Association of Urinary Metals With Cardiovascular Disease Incidence and All-Cause Mortality in the Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND: Exposure to metals has been associated with cardiovascular disease (CVD) end points and mortality, yet prospective evidence is limited beyond arsenic, cadmium, and lead. In this study, we assessed the prospective association of urinary metals with incident CVD and all-cause mortality in a racially diverse population of US adults from MESA (Multi-Ethnic Study of Atherosclerosis). METHODS: We included 6599 participants (mean [SD] age, 62.1 [10.2] years; 53% female) with urinary metals available at baseline (2000 to 2001) and followed through December 2019. We used Cox proportional hazards models to estimate the adjusted hazard ratio and 95% CI of CVD and all-cause mortality by baseline urinary levels of cadmium, tungsten, and uranium (nonessential metals), and cobalt, copper, and zinc (essential metals). The joint association of the 6 metals as mixture and the corresponding 10-year survival probability was calculated using Cox Elastic-Net. RESULTS: During follow-up, 1162 participants developed CVD, and 1844 participants died. In models adjusted by behavioral and clinical indicators, the HR (95% CI) for incident CVD and all-cause mortality comparing the highest with the lowest quartile were, respectively: 1.25 (1.03, 1.53) and 1.68 (1.43, 1.96) for cadmium; 1.20 (1.01, 1.42) and 1.16 (1.01, 1.33) for tungsten; 1.32 (1.08, 1.62) and 1.32 (1.12, 1.56) for uranium; 1.24 (1.03, 1.48) and 1.37 (1.19, 1.58) for cobalt; 1.42 (1.18, 1.70) and 1.50 (1.29, 1.74) for copper; and 1.21 (1.01, 1.45) and 1.38 (1.20, 1.59) for zinc. A positive linear dose-response was identified for cadmium and copper with both end points. The adjusted HRs (95% CI) for an interquartile range (IQR) increase in the mixture of these 6 urinary metals and the corresponding 10-year survival probability difference (95% CI) were 1.29 (1.11, 1.56) and -1.1% (-2.0, -0.05) for incident CVD and 1.66 (1.47, 1.91) and -2.0% (-2.6, -1.5) for all-cause mortality. CONCLUSIONS: This epidemiological study in US adults indicates that urinary metal levels are associated with increased CVD risk and mortality. These findings can inform the development of novel preventive strategies to improve cardiovascular health.

High prevalence of hepatitis C virus infection among incarcerated persons: Results from the Louisiana Hepatitis C Elimination Plan's opt-out testing program in prisons.

In the United States, modelling studies suggest a high prevalence of hepatitis C virus (HCV) infection in incarcerated populations. However, limited HCV testing has been conducted in prisons. Through the Louisiana Hepatitis C Elimination Plan, persons incarcerated in the eight state prisons were offered HCV testing from 20 September 2019 to 14 July 2022, and facility entry/exit HCV testing was introduced. Multivariable logistic regression was used to evaluate associations with HCV antibody (anti-HCV) positivity and viremia. Of 17,231 persons in the eight state prisons screened for anti-HCV, 95.1% were male, 66.7% were 30-57 years old, 3% were living with HIV, 68.2% were Black and 2904 (16.9%) were anti-HCV positive. HCV RNA was detected in 69.3% of anti-HCV positive individuals tested. In the multivariable model, anti-HCV positivity was associated with older age including those 30-57 (odds ratio [OR] 3.53, 95% confidence interval [CI] 2.96-4.20) and those ≥58 (OR 10.43, 95% CI 8.66-12.55) as compared to those ≤29 years of age, living with HIV (OR 1.68, 95% CI 1.36-2.07), hepatitis B (OR 1.83, 95% CI 1.25-2.69) and syphilis (OR 1.51, 95% CI 1.23-1.86). HCV viremia was associated with male sex (OR 1.89, 95% CI 1.36-2.63) and Black race (OR 1.42, 95% CI 1.20-1.68). HCV prevalence was high in the state prisons in Louisiana compared to community estimates. To the extent that Louisiana is representative, to eliminate HCV in the United States, it will be important for incarcerated persons to have access to HCV testing and treatment.

Method validation for (ultra)-trace element concentrations in urine for small sample volumes in large epidemiological studies: application to the population-based epidemiological multi-ethnic study of atherosclerosis (MESA).

Analysis of essential and non-essential trace elements in urine has emerged as a valuable tool for assessing occupational and environmental exposures, diagnosing nutritional status and guiding public health and health care intervention. Our study focused on the analysis of trace elements in urine samples from the Multi-Ethnic Study of Atherosclerosis (MESA), a precious resource for health research with limited sample volumes. Here we provide a comprehensive and sensitive method for the analysis of 18 elements using only 100 µL of urine. Method sensitivity, accuracy, and precision were assessed. The analysis by inductively coupled plasma mass spectrometry (ICP-MS) included the measurement of antimony (Sb), arsenic (As), barium (Ba), cadmium (Cd), cesium (Cs), cobalt (Co), copper (Cu), gadolinium (Gd), lead (Pb), manganese (Mn), molybdenum (Mo), nickel (Ni), selenium (Se), strontium (Sr), thallium (Tl), tungsten (W), uranium (U), and zinc (Zn). Further, we reported urinary trace element concentrations by covariates including gender, ethnicity/race, smoking and location. The results showed good accuracy and sensitivity of the ICP-MS method with the limit of detections rangings between 0.001 µg L-1 for U to 6.2 µg L-1 for Zn. Intra-day precision for MESA urine analysis varied between 1.4% for Mo and 26% for Mn (average 6.4% for all elements). The average inter-day precision for most elements was <8.5% except for Gd (20%), U (16%) and Mn (19%) due to very low urinary concentrations. Urinary mean concentrations of non-essential elements followed the order of Sr > As > Cs > Ni > Ba > Pb > Cd > Gd > Tl > W > U. The order of urinary mean concentrations for essential trace elements was Zn > Se > Mo > Cu > Co > Mn. Non-adjusted mean concentration of non-essential trace elements in urine from MESA participants follow the order Sr > As > Cs > Ni > Ba > Pb > Cd > Gd > Tl > W > U. The unadjusted urinary mean concentrations of essential trace elements decrease from Zn > Se > Mo > Cu > Co > Mn.

Urinary Metal Levels and Coronary Artery Calcification: Longitudinal Evidence in the Multi-Ethnic Study of Atherosclerosis (MESA).

Objective: Growing evidence indicates that exposure to metals are risk factors for cardiovascular disease (CVD). We hypothesized that higher urinary levels of metals with prior evidence of an association with CVD, including non-essential (cadmium , tungsten, and uranium) and essential (cobalt, copper, and zinc) metals are associated with baseline and rate of change of coronary artery calcium (CAC) progression, a subclinical marker of atherosclerotic CVD. Methods: We analyzed data from 6,418 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) with spot urinary metal levels at baseline (2000-2002) and 1-4 repeated measures of spatially weighted coronary calcium score (SWCS) over a ten-year period. SWCS is a unitless measure of CAC highly correlated to the Agatston score but with numerical values assigned to individuals with Agatston score=0. We used linear mixed effect models to assess the association of baseline urinary metal levels with baseline SWCS, annual change in SWCS, and SWCS over ten years of follow-up. Urinary metals (adjusted to µg/g creatinine) and SWCS were log transformed. Models were progressively adjusted for baseline sociodemographic factors, estimated glomerular filtration rate, lifestyle factors, and clinical factors. Results: At baseline, the median and interquartile range (25th, 75th) of SWCS was 6.3 (0.7, 58.2). For urinary cadmium, the fully adjusted geometric mean ratio (GMR) (95%Cl) of SWCS comparing the highest to the lowest quartile was 1.51 (1.32, 1.74) at baseline and 1.75 (1.47, 2.07) at ten years of follow-up. For urinary tungsten, uranium, and cobalt the corresponding GMRs at ten years of follow-up were 1.45 (1.23, 1.71), 1.39 (1.17, 1.64), and 1.47 (1.25, 1.74), respectively. For copper and zinc, the association was attenuated with adjustment for clinical risk factors; GMRs at ten years of follow-up before and after adjustment for clinical risk factors were 1.55 (1.30, 1.84) and 1.33 (1.12, 1.58), respectively, for copper and 1.85 (1.56, 2.19) and 1.57 (1.33, 1.85) for zinc. Conclusion: Higher levels of cadmium, tungsten, uranium, cobalt, copper, and zinc, as measured in urine, were associated with subclinical CVD at baseline and at follow-up. These findings support the hypothesis that metals are pro-atherogenic factors.

