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Background: Ambient particulate matter (PM) air pollution is associated with coronary heart disease, but the pathways underlying the association remain to be elucidated.
Methods: We studied the association between PM and ischemia among 57,908 Women’s Health Initiative clinical trial participants from 1999–2003. We used the Minnesota Code criteria to identify ST-segment and T-wave abnormalities, and estimated T amplitude (microvolt) from resting, standard 12-lead electrocardiogram (ECG). We used U.S. Environmental Protection Agency’s monitor data to estimate concentrations of PM < 2.5 μm (PM2.5) at geocoded participant addresses over 6 days before the ECGs (lag0 through lag5). We excluded 2,379 women with ECG QRS duration ≥ 120 msec.
Results: Overall, 6% of the remaining 55,529 women (52–90 years of age; 83% non-Hispanic white) had ST abnormalities and 16% had T abnormalities. Lead-specific T amplitude was normally distributed (range of means from −14 to 349 μV). PM2.5 (mean ± SD) averaged over lag0–2 was 14 ± 7 μg/m. In logistic and linear regression models adjusted for demographic, clinical, temporal, and climatic factors, a 10-μg/m increase in lag0–2 PM2.5 was associated with a 4% [95% confidence interval (CI), −3%, to 10%] increase in the odds of ST abnormality and a 5% (95% CI, 0% to 9%) increase in the odds of T abnormality. We observed corresponding decreases in T amplitude in all exam sites and leads except lead V1, reaching a minimum of −2 μV (95% CI, −5 to 0 μV) in lead V3.
Conclusions: Short-term PM2.5 exposure is associated with ECG evidence of myocardial ischemia among postmenopausal women. The principal manifestations include subclinical but potentially arrhythmogenic ST–T abnormalities and decreases in T amplitude.
Background: Population-based studies have estimated health risks of short-term exposure to fine particles using mass of PM2.5 (particulate matter ≤ 2.5 μm in aerodynamic diameter) as the indicator. Evidence regarding the toxicity of the chemical components of the PM2.5 mixture is limited.
Objective: In this study we investigated the association between hospital admission for cardiovascular disease (CVD) and respiratory disease and the chemical components of PM2.5 in the United States.
Methods: We used a national database comprising daily data for 2000–2006 on emergency hospital admissions for cardiovascular and respiratory outcomes, ambient levels of major PM2.5 chemical components [sulfate, nitrate, silicon, elemental carbon (EC), organic carbon matter (OCM), and sodium and ammonium ions], and weather. Using Bayesian hierarchical statistical models, we estimated the associations between daily levels of PM2.5 components and risk of hospital admissions in 119 U.S. urban communities for 12 million Medicare enrollees (≥ 65 years of age).
Results: In multiple-pollutant models that adjust for the levels of other pollutants, an interquartile range (IQR) increase in EC was associated with a 0.80% [95% posterior interval (PI), 0.34–1.27%] increase in risk of same-day cardiovascular admissions, and an IQR increase in OCM was associated with a 1.01% (95% PI, 0.04–1.98%) increase in risk of respiratory admissions on the same day. Other components were not associated with cardiovascular or respiratory hospital admissions in multiple-pollutant models.
Conclusions: Ambient levels of EC and OCM, which are generated primarily from vehicle emissions, diesel, and wood burning, were associated with the largest risks of emergency hospitalization across the major chemical constituents of PM2.5.
Background: Cardiovascular disease (CVD) affects 71 million American adults and remains the leading cause of death in the United States and Europe. Despite studies that suggest that the development of CVD may be linked to intrauterine growth or early events in childhood, little direct experimental evidence supports the notion.
Objective: We investigated whether exposure to cigarette smoke in utero alters the risk of developing CVD later in life.
Methods: We exposed B6C3F1 mice (via whole-body inhalation) to either filtered air or mainstream cigarette smoke (MCS, at a particle concentration of 15 mg/m) from gestational day 4 to parturition. Adult offspring were fed a normal chow diet or switched to a high-fat diet 2 weeks before sacrifice. We measured dam and offspring body weight, plasma lipid parameters, lipoprotein subclass particle numbers and sizes, and total antioxidant capacities.
