Urban heat island impacts on heat-related cardiovascular morbidity: A time series analysis of older adults in US metropolitan areas.

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.

Association between short-term exposure to ambient fine particulate matter and myocardial injury in the CATHGEN cohort.

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 µg/m3) 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.

Accelerated epigenetic age as a biomarker of cardiovascular sensitivity to traffic-related air pollution.

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.

Annual PM2.5 and cardiovascular mortality rate data: Trends modified by county socioeconomic status in 2,132 US counties.

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).

Associations Between Long-Term Fine Particulate Matter Exposure and Mortality in Heart Failure Patients.

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.

Impact of Reductions in Emissions from Major Source Sectors on Fine Particulate Matter-Related Cardiovascular Mortality.

BACKGROUND: Reductions in ambient concentrations of fine particulate matter (PM2.5) have contributed to reductions in cardiovascular (CV) mortality. OBJECTIVES: We examined changes in CV mortality attributed to reductions in emissions from mobile, point, areal, and nonroad sources through changes in concentrations of PM2.5 and its major components [nitrates, sulfates, elemental carbon (EC), and organic carbon (OC)] in 2,132 U.S. counties between 1990 and 2010. METHODS: Using Community Multiscale Air Quality model estimated PM2.5 total and component concentrations, we calculated population-weighted annual averages for each county. We estimated PM2.5 total- and component-related CV mortality, adjusted for county-level population characteristics and baseline PM2.5 concentrations. Using the index of Emission Mitigation Efficiency for primary emission-to-particle pathways, we expressed changes in particle-related mortality in terms of precursor emissions by each sector. RESULTS: PM2.5 reductions represented 5.7% of the overall decline in CV mortality. Large point source emissions of sulfur dioxide accounted for 6.685 [95% confidence interval (CI): 5.703, 7.667] fewer sulfate-related CV deaths per 100,000 people. Mobile source emissions of primary EC and nitrous oxides accounted for 3.396 (95% CI: 2.772, 4.020) and 3.984 (95% CI: 2.472, 5.496) fewer CV deaths per 100,000 people respectively. Increased EC and OC emissions from areal sources increased carbon-related CV mortality by 0.788 (95% CI: -0.540, 2.116) and 0.245 (95% CI: -0.697, 1.187) CV deaths per 100,000 people. DISCUSSION: In a nationwide epidemiological study of emission sector contribution to PM2.5-related mortality, we found that reductions in sulfur-dioxide emissions from large point sources and nitrates and EC emissions from mobile sources contributed the largest reduction in particle-related mortality rates respectively. https://doi.org/10.1289/EHP5692.

C-reactive protein from dried blood spots: Application to household air pollution field studies.

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-hour 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 ρ = .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.

The contribution of improved air quality to reduced cardiovascular mortality: Declines in socioeconomic differences over time.

Major improvements in air quality since 1990, observed through reductions in fine particulate matter (PM2.5), have been associated with reduced cardiovascular mortality rates (CMR). However, it is not well understood whether the health benefit attributed to PM2.5 reductions has been similar across strata of socioeconomic deprivation (SED). Using mixed effect regression models, we estimated the PM2.5-related change in the CMR across 2,132 US counties in five SED strata between 1990 and 2010. The analysis included annual county CMR (deaths/100,000 person-year), annual county PM2.5 (µg/m3), and an index of county SED based on socioeconomic factors from the 1990 US Census. The contribution of PM2.5 reductions to decreased CMR varied by SED strata and over time. Yearly differences resulted from varying rates of PM2.5 reduction and because of the non-linear relationship between CMR and PM2.5 concentration. In early years, PM2.5-related CMR reductions were smallest in the most deprived counties compared to all other counties (range: 0.4-0.6 vs 0.7-1.6 fewer deaths/100,000 person-year), due to slower rates of PM2.5 reduction in these counties. However, in later years, PM2.5-related CMR reductions were highest counties with moderate to high deprivation, compared to counties with the least deprivation (range: 1.0-2.2 vs 0.5-0.9 fewer deaths/100,000 person-year) due to larger CMR reductions per decrease in PM2.5. We identified that CMR reductions related to air quality improvements have become more similar over time between socioeconomic strata.

