the concept that walnuts are a healthy food, with specific benefits in a mouse model of breast cancer growth, reductions in cardiovascular disease risk factors in humans, and motor performance and in vitro, in vivo, and ex vivo cellular response to challenge in an aged-rat model. [ABSTRACT FROM AUTHOR]

Abstract: Objective: A low ankle-brachial index is associated with cardiovascular disease and reduced arterial compliance. A high ankle-brachial index is also associated with an increased risk of cardiovascular events. We tested the hypothesis that subjects with a high ankle-brachial index demonstrate a lower arterial compliance. In addition, we assessed whether pulse pressure amplification is increased among subjects with a high ankle-brachial index. Methods: We studied 6814 adults enrolled in the multiethnic study of atherosclerosis who were, by definition, free of clinical cardiovascular disease at baseline. Differences in total arterial compliance (ratio of stroke volume to pulse pressure), aortic and carotid distensibility (measured with magnetic resonance imaging and duplex ultrasound, respectively) were compared across ankle-brachial index subclasses (≤0.90, 0.91–1.29; ≥1.30) with analyses adjusted for cardiovascular risk factors and subclinical atherosclerosis. Results: Peripheral arterial disease was detected in 230 (3.4%) and high ABI in 648 (9.6%) of subjects. Those with high ankle-brachial index demonstrated greater aortic/radial pulse pressure amplification than those with a normal ankle-brachial index. In adjusted models aortic and carotid distensibility as well as total arterial compliance, were lowest among those with ankle-brachial index ≤0.9 (p < 0.01 vs. all), but were not reduced in subjects with an ankle-brachial index ≥1.3. Conclusion: Lower aortic, carotid and total arterial compliance is not present in subjects free of overt cardiovascular disease and with a high ankle-brachial index. However, increased pulse pressure amplification contributes to a greater ankle-brachial index in the general population and may allow better characterization of individuals with this phenotype. [Copyright &y& Elsevier]

Abstract: Background: Framingham risk score (FRS) underestimates risk in young adults. Left ventricular mass (LVM) relates to cardiovascular disease (CVD), with unclear value in youth. In a young biracial cohort, we investigate how FRS predicts CVD over 20years and the incremental value of LVM. We also explore the predictive ability of different cut-points for hypertrophy. Methods: We assessed FRS and echocardiography-derived LVM (indexed by body surface area or height2.7) from 3980 African–American and white Coronary Artery Risk Development in Young Adults (CARDIA) participants (1990–1991); and followed over 20years for a combined endpoint: cardiovascular death; nonfatal myocardial infarction, heart failure, cerebrovascular disease, and peripheral artery disease. We assessed the predictive ability of FRS for CVD and also calibration, discrimination, and net reclassification improvement for adding LVM to FRS. Results: Mean age was 30±4years, 46% males, and 52% white. Event incidence (n =118) across FRS groups was, respectively, 1.3%, 5.4%, and 23.1% (p <0.001); and was 1.4%, 1.3%, 3.7%, and 5.4% (p <0.001) across quartiles of LVM (cut-points 117g, 144g, and 176g). LVM predicted CVD independently of FRS, with the best performance in normal weight participants. Adding LVM to FRS modestly increased discrimination and had a statistically significant reclassification. The 85th percentile (≥116g/m2 for men; ≥96g/m2 for women) showed event prediction more robust than currently recommended cut-points for hypertrophy. Conclusion: In a biracial cohort of young adults, FRS and LVM are helpful independent predictors of CVD. LVM can modestly improve discrimination and reclassify participants beyond FRS. Currently recommended cut-points for hypertrophy may be too high for young adults. [Copyright &y& Elsevier]

Background: Children of workers exposed to pesticides are at risk of secondary pesticide exposure. We evaluated the potential for lower acetylcholinesterase activity in children cohabiting with fresh-cut flower plantation workers, which would be expected from organophosphate and carbamate insecticide exposure. Parental home surveys were performed and acetylcholinesterase activity was measured in 277 children aged 4–9 years in the Secondary Exposure to Pesticides among Infants, Children and Adolescents (ESPINA) study. Participants lived in a rural county in Ecuador with substantial flower plantation activity. RESULTS: Mean acetylcholinesterase activity was 3.14U/ml, standard deviation (SD) of 0.49. It was lower by 0.09U/ml (95% confidence interval (CI) −0.19, −0.001) in children of flower workers (57% of participants) than non-flower workers’ children, after adjustment for gender, age, height-for-age, hemoglobin concentration, income, pesticide use within household lot, pesticide use by contiguous neighbors, examination date and residence distance to nearest flower plantation. Using a 4 level polychotomous acetylcholinesterase activity dependent variable, flower worker cohabitation (vs. not) had odds ratio 3.39 (95% CI 1.19, 9.64) for being <15th percentile compared to the highest tertile. Children cohabitating for ≥5 years (vs. never) had OR of 4.11 (95% CI: 1.17, 14.38) of AChE activity within <15th percentile compared to the highest tertile. Conclusions: Cohabitation with a flower worker was related to lower acetylcholinesterase activity in children. This supports the hypothesis that the amount of take-home pesticides from flower workers suffices to decrease acetylcholinesterase activity, with lower activity associated with longer exposure. [Copyright &y& Elsevier]

