Proteomics, Human Environmental Exposure, and Cardiometabolic Risk.

BACKGROUND: The biological mechanisms linking environmental exposures with cardiovascular disease pathobiology are incompletely understood. We sought to identify circulating proteomic signatures of environmental exposures and examine their associations with cardiometabolic and respiratory disease in observational cohort studies. METHODS: We tested the relations of >6500 circulating proteins with 29 environmental exposures across the built environment, green space, air pollution, temperature, and social vulnerability indicators in ≈3000 participants of the CARDIA study (Coronary Artery Risk Development in Young Adults) across 4 centers using penalized and ordinary linear regression. In >3500 participants from FHS (Framingham Heart Study) and JHS (Jackson Heart Study), we evaluated the prospective relations of proteomic signatures of the envirome with cardiovascular disease and mortality using Cox models. RESULTS: Proteomic signatures of the envirome identified novel/established cardiovascular disease-relevant pathways including DNA damage, fibrosis, inflammation, and mitochondrial function. The proteomic signatures of the envirome were broadly related to cardiometabolic disease and respiratory phenotypes (eg, body mass index, lipids, and left ventricular mass) in CARDIA, with replication in FHS/JHS. A proteomic signature of social vulnerability was associated with a composite of cardiovascular disease/mortality (1428 events; FHS: hazard ratio, 1.16 [95% CI, 1.08-1.24]; P=1.77×10-5; JHS: hazard ratio, 1.25 [95% CI, 1.13-1.38]; P=6.38×10-6; hazard ratioexpressed as per 1 SD increase in proteomic signature), robust to adjustment for known clinical risk factors. CONCLUSIONS: Environmental exposures are related to an inflammatory-metabolic proteome, which identifies individuals with cardiometabolic disease and respiratory phenotypes and outcomes. Future work examining the dynamic impact of the environment on human cardiometabolic health is warranted.

Association of Water Arsenic With Incident Diabetes in U.S. Adults: The Multi-Ethnic Study of Atherosclerosis and the Strong Heart Study.

OBJECTIVE: We examined the association of arsenic in federally regulated community water systems (CWSs) and unregulated private wells with type 2 diabetes (T2D) incidence in the Strong Heart Family Study (SHFS), a prospective study of American Indian communities, and the Multi-Ethnic Study of Atherosclerosis (MESA), a prospective study of racially and ethnically diverse urban U.S. communities. RESEARCH DESIGN AND METHODS: We evaluated 1,791 participants from SHFS and 5,777 participants from MESA who had water arsenic estimates available and were free of T2D at baseline (2001-2003 and 2000-2002, respectively). Participants were followed for incident T2D until 2010 (SHFS cohort) or 2019 (MESA cohort). We used Cox proportional hazards mixed-effects models to account for clustering by family and residential zip code, with adjustment for sex, baseline age, BMI, smoking status, and education. RESULTS: T2D incidence was 24.4 cases per 1,000 person-years (mean follow-up, 5.6 years) in SHFS and 11.2 per 1,000 person-years (mean follow-up, 14.0 years) in MESA. In a meta-analysis across the SHFS and MESA cohorts, the hazard ratio (95% CI) per doubling in CWS arsenic was 1.10 (1.02, 1.18). The corresponding hazard ratio was 1.09 (0.95, 1.26) in the SHFS group and 1.10 (1.01, 1.20) in the MESA group. The corresponding hazard ratio (95% CI) for arsenic in private wells and incident T2D in SHFS was 1.05 (0.95, 1.16). We observed statistical interaction and larger magnitude hazard ratios for participants with BMI <25 kg/m2 and female participants. CONCLUSIONS: Low to moderate water arsenic levels (<10 µg/L) were associated with T2D incidence in the SHFS and MESA cohorts.

The Contribution of Declines in Blood Lead Levels to Reductions in Blood Pressure Levels: Longitudinal Evidence in the Strong Heart Family Study.