Early Life Exposure to Air Pollution and Autism Spectrum Disorder: Findings from a Multisite Case-Control Study.

BACKGROUND: Epidemiologic studies have reported associations between prenatal and early postnatal air pollution exposure and autism spectrum disorder (ASD); however, findings differ by pollutant and developmental window. OBJECTIVES: We examined associations between early life exposure to particulate matter ≤2.5 µm in diameter (PM2.5) and ozone in association with ASD across multiple US regions. METHODS: Our study participants included 674 children with confirmed ASD and 855 population controls from the Study to Explore Early Development, a multi-site case-control study of children born from 2003 to 2006 in the United States. We used a satellite-based model to assign air pollutant exposure averages during several critical periods of neurodevelopment: 3 months before pregnancy; each trimester of pregnancy; the entire pregnancy; and the first year of life. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for study site, maternal age, maternal education, maternal race/ethnicity, maternal smoking, and month and year of birth. RESULTS: The air pollution-ASD associations appeared to vary by exposure time period. Ozone exposure during the third trimester was associated with ASD, with an OR of 1.2 (95% CI: 1.1, 1.4) per 6.6 ppb increase in ozone. We additionally observed a positive association with PM2.5 exposure during the first year of life (OR = 1.3 [95% CI: 1.0, 1.6] per 1.6 µg/m increase in PM2.5). CONCLUSIONS: Our study corroborates previous findings of a positive association between early life air pollution exposure and ASD, and identifies a potential critical window of exposure during the late prenatal and early postnatal periods.

Air pollution, neighborhood deprivation, and autism spectrum disorder in the Study to Explore Early Development.

BACKGROUND: To examine whether neighborhood deprivation modifies the association between early life air pollution exposure and autism spectrum disorder (ASD), we used resources from a multisite case-control study, the Study to Explore Early Development. METHODS: Cases were 674 children with confirmed ASD born in 2003-2006; controls were 855 randomly sampled children born during the same time period and residents of the same geographic areas as cases. Air pollution was assessed by roadway proximity and particulate matter <2.5 µm (PM2.5) exposure during pregnancy and first year of life. To characterize neighborhood deprivation, an index was created based on eight census tract-level socioeconomic status-related parameters. The continuous index was categorized into tertiles, representing low, moderate, and high deprivation. Logistic regression was used to estimate odds ratios (ORs) and corresponding 95% confidence intervals (CIs). RESULTS: Neighborhood deprivation modified (P for interaction = 0.08) the association between PM2.5 exposure during the first year of life and ASD, with a stronger association for those living in high (OR = 2.42, 95% CI = 1.20, 4.86) rather than moderate (OR=1.21, 95% CI = 0.67, 2.17) or low (OR=1.46, 95% CI = 0.80, 2.65) deprivation neighborhoods. Departure from additivity or multiplicativity was not observed for roadway proximity or exposures during pregnancy. CONCLUSION: These results provide suggestive evidence of interaction between neighborhood deprivation and PM2.5 exposure during the first year of life in association with ASD.

Association of long-term PM2.5 exposure with traditional and novel lipid measures related to cardiovascular disease risk.

BACKGROUND: Fine particulate matter (PM2.5) exposure is associated with increased morbidity and mortality, particularly for cardiovascular disease. The association between long-term exposure to PM2.5 and measures of lipoprotein subfractions remains unclear. Therefore, we examined associations between long-term PM2.5 exposure and traditional and novel lipoprotein measures in a cardiac catheterization cohort in North Carolina. METHODS: This cross-sectional study included 6587 patients who had visited Duke University for a cardiac catheterization between 2001 and 2010 and resided in North Carolina. We used estimates of daily PM2.5 concentrations on a 1 km-grid based on satellite measurements. PM2.5 predictions were matched to the address of each patient and averaged for the year prior to catheterization date. Serum lipids included HDL, LDL, and triglyceride-rich particle, and apolipoprotein B concentrations (HDL-P, LDL-P, TRL-P, and apoB, respectively). Linear and quantile regression models were used to estimate change in lipoprotein levels with each µg/m3 increase in annual average PM2.5. Models were adjusted for age, sex, race/ethnicity, history of smoking, area-level education, urban/rural status, body mass index, and diabetes. RESULTS: For a 1-µg/m3 increment in PM2.5 exposure, we observed increases in total and small LDL-P, LDL-C, TRL-P, apoB, total cholesterol, and triglycerides. The percent change from the mean outcome level was 2.00% (95% CI: 1.38%, 2.64%) for total LDL-P and 2.25% (95% CI: 1.43%, 3.06%) for small LDL-P. CONCLUSION: Among this sample of cardiac catheterization patients residing in North Carolina, long-term PM2.5 exposure was associated with increases in several lipoprotein concentrations. This abstract does not necessarily reflect U.S. EPA policy.

