Polychlorinated biphenyls and incident coronary heart disease-related outcomes in Great Lakes fish consumers.

BACKGROUND: Exposure to polychlorinated biphenyls (PCBs) has been linked to risk factors for cardiovascular disease such as increased inflammation, accelerated atherosclerosis, diabetes, and sex hormone dysregulation. Furthermore, there is increasing evidence suggesting associations between internal dose of PCBs and cardiovascular outcomes. OBJECTIVES: The purpose of this study is to investigate longitudinal associations of PCBs with coronary heart disease (CHD)-related outcomes in a cohort of Great Lakes sport fish consumers. METHODS: The Great Lakes Sport Fish Consumer cohort was established in the early 1990's. Eight hundred nineteen participants were followed from 1993 to 2017. Serum PCBs were measured in 1994/1995 (baseline), in 2001, and in 2004, while health history questionnaires were administered in 1996, 2003, 2010, and 2017. Cox models were used to prospectively investigate associations of total PCBs and PCB groupings, based on aryl hydrocarbon receptor activity, with incident self-reported physician diagnosis of coronary heart disease (CHD), myocardial infarction (MI), and angina pectoris. RESULTS: A 2-fold increase in phenobarbital-type PCBs was associated with a 72% increase in likelihood of self-reported incident diagnosis of CHD (HR=1.72, 95% CI: 1.06-2.81; p=0.0294). Similar results were observed for total PCBs (HR=1.68, 95% CI: 1.05-2.69; p=0.0306) and mixed methacholine/phenobarbital type (mixed-type) PCBs (HR=1.60, 95% CI: 1.02-2.52; p=0.0427), but not methacholine-type PCBs. PCBs were not strongly associated with risk of MI or angina. CONCLUSIONS: This study presents evidence that exposure to PCBs increases the risk of developing coronary heart disease. Given the large number of risk factors and causal pathways for CHD, future research is required to better understand biological mechanisms of action for PCBs on CHD.

Thyroid-related Hormones and Hypertension Incidence in Middle-Aged and Older Hispanic/Latino Adults: The HCHS/SOL Study.

Background: Thyroid-related hormones act to regulate metabolic pathways and blood pressure (BP). However, the relationship of TSH and peripheral thyroid hormones and the role of the hypothalamic-pituitary-thyroid axis on hypertension development is not fully understood. We assessed sex-specific associations of thyroid-related hormones with BP and hypertension in Hispanic/Latino adults followed for 6 years. Methods: We studied 1789 adults, ages 45 to 74, free of diabetes at baseline from a subcohort of the Hispanic Community Health Study/Study of Latinos. We assessed TSH, free T4 (FT4), T3, and various indicators of thyroid axis. Using multivariable linear and Poisson regression adjusted for survey design and confounding variables, we estimated a priori sex-specific associations of thyroid-related hormones with changes in BP and hypertension development. Results: In men and women, TSH and TSH/FT4 ratios were associated with changes in diastolic BP and T3 with changes in pulse pressure and the development of hypertension from prehypertension. In men, a 1-SD increase in TSH [incident rate ratio (IRR) = 1.42; 95% confidence interval (CI): 1.15, 1.75] and TSH/FT4 ratio (IRR = 1.20; 95% CI: 1.07, 1.35) were positively associated with the development of hypertension from prehypertension while the TSH/FT4 ratio (IRR = 0.85; 95% CI: .72, 1.00) was protective in women. We observed sex-specific differences in associations of the T3/FT4 ratio and indices of pituitary sensitivity to thyroid hormones with changes in pulse pressure and hypertension development. Conclusion: Thyroid-related hormones are associated with sex-specific changes in BP and hypertension among Hispanic/Latino adults consistent with selected studies conducted in other populations. Mechanisms underlying associations of pituitary sensitivity to thyroid hormones with BP and hypertension development warrant further study.

Thyroid Hormones and Diabetes in Euthyroid Hispanic/Latino Adults of Diverse Backgrounds: HCHS/SOL.

