Search

Background: Exposure to fine particulate matter (<2.5 um, particulate matter with an aerodynamic diameter <2.5 microns [PM 2.5 ]) has been implicated in atherogenesis. Limited data in animal studies suggest that PM 2.5 exposure leads to myocardial fibrosis and increased incidence of heart failure (HF). Whether PM 2.5 is associated with adverse outcomes in patients with preexisting HF has not been widely studied., Methods and Results: In this retrospective cohort study, Medicare patients hospitalized with first HF between 2013 and 2020 were identified from the Medicare Provider Analysis and Review Part A 100% files. Patients were linked with integrated estimates of ambient PM 2.5 obtained at 1×1 km using the zip code of participants' residence. The study outcomes were all-cause death, HF, and all-cause readmissions burden. A total of 2 599 525 patients were included in this study, with 6 321 731 person-years of follow-up. Mean PM 2.5 was 7.3±1.7 μg/m 3 . Each interquartile range of PM 2.5 was associated with 0.9% increased hazard of all-cause death, 4.5% increased hazard of first HF readmission, 3.1% increased risk of HF hospitalization burden, and 5.2% increase in all-cause readmission burden, after adjusting for 11 sociodemographic and medical factors. Subgroup analyses showed that the effects were more pronounced at levels <7 μg/m 3 and in patients aged <75 years, Asians, and those residing in rural areas., Conclusions: Ambient air pollution is associated with higher risk of adverse events in Medicare beneficiaries with established HF. These associations persist below the National Air Quality Standards (12 μg/m 3 ), supporting that no threshold effect exists for health effects of air pollution exposure.

This randomized crossover trial sought to determine whether wearing a high-efficiency particulate-filtering respirator (PFR) improves cardiovascular function over 48 h among healthy college students in Tehran. This trial was conducted from February 14th to 23rd, 2019 and twenty-six participants completed two 48-h intervention periods. Brachial blood pressure (BP) measured by 24-h ambulatory monitoring was the primary health outcome. Secondary outcomes included 48-h heart rate variability (HRV) indices, high-sensitive cardiac troponin (hs-TnT) and other biomarkers. The participants wore the PFR between 10.2 and 11.1 h while awake during the interventions. More than 80% of participants reported increased respiratory resistance while wearing the PFR due to a lack of an exhalation valve. There were no significant differences in brachial BP levels between subjects who wore PFR respirator and those did not. Except for high frequency (HF) power and heart rate (HR), no significant differences between interventions were observed for other HRV metrics. Wearing the PFR led to an increase of 66.0 ms 2 (95% confidence interval [CI], 9.6-110.5) and 79.6 ms 2 (95% CI, 19.0-140.1) in HF power during the first day when the two groups of participants wore the PFR. Night-time HR was significantly increased during the PFR intervention period. Other secondary outcomes were not significantly different between interventions. It is plausible that incomplete exposure reduction due to wearing the PFR less than half of the time or increased respiratory resistance mitigated potential health benefits. Additional trials are warranted to validate the CV protection of wearing PFRs in heavily-polluted cities., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Exposure to traffic-related air pollution (TRAP) may contribute to increased prevalence of hypertension and elevated blood pressure (BP) for residents of near-highway neighborhoods. Relatively few studies have investigated the effects of reducing TRAP exposure on short-term changes in BP. We assessed whether reducing indoor TRAP concentrations by using stand-alone high-efficiency particulate arrestance (HEPA) filters and limiting infiltration through doors and windows effectively prevented acute (ie, over a span of hours) increases in BP. Using a 3-period crossover design, 77 participants were randomized to attend three 2-hour-long exposure sessions separated by 1-week washout periods. Each participant was exposed to high, medium, and low TRAP concentrations in a room near an interstate highway. Particle number concentrations, black carbon concentrations, and temperature were monitored continuously. Systolic BP (SBP), diastolic BP, and heart rate were measured every 10 minutes. Outcomes were analyzed with a linear mixed model. The primary outcome was the change in SBP from 20 minutes from the start of exposure. SBP increased with exposure duration, and the amount of increase was related to the magnitude of exposure. The mean change in SBP was 0.6 mm Hg for low exposure (mean particle number and black carbon concentrations, 2500 particles/cm 3 and 149 ng/m 3 ), 1.3 mm Hg for medium exposure (mean particle number and black carbon concentrations, 11 000 particles/cm 3 and 409 ng/m 3 ), and 2.8 mm Hg for high exposure (mean particle number and black carbon concentrations, 30 000 particles/cm 3 and 826 ng/m 3 ; linear trend P =0.019). There were no statistically significant differences in the secondary outcomes, diastolic BP, or heart rate. In conclusion, reducing indoor concentrations of TRAP was effective in preventing acute increases in SBP.

Fine particulate matter <2.5 µm (PM 2.5 ) air pollution is implicated in global mortality, especially from cardiovascular causes. A large body of evidence suggests a link between PM 2.5 and elevation in blood pressure (BP), with the latter implicated as a potential mediator of cardiovascular events. We sought to determine if the outcomes of intensive BP lowering (systolic BP <120 mm Hg) on cardiovascular events are modified by PM 2.5 exposure in the SPRINT (Systolic BP Intervention Trial). We linked annual PM 2.5 exposure estimates derived from an integrated model to subjects participating in SPRINT. We evaluated the effect of intensive BP lowering by PM 2.5 exposure on the primary outcome in SPRINT using cox-proportional hazard models. A total of 9286 participants were linked to PM 2.5 levels (mean age 68±9 years). Intensive BP-lowering decreased risk of the primary outcome more among patients exposed to higher PM 2.5 ( P interaction =0.047). The estimate for lowering of primary outcome was numerically lower in the highest than in the lower quintiles. The benefits of intensive BP-lowering were larger among patients chronically exposed to PM 2.5 levels above US National Ambient Air Quality Standards of 12 µg/m 3 (hazard ratio, 0.47 [95% CI, 0.29-0.74]) compared with those living in cleaner locations (hazard ratio, 0.81 [95% CI, 0.68-0.97]), P interaction =0.037. This exploratory nonprespecified post hoc analysis of SPRINT suggests that the benefits of intensive BP lowering on the primary outcome was greater in patients exposed to higher PM 2.5 , suggesting that the magnitude of benefit may depend upon the magnitude of antecedent PM 2.5 exposure.

Ambient air pollution due to particulate matter ≤2.5 μ is the leading environmental risk factor contributing to global mortality, with a preponderant majority of these deaths attributable to atherosclerotic cardiovascular disease (ASCVD) causes such as stroke and myocardial infarction. Epidemiological studies in humans have provided refined estimates of exposure risk, with evidence suggesting that risk association with particulate matter ≤2.5 levels and ASCVD continues at levels well below air quality guidelines in North America and Europe. Mechanistic studies in animals and humans have provided a framework of understanding of the duration and pathways by which air pollution exposure may predispose to atherosclerosis. Although acute exposure to particulate matter ≤2.5 is associated with oxidative stress and inflammation, system transmission of signals from the lungs to extrapulmonary sites may involve direct translocation of components, biologic intermediates, and autonomic nervous system activation. End-organ effector pathways such as endothelial barrier disruption/dysfunction, thrombosis, vasoconstriction/increased blood pressure, and plaque instability, may contribute to ASCVD. The strength of the association of air pollution with ASCVD offers an opportunity to mitigate its consequences. Although elimination of anthropogenic sources of air pollution with a switch to clean energy provides the ultimate solution, this may not be possible in the interim and may require personal protection efforts and an integrated approach to managing risk posed by air pollution for ASCVD.