BACKGROUND: Chronic lead exposure is associated with both subclinical and clinical cardiovascular disease. We evaluated whether declines in blood lead were associated with changes in systolic and diastolic blood pressure in adult American Indian participants from the SHFS (Strong Heart Family Study). METHODS AND RESULTS: Lead in whole blood was measured in 285 SHFS participants in 1997 to 1999 and 2006 to 2009. Blood pressure and measures of cardiac geometry and function were obtained in 2001 to 2003 and 2006 to 2009. We used generalized estimating equations to evaluate the association of declines in blood lead with changes in blood pressure; cardiac function and geometry measures were considered secondary. Mean blood lead was 2.04 µg/dL at baseline. After ≈10 years, mean decline in blood lead was 0.67 µg/dL. In fully adjusted models, the mean difference in systolic blood pressure comparing the highest to lowest tertile of decline (>0.91 versus <0.27 µg/dL) in blood lead was -7.08 mm Hg (95% CI, -13.16 to -1.00). A significant nonlinear association between declines in blood lead and declines in systolic blood pressure was detected, with significant linear associations where blood lead decline was 0.1 µg/dL or higher. Declines in blood lead were nonsignificantly associated with declines in diastolic blood pressure and significantly associated with declines in interventricular septum thickness. CONCLUSIONS: Declines in blood lead levels in American Indian adults, even when small (0.1-1.0 µg/dL), were associated with reductions in systolic blood pressure. These findings suggest the need to further study the cardiovascular impacts of reducing lead exposures and the importance of lead exposure prevention.

Regional and racial/ethnic inequalities in public drinking water fluoride concentrations across the US.

BACKGROUND: Although the US Centers for Disease Control and Prevention (CDC) considers fluoridation of community water systems (CWSs) to be a major public health achievement responsible for reducing dental disease, recent epidemiologic evidence suggests that chronic exposure to population-relevant levels of fluoride may also be associated with adverse child neurodevelopmental outcomes. To our knowledge, a nationally representative database of CWS fluoride concentration estimates that can be readily linked to US epidemiologic cohorts for further study is not publicly available. Our objectives were to evaluate broad regional and sociodemographic inequalities in CWS fluoride concentrations across the US, and to determine if county-level racial/ethnic composition was associated with county-level CWS fluoride. METHODS: We generated CWS-level (N = 32,495) and population weighted county-level (N = 2152) fluoride concentration estimates using over 250,000 routine compliance monitoring records collected from the US Environmental Protection Agency's (EPA) Third Six Year Review (2006-2011). We compared CWS-level fluoride distributions across subgroups including region, population size served, and county sociodemographic characteristics. In county-level spatial error models, we also evaluated geometric mean ratios (GMRs) of CWS fluoride per 10% higher proportion of residents belonging to a given racial/ethnic subgroup. RESULTS: 4.5% of CWSs (serving >2.9 million residents) reported mean 2006-2011 fluoride concentrations ≥1500 µg/L (the World Health Organization's guideline for drinking water quality). Arithmetic mean, 90th, and 95th percentile contaminant concentrations were greatest in CWSs reliant on groundwater, located in the Southwest and Eastern Midwest, and serving Semi-Urban, Hispanic communities. In fully adjusted spatial error models, the GMR (95% CI) of CWS fluoride per a 10% higher proportion of county residents that were Hispanic/Latino was 1.16 (1.10, 1.23). IMPACT STATEMENT: We find that over 2.9 million US residents are served by public water systems with average fluoride concentrations exceeding the World Health Organization's guidance limit. We also find significant inequalities in community water system fluoride concentration estimates (2006-2011) across the US, especially for Hispanic/Latino communities who also experience elevated arsenic and uranium in regulated public drinking water systems. Our fluoride estimates can be leveraged in future epidemiologic studies to assess the potential association between chronic fluoride exposure and related adverse outcomes.

US drinking water quality: exposure risk profiles for seven legacy and emerging contaminants.

BACKGROUND: Advances in drinking water infrastructure and treatment throughout the 20th and early 21st century dramatically improved water reliability and quality in the United States (US) and other parts of the world. However, numerous chemical contaminants from a range of anthropogenic and natural sources continue to pose chronic health concerns, even in countries with established drinking water regulations, such as the US. OBJECTIVE/METHODS: In this review, we summarize exposure risk profiles and health effects for seven legacy and emerging drinking water contaminants or contaminant groups: arsenic, disinfection by-products, fracking-related substances, lead, nitrate, per- and polyfluorinated alkyl substances (PFAS) and uranium. We begin with an overview of US public water systems, and US and global drinking water regulation. We end with a summary of cross-cutting challenges that burden US drinking water systems: aging and deteriorated water infrastructure, vulnerabilities for children in school and childcare facilities, climate change, disparities in access to safe and reliable drinking water, uneven enforcement of drinking water standards, inadequate health assessments, large numbers of chemicals within a class, a preponderance of small water systems, and issues facing US Indigenous communities. RESULTS: Research and data on US drinking water contamination show that exposure profiles, health risks, and water quality reliability issues vary widely across populations, geographically and by contaminant. Factors include water source, local and regional features, aging water infrastructure, industrial or commercial activities, and social determinants. Understanding the risk profiles of different drinking water contaminants is necessary for anticipating local and general problems, ascertaining the state of drinking water resources, and developing mitigation strategies. IMPACT STATEMENT: Drinking water contamination is widespread, even in the US. Exposure risk profiles vary by contaminant. Understanding the risk profiles of different drinking water contaminants is necessary for anticipating local and general public health problems, ascertaining the state of drinking water resources, and developing mitigation strategies.