Short-term effects of fine particulate matter and ozone on the cardiac conduction system in patients undergoing cardiac catheterization.

BACKGROUND: Air pollution-induced changes in cardiac electrophysiological properties could be a pathway linking air pollution and cardiovascular events. The evidence of air pollution effects on the cardiac conduction system is incomplete yet. We investigated short-term effects of particulate matter ≤ 2.5 µm in aerodynamic diameter (PM2.5) and ozone (O3) on cardiac electrical impulse propagation and repolarization as recorded in surface electrocardiograms (ECG). METHODS: We analyzed repeated 12-lead ECG measurements performed on 5,332 patients between 2001 and 2012. The participants came from the Duke CATHGEN Study who underwent cardiac catheterization and resided in North Carolina, United States (NC, U.S.). Daily concentrations of PM2.5 and O3 at each participant's home address were predicted with a hybrid air quality exposure model. We used generalized additive mixed models to investigate the associations of PM2.5 and O3 with the PR interval, QRS interval, heart rate-corrected QT interval (QTc), and heart rate (HR). The temporal lag structures of the associations were examined using distributed-lag models. RESULTS: Elevated PM2.5 and O3 were associated with four-day lagged lengthening of the PR and QRS intervals, and with one-day lagged increases in HR. We observed immediate effects on the lengthening of the QTc interval for both PM2.5 and O3, as well as delayed effects for PM2.5 (lagged by 3 - 4 days). The associations of PM2.5 and O3 with the PR interval and the association of O3 with the QRS interval persisted until up to seven days after exposure. CONCLUSIONS: In patients undergoing cardiac catheterization, short-term exposure to air pollution was associated with increased HR and delays in atrioventricular conduction, ventricular depolarization and repolarization.

Associations Between Residential Proximity to Traffic and Vascular Disease in a Cardiac Catheterization Cohort.

OBJECTIVE: Exposure to mobile source emissions is nearly ubiquitous in developed nations and is associated with multiple adverse health outcomes. There is an ongoing need to understand the specificity of traffic exposure associations with vascular outcomes, particularly in individuals with cardiovascular disease. APPROACH AND RESULTS: We performed a cross-sectional study using 2124 individuals residing in North Carolina, United States, who received a cardiac catheterization at the Duke University Medical Center. Traffic-related exposure was assessed via 2 metrics: (1) the distance between the primary residence and the nearest major roadway; and (2) location of the primary residence in regions defined based on local traffic patterns. We examined 4 cardiovascular disease outcomes: hypertension, peripheral arterial disease, the number of diseased coronary vessels, and recent myocardial infarction. Statistical models were adjusted for race, sex, smoking, type 2 diabetes mellitus, body mass index, hyperlipidemia, and home value. Results are expressed in terms of the odds ratio (OR). A 23% decrease in residential distance to major roadways was associated with higher prevalence of peripheral arterial disease (OR=1.29; 95% confidence interval, 1.08-1.55) and hypertension (OR=1.15; 95% confidence interval, 1.01-1.31). Associations with peripheral arterial disease were strongest in men (OR=1.42; 95% confidence interval, 1.17-1.74) while associations with hypertension were strongest in women (OR=1.21; 95% confidence interval, 0.99-1.49). Neither myocardial infarction nor the number of diseased coronary vessels were associated with traffic exposure. CONCLUSIONS: Traffic-related exposure is associated with peripheral arterial disease and hypertension while no associations are observed for 2 coronary-specific vascular outcomes.