Context: Previous studies have demonstrated associations of endogenous thyroid hormones with diabetes; less is known about stages of diabetes development at which they are operative, mechanisms of associations, and the role of the hypothalamic-pituitary-thyroid axis. Objective: This study examined associations of thyroid hormones with incident prediabetes and diabetes and with changes in glycemic traits in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), the largest cohort of Hispanic/Latino adults with diverse backgrounds in the United States. Methods: The study includes 592 postmenopausal euthyroid women and 868 euthyroid men aged 45 to 74 years without diabetes at baseline participating in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Baseline hormones included thyrotropin (TSH), free thyroxine (FT4), total triiodothyronine (T3), and indices calculated from thyroid hormones evaluating pituitary sensitivity to thyroid hormone. Transitions to diabetes and prediabetes, and changes in glycemic traits determined at the 6-year follow-up visit, were examined using multivariable Poisson and linear regressions. Results: Among women, T3 (incident rate ratio [IRR] = 1.65; 95% CI, 1.22-2.24; P = .001) and TSH (IRR = 2.09; 95% CI, 1.01-4.33; P = .047) were positively, while FT4 (IRR = 0.59; 95% CI, 0.39-0.88; P = .011) was inversely, associated with transition from prediabetes to diabetes. Among men, the T3/FT4 ratio was positively associated with transition from normoglycemia to prediabetes but not from prediabetes to diabetes. Indices measuring sensitivity of the pituitary to thyroid hormone suggested increased sensitivity in men who transitioned from prediabetes to diabetes. Conclusion: Positive associations in women of T3 and TSH and inverse associations of FT4, as well as inverse associations of thyroid indices in men with transition from prediabetes to diabetes, but not from normoglycemia to diabetes, suggest decreased pituitary sensitivity to thyroid hormones in women and increased sensitivity in men later in the development of diabetes.

Association of Acculturation and Hispanic/Latino Background with Endogenous Sex and Thyroid-Related Hormones Among Middle-Aged and Older Hispanic/Latino Adults: the HCHS/SOL Study.

BACKGROUND: Hormones are linked to cardiometabolic diseases and may be impacted by acculturation though multiple mechanisms. We evaluated associations of Hispanic/Latino background and acculturation with levels of sex- and thyroid-related hormones and the potential mediating effect of adiposity, lifestyle factors, and sleep apnea syndrome on these associations. METHODS: We studied 1789 adults, aged 45-74, from a sub-cohort of the Hispanic Community Health Survey/Study of Latinos. Peri/pre-menopausal women and individuals on medications related to hormones were excluded. Our study assessed eleven sex- and thyroid-related hormones, Hispanic/Latino background, and five acculturation measures. Associations were assessed using multivariable linear and logistic regression adjusted for survey design and confounding variables. We explored potential mediation using a path analysis. RESULTS: In postmenopausal women, acculturation score-MESA was associated with decreased thyroid-stimulating hormone (ß = - 0.13;95%CI = - 0.22, - 0.03) while age at immigration greater than the median (vs US-born) was associated with decreased (ß = - 14.6; 95%CI = - 28.2, - 0.99) triiodothyronine (T3). In men, language acculturation and acculturation score-MESA were associated with increased estradiol and sex hormone-binding globulin (SHBG) while age at immigration greater and lesser than the median (vs US-born) was associated with decreased SHBG. Hispanic/Latino background (Mexicans as reference) were selectively associated with sex- and thyroid-related hormone levels in both sexes. Current smoking and sleep apnea syndrome partially mediated the association of Cuban and Puerto Rican heritage (vs Mexican) with T3 levels in men and postmenopausal women, respectively. CONCLUSION: Selected acculturation measures were associated with thyroid-related hormones in postmenopausal women and sex-related hormones in men. Understanding the mechanisms involved in the relationship of acculturation and Hispanic/Latino background with hormones warrants additional investigation.

Sex Hormones and Diabetes in 45- to 74-year-old Men and Postmenopausal Women: The Hispanic Community Health Study.

Previous studies demonstrated associations of endogenous sex hormones with diabetes. Less is known about their dynamic relationship with diabetes progression through different stages of the disease, independence of associations, and role of the hypothalamic-pituitary gonadal axis. The purpose of this analysis was to examine relationships of endogenous sex hormones with incident diabetes, prediabetes, and diabetes traits in 693 postmenopausal women and 1015 men aged 45 to 74 years without diabetes at baseline participating in the Hispanic Community Health Study/Study of Latinos and followed for 6 years. Baseline hormones included estradiol, luteinizing hormone (LH), follicle stimulating hormone (FSH), sex hormone-binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEAS), and, in men, testosterone and bioavailable testosterone. Associations were analyzed using multivariable Poisson and linear regressions. In men, testosterone was inversely associated with conversion from prediabetes to diabetes (incidence rate ratio [IRR] for 1 SD increase in testosterone: 0.821; 95% CI, 0.676, 0.997; P = 0.046), but not conversion from normoglycemia to prediabetes. Estradiol was positively associated with increase in fasting insulin and homeostatic model assessment of insulin resistance. In women, SHBG was inversely associated with change in glycosylated hemoglobin, postload glucose, and conversion from prediabetes to diabetes (IRR = 0.62; 95% CI, 0.44, 0.86, P = 0.005) but not from normoglycemia to prediabetes. Relationships with other hormones varied across glycemic measures. Stronger associations of testosterone and SHBG with transition from prediabetes to diabetes than from normoglycemic to prediabetes suggest they are operative at later stages of diabetes development. Biologic pathways by which sex hormones affect glucose homeostasis await future studies.

Association of Blood Total Mercury with Dyslipidemia in a sample of U.S. Adolescents: Results from the National Health and Nutrition Examination Survey Database, 2011-2018.

Background: Abnormal lipid profiles in adolescents predict metabolic and cardiovascular diseases in adulthood. While seafood consumption is the primary source of mercury exposure, it also provides beneficial nutrients such as omega-3 fatty acids (O3FA). Prior studies indicate that blood total mercury (TBHg) has endocrine disrupting effects and may be associated with abnormal lipid profiles in adolescents. However, the impact of beneficial nutrients on this relationship has not been examined. Our study investigated the relationship of TBHg with dyslipidemia and lipid profiles and potential confounding and modification of these relationships by sex, body mass index (BMI), selenium and O3FA from seafood consumption. Methods: We examined 1,390 National Health and Nutrition Examination Survey participants 12-19 years of age from the 2011-2018 cycles. Using logistic and linear regression adjusted for survey design variables and stratified by sex a priori, we estimated the associations of TBHg and methylmercury with dyslipidemia, and with total cholesterol (TC), high (HDL-C) and low-density lipoprotein cholesterol (LDL-C) and triglycerides. Results: The geometric mean of TBHg in this adolescent population was 0.44 µg/L. After controlling for socio-demographic covariates, BMI, serum selenium, age at menarche (females only) and average daily intake of O3FA; TBHg was significantly associated with higher TC levels (ß=3.34, 95% CI: 0.19, 6.50; p<0.05) in females but not males. Methyl Hg was also associated with increased TC, as well as decreased HDL-C in females but not males. We did not find significant associations of Hg exposure with dyslipidemia, LDL-C or triglycerides levels in either male or female adolescents. However, we observed evidence of effect modification by BMI and serum selenium for associations of TBHg with TC levels in male and female adolescents, respectively. Conclusion: Our findings of elevated TC levels in females but not males necessitates further research to better understand the underlying mechanisms driving these sex-specific associations.

Associations of exposure to metal and metal mixtures with thyroid hormones: Results from the NHANES 2007-2012.

BACKGROUND: Disrupted thyroid homeostasis plays a role in neurocognitive dysfunction and metabolic disorders. Since individuals are exposed to multiple metals simultaneously, it is important to assess the effects of metal mixtures on thyroid hormone status. This study aimed to investigate the associations of metal mixtures and individual metals with thyroid hormone levels. METHODS: Data included 2399 men and 1988 women from the 2007-2012 National Health and Nutrition Examination Survey (2007-2012). Thyroid hormones measured included total triiodothyronine (T3), total thyroxine (T4), free forms of T3 (FT3) and T4 (FT4), and thyroid stimulating hormone (TSH). We included twelve metals (arsenic, barium, cobalt, cesium, molybdenum, antimony, thallium, tungsten, and uranium from urine; cadmium, lead, and mercury from blood) in traditional linear regression models controlling for 12 metals simultaneously and in quantile-based g-computation (QGC) to assess the relative contribution of each metal as well as the overall association with thyroid hormones as a metal mixture. RESULTS: There were associations of the total metal mixture with thyroid hormones for T3 (beta: -0.023, 95% CI: -0.04, -0.01, in women), T4 (beta: -0.03, 95% CI: -0.05, -0.01, in men; beta: -0.026, 95% CI: -0.04, -0.01, in women), and the T3:T4 ratio (beta: 0.026, 95% CI: 0.01, 0.05, in men). Arsenic had negative contributions to T3 and T4. Cadmium had a positive contribution to T4 but negative contributions to T3 and T3:T4. Lead had a positive contribution to T3 and T3:T4, but a negative contribution to T4. CONCLUSION: Multiple metals as a mixture were associated with thyroid hormone levels. Arsenic, cadmium, and lead were individually associated with multiple thyroid hormones. Examination of associations of metal mixtures and individual metals with thyroid hormones can contribute to an understanding of thyroid hormone homeostasis and provide evidence for developing intervention and guidance for health promotion.

Statistical Methods for Assessing the Explained Variation of a Health Outcome by a Mixture of Exposures.

Exposures to environmental pollutants are often composed of mixtures of chemicals that can be highly correlated because of similar sources and/or chemical structures. The effect of an individual chemical on a health outcome can be weak and difficult to detect because of the relatively low level of exposures to many environmental pollutants. To tackle the challenging problem of assessing the health risk of exposure to a mixture of environmental pollutants, we propose a statistical approach to assessing the proportion of the variation of an outcome explained by a mixture of pollutants. The proposed approach avoids the difficult task of identifying specific pollutants that are responsible for the effects and may also be used to assess interactions among exposures. Extensive simulation results demonstrate that the proposed approach has very good performance. Application of the proposed approach is illustrated by investigating the main and interaction effects of the chemical pollutants on systolic and diastolic blood pressure in participants from the National Health and Nutrition Examination Survey.

Assessment of Metal Concentrations and Associations with Pulmonary Function among Children with Asthma in Chicago, Illinois.

Individuals living in areas with the potential for elevated metal exposure from industrial sources may have reduced pulmonary function. We evaluated cross-sectional associations of toenail concentrations of 17 metals within a community area of residence and asthma control in 75 children, and pulmonary function measures [forced expiratory volume in one second (FEV1; liters), forced vital capacity (FVC; liters), FEV1 to FVC ratio (FEV1:FVC), and mid-exhalation forced expiratory flow rate (FEF 25-75%; liters/second)], in a subsample of 39 children with diagnosed asthma in Chicago, Illinois. Linear regression models were used to estimate adjusted regression coefficients and standard errors (SE) for the associations between ≥ median versus

Exposure to metal mixtures in relation to blood pressure among children 5-7 years old: An observational study in Bangladesh.

Hypertension in later life, a significant risk factor for cardiovascular disease, has been linked to elevated blood pressure in early life. Exposure to metals may influence childhood blood pressure; however, previous research is limited and has mainly focused on evaluating the toxicity of single metal exposures. This study evaluates the associations between exposure to metal mixtures and blood pressure among Bangladeshi children age 5-7 years. METHODS: We investigated the associations of 17 toenail metal concentrations with blood pressure using linear regression models. Principal component analysis (PCA), weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) were conducted as secondary analyses. RESULTS: Associations were observed for selenium with diastolic blood pressure (per doubling of exposure ß = 2.91, 95% confidence interval [CI] = 1.08, 4.75), molybdenum with systolic (ß = 0.33, 95% CI = 0.05, 0.61) and diastolic blood pressure (ß = 0.39, 95% CI = 0.12, 0.66), tin with systolic blood pressure (ß = -0.33, 95% CI = -0.60, -0.06), and mercury with systolic (ß = -0.83, 95% CI = -1.49, -0.17) and diastolic blood pressure (ß = -0.89, 95% CI = -1.53, -0.26). Chromium was associated with diastolic blood pressure among boys only (ß = 1.10, 95% CI = 0.28, 1.92, P for interaction = 0.02), and copper was associated with diastolic blood pressure among girls only (ß = -1.97, 95% CI = -3.63, -0.32, P for interaction = 0.01). These findings were largely robust to the secondary analyses that utilized mixture modeling approaches (PCA, WQS, and BKMR). CONCLUSIONS: Future prospective studies are needed to investigate further the impact of early life exposure to metal mixtures on children's blood pressure trajectories and cardiovascular disease risk later in life.

Multiple organochlorine pesticide exposures and measures of sex steroid hormones in adult males: Cross-sectional findings from the 1999-2004 National Health and Nutrition Examination Survey.