Fine particulate air pollution <2.5 μm in diameter (PM 2.5 ) is a major environmental threat to global public health. Multiple national and international medical and governmental organizations have recognized PM 2.5 as a risk factor for cardiopulmonary diseases. A growing body of evidence indicates that several personal-level approaches that reduce exposures to PM 2.5 can lead to improvements in health endpoints. Novel and forward-thinking strategies including randomized clinical trials are important to validate key aspects (e.g., feasibility, efficacy, health benefits, risks, burden, costs) of the various protective interventions, in particular among real-world susceptible and vulnerable populations. This paper summarizes the discussions and conclusions from an expert workshop, Reducing the Cardiopulmonary Impact of Particulate Matter Air Pollution in High Risk Populations, held on May 29 to 30, 2019, and convened by the National Institutes of Health, the U.S. Environmental Protection Agency, and the U.S. Centers for Disease Control and Prevention., Competing Interests: Author Disclosures The views expressed in this paper are those of the authors and do not necessarily represent the views of the National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI), National Institute of Environmental Health Sciences, Environmental Protection Agency, Centers for Disease Control and Prevention, or the United States Department of Health and Human Services. Drs. Bhatt and Brooks served as co-chairs of this NIH/NHLBI/EPA/CDC Expert Workshop on air pollution. Dr. Newman has received grant support from the NIH (K23HL125991). Dr. Bhatt has served on the advisory board of Cardax, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, Level Ex, Medscape Cardiology, PhaseBio, PLx Pharma, and Regado Biosciences; has served on the Board of Directors for Boston VA Research Institute, Society of Cardiovascular Patient Care, and TobeSoft; has served as chair of the American Heart Association Quality Oversight Committee, NCDR-ACTION Registry Steering Committee, and VA CART Research and Publications Committee; has served on the data monitoring committees of Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Cleveland Clinic (including for the ExCEED trial, funded by Edwards), Contego Medical (Chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi-Sankyo), and the Population Health Research Institute; has received honoraria from the American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Vice-Chair, ACC Accreditation Committee), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (Editor-in-Chief, Harvard Heart Letter), Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor-in-Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), K2P (Co-Chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), Slack Publications (Chief Medical Editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), and WebMD (CME steering committees); has served as Deputy Editor of Clinical Cardiology; has received research funding from Abbott, Afimmune, Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardax, Chiesi, CSL Behring, Eisai, Ethicon, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Idorsia, Ironwood, Ischemix, Lexicon, Lilly, Medtronic, Pfizer, PhaseBio, PLx Pharma, Regeneron, Roche, Sanofi, Synaptic, and The Medicines Company; has received royalties from Elsevier (Editor, Cardiovascular Intervention: A Companion to Braunwald’s Heart Disease); has served as site co-investigator for Biotronik, Boston Scientific, CSI, St. Jude Medical (now Abbott), and Svelte; served as a trustee of the American College of Cardiology; and has received unfunded research from FlowCo, Merck, Novo Nordisk, and Takeda. Dr. Balmes is the Physician Member of the California Air Resources Board. Dr. Brook has received an investigator-initiated grant from RB, Inc.; and has received support from NIH awards 2R01-ES019616 and 2R01-NR014484. Dr. Brauer has received grant support from the Health Effects Institute, the Canadian Institutes of Health Research, The Terry Fox Research Institute, and the Wellcome Trust. Dr. Hansel has received grant support from the NIH, EPA, NHLBI, National Institute of Environmental Health Sciences, COPD Foundation, and Boehringer Ingelheim; and has participated in advisory boards for GlaxoSmithKline, AstraZeneca, and Mylan. Dr. Hernandez has received research funding from American Regent, AstraZeneca, Boehringer Ingelheim, Merck, Novartis, and Verily; and has served as a consultant for Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Merck, Novartis, and Relypsa. Dr. Hochman has received grant support from the NHLBI for the ISCHEMIA Trial, for which there were in-kind donations for participating sites from Abbott Vascular, Medtronic, Inc., St. Jude Medical, Inc., Volcano Corporation, Arbor Pharmaceuticals, AstraZeneca Pharmaceuticals, Merck Sharp & Dohme Corp., Omron Healthcare, Inc., and Amgen Inc; has received financial donations from Arbor Pharmaceuticals and AstraZeneca Pharmaceuticals; and has served as PI for the ZEDS (Long-term Suppressive Valacyclovir Treatment for Herpes Zoster Ophthalmicus) Study, supported by NIH/National Eye Institute. Dr. Kaufman has received grant support from the National Institutes of Health and the Environmental Protection Agency. Dr. Malik is supported by the NHLBI of the NIH under Award Number T32HL110837. Dr. Peel has received research funding from the NIH (1UM1HL134590 and R01ES023688). Dr. Rajagopalan has received research funding from the NIH; and has served as a consultant to Novo Nordisk, Takeda, GlaxoSmithKline, and AstraZeneca. Dr. Zhang’s research has been partly funded by the NIH, Underwriter’s Laboratory, and Natural Science Foundation of China (via Duke Kunshan University in China). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2020 American College of Cardiology Foundation. All rights reserved.)

Since the publication of the last American Heart Association scientific statement on air pollution and cardiovascular disease in 2010, unequivocal evidence of the causal role of fine particulate matter air pollution (PM 2.5 , or particulate matter ≤2.5 μm in diameter) in cardiovascular disease has emerged. There is a compelling case to provide the public with practical personalized approaches to reduce the health effects of PM 2.5 . Such interventions would be applicable not only to individuals in heavily polluted countries, high-risk or susceptible individuals living in cleaner environments, and microenvironments with higher pollution exposures, but also to those traveling to locations with high levels of PM 2.5 . The overarching motivation for this document is to summarize the current evidence supporting personal-level strategies to prevent the adverse cardiovascular effects of PM 2.5 , guide the use of the most proven/viable approaches, obviate the use of ineffective measures, and avoid unwarranted interventions. The significance of this statement relates not only to the global importance of PM 2.5 , but also to its focus on the most tested interventions and viable approaches directed at particulate matter air pollution. The writing group sought to provide expert consensus opinions on personal-level measures recognizing the current uncertainty and limited evidence base for many interventions. In doing so, the writing group acknowledges that its intent is to assist other agencies charged with protecting public health, without minimizing the personal choice considerations of an individual who may decide to use these interventions in the face of ongoing air pollution exposure.

Purpose: Fine particulate matter (PM2.5) air pollution is a leading risk factor for cardiovascular disease. Even low levels common to millions of Americans pose health risks. However, no study has tested protective measures such as in-home portable air cleaners (PACs) among at-risk cardiac patients. We conducted a pilot phase of the Cardiac Rehabilitation Air Filter Trial (CRAFT)-a randomized, double-blind, crossover study of outpatient cardiac rehabilitation patients at Michigan Medicine., Methods: During a routine visit, patients were provided with 2 PACs to run continuously for 5 d in both the bedroom and the main living space. PACs were randomized as active (with HEPA filter) versus sham. On day 4, subjects wore a personal PM2.5 monitor for 24-hr without activity restrictions. After a 1-wk washout, patients crossed over to the opposite mode., Results: Patients (n = 20; 4 women) were elderly (70.8 ± 9.6 yr) nonsmokers with cardiovascular disease living near the facility (10.7 ± 6.0 mi). Compared with sham, active in-home PAC use significantly lowered personal-level 24-hr PM2.5 exposures by 43.8% (-12.2 μg·m; 95% CI, -24.2 to -0.2). Sensitivity analyses corroborated the reductions in most patients., Conclusion: An inexpensive in-home PAC can effectively lower personal PM2.5 exposures in cardiac patients. These benefits occurred even in a region with overall good air quality and if maintained over the long-term could translate into major reductions in cardiovascular events.

Household air pollution from combustion of solid fuels is an important risk factor for morbidity and mortality, causing an estimated 2.6 million premature deaths globally in 2016. Self-reported health symptoms are a meaningful measure of quality of life, however, few studies have evaluated symptoms and quantitative measures of exposure to household air pollution. We assessed the cross-sectional association of self-reported symptoms and exposures to household air pollution among women in rural Honduras using stove type (traditional [n = 76]; cleaner-burning Justa [n = 74]) and 24-hour average personal and kitchen fine particulate matter (PM 2.5 ) concentrations. The odds of prevalent symptoms were higher among women using traditional stoves vs Justa stoves (e.g. headache: odds ratio = 2.23; 95% confidence interval = 1.13-4.39). Associations between symptoms and measured PM 2.5 were generally consistent with the null. These results add to the evidence suggesting reduced exposures and better health-related quality of life among women using cleaner-burning biomass stoves.

Background: The risk for cardiovascular events increases within hours of near-roadway exposures. We aimed to determine the traffic-related air pollution (TRAP) and biological mechanisms involved and if reducing particulate matter <2.5 µm (PM2.5) inhalation is protective., Methods: Fifty healthy-adults underwent multiple 2-hour near-roadway exposures (Tuesdays to Fridays) in Ann Arbor during 2 separate weeks (randomized to wear an N95 respirator during 1 week). Monday both weeks, participants rested 2 hours in an exam room (once wearing an N95 respirator). Brachial blood pressure, aortic hemodynamics, and heart rate variability were repeatedly measured during exposures. Endothelial function (reactive hyperemia index [RHI]) was measured post-exposures (Thursdays). Black carbon (BC), total particle count (PC), PM2.5, noise and temperature were measured throughout exposures., Results: PM2.5 (9.3 ± 7.7 µg/m3), BC (1.3 ± 0.6 µg/m3), PC (8,375 ± 4,930 particles/cm3) and noise (69.2 ± 4.2 dB) were higher (P values <0.01) and aortic hemodynamic parameters trended worse while near-roadway (P values<0.15 vs. exam room). Other outcomes were unchanged. Aortic hemodynamics trended towards improvements with N95 respirator usage while near-roadway (P values<0.15 vs. no-use), whereas other outcomes remained unaffected. Higher near-roadway PC and BC exposures were associated with increases in aortic augmentation pressures (P values<0.05) and trends toward lower RHI (P values <0.2). N95 respirator usage did not mitigate these adverse responses (nonsignificant pollutant-respirator interactions). Near-roadway outdoor-temperature and noise were also associated with cardiovascular changes., Conclusions: Exposure to real-world combustion-derived particulates in TRAP, even at relatively low concentrations, acutely worsened aortic hemodynamics. Our mixed findings regarding the health benefits of wearing N95 respirators support that further studies are needed to validate if they adequately protect against TRAP given their growing worldwide usage., (© American Journal of Hypertension, Ltd 2019. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background Exposure to air pollution from solid fuel used in residential cookstoves is considered a leading environmental risk factor for disease globally, but evidence for this relationship is largely extrapolated from literature on smoking, secondhand smoke, and ambient fine particulate matter ( PM 2.5 ). Methods and Results We conducted a controlled human-exposure study (STOVES [the Subclinical Tests on Volunteers Exposed to Smoke] Study) to investigate acute responses in blood pressure following exposure to air pollution emissions from cookstove technologies. Forty-eight healthy adults received 2-hour exposures to 5 cookstove treatments (three stone fire, rocket elbow, fan rocket elbow, gasifier, and liquefied petroleum gas), spanning PM 2.5 concentrations from 10 to 500 μg/m 3 , and a filtered air control (0 μg/m 3 ). Thirty minutes after exposure, systolic pressure was lower for the three stone fire treatment (500 μg/m 3 PM 2.5 ) compared with the control (-2.3 mm Hg; 95% CI, -4.5 to -0.1) and suggestively lower for the gasifier (35 μg/m 3 PM 2.5 ; -1.8 mm Hg; 95% CI , -4.0 to 0.4). No differences were observed at 3 hours after exposure; however, at 24 hours after exposure, mean systolic pressure was 2 to 3 mm Hg higher for all treatments compared with control except for the rocket elbow stove. No differences were observed in diastolic pressure for any time point or treatment. Conclusions Short-term exposure to air pollution from cookstoves can elicit an increase in systolic pressure within 24 hours. This response occurred across a range of stove types and PM 2.5 concentrations, raising concern that even low-level exposures to cookstove air pollution may pose adverse cardiovascular effects.

The adverse health effects of fine particulate matter (PM < 2.5 μm in diameter [PM 2.5 ]) air pollution are well-documented. There is a growing body of evidence that high-efficiency particulate arrestance (HEPA) filtration can reduce indoor PM 2.5 concentrations and deliver some health benefits via the reduction of exposure to PM. However, few studies have tested the ability of portable air filtration systems to lower overall personal-level PM 2.5 exposures. The Reducing Air Pollution in Detroit Intervention Study (RAPIDS) was designed to evaluate cardiovascular health benefits and personal PM 2.5 exposure reductions via indoor portable air filtration systems among senior citizens in Detroit, Michigan. We evaluated the utility of two commercially available high-efficiency (HE: true-HEPA) and low-efficiency (LE: HEPA-type) indoor air filtration to reduce indoor PM 2.5 concentrations and personal PM 2.5 exposures for 40 participants in a double-blinded randomized crossover intervention. Each participant was subjected to three intervention scenarios: HE, LE, or no filter (control) of three consecutive days each, during which personal, indoor, and outdoor PM 2.5 concentrations were measured daily. For mean indoor PM 2.5 concentrations, we observed 60 and 52% reductions using HE and LE filters, respectively, relative to no filtration. Personal PM 2.5 exposures were reduced by 53 and 31% using HE and LE filters, respectively, when compared with the control scenario. To our knowledge, this is the first indoor air filtration intervention study to examine the effectiveness of both HE and LE filters in reducing personal PM 2.5 exposures.

Importance: Fine particulate matter (smaller than 2.5 μm) (PM2.5) air pollution is a major global risk factor for cardiovascular (CV) morbidity and mortality. Few studies have tested the benefits of portable air filtration systems in urban settings in the United States., Objective: To investigate the effectiveness of air filtration at reducing personal exposures to PM2.5 and mitigating related CV health effects among older adults in a typical US urban location., Design, Setting, and Participants: This randomized, double-blind crossover intervention study was conducted from October 21, 2014, through November 4, 2016, in a low-income senior residential building in Detroit, Michigan. Forty nonsmoking older adults were enrolled, with daily CV health outcome and PM2.5 exposure measurements., Interventions: Participants were exposed to the following three 3-day scenarios separated by 1-week washout periods: unfiltered air (sham filtration), low-efficiency (LE) high-efficiency particulate arrestance (HEPA)-type filtered air, and high-efficiency (HE) true-HEPA filtered air using filtration systems in their bedroom and living room., Main Outcomes and Measures: The primary outcome was brachial blood pressure (BP). Secondary outcomes included aortic hemodynamics, pulse-wave velocity, and heart rate variability. Exposures to PM2.5 were measured in the participants' residences and by personal monitoring., Results: The 40 participants had a mean (SD) age of 67 (8) years (62% men). Personal PM2.5 exposures were significantly reduced by air filtration from a mean (SD) of 15.5 (10.9) μg/m3 with sham filtration to 10.9 (7.4) μg/m3 with LE fitration and 7.4 (3.3) μg/m3 with HE filtration. Compared with sham filtration, any filtration for 3 days decreased brachial systolic and diastolic BP by 3.2 mm Hg (95% CI, -6.1 to -0.2 mm Hg) and 1.5 mm Hg (95% CI, -3.3 to 0.2 mm Hg), respectively. A continuous decrease occurred in systolic and diastolic BP during the 3-day period of LE filtration, with a mean of 3.4 mm Hg (95% CI, -6.8 to -0.1 mm Hg) and 2.2 mm Hg (95% CI, -4.2 to -0.3 mm Hg), respectively. For HE filtration, systolic and diastolic BP decreased by 2.9 mm Hg (95% CI, -6.2 to 0.5 mm Hg) and 0.8 mm Hg (95% CI, -2.8 to 1.2 mm Hg), respectively. Most secondary outcomes were not significantly improved., Conclusions and Relevance: Results of this study showed that short-term use of portable air filtration systems reduced personal PM2.5 exposures and systolic BP among older adults living in a typical US urban location. The use of these relatively inexpensive systems is potentially cardioprotective against PM2.5 exposures and warrants further research., Trial Registration: ClinicalTrials.gov identifier: NCT03334565.

Fine particulate matter (PM 2.5 ) air pollution and environmental temperatures influence cardiovascular morbidity and mortality. Recent evidence suggests that several air pollutants can promote dyslipidemia; however, the impact of ambient PM 2.5 and temperature on high-density lipoprotein (HDL) function remains unclear. We hypothesized that daily exposures to higher levels of ambient PM 2.5 and colder outdoor temperatures would impair HDL functionality. Lipoproteins, serum cholesterol efflux capacity (CEC), and HDL oxidation markers were measured twice in 50 healthy adults (age 32.1 ± 9.6 years) living in southeast Michigan and associated with ambient and personal-level exposures using mixed models. Although previous 7-day mean outdoor temperature (4.4 ± 9.8°C) and PM 2.5 levels (9.1 ± 1.8 µg/m 3 ) were low, higher ambient PM 2.5 exposures (per 10 µg/m 3 ) were associated with significant increases in the total cholesterol-to-HDL-C ratio (rolling average lag days 1 and 2) as well as reductions in CEC by -1.93% (lag day 5, p = 0.022) and -1.62% (lag day 6, p = 0.032). Colder outdoor temperatures (per 10°C) were also associated with decreases in CEC from -0.62 to -0.63% (rolling average lag days 5 and 7, p = 0.027 and 0.028). Previous 24-hour personal-level PM 2.5 and temperature exposures did not impact outcomes, nor were any exposures associated with changes in HDL-oxidation metrics. In conclusion, we provide the first evidence that ambient PM 2.5 (even at low levels) and outdoor temperatures may influence serum CEC, a critical antiatherosclerotic HDL function., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Fine particulate matter (PM2.5) air pollution is a leading cause of global cardiovascular mortality. A key mechanism may be PM2.5-induced blood pressure (BP) elevations. Whether consistent prohypertensive responses persist across the breadth of worldwide pollution concentrations has never been investigated., Methods: We evaluated the hemodynamic impact of short-term exposures to ambient PM2.5 in harmonized studies of healthy normotensive adults (4 BP measurements per participant) living in both a highly polluted (Beijing) and clean (Michigan) location., Results: Prior 7-day outdoor-ambient and 24-hour personal-level PM2.5 concentration averages were much higher in Beijing (86.7 ± 52.1 and 52.4 ± 79.2 µg/m3) compared to Michigan (9.1 ± 1.8 and 12.2 ± 17.0 µg/m3). In Beijing (n = 73), increased outdoor-ambient exposures (per 10 µg/m3) during the prior 1-7 days were associated with significant elevations in diastolic BP (0.15-0.17 mm Hg). In overweight adults (body mass index ≥25 kg/m2), significant increases in both systolic (0.34-0.44 mm Hg) and diastolic (0.22-0.66 mm Hg) BP levels were observed. Prior 24-hour personal-level exposures also significantly increased BP (0.41/0.61 mm Hg) in overweight participants. Conversely, low PM2.5 concentrations in Michigan (n = 50), on average within Air Quality Guidelines, were not associated with BP elevations., Conclusions: Our findings demonstrate that short-term exposures to ambient PM2.5 in a highly polluted environment can promote elevations in BP even among healthy adults. The fact that no adverse hemodynamic responses were observed in a clean location supports the key public health importance of international efforts to improve air quality as part of the global battle against hypertension.

Significance: Particulate matter (PM) air pollution is a leading cause of global cardiovascular morbidity and mortality. Understanding the biological action of PM is of particular importance in improvement of public health. Recent Advances: Both fine (PM <2.5 μM) and ultrafine particles (<0.1 μM) are widely believed to mediate their effects through redox regulated pathways. A rather simplistic graded ramp model of redox stress has been replaced by a more sophisticated understanding of the role of oxidative stress in signaling, and the realization that many of the observed effects may involve disruption and/or enhancement of normal endogenous redox signaling and induction of a potent immune-mediated response, through entrainment of multiple reactive oxygen species (ROS)., Critical Issues: The molecular events by which pulmonary oxidative stress in response to inhalational exposure to air pollution triggers inflammation, major ROS (e.g., superoxide, hydroxyl radical, nitric oxide, and peroxynitrite) generated in air pollution exposure, types of oxidative tissue damage in target organs, contributions of nonimmune and immune cells in inflammation, and the role of protective proteins (e.g., surfactant, proteins, and antioxidants) are highly complex and may differ depending on models and concomitant disease states., Future Directions: While the role of oxidative stress in the lung has been well demonstrated, the role of oxidative stress in mediating systemic effects especially in inflammation and injury processes needs further work. The role of antioxidant defenses with chronic exposure will also need further exploration. Antioxid. Redox Signal. 28, 797-818.

Ambient air pollution is an independent risk factor for cardiovascular diseases. However, the underlying mechanisms have yet to be fully elucidated. We performed a panel study on 65 nonsmoking patients with metabolic syndrome, with four repeated clinical visits between 2012 and 2013 in Beijing, China. Cardiac and central aortic hemodynamic parameters were measured by pulse wave analyses as subendocardial viability ratio, ejection duration, and central aortic pressure. We also calculated rate-pressure product parameter and collected peripheral blood for analyses. High levels of ambient particulate matter with diameter ≤10 and 2.5 μm (PM 10 and PM 2.5 ), black carbon, sulfur dioxide, and nitrogen dioxide were 121.3, 99.5, 6.5, 24.5, and 59.2 μg/m 3 , respectively. Short- to medium-term exposures to high levels of ambient air pollution adversely impacted central hemodynamics-derived surrogates of myocardial perfusion and oxygen demand. Each 10 μg/m 3 increase in PM 2.5 was associated with significant decreases of 0.67% (95% confidence interval: -2.84, -0.22) in subendocardial viability ratio at moving average 35 days (MA35) and an increase of 0.31 in rate-pressure product (95% confidence interval: 0.03, 0.59) at MA5. In conclusion, our results suggest that impaired myocardial perfusion and increased myocardial oxygen demand may play importantly mechanistic roles in air pollution-attributed cardiovascular diseases., (Copyright © 2017 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.)

Background: Survivors of acute myocardial infarction (AMI) are at increased risk of dying within several hours to days following exposure to elevated levels of ambient air pollution. Little is known, however, about the influence of long-term (months to years) air pollution exposure on survival after AMI., Objective: We conducted a population-based cohort study to determine the impact of long-term exposure to fine particulate matter ≤ 2.5 μm in diameter (PM2.5) on post-AMI survival., Methods: We assembled a cohort of 8,873 AMI patients who were admitted to 1 of 86 hospital corporations across Ontario, Canada in 1999-2001. Mortality follow-up for this cohort extended through 2011. Cumulative time-weighted exposures to PM2.5 were derived from satellite observations based on participants' annual residences during follow-up. We used standard and multilevel spatial random-effects Cox proportional hazards models and adjusted for potential confounders., Results: Between 1999 and 2011, we identified 4,016 nonaccidental deaths, of which 2,147 were from any cardiovascular disease, 1,650 from ischemic heart disease, and 675 from AMI. For each 10-μg/m3 increase in PM2.5, the adjusted hazard ratio (HR10) of nonaccidental mortality was 1.22 [95% confidence interval (CI): 1.03, 1.45]. The association with PM2.5 was robust to sensitivity analyses and appeared stronger for cardiovascular-related mortality: ischemic heart (HR10 = 1.43; 95% CI: 1.12, 1.83) and AMI (HR10 = 1.64; 95% CI: 1.13, 2.40). We estimated that 12.4% of nonaccidental deaths (or 497 deaths) could have been averted if the lowest measured concentration in an urban area (4 μg/m3) had been achieved at all locations over the course of the study., Conclusions: Long-term air pollution exposure adversely affects the survival of AMI patients., Citation: Chen H, Burnett RT, Copes R, Kwong JC, Villeneuve PJ, Goldberg MS, Brook RD, van Donkelaar A, Jerrett M, Martin RV, Brook JR, Kopp A, Tu JV. 2016. Ambient fine particulate matter and mortality among survivors of myocardial infarction: population-based cohort study. Environ Health Perspect 124:1421-1428; http://dx.doi.org/10.1289/EHP185., Competing Interests: The opinions, results, and conclusions reported in this paper do not necessarily represent the views of the Institute for Clinical Evaluative Sciences or the Ministry of Health and Long-term Care. The authors declare they have no actual or potential competing financial interests.

Background: Exposures to ambient particulate matter (PM) are associated with increased morbidity and mortality. PM2.5 (<2.5 μm) and ozone exposures have been shown to associate with carotid intima media thickness in humans. Animal studies support a causal relationship between air pollution and atherosclerosis and identified adverse PM effects on HDL functionality. We aimed to determine whether brief exposures to PM2.5 and/or ozone could induce effects on HDL anti-oxidant and anti-inflammatory capacity in humans., Methods: Subjects were exposed to fine concentrated ambient fine particles (CAP) with PM2.5 targeted at 150 μg/m(3), ozone targeted at 240 μg/m(3) (120 ppb), PM2.5 plus ozone targeted at similar concentrations, and filtered air (FA) for 2 h, on 4 different occasions, at least two weeks apart, in a randomized, crossover study. Blood was obtained before exposures (baseline), 1 h after and 20 h after exposures. Plasma HDL anti-oxidant/anti-inflammatory capacity and paraoxonase activity were determined. HDL anti-oxidant/anti-inflammatory capacity was assessed by a cell-free fluorescent assay and expressed in units of a HDL oxidant index (HOI). Changes in HOI (ΔHOI) were calculated as the difference in HOI from baseline to 1 h after or 20 h after exposures., Results: There was a trend towards bigger ΔHOI between PM2.5 and FA 1 h after exposures (p = 0.18) but not 20 h after. This trend became significant (p <0.05) when baseline HOI was lower (<1.5 or <2.0), indicating decreased HDL anti-oxidant/anti-inflammatory capacity shortly after the exposures. There were no significant effects of ozone alone or in combination with PM2.5 on the change in HOI at both time points. The change in HOI due to PM2.5 showed a positive trend with particle mass concentration (p = 0.078) and significantly associated with the slope of systolic blood pressure during exposures (p = 0.005)., Conclusions: Brief exposures to concentrated PM2.5 elicited swift effects on HDL anti-oxidant/anti-inflammatory functionality, which could indicate a potential mechanism for how particulate air pollution induces harmful cardiovascular effects.

Background: Clinical studies have shown that exposure to fine particulate matter (PM2.5) can increase insulin resistance and blood pressure. The epidemiologic evidence for an association of PM2.5 exposure with the incidence of type 2 diabetes or hypertension is inconsistent. Even a modest association would have great public health importance given the ubiquity of exposure and high prevalence of the conditions., Methods: We used Cox proportional hazards models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident type 2 diabetes and hypertension associated with exposure to PM2.5 in a large cohort of African American women living in 56 metropolitan areas across the US, using data from the Black Women's Health Study. Pollutant levels were estimated at all residential locations over follow-up with a hybrid model incorporating land use regression and Bayesian Maximum Entropy techniques., Results: During 1995 to 2011, 4,387 cases of diabetes and 9,570 cases of hypertension occurred. In models controlling for age, questionnaire cycle, and metro area, there were positive associations with diabetes (HR = 1.13, 95% CI = 1.04, 1.24) and hypertension (HR = 1.06, 95% CI = 1.00, 1.12) per interquartile range of PM2.5 (2.9 μg/m). Multivariable HRs, however, were 0.99 (95% CI = 0.90, 1.09) for diabetes and 0.99 (95% CI = 0.93, 1.06) for hypertension., Conclusions: Our results provide little support for an association of PM2.5 with diabetes or hypertension incidence.

Particulate matter (PM) air pollution is a leading global risk factor for cardiovascular mortality. Although exposure to fine PM <2.5 μm raises arterial blood pressure (BP), few studies have evaluated the impact of coarse PM which differs in size (2.5-10 μm), sources, and chemistry. Twenty-nine healthy adults (30.4 ± 8.2 years) underwent a randomized double-blind crossover study involving 2-hour exposures to concentrated ambient coarse PM (164.2 ± 80.4 μg/m(3)) at an urban location (Dearborn, Michigan) versus filtered air. Cardiovascular outcomes were measured during, immediately, and 2 hours after exposures. Both systolic (1.9 mm Hg; 95% confidence interval: 0.96, 2.8; P < .001) and diastolic (1.9 mm Hg; 95% confidence interval: 1.1, 2.7; P < .001) BP levels were higher throughout coarse PM compared with filtered air exposures by mixed-model analyses. Heart rate variability, endothelial function, and arterial compliance were not significantly affected. Brief exposure to coarse PM in an urban environment raises arterial BP. These findings add mechanistic support to the contention that coarse PM may be capable of promoting cardiovascular events., (Copyright © 2016 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.)