Fine particulate matters: The impact of air quality standards on cardiovascular mortality.

BACKGROUND: In 1997 the U.S. Environmental Protection Agency set the first annual National Ambient Air Quality Standard (NAAQS) for fine particulate matter (PM2.5). Although the weight of scientific evidence has determined that a causal relationship exists between PM2.5 exposures and cardiovascular effects, few studies have concluded whether NAAQS-related reductions in PM2.5 led to improvements in public health. METHODS: We examined the change in cardiovascular (CV) mortality rate and the association between change in PM2.5 and change in CV-mortality rate before (2000-2004) and after implementation of the 1997 annual PM2.5 NAAQS (2005-2010) among U.S. counties. We further examined how the association varied with respect to two factors related to NAAQS compliance: attainment status and design values (DV). We used difference-in-differences and linear regression models, adjusted for sociodemographic confounders. FINDINGS: Across 619 counties, there were 1.10 (95% CI: 0.37, 1.82) fewer CV-deaths per year per 100,000 people for each 1µg/m3 decrease in PM2.5. Nonattainment counties had a twofold larger reduction in mean annual PM2.5, 2.1µg/m3, compared to attainment counties, 0.97µg/m3. CV-mortality rate decreased by 0.59 (95% CI: -0.54, 1.71) in nonattainment and 1.96 (95% CI: 0.77, 3.15) deaths per 100,000 people for each 1µg/m3 decrease in PM2.5 in attainment counties. When stratifying counties by DV, results were similar: counties with DV greater than 15µg/m3 experienced the greatest decrease in mean annual PM2.5 (2.29µg/m3) but the smallest decrease in CV-mortality rate per unit decrease in PM2.5, 0.73 (95% CI: -0.57, 2.02). INTERPRETATION: We report a significant association between the change in PM2.5 and the change in CV-mortality rate before and after the implementation of NAAQS and note that the health benefits per 1µg/m3 decrease in PM2.5 persist at levels below the current national standard. FUNDING: US EPA intermural research.

Fine particulate matter and cardiovascular disease: Comparison of assessment methods for long-term exposure.

BACKGROUND: Adverse cardiovascular events have been linked with PM2.5 exposure obtained primarily from air quality monitors, which rarely co-locate with participant residences. Modeled PM2.5 predictions at finer resolution may more accurately predict residential exposure; however few studies have compared results across different exposure assessment methods. METHODS: We utilized a cohort of 5679 patients who had undergone a cardiac catheterization between 2002-2009 and resided in NC. Exposure to PM2.5 for the year prior to catheterization was estimated using data from air quality monitors (AQS), Community Multiscale Air Quality (CMAQ) fused models at the census tract and 12km spatial resolutions, and satellite-based models at 10km and 1km resolutions. Case status was either a coronary artery disease (CAD) index >23 or a recent myocardial infarction (MI). Logistic regression was used to model odds of having CAD or an MI with each 1-unit (µg/m3) increase in PM2.5, adjusting for sex, race, smoking status, socioeconomic status, and urban/rural status. RESULTS: We found that the elevated odds for CAD>23 and MI were nearly equivalent for all exposure assessment methods. One difference was that data from AQS and the census tract CMAQ showed a rural/urban difference in relative risk, which was not apparent with the satellite or 12km-CMAQ models. CONCLUSIONS: Long-term air pollution exposure was associated with coronary artery disease for both modeled and monitored data.

A genome-wide trans-ethnic interaction study links the PIGR-FCAMR locus to coronary atherosclerosis via interactions between genetic variants and residential exposure to traffic.

Air pollution is a worldwide contributor to cardiovascular disease mortality and morbidity. Traffic-related air pollution is a widespread environmental exposure and is associated with multiple cardiovascular outcomes such as coronary atherosclerosis, peripheral arterial disease, and myocardial infarction. Despite the recognition of the importance of both genetic and environmental exposures to the pathogenesis of cardiovascular disease, studies of how these two contributors operate jointly are rare. We performed a genome-wide interaction study (GWIS) to examine gene-traffic exposure interactions associated with coronary atherosclerosis. Using race-stratified cohorts of 538 African-Americans (AA) and 1562 European-Americans (EA) from a cardiac catheterization cohort (CATHGEN), we identify gene-by-traffic exposure interactions associated with the number of significantly diseased coronary vessels as a measure of chronic atherosclerosis. We found five suggestive (P<1x10-5) interactions in the AA GWIS, of which two (rs1856746 and rs2791713) replicated in the EA cohort (P < 0.05). Both SNPs are in the PIGR-FCAMR locus and are eQTLs in lymphocytes. The protein products of both PIGR and FCAMR are implicated in inflammatory processes. In the EA GWIS, there were three suggestive interactions; none of these replicated in the AA GWIS. All three were intergenic; the most significant interaction was in a regulatory region associated with SAMSN1, a gene previously associated with atherosclerosis and B cell activation. In conclusion, we have uncovered several novel genes associated with coronary atherosclerosis in individuals chronically exposed to increased ambient concentrations of traffic air pollution. These genes point towards inflammatory pathways that may modify the effects of air pollution on cardiovascular disease risk.

Associations among plasma metabolite levels and short-term exposure to PM2.5 and ozone in a cardiac catheterization cohort.

RATIONALE: Exposure to ambient particulate matter (PM) and ozone has been associated with cardiovascular disease (CVD). However, the mechanisms linking PM and ozone exposure to CVD remain poorly understood. OBJECTIVE: This study explored associations between short-term exposures to PM with a diameter <2.5µm (PM2.5) and ozone with plasma metabolite concentrations. METHODS AND RESULTS: We used cross-sectional data from a cardiac catheterization cohort at Duke University, North Carolina (NC), USA, accumulated between 2001 and 2007. Amino acids, acylcarnitines, ketones and total non-esterified fatty acid plasma concentrations were determined in fasting samples. Daily concentrations of PM2.5 and ozone were obtained from a Bayesian space-time hierarchical model, matched to each patient's residential address. Ten metabolites were selected for the analysis based on quality criteria and cluster analysis. Associations between metabolites and PM2.5 or ozone were analyzed using linear regression models adjusting for long-term trend and seasonality, calendar effects, meteorological parameters, and participant characteristics. We found delayed associations between PM2.5 or ozone and changes in metabolite levels of the glycine-ornithine-arginine metabolic axis and incomplete fatty acid oxidation associated with mitochondrial dysfunction. The strongest association was seen for an increase of 8.1µg/m3 in PM2.5 with a lag of one day and decreased mean glycine concentrations (-2.5% [95% confidence interval: -3.8%; -1.2%]). CONCLUSIONS: Short-term exposures to ambient PM2.5 and ozone is associated with changes in plasma concentrations of metabolites in a cohort of cardiac catheterization patients. Our findings might help to understand the link between air pollution and cardiovascular disease.

Genetic Variants in the Bone Morphogenic Protein Gene Family Modify the Association between Residential Exposure to Traffic and Peripheral Arterial Disease.

There is a growing literature indicating that genetic variants modify many of the associations between environmental exposures and clinical outcomes, potentially by increasing susceptibility to these exposures. However, genome-scale investigations of these interactions have been rarely performed particularly in the case of air pollution exposures. We performed race-stratified genome-wide gene-environment interaction association studies on European-American (EA, N = 1623) and African-American (AA, N = 554) cohorts to investigate the joint influence of common single nucleotide polymorphisms (SNPs) and residential exposure to traffic ("traffic exposure")-a recognized vascular disease risk factor-on peripheral arterial disease (PAD). Traffic exposure was estimated via the distance from the primary residence to the nearest major roadway, defined as the nearest limited access highways or major arterial. The rs755249-traffic exposure interaction was associated with PAD at a genome-wide significant level (P = 2.29x10-8) in European-Americans. Rs755249 is located in the 3' untranslated region of BMP8A, a member of the bone morphogenic protein (BMP) gene family. Further investigation revealed several variants in BMP genes associated with PAD via an interaction with traffic exposure in both the EA and AA cohorts; this included interactions with non-synonymous variants in BMP2, which is regulated by air pollution exposure. The BMP family of genes is linked to vascular growth and calcification and is a novel gene family for the study of PAD pathophysiology. Further investigation of BMP8A using the Genotype Tissue Expression Database revealed multiple variants with nominally significant (P < 0.05) interaction P-values in our EA cohort were significant BMP8A eQTLs in tissue types highlight relevant for PAD such as rs755249 (tibial nerve, eQTL P = 3.6x10-6) and rs1180341 (tibial artery, eQTL P = 5.3x10-6). Together these results reveal a novel gene, and possibly gene family, associated with PAD via an interaction with traffic air pollution exposure. These results also highlight the potential for interactions studies, particularly at the genome scale, to reveal novel biology linking environmental exposures to clinical outcomes.