BACKGROUND: Organochlorine pesticides are detectable in serum from most adults. Animal studies provide evidence of pesticide effects on sex hormones, suggesting that exposures may impact human reproductive function. Mounting evidence of sex differences in chronic diseases suggest that perturbations in endogenous sex hormones may influence disease risk. However, the association between organochlorine pesticide exposure and sex hormone levels in males across the lifespan is not well understood. METHODS: We evaluated cross-sectional associations of lipid-adjusted serum concentrations of ß-hexachlorocyclohexane, hexachlorobenzene, heptachlor epoxide, oxychlordane, dichlorodiphenyldichloroethylene (DDE), p,p'-dichlorodiphenyltrichloroethane (DDT), trans-nonachlor, and mirex in relation to sex steroid hormone levels [testosterone (ng/dL), sex hormone binding globulin (SHBG; nmol/L), estradiol (pg/mL), and androstanediol glucuronide (ng/dL)] in a sample of 748 males aged 20 years and older from the 1999-2004 cycles of the National Health and Nutrition Examination Survey (NHANES). Survey-weighted linear regression models were performed to estimate geometric means (GM) and their 95% confidence intervals (CIs) for quartiles of lipid-adjusted pesticide concentrations, adjusting for age, race, body mass index, serum lipids, smoking, education, and survey cycle. RESULTS: Hexachlorobenzene concentration was positively associated with total estradiol (GM Q4 = 43.2 pg/mL (95% CI 36.5-51.1) vs. Q1 GM = 25.6 pg/mL (24.1-27.3), p-trend <0.0001) and free estradiol (GM Q4 = 0.77 pg/mL (95% CI 0.64-0.93) vs. Q1 GM = 0.47 pg/mL (0.44-0.51), p-trend = 0.002). Serum DDT concentration was positively associated with total estradiol (GM Q4 = 31.6 pg/mL (95% CI 25.9-38.5) vs. Q1 GM = 27.3 pg/mL (25.9-28.7), p-trend = 0.05) and free estradiol (GM Q4 = 0.60 pg/mL (95% CI 0.48-0.76) vs. Q1 GM = 0.50 pg/mL (0.47-0.53), p-trend 0.02). There was a suggestive inverse association of DDT and SHBG (GM Q4 = 29.2 nmol/L (95% CI 23.8-35.9) vs. Q1 GM = 33.9 nmol/L (32.3-35.5), p-trend 0.07). A positive association of ß-hexachlorocyclohexane with total estradiol (GM Q4 = 30.3 pg/mL (95% CI 26.5-34.6) vs. Q1 GM = 26.7 pg/mL (24.5-29.0), p-trend = 0.09) was also suggestive but did not reach statistical significance. No distinct associations were observed for other hormone levels or other organochlorine pesticides. CONCLUSIONS: Our findings suggest that select organochlorine pesticides may alter male estradiol levels. The positive associations with estradiol may implicate sex hormones as a possible mechanism for disease risk among those with organochlorine pesticide exposure.

Associations of PCBS, dioxins and furans with follicle-stimulating hormone and luteinizing hormone in postmenopausal women: National Health and Nutrition Examination Survey 1999-2002.

BACKGROUND: The general population is exposed to the group of endocrine disrupting chemicals persistent organic pollutants (POPs), that includes polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs). OBJECTIVES: The aim of this research was to evaluate the associations of serum levels of PCB, PCDD, and PCDF congeners with follicle stimulating hormone (FSH) and luteinizing hormone (LH) in postmenopausal women not taking exogenous hormones. We hypothesized that associations of POPs with these gonadotropins could be modified by factors affecting endogenous hormones. METHODS: Cross-sectional analyses were conducted on data from 89 postmenopausal women using data from the National Health and Nutrition Examination Survey (NHANES). POPs were summarized based on classification schemes thought to reflect toxicological properties. Associations of POPs and gonadotropin hormones were modeled with multivariable regression models. When evidence of interaction was found, conditional effects were estimated. RESULTS: We found inverse associations of LH, but not FSH, with exposure to anti-estrogenic and/or dioxin-like POPs, but not with non dioxin-like PCBs. A doubling of dioxin-like toxic equivalents (TEQs) was associated with a decrease in LH of 11.9% (95% CI = -21.3%, -1.4%, p = 0.03). Inverse associations were enhanced by potential effect modifiers related to both direct and indirect estrogenicity, including obesity and the obesity-related condition inflammation. CONCLUSIONS: These investigations support a pattern of endocrine-disrupting effects by dioxin-like POPs among postmenopausal women, especially those with conditions related to peripheral estrogenicity.

Neighborhood Food Outlet Access and Dietary Intake among Adults with Chronic Kidney Disease: Results from the Chronic Renal Insufficiency Cohort Study.