Background: Few studies examining the associations between long-term exposure to ambient air pollution and mortality have considered multiple pollutants when assessing changes in exposure due to residential mobility during follow-up., Objective: We investigated associations between cause-specific mortality and ambient concentrations of fine particulate matter (≤ 2.5 μm; PM2.5), ozone (O3), and nitrogen dioxide (NO2) in a national cohort of about 2.5 million Canadians., Methods: We assigned estimates of annual concentrations of these pollutants to the residential postal codes of subjects for each year during 16 years of follow-up. Historical tax data allowed us to track subjects' residential postal code annually. We estimated hazard ratios (HRs) for each pollutant separately and adjusted for the other pollutants. We also estimated the product of the three HRs as a measure of the cumulative association with mortality for several causes of death for an increment of the mean minus the 5th percentile of each pollutant: 5.0 μg/m3 for PM2.5, 9.5 ppb for O3, and 8.1 ppb for NO2., Results: PM2.5, O3, and NO2 were associated with nonaccidental and cause-specific mortality in single-pollutant models. Exposure to PM2.5 alone was not sufficient to fully characterize the toxicity of the atmospheric mix or to fully explain the risk of mortality associated with exposure to ambient pollution. Assuming additive associations, the estimated HR for nonaccidental mortality corresponding to a change in exposure from the mean to the 5th percentile for all three pollutants together was 1.075 (95% CI: 1.067, 1.084). Accounting for residential mobility had only a limited impact on the association between mortality and PM2.5 and O3, but increased associations with NO2., Conclusions: In this large, national-level cohort, we found positive associations between several common causes of death and exposure to PM2.5, O3, and NO2., Citation: Crouse DL, Peters PA, Hystad P, Brook JR, van Donkelaar A, Martin RV, Villeneuve PJ, Jerrett M, Goldberg MS, Pope CA III, Brauer M, Brook RD, Robichaud A, Menard R, Burnett RT. 2015. Ambient PM2.5, O3, and NO2 exposures and associations with mortality over 16 years of follow-up in the Canadian Census Health and Environment Cohort (CanCHEC). Environ Health Perspect 123:1180-1186; http://dx.doi.org/10.1289/ehp.1409276.

Objective: Fine particulate matter air pollution (PM2.5) and extreme temperatures have both been associated with alterations in blood pressure (BP). However, few studies have evaluated their joint haemodynamic actions among individuals at high risk for cardiovascular events., Methods: We assessed the effects of short-term exposures during the prior week to ambient PM2.5 and outdoor temperature levels on resting seated BP among 2078 patients enrolling into a cardiac rehabilitation programme at the University of Michigan (from 2003 to 2011) using multiple linear regression analyses adjusting for age, sex, BMI, ozone and the same-day alternate environmental factor (i.e. PM2.5 or temperature)., Results: Mean PM2.5 and temperature levels were 12.6 ± 8.2 μg/m and 10.3 ± 10.4°C, respectively. Each standard deviation elevation in PM2.5 concentration during lag days 4-6 was associated with significant increases in SBP (2.1-3.5 mmHg) and DBP (1.7-1.8 mmHg). Conversely, higher temperature levels (per 10.4°C) during lag days 4-6 were associated with reductions in both SBP (-3.6 to -2.3 mmHg) and DBP (-2.5 to -1.8 mmHg). There was little evidence for consistent effect modification by other covariates (e.g. demographics, seasons, medication usage)., Conclusion: Short-term exposures to PM2.5, even at low concentrations within current air quality standards, are associated with significant increases in BP. Contrarily, higher ambient temperatures prompt the opposite haemodynamic effect. These findings demonstrate that both ubiquitous environmental exposures have clinically meaningful effects on resting BP among high-risk cardiac patients.

Short-term exposure to particulate matter (PM) is associated with increased blood pressure (BP) in epidemiological studies. Understanding the impact of specific PM components on BP is essential in developing effective risk-reduction strategies. We investigated the association between endotoxin and β-1,3-d-Glucan-two major biological PM components-and BP. We also examined whether vascular endothelial growth factor, a vasodilatory inflammatory marker, modified these associations. We conducted a single-blind, randomized, crossover trial of controlled human exposure to concentrated ambient particles with 50 healthy adults. Particle-associated-endotoxin and β-1,3-d-Glucan were sampled using polycarbonate-membrane-filters. Supine resting systolic BP and diastolic BP were measured pre-, 0.5-hour post-, and 20-hour postexposure. Urine vascular endothelial growth factor concentration was determined using enzyme-linked immunosorbant assay and creatinine-corrected. Exposures to endotoxin and β-1,3-d-Glucan for 130 minutes were associated with increases in BPs: at 0.5-hour postexposure, every doubling in endotoxin concentration was associated with 1.73 mm Hg higher systolic BP (95% confidence interval, 0.28, 3.18; P=0.02) and 2.07 mm Hg higher diastolic BP (95% confidence interval, 0.74, 3.39; P=0.003); every doubling in β-1,3-d-Glucan concentration was associated with 0.80 mm Hg higher systolic BP (95% confidence interval, -0.07, 1.67; P=0.07) and 0.88 mm Hg higher diastolic BP (95% confidence interval, 0.09, 1.66; P=0.03). Vascular endothelial growth factor rose after concentrated ambient particle endotoxin exposure and attenuated the association between endotoxin and 0.5-hour postexposure diastolic BP (Pinteraction=0.02). In healthy adults, short-term endotoxin and β-1,3-d-Glucan exposures were associated with increased BP. Our findings suggest that the biological PM components contribute to PM-related cardiovascular outcomes, and postexposure vascular endothelial growth factor elevation might be an adaptive response that attenuates these effects., (© 2015 American Heart Association, Inc.)

Objective: Fine particulate matter (PM2.5) air pollution and variations in ambient temperature have been linked to increased cardiovascular morbidity and mortality. However, no large-scale study has assessed their effects on directly measured aerobic functional capacity among high-risk patients., Methods: Using a cross-sectional observational design, we evaluated the effects of ambient PM2.5 and temperature levels over 7 days on cardiopulmonary exercise test results performed among 2078 patients enrolling into a cardiac rehabilitation programme at the University of Michigan (from January 2003 to August 2011) using multiple linear regression analyses (controlling for age, sex, body mass index)., Results: Peak exercise oxygen consumption was significantly decreased by approximately 14.9% per 10 μg/m(3) increase in ambient PM2.5 levels (median 10.7 μg/m(3), IQR 10.1 μg/m(3)) (lag days 6-7). Elevations in PM2.5 were also related to decreases in ventilatory threshold (lag days 5-7) and peak heart rate (lag days 2-3) and increases in peak systolic blood pressure (lag days 4-5). A 10°C increase in temperature (median 10.5°C, IQR 17.5°C) was associated with reductions in peak exercise oxygen consumption (20.6-27.3%) and ventilatory threshold (22.9-29.2%) during all 7 lag days. In models including both factors, the outcome associations with PM2.5 were attenuated whereas the effects of temperature remained significant., Conclusions: Short-term elevations in ambient PM2.5, even at low concentrations within current air quality standards, and/or higher temperatures were associated with detrimental changes in aerobic exercise capacity, which can be linked to a worse quality of life and cardiovascular prognosis among cardiac rehabilitation patients., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Although fine particulate matter (PM) air pollution <2.5 μm in aerodynamic diameter (PM2.5) is a leading cause of global morbidity and mortality, the potential health effects of coarse PM (2.5-10 μm in aerodynamic diameter; PM10-2.5) remain less clearly understood. We aimed to elucidate the components within coarse PM most likely responsible for mediating these hemodynamic alterations. Thirty-two healthy adults (25.9 ± 6.6 years) were exposed to concentrated ambient coarse PM (CAP) (76.2 ± 51.5 μg/m(3)) and filtered air (FA) for 2 h in a rural location in a randomized double-blind crossover study. The particle constituents (24 individual elements, organic and elemental carbon) were analyzed from filter samples and associated with the blood pressure (BP) and heart rate (HR) changes occurring throughout CAP and FA exposures in mixed model analyses. Total coarse PM mass along with most of the measured elements were positively associated with similar degrees of elevations in both systolic BP and HR. Conversely, total PM mass was unrelated, whereas only two elements (Cu and Mo) were positively associated with and Zn was inversely related to diastolic BP changes during exposures. Inhalation of coarse PM from a rural location rapidly elevates systolic BP and HR in a concentration-responsive manner, whereas the particulate composition does not appear to be an important determinant of these responses. Conversely, exposure to certain PM elements may be necessary to trigger a concomitant increase in diastolic BP. These findings suggest that particulate mass may be an adequate metric of exposure to predict some, but not all, hemodynamic alterations induced by coarse PM mass.

The objective was to explore associations of chemical components and source factors of ambient fine particulate matter (aerodynamic diameter ≤ 2.5 μm; PM2.5) with cardiovascular (CV) changes following same-day exposure to ambient PM2.5. Twenty-five healthy adults living in rural Michigan were exposed to ambient air in an urban/industrial community for 4 to 5 h daily for five consecutive days. CV health outcomes were measured 1-2 h post exposure. Contributing emission sources were identified via positive matrix factorization. We examined associations between PM2.5 mass, composition and source factors, and same-day changes in CV outcomes using mixed-model analyses. PM2.5 mass (10.8 ± 6.8 μg/m(3)), even at low ambient levels, was significantly associated with increased heart rate (HR). Trace elements as well as secondary aerosol, diesel/urban dust and iron/steel manufacturing factors potentially explained the HR changes. However, trace element analysis demonstrated additional associations with other CV responses including changes in blood pressure (BP), arterial compliance, autonomic balance and trends toward reductions in endothelial function. Two factors were related to BP changes (diesel/urban dust, motor vehicle) and trends toward impaired endothelial function (diesel/urban dust). This study indicates composition of PM2.5 and its sources may contribute to CV health effects independently of PM2.5 mass.

Rationale: Growing evidence suggests that long-term exposure to fine particulate matter (PM2.5) air pollution contributes to risk of cardiovascular disease (CVD) morbidity and mortality. There is uncertainty about who are most susceptible. Individuals with underlying cardiometabolic disorders, including hypertension, diabetes mellitus, and obesity, may be at greater risk. PM2.5 pollution may also contribute to cardiometabolic disorders, augmenting CVD risk., Objective: This analysis evaluates relationships between long-term PM2.5 exposure and cardiometabolic disease on risk of death from CVD and cardiometabolic conditions., Methods and Results: Data on 669 046 participants from the American Cancer Society Cancer Prevention Study II cohort were linked to modeled PM2.5 concentrations at geocoded home addresses. Cox proportional hazards regression models were used to estimate adjusted hazards ratios for death from CVD and cardiometabolic diseases based on death-certificate information. Effect modification by pre-existing cardiometabolic risk factors on the PM2.5-CVD mortality association was examined. PM2.5 exposure was associated with CVD mortality, with the hazards ratios (95% confidence interval) per 10 μg/m(3) increase in PM2.5 equal to 1.12 (1.10-1.15). Deaths linked to hypertension and diabetes mellitus (mentioned on death certificate as either primary or contributing cause of death) were also associated with PM2.5. There was no consistent evidence of effect modification by cardiometabolic disease risk factors on the PM2.5-CVD mortality association., Conclusions: Pollution-induced CVD mortality risk is observed for those with and without existing cardiometabolic disorders. Long-term exposure may also contribute to the development or exacerbation of cardiometabolic disorders, increasing risk of CVD, and cardiometabolic disease mortality., (© 2014 American Heart Association, Inc.)

Background: Prior experimental and epidemiologic data support a link between exposure to fine ambient particulate matter (<2.5 μm in aerodynamic diameter, PM2.5) and development of insulin resistance/Type II diabetes mellitus (Type II DM). We investigated the role of hypothalamic inflammation in PM2.5-mediated diabetes development., Methods: KKay mice, a genetically susceptible model of Type II DM, were assigned to either concentrated PM2.5 or filtered air (FA) for 4-8 weeks via a versatile aerosol concentrator and exposure system, or administered intra-cerebroventricular with either IKKβ inhibitor (IMD-0354) or TNFα antibody (infliximab) for 4-5 weeks simultaneously with PM2.5 exposure. Glucose tolerance, insulin sensitivity, oxygen consumption and heat production were evaluated. At euthanasia, blood, spleen, visceral adipose tissue and hypothalamus were collected to measure inflammatory cells using flow cytometry. Standard immunohistochemical methods and quantitative PCR were used to assess targets of interest., Results: PM2.5 exposure led to hyperglycemia and insulin resistance, which was accompanied by increased hypothalamic IL-6, TNFα, and IKKβ mRNA expression and microglial/astrocyte reactivity. Targeting the NFκB pathway with intra-cerebroventricular administration of an IKKβ inhibitor [IMD-0354, n = 8 for each group)], but not TNFα blockade with infliximab [(n = 6 for each group], improved glucose tolerance, insulin sensitivity, rectified energy homeostasis (O2 consumption, CO2 production, respiratory exchange ratio and heat generation) and reduced peripheral inflammation in response to PM2.5., Conclusions: Central inhibition of IKKβ prevents PM2.5 mediated peripheral inflammation and exaggeration of type II diabetes. These results provide novel insights into how air pollution may mediate susceptibility to insulin resistance and Type II DM.

The US Environmental Protection Agency's (US EPA) Detroit Exposure and Aerosol Research Study (DEARS) has provided extensive data on human exposures to a wide variety of air pollutants and their impact on human health. Previous analyses in the DEARS revealed select cardiovascular (CV) health outcomes such as increase in heart rate (HR) associated with hourly based continuous personal fine particulate matter (PM2.5) exposures in this adult, non-smoking cohort. Examination of time activity diary (TAD), follow-up questionnaire (FQ) and the continuous PM2.5 personal monitoring data provided the means to more fully examine the impact of discreet human activity patterns on personal PM2.5 exposures and changes in CV outcomes. A total of 329 343 min-based PM2.5 personal measurements involving 50 participants indicated that ∼75% of these total events resulted in exposures <35 μg/m(3). Cooking and car-related events accounted for nearly 10% of the hourly activities that were identified with observed peaks in personal PM2.5 exposures. In-residence cooking often resulted in some of the highest incidents of 1 min exposures (33.5-17.6 μg/m(3)), with average peaks for such events in excess of 209 μg/m(3). PM2.5 exposure data from hourly based personal exposure activities (for example,, cooking, cleaning and household products) were compared with daily CV data from the DEARS subject population. A total of 1300 hourly based lag risk estimates associated with changes in brachial artery diameter and flow-mediated dilatation (BAD and FMD, respectively), among others, were defined for this cohort. Findings indicate that environmental tobacco smoke (ETS) exposures resulted in significant HR changes between 3 and 7 h following the event, and exposure to smells resulted in increases in BAD on the order of 0.2-0.7 mm/μg/m(3). Results demonstrate that personal exposures may be associated with several biological responses, sometimes varying in degree and direction in relation to the extent of the exposure.

Background: Fine particulate matter (PM) air pollution is associated with numerous adverse health effects, including increased blood pressure (BP) and vascular dysfunction. Coarse PM substantially contributes to global air pollution, yet differs in characteristics from fine particles and is currently not regulated. However, the cardiovascular (CV) impacts of coarse PM exposure remain largely unknown., Objectives: Our goal was to elucidate whether coarse PM, like fine PM, is itself capable of eliciting adverse CV responses., Methods: We performed a randomized double-blind crossover study in which 32 healthy adults (25.9 ± 6.6 years of age) were exposed to concentrated ambient coarse particles (CAP; 76.2 ± 51.5 μg/m(3)) in a rural location and filtered air (FA) for 2 hr. We measured CV outcomes during, immediately after, and 2 hr postexposures., Results: Both systolic (mean difference = 0.32 mmHg; 95% CI: 0.05, 0.58; p = 0.021) and diastolic BP (0.27 mmHg; 95% CI: 0.003, 0.53; p = 0.05) linearly increased per 10 min of exposure during the inhalation of coarse CAP when compared with changes during FA exposure. Heart rate was on average higher (4.1 bpm; 95% CI: 3.06, 5.12; p < 0.0001) and the ratio of low-to-high frequency heart rate variability increased (0.24; 95% CI: 0.07, 0.41; p = 0.007) during coarse particle versus FA exposure. Other outcomes (brachial flow-mediated dilatation, microvascular reactive hyperemia index, aortic hemodynamics, pulse wave velocity) were not differentially altered by the exposures., Conclusions: Inhalation of coarse PM from a rural location is associated with a rapid elevation in BP and heart rate during exposure, likely due to the triggering of autonomic imbalance. These findings add mechanistic evidence supporting the biological plausibility that coarse particles could contribute to the triggering of acute CV events.

Few prospective studies have assessed the blood pressure effect of extremely high air pollution encountered in Asia's megacities. The objective of this study was to evaluate the association between combustion-related air pollution with ambulatory blood pressure and autonomic function. During February to July 2012, personal black carbon was determined for 5 consecutive days using microaethalometers in patients with metabolic syndrome in Beijing, China. Simultaneous ambient fine particulate matter concentration was obtained from the Beijing Municipal Environmental Monitoring Center and the US Embassy. Twenty-four-hour ambulatory blood pressure and heart rate variability were measured from day 4. Arterial stiffness and endothelial function were obtained at the end of day 5. For statistical analysis, we used generalized additive mixed models for repeated outcomes and generalized linear models for single/summary outcomes. Mean (SD) of personal black carbon and fine particulate matter during 24 hours was 4.66 (2.89) and 64.2 (36.9) μg/m(3). Exposure to high levels of black carbon in the preceding hours was associated significantly with adverse cardiovascular responses. A unit increase in personal black carbon during the previous 10 hours was associated with an increase in systolic blood pressure of 0.53 mm Hg and diastolic blood pressure of 0.37 mm Hg (95% confidence interval, 0.17-0.89 and 0.10-0.65 mm Hg, respectively), a percentage change in low frequency to high frequency ratio of 5.11 and mean interbeat interval of -0.06 (95% confidence interval, 0.62-9.60 and -0.11 to -0.01, respectively). These findings highlight the public health effect of air pollution and the importance of reducing air pollution.

Background: Laboratory studies suggest that exposure to fine particulate matter (≤2.5 μm in diameter) (PM2.5) can trigger a combination of pathophysiological responses that may induce the development of hypertension. However, epidemiological evidence relating PM2.5 and hypertension is sparse. We thus conducted a population-based cohort study to determine whether exposure to ambient PM2.5 is associated with incident hypertension., Methods and Results: We assembled a cohort of 35 303 nonhypertensive adults from Ontario, Canada, who responded to 1 of 4 population-based health surveys between 1996 and 2005 and were followed up until December 31, 2010. Incident diagnoses of hypertension were ascertained from the Ontario Hypertension Database, a validated registry of persons diagnosed with hypertension in Ontario (sensitivity=72%, specificity=95%). Estimates of long-term exposure to PM2.5 at participants' postal-code residences were derived from satellite observations. We used Cox proportional hazards models, adjusting for various individual and contextual risk factors including body mass index, smoking, physical activity, and neighbourhood-level unemployment rates. We conducted various sensitivity analyses to assess the robustness of the effect estimate, such as investigating several time windows of exposure and controlling for potential changes in the risk of hypertension over time. Between 1996 and 2010, we identified 8649 incident cases of hypertension and 2296 deaths. For every 10-µg/m(3) increase of PM2.5, the adjusted hazard ratio of incident hypertension was 1.13 (95% confidence interval, 1.05-1.22). Estimated associations were comparable among all sensitivity analyses., Conclusions: This study supports an association between PM2.5 and incident hypertension.

Background: High ambient levels of ozone (O3) and fine particulate matter (PM2.5) are associated with cardiovascular morbidity and mortality, especially in people with preexisting cardiopulmonary diseases. Enhanced susceptibility to the toxicity of air pollutants may include individuals with metabolic syndrome (MetS)., Objective: We tested the hypothesis that cardiovascular responses to O3 and PM2.5 will be enhanced in rats with diet-induced MetS., Methods: Male Sprague-Dawley rats were fed a high-fructose diet (HFrD) to induce MetS and then exposed to O3, concentrated ambient PM2.5, or the combination of O3 plus PM2.5 for 9 days. Data related to heart rate (HR), HR variability (HRV), and blood pressure (BP) were collected., Results: Consistent with MetS, HFrD rats were hypertensive and insulin resistant, and had elevated fasting levels of blood glucose and triglycerides. Decreases in HR and BP, which were found in all exposure groups, were greater and more persistent in HFrD rats compared with those fed a normal diet (ND). Coexposure to O3 plus PM2.5 induced acute drops in HR and BP in all rats, but only ND rats adapted after 2 days. HFrD rats had little exposure-related changes in HRV, whereas ND rats had increased HRV during O3 exposure, modest decreases with PM2.5, and dramatic decreases during O3 plus PM2.5 coexposures., Conclusions: Cardiovascular depression in O3- and PM2.5-exposed rats was enhanced and prolonged in rats with HFrD-induced MetS. These results in rodents suggest that people with MetS may be prone to similar exaggerated BP and HR responses to inhaled air pollutants.

Context: High-density lipoprotein (HDL) particles perform numerous vascular-protective functions. Animal studies demonstrate that exposure to fine or ultrafine particulate matter (PM) can promote HDL dysfunction. However, the impact of PM on humans remains unknown., Objective: We aimed to determine the effect of exposure to coarse concentrated ambient particles (CAP) on several metrics of HDL function in healthy humans., Methods: Thirty-two adults (25.9 ± 6.6 years) were exposed to coarse CAP [76.2 ± 51.5 µg·m(-3)] in a rural location and filtered air (FA) for 2 h in a randomized double-blind crossover study. Venous blood collected 2- and 20-h post-exposures was measured for HDL-mediated efflux of [(3)H]-cholesterol from cells and 20-h exposures for HDL anti-oxidant capacity by a fluorescent assay and paraoxonase activity. The changes [median (first, third quartiles)] between exposures among 29 subjects with available results were compared by matched Wilcoxon tests., Results: HDL-mediated cholesterol efflux capacity did not differ between exposures at either time point [16.60% (15.17, 19.19) 2-h post-CAP versus 17.56% (13.43, 20.98) post-FA, p  =  0.768 and 14.90% (12.47, 19.15) 20-h post-CAP versus 17.75% (13.22, 23.95) post-FA, p  =  0.216]. HOI [0.26 (0.24, 0.35) versus 0.28 (0.25, 0.40), p = 0.198] and paraoxonase activity [0.54 (0.39, 0.82) versus 0.60 μmol·min(-1 )ml plasma(-1) (0.40, 0.85), p = 0.137] did not differ 20-h post-CAP versus FA, respectively., Conclusions: Brief inhalation of coarse PM from a rural location did not acutely impair several facets of HDL functionality. Whether coarse PM derived from urban sites, fine particles or longer term PM exposures can promote HDL dysfunction warrant future investigations.

Background: Exposure to particulate matter≤2.5 μm in diameter (PM2.5) increases blood pressure (BP) in humans and animal models. Abnormal activation of the sympathetic nervous system may have a role in the acute BP response to PM2.5 exposure. The mechanisms responsible for sympathetic nervous system activation and its role in chronic sustenance of hypertension in response to PM2.5 exposure are currently unknown., Objectives: We investigated whether central nervous system inflammation may be implicated in chronic PM2.5 exposure-induced increases in BP and sympathetic nervous system activation., Methods: C57BL/6J mice were exposed to concentrated ambient PM2.5 (CAPs) for 6 months, and we analyzed BP using radioactive telemetric transmitters. We assessed sympathetic tone by measuring low-frequency BP variability (LF-BPV) and urinary norepinephrine excretion. We also tested the effects of acute pharmacologic inhibitors of the sympathetic nervous system and parasympathetic nervous system., Results: Long-term CAPs exposure significantly increased basal BP, paralleled by increases in LF-BPV and urinary norepinephrine excretion. The increased basal BP was attenuated by the centrally acting α2a agonist guanfacine, suggesting a role of increased sympathetic tone in CAPs exposure-induced hypertension. The increase in sympathetic tone was accompanied by an inflammatory response in the arcuate nucleus of the hypothalamus, evidenced by increased expression of pro-inflammatory genes and inhibitor kappaB kinase (IKK)/nuclear factor-kappaB (NF-κB) pathway activation., Conclusion: Long-term CAPs exposure increases BP through sympathetic nervous system activation, which may involve hypothalamic inflammation.

Objective: Recent studies suggest that chronic exposure to air pollution can promote the development of diabetes. However, whether this relationship actually translates into an increased risk of mortality attributable to diabetes is uncertain., Research Design and Methods: We evaluated the association between long-term exposure to ambient fine particulate matter (PM2.5) and diabetes-related mortality in a prospective cohort analysis of 2.1 million adults from the 1991 Canadian census mortality follow-up study. Mortality information, including ∼5,200 deaths coded as diabetes being the underlying cause, was ascertained by linkage to the Canadian Mortality Database from 1991 to 2001. Subject-level estimates of long-term exposure to PM2.5 were derived from satellite observations. The hazard ratios (HRs) for diabetes-related mortality were related to PM2.5 and adjusted for individual-level and contextual variables using Cox proportional hazards survival models., Results: Mean PM2.5 exposure levels for the entire population were low (8.7 µg/m3; SD, 3.9 µg/m3; interquartile range, 6.2 µg/m3). In fully adjusted models, a 10-µg/m3 elevation in PM2.5 exposure was associated with an increase in risk for diabetes-related mortality (HR, 1.49; 95% CI, 1.37-1.62). The monotonic change in risk to the population persisted to PM2.5 concentration<5 µg/m3., Conclusions: Long-term exposure to PM2.5, even at low levels, is related to an increased risk of mortality attributable to diabetes. These findings have considerable public health importance given the billions of people exposed to air pollution and the worldwide growing epidemic of diabetes.

Background: Inflammation and oxidative stress play critical roles in the pathogenesis of inhaled air pollutant-mediated metabolic disease. Inflammation in the adipose tissues niches are widely believed to exert important effects on organ dysfunction. Recent data from both human and animal models suggest a role for inflammation and oxidative stress in epicardial adipose tissue (EAT) as a risk factor for the development of cardiovascular disease. We hypothesized that inhalational exposure to concentrated ambient fine particulates (CAPs) and ozone (O3) exaggerates inflammation and oxidative stress in EAT and perirenal adipose tissue (PAT)., Methods: Eight- week-old Male Sprague-Dawley rats were fed a normal diet (ND) or high fructose diet (HFr) for 8 weeks, and then exposed to ambient AIR, CAPs at a mean of 356 μg/m3, O3 at 0.485 ppm, or CAPs (441 μg/m3) + O3 (0.497 ppm) in Dearborn, MI, 8 hours/day, 5 days/week, for 9 days over 2 weeks., Results: EAT and PAT showed whitish color in gross, and less mitochondria, higher mRNA expression of white adipose specific and lower brown adipose specific genes than in brown adipose tissues. Exposure to CAPs and O3 resulted in the increase of macrophage infiltration in both EAT and PAT of HFr groups. Proinflammatory genes of Tnf-α, Mcp-1 and leptin were significantly upregulated while IL-10 and adiponectin, known as antiinflammatory genes, were reduced after the exposures. CAPs and O3 exposures also induced an increase in inducible nitric oxide synthase (iNOS) protein expression, and decrease in mitochondrial area in EAT and PAT. We also found significant increases in macrophages of HFr-O3 rats. The synergetic interaction of HFr and dirty air exposure on the inflammation was found in most of the experiments. Surprisingly, exposure to CAPs or O3 induced more significant inflammation and oxidative stress than co-exposure of CAPs and O3 in EAT and PAT., Conclusion: EAT and PAT are both white adipose tissues. Short-term exposure to CAPs and O3, especially with high fructose diet, induced inflammation and oxidative stress in EAT and PAT in rats. These findings may provide a link between air-pollution exposure and accelerated susceptibility to cardiovascular disease and metabolic complications.