Background. The NCEP metabolic syndrome (MetS) is a combination of dichotomized interrelated risk factors from predominantly Caucasian populations. We propose a continuous MetS score based on principal component analysis (PCA) of the same risk factors in a multiethnic cohort and compare prediction of incident CVD events with NCEP MetS definition. Additionally, we replicated these analyses in the Health, Aging, and Body composition (Health ABC) study cohort. Methods and Results. We performed PCA of the MetS elements (waist circumference, HDL, TG, fasting blood glucose, SBP, and DBP) in 2610 Caucasian Americans, 801 Chinese Americans, 1875 African Americans, and 1494 Hispanic Americans in the multiethnic study of atherosclerosis (MESA) cohort. We selected the first principal component as a continuous MetS score (MetS-PC). Cox proportional hazards models were used to examine the association between MetS-PC and 5.5 years of CVD events (n = 377) adjusting for age, gender, race, smoking and LDL-C, overall and by ethnicity. To facilitate comparison of MetS-PC with the binary NCEP definition, a MetS-PC cut point was chosen to yield the same 37% prevalence of MetS as the NCEP definition (37%) in the MESA cohort. Hazard ratio (HR) for CVD events were estimated using the NCEP and Mets-PC-derived binary definitions. In Cox proportional models, the HR (95% CI) for CVD events for 1-SD (standard deviation) of MetS-PC was 1.71 (1.54-1.90) (P < 0.0001) overall after adjusting for potential confounders, and for each ethnicity, HRs were: Caucasian, 1.64 (1.39-1.94), Chinese, 1.39 (1.06-1.83), African, 1.67 (1.37-2.02), and Hispanic, 2.10 (1.66-2.65). Finally, when binary definitions were compared, HR for CVD events was 2.34 (1.91-2.87) for MetS-PC versus 1.79 (1.46-2.20) for NCEP MetS. In the Health ABC cohort, in a fully adjusted model, MetSPC per 1-SD (Health ABC) remained associated with CVD events (HR = 1.21, 95%CI 1.12-1.32) overall, and for each ethnicity, Caucasian (HR = 1.24, 95%CI 1.12-1.39) and African Americans (HR = 1.16, 95%CI 1.01-1.32). Finally, when using a binary definition of MetS-PC (cut point 0.505) designed to match the NCEP definition in terms of prevalence in the Health ABC cohort (35%), the fully adjusted HR for CVD events was 1.39, 95%CI 1.17-1.64 compared with 1.46, 95%CI 1.23-1.72 using the NCEP definition. Conclusion. MetS-PC is a continuous measure of metabolic syndrome and was a better predictor of CVD events overall and in individual ethnicities. Additionally, a binary MetS-PC definition was better than the NCEP MetS definition in predicting incident CVD events in the MESA cohort, but this superiority was not evident in the Health ABC cohort. [ABSTRACT FROM AUTHOR]

Functional biomarkers like large artery elasticity (LAE) and small artery elasticity (SAE) may predict cardiovascular disease (CVD) events beyond blood pressure. The authors examined the prognostic value of LAE and SAE for clinical CVD events among 6,235 Multi-Ethnic Study of Atherosclerosis participants who were initially aged 45–84 years and without symptomatic CVD. LAE and SAE were derived from diastolic pulse contour analysis. During a median 5.8 years of follow-up between 2000 and 2008, 454 adjudicated CVD events occurred, including 256 cases of coronary heart disease (CHD), 93 strokes, and 126 heart failures (multiple diagnoses were possible). After adjustment for age, race/ethnicity, sex, clinic, height, heart rate, body mass index, systolic and diastolic blood pressure, use of antihypertensive and cholesterol-lowering medications, smoking, total cholesterol, high density lipoprotein cholesterol, triglycerides, diabetes, and high-sensitivity C-reactive protein, the hazard ratio for any CVD per standard-deviation increase in SAE was 0.71 (95% confidence interval: 0.61, 0.83; P < 0.0001). The lowest (stiffest) SAE quartile had a hazard ratio of 2.28 (95% confidence interval: 1.55, 3.36) versus the highest (most elastic) quartile. The net reclassification index, conditional on base risk, was 0.11. SAE was significantly associated with future CHD, stroke, and heart failure. After adjustment, LAE was not significantly related to CVD. In asymptomatic participants free of overt CVD, lower SAE added prognostic information for CVD, CHD, stroke, and heart failure events. [ABSTRACT FROM PUBLISHER]