Evaluation of Predict, a prognostic risk tool, after diagnosis of a second breast cancer.

BACKGROUND: The UK National Health Service's Predict is a clinical tool widely used to estimate the prognosis of early-stage breast cancer. The performance of Predict for a second primary breast cancer is unknown. METHODS: Women 18 years of age or older diagnosed with a first or second invasive breast cancer between 2000 and 2013 and followed for at least 5 years were identified from the US Surveillance, Epidemiology, and End Results (SEER) database. Model calibration of Predict was evaluated by comparing predicted and observed 5-year breast cancer-specific mortality separately by estrogen receptor status for first vs second breast cancer. Receiver operating characteristic curves and areas under the curve were used to assess model discrimination. Model performance was also evaluated for various races and ethnicities. RESULTS: The study population included 6729 women diagnosed with a second breast cancer and 357 204 women with a first breast cancer. Overall, Predict demonstrated good discrimination for first and second breast cancers (areas under the curve ranging from 0.73 to 0.82). Predict statistically significantly underestimated 5-year breast cancer mortality for second estrogen receptor-positive breast cancers (predicted-observed = ‒6.24%, 95% CI = ‒6.96% to ‒5.49%). Among women with a first estrogen receptor-positive cancer, model calibration was good (predicted-observed = ‒0.22%, 95% CI = ‒0.29% to ‒0.15%), except in non-Hispanic Black women (predicted-observed = ‒2.33%, 95% CI = ‒2.65% to ‒2.01%) and women 80 years of age or older (predicted-observed = ‒3.75%, 95% CI = ‒4.12% to ‒3.41%). Predict performed well for second estrogen receptor-negative cancers overall (predicted-observed = ‒1.69%, 95% CI = ‒3.99% to 0.16%) but underestimated mortality among those who had previously received chemotherapy or had a first cancer with more aggressive tumor characteristics. In contrast, Predict overestimated mortality for first estrogen receptor-negative cancers (predicted-observed = 4.54%, 95% CI = 4.27% to 4.86%). CONCLUSION: The Predict tool underestimated 5-year mortality after a second estrogen receptor-positive breast cancer and in certain subgroups of women with a second estrogen receptor-negative breast cancer.

Contaminant Metals as Cardiovascular Risk Factors: A Scientific Statement From the American Heart Association.

Exposure to environmental pollutants is linked to increased risk of cardiovascular disease. Beyond the extensive evidence for particulate air pollution, accumulating evidence supports that exposure to nonessential metals such as lead, cadmium, and arsenic is a significant contributor to cardiovascular disease worldwide. Humans are exposed to metals through air, water, soil, and food and extensive industrial and public use. Contaminant metals interfere with critical intracellular reactions and functions leading to oxidative stress and chronic inflammation that result in endothelial dysfunction, hypertension, epigenetic dysregulation, dyslipidemia, and changes in myocardial excitation and contractile function. Lead, cadmium, and arsenic have been linked to subclinical atherosclerosis, coronary artery stenosis, and calcification as well as to increased risk of ischemic heart disease and stroke, left ventricular hypertrophy and heart failure, and peripheral artery disease. Epidemiological studies show that exposure to lead, cadmium, or arsenic is associated with cardiovascular death mostly attributable to ischemic heart disease. Public health measures reducing metal exposure are associated with reductions in cardiovascular disease death. Populations of color and low socioeconomic means are more commonly exposed to metals and therefore at greater risk of metal-induced cardiovascular disease. Together with strengthening public health measures to prevent metal exposures, development of more sensitive and selective measurement modalities, clinical monitoring of metal exposures, and the development of metal chelation therapies could further diminish the burden of cardiovascular disease attributable to metal exposure.