The Association between Dust Storms and Daily Non-Accidental Mortality in the United States, 1993-2005.

BACKGROUND: The impact of dust storms on human health has been studied in the context of Asian, Saharan, Arabian, and Australian storms, but there has been no recent population-level epidemiological research on the dust storms in North America. The relevance of dust storms to public health is likely to increase as extreme weather events are predicted to become more frequent with anticipated changes in climate through the 21st century. OBJECTIVES: We examined the association between dust storms and county-level non-accidental mortality in the United States from 1993 through 2005. METHODS: Dust storm incidence data, including date and approximate location, are taken from the U.S. National Weather Service storm database. County-level mortality data for the years 1993-2005 were acquired from the National Center for Health Statistics. Distributed lag conditional logistic regression models under a time-stratified case-crossover design were used to study the relationship between dust storms and daily mortality counts over the whole United States and in Arizona and California specifically. End points included total non-accidental mortality and three mortality subgroups (cardiovascular, respiratory, and other non-accidental). RESULTS: We estimated that for the United States as a whole, total non-accidental mortality increased by 7.4% (95% CI: 1.6, 13.5; p = 0.011) and 6.7% (95% CI: 1.1, 12.6; p = 0.018) at 2- and 3-day lags, respectively, and by an average of 2.7% (95% CI: 0.4, 5.1; p = 0.023) over lags 0-5 compared with referent days. Significant associations with non-accidental mortality were estimated for California (lag 2 and 0-5 day) and Arizona (lag 3), for cardiovascular mortality in the United States (lag 2) and Arizona (lag 3), and for other non-accidental mortality in California (lags 1-3 and 0-5). CONCLUSIONS: Dust storms are associated with increases in lagged non-accidental and cardiovascular mortality. Citation: Crooks JL, Cascio WE, Percy MS, Reyes J, Neas LM, Hilborn ED. 2016. The association between dust storms and daily non-accidental mortality in the United States, 1993-2005. Environ Health Perspect 124:1735-1743; http://dx.doi.org/10.1289/EHP216.

Association between satellite-based estimates of long-term PM2.5 exposure and coronary artery disease.

BACKGROUND: Epidemiological studies have identified associations between long-term PM2.5 exposure and cardiovascular events, though most have relied on concentrations from central-site air quality monitors. METHODS: We utilized a cohort of 5679 patients who had undergone cardiac catheterization at Duke University between 2002-2009 and resided in North Carolina. We used estimates of daily PM2.5 concentrations for North Carolina during the study period based on satellite derived Aerosol Optical Depth (AOD) measurements and PM2.5 concentrations from ground monitors, which were spatially resolved with a 10×10km resolution, matched to each patient's residential address and averaged for the year prior to catheterization. The Coronary Artery Disease (CAD) index was used to measure severity of CAD; scores >23 represent a hemodynamically significant coronary artery lesion in at least one major coronary vessel. Logistic regression modeled odds of having CAD or an MI with each 1µg/m(3) increase in annual average PM2.5, adjusting for sex, race, smoking status and socioeconomic status. RESULTS: In adjusted models, a 1µg/m(3) increase in annual average PM2.5 was associated with an 11.1% relative increase in the odds of significant CAD (95% CI: 4.0-18.6%) and a 14.2% increase in the odds of having a myocardial infarction (MI) within a year prior (95% CI: 3.7-25.8%). CONCLUSIONS: Satellite-based estimates of long-term PM2.5 exposure were associated with both coronary artery disease (CAD) and incidence of myocardial infarction (MI) in a cohort of cardiac catheterization patients.