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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.

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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.

Air pollution is well recognized as a major risk factor for chronic non-communicable diseases and has been estimated to contribute more to global morbidity and mortality than all other known environmental risk factors combined. Although air pollution contains a heterogeneous mixture of gases, the most robust evidence for detrimental effects on health is for fine particulate matter (particles ≤2.5 µm in diameter (PM 2.5 )) and ozone gas and, therefore, these species have been the main focus of environmental health research and regulatory standards. The evidence to date supports a strong link between the risk of cardiovascular events and all-cause mortality with PM 2.5 across a range of exposure levels, including to levels below current regulatory standards, with no 'safe' lower exposure levels at the population level. In this comprehensive Review, the empirical evidence supporting the effects of air pollution on cardiovascular health are examined, potential mechanisms that lead to increased cardiovascular risk are described, and measures to reduce this risk and identify key gaps in our knowledge that could help address the increasing cardiovascular morbidity and mortality associated with air pollution are discussed.

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: Growing evidence links household air pollution exposure from biomass-burning cookstoves to cardiometabolic disease risk. Few randomized controlled interventions of cookstoves (biomass or otherwise) have quantitatively characterized changes in exposure and indicators of cardiometabolic health, a growing and understudied burden in low- and middle-income countries (LMICs). Ideally, the solution is to transition households to clean cooking, such as with electric or liquefied petroleum gas stoves; however, those unable to afford or to access these options will continue to burn biomass for the foreseeable future. Wood-burning cookstove designs such as the Justa (incorporating an engineered combustion zone and chimney) have the potential to substantially reduce air pollution exposures. Previous cookstove intervention studies have been limited by stove types that did not substantially reduce exposures and/or by low cookstove adoption and sustained use, and few studies have incorporated community-engaged approaches to enhance the intervention., Methods/design: We conducted an individual-level, stepped-wedge randomized controlled trial with the Justa cookstove intervention in rural Honduras. We enrolled 230 female primary cooks who were not pregnant, non-smoking, aged 24-59 years old, and used traditional wood-burning cookstoves at baseline. A community advisory board guided survey development and communication with participants, including recruitment and retention strategies. Over a 3-year study period, participants completed 6 study visits approximately 6 months apart. Half of the women received the Justa after visit 2 and half after visit 4. At each visit, we measured 24-h gravimetric personal and kitchen fine particulate matter (PM 2.5 ) concentrations, qualitative and quantitative cookstove use and adoption metrics, and indicators of cardiometabolic health. The primary health endpoints were blood pressure, C-reactive protein, and glycated hemoglobin. Overall study goals are to explore barriers and enablers of new cookstove adoption and sustained use, compare health endpoints by assigned cookstove type, and explore the exposure-response associations between PM 2.5 and indicators of cardiometabolic health., Discussion: This trial, utilizing an economically feasible, community-vetted cookstove and evaluating endpoints relevant for the major causes of morbidity and mortality in LMICs, will provide critical information for household air pollution stakeholders globally., Trial Registration: ClinicalTrials.gov Identifier NCT02658383 , posted January 18, 2016, field work completed May 2018. Official title, "Community-Based Participatory Research: A Tool to Advance Cookstove Interventions." Principal Investigator Maggie L. Clark, Ph.D. Last update posted July 12, 2018.

Rationale: The pathophysiologic mechanisms of air pollution-associated exacerbation of cardiovascular events remain incompletely understood., Objective: To assess whether ambient air pollution can be a trigger of the vulnerable plaque and heightened thrombogenicity through systemic inflammatory pathways., Methods and Results: In Beijing AIRCHD study (Air Pollution and Cardiovascular Dysfunctions in Healthy Adults Living in Beijing), 73 healthy adults (mean±SD, 23.3±5.4 years) were followed up in 2014 to 2016. We estimated associations between air pollutants and biomarkers relevant to atherosclerotic plaque vulnerability, thrombogenicity, and inflammation using linear mixed-effects models and elucidated the biological pathways involved using mediation analyses. Receiver operating characteristic analyses were conducted to assess the ability of each biomarker to predict ambient air pollution exposures. High average concentrations of particulate matter in diameter <2.5 μm (91.8±63.8 µg/m 3 ) were observed during the study period. Significant increases in circulating biomarkers of plaque vulnerability, namely MMPs (matrix metalloproteinases; MMP-1, 2, 3, 7, 8, and 9), of 8.6% (95% CI, 0.1-17.8) to 141.4% (95% CI, 111.8-171.0) were associated with interquartile range increases in moving averages of particulate matter in diameter <2.5 μm, number concentrations of particles in sizes of 5 to 560 nm and black carbon, during the last 1 to 7 days before each participant's clinic visit. Higher air pollutant levels were also significantly associated with decreases in TIMP (tissue inhibitors of MMPs; TIMP-1 and 2), heightened thrombogenicity (shortened prothrombin time and increases in sCD40L [soluble CD40 ligand], sCD62P [soluble P-selectin], and fibrinogen/fibrin degradation products), and elevations in systemic inflammation (IL-1β [interleukin-1β], CRP [C-reactive protein], MIP-1α/β [macrophage inflammatory protein-1α/β], sRAGE [soluble receptor for advanced glycation end products], and IGFBP [insulin-like growth factor-binding protein]-1 and 3). Receiver operating characteristic curves showed that several biomarkers can serve as robust pollutant-specific predictors with high versus low black carbon exposure (area under the receiver operating characteristic curve of 0.974 [95% CI, 0.955-0.992] for MMP-8 and 0.962 [95% CI, 0.935-0.988] for sRAGE). Mediation analysis further showed that systemic inflammation can mediate ≤46% of the changes in MMPs and thrombogenicity associated with interquartile range increases in air pollutants., Conclusions: Our results suggest that air pollution may prompt cardiovascular events by triggering vulnerable plaque along with heightened thrombogenicity possibly through systemic inflammatory pathways.

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.

High blood pressure (BP) affects over one billion people and is the leading risk factor for global mortality. While many lifestyle and genetic risk factors are well-accepted to increase BP, the role of the external environment is typically overlooked. Mounting evidence now supports that numerous environmental factors can promote an elevation in BP. Broadly speaking these include aspects of the natural environment (e.g., cold temperatures, higher altitude, and winter season), natural disasters (e.g., earthquakes, volcanic eruptions), and man-made exposures (e.g., noise, air pollutants, and toxins/chemicals). This is important for health care providers to recognize as one (or several) of these environmental factors could be playing a clinically meaningful role in elevating BP or disrupting hypertension control among their patients. At the population level, certain environmental exposures may even be contributing to the growing pandemic of hypertension. Here we provide an updated review of the literature linking environment exposures with high BP and outline practical recommendations for clinicians.

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.

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.)

Environmental temperatures influence cardiovascular physiology. However, the majority of time is spent indoors, making outdoor-ambient temperatures inaccurate estimates of true exposures encountered by most individuals. We evaluated in 50 healthy adults the associations between previous 7-day outdoor-ambient (four occasions) and prior 24-hour personal-level (two occasions) environmental temperature exposures with blood pressure, heart rate variability, sleep parameters, and endothelial-dependent vasodilatation (brachial flow-mediated dilatation [FMD]) using generalized estimating equations. Participants (34 females; age, 32.1 ± 9.6 years) had normal blood pressures (107.8 ± 13.3/70.2 ± 9.4 mm Hg), FMD (7.4 ± 2.8%), as well as sleep and heart rate variability parameters. Mean 7-day outdoor-ambient (4.6 ± 9.7°C) differed from personal-level temperature exposures (22.0 ± 3.0°C). Colder outdoor-ambient temperatures (per -10°C) over the previous 1-6 days (rolling averages) were associated with decreases in FMD: -0.57% (95% confidence interval [CI]: -1.14% to 0.01%, P = .055) to -0.62% (95% CI: -1.07% to -0.18%, P = .006). However, a 10°C decrease in personal-level temperature during the prior 24 hours was associated with a greater decrement in FMD: -2.44% (95% CI: -4.74% to -0.13%, P = .038). Both were also linearly related to FMD during all seasons and without a threshold temperature. Other end points were not significantly related to either temperature level in this study. Short-term exposures to colder environmental temperatures reduced endothelial-dependent vasodilatation, supporting the epidemiologic associations with heightened cardiovascular risk. We show here for the first time that temperature exposures characterized at the personal level may be more robust predictors of endothelial function than outdoor-ambient levels., (Copyright © 2017 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.)

Over the past few decades, a growing body of epidemiological and clinical evidence has led to heightened concerns about the potential short- and long-term deleterious effects of the environment on cardiovascular health, including the risk for acute myocardial infarction (AMI). This review highlights the increased risk of AMI caused by exposure to air pollution and cold temperatures. These factors should be considered modifiable risk factors in the prevention of cardiovascular disease. The current body of knowledge about the biological mechanisms linking environmental changes to atherothrombotic events and the impact of climate change on cardiovascular health are discussed. Finally, recommendations for prevention and public policy are presented., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)

Background: Evidence shows that exposure to air pollutants can increase blood pressure in the short and long term. Some studies show higher levels of hypertension prevalence in areas of high pollution. Few data exist on the association of air pollution with hypertension incidence. The purpose of the present study was to prospectively assess the associations of the traffic-related nitrogen dioxide (NO2) and of ozone with the incidence of hypertension in the Black Women's Health Study (BWHS), a large cohort study of African American women., Methods: We used Cox proportional hazards models to calculate hazard ratios (HRs) and 95% confidence intervals (CI) for hypertension associated with exposure to NO2 and ozone among 33,771 BWHS participants. NO2 and ozone levels at participant residential locations were estimated with validated models., Results: From 1995 to 2011, 9,570 incident cases of hypertension occurred in a total of 348,154 person-years (median follow-up time, 11 years). The multivariable HRs per interquartile range of NO2 (9.7 ppb) and ozone (6.7 ppb) were 0.92 (95% CI = 0.86, 0.98) and 1.09 (95% CI = 1.00, 1.18)., Conclusions: In this large cohort of African American women, higher ozone levels were associated with an increase in hypertension incidence. Higher NO2 levels were not associated with greater hypertension incidence; indeed, incidence was lower at higher NO2 levels., (© American Journal of Hypertension, Ltd 2017. All rights reserved. For Permissions, please email: journals.permissions@oup.com)

Traffic noise and air pollution together represent the two most important environmental risk factors in urbanized societies. The first of this two-part review discusses the epidemiologic evidence in support of the existence of an association between these risk factors with cardiovascular and metabolic disease. While independent effects of these risk factors have now clearly been shown, recent studies also suggest that the two exposures may interact with each other and with traditional risk factors such as hypertension and type 2 diabetes. From a societal and policy perspective, the health effects of both air pollution and traffic noise are observed for exposures well below the thresholds currently accepted as being safe. Current gaps in knowledge, effects of intervention and their impact on cardiovascular disease, will be discussed in the last section of this review. Increased awareness of the societal burden posed by these novel risk factors and acknowledgement in traditional risk factor guidelines may intensify the efforts required for effective legislation to reduce air pollution and noise., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions please email: journals.permissions@oup.com.)

Environmental factors can act as facilitators of chronic non-communicable diseases. Ambient noise and air pollution collectively outrank all other environmental risk factors in importance, contributing to over 75% of the disease and disability burden associated with known environmental risk factors. In the first part of this review, we discussed the global burden and epidemiologic evidence supporting the importance of these novel risk factors as facilitators of cardiometabolic disease. In this part, we will discuss pathophysiological mechanisms responsible for noise and air pollution-mediated effects. Akin to traditional cardiovascular risk factors, a considerable body of evidence suggests that these environmental agents induce low-grade inflammation, oxidative stress, vascular dysfunction, and autonomic nervous system imbalance, thereby facilitating the development of diseases such as hypertension and diabetes. Through their impact on traditional risk factors and via additional novel mechanisms, environmental risk factors may have much larger impact on cardiovascular events than currently appreciated. In the second part of this review, we discuss deficiencies and gaps in knowledge and opportunities for new research., (© The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology.)

The American Thoracic Society has previously published statements on what constitutes an adverse effect on health of air pollution in 1985 and 2000. We set out to update and broaden these past statements that focused primarily on effects on the respiratory system. Since then, many studies have documented effects of air pollution on other organ systems, such as on the cardiovascular and central nervous systems. In addition, many new biomarkers of effects have been developed and applied in air pollution studies.This current report seeks to integrate the latest science into a general framework for interpreting the adversity of the human health effects of air pollution. Rather than trying to provide a catalogue of what is and what is not an adverse effect of air pollution, we propose a set of considerations that can be applied in forming judgments of the adversity of not only currently documented, but also emerging and future effects of air pollution on human health. These considerations are illustrated by the inclusion of examples for different types of health effects of air pollution., (Copyright ©ERS 2017.)

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.

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.

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.

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.

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: 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.)

Background: Epidemiological studies have assessed T-wave alternans (TWA) as a possible mechanism of cardiac arrhythmias related to air pollution in high-risk subjects and have reported associations with increased TWA magnitude., Objective: In this controlled human exposure study, we assessed the impact of exposure to concentrated ambient particulate matter (CAP) and ozone (O3) on T-wave alternans in resting volunteers without preexisting cardiovascular disease., Methods: Seventeen participants without preexisting cardiovascular disease were randomized to filtered air (FA), CAP (150 μg/m3), O3 (120 ppb), or combined CAP + O3 exposures for 2 hr. Continuous electrocardiograms (ECGs) were recorded at rest and T-wave alternans (TWA) was computed by modified moving average analysis with QRS alignment for the artifact-free intervals of 20 beats along the V2 and V5 leads. Exposure-induced changes in the highest TWA magnitude (TWAMax) were estimated for the first and last 5 min of each exposure (TWAMax&#95;Early and TWAMax&#95;Late respectively). ΔTWAMax (Late-Early) were compared among exposure groups using analysis of variance., Results: Mean ± SD values for ΔTWAMax were -2.1 ± 0.4, -2.7 ± 1.1, -1.9 ± 1.5, and -1.2 ± 1.5 in FA, CAP, O3, and CAP + O3 exposure groups, respectively. No significant differences were observed between pollutant exposures and FA., Conclusion: In our study of 17 volunteers who had no preexisting cardiovascular disease, we did not observe significant changes in T-wave alternans after 2-hr exposures to CAP, O3, or combined CAP + O3. This finding, however, does not preclude the possibility of pollution-related effects on TWA at elevated heart rates, such as during exercise, or the possibility of delayed responses.

Background: Numerous studies have reported associations between air pollution and cardiovascular diseases. While several studies illustrate that exposures to air pollutants can elevate blood pressure, few have evaluated the clinical relevance of this relationship. Hence, we aimed to explore the associations between daily concentrations of several air pollutants and emergency department visits for hypertension., Methods: Odds ratios (ORs) for emergency department visits for hypertension in Edmonton, Canada, from April 1992 to March 2002 were associated with pollutant levels (CO, NO(2), SO(2), O(3), and particulate matter [PM] < 10 microns [PM(10)] and < 2.5 microns [PM(2.5)] in aerodynamic diameter, respectively) by means of a case-crossover technique with time-stratified strategy to define controls. The analysis was performed for all (N = 5365), male (N = 2069), and female (N = 3296) patients and for six air pollutants lagged by 0 to 9 days. ORs and their 95% confidence intervals (CIs) were reported for an increase in an interquartile range (IQR) for each pollutant., Results: We observed associations for all patients and levels of NO(2) (IQR = 12.8 parts per billion; OR, 1.06; 95% CI, 1.00-1.12), SO(2) (IQR = 2.3 parts per billion; OR, 1.04; 95% CI, 1.00-1.08), and PM(10) (IQR = 15.0 μg/m(3); OR, 1.06; 95% CI, 1.01-1.11) for lag day 3, as well as for PM(10) (IQR = 15.0 μg/m(3); OR, 1.06; 95% CI, 1.01-1.11) and PM(2.5) (IQR = 6.2 μg/m(3); OR, 1.07; 95% CI, 1.01-1.11) for lag day 6., Conclusions: These findings support the contention that ambient pollution can produce clinically meaningful increases in blood pressure., (Copyright © 2012 Canadian Cardiovascular Society. All rights reserved.)

Environmental temperatures are inversely related to BP; however, the effects of short-term temperature changes within a 24-hour period and measured with high accuracy at the personal level have not been described. Fifty-one nonsmoking patients living in the Detroit area had up to 5 consecutive days of 24-hour personal-level environmental temperature (PET) monitoring along with daily cardiovascular measurements, including BP, performed mostly between 5 pm and 7 pm during summer and/or winter periods. The associations between hour-long mean PET levels during the previous 24 hours with the outcomes were assessed by linear mixed models. Accounting for demographics, environmental factors, and monitoring compliance, systolic and diastolic BP were positively associated with several hour-long PET measurements ending from 10 to 15 hours beforehand. During this time, corresponding mostly to a period starting from between 1 am and 3 am to ending between 7 am and 9 am, an increase of 1°C was associated with a 0.81 mm Hg to 1.44 mm Hg and 0.59 mm Hg to 0.83 mm Hg elevation in systolic and diastolic BP, respectively. Modestly warmer, commonly encountered PET levels posed a clinically meaningful effect (eg, a 6.95 mm Hg systolic pressure increase per interquartile range (4.8°C) elevation at lag hour 10). Community-level outdoor ambient temperatures were not related to BP. The authors provide the first evidence that personal exposure to warmer nighttime and early-morning environmental temperatures might lead to an increase in BP during the ensuing day., (© 2011 Wiley Periodicals, Inc.)

Particulate matter (PM) air pollution less than 2.5 microm in diameter (PM(2.5)), which is now an all-pervading element of modern-day society, is associated with heightened cardiovascular morbidity and mortality. Not only can short-term PM(2.5) exposure trigger acute cardiovascular events, but longer-term exposure over years augments cardiovascular risk to an even greater extent. One biological mechanism capable of explaining this observation is that chronic exposure may promote the progression and vulnerability of atherosclerotic plaques. Indeed, recent epidemiologic studies have demonstrated an association between ambient PM(2.5) exposure and the presence or extent of atherosclerosis in humans. Several animal experiments have provided corroborating evidence that chronic exposures in fact do enhance the progression and perhaps vulnerability of atherosclerotic lesions. Due to the billions of people continually exposed to PM(2.5), the long-term pro-atherosclerotic effects of this ubiquitous air pollutant are likely to be of enormous and growing global public health importance.

Exposure to ambient levels of particulate matter (PM) air pollution increases the risk of a host of cardiovascular diseases and events. One potential mechanism explaining this association is that acute exposure to PM at high concentrations is capable of raising blood pressure within hours to days. Epidemiologic studies confirm that even commonly encountered levels of airborne pollutants can result in a prohypertensive response in humans. Several biologic pathways may be involved, including autonomic nervous system imbalance and arterial vascular dysfunction/vasoconstriction due to systemic oxidative stress/inflammation triggered by PM inhalation. The clinical importance of this vasopressor response and its relative role in promoting cardiovascular events associated with PM remain unclear. Because air pollution exposure is ubiquitous throughout the world, however, all health care providers and especially those who treat hypertension should be aware of this emerging and important biologic relationship.

Particulate matter (PM) air pollution is associated with an increased risk of cardiovascular morbidity and mortality. The focus of this review will be on the role that both acute and chronic exposure to PM plays in causing cardiovascular disease and on the latest major new findings and controversies in this field of research. Even short-term exposure to PM2.5 over a few hours can trigger myocardial infarctions, cardiac ischemia, arrhythmias, heart failure, stroke, exacerbation of peripheral arterial disease, and sudden death. Chronic exposure to moderately elevated levels also enhances the risk for developing a variety of cardiovascular diseases, possibly including hypertension and systemic atherosclerosis. Recent epidemiologic studies have furthered our understanding of the linkage between air pollutants and human health, with a multitude of plausible mechanistic explanations having been demonstrated experimentally during the past few years. Although a number of finer details relating to both the epidemiology and the mechanisms involved require more investigation, the overall weight of evidence is now sufficient to implicate PM exposure as a cause of cardiovascular disease. Without doubt, exposure to particulate matter can play a causal role in triggering a host of acute cardiovascular events via many mechanisms. Although long-term air pollution exposure has been shown to promote the development of atherosclerosis, the clinical significance of this relation requires more investigation.