Racial and ethnic disparities in mortality among breast cancer survivors after a second malignancy.

BACKGROUND: Racial and ethnic differences in survival after a first cancer are well established but have not been examined after a second primary cancer (SPC) despite the increasing incidence among survivors. METHODS: We examined 39 029 female breast cancer survivors who developed an SPC between 2000 and 2014 in the Surveillance, Epidemiology, and End Results 18 database. Multivariable Cox proportional hazards regression for competing risks data was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for cancer and cardiovascular disease mortality after SPCs comparing Hispanic, Non-Hispanic Asian, and Non-Hispanic Black survivors with Non-Hispanic White survivors. Models were adjusted for sociodemographics, tumor characteristics, and treatments of the first and second cancer. Analyses were stratified by SPC type. RESULTS: During 17 years of follow-up, there were 15 117 deaths after SPCs. The risk of cancer death was 12% higher among Non-Hispanic Black survivors (HR = 1.12, 95% CI = 1.05 to 1.19) and 8% higher among Hispanic survivors (HR = 1.08, 95% CI = 1.00 to 1.16) compared with Non-Hispanic White survivors. In subgroup analyses, the strongest associations were observed among Non-Hispanic Black survivors with a second breast or uterine cancer and among Hispanic survivors with a second breast cancer. Non-Hispanic Black survivors also experienced a 44% higher risk of cardiovascular disease death after SPC diagnosis than Non-Hispanic White survivors (HR = 1.44, 95% CI = 1.20 to 1.74). CONCLUSIONS: Higher cancer mortality among Non-Hispanic Black and Hispanic survivors and higher cardiovascular mortality among Non-Hispanic Black survivors exist among women who survive a first breast cancer to develop an SPC. Studies focused on identifying the contributors to these disparities are needed to enable implementation of effective mitigation strategies.

Neighborhood segregation and cognitive change: Multi-Ethnic Study of Atherosclerosis.

INTRODUCTION: We investigated associations between neighborhood racial/ethnic segregation and cognitive change. METHODS: We used data (n = 1712) from the Multi-Ethnic Study of Atherosclerosis. Racial/ethnic segregation was assessed using Getis-Ord (Gi*) z-scores based on American Community Survey Census tract data (higher Gi* = greater spatial clustering of participant's race/ethnicity). Global cognition and processing speed were assessed twice, 6 years apart. Adjusted multilevel linear regression tested associations between Gi* z-scores and cognition. Effect modification by race/ethnicity, income, education, neighborhood socioeconomic status, and neighborhood social support was tested. RESULTS: Participants were on average 67 years old; 43% were White, 11% Chinese, 29% African American/Black, 17% Hispanic; 40% had high neighborhood segregation (Gi* > 1.96). African American/Black participants with greater neighborhood segregation had greater processing speed decline in stratified analyses, but no interactions were significant. DISCUSSION: Segregation was associated with greater processing speed declines among African American/Black participants. Additional follow-ups and comprehensive cognitive batteries may further elucidate these findings. HIGHLIGHTS: A study of neighborhood racial/ethnic segregation and change in cognition. Study was based on a racially and geographically diverse, population-based cohort of older adults. Racial/ethnic segregation (clustering) was measured by the Getis-ord (Gi*) statistic. We saw faster processing speed decline among Black individuals in segregated neighborhoods.

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.

Mortality after second malignancy in breast cancer survivors compared to a first primary cancer: a nationwide longitudinal cohort study.

Limited information exists about survival outcomes after second primary cancers (SPCs) among breast cancer survivors. Studies suggest that mortality after certain SPCs may be higher than mortality after first primary cancers (FPCs) of the same type. A cohort study was conducted among 63,424 US women using the Surveillance, Epidemiology, and End Results 18 database (2000-2016) to compare mortality after a SPC among breast cancer survivors to mortality among women after a FPC using Cox proportional hazard regression. Propensity scores were used to match survivors with SPCs to women with FPCs 1:1 based on cancer type and prognostic factors. During a median follow-up of 42 months, 11,532 cancer deaths occurred after SPCs among survivors compared to 9305 deaths after FPCs. Cumulative cancer mortality was 44.7% for survivors with SPCs and 35.2% for women with FPCs. Survivors with SPCs had higher risk of cancer death (hazard ratio (HR): 1.27, 95% CI: 1.23-1.30) and death overall (HR: 1.18, 95% CI: 1.15-1.21) than women with FPCs. Increased risk of cancer death after SPCs compared to FPCs was observed for cancer in breast, lung, colon and/or rectum, uterus, lymphoma, melanoma, thyroid, and leukemia. Estrogen receptor status and treatment of the prior breast cancer as well as time between prior breast cancer and SPC significantly modified the mortality difference between women with SPC and FPC. A more tailored approach to early detection and treatment could improve outcomes from second cancer in breast cancer survivors.

Ambient Air Pollution and Adverse Waitlist Events Among Lung Transplant Candidates.

BACKGROUND: Air pollution is associated with cardiopulmonary disease and death in the general population. Fine particulate matter (PM2.5) is particularly harmful due to its ability to penetrate into areas of gas exchange within the lungs. Persons with advanced lung disease are believed to be particularly susceptible to PM2.5 exposure, but only a few studies have examined the effect of exposure on this population. Here we investigate the association between PM2.5 exposure and adverse waitlist events among lung transplant (LT) candidates. METHODS: US registry data were used to identify LT candidates listed between January 1, 2010 and December 31, 2016. Annual PM2.5 concentration at year of listing was estimated for each candidate's ZIP Code using National Aeronautics and Space Administration's (NASA) Socioeconomic Data and Applications Center Global Annual PM2.5 Grids. We estimated crude and adjusted hazard ratios for adverse waitlist events, defined as death or removal, using Cox proportional hazards regression. RESULTS: Of the 15 075 included candidates, median age at listing was 60, 43.8% were female individuals, and 81.7% were non-Hispanic White. Median ZIP Code PM2.5 concentration was 9.06 µg/m3. When compared with those living in ZIP Codes with lower PM2.5 exposure (PM2.5 <10.53 µg/m3), candidates in ZIP Codes in the highest quartile of PM2.5 exposure (≥10.53 µg/m3) had 1.14-fold (95% confidence interval, 1.04-1.25) risk of adverse waitlist events. The result remained significant after adjusting for demographics, education, insurance, smoking, lung allocation score, body mass index, and blood type (hazard ratio, 1.17; 95% confidence interval, 1.07-1.29). CONCLUSIONS: Elevated ambient PM2.5 concentration was associated with adverse waitlist events among LT candidates. These findings highlight the impact of air pollution on clinical outcomes in this critically ill population.

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.

Racial Segregation and Respiratory Outcomes among Urban Black Residents with and at Risk of Chronic Obstructive Pulmonary Disease.