Contribution of arsenic and uranium in private wells and community water systems to urinary biomarkers in US adults: The Strong Heart Study and the Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Chronic exposure to inorganic arsenic (As) and uranium (U) in the United States (US) occurs from unregulated private wells and federally regulated community water systems (CWSs). The contribution of water to total exposure is assumed to be low when water As and U concentrations are low. OBJECTIVE: We examined the contribution of water As and U to urinary biomarkers in the Strong Heart Family Study (SHFS), a prospective study of American Indian communities, and the Multi-Ethnic Study of Atherosclerosis (MESA), a prospective study of racially/ethnically diverse urban U.S. communities. METHODS: We assigned residential zip code-level estimates in CWSs (µg/L) and private wells (90th percentile probability of As >10 µg/L) to up to 1485 and 6722 participants with dietary information and urinary biomarkers in the SHFS (2001-2003) and MESA (2000-2002; 2010-2011), respectively. Urine As was estimated as the sum of inorganic and methylated species, and urine U was total uranium. We used linear mixed-effects models to account for participant clustering and removed the effect of dietary sources via regression adjustment. RESULTS: The median (interquartile range) urine As was 5.32 (3.29, 8.53) and 6.32 (3.34, 12.48) µg/L for SHFS and MESA, respectively, and urine U was 0.037 (0.014, 0.071) and 0.007 (0.003, 0.018) µg/L. In a meta-analysis across both studies, urine As was 11% (95% CI: 3, 20%) higher and urine U was 35% (5, 73%) higher per twofold higher CWS As and U, respectively. In the SHFS, zip-code level factors such as private well and CWS As contributed 46% of variation in urine As, while in MESA, zip-code level factors, e.g., CWS As and U, contribute 30 and 49% of variation in urine As and U, respectively. IMPACT STATEMENT: We found that water from unregulated private wells and regulated CWSs is a major contributor to urinary As and U (an estimated measure of internal dose) in both rural, American Indian populations and urban, racially/ethnically diverse populations nationwide, even at levels below the current regulatory standard. Our findings indicate that additional drinking water interventions, regulations, and policies can have a major impact on reducing total exposures to As and U, which are linked to adverse health effects even at low levels.

Geospatial Assessment of Racial/Ethnic Composition, Social Vulnerability, and Lead Water Service Lines in New York City.

BACKGROUND: The state of New York expects to receive $115 million in 2022 alone from the U.S. Infrastructure Investment and Jobs Act to support the replacement of lead water service lines. OBJECTIVES: Our objective was to determine the number and proportion of potential lead water service lines across New York City (NYC) and to evaluate the association between census tract-level racial/ethnic composition, housing vulnerability, and child lead exposure vulnerability with service line type (Potential Lead, Unknown) for n=2,083 NYC tracts. METHODS: We conducted a descriptive analysis assessing water service line material recorded in the NYC Department of Environmental Protection's Lead Service Line Location Coordinates database. We used conditional autoregressive Bayesian Poisson models to assess the relative risk [RR; median posterior estimates, and 95% credible interval (CrI)] of service line type per 20% higher proportion of residents in a given racial/ethnic group and per higher housing vulnerability and child lead exposure vulnerability index scores corresponding to the interquartile range. We also evaluated the associations in flexible natural cubic spline models. RESULTS: Out of 854,672 residential service line records, 136,891 (16.0%) were Potential Lead, and 227,443 (26.6%) were Unknown. In fully adjusted models, higher proportions of Hispanic/Latino residents and higher child lead exposure vulnerability were associated with Potential Lead service lines in flexible spline models and linear models [RR=1.15 (95% CrI: 1.11, 1.21) and RR=1.11 (95% CrI: 1.02, 1.20), respectively]. Associations were modified by borough; Potential Lead service lines were associated with higher proportions of non-Hispanic White and non-Hispanic Asian residents in the Bronx and Manhattan, and with higher proportions of non-Hispanic Black residents in Queens. DISCUSSION: NYC has a high number of Potential Lead and Unknown water service lines. Communities with a high proportion of Hispanic/Latino residents and those with children who are already highly vulnerable to lead exposures from numerous sources are disproportionately impacted by Potential Lead service lines. These findings can inform equitable service line replacement across New York state and NYC. https://doi.org/10.1289/EHP12276.