Results: Adult female mice prenatally exposed to MCS demonstrated significantly higher body weight and levels of plasma high-density lipoprotein (HDL) and low-density lipoprotein than did their air-exposed counterparts. When fed a high-fat diet for 2 weeks, males, but not females, exposed prenatally to MCS gained substantially more weight and exhibited dramatic alterations in total cholesterol and HDL levels compared with their air-exposed counterparts.
Conclusions: These data provide, for the first time, direct experimental evidence supporting the notion that prenatal exposure to cigarette smoke affects offspring weight gain and induces a lipid profile that could alter the offspring’s risk of developing CVD later in life.
Background: Long-term exposure to urban air pollution may accelerate atherogenesis, but mechanisms are still unclear. The induction of a low-grade systemic inflammatory state is a plausible mechanistic pathway. Objectives: We analyzed the association of residential long-term exposure to particulate matter (PM) and high traffic with systemic inflammatory markers.
Methods: We used baseline data from the German Heinz Nixdorf Recall Study, a population-based, prospective cohort study of 4,814 participants that started in 2000. Fine PM [aerodynamic diameter ≤ 2.5 μm (PM2.5)] exposure based on a small-scale dispersion and chemistry transport model was assigned to each home address. We calculated distances between residences and major roads. Long-term exposure to air pollution (annual PM2.5 and distance to high traffic) and concentration of inflammatory markers [high-sensitivity C-reactive protein (hs-CRP) and fibrinogen] on the day of the baseline visit were analyzed with sex-stratified multiple linear regression, controlling for individual-level risk factors.
Results: In the adjusted analysis, a cross-sectional exposure difference of 3.91 μg/m in PM2.5 (interdecile range) was associated with increases in hs-CRP of 23.9% [95% confidence interval (CI), 4.1 to 47.4%] and fibrinogen of 3.9% (95% CI, 0.3 to 7.7%) in men, whereas we found no association in women. Chronic traffic exposure was not associated with inflammatory markers. Short-term exposures to air pollutants and temperature did not influence the results markedly.
Conclusions: Our study indicates that long-term residential exposure to high levels of PM2.5 is associated with systemic inflammatory markers in men. This might provide a link between air pollution and coronary atherosclerosis.
Background: Air pollution has consistently been associated with increased morbidity and mortality due to respiratory and cardiovascular disease. Underlying biological mechanisms are not entirely clear, and hemostasis and inflammation are suggested to be involved.
Objectives: Our aim was to study the association of the variation in local concentrations of airborne particulate matter (PM) with aerodynamic diameter < 10 μm, carbon monoxide, nitrogen monoxide, nitrogen dioxide, and ozone with platelet aggregation, thrombin generation, fibrinogen, and C-reactive protein (CRP) levels in healthy individuals.
Methods: From 40 healthy volunteers, we collected 13 consecutive blood samples within a 1-year period and measured light-transmittance platelet aggregometry, thrombin generation, fibrinogen, and CRP. We performed regression analysis using generalized additive models to study the association between the hemostatic and inflammatory variables, and local environmental concentrations of air pollutants for time lags within 24 hr before blood sampling or 24–96 hr before blood sampling.
Results: In general, air pollutants were associated with platelet aggregation [average, +8% per interquartile range (IQR), p < 0.01] and thrombin generation (average, +1% per IQR, p < 0.05). Platelet aggregation was not affected by in vitro incubation of plasma with PM. We observed no relationship between any of the air pollutants and fibrinogen or CRP levels.
Conclusions: Air pollution increased platelet aggregation as well as coagulation activity but had no clear effect on systemic inflammation. These prothrombotic effects may partly explain the relationship between air pollution and the risk of ischemic cardiovascular disease.
Background: The southern United States (excluding Florida) has the highest age-adjusted rate of cardiovascular disease (CVD) in the country, with African Americans having a higher prevalence of CVD than Caucasians. Paraoxonase-1 (PON1), an enzyme associated with high-density lipoprotein particles, participates both in the hydrolysis of oxidized lipids (thus protecting against atherosclerosis) and in the hydrolysis of organophosphates. Higher paraoxonase activity has been associated with lower risk of atherosclerosis.