Rationale: Racial residential segregation has been associated with worse health outcomes, but the link with chronic obstructive pulmonary disease (COPD) morbidity has not been established.Objectives: To investigate whether racial residential segregation is associated with COPD morbidity among urban Black adults with or at risk of COPD.Methods: Racial residential segregation was assessed using isolation index, based on 2010 decennial census and baseline address, for Black former and current smokers in the multicenter SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study), a study of adults with or at risk for COPD. We tested the association between isolation index and respiratory symptoms, physiologic outcomes, imaging parameters, and exacerbation risk among urban Black residents, adjusting for established COPD risk factors, including smoking. Additional mediation analyses were conducted for factors that could lie on the pathway between segregation and COPD outcomes, including individual and neighborhood socioeconomic status, comorbidity burden, depression/anxiety, and ambient pollution.Measurements and Main Results: Among 515 Black participants, those residing in segregated neighborhoods (i.e., isolation index ⩾0.6) had worse COPD Assessment Test score (ß = 2.4; 95% confidence interval [CI], 0.7 to 4.0), dyspnea (modified Medical Research Council scale; ß = 0.29; 95% CI, 0.10 to 0.47), quality of life (St. George's Respiratory Questionnaire; ß = 6.1; 95% CI, 2.3 to 9.9), and cough and sputum (ß = 0.8; 95% CI, 0.1 to 1.5); lower FEV1% predicted (ß = -7.3; 95% CI, -10.9 to -3.6); higher rate of any and severe exacerbations; and higher percentage emphysema (ß = 2.3; 95% CI, 0.7 to 3.9) and air trapping (ß = 3.8; 95% CI, 0.6 to 7.1). Adverse associations attenuated with adjustment for potential mediators but remained robust for several outcomes, including dyspnea, FEV1% predicted, percentage emphysema, and air trapping.Conclusions: Racial residential segregation was adversely associated with COPD morbidity among urban Black participants and supports the hypothesis that racial segregation plays a role in explaining health inequities affecting Black communities.

Ambient air pollution and posttransplant outcomes among kidney transplant recipients.

Fine particulate matter (PM2.5 ), a common form of air pollution which can induce systemic inflammatory response, is a risk factor for adverse health outcomes. Kidney transplant (KT) recipients are likely vulnerable to PM2.5 due to comorbidity and chronic immunosuppression. We sought to quantify the association between PM2.5 and post-KT outcomes. For adult KT recipients (1/1/2010-12/31/2016) in the Scientific Registry of Transplant Recipients, we estimated annual zip-code level PM2.5 concentrations at the time of KT using NASA's SEDAC Global PM2.5 Grids. We determined the associations between PM2.5 and delayed graft function (DGF) and 1-year acute rejection using logistic regression and death-censored graft failure (DCGF) and mortality using Cox proportional hazard models. All models were adjusted for sociodemographics, recipient, transplant, and ZIP code level confounders. Among 87 233 KT recipients, PM2.5 was associated with increased odds of DGF (OR = 1.59; 95% CI: 1.48-1.71) and 1-year acute rejection (OR = 1.31; 95% CI: 1.17-1.46) and increased risk of all-cause mortality (HR = 1.15; 95% CI: 1.07-1.23) but not DCGF (HR = 1.05; 95% CI: 0.97-1.51). In conclusion, PM2.5 was associated with higher odds of DGF and 1-year acute rejection and elevated risk of mortality among KT recipients. Our study highlights the importance of considering environmental exposure as risk factors for post-KT outcomes.

Ambient Air Pollution and Mortality among Older Patients Initiating Maintenance Dialysis.

BACKGROUND: Fine particulate matter (particulate matter with diameter <2.5 µm [PM2.5]) is associated with CKD progression and may impact the health of patients living with kidney failure. While older (aged ≥65 years) adults are most vulnerable to the impact of PM2.5, it is unclear whether older patients on dialysis are at elevated risk of mortality when exposed to fine particulate matter. METHODS: Older adults initiating dialysis (2010-2016) were identified from US Renal Data System (USRDS). PM2.5 concentrations were obtained from NASA's Socioeconomic Data and Application Center (SEDAC) Global Annual PM2.5 Grids. We investigated the association between PM2.5 and all-cause mortality using Cox proportional hazard models with linear splines [knot at the current Environmental Protection Agency (EPA) National Ambient Air Quality Standard for PM2.5 of 12 µg/m3] and robust variance. RESULTS: For older dialysis patients who resided in areas with high PM2.5, a 10 µg/m3 increase in PM2.5 was associated with 1.16-fold (95% CI: 1.08-1.25) increased risk of mortality; furthermore, those who were female (aHR = 1.26, 95% CI: 1.13-1.42), Black (aHR = 1.31, 95% CI: 1.09-1.59), or had diabetes as a primary cause of kidney failure (aHR = 1.25, 95% CI: 1.13-1.38) were most vulnerable to high PM2.5. While the mortality risk associated with PM2.5 was stronger at higher levels (aHR = 1.19, 95% CI: 1.08-1.32), at lower levels (≤12 µg/m3), PM2.5 was significantly associated with mortality risk (aHR = 1.04, 95% CI: 1.00-1.07) among patients aged ≥75 years (Pslope difference = 0.006). CONCLUSIONS: Older adults initiating dialysis who resided in ZIP codes with PM2.5 levels >12 µg/m3 are at increased risk of mortality. Those aged >75 were at elevated risk even at levels below the EPA Standard for PM2.5.