Blood and Urinary Metal Levels among Exclusive Marijuana Users in NHANES (2005-2018).

BACKGROUND: Marijuana is the third most used drug in the world. OBJECTIVES: Because the cannabis plant is a known scavenger of metals, we hypothesized that individuals who use marijuana will have higher metal biomarker levels compared with those who do not use. METHODS: We combined data from the National Health and Nutrition Examination Survey (2005-2018) for n=7,254 participants, classified by use: non-marijuana/non-tobacco, exclusive marijuana, exclusive tobacco, and dual marijuana and tobacco use. Five metals were measured in blood and 16 in urine using inductively coupled plasma mass spectrometry; urinary metals were adjusted for urinary creatinine. RESULTS: Participants reporting exclusive marijuana use compared with non-marijuana/non-tobacco use had statistically significantly higher mean cadmium levels in blood [1.22µg/L (95% CI: 1.11, 1.34); p<0.001] and urine [1.18µg/g (95% CI: 1.0, 1.31); p=0.004] and statistically significantly higher mean lead levels in blood [1.27µg/dL (95% CI: 1.07, 1.50); p=0.006] and urine [1.21µg/g (95% CI: -0.006, 1.50); p=0.058]. DISCUSSION: Our results suggest marijuana is a source of cadmium and lead exposure. Research regarding cannabis use and cannabis contaminants, particularly metals, should be conducted to address public health concerns related to the growing number of cannabis users. https://doi.org/10.1289/EHP12074.

Associations between area-level arsenic exposure and adverse birth outcomes: An Echo-wide cohort analysis.

BACKGROUND: Drinking water is a common source of exposure to inorganic arsenic. In the US, the Safe Drinking Water Act (SDWA) was enacted to protect consumers from exposure to contaminants, including arsenic, in public water systems (PWS). The reproductive effects of preconception and prenatal arsenic exposure in regions with low to moderate arsenic concentrations are not well understood. OBJECTIVES: This study examined associations between preconception and prenatal exposure to arsenic violations in water, measured via residence in a county with an arsenic violation in a regulated PWS during pregnancy, and five birth outcomes: birth weight, gestational age at birth, preterm birth, small for gestational age (SGA), and large for gestational age (LGA). METHODS: Data for arsenic violations in PWS, defined as concentrations exceeding 10 parts per billion, were obtained from the Safe Drinking Water Information System. Participants of the Environmental influences on Child Health Outcomes Cohort Study were matched to arsenic violations by time and location based on residential history data. Multivariable, mixed effects regression models were used to assess the relationship between preconception and prenatal exposure to arsenic violations in drinking water and birth outcomes. RESULTS: Compared to unexposed infants, continuous exposure to arsenic from three months prior to conception through birth was associated with 88.8 g higher mean birth weight (95% CI: 8.2, 169.5), after adjusting for individual-level confounders. No statistically significant associations were observed between any preconception or prenatal violations exposure and gestational age at birth, preterm birth, SGA, or LGA. CONCLUSIONS: Our study did not identify associations between preconception and prenatal arsenic exposure, defined by drinking water exceedances, and adverse birth outcomes. Exposure to arsenic violations in drinking water was associated with higher birth weight. Future studies would benefit from more precise geodata of water system service areas, direct household drinking water measurements, and exposure biomarkers.

Impact of lowering the US maximum contaminant level on arsenic exposure: Differences by race, region, and water arsenic in NHANES 2003-2014.

