Identifying the cardiovascular effects of multiple pollutants.

Cardiovascular disease (CVD) is the leading cause of death from environmental exposures. Although exposure to PM2.5 is an established risk factor for CVD, the contribution of other hazardous pollutant exposure to CVD is less clear. Overall, this work aimed to examine the effect of pollutants with lesser documented effects on cardiovascular disease using a multi-pronged approach to exposure assessment. The three aims were to examine the relationship between county-level toxic chemical releases and CVD mortality in the contiguous United States between 2002 and 2012, to assess the relationship between individual-level VOC metabolites and vascular function, and to build multipollutant models from the previous two aims to assess the role of mixtures and mixture components in CVD mortality and vascular function. In our national, county-level study, we found that for every 25% increase in annual county-level toxic release, we found a 2.8% (1.2, 4.4; p-value=0.0006) increase in CVD mortality rate. We also found that for every 25% increase in annual county-level risk score, there was a 3.0% (95%CI 1.3, 4.6; p-value=0.0003) increase in CVD mortality. Using the multipollutant method, elastic net, we identified five out of 467 potentially toxic chemicals at the county-level: bromoform, dichlorobromomethane, dichlorotrifluoroethane, nitrophenol, and thallium. In our study of individual-level VOC metabolites, we found that the acrolein metabolite, 3HPMA, was positively associated with systolic BP (+0.98 per SD of 3HPMA; CI: 0.04, 1.91; P=0.04). For each IQR of 3HPMA or DHBMA (a 1,3-butadiene metabolite), there was a 3.3% (CI: -6.18, -0.37; p-value: 0.03) or a 4.0% (CI: -7.72, -0.12; P=0.04) decrease in endothelial function. Urinary levels of the 1,3-butadiene metabolite, MHBMA3, were positively associated with a 2.9% increase in urinary epinephrine (CI: 0.48, 5.37; P=0.02). Using the multipollutant method, Bayesian Kernel Machine Regression, we found that the whole mixture of VOC metabolites (CEMA, 3HPMA, DHBMA, MHBMA3, and HPMMA) was significantly associated with blood pressure, which was primarily driven by 3HPMA. Taken together, these findings suggest that exposure to under regulated pollutants like TRI chemicals and VOCs contribute to CVD mortality and vascular dysfunction. Further research is required to corroborate these findings

What is the status of the Lee’s Lane Landfill Superfund Site?

The Lee’s Lane Landfill is located in western Louisville, KY along the Ohio River (Fig. 1) [1]. The site was used as a quarry in the 1940s before being repurposed as a landfill from 1948 to 1975 (Fig. 2). At least 212,400 tons of municipal and industrial waste were disposed of in the landfill during this period. In 1980, the Kentucky Department of Hazardous Materials and Waste Management discovered approximately 400 drums of hazardous waste within the landfill; these drums were removed by the landfill owners in the fall of 1981, but the remaining drums of non-hazardous material, as well as any empty drums, were buried in place on the landfill. The buried and capped landfill waste covers an area of 112 acres. The United States Environmental Protection Agency (EPA) placed the Lee’s Lane Landfill site on the National Priorities List (NPL) in 1983. Cleanup efforts concluded in 1988 and monitoring of the site has continued since. This white paper summarizes reports published from 2013 through 2018 documenting Lee’s Lane Landfill site conditions and the effectiveness of the cap and other remedies put in place to protect human health. The condition of the site must be reviewed every five years by the EPA, and those results are made available to the public in what is referred to as a Five-Year Review (FYR). The Lee’s Lane Landfill FYR relies on information provided to the EPA by the Kentucky State Department of Environmental Protection (KDEP), information collected by the Lee’s Lane Landfill Group, monitoring data and conclusions from the Louisville and Jefferson County Metropolitan Sewer District’s (MSD) Conceptual Site Model (CSM) report, [2] and other interim communications. Using the information in these reports as well as relevant current and historical research documents, we identify questions that remain unanswered and need to be addressed in order to confirm that the contaminants present on the site do not pose a risk to public health and to determine whether the site is ready for re-use. We conclude by proposing several next steps to fill the identified gaps in information and confirm the conclusions in the reports

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.The Multi-Ethnic Study of Atherosclerosis (MESA) is supported by contracts 75N92020D00001, HHSN268201500003I, N01-HC-95159, 75N92020D00005, N01-HC-95160, 75N92020D00002, N01-HC-95161, 75N92020D00003, N01-HC-95162, 75N92020D00006, N01-HC-95163, 75N92020D00004, N01-HC-95164, 75N92020D00007, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168 and N01-HC-95169 from the National Heart, Lung, and Blood Institute, and by grants UL1-TR-000040, UL1-TR-001079, and UL1-TR-001420 from the National Center for Advancing Translational Sciences (NCATS). This publication was developed under the Science to Achieve Results (STAR) research assistance agreements, No. RD831697 (MESA Air) and RD-83830001 (MESA Air Next Stage), awarded by the U.S Environmental Protection Agency (EPA). It has not been formally reviewed by the EPA. The views expressed in this document are solely those of the authors and the EPA does not endorse any products or commercial services mentioned in this publication. Dr. Maria Tellez-Plaza was supported by grants PI15/00071 and PI22/00029 from the Strategic Action for Health Research, Instituto de Salud Carlos III and the Spanish Ministry of Science and Innovation, and co-funded with European Funds for Regional Development (FEDER). The opinions and views expressed in this article are those of the authors and do not necessarily represent the official position of the Instituto de Salud Carlos III (Spain). Work in the authors? laboratories is also supported in part by NIH grants P42ES023716, P42ES010349, P42ES033719, P30ES009089, T32ES007322, R01ES029967, R01HL155576. The authors thank the other investigators, the staff, and the participants of the MESA study for their valuable contributions. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org. This paper has been reviewed and approved by the MESA Publications and Presentations Committee.N