Assessing the spatial heterogeneity in black-white differences in optimal cardiovascular health and the impact of individual- and neighborhood-level risk factors: The Multi-Ethnic Study of Atherosclerosis (MESA).

Racial disparities in cardiovascular health (CVH) continue to remain a public health concern in the United States. We use unique population-based data from the Multi-Ethnic Study of Atherosclerosis cohort to explore the black-white differences in optimal CVH. Utilizing geographically weighted regression methods, we assess the spatial heterogeneity in black-white differences in optimal CVH and the impact of both individual- and neighborhood-level risk factors. We found evidence of significant spatial heterogeneity in black-white differences that varied within and between the five sites. Initial models showed decreased odds of optimal CVH for blacks that ranged from 60% to 70% reduced odds - with noticeable variation of these decreased odds within each site. Adjusting for risk factors resulted in reductions in the black-white differences in optimal CVH. Further understanding of the reasons for spatial heterogeneities in black-white differences in nationally representative cohorts may provide important clues regarding the drivers of these differences.

Rice Intake, Arsenic Exposure, and Subclinical Cardiovascular Disease Among US Adults in MESA.

Background Arsenic-related cardiovascular effects at exposure levels below the US Environmental Protection Agency's standard of 10 µg/L are unclear. For these populations, food, especially rice, is a major source of exposure. We investigated associations of rice intake, a marker of arsenic exposure, with subclinical cardiovascular disease (CVD) markers in a multiethnic population. Methods and Results Between 2000 and 2002, MESA (Multi-Ethnic Study of Atherosclerosis) enrolled 6814 adults without clinical CVD. We included 5050 participants with baseline data on rice intake and markers of 3 CVD domains: inflammation (hsCRP [high-sensitivity C-reactive protein], interleukin-6, and fibrinogen), vascular function (aortic distensibility, carotid distensibility, and brachial flow-mediated dilation), and subclinical atherosclerosis at 3 vascular sites (carotid intima-media thickness, coronary artery calcification, and ankle-brachial index). We also evaluated endothelial-related biomarkers previously associated with arsenic. Rice intake was assessed by food frequency questionnaire. Urinary arsenic was measured in 310 participants. A total of 13% of participants consumed ≥1 serving of rice/day. Compared with individuals consuming <1 serving of rice/week, ≥1 serving of rice/day was not associated with subclinical markers after demographic, lifestyle, and CVD risk factor adjustment (eg, geometric mean ratio [95% CI] for hsCRP, 0.98 [0.86-1.11]; aortic distensibility, 0.99 [0.91-1.07]; and carotid intima-media thickness, 0.98 [0.91-1.06]). Associations with urinary arsenic were similar to those for rice intake. Conclusions Rice intake was not associated with subclinical CVD markers in a multiethnic US population. Research using urinary arsenic is needed to assess potential CVD effects of low-level arsenic exposure. Understanding the role of low-level arsenic as it relates to subclinical CVD may contribute to CVD prevention and control.

Ambient air pollution as a mediator in the pathway linking race/ethnicity to blood pressure elevation: The multi-ethnic study of atherosclerosis (MESA).