Our objective was to evaluate regional and sociodemographic inequalities in water arsenic exposure reductions associated with the US Environmental Protection Agency's Final Arsenic Rule, which lowered the arsenic maximum contaminant level to 10 µg/L in public water systems. We analyzed 8544 participants from the 2003-14 National Health and Nutrition Examination Survey (NHANES) reliant on community water systems (CWSs). We estimated arsenic exposure from water by recalibrating urinary dimethylarsinate (rDMA) to remove smoking and dietary contributions. We evaluated mean differences and corresponding percent reductions of urinary rDMA comparing subsequent survey cycles to 2003-04 (baseline), stratified by region, race/ethnicity, educational attainment, and tertile of CWS arsenic assigned at the county level. The overall difference (percent reduction) in urine rDMA was 0.32 µg/L (9%) among participants with the highest tertile of CWS arsenic, comparing 2013-14 to 2003-04. Declines in urinary rDMA were largest in regions with the highest water arsenic: the South [0.57 µg/L (16%)] and West [0.46 µg/L, (14%)]. Declines in urinary rDMA levels were significant and largest among Mexican American [0.99 µg/L (26%)] and Non-Hispanic White [0.25 µg/L (10%)] participants. Reductions in rDMA following the Final Arsenic Rule were highest among participants with the highest CWS arsenic concentrations, supporting legislation can benefit those who need it the most, although additional efforts are still needed to address remaining inequalities in CWS arsenic exposure.

Cross-sectional associations between drinking water arsenic and urinary inorganic arsenic in the United States: NHANES 2003-2014.

BACKGROUND: Inorganic arsenic is a potent carcinogen and toxicant associated with numerous adverse health outcomes. The contribution of drinking water from private wells and regulated community water systems (CWSs) to total inorganic arsenic exposure is not clear. OBJECTIVES: To determine the association between drinking water arsenic estimates and urinary arsenic concentrations in the 2003-2014 National Health and Nutrition Examination Survey (NHANES). METHODS: We evaluated 11,088 participants from the 2003-2014 NHANES cycles. For each participant, we assigned private well and CWS arsenic levels according to county of residence using estimates previously derived by the U.S. Environmental Protection Agency and U.S. Geological Survey. We used recalibrated urinary dimethylarsinate (rDMA) to reflect the internal dose of estimated water arsenic by applying a previously validated, residual-based method that removes the contribution of dietary arsenic sources. We compared the adjusted geometric mean ratios and corresponding percent change of urinary rDMA across tertiles of private well and CWS arsenic levels, with the lowest tertile as the reference. Comparisons were made overall and stratified by census region and race/ethnicity. RESULTS: Overall, the geometric mean of urinary rDMA was 2.52 (2.30, 2.77) µg/L among private well users and 2.64 (2.57, 2.72) µg/L among CWS users. Urinary rDMA was highest among participants in the West and South, and among Mexican American, Other Hispanic, and Non-Hispanic Other participants. Urinary rDMA levels were 25% (95% confidence interval (CI): 17-34%) and 20% (95% CI: 12-29%) higher comparing the highest to the lowest tertile of CWS and private well arsenic, respectively. The strongest associations between water arsenic and urinary rDMA were observed among participants in the South, West, and among Mexican American and Non-Hispanic White and Black participants. DISCUSSION: Both private wells and regulated CWSs are associated with inorganic arsenic internal dose as reflected in urine in the general U.S.

Nationwide geospatial analysis of county racial and ethnic composition and public drinking water arsenic and uranium.

There is no safe level of exposure to inorganic arsenic or uranium, yet recent studies identified sociodemographic and regional inequalities in concentrations of these frequently detected contaminants in public water systems across the US. We analyze the county-level association between racial/ethnic composition and public water arsenic and uranium concentrations from 2000-2011 using geospatial models. We find that higher proportions of Hispanic/Latino and American Indian/Alaskan Native residents are associated with significantly higher arsenic and uranium concentrations. These associations differ in magnitude and direction across regions; higher proportions of non-Hispanic Black residents are associated with higher arsenic and uranium in regions where concentrations of these contaminants are high. The findings from this nationwide geospatial analysis identifying racial/ethnic inequalities in arsenic and uranium concentrations in public drinking water across the US can advance environmental justice initiatives by informing regulatory action and financial and technical support to protect communities of color.

Socioeconomic vulnerability and public water arsenic concentrations across the US.