BACKGROUND: Healthy diet is essential in the management of chronic kidney disease (CKD) and preventing related comorbidities. Food outlet access has been studied in the general population; however, the influence of the local food environment on dietary intake among people with CKD has not been evaluated. OBJECTIVES: This study examined the associations of food outlet density and type of outlets with dietary intake in a multicenter cohort of racially and ethnically diverse patients with CKD. METHODS: The Chronic Renal Insufficiency Cohort Study is a multicenter prospective study of patients with CKD that used a validated food frequency questionnaire to capture dietary intake at the baseline visit. This is a cross-sectional analysis of 2,484 participants recruited in 2003-2006 from seven Chronic Renal Insufficiency Cohort Study centers. Food outlet data were used to construct a count of the number of fast-food restaurants, convenience stores, and grocery stores per 10,000 population for each geocoded census block group. Multivariable linear and logistic regression models were used to evaluate the associations between measures of food outlet availability and dietary factors. RESULTS: The proportion of participants living in zero-, low-, and high-food outlet density areas differed by gender, race or ethnicity, and income level. Among male subjects, living in areas with zero or the highest number of outlets was associated with having the highest caloric intakes in multivariable models. Male subjects living in areas with zero outlets consumed the highest levels of sodium and phosphorous. Female subjects living in areas with zero outlets had the lowest average intake of calories, sodium, and phosphorous. Among low-income female subjects, close proximity to more outlets was associated with higher calorie consumption. Among all participants, access to fast-food restaurants was not associated with an unhealthy diet score, and access to grocery stores was not associated with a healthy diet score. CONCLUSIONS: Average caloric and nutrient intakes differed by outlet availability; however, there were no strong associations with type of food outlet. This should be considered when developing food-focused public health policies.

Changes in blood pressure associated with lead, manganese, and selenium in a Bangladeshi cohort.

BACKGROUND: Heavy metal contamination is widespread in Bangladesh. Previous studies have observed lead increases blood pressure over time. However, the role of other metal contaminants and essential micronutrients, which could also adversely affect blood pressure or act as protective factors, is understudied. OBJECTIVES: We therefore evaluated the associations of lead, manganese, and selenium with blood and pulse pressure trajectories. METHODS: We prospectively followed placebo-assigned participants nested within a randomized trial for the prevention of arsenic-related skin cancer (n = 255). Blood lead, manganese, and selenium were measured at baseline; blood pressure was measured at baseline and at 3 biennial follow-up examinations. Mixed-effect linear regression models were used to estimate associations with average annual changes in systolic, diastolic, and pulse pressure. RESULTS: In models simultaneously adjusted for baseline blood lead, manganese, and selenium concentrations in addition to other potential confounders, lead was linearly associated with increases in systolic blood pressure, but not with diastolic blood pressure or pulse pressure. A non-linear association was observed for manganese, such that mid-range concentrations were associated with decreases in systolic, diastolic, and pulse pressure. Baseline selenium concentrations in the highest quartile were also associated with longitudinal decreases in both systolic and diastolic blood pressure, while null associations were observed with pulse pressure. In exploratory analyses, the combination of mid-range manganese and high selenium concentrations completely offset lead-associated increases in blood and pulse pressure. CONCLUSIONS: The results indicate a direct, linear association of lead exposure with systolic blood pressure, and manganese and selenium exposures within certain ranges may have a blood pressure-lowering effect in this population.

Associations between blood cadmium concentration and kidney function in the U.S. population: Impact of sex, diabetes and hypertension.

BACKGROUND: Exposure to cadmium has been associated with nephropathy and implicated in the development of diabetes and hypertension. The role of environmental metal exposure may be an underexplored risk factor for decreased kidney function among people with diabetes and/or hypertension. The objective of this study was to examine the association of blood concentration of cadmium with kidney function parameters and evaluate sex, diabetes, and hypertension as effect modifiers of the association. METHODS: This study used data from 12,577 adult participants in the National Health and Nutrition Examination Survey (NHANES) 2007-2012 cycles. We used multivariable linear and logistic regression models to conduct a cross-sectional analysis of the association between cadmium exposure quartiles and estimated glomerular filtration rate (eGFR), urine albumin to creatinine ratio (UACR), low eGFR (defined as eGFR <60 mL/minute/1.73 m2), and albuminuria (defined as UACR ≥ 30 mg/g). Models were adjusted for confounders and interaction terms were evaluated for cadmium concentration and sex, diabetes, and hypertension. Final models were stratified by sex and indices of existing diabetes and hypertension status. RESULTS: The mean eGFR was 94.3 mL/minute/1.73 m2 (SD 21.5) and the geometric mean of UACR was 7.9 mg/g (95% CI 7.6-8.2 mg/g). Blood cadmium concentration was inversely associated with eGFR and positively associated with UACR. We found significant effect modification of the association of eGFR with cadmium, predominantly for sex and hypertension. The strength of the association between cadmium quartiles and eGFR was more pronounced among females compared to males. Among females with hypertension and diabetes, eGFR was lower on average by 4.9 mL/minute/1.73 m2 (95% CI -10.1 to 0.29) in the highest versus lowest cadmium quartile, and in females with hypertension alone, eGFR was lower on average by 5.8 mL/minute/1.73 m2 (95% CI -8.2 to -3.3) in the highest versus lowest cadmium quartile. Among those in the highest exposure quartile, higher mean UACR was observed among participants with hypertension compared to those without. CONCLUSIONS: Our results confirm that cadmium exposure is associated with decreased glomerular filtration and increased urine protein excretion, and provide evidence that the magnitude of these associations differ by sex and may vary based on preexisting diabetes and hypertension. Future prospective sex-specific investigations are necessary to address concerns of reverse causality and efforts should be made to reduce smoking and environmental contamination from cadmium to protect human health.