Context: Fine particulate matter (PM) air pollution has been associated with alterations in circulating endothelial progenitor cell (EPC) levels, which may be one mechanism whereby exposures promote cardiovascular diseases. However, the impact of coarse PM on EPCs is unknown., Objective: We aimed to determine the effect of acute exposure to coarse concentrated ambient particles (CAP) on circulating EPC levels., Methods: Thirty-two adults (25.9 ± 6.6 years) were exposed to coarse CAP (76.2 ± 51.5 μg m(-3)) in a rural location and filtered air (FA) for 2 h in a randomized double-blind crossover study. Peripheral venous blood was collected 2 and 20 h post-exposures for circulating EPC (n = 21), white blood cell (n = 24) and vascular endothelial growth factor (VEGF) (n = 16-19) levels. The changes between exposures were compared by matched Wilcoxon signed-rank tests., Results: Circulating EPC levels were elevated 2 [108.29 (6.24-249.71) EPC mL(-1); median (25th-75th percentiles), p = 0.052] and 20 h [106.86 (52.91-278.35) EPC mL(-1), p = 0.008] post-CAP exposure compared to the same time points following FA [38.47 (0.00-84.83) and 50.16 (0.00-104.79) EPC mL(-1)]. VEGF and white blood cell (WBC) levels did not differ between exposures., Conclusions: Brief inhalation of coarse PM from a rural location elicited an increase in EPCs that persisted for at least 20 h. The underlying mechanism responsible may reflect a systemic reaction to an acute "endothelial injury" and/or a circulating EPC response to sympathetic nervous system activation.

Background: Laboratory studies suggest that fine particulate matter (≤ 2.5 µm in diameter; PM(2.5)) can activate pathophysiological responses that may induce insulin resistance and type 2 diabetes. However, epidemiological evidence relating PM2.5 and diabetes is sparse, particularly for incident diabetes., Objectives: We conducted a population-based cohort study to determine whether long-term exposure to ambient PM(2.5) is associated with incident diabetes., Methods: We assembled a cohort of 62,012 nondiabetic adults who lived in Ontario, Canada, and completed one of five population-based health surveys between 1996 and 2005. Follow-up extended until 31 December 2010. Incident diabetes diagnosed between 1996 and 2010 was ascertained using the Ontario Diabetes Database, a validated registry of persons diagnosed with diabetes (sensitivity = 86%, specificity = 97%). Six-year average concentrations of PM2.5 at the postal codes of baseline residences were derived from satellite observations. We used Cox proportional hazards models to estimate the associations, adjusting for various individual-level risk factors and contextual covariates such as smoking, body mass index, physical activity, and neighborhood-level household income. We also conducted multiple sensitivity analyses. In addition, we examined effect modification for selected comorbidities and sociodemographic characteristics., Results: There were 6,310 incident cases of diabetes over 484,644 total person-years of follow-up. The adjusted hazard ratio for a 10-µg/m(3) increase in PM(2.5) was 1.11 (95% CI: 1.02, 1.21). Estimated associations were comparable among all sensitivity analyses. We did not find strong evidence of effect modification by comorbidities or sociodemographic covariates., Conclusions: This study suggests that long-term exposure to PM2.5 may contribute to the development of diabetes.

Background: Short-term exposures to fine (<2.5 μm aerodynamic diameter) ambient particulate-matter (PM) have been related with increased blood pressure (BP) in controlled-human exposure and community-based studies. However, whether coarse (2.5 to 10 μm) PM exposure increases BP is uncertain. Recent observational studies have linked PM exposures with blood DNA hypomethylation, an epigenetic alteration that activates inflammatory and vascular responses. No experimental evidence is available to confirm those observational data and demonstrate the relations between PM, hypomethylation, and BP., Methods and Results: We conducted a cross-over trial of controlled-human exposure to concentrated ambient particles (CAPs). Fifteen healthy adult participants were exposed for 130 minutes to fine CAPs, coarse CAPs, or HEPA-filtered medical air (control) in randomized order with ≥2-week washout. Repetitive-element (Alu, long interspersed nuclear element-1 [LINE-1]) and candidate-gene (TLR4, IL-12, IL-6, iNOS) blood methylation, systolic and diastolic BP were measured pre- and postexposure. After adjustment for multiple comparisons, fine CAPs exposure lowered Alu methylation (β-standardized=-0.74, adjusted-P=0.03); coarse CAPs exposure lowered TLR4 methylation (β-standardized=-0.27, adjusted-P=0.04). Both fine and coarse CAPs determined significantly increased systolic BP (β=2.53 mm Hg, P=0.001; β=1.56 mm Hg, P=0.03, respectively) and nonsignificantly increased diastolic BP (β=0.98 mm Hg, P=0.12; β=0.82 mm Hg, P=0.11, respectively). Decreased Alu and TLR4 methylation was associated with higher postexposure DBP (β-standardized=0.41, P=0.04; and β-standardized=0.84, P=0.02; respectively). Decreased TLR4 methylation was associated with higher postexposure SBP (β-standardized=1.45, P=0.01)., Conclusions: Our findings provide novel evidence of effects of coarse PM on BP and confirm effects of fine PM. Our results provide the first experimental evidence of PM-induced DNA hypomethylation and its correlation to BP.

Epidemiological studies suggest that fine particulate matter (PM2.5) may increase the risk for developing diabetes mellitus (DM). To evaluate possible mechanisms explaining these associations, we investigated if sub-acute ambient-level exposures can impair insulin sensitivity. Twenty-five healthy adults living in rural Michigan were transported to an urban location for 5 consecutive days (exposure-block) of daily 4- to 5-hour-long ambient air pollution exposures. Health outcomes, including the homeostasis model assessment of insulin resistance (HOMA-IR) the primary outcome of insulin sensitivity, were measured at 3 time points in relation to exposure-blocks: 7days prior to start; on the last exposure-day; and 7days after completion. PM2.5 was monitored at the urban exposure site and at community monitors near subjects' residences. We calculated 3 "sub-acute" exposure periods (approximately 5-days-long) starting retrospective from the time of health outcome measurements (PM2.5 ranges: 9.7±3.9 to 11.2±3.9μg·m(-3)). A 10μg·m(-3) increase in sub-acute PM2.5 exposures was associated with increased HOMA-IR (+0.7, 95% confidence interval (CI) 0.1 to 1.3; p=0.023) and reduced heart rate variability (standard deviation of normal-to-normal intervals [-13.1ms, 95%CI -25.3 to -0.9; p=0.035]). No alterations in other outcomes (inflammatory markers, vascular function) occurred in relation to PM2.5 exposures. Our findings suggest that ambient PM2.5, even at low levels, may reduce metabolic insulin sensitivity supporting the plausibility that air pollution could potentiate the development of DM., (Copyright © 2012 Elsevier B.V. All rights reserved.)

There is a paucity of prospective cohort studies investigating the impact of environmental factors on the development of cardiometabolic (CM) disorders like type II diabetes (T2DM). The objective of the Air-Pollution and Cardiometabolic Diseases (AIRCMD) study is to investigate the impact of personal level air pollution measures [personal black carbon (BC)/sulfate measures] and ambient fine particulate matter [(PM2.5)/NO2] levels on propensity to type II diabetes in Beijing, China. Subjects with metabolic syndrome will undergo four repeated study visits within each season over a one year period following an initial screening visit. At each study visit, subjects will be monitored for sub-acute exposure to personal and ambient measures of air-pollution exposure and will undergo a series of functional CM outcomes. The primary endpoints include independent associations between integrated 5-day mean exposure to PM2.5 and BC and homeostasis model assessment of insulin resistance (HOMA-IR) measures, 24-hour mean diastolic and mean arterial pressure and endothelial-dependent vasodilatation. The secondary endpoints will explore the mechanistic explanation for a causal relationship between exposures and propensity for type II diabetes and will include additional functional outcomes such as arterial compliance, heart rate variability and plasma adipokines. The novel aspects of the study include the launch of infrastructure for future translational investigations in highly polluted urbanized environments and the creation of novel methodologies for linking personalized exposure measurements with functional CM outcomes. We believe that AIRCMD will allow for unprecedented new investigations into the association between environmental risk factors and CM disorders., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: Evidence suggests that longer-term exposure to air pollutants over years confers higher risks of cardiovascular morbidity and mortality than shorter-term exposure. One explanation is that the cumulative adverse effects that develop over longer durations lead to the genesis of chronic disease. Preliminary epidemiological and clinical evidence suggests that air pollution may contribute to the development of hypertension and type 2 diabetes mellitus., Methods and Results: We used Cox proportional hazards models to assess incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for incident hypertension and diabetes mellitus associated with exposure to fine particulate matter (PM(2.5)) and nitrogen oxides in a cohort of black women living in Los Angeles. Pollutant levels were estimated at participants' residential addresses with land use regression models (nitrogen oxides) and interpolation from monitoring station measurements (PM(2.5)). Over follow-up from 1995 to 2005, 531 incident cases of hypertension and 183 incident cases of diabetes mellitus occurred. When pollutants were analyzed separately, the IRR for hypertension for a 10-μg/m(3) increase in PM(2.5) was 1.48 (95% CI, 0.95-2.31), and the IRR for the interquartile range (12.4 parts per billion) of nitrogen oxides was 1.14 (95% CI, 1.03-1.25). The corresponding IRRs for diabetes mellitus were 1.63 (95% CI, 0.78-3.44) and 1.25 (95% CI, 1.07-1.46). When both pollutants were included in the same model, the IRRs for PM(2.5) were attenuated and the IRRs for nitrogen oxides were essentially unchanged for both outcomes., Conclusion: Our results suggest that exposure to air pollutants, especially traffic-related pollutants, may increase the risk of type 2 diabetes mellitus and possibly of hypertension.