Inorganic arsenic is a known human carcinogen and is routinely detected in US community water systems (CWSs). Inequalities in CWS arsenic exist across broad sociodemographic subgroups. Our objective was to evaluate the county-level association between socioeconomic vulnerability and CWS arsenic concentrations across the US. We evaluated previously developed, population-weighted CWS arsenic concentrations (2006-2011) and three socioeconomic domains (the proportion of adults with a high school diploma, median household income, and the Centers for Disease Control and Prevention's overall socioeconomic vulnerability score) for 2,604 conterminous US counties. We used spatial lag models and evaluated the adjusted geometric mean ratio (GMR) of CWS arsenic concentrations per higher socioeconomic domain score corresponding to the interquartile range, and also evaluated flexible quadratic spline models. We also stratified by region and by United States Department of Agriculture Rural-Urban Continuum Codes to assess potential effect measure modification by region and rurality. Associations between socioeconomic vulnerability and CWS arsenic were modified by region and rurality and specific to socioeconomic domain. The fully adjusted GMR (95% CIs) of CWS arsenic per interquartile range higher proportion of adults with a high school education was 0.83 (0.71, 0.98) in the Southwest (corresponding to 17% lower arsenic with higher education), 0.82 (0.71, 0.94) in the Eastern Midwest (18% lower), and 0.65 (0.31, 1.36) in New England (35% lower). Associations between median household income and CWS arsenic were largely null. Higher overall socioeconomic vulnerability was significantly associated with lower CWS arsenic, but only in counties in the Central Midwest and those with total populations less than 20,000. Findings may reflect regional/local differences in both socioeconomic/socio-cultural context and public drinking water regulatory efforts. Across the US, individual domains of socioeconomic vulnerability (especially educational attainment) are more strongly associated with inequalities in CWS arsenic than the complex overall socioeconomic vulnerability index.

Blood cadmium, lead, manganese, mercury, and selenium levels in American Indian populations: The Strong Heart Study.

BACKGROUND: Many American Indian (AI) communities are in areas affected by environmental contamination, such as toxic metals. However, studies assessing exposures in AI communities are limited. We measured blood metals in AI communities to assess historical exposure and identify participant characteristics associated with these levels in the Strong Heart Study (SHS) cohort. METHOD: Archived blood specimens collected from participants (n = 2014, all participants were 50 years of age and older) in Arizona, Oklahoma, and North and South Dakota during SHS Phase-III (1998-1999) were analyzed for cadmium, lead, manganese, mercury, and selenium using inductively coupled plasma triple quadrupole mass spectrometry. We conducted descriptive analyses for the entire cohort and stratified by selected subgroups, including selected demographics, health behaviors, income, waist circumference, and body mass index. Bivariate associations were conducted to examine associations between blood metal levels and selected socio-demographic and behavioral covariates. Finally, multivariate regression models were used to assess the best model fit that predicted blood metal levels. FINDINGS: All elements were detected in 100% of study participants, with the exception of mercury (detected in 73% of participants). The SHS population had higher levels of blood cadmium and manganese than the general U.S. population 50 years and older. The median blood mercury in the SHS cohort was at about 30% of the U.S. reference population, potentially due to low fish consumption. Participants in North Dakota and South Dakota had the highest blood cadmium, lead, manganese, and selenium, and the lowest total mercury levels, even after adjusting for covariates. In addition, each of the blood metals was associated with selected demographic, behavioral, income, and/or weight-related factors in multivariate models. These findings will help guide the tribes to develop education, outreach, and strategies to reduce harmful exposures and increase beneficial nutrient intake in these AI communities.

Association of blood manganese, selenium with steatosis, fibrosis in the National Health and Nutrition Examination Survey, 2017-18.

