Torco Res, ‘Vol. 30, No. 2, pp. 71-75 (2014) Toxicological Research ite dotorg/0487/7R2014302.071 oft Jour of ISSN 19766257 elSSN-2234-2753 Thematie Perspectives Korean Society of Toneoiogy Air Pollution Exposure and Cardiovascular Disease Bycong-Jae Lee’, Bumseok Kim’ and Kyuhong Lee"? ‘inhalation Toxicology Research Center, Korea Institut of Toxicology Jeonbuk Korea “Biosoft Research Insitute and Laboratry of Pathology, Calegeof Veterinary Medcne,Chanbuk National Univers, Jeonju Korea “vuman and Environment Toxicology, University of Science and Technology, Daejeon, Korea ‘eceived June 19, 2014; Revised June 26, 2014; Accepted June 27,2014) ‘Ambient air pollution (AAP) and particulate matters (PM) have been closely associated with adverse heath effects suchas respiratory disease and cardiovascular diseases. Previous studies have examined the adverse health effets associated with short-and long-term exposure t© AAP and outdoor PM on respi tory disease. However, the effect of PM size (PML «and PM,,) on cardiovascular disease has not been well studied. Thus, it remains unclear how the sizeof the inhalable particles (coarse, fine, or ultrafine) affects ‘mortality’ and morbidity. Airbome PM concentrations are commonly used for ambient ae quality manage- ‘ment worldwide, owing tothe known effets on eardiorespiratory health. In this article, we assess the rela- tionship between cardiovascular diseases and PM, with a particular focus on PM size. We discuss the association of PM, and PM, nitrogen dioxide (NO.), and elemental carbon with morality and morbid- ity due to cardiovaseular diseases, stroke, and altered blood pressure, base on epidemiological tues. In audition, we provide evidence thatthe adverse health effects of AAP and PM are more pronounced among the elderly, children, and people with preexisting cardiovascular and respiratory conditions. Finally, we crtcally summarize the literature pertaining to cardiovascular diseases, including atherosclerosis and stroke, and introduce potential studies to beter understand the health significance of AP and PM on car- diovascular disease, ‘Key words: Pariculate mate, Air pollution, Cardiovascular disease INTRODUCTION concer to governments and health organizations world- wide (12). The plmonary effects of air pollution eontain- ‘The adverse health effets of exposure to particulate mat- ing PMs and PM, inlude increased respiratory symptoms, ter (PM), including particles with a median acrodynamic decreased lung funtion, and increased incidence of chronic diameter <2.5 ym (PMs) and < 10 um (PM,.) are of eat cough, bronchitis, and conjunctivitis (3-5). Furthermore, ep- demiological and clinical studies have increasingly shown orespondence to: Kyuhong Lee, inhalation ToxkologyReseorch that ar pollution is assoeated with not only respiratory and enter Koes Insts of Toxcotogy, 30, Bakhak II Jeongeup- pulmonary diseases but also cardiovascular diseases. AS a Si Jel 58-185, Kove esl, the adverse health effets ofa pollution have been Em knocsltenvee ksektsgmaiicom eee ee Abbreiatons: AAP Ambient a potion, Martane Mat, _Cnjal, mechani, an epidemiological shies of the NO; Nitegen desde CO: Carbon monoxide, SO, Saf cose, Soe ee ect cee seaeworttg staf long and shoresem expose tai poliion nd gen diode, NO; Nic oxide, AD: Aerodynamic ameter WHO: the sizes of PM have provided evidence supporting adverse ‘World Heath Organization, Ri Relative ik Cl: Confidence inter. ealth effects after air pollution exposure. Epidemiological val AM Acute Myocardial infrcton NMIVAPS: The Natonal Nor~ studies and pathophysological data have also shown that bid. Morality and Ai Polaion Study, APHEA: Ar Politon 3nd air polution exposure is related with general morbidity and Health European Approach, DBP: Dias Blood ese ee a anne lat dice Systolic Blood Pressure = 6,6,389.10.11,2). Furthermore, the acrotynamies of PM. This an OpemAces aril touted under the tes ofthe Gay fst the severity af averse health eft. In genera ‘cathe Commons Atuibution Non-Commercial Lense (Mt! Nt With lower seronvnumnie diameter, including fine and reavecommensorgerses/y 1/30) which permis Uvested including fomcommercsl use, dstbtion, and reproduction inary laf (< 100 nm) PM, are assoeated with more serious medium, provided the crignal works propery ed elects aller both shorcterm exposure to an ele- nn Bus. Lee etal vated concentration of pollutants or after long-term expo- sure (13,14). In addition, adverse health effects can be exacerbated in vulnerable populations, including those with preexisting cardi-respiratory diseases and the elderly. AS a result, these populations tend to have more complicated health problem after air pollution exposure than healthy groups (15), The relationship between air pollution and respiratory diseases, such as chronic obstructive pulmonary disease and asthma, is well established. However, the relationship between, air pollution and cardiovascular disease remains unclear. Nevertheless, recent clinical and