Kelly AS, Jacobs DR Jr, Sinaiko AR, Moran A, Steffen LM, Steinberger J. Relation of circulating oxidized LDL to obesity and insulin resistance in children. Introduction: Circulating oxidized low-density lipoprotein (LDL), a marker of oxidative stress, is associated with obesity, insulin resistance, metabolic syndrome, and cardiovascular disease in adults. However, little is known about its relation to insulin resistance and cardiovascular risk factors in children. The purpose of this study was to assess the relation of oxidative stress, measured by circulating oxidized LDL, with measures of adiposity and insulin resistance in children. Methods: Oxidized LDL, measures of body fatness (body mass index: BMI, percent body fat, waist circumference, percent trunk fat, abdominal visceral and subcutaneous fat), insulin resistance with euglycemic insulin clamp (Mlbm), blood pressure, and blood lipids were obtained in 78 children. Oxidized LDL was compared between normal weight children (BMI < 85th percentile) and overweight/obese children (BMI ≥ 85th percentile) and levels were evaluated for associations with body fatness and insulin resistance. Results: Oxidized LDL levels were significantly higher in overweight/obese vs. normal weight children (p < 0.0001). Oxidized LDL was significantly correlated with BMI, percent body fat, waist circumference, percent trunk fat, abdominal visceral fat, and abdominal subcutaneous fat (all p-values <0.0001). Moreover, oxidized LDL was negatively correlated with Mlbm, even after adjustment for adiposity (p < 0.01). Conclusions: Oxidized LDL is significantly associated with adiposity and with insulin resistance, independent of body fatness, in children. Oxidative stress may be independently related to the development of insulin resistance early in life, especially in obese youth. [ABSTRACT FROM AUTHOR]

Background: Building on known associations between active commuting and reduced cardiovascular disease (CVD) risk, this study examines active transit to neighborhood amenities and differences between walking and cycling for transportation. Methods: Year-20 data from the Coronary Artery Risk Development in Young Adults study (3549 black and white adults aged 38–50 years in 2005–2006) were analyzed in 2008–2009. Sociodemographic correlates of transportation mode (car-only, walk-only, any cycling, other) to neighborhood amenities were examined in multivariable multinomial logistic models. Gender-stratified multivariable linear or multinomial regression models compared CVD risk factors across transit modes. Results: Active transit was most common to parks and public transit stops; walking was more common than cycling. Among those who used each amenity, active transit (walk-only and any cycling versus car-only transit) was more common in men and those with no live-in partner and less than full-time employment (significant ORs [95% CI] ranging from 1.56 [1.08, 2.27] to 4.54 [1.70, 12.14]), and less common in those with children. Active transit to any neighborhood amenity was associated with more favorable BMI, waist circumference, and fitness (largest coefficient [95% CI] −1.68 [−2.81, −0.55] for BMI, −3.41 [−5.71, −1.11] for waist circumference [cm], and 36.65 [17.99, 55.31] for treadmill test duration [seconds]). Only cycling was associated with lower lifetime CVD risk classification. Conclusions: Active transit to neighborhood amenities was related to sociodemographics and CVD risk factors. Variation in health-related benefits by active transit mode, if validated in prospective studies, may have implications for transportation planning and research. [Copyright &y& Elsevier]

It was previously hypothesized that serum gamma-glutamyltransferase (GGT) within its reference range predicts various clinical outcomes as a sensitive marker of oxidative stress in humans. This study further hypothesizes that serum GGT can mark exposure to various environmental pollutants, based both on recent epidemiological findings and on well-established biochemical features of cellular GGT. Cellular GGT is a prerequisite for metabolism of GSH conjugates that detoxify xenobiotics to mercapturic acid. Under this concept, serum GGT may increase with increasing exposure to environmental pollutants which need to be conjugated to GSH. Supporting this concept, it was recently reported that serum GGT within its reference range was linearly associated with important environmental pollutants, including lead, cadmium, dioxin and organochlorine pesticides. As a marker of the amount of conjugated xenobiotics, recent epidemiological findings about serum GGT imply the possibility of harmful effects of various environmental pollutants at background levels currently regarded as safe. [ABSTRACT FROM AUTHOR]

Abstract: Previous research shows that cardiovascular risk factors in mid-adulthood could increase the risk of dementia later in life, but studies with very long follow-up are still scarce. We assessed whether cardiovascular risk factors measured in midlife were associated with dementia mortality during a 40-year follow-up. 10,211 men, aged 40–59 at baseline, from 13 cohorts of the Seven Countries Study were followed for 40 years. Information on cardiovascular risk factors was obtained at baseline from questionnaires and a physical examination. Dementia death was assigned if there was any mention of dementia on the death certificate. Associations between cardiovascular risk factors and death from dementia were estimated through Cox proportional hazards models. We identified 160 dementia deaths during the follow-up. Smoking, hypercholesterolemia, high blood pressure, low forced vital capacity and previous history of cardiovascular disease at baseline were associated with a higher risk of death from dementia in the follow-up. The hazard ratio (HR) of dementia death among heavy smokers was 1.58 (95% confidence interval (CI) 1.03, 2.43) compared to non-smokers. Similarly, the HR (95% CI) among those with systolic BP≥160 or diastolic BP≥95 mm Hg compared to normotensives (<140/90) was 1.55 (1.02, 2.35). Individuals with the largest forced vital capacity had a lower risk of dying of dementia (HR 0.54, 95% CI 0.30, 0.98). Finally, total serum cholesterol was directly associated with higher risk of dementia mortality (p for trend=0.03). In men, cardiovascular risk factors in midlife are associated with increased risk of dementia death later in life. [Copyright &y& Elsevier]