BACKGROUND & AIMS: Chronic liver disease is a growing health burden worldwide. Chronic metal exposures may be associated with non-alcoholic fatty liver disease (NAFLD). We aimed to evaluate the association of blood cadmium (Cd), mercury (Hg), lead (Pb), manganese (Mn), and selenium (Se) with two hallmark features of NAFLD: liver steatosis and fibrosis in the general U.S. METHODS: We analyzed transient liver elastography data from participants of the National Health and Nutrition Examination Survey (NHANES) 2017-18, using ordinal logistic regression analyses to evaluate the cross-sectional association between blood metal concentrations and clinical stages of steatosis and fibrosis. We applied survey weights, strata, and primary sampling units and analyses were conducted using the R survey package. RESULTS: 4,154 participants were included. Median (IQR) for blood Mn and blood Se were 9.28 (7.48-11.39) and 191.08 (176.55-207.16) µg/L, respectively. Per interquartile range increase of natural log transformed blood Mn, the adjusted odds ratio (OR) (95% CI) was 1.59 (1.13-2.23) for a higher grade of steatosis and 1.16 (0.67-2.00) for liver fibrosis. The corresponding OR for steatosis was 2.00 (1.24-3.24) and 2.14 (1.04-4.42) in Black and Mexican American participants, respectively. The corresponding OR for liver fibrosis was 2.96 (1.42-6.17) for females. Per interquartile range increase of natural log transformed blood Se, the adjusted OR was 2.25 (1.30-3.89) for steatosis but 0.31 (0.13-0.72) for liver fibrosis. The inverse association of blood Se with liver fibrosis was also observed in males and White participants. Blood Cd, Hg, and Pb were not associated with liver steatosis and fibrosis in fully-adjusted models overall. CONCLUSIONS: In NHANES 2017-18, higher blood Mn was positively associated with liver steatosis, and higher Se was positively associated with liver steatosis but negatively associated with liver fibrosis. Longitudinal studies are needed to examine the association of Mn and Se with fibrosis progression.

Sociodemographic inequalities in uranium and other metals in community water systems across the USA, 2006-11: a cross-sectional study.

BACKGROUND: The US Environmental Protection Agency (EPA) currently sets maximum contaminant levels (MCLs) for ten metals or metalloids in public drinking water systems. Our objective was to estimate metal concentrations in community water systems (CWSs) across the USA, to establish if sociodemographic or regional inequalities in the metal concentrations exist, and to identify patterns of concentrations for these metals as a mixture. METHODS: We evaluated routine compliance monitoring records for antimony, arsenic, barium, beryllium, cadmium, chromium, mercury, selenium, thallium, and uranium, collected from 2006-11 (2000-11 for uranium; timeframe based on compliance monitoring requirements) by the US EPA in support of their second and third Six-Year Reviews for CWSs. Arsenic, barium, chromium, selenium, and uranium (detectable in >10% records) were included in the main analyses (subgroup and metal mixture analyses; arsenic data reported previously). We compared the mean, 75th percentile, and 95th percentile contaminant concentrations and the percentage of CWSs with concentrations exceeding the MCL across subgroups (region, sociodemographic county-cluster, size of population served, source water type, and CWSs exclusively serving correctional facilities). We evaluated patterns in CWS metal concentration estimate profiles via hierarchical cluster analysis. We created an online interactive map and dashboard of estimated CWS metal concentrations for use in future analyses. FINDINGS: Average metal concentrations were available for a total of 37 915 CWSs across the USA. The total number of monitoring records available was approximately 297 000 for arsenic, 165 000 for barium, 167 000 for chromium, 165 000 for selenium, and 128 000 for uranium. The percentage of analysed CWSs with average concentrations exceeding the MCL was 2·6% for arsenic (MCL=10 µg/L; nationwide mean 1·77 µg/L; n=36 798 CWSs), 2·1% for uranium (MCL=30 µg/L; nationwide mean 4·37 µg/L; n=14 503 CWSs), and less than 0·1% for the other metals. The number of records with detections was highest for uranium (63·1%). 75th and 95th percentile concentrations for uranium, chromium, barium, and selenium were highest for CWSs serving Semi-Urban, Hispanic communities, CWSs reliant on groundwater, and CWSs in the Central Midwest. Hierarchical cluster analysis revealed two distinct clusters: an arsenic-uranium-selenium cluster and a barium-chromium cluster. INTERPRETATIONS: Uranium is an under-recognised contaminant in CWSs. Metal concentrations (including uranium) are elevated in CWSs serving Semi-Urban, Hispanic communities independent of location or region, highlighting environmental justice concerns. FUNDING: US National Institutes of Health Office of the Director, US National Institutes for Environmental Health Sciences, and US National Institute of Dental and Craniofacial Research.

High Level of Selenium Exposure in the Strong Heart Study: A Cause for Incident Cardiovascular Disease?

