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.

Objective—: We aimed to assess whether exposure to higher levels of ambient air pollution impairs HDL (high-density lipoprotein) function and to elucidate the underlying biological mechanisms potentially involved. Approach and Results—: In the Beijing AIRCHD study (Air Pollution and Cardiovascular Dysfunction in Healthy Adults), 73 healthy adults (23.3±5.4 years) were followed-up with 4 repeated study visits in 2014 to 2016. During each visit, ambient air pollution concentrations, HDL function metrics, and parameters of inflammation and oxidative stress were measured. Average daily concentrations of ambient particulate matter in diameter <2.5 μm were 62.9 µg/m ³ (8.1–331.0 µg/m ³ ). We observed significant decreases in HDL cholesterol efflux capacity of 2.3% (95% CI, −4.3 to −0.3) to 5.0% (95% CI, −7.6 to −2.4) associated with interquartile range increases in moving average concentrations of particulate matter in diameter <2.5 μm and traffic-related air pollutants (black carbon, nitrogen dioxide, and carbon monoxide) during the 1 to 7 days before each participant’s clinic visit. Higher ambient air pollutant levels were also associated with significant reductions in circulating HDL cholesterol and apoA-I (apolipoprotein A-I), as well as elevations in HDL oxidation index, oxidized LDL (low-density lipoprotein), malondialdehyde, and high-sensitivity C-reactive protein. Conclusions—: Higher ambient air pollution concentrations were associated with impairments in HDL functionality, potentially because of systemic inflammation and oxidative stress. These novel findings further our understanding of the mechanisms whereby air pollutants promote cardiometabolic disorders.

Numerous epidemiologic studies on adverse health effects of air pollution have been well documented; however, assessment on health benefits of air quality improvement from air pollution control measures has been limited in developing countries. We assessed the mortality benefits associated with air pollution improvement over 11 years in Guangzhou, China (2006-2016). A time series analysis with Generalized additive Poisson models was used to estimate mortality effects of ozone (O3) and nitrogen dioxide (NO2), adjusting for time trend, day of week, public holiday, temperature and relative humidity. We further estimated the changes in mortality burden of O3 and NO2, including attributable fraction (AF, in %) and attributable mortality (AM, in number of death) during study period. We lastly estimated mortality effects during the 2010 Asian Games (November 12 to December 18, 2010) compared to a baseline period consisting of 4-week before and 4-week after the game. During the study period, average annual concentrations of NO2 decreased from 42.3 μg/m3 in 2006 to 33.8 μg/m3 in 2016; while O3 levels remained stable over time. We observed significant increases in mortality of O3 and NO2, with approximately linear exposure-response relationships. In specific, each increase of 10 μg/m3 in O3 and NO2 at 2 prior days was associated with increases of 0.60% (95% confidence interval (CI): 0.47, 0.74) and 1.89% (95%CI: 1.49, 2.29) in total mortality, respectively. We further estimated that AF on total mortality attributed to NO2 decreased from 1.38% (95%CI: 1.09, 1.68) in 2006-2010 to 0.43% (95%CI: 0.34, 0.52) in 2011-2016, corresponding to AM on total mortality of 2496 deaths (95%CI: 1964, 3033) to 1073 deaths (95%CI: 846, 1301). During the 2010 Asian Games, we observed decrease in total mortality of 9.3% (95%CI: -15.0, -3.2) in comparison with that observed in the baseline period. Similar mortality benefits in cardiovascular diseases were also observed. Our results showed reduced mortality burden from air pollution improvement in Guangzhou in recent years, which provide strong rationale for continuing to reduce air pollution through comprehensive and rigorous air quality management in the area.

The mechanisms whereby ambient air pollution and temperature changes promote cardiac events remain incompletely described. Seventy-three nonsmoking healthy adults (mean age 23.3, SD 5.4 years) were followed with up to four repeated visits across 15 months in Beijing in 2014–2016. Biomarkers relevant to myocardial damage (high-sensitivity cardiac troponin I [hs-cTnI]), inflammation (growth differentiation factor-15 [GDF-15]), and oxidative stress (8-hydroxy-2′-deoxyguanosine [8-OHdG]) were measured at each visit, while ambient air pollution and temperature were monitored throughout the study. Linear mixed-effects models coupled with distributed lag nonlinear models were used to assess the impacts of each exposure measure on study outcomes. During follow-up, average daily concentrations of fine particulate matter and outdoor temperature were 62.9 µg/m³ (8.1–331.0 µg/m³) and 10.1 °C (−6.5°C to 29.5°C). Serum hs-cTnI levels were detectable in 18.2% of blood samples, with 27.4% of individuals having ≥1 detectable values. Higher levels of ambient particulates and gaseous pollutants (per interquartile range) up to 14 days before clinical visits were associated with significant alterations in hs-cTnI levels of 22.9% (95% CI, 6.4, 39.4) to 154.7% (95% CI, 94.4, 215.1). These changes were accompanied by elevations of circulating GDF-15 and urinary 8-OHdG levels. Both low (5th percentile, −2.5 °C) and high (95th percentile, 24.8°C) outdoor temperatures, with breakpoint at ~13.0°C as the reference level, were also associated with elevations of hs-cTnI levels. Short-term exposure to ambient air pollution and temperature was associated with cardiac troponin, a biomarker of myocardial damage, along with increased inflammation and oxidative stress responses. These findings extend our understanding of the biological mechanisms linking pervasive environmental exposure to adverse cardiac events.

Background: Ambient fine particulate matter with aerodynamic diameter less than 2.5 µm (PM_2.5) has been associated with deteriorated respiratory health, but evidence on particles in smaller sizes and childhood respiratory health has been limited.Methods: We collected time-series data on daily respiratory emergency room visits (ERVs) among children under 14 years old in Beijing, China, during 2015–2017. Concurrently, size-fractioned number concentrations of particles in size ranges of 5–560 nm (PNC_5–560) and mass concentrations of PM_2.5, black carbon (BC) and nitrogen dioxide (NO₂) were measured from a fixed-location monitoring station in the urban area of Beijing. Confounder-adjusted Poisson regression models were used to estimate excessive risks (ERs) of particle size fractions on childhood respiratory ERVs, and positive matrix factorisation models were applied to apportion the sources of PNC_5–560.Results: Among the 136 925 cases of all-respiratory ERVs, increased risks were associated with IQR increases in PNC_25–100 (ER=5.4%, 95% CI 2.4% to 8.6%), PNC_100–560 (4.9%, 95% CI 2.5% to 7.3%) and PM_2.5 (1.3%, 95% CI 0.1% to 2.5%) at current and 1 prior days (lag0–1). Major sources of PNC_5–560 were identified, including nucleation (36.5%), gasoline vehicle emissions (27.9%), diesel vehicle emissions (18.9%) and secondary aerosols (10.6%). Emissions from gasoline and diesel vehicles were found of significant associations with all-respiratory ERVs, with increased ERs of 6.0% (95% CI 2.5% to 9.7%) and 4.4% (95% CI 1.7% to 7.1%) at lag0–1 days, respectively. Exposures to other traffic-related pollutants (BC and NO₂) were also associated with increased respiratory ERVs.Conclusion: Our findings suggest that exposures to higher levels of PNC_5–560 from traffic emissions could be attributed to increased childhood respiratory morbidity, which supports traffic emission control priority in urban areas.