BACKGROUND: Racial/ethnic disparities in blood pressure and hypertension have been evident in previous studies, as were associations between race/ethnicity with ambient air pollution and those between air pollution with hypertension. The role of air pollution exposure to racial/ethnic differences in hypertension has not been explored. OBJECTIVE: To assess the potential mediating effects of ambient air pollution on the association between race/ethnicity and blood pressure levels. METHODS: We studied 6,463 White, Black, Hispanic and Chinese adults enrolled across 6 US cities. Systolic (SBP) and diastolic blood pressure (DBP) were measured at Exam 1 (2000-2002) and Exam 2 (2002-2004). Household-level annual average concentrations of fine particulate matter (PM2.5), oxides of nitrogen (NOX), and ozone (O3) for the year 2000 were estimated for participants. RESULTS: The difference in SBP levels by race/ethnicity that was related to higher PM2.5 concentrations compared with White men ("indirect associations") was 0.3 (95% CI: 0.1, 0.6) mmHg for Black men, 0.3 (95% CI: 0.1, 0.6) mmHg for Hispanic men and 1.0 (95% CI: 0.2, 1.8) mmHg for Chinese men. Findings were similar although not statistically significant for women. PM2.5 did not mediate racial/ethnic differences in DBP. Indirect associations were significant for O3 for SBP among women and men and for DBP among men. In contrast, racial/ethnic disparities were attenuated due to exposure to NOX. CONCLUSION: Racial disparities in blood pressure were reduced after accounting for PM2.5 and ozone while increased after accounting for NOX.

Prenatal Opioid Exposure: Neurodevelopmental Consequences and Future Research Priorities.

Neonatal opioid withdrawal syndrome (NOWS) has risen in prevalence from 1.2 per 1000 births in 2000 to 5.8 per 1000 births in 2012. Symptoms in neonates may include high-pitched cry, tremors, feeding difficulty, hypertonia, watery stools, and breathing problems. However, little is known about the neurodevelopmental consequences of prenatal opioid exposure in infancy, early childhood, and middle childhood. Even less is known about the cognitive, behavioral, and academic outcomes of children who develop NOWS. We review the state of the literature on the neurodevelopmental consequences of prenatal opioid exposure with a particular focus on studies in which NOWS outcomes were examined. Aiming to reduce the incidence of prenatal opioid exposure in the near future, we highlight the need for large studies with prospectively recruited participants and longitudinal designs, taking into account confounding factors such as socioeconomic status, institutional variations in care, and maternal use of other substances, to independently assess the full impact of NOWS. As a more immediate solution, we provide an agenda for future research that leverages the National Institutes of Health Environmental Influences on Child Health Outcomes program to address many of the serious methodologic gaps in the literature, and we answer key questions regarding the short- and long-term neurodevelopmental health of children with prenatal opioid exposure.

Rice Consumption and Subclinical Lung Disease in US Adults: Observational Evidence From the Multi-Ethnic Study of Atherosclerosis.

Rice accumulates arsenic, an established lung toxicant. Little is known about the association of rice consumption with arsenic-related health effects, particularly interstitial lung disease. Between 2000 and 2002, 6,814 white, black, Hispanic, and Chinese adults from 6 US cities were enrolled in the Multi-Ethnic Study of Atherosclerosis. We included 2,250 participants who had spirometry data, 2,557 with full-lung computed tomography (CT) scans, and 5,710 with cardiac CT scans. Rice consumption and 310 participants with urinary arsenic were assessed at baseline. Spirometry and full-lung CT-derived measures of total lung capacity and high attenuation area (HAA), and interstitial lung abnormalities were measured at examination 5. Cardiac CT-derived HAA was measured at 1-3 visits. Twelve percent of participants reported eating at least 1 serving of rice daily. Comparing data between that group with those who ate less than 1 serving weekly, the mean difference for forced vital capacity was -102 (95% confidence interval (CI): -198, -7) mL, and for forced expiratory volume in 1 second was -90 (95% CI: -170, -11) mL after adjustment for demographics, anthropometrics, dietary factors, and smoking. The cross-sectional adjusted percent difference for total lung capacity was -1.33% (95% CI: -4.29, 1.72) and for cardiac-based HAA was 3.66% (95% CI: 1.22, 6.15). Sensitivity analyses for urinary arsenic were consistent with rice findings. Daily rice consumption was associated with reduced lung function and greater cardiac-based HAA.