Increasing evidence suggests that high selenium (Se) exposure is associated with adverse health effects. However, limited evidence exists on the association of Se exposure with cardiovascular disease (CVD), especially in communities affected by high naturally occurring Se in environmental media. We evaluated the prospective association between urinary Se levels and CVD incidence and mortality for 2727 American Indian adults who participated in the Strong Heart Study, with urinary Se levels measured at baseline (1989-1991) and CVD outcomes ascertained through 2017. The median (interquartile range) of urinary Se was 49.0 (36.7-67.4) µg/g creatinine. The multivariable adjusted hazard ratios (95% confidence interval) of incident CVD, coronary heart disease, and stroke comparing the 75th versus 25th percentile of urinary Se distributions were 1.11 (1.01-1.22), 1.05 (0.94-1.17), and 1.08 (0.88-1.33), respectively. In flexible dose-response models, increased risk for CVD incidence was only observed when the urinary Se level exceeded 60 µg/g creatinine. For CVD mortality, a nonstatistically significant U-shaped relationship was found across urinary Se levels. There was no evidence of effect modification by other urinary metal/metalloid levels. Our observation leads to the hypothesis that elevated Se exposure is a risk factor for CVD, especially in Se-replete populations. Antioxid. Redox Signal. 37, 990-997.

Urinary arsenic and heart disease mortality in NHANES 2003-2014.

BACKGROUND: Evidence evaluating the prospective association between low-to moderate-inorganic arsenic (iAs) exposure and cardiovascular disease in the general US population is limited. We evaluated the association between urinary arsenic concentrations in National Health and Nutrition Examination Survey (NHANES) 2003-2014 and heart disease mortality linked from the National Death Index through 2015. METHODS: We modeled iAs exposure as urinary total arsenic and dimethylarsinate among participants with low seafood intake, based on low arsenobetaine levels (N = 4990). We estimated multivariable adjusted hazard ratios (HRs) for heart disease mortality per interquartile range (IQR) increase in urinary arsenic levels using survey-weighted, Cox proportional hazards models, and evaluated flexible dose-response analyses using restricted quadratic spline models. We updated a previously published relative risk of coronary heart disease mortality from a dose-response meta-analysis per a doubling of water iAs (e.g., from 10 to 20 µg/L) with our results from NHANES 2003-2014, assuming all iAs exposure came from drinking water. RESULTS: A total of 77 fatal heart disease events occurred (median follow-up time 75 months). The adjusted HRs (95% CI) of heart disease mortality for an increase in urinary total arsenic and DMA corresponding to the interquartile range were 1.20 (0.83, 1.74) and 1.18 (0.68, 2.05), respectively. Restricted quadratic splines indicate a significant association between increasing urinary total arsenic and the HR of fatal heart disease for all participants at the lowest exposure levels <4.5 µg/L. The updated pooled relative risk of coronary heart disease mortality per doubling of water iAs (µg/L) was 1.16 (95% CI 1.07, 1.25). CONCLUSIONS: Despite a small number of events, relatively short follow-up time, and high analytical limits of detection for urinary arsenic species, iAs exposure at low-to moderate-levels is consistent with increased heart disease mortality in NHANES 2003-2014 although the associations were only significant in flexible dose-response models.

Associations between private well water and community water supply arsenic concentrations in the conterminous United States.

Geogenic arsenic contamination typically occurs in groundwater as opposed to surface water supplies. Groundwater is a major source for many community water systems (CWSs) in the United States (US). Although the US Environmental Protection Agency sets the maximum contaminant level (MCL enforceable since 2006: 10 µg/L) for arsenic in CWSs, private wells are not federally regulated. We evaluated county-level associations between modeled values of the probability of private well arsenic exceeding 10 µg/L and CWS arsenic concentrations for 2231 counties in the conterminous US, using time invariant private well arsenic estimates and CWS arsenic estimates for two time periods. Nationwide, county-level CWS arsenic concentrations increased by 8.4 µg/L per 100% increase in the probability of private well arsenic exceeding 10 µg/L for 2006-2008 (the initial compliance monitoring period after MCL implementation), and by 7.3 µg/L for 2009-2011 (the second monitoring period following MCL implementation) (1.1 µg/L mean decline over time). Regional differences in this temporal decline suggest that interventions to implement the MCL were more pronounced in regions served primarily by groundwater. The strong association between private well and CWS arsenic in Rural, American Indian, and Semi Urban, Hispanic counties suggests that future research and regulatory support are needed to reduce water arsenic exposures in these vulnerable subpopulations. This comparison of arsenic exposure values from major private and public drinking water sources nationwide is critical to future assessments of drinking water arsenic exposure and health outcomes.