Objectives: In this study we characterized the distribution of the functional PON1Q192R polymorphisms (PON status as assessed by diazoxonase to paraoxonase ratios) and the PON1 activity levels in 200 adult males and females of both races (50 in each race/sex class) from the southern United States from commercially obtained blood bank serum samples.
Methods: We used spectrophotometric methods with serum to determine PON1 status, arylesterase activities (phenyl acetate hydrolysis), and levels of cotinine and C-reactive protein (CRP).
Results: African Americans had higher paraoxonase activities but lower diazoxonase activities than did Caucasians, consistent with African Americans having a lower proportion of the functional genotype QQ (QQ 15%, QR 34%, RR 44%, 7% indeterminate), than did Caucasians (QQ 60%, QR 31%, RR 7%, 2% indeterminate). Cotinine levels indicated that all samples came from non-smokers and that CRP levels were higher in African Americans than in Caucasians and higher in females than in males. CRP levels showed no association with paraoxonase activities.
Conclusions: These data present initial observations for use in characterizing the poorer cardiovascular health status of the population in the southern United States and more specifically southern African Americans.
Background: The relationship of fine particulate matter < 2.5 μm in diameter (PM2.5) air pollution with mortality and cardiovascular disease is well established, with more recent long-term studies reporting larger effect sizes than earlier long-term studies. Some studies have suggested the coarse fraction, particles between 2.5 and 10 μm (PM10–2.5), may also be important. With respect to mortality and cardiovascular events, questions remain regarding the relative strength of effect sizes for chronic exposure to fine and coarse particles.
Objectives: We examined the relationship of chronic PM2.5 and PM10–2.5 exposures with all-cause mortality and fatal and nonfatal incident coronary heart disease (CHD), adjusting for time-varying covariates.
Methods: The current study included women from the Nurses’ Health Study living in metropolitan areas of the northeastern and midwestern United States. Follow-up was from 1992 to 2002. We used geographic information systems–based spatial smoothing models to estimate monthly exposures at each participant’s residence.
Results: We found increased risk of all-cause mortality [hazard ratio (HR), 1.26; 95% confidence interval (CI), 1.02–1.54] and fatal CHD (HR = 2.02; 95% CI, 1.07–3.78) associated with each 10-μg/m increase in annual PM2.5 exposure. The association between fatal CHD and PM10–2.5 was weaker.
Conclusions: Our findings contribute to growing evidence that chronic PM2.5 exposure is associated with risk of all-cause and cardiovascular mortality.
Background: Several studies show an association between exposure to aircraft or road traffic noise and cardiovascular effects, which may be mediated by a noise-induced release of stress hormones.
Objective: Our objective was to assess saliva cortisol concentration in relation to exposure to aircraft noise.
Method: A multicenter cross-sectional study, HYENA (Hypertension and Exposure to Noise near Airports), comprising 4,861 persons was carried out in six European countries. In a subgroup of 439 study participants, selected to enhance the contrast in exposure to aircraft noise, saliva cortisol was assessed three times (morning, lunch, and evening) during 1 day.
Results: We observed an elevation of 6.07 nmol/L [95% confidence interval (CI), 2.32–9.81 nmol/L] in morning saliva cortisol level in women exposed to aircraft noise at an average 24-hr sound level (LAeq,24h) > 60 dB, compared with women exposed to LAeq,24h ≤ 50 dB, corresponding to an increase of 34%. Employment status appeared to modify the response. We found no association between noise exposure and saliva cortisol levels in men.
Conclusions: Our results suggest that exposure to aircraft noise increases morning saliva cortisol levels in women, which could be of relevance for noise-related cardiovascular effects.
Background: The mechanisms for the relationship between particulate pollution and cardiac disease are not fully understood.
Objective: We examined the effects and time course of exposure to fine particulate matter ≤ 2.5 μm in aerodynamic diameter (PM2.5) on ventricular repolarization of 106 nonsmoking adults who were living in communities in central Pennsylvania.
Methods: The 24-hr beat-to-beat electrocardiