ABSTRACTObjectivesA nationwide study of the impact of high temperature on respiratory disease hospitalizations among older adults (65+) living in large urban centers.MethodsDaily rates of short-stay, inpatient respiratory hospitalizations were examined with respect to variations in ZIP-code-level daily mean temperature in the 120 largest US cities between 2000-2017. For each city, we estimated cumulative associations (lag-days 0-6) between warm-season temperatures (June-September) and cause-specific respiratory hospitalizations using time-stratified conditional quasi-Poisson regression with distributed lag non-linear models. We estimated nationwide associations using meta-regression and updated city-specific associations via best linear unbiased prediction. With stratified models, we explored effect modification by age, sex, and race (Black/white). Results were reported as percent change in hospitalizations at high temperatures (95th percentile) compared to median temperatures for each outcome, demographic-group, and metropolitan area. Excess hospitalization rates were estimated for days above median temperatures.ResultsAt high temperatures, we observed increases in the percent of all-cause respiratory hospitalizations [1.2 (0.4, 2.0)], primarily driven by an increase in respiratory tract infections [1.8 (0.6, 3.0)], and chronic respiratory diseases/respiratory failure [1.2 (0.0, 2.4)]. East North Central, New England, Mid-Atlantic, and Pacific cities accounted for 98.5% of the excess burden. By demographic group, we observed disproportionate burdens of heat-related respiratory hospitalizations among the oldest beneficiaries (85+ years), and among Black beneficiaries living in South Atlantic cities.ConclusionThis study found robust impacts of high temperature on respiratory failure and chronic inflammatory and fibrotic diseases among older adults. The geographic variation suggests that contextual factors account for disproportionate burdens.

Background: Per- and polyfluoroalkyl substances (PFAS) are persistent organic pollutants with emerging environmental and regulatory concerns. Objectives: This study aimed to estimate the burden of PFAS exposures through ground water on the incidence of chronic health conditions among Medicare beneficiaries aged 65 years and older. Methods: We estimated PFAS groundwater concentrations for every ZIP code tabulated area (ZCTA) in California counties where 25 percent or more of the population drinking water was derived from groundwater. We calculated the annual incidence of non-cancer chronic health conditions among 1,696,247 Medicare beneficiaries aged 65 and older by residential ZCTA over the seven-year study period (2011-2017). A Poisson regression model was used to estimate associations between PFAS groundwater concentration and chronic condition incidence with an offset for the number of beneficiary-years at risk and adjusting for bias due to non-random sampling of wells, use of groundwater for drinking water, demographic characteristics, and lung cancer incidence as a control for smoking. Results: Results suggest an association between a 10 ng/L increment in PFAS contaminated groundwater and chronic health conditions including hypertension (+1.15%, 95% confidence interval (CI) 1.01, 1.30), chronic kidney disease (+0.83%, 95% CI 0.68, 0.99) and cataracts (+1.50%, 95% CI 1.35, 1.66). Discussion: This small increment in the incidence rate would produce an additional 1,700 new cases of hypertension each year in the study population.### Competing Interest StatementThe authors have declared no competing interest.### Funding StatementThis research was conducted with intramural EPA funds.### Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:UNC Institutional Review BoardI confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.YesAll exposure data and analytical code will be posted after the manuscript is accepted. Health data is considered sensitive and cannot be posted publicly.

BACKGROUND AND AIM: Extreme heat exposure is a well-known cause of mortality, particularly among older adults. However, evidence of the effect of extreme heat on morbidity is inconsistent. We applied a uniform modeling approach across 120 of the largest US metropolitan areas to assess heat-related hospitalizations for respiratory disease among older adults. METHOD: We obtained ZIP code-level daily counts of respiratory disease hospitalizations using Medicare billing claims from short-stay, inpatient hospitalizations. We estimated ambient heat exposure using spatially interpolated, population weighted weather station data. To estimate heat-health impacts during the warm season (June-Sept), we explored lag days 0-6, and used conditional Poisson with a distributed lag non-linear model, matched on ZIP code of residence, month, and day of hospitalization. We fit separate models for three heat exposure metrics; all models were adjusted for temporal trends and meteorology. RESULTS: From 2000 to 2017, we identified 9,141,138 respiratory disease hospitalizations during the warm season. Associations between respiratory hospitalizations and extreme heat days - defined as the 95th percentile of the city-specific warm season temperature - exhibited substantial geographic variation. When comparing the 95th percentile to the 50th percentile of temperature, cumulative odds ratios ranged from 1.09 (95% CI: 1.03, 1.15) in Palm Bay, Florida to 0.95 (95% CI: 0.89, 1.00) in Boise City, Idaho. Geographical variation was not explained by U.S. region/division or Köppen classification of climate zones. Associations were generally larger on lag days 0-2 compared to later lag periods. CONCLUSIONS: Considerable geographical variation in the magnitude and direction of odds ratios suggest that drivers of heat-health impacts are occurring at the local level. Future work should investigate area-level factors that modify risk. This work was supported by a cooperative agreement between the U.S. EPA and University of North Carolina-Chapel Hill. The abstract does not necessarily reflect the views and policies of the U.S. EPA.

Many United States (US) cities are experiencing urban heat islands (UHIs) and climate change-driven temperature increases. Extreme heat increases cardiovascular disease (CVD) risk, yet little is known about how this association varies with UHI intensity (UHII) within and between cities. We aimed to identify the urban populations most at-risk of and burdened by heat-related CVD morbidity in UHI-affected areas compared to unaffected areas. ZIP code-level daily counts of CVD hospitalizations among Medicare enrollees, aged 65-114, were obtained for 120 US metropolitan statistical areas (MSAs) between 2000 and 2017. Mean ambient temperature exposure was estimated by interpolating daily weather station observations. ZIP codes were classified as low and high UHII using the first and fourth quartiles of an existing surface UHII metric, weighted to each have 25% of all CVD hospitalizations. MSA-specific associations between ambient temperature and CVD hospitalization were estimated using quasi-Poisson regression with distributed lag non-linear models and pooled via multivariate meta-analyses. Across the US, extreme heat (MSA-specific 99th percentile, on average 28.6 °C) increased the risk of CVD hospitalization by 1.5% (95% CI: 0.4%, 2.6%), with considerable variation among MSAs. Extreme heat-related CVD hospitalization risk in high UHII areas (2.4% [95% CI: 0.4%, 4.3%]) exceeded that in low UHII areas (1.0% [95% CI: -0.8%, 2.8%]), with upwards of a 10% difference in some MSAs. During the 18-year study period, there were an estimated 37,028 (95% CI: 35,741, 37,988) heat-attributable CVD admissions. High UHII areas accounted for 35% of the total heat-related CVD burden, while low UHII areas accounted for 4%. High UHII disproportionately impacted already heat-vulnerable populations; females, individuals aged 75-114, and those with chronic conditions living in high UHII areas experienced the largest heat-related CVD impacts. Overall, extreme heat increased cardiovascular morbidity risk and burden in older urban populations, with UHIs exacerbating these impacts among those with existing vulnerabilities.

BACKGROUND:Neighborhood-level socioeconomic status (SES) is associated with health outcomes, including cardiovascular disease and diabetes, but these associations are rarely studied across large, diverse populations. METHODS:We used Ward's Hierarchical clustering to define eight neighborhood clusters across North Carolina using 11 census-based indicators of SES, race, housing, and urbanicity and assigned 6992 cardiac catheterization patients at Duke University Hospital from 2001 to 2010 to clusters. We examined associations between clusters and coronary artery disease index > 23 (CAD), history of myocardial infarction, hypertension, and diabetes using logistic regression adjusted for age, race, sex, body mass index, region of North Carolina, distance to Duke University Hospital, and smoking status. RESULTS:Four clusters were urban, three rural, and one suburban higher-middle-SES (referent). We observed greater odds of myocardial infarction in all six clusters with lower or middle-SES. Odds of CAD were elevated in the rural cluster that was low-SES and plurality Black (OR 1.16, 95% CI 0.94-1.43) and in the rural cluster that was majority American Indian (OR 1.31, 95% CI 0.91-1.90). Odds of diabetes and hypertension were elevated in two urban and one rural low- and lower-middle SES clusters with large Black populations. CONCLUSIONS:We observed higher prevalence of cardiovascular disease and diabetes in neighborhoods that were predominantly rural, low-SES, and non-White, highlighting the importance of public health and healthcare system outreach into these communities to promote cardiometabolic health and prevent and manage hypertension, diabetes and coronary artery disease.

BACKGROUND AND AIM. Extreme heat increases the risk of hospitalization due to cardiovascular disease (CVD). The United States (US) population largely resides in urban areas where climate change is projected to increase temperatures, yet little is known about this association across urban heat islands (UHIs). We aimed to identify the urban populations most at risk of and burdened by heat-related CVD morbidity. METHODS. We obtained daily counts of CVD hospital admissions (HAs) for Medicare enrollees (aged 65+) in 120 metropolitan areas (MSAs) in the contiguous US between 2000-2017. Daily average temperatures were estimated through the interpolation of monitor observations. A measure of UHI intensity was estimated from satellite-derived temperatures in urban vs. non-urban areas. We used quasi-Poisson regression with distributed-lag, non-linear models to estimate MSA-specific associations and pooled these estimates with multivariate meta-analyses. Stratified analyses were performed by UHI intensity quartile. We also calculated the number of CVD HAs attributable to heat in each MSA. RESULTS. Overall, extreme heat (99th percentile, ~28.6°C) was associated with a 3.0% [1.4%, 4.6%] increase in CVD HA risk relative to the minimum hospitalization temperature (MHT) (91st percentile, ~25.4°C). MSA-specific risks showed substantial differences, with higher risk in MSAs with lower annual average temperatures. We estimate that 1.6% (31,498) of CVD HAs on days above the MHT were attributable to heat. Although the interquartile risk differences were not significant, the highest quartile of UHI intensity was responsible for 47% (14,636) of all heat-attributable CVD HAs. CONCLUSIONS. Our results show that extreme heat increases the risk of CVD HAs among older adults in US urban areas, with considerable variation between cities. Areas with higher UHI intensity had the highest heat-related burden, indicating a potentially vulnerable subset of the urban population. This abstract does not necessarily reflect EPA policy. KEYWORDS. Extreme heat, cardiovascular morbidity, urban heat islands

Background: Contaminated sites known as brownfields contribute to air, water, and land pollution and also prevent the beneficial use of lands by the community. The health effects surrounding brownfields have been understudied which can impair efforts to quantify the benefits of their remediation. Methods: Our study cohort was composed of 21,776 heart failure patients diagnosed between 2004 and 2016 at a University of North Carolina Healthcare System affiliated hospital or clinic. We examined the associations between brownfields and hospital readmissions. We used proximity to the nearest brownfield as our exposure based on the primary residence at the time of heart failure diagnosis. Zero-inflated Poisson models were used to associate distance to the nearest brownfield with readmissions while adjusting for age, race, sex, and socioeconomic status indicators based on the 2010 US Census. In sensitivity analyses we examined log transformed distance, restricted to only those brownfields within 2 km of an individual, and further adjusted for county-level indicators of access to healthcare. Results: A 1 km increase in distance to the nearest brownfield was associated with a 1.29% (95% confidence interval = 0.43-2.14%) decrease in 7-day readmissions as well as a 0.55% decrease (95% confidence interval = 0.20-0.90%) in 30-day readmissions. Associations with 7-day readmissions remained when restricting to brownfields within 2km, in the log-transformed distance models, and after adjusting for county-level indicators of access to healthcare. Associations with 30-day readmissions were substantially attenuated under all sensitivity analyses. Conclusion: Proximity to brownfields is associated with increases in hospital visits and readmissions among heart failure patients. These associations may reflect exposure to chemicals present in the brownfields as well as land disinvestment. Understanding the health risks surrounding brownfields may help communities to better protect their environmental health. This abstract does not necessarily represent the views or policies of the US EPA.

Exposure to air pollution is a major risk factor for cardiovascular disease, disease risk factors, and mortality. Specifically, particulate matter (PM), and to some extent ozone, are contributors to these effects. In addition, exposures to these pollutants may be especially dangerous for susceptible populations. In this repeated-visit panel study, cardiovascular markers were collected from thirteen male participants with stable coronary artery disease. For 0-4 days prior to the health measurement collections, daily concentrations of fine PM (PM2.5) and ozone were obtained from local central monitoring stations located near the participant's homes. Then, single (PM2.5) and two-pollutant (PM2.5 and ozone) models were used to assess whether there were short-term changes in cardiovascular health markers. Per interquartile range increase in PM2.5, there were decrements in several heart rate variability metrics, including the standard deviation of the normal-to-normal intervals (lag 3, -5.8%, 95% confidence interval (CI) = -11.5, 0.3) and root-mean squared of successive differences (five day moving average, -8.1%, 95% CI = -15.0, -0.7). In addition, increases in PM2.5 were also associated with changes in P complexity (lag 1, 4.4%, 95% CI = 0.5, 8.5), QRS complexity (lag 1, 4.9%, 95% CI = 1.4, 8.5), total cholesterol (five day moving average, -2.1%, 95% CI = -4.1, -0.1), and high-density lipoprotein cholesterol (lag 2, -1.6%, 95% CI = -3.1, -0.1). Comparisons to our previously published work on ozone were conducted. We found that ozone affected inflammation and endothelial function, whereas PM2.5 influenced heart rate variability, repolarization, and lipids. All the health changes from these two studies were found at concentrations below the United States Environmental Protection Agency's National Ambient Air Quality Standards. Our results imply clear differences in the cardiovascular outcomes observed with exposure to the two ubiquitous air pollutants PM2.5 and ozone; this observation suggests different mechanisms of toxicity for these exposures.

Multi-city epidemiologic studies examining short-term (daily) differences in fine particulate matter (PM2.5) provide evidence of substantial spatial heterogeneity in city-specific mortality risk estimates across the United States. Because PM2.5 is a mixture of particles, both directly emitted from sources or formed through atmospheric reactions, some of this heterogeneity may be due to regional variations in PM2.5 toxicity. Using inverse variance weighted linear regression, we examined change in percent change in mortality in association with 24 "exposure" determinants representing three basic groupings based on potential explanations for differences in PM toxicity - size, source, and composition. Percent changes in mortality for the PM2.5-mortality association for 313 core-based statistical areas and their metropolitan divisions over 1999-2005 were used as the outcome. Several determinants were identified as potential contributors to heterogeneity: all mass fraction determinants, vehicle miles traveled (VMT) for diesel total, VMT gas per capita, PM2.5 ammonium, PM2.5 nitrate, and PM2.5 sulfate. In multivariable models, only daily correlation of PM2.5 with PM10 and long-term average PM2.5 mass concentration were retained, explaining approximately 10% of total variability. The results of this analysis contribute to the growing body of literature specifically focusing on assessing the underlying basis of the observed spatial heterogeneity in PM2.5-mortality effect estimates, continuing to demonstrate that this heterogeneity is multifactorial and not attributable to a single aspect of PM.

Long-term air pollution exposure, notably fine particulate matter, is a global contributor to morbidity and mortality and a known risk factor for coronary artery disease (CAD) and myocardial infarctions (MI). Knowledge of impacts related to source-apportioned PM2.5 is limited. New modeling methods allow researchers to estimate source-specific long-term impacts on the prevalence of CAD and MI. The Catheterization Genetics (CATHGEN) cohort consists of patients who underwent a cardiac catheterization at Duke University Medical Center between 2002 and 2010. Severity of coronary blockage was determined by coronary angiography and converted into a binary indicator of clinical CAD. History of MI was extracted from medical records. Annual averages of source specific PM2.5 were estimated using an improved gas-constrained source apportionment model for North Carolina from 2002 to 2010. We tested six sources of PM2.5 mass for associations with CAD and MI using mixed effects multivariable logistic regression with a random intercept for county and multiple adjustments. PM2.5 fractions of ammonium bisulfate and ammonium nitrate were associated with increased prevalence of CAD (odds ratio [OR] 1.20; 95% CI=1.11, 1.22 and OR 1.18; 95% CI=1.05, 1.32, respectively). PM2.5 from ammonium bisulfate and ammonium nitrate were also associated with increased prevalence of MI (OR 1.20; 95% CI=1.10, 1.29 and OR 1.35; 95% CI=1.20, 1.53, respectively). Greater PM2.5 concentrations of ammonium bisulfate and ammonium nitrate are associated with greater MI and CAD prevalence. The association with bisulfate suggests aerosol acidity may play a role. Our findings suggest analyses of source specific PM2.5 mass can reveal novel associations.

Exposure to fine particulate matter (PM2.5) has been associated with a higher risk for coronary events. Elevated circulating cardiac troponins (cTn) are suggestive of myocardial injury in both ischemic and non-ischemic conditions. However, little is known about the association between PM2.5 and cTn. In this study, we investigated short-term PM2.5 effects on cardiac troponin T (cTnT), as well as N-terminal-pro brain natriuretic peptide (NT-pro BNP) and inflammatory biomarkers among cardiac catheterized participants. We analyzed 7444 plasma cTnT measurements in 2732 participants who presented to Duke University Hospital with myocardial infarction symptoms between 2001 and 2012, partly along with measurements of NT-pro BNP and inflammatory biomarkers. Daily PM2.5 concentrations were predicted by a neural network-based hybrid model and were assigned to participants' residential addresses. We applied generalized estimating equations to assess associations of PM2.5 with biomarker levels and the risk of a positive cTnT test (cTnT > 0.1 ng/mL). The median plasma cTnT concentration at presentation was 0.05 ng/mL and the prevalence of a positive cTnT test was 35.4%. For an interquartile range (7.6 mg/m(3)) increase in PM2.5 on the previous day, cTnT concentrations increased by 7.7% (95% CI: 3.4-12.3) and the odds ratio of a positive cTnT test was 1.08 (1.01-1.16). Participants under 60 years (effect estimate: 15.2%; 95% CI: 7.4-23.5) or living in rural areas (12.3%; 95% CI: 4.8-20.3) were more susceptible. There was evidence for increases in fibrinogen and NT-pro BNP associated with elevated PM2.5 on the concurrent and previous two days. Our study suggests that acute PM2.5 exposure may elevate indicators of myocardial tissue damage. This finding substantiates the association of air pollution exposure with adverse cardiovascular events. (C) 2021 Elsevier Ltd. All rights reserved.

Background: Comparisons of greenspace between metropolitan areas generally reflect regional differences in soil characteristics and climatic zone, while greenspace differences within a metropolitan area at the postal code level avoid these regional differences. We examined local differences and trends in greenspace as determinants of local differences and trends in cardiovascular health.Methods: We calculated annual age-adjusted cardiovascular hospital admission rates (admissions per 100,000 person-years at risk, CHR) among Medicare beneficiaries aged 65 years and older for 2002-2013 across 10,097 ZIP codes (postal codes) in 123 major metropolitan core-based statistical areas (CBSA). We obtained monthly normalized difference vegetative index (NDVI) from the Terra satellite (1km grid) mapped to metropolitan ZIP code, determined the month with maximum NDVI for each metropolitan area, and finally assigned maximum-month values of NDVI for each ZIP code and year. Finally, we modeled the associations scaled to the interquartile range (IQR) both for centered means and for 12-year trends in CHR and NDVI, adjusting for CBSA and for levels and trends in adjusted gross income, proportion White and population density.Results: Across 123 major US metropolitan areas for 2002-2013, CHR had a mean of 5,903 admissions per 100,000 person-years at risk and a trend of -122 per year. An IQR increment of 0.121 in the mean NDVI was associated with a 52.4 lower CHR (95% CI 20.4, 84.3), while an IQR increment of 0.018 in the annual trend in NDVI was associated with a 6.4 per year greater decrease in CHR (95% CI 4.5, 8.3).Conclusion: Thus, after adjustment for metropolitan area characteristics and for cardiovascular risk factors, we have shown that local improvements in greenspace (NDVI) lead to local improvements in cardiovascular health among Medicare beneficiaries.This abstract does not necessarily represent the views or policies of the U.S. Environmental Protection Agency.

This article contains data on county-level socioeconomic status for 2132 US counties and each county's average annual cardiovascular mortality rate (CMR) and fine particulate matter (PM2.5) concentration for 21 years (1990–2010). County CMR, PM2.5, and socioeconomic data were obtained from the US National Center for Health Statistics, US Environmental Protection Agency's Community Multiscale Air Quality modeling system, and the US Census, respectively. Annual socioeconomic indices were created using seven county-level measures from the 1990, 2000, and 2010 US Census using factor analysis. Quintiles of this index were used to generate categories of county socioeconomic status. This national data set contains data for annual PM2.5 and CMR changes over a time-period when there was a significant reduction in US air pollutants (following the enactment of the 1970 Clean Air Act). These data are associated with the article “The contribution of improved air quality to reduced cardiovascular mortality: Declines in socioeconomic differences over time” [1]. Data are stored in a comma separated value format and can be downloaded from the USEPA ScienceHub data repository (https://doi.org/10.23719/1506014).

Background/Aim: Fine particles (PM2.5) are associated with a higher risk for coronary events. Cardiac troponin T (cTnT) is a myocardium-specific protein which is measured clinically for the diagnosis and prognosis of myocardial infarction (MI). An elevation in circulating cTnT also occurs in non-ischemic conditions and indicates myocardial damage. We aimed to investigate short-term PM2.5 effects on cTnT and other myocardial injury-related biomarkers among participants undergoing cardiac catheterizations.Methods: This study included 7,497 plasma cTnT measurements conducted in 2,739 participants presenting to Duke University Hospital (2000 to 2012), partly alongside with measurements of C-reactive protein, fibrinogen, white blood cells, N-terminal-pro brain natriuretic peptide (NT-pro BNP), and partial oxygen pressure (PaO2). Daily PM2.5 was predicted by a neural network-based hybrid model at a 1km resolution and was assigned to participants' residential addresses. We applied generalized estimating equations to assess associations of PM2.5 with biomarker levels and the risk of a positive cTnT test (cTnT>0.1ng/mL).Results: Mean PM2.5 concentration was 11.8 μg/m3. Median plasma cTnT was 0.05 ng/mL and the prevalence of a positive cTnT test was 35.6% at presentation. For a 10µg/m3 increase in PM2.5 one day before cTnT measurement, plasma cTnT increased by 11.1% (95% CI: 5.3–17.4) and the odds ratio of a positive cTnT test was 1.12 (95% CI: 1.03–1.23). Participants under 60 years [20.9% (95% CI: 10.2–32.6)] or living in rural areas [17.6% (95% CI: 7.3–28.7)] had stronger associations. There was additionally evidence for positive associations of PM2.5 with fibrinogen and NT-pro BNP within one day after exposure, as well as negative associations with PaO2 at lag 3-4 days. Conclusions: Our study suggests that acute PM2.5 exposure may elevate indicators of myocardial injury and exertion, which substantiates the association of air pollution exposure with adverse cardiovascular events. This abstract does not necessarily represent EPA policy.

Background: Accelerated epigenetic age has been proposed as a biomarker of increased aging, which may indicate disruptions in cellular and organ system homeostasis and thus contribute to sensitivity to environmental exposures. Methods: Using 497 participants from the CATHGEN cohort, we evaluated whether accelerated epigenetic aging increases cardiovascular sensitivity to traffic-related air pollution (TRAP) exposure. We used residential proximity to major roadways and source apportioned air pollution models as measures of TRAP exposure, and chose peripheral arterial disease (PAD) and blood pressure as outcomes based on previous associations with TRAP. We used Horvath epigenetic age acceleration (AAD) and phenotypic age acceleration (PhenoAAD) as measures of age acceleration, and adjusted all models for chronological age, race, sex, smoking, and socioeconomic status. Results: We observed significant interactions between TRAP and both AAD and PhenoAAD. Interactions indicated that increased epigenetic age acceleration elevated associations between proximity to roadways and PAD. Interactions were also observed between AAD and gasoline and diesel source apportioned PM2.5. Conclusion: Epigenetic age acceleration may be a biomarker of sensitivity to air pollution, particularly for TRAP in urban cohorts. This presents a novel means by which to understand sensitivity to air pollution and provides a molecular measure of environmental sensitivity.

Background Both exposure to PM2.5 air pollution and neighborhood socioeconomic status (SES) are associated with adverse cardiovascular outcomes, including hypertension. We used the EPA-CARES electronic health record database to study the joint impact of neighborhood SES and PM2.5 exposure on hypertension among patients with heart failure in North Carolina. Methods We used block-group level factors of urbanicity, housing, and SES from the 2010 Census to identify seven neighborhood clusters (spatially noncontiguous) using Ward's hierarchical clustering algorithm. We then assigned neighborhood clusters to the primary residence of heart failure patients(N = 30,060). Participant residence-specific estimates of annual average PM2.5 concentrations were modeled at a 1x1 km resolution using a hybrid satellite-based model developed at Harvard University. We examined the associations between PM2.5 and hypertension, by neighborhood cluster and overall, using logistic regression models adjusted for age, sex, race, chronic kidney disease, diabetes, peripheral artery disease, hyperlipidemia, and chronic obstructive pulmonary disease. Results PM2.5 concentrations ranged from 9.5 µg/m3 (IQR 1.8 µg/m3) in lower-SES rural cluster to 10.4 µg/m3 (IQR 2.8 µg/m3) in upper-middle-SES urban cluster. We observed associations between a 1 µg/m3 increment in PM2.5 and hypertension among lower-SES urban (OR=1.05, 95% CI 1.00-1.10), lower-middle-SES urban (OR=1.03, 95% CI 1.00-1.07), and middle-SES urban (OR 1.04, 95% CI 0.98-1.10) clusters and overall (OR=1.02, 95% CI 1.00-1.04). We did not observe associations between PM2.5 and hypertension in rural, suburban, or upper-SES urban clusters. Conclusions Among heart failure patients, we observed associations between PM2.5 and hypertension in lower- and middle-SES urban areas. These results suggest that associations between PM2.5 and hypertension can vary by neighborhood among individuals with severe cardiovascular disease. This abstract does not necessarily reflect EPA policy.

Household air pollution (HAP) is estimated to be an important risk factor for cardiovascular disease, but little clinical evidence exists and collecting biomarkers of disease risk is difficult in low-resource settings. Among 54 Nicaraguan women with woodburning cookstoves, we evaluated cross-sectional associations between 48-our measures of HAP (eg, fine particulate matter, PM2.5) and C-reactive protein (CRP) via dried blood spots; secondary analyses included seven additional biomarkers of systemic injury and inflammation. We conducted sub-studies to calculate the intraclass correlation coefficient (ICC) in biomarkers collected over four consecutive days in Nicaragua and to assess the validity of measuring biomarkers in dried blood by calculating the correlation with paired venous-drawn samples in Colorado. Measures of HAP were associated with CRP (eg, a 25% increase in indoor PM2.5 was associated with a 7.4% increase in CRP [95% confidence interval: 0.7, 14.5]). Most of the variability in CRP concentrations over the 4-day period was between-person (ICC: 0.88), and CRP concentrations were highly correlated between paired dried blood and venous-drawn serum (Spearman rho =.96). Results for secondary biomarkers were primarily consistent with null associations, and the sub-study ICCs and correlations were lower. Assessing CRP via dried blood spots provides a feasible approach to elucidate the association between HAP and cardiovascular disease risk.

Background Environmental health risks for individuals with heart failure (HF) have been inadequately studied, as these individuals are not well represented in traditional cohort studies. To address this we studied associations between long‐term air pollution exposure and mortality in HF patients. Methods and Results The study population was a hospital‐based cohort of individuals diagnosed with HF between July 1, 2004 and December 31, 2016 compiled using electronic health records. Individuals were followed from 1 year after initial diagnosis until death or the end of the observation period (December 31, 2016). We used Cox proportional hazards models to evaluate the association of annual average fine particulate matter (PM2.5) exposure at the time of initial HF diagnosis with all‐cause mortality, adjusted for age, race, sex, distance to the nearest air pollution monitor, and socioeconomic status indicators. Among 23 302 HF patients, a 1 μg/m3 increase in annual average PM2.5 was associated with an elevated risk of all‐cause mortality (hazard ratio 1.13; 95% CI, 1.10–1.15). As compared with people with exposures below the current national PM2.5 exposure standard (12 μg/m3), those with elevated exposures experienced 0.84 (95% CI, 0.73–0.95) years of life lost over a 5‐year period, an observation that persisted even for those residing in areas with PM2.5 concentrations below current standards. Conclusions Residential exposure to elevated concentrations of PM2.5 is a significant mortality risk factor for HF patients. Elevated PM2.5 exposures result in substantial years of life lost even at concentrations below current national standards.