Multiple metal exposures and metabolic syndrome: A cross-sectional analysis of the National Health and Nutrition Examination Survey 2011-2014.

BACKGROUND: Epidemiologic studies suggest toxic metals are linked with diabetes and cardiovascular disease, while experimental studies indicate nutritionally essential metals are involved in the metabolism of macronutrients and defense against oxidative stress. OBJECTIVES: We sought to evaluate how essential and toxic metals are cross-sectionally related to metabolic syndrome, a clustering of cardiometabolic conditions. METHODS: Using data from the 2011-2014 National Health and Nutrition Examination Survey (n = 1088), we characterized metal concentrations as measured in spot urine (arsenic, cadmium, and inorganic/elemental mercury), whole blood (manganese, lead, methylmercury, and selenium), and serum (copper and zinc) samples. Principal component analysis was performed to derive patterns of exposures. Metabolic syndrome was defined according to the 2009 Joint Scientific Statement as the presence of ≥ 3 of the following conditions: high blood pressure, high triglycerides, low HDL cholesterol, high fasting glucose, and abdominal obesity. RESULTS: After adjustment for potential confounders, prevalence ratios for metabolic syndrome comparing the highest to the lowest quartiles were 1.41 (95% CI: 1.18-1.67) for the arsenic-inorganic/elemental mercury pattern, 0.95 (0.78-1.16) for the methylmercury-manganese pattern, 0.73 (0.57-0.94) for the cadmium-lead pattern, 0.91 (0.76-1.10) for the copper pattern, and 1.36 (1.13-1.63) for the selenium-zinc pattern. The positive associations observed for the arsenic-inorganic/elemental mercury pattern were due to an elevated prevalence of high blood pressure, low HDL cholesterol, and high triglycerides among those with greater exposures. Associations for the selenium-zinc pattern were driven by a positive relationship with high triglycerides. Greater lead-cadmium co-exposures were related to a lower prevalence of dyslipidemia and abdominal obesity. CONCLUSIONS: These cross-sectional findings suggest both toxic and essential metal exposures may contribute to cardiometabolic health, but need to be confirmed with prospective data.

Association of occupational exposures with cardiovascular disease among US Hispanics/Latinos.

OBJECTIVE: Cardiovascular disease (CVD) is a leading cause of mortality and morbidity in the USA. The role of occupational exposures to chemicals in the development of CVD has rarely been studied even though many agents possess cardiotoxic properties. We therefore evaluated associations of self-reported exposures to organic solvents, metals and pesticides in relation to CVD prevalence among diverse Hispanic/Latino workers. METHODS: Cross-sectional data from 7404 employed individuals, aged 18-74 years, enrolled in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) were analysed. Participants from four US cities provided questionnaire data and underwent clinical examinations, including ECGs. CVD was defined as the presence of at least one of the following: coronary heart disease, atrial fibrillation, heart failure or cerebrovascular disease. Prevalence ratios reflecting the relationship between each occupational exposure and CVD as well as CVD subtypes were calculated using Poisson regression models. RESULTS: Hispanic/Latino workers reported exposures to organic solvents (6.5%), metals (8.5%) and pesticides (4.7%) at their current jobs. Overall, 6.1% of participants had some form of CVD, with coronary heart disease as the most common (4.3%) followed by cerebrovascular disease (1.0%), heart failure (0.8%) and atrial fibrillation (0.7%). For individuals who reported working with pesticides, the prevalence ratios for any CVD were 2.18 (95% CI 1.34 to 3.55), coronary heart disease 2.20 (95% CI 1.31 to 3.71), cerebrovascular disease 1.38 (95% CI 0.62 3.03), heart failure 0.91 (95% CI 0.23 to 3.54) and atrial fibrillation 5.92 (95% CI 1.89 to 18.61) after adjustment for sociodemographic, acculturation, lifestyle and occupational characteristics. Metal exposures were associated with an almost fourfold (3.78, 95% CI 1.24 to 11.46) greater prevalence of atrial fibrillation. Null associations were observed for organic solvent exposures. CONCLUSIONS: Our results suggest that working with metals and pesticides could be risk factors for CVD among Hispanic/Latino workers. Further work is needed to evaluate these relationships prospectively.