Abstract: Whether cardiorespiratory fitness relates to early subclinical atherosclerotic vascular disease remains unknown. We investigated the relation of cardiorespiratory fitness to coronary artery calcification (CAC) in 2373 African-American and White young adults from the Coronary Artery Risk Development in Young Adults (CARDIA) Study. We measured cardiorespiratory fitness in 1985–1986 (baseline) using a symptom-limited exercise test on a treadmill. Coronary calcium scores were measured in 2001–2002 (year 15) using electron-beam or multi-detector computed tomography. CAC was classified as present or absent, while cardiorespiratory fitness was classified as sex-specific low, moderate, and high fitness categories. After adjustment for age, sex, race, clinical center, education, cigarette smoking, waist girth, alcohol intake, physical activity, systolic blood pressure, antihypertensive medication use, diabetes mellitus, and fasting insulin, baseline cardiorespiratory fitness was inversely associated with prevalence of CAC in young adults (P for trend=0.03). The odds ratios of having CAC for persons in the moderately and highly fit individuals were 0.80 (95% confidence interval (CI), 0.55–1.15) and 0.59 (95% CI, 0.36–0.97), respectively, as compared with the low-fit individuals. High levels of cardiorespiratory fitness were associated with a lower risk of having coronary calcification 15 years later in African-American and White young adults. [Copyright &y& Elsevier]

The prevalence of obesity increased in the United States through the 1980s. The authors examined 10-year aging and secular (time-related) trends in the Coronary Artery Risk Development in Young Adults (CARDIA) cohort for indications of whether these trends are continuing and for ages of peak weight gain in young adults. CARDIA is a population-based, prospective study of 5, 115 African-American and White men and women aged 18–30 years at baseline. Body weight and overweight prevalence were measured at five time points from 1985–1986 to 1995–1996. Linear, mixed-model regression was used to partition weight gain into that due to secular trends and that due to aging. Prevalence of overweight (body mass index (BMI) ≥25.0 kg/m2) increased markedly, and prevalence of severe obesity (BMI ≥ 40.0 kg/m2) doubled in all race-sex groups. Each race-sex group experienced significant secular weight gains, ranging from 0.96 kg/year (95/ confidence interval: 79, 1.13) in African-American women to 0.55 kg/year (95% confidence interval: 0.41, 0.69) in White women. Significant secular gains were present during each follow-up period. Each race-sex group also experienced significant weight increases related to aging during their early to midtwenties. Secular trends for weight gain are continuing in CARDIA, but the magnitude of weight gain differed among the four race-sex groups. Am J Epidemiol 2000; 151: 1172-81. [ABSTRACT FROM PUBLISHER]

In contrast of clinical trials using statin drugs, which suggest that cholesterol lowering from high to moderate levels is safe, many but not all, prospective studies report higher nonatherosclerotic disease rates in people with low serum total cholesterol, even after deleting deaths in the 5 years after cholesterol determination. A perplexing and unanswered question is whether low cholesterol is causally related to nonatherosclerotic disease risk. Cholesterol is reduced during the acute phase reaction; a state of immune activation that persists for more than 5 years may explain the prospective observations. Higher cholesterol may be a marker for other protective substances such as fat-soluble antioxidants. Low cholesterol might mark poor nutrition, for example, during depression. Alternatively, higher cholesterol levels may result in enhanced delivery of lipids to cells during the immune response or tissue repair or may enhance defense against endotoxins and viruses. Although we believe that populationwide efforts to lower cholesterol should continue, we think that important biology may be reflected in the repeatedly observed associations of low cholesterol with nonatherosclerotic disease. The authors urge that research continue to elucidate any biologic bases of these relations. Am J Epidemiol 2000;151:748–51. [ABSTRACT FROM PUBLISHER]

Objective: Even though persistent organic pollutants (POPs) are well-known neurotoxicants, there is no previous study, even cross-sectional, on the association between background exposure to POPs and clinically significant developmental disorders, such as learning disability (LD) or attention deficit disorder (ADD), among children from a general population. Design: Cross-sectional study. Setting: Study subjects were 278 children aged 12-15 years included in the National Health and Nutrition Examination Survey 1999-2000. The seven most commonly detected POPs (each detectable in ≥20% of children: 3,3′,4,4′,5-pentachlorobiphenyl; 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin (HPCDD); 1,2,3,4,6,7,8,9-octachlorodibenzo-p-dioxin (OCDD); 1,2,3,4,6,7,8-heptachlorodibenzofuran (HPCDF); β-hexachlorocyclohexane; p,p′-dichlorodiphenyltrichloroethane; and trans-nonachlor) were selected. Main results: Compared with children with non-detectable levels of POPs, adjusted prevalence ORs (95% CIs) of LD among those with detectable levels of HPCDD, OCDD or HPCDF were 2.08 (1.17 to 3.68), 2.72 (1.24 to 5.99) and 2.18 (1.15 to 4.15), respectively. For ADD, the corresponding figures were 3.41 (1.08 to 10.8), 3.33 (0.94 to 11.8) and 2.31 (0.62 to 8.63), respectively. Conclusions: Associations were observed between serum concentrations of POPs belonging to the categories of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans and the prevalence of two clinically significant development problems, LD and ADD. The nature of these associations needs to be clarified by prospective studies. [ABSTRACT FROM AUTHOR]