epidemiological data sug- test the two may be related. In this review, we discuss how air pollution and PM may affect the pathogenesis of eardio- vascular disease, with a particular focus onthe effect of PM size on cardiovascular disease. PARTICULATE MATTER (PM, , AND PM.) The many sources of air poltution are broadly divided into two categories, natural phenomena and human activi= ties. For example, voleanoes, wildfies, or land dust are classified as natural phenomena, whereas human activities, also termed anthropogenic sources, include carbon monox- ide (CO) from vehicle exhausts or sulfur dioxide (SO,) from industrial process. Human-generated sources of ait pollution are a major problem and cause most harmful adverse health effects. In addition, chemical reactions of primary emissions in the atmosphere cause the formation of secondary pollutants. For example, ozone (Q,) is generated. by the reaction of volatile hydrocarbons with sunlight Sec- ‘ondary air pollution particles result in @ complex mixture of gaseous substances, including earbon monoxide (CO), ear bon dioxide (CO.), nitrogen dioxide (NO.), and nitric oxide (NO,), a8 well as PM. PM is associated with the most severe air pollution= induced health effets. Like other components of air pollu: tion, PM may contain toxie substances and transport them nto the respiratory tract. The effect of PM on the body can depend on PM size, which is related to its aerodynamic diameter (AD). Most PM, particles have an AD range from 2.5 to 10 um, and are deposited in the nasal cavities and upper always. However, PM,, and PMg, particles with ADs <25 and <0.1 ym, respectively, may penetrate the Jung alveoli and enter into the bloodstream, thereby exert- ing their adverse heath effects (16-18). Furthermore, stud jes in animal models have shown that PMz, can be taken up by alveolar macrophages and endothelial cells indicating that air pollution can have direct health effets (16,17,19,20) Consequently, the ambient PM composition and size are considered the most important indicator of the adverse health effect effets of ar pollution. However, recent analy sis suggests thatthe greatest heath threat due to air pollu tion is eardiovaseular disease EPIDEMIOLOGICAL STUDIES OF PM, AND PM, Epidemiological studies assessing the relationship between air pollution and cardiovascular disease have emerged in the past twenty years. Using clinical data, these studies have distinguished the short- and long-term elects of air polli- tion on cardiovascular disease (3,9.21,10,22,23). Epidemio~ Joical studies have shown that PM, has a stronger correlation with adverse health effects than PM,,, However, assessing only PM, levels is not adequate for understanding the risk for adverse events, as larger particles can be detrimental 10 health, such as through the exacerbation of asthma, ‘There is a substantial health affected associated! with a short-term exposure to PMjy. which is related t0 black: smoke and the total suspended particles in the air. How= ever, fine particles (PM,,) also caused adverse health effects. Importantly, ultrafine particles (UPS or PMO.1) ean cause health effects through translocation ditectly into the systemic circulation. ‘The World Health Organization (WHO) reported that ambient air pollution was responsible for 3.7 million deaths in 2012, representing 6.7% of total deaths worldwide, and was the cause of 16% of lung cancer deaths, 11% of chronic obstructive pulmonary disease-related death, 29% of heart disease and stroke, and approximately 13% of deaths due to respiratory infection. Exposure to air pollution containing PM.. is closely associated with cardiovascular disease, as assessed in a lange study from metropolitan areas in the United States. The increased risk of lung cancer and cardio- vascular death after exposure 10 PM< was also seen in a cross-sectional study. In a study tha followed 8111 adults in six cities in the United States (U.S.) over |4-to-I6-years, morality rates were 1.26 fold and 1.37% higher among, people who lived in the most polluted cites versus in the least poltuted sites (24,25). Similar results were obtained when examining the association between air pollution and Iung cancer (Relative Risk (RR) 1.27; 95% Confidence Inter- val (Cl) 0.96-1.69) and cardiovascular deaths in adult cohort, from 1974 to 1990 in six US. cities. In this work, the authors found thatthe risk of death due to cardiovascular disease increased with every 10 ygim’ of PM, in the air G2. CARDIOVASCULAR DISEASES ASSOCIATED WITH PM, 5 Several reports document the relationship between PM.» and cardiovascular disease. Gold ef al, 26) demonstrated a significant increase in cardiovascular disease, from 0.5% to 1.5%, for every 5~6 pg/m’ increase in PMs. Further, they showed a 69% increase in cardiovascular deaths after acute exposure to particulate air pollution. Interestingly, acute exposure to PM, resulted in a higher rate of death due to cardiovascular than respiratory disease (69% candiovascu-