Associations of urban greenness with asthma and respiratory symptoms in Mexican American children.

BACKGROUND: Evidence on the association between residential surrounding greenness (RSG) in urban areas with asthma and asthma symptoms is inconsistent. OBJECTIVE: To examine the association of RSG with respiratory outcomes in a sample of Mexican American children living in inner-city Chicago, Illinois. METHODS: This study is based on parent-reported data on 1915 Mexican American children. We calculated RSG using the normalized difference vegetation index based on satellite imagery within buffers of 100, 250, and 500 m of each child's residence. Multivariable multilevel mixed-effect logistic regression was used to estimate adjusted odds ratios (aORs) for the effect of a 1-interquartile range increase in greenness. RESULTS: In adjusted analyses, a protective effect of greenness within 100 m was observed for lifetime wheezing (aOR, 0.82; 95% CI, 0.69-0.96). Environmental tobacco smoke (ETS) exposure modified the association of RSG with lifetime asthma and current dry cough at night. For all buffer distances, increased greenness was associated with lower odds of lifetime asthma among children with current ETS exposure (100 m: aOR, 0.43; 95% CI, 0.22-0.87; 250 m: aOR, 0.39; 95% CI, 0.18-0.84; 500 m: aOR, 0.48; 95% CI, 0.26-0.90) and lower odds of current dry cough at night among children with perinatal ETS exposure (100 m: aOR, 0.53; 95% CI, 0.31-0.92; 250 m: aOR, 0.55; 95% CI, 0.31-0.98; 500 m: aOR, 0.55; 95% CI, 0.35-0.87). CONCLUSION: Our results suggest inverse associations of urban greenness with respiratory outcomes, especially in children exposed to ETS. Further research is needed to examine the mechanisms through which RSG may be associated with the risk of asthma and contribute to health.

Association of heavy metals with measures of pulmonary function in children and youth: Results from the National Health and Nutrition Examination Survey (NHANES).

INTRODUCTION: Exposure to cadmium, cobalt, lead, and manganese has been associated with decreased pulmonary function in adults. Little is known about the magnitude of these associations among children in the United States. OBJECTIVES: We evaluated cross-sectional associations of blood and urinary concentrations of cadmium, cobalt, lead, and manganese with pulmonary function measures [forced expiratory volume in one second (FEV1; milliliters), forced vital capacity (FVC; milliliters), ratio of FEV1 to FVC (FEV1:FVC), and mid-exhalation forced expiratory flow rate (FEF 25-75%; milliliters/second)] in a sample of 1234 6-17 year olds, who participated in the 2011-2012 survey cycle of the National Health and Nutrition Examination Survey (NHANES). METHODS: Survey-weighted linear regression was used to estimate beta coefficients and 95% confidence intervals (CIs) for the associations between metal exposure tertiles or quartiles and pulmonary function test parameters, with adjustment for relevant covariates. RESULTS: Blood manganese concentration was inversely associated with FVC (ß for highest versus lowest quartile = -97.1, 95% CI = -230.6, 36.4; p for trend = 0.03). Urinary manganese was inversely associated with FEV1:FVC and FEF 25-75% (p for trend = 0.05 and 0.02, respectively). Urinary lead was inversely associated with FEF 25-75% (p for trend = 0.01). The associations between blood manganese and both FEV1 and FVC differed by age (p for interaction = 0.04 and 0.04, respectively), indicating an inverse trend that was strongest among older youth. CONCLUSIONS: Environmental exposure to manganese and lead may adversely impact the pulmonary function of young people in the United States. Our findings highlight a need to prioritize children's environmental health and evaluate these associations prospectively.