Abstract: Objective : There has been reduced active smoking, decreased societal acceptance for smoking indoors, and changing smoking policy since the mid-1980s. We quantified passive smoke exposure trends and their relationship with workplace policy. Method : We studied 2504 CARDIA participants (Blacks and Whites, 18–30 years old when recruited in 1985–86 from four US cities, reexamination 2, 5, 7, 10, and 15 years later) who never reported current smoking and attended examinations at 10 or 15 years. Results.: In non-smokers with a college degree (n =1581), total passive smoke exposure declined from 16.3 h/week in 1985/86 to 2.3 h/week in 2000/01. Less education tended to be associated with more exposure at all timepoints, for example, in high school or less (n =292) 22.2 h/week in 1985/86 to 8.5 h/week in 2000/01. Those who experienced an increase in the restrictiveness of self-reported workplace smoking policy from 1995/96 to 2000/01 were exposed to almost 3 h per week less passive smoke than those whose workplace policies became less restrictive in this time period. Conclusions : The increasing presence of restrictive workplace policies seemed to be a component of the substantial decline in self-reported passive smoke exposure since 1985. [Copyright &y& Elsevier]

Recent findings associate periodontal disease with established coronary heart disease (CHD) and with disorders of the carotid artery. Besides measures of the carotid artery, a number of other noninvasive subclinical markers of cardiovascular disease exist and are summarized here. Included are computed tomography (CT) of the coronary arteries, ultrasound of the carotid arteries, echocardiography, magnetic resonance imaging (MRI), ankle–brachial index, microalbuminuria, and other biochemical measures of kidney dysfunction, flow-mediated dilation in the brachial artery, and pulse wave form analysis. Use of these measures may simplify and add depth to studies of oral health and cardiovascular disease. However, it is noted that the measures are not highly correlated with each other (based on 6,814 persons in the Multiethnic Study of Atherosclerosis, Pearson correlations among the above subclinical measures, range from about 0.1–0.4), do not include propensity for the important atherosclerotic phase of plaque rupture, and do not fully substitute for studies of clinical cardiovascular disease endpoints. [ABSTRACT FROM AUTHOR]

We examined the 16-year mortality experience among participants in the baseline examination (1985–86) of the Coronary Artery Risk Development in Young Adults (CARDIA) Study, a U.S. cohort of 5115 urban adults initially 18–30 years old and balanced by sex and race (black and whites) in the USA. We observed 127 deaths (annual mortality of 0.15%). Compared to white women, the rate ratio (95% confidence interval) of all-cause mortality was 9.3 (4.4, 19.4) among black men, 5.3 (2.5, 11.4) among white men and 2.7 (1.2, 6.1) among black women. The predominant causes of death, which also differed greatly by sex–race, were AIDS (28% of deaths), homicide (16%), unintentional injury (10%), suicide (7%), cancer (7%) and coronary disease (7%). The significant baseline predictors of all-cause mortality in multivariate analysis were male sex, black race, diabetes, self-reported liver and kidney disease, current cigarette smoking and low social support. Two other factors, self-reported thyroid disease and high hostility, were significant predictors in analyses adjusted for age, sex and race. In conclusion, we found striking differences in the rates and underlying cause of death across sex–race groups and several independent predictors of young adult mortality that have major implications for preventive medicine and social policies. [Copyright &y& Elsevier]

Abstract: A series of epidemiological studies have suggested serum gamma glutamyltransferase (GGT) within its normal range might be an early marker of oxidative stress. Oxidative stress appears to be a key component of many reactions associated with chronic inflammation. Therefore, we examined the cross-sectional association between deciles of serum GGT and concentrations of serum C-reactive protein (CRP), a marker of chronic inflammation, among 12,110 adult participants in the third U.S. National Health and Nutrition Examination Survey. After adjustment for race, sex, age, cigarette smoking, alcohol intake, and body mass index (BMI), serum concentration of GGT across all deciles was positively associated with serum concentrations of CRP (P for trend<0.01). For example, adjusted relative risks of serum CRP≥3.0mg/L by deciles of serum GGT were 1.0, 1.23, 1.40, 1.59, 1.62, 1.61, 2.17, 2.38, 2.45, and 3.41 (P for trend<0.01). This association was consistently observed among all subgroups; Non-Hispanic White, Non-Hispanic Black, Mexican American, men, women, non-drinkers, drinkers, non-smokers, ex-smokers, current smokers, BMI<25, BMI 25–29.9, and BMI≥30. The strong association of serum GGT and CRP suggest that further studies on cellular and/or serum GGT might help to elucidate the association between oxidative stress and inflammation. [Copyright &y& Elsevier]

Objective: A relationship between birth weight and the insulin resistance syndrome has been reported in adults but has not been defined in adolescents.Research Design and Methods: Data were analyzed in 296 children (132 girls and 164 boys) mean age 15.0 +/- 1.2 years who had euglycemic insulin clamp studies (intravenous administration of 1 mU. kg(-1). min(-1) of insulin balanced by a variable infusion of 20% glucose to maintain blood glucose at 100 mg/dl). Insulin sensitivity (M(LBM)) was determined by glucose uptake per kg lean body mass (LBM), and parents reported birth weight.Results: Birth weight ranged from 1,021 to 4,848 g (mean +/- SD 3,433 +/- 551), with 4.0% <2,500 g. Fat mass and BMI had U-shaped relations with birth weight after adjustment for race, age, sex, and blood pressure. Lean mass index (lean mass/height squared) was stable across birth weight quartiles. Fasting insulin decreased nonsignificantly across birth weight quartiles but became significant after adjustment for adolescent weight (P = 0.008). Although M(LBM) was highest in the highest birth weight quartile, the pattern was not significant. Triglycerides tended to increase with birth weight, whereas LDL cholesterol (LDL-C) and HDL cholesterol (HDL-C) tended to decrease. Blood pressure was unrelated to birth weight.Conclusions: In this cohort, fat mass was greater in adolescents with low and high birth weight; fasting insulin was lower with higher birth weight after adjustment for adolescent weight. Insulin sensitivity increased nonsignificantly with birth weight. [ABSTRACT FROM AUTHOR]

Objective: To examine associations of neighborhood characteristics with six components of the insulin resistance syndrome (IRS) in young adults.Research Design and Methods: Cross-sectional data from the Coronary Artery Risk Development in Young Adults (CARDIA) Study were used to examine associations of neighborhood characteristics with the IRS in 3,093 nondiabetic adults aged 28-40 years. Measures of BMI, fasting HDL cholesterol, triglycerides, insulin, glucose, and systolic blood pressure were combined into an IRS score. U.S. Census-derived neighborhood characteristics were summarized into a neighborhood socioeconomic score, with an increasing score signifying increasing socioeconomic advantage.Results: Among white men and women, the IRS score was inversely related to neighborhood socioeconomic score. Neighborhood characteristics remained associated with the IRS score after controlling for personal income and education (adjusted mean differences for 95th vs. 5th percentile of neighborhood score: -0.24 standard deviation units [SE = 0.12] in men and -0.56 standard deviation units [SE = 0.10] in women). Among black participants, neighborhood score was inversely associated with IRS score in persons of high income and education (mean differences 95th vs. 5th percentile -0.54 [SE 0.26] in men and -0.52 [SE 0.26] in women) but positively associated or not associated with IRS score in persons of low income and education (mean differences 0.60 [SE 0.21] in men and 0.00 [SE 0.16] in women).Conclusions: The IRS score is associated with neighborhood characteristics as early as young adulthood. Features of residential environments may be related to the development of insulin resistance. [ABSTRACT FROM AUTHOR]

It is hypothesized that diets deficient in folate, methionine, and vitamins B-6 and B-12 cause DNA hypomethylation and, as a result, increase risk of colorectal cancers. Furthermore, it is proposed that alcohol, a methyl group antagonist, increases risk of colorectal cancers among those with low intake of folate. Data from the Iowa Women's Health Study, a population-based cohort of incident cancer, were used to examine the relationship of folate, methionine, and vitamins B-6 and B-12 to occurrence of cancers of the colon (n = 598) and rectum (n = 123) over 13 yr of follow-up. There were no independent associations of folate, methionine, or vitamins B-6 and B-12 derived from a food frequency questionnaire with incidence of colon cancer. Adjusted relative risks (RRs) of rectal cancer were similar across categories of folate, vitamin B-12, and methionine intake, but RRs increased progressively with increasing intake of vitamin B-6 [P (for trend) = 0.03]. RRs suggested that incidence of cancer of the proximal colon was lower among those with 1) high folate and high vitamin B-12 intake [RR = 0.59, 95% confidence interval (CI) = 0.39-0.89] and 2) high folate and high vitamin B-6 intake (RR = 0.65, 95% CI = 0.50-0.84) than among those with the lowest intake of these nutrients. Incidence of cancer of the proximal colon was also somewhat lower among those with high folate and low alcohol intake (RR = 0.44, 95% CI = 0.22-0.89). Findings provide limited support for an association between dietary factors involved in DNA methylation and risk of cancers of the colon and rectum. [ABSTRACT FROM AUTHOR]

AbstractThe objectives of this study were to evaluate the possible association of periodontal disease with (1) femoral bone mineral density (BMD), and (2) estrogen replacement therapy in a large sample of US adults (N=11,655). The mean clinical attachment loss (CAL) per person was the main outcome variable. Based on the total BMD of the proximal femur and using the WHO diagnostic criteria, subjects were classified as having osteoporosis, osteopenia, or normal BMD. After adjusting for confounders, females with high calculus scores and low BMD had significantly more CAL than females with normal BMD and similar calculus scores (p<0.0001). No association was observed among women with low and intermediate levels of calculus. The greater CAL present among women with low BMD was associated with gingival recession. Patterns of findings were similar but equivocal among men, of whom only 66 were osteoporotic. After adjustment for possible confounders, postmenopausal women who reported having used estrogen replacement therapy presented significantly less mean CAL than those who never used estrogen. These findings indicate that in the presence of high calculus scores, females with osteoporosis are at increased risk for attachment loss and that this risk may be attenuated by the use of estrogen replacement therapy. [ABSTRACT FROM AUTHOR]

Objectives: We examined cross-sectional relationships among depressive symptoms, anxiety, alcohol intake, and blood pressure. Test hypotheses were that: (1) alcohol intake, depressive symptoms, and anxiety would be positively related to blood pressure; (2) depressive symptoms and anxiety would have a stronger association with alcohol intake in Blacks than in Whites; and (3) adjustment for differences in depressive symptoms, anxiety, and alcohol intake would reduce Black-White blood pressure differences. Methods: Study hypotheses were tested in a sample of 4,352 Black and White adults, participating in the CARDIA study. Hypotheses were tested using multiple linear regression. Results: Alcohol intake was positively related to systolic ( p= 0.0001) and diastolic ( p= 0.0004) blood pressure in men, but not in women. Depressive symptoms and anxiety were unrelated to blood pressure. The relationship between alcohol intake and depressive symptoms differed by race/ethnicity in men ( p= 0.0719) and in women ( p= 0.0002). Alcohol intake increased with increasing levels of depressive symptoms, but the increase was greater in Blacks than in Whites. After accounting for alcohol intake, body mass index, and other variables, Black-White blood pressure differences were reduced in men, but not in women; most of the reduction was caused by body mass index. Conclusions: Blacks may respond differently than Whites to psychological distress. [ABSTRACT FROM AUTHOR]

Compares the relationship between serum total cholesterol and long-term mortality from coronary heart disease (CHD) in different cultures. Measurement of total cholesterol at baseline in 16 cohorts located in seven countries; Increase in relative risks for 25-year CHD mortality for cholesterol quartiles; Age-standardized CHD mortality rates.

Presents the results of a study which identifies the predictors of red cell folate level in women attempting to become pregnant. Design; Setting; Participants; Main outcome measure; Results; Conclusions.

A response by David R. Jacobs Jr. and Lyndia C. Brumback to a letter about their article "Association of Small Artery Elasticity With Incident Cardiovascular Disease in Older Adults: The Multi-Ethnic Study of Atherosclerosis" in the September 1, 2011 issue is presented.

New sex-specific equations, each with race/ethnic-specific intercept, for predicted lung function illustrate a methodological point, that complex differences between groups may not imply interactions with other predictors, such as age and height. The new equations find that race/ethnic identity does not interact with either age or height in the prediction equations, although there are race/ethnic-specific offsets. Further study is warranted of the effect of possible small race/ethnic interactions on disease classification. Additional study of repeated measures of lung function is warranted, given that the new equations were developed in cross-sectional designs. Predicting lung function is more than a methodological exercise. Predicted values are important in disease diagnosis and monitoring. It is suggested that measurement and tracking of lung function throughout young adulthood could be used to provide an early warning of potential long-term lung function losses to encourage improvement of risky behaviors including smoking and failure to maintain normal body weight in the general population. [ABSTRACT FROM PUBLISHER]

Background: We recently hypothesized that serum γ-glutamyltransferase (GGT), within its reference range, predicts many diseases as a biomarker for background exposure to various xenobiotics. Even though normal serum GGT was associated with xenobiotics having very long half-lives (heavy metals, dioxin, or organochlorine pesticides), it was unknown whether GGT was associated with xenobiotics with short half-lives, including polycyclic aromatic hydrocarbons (PAHs), well known carcinogens. Methods: Among 1256 adult participants in the National Health and Nutrition Examination Survey (NHANES) 2003–2004, urinary metabolites of PAH (monohydroxy-PAH), and serum GGT were measured. We selected the 10 monohydroxy-PAHs (OH-PAHs) for which at least 90% of participants had concentrations greater than the limit of detection. Results: Among the 10 OH-PAHs, eight had significant positive correlations with serum GGT. These correlations were similarly observed in men and women, and in individuals under 60 years of age. Unlike serum GGT, alanine aminotransferase, another liver enzyme, was not associated with OH-PAHs. Conclusions: Taken together with the previous epidemiological evidence, the associations of serum GGT with OH-PAHs reinforce the concept that serum GGT is a marker for various environmental pollutants encountered at background levels in the general population. Clin Chem Lab Med 2009;47:860–2. [ABSTRACT FROM AUTHOR]

Aim: We investigated whether periodontal measures are cross‐sectionally associated with prediabetes and cardiometabolic biomarkers among non‐diabetic younger adults. Materials and Methods: One thousand seventy‐one participants (mean age = 32.2 years [SE = 0.3]; 73% female) from the Oral Infections, Glucose Intolerance and Insulin Resistance Study were enrolled. Full‐mouth clinical attachment loss (fm‐CAL), probing depth (fm‐PD) and bleeding on probing were ascertained. Interproximal CAL (i‐CAL) and probing depths (i‐PD) served as our primary exposures. Glucose, HbA1c, insulin and insulin resistance (HOMA‐IR) outcomes were assessed from fasting blood. Prediabetes was defined per American Diabetes Association guidelines. Prediabetes prevalence ratios (PR [95% CI]) and mean [SE] cardiometabolic biomarkers were regressed on periodontal variables via multivariable robust variance Poisson regression or multivariable linear regression. Results: Prevalence of prediabetes was 12.5%. Fully adjusted prediabetes PR in Tertiles 3 versus 1 of mean i‐CAL was 2.42 (1.77, 3.08). Fully adjusted fasting glucose estimates across i‐CAL tertiles were 83.29 [0.43], 84.31 [0.37], 86.48 [0.46]; p for trend <.01. Greater percent of sites with i‐PD ≥3 mm showed elevated natural‐log‐HOMA‐IR after adjustment (0%–12% of sites = 0.33 [0.03], 13%–26% of sites = 0.39 [0.03], ≥27% of sites = 0.42 [0.03]; p for trend =.04). Conclusions: i‐CAL (vs. fm‐CAL) was associated with elevated fasting glucose and prediabetes, whereas i‐PD (vs. fm‐PD) was associated with insulin resistance. Future studies are needed to examine periodontal disease and incident prediabetes. [ABSTRACT FROM AUTHOR]

Background: Circulating markers of oxidative stress have been associated with lower lung function. Our objective was to study the association of gene expression levels of oxidative stress pathway genes (ALOX12, ALOX15, ARG2, GSTT1, LPO, MPO, NDUFB3, PLA2G7, and SOD3) and lung function forced expiratory volume in one second (FEV1), forced vital capacity (FVC) in Coronary Artery Risk Development in Young Adults study. Methods: Lung function was measured using spirometry and the Nanostring platform was used to estimate gene expression levels. Linear regression models were used to study association of lung function measured at year 30, 10‐year decline in lung function and gene expression after adjustment for center, smoking, and BMI, measured at year 25. Results: The 10‐year decline of FEV1 was faster in highest NDUFB3 quartile compared to the lowest (difference = −2.09%; p = 0.001) after adjustment for multiple comparisons. The 10‐year decline in FEV1 and FVC was nominally slower in highest versus lowest quartile of PLA2G7 (difference = 1.14%; p = 0.02, and difference = 1.06%; p = 0.005, respectively). The other genes in the study were not associated with FEV1 or FVC. Conclusion: Higher gene expression levels in oxidative stress pathway genes are associated with faster 10‐year FEV1 decline. [ABSTRACT FROM AUTHOR]

Background Adrenal and sex hormone dysregulation have been independently associated with increased depression and anxiety. Cortisol can modify production of sex hormones and hormone-mood associations. This study evaluated associations and interplay of sex and adrenal hormones with depression and anxiety. Methods We assessed 545 Ecuadorian adolescents (11-17y, 50.4% female, ESPINA) for depression and anxiety symptoms using standardized scales. Testosterone, cortisol, dehydroepiandrosterone (DHEA), and estradiol (boys only) were measured in saliva. We performed logistic regression modeling to calculate odds ratios (OR) of elevated depression or anxiety (scores ≥60) comparing participants with low (<10th percentile) and elevated hormones (≥90th percentile) to normal concentrations (10th-90th percentile). Effect modification by cortisol and testosterone was assessed. Models adjusted for demographic, anthropometric, and circadian measures. Results In all participants, elevated testosterone (OR [95%CI:]=1.78 [0.98, 3.23]) and cortisol (OR=1.69 [0.95, 2.99]) were marginally associated with elevated anxiety scores. In boys, elevated estradiol was associated with elevated depression (OR=4.75 [1.95, 11.56]) and anxiety scores (OR=2.43 [1.01, 5.84]). In linear regression, estradiol was positively associated with depression (difference/10% hormone increase (β=0.45 [0.15, 0.75]) and anxiety scores (β=0.42 [0.13, 0.72]). Higher cortisol levels strengthened the depression association with estradiol in boys (β=0.54 [0.12, 0.96]), and with testosterone (β= -0.19 [-0.35, -0.03]) and DHEA (β= -0.12 [-0.22, -0.02]) in girls. Testosterone also modified associations. Limitations This was a cross-sectional analysis. Discussion Elevated testosterone, cortisol, and estradiol (≥90th percentile) were associated with altered mood. Cortisol and testosterone were considerable effect modifiers to the associations of most hormones with depression and anxiety. [ABSTRACT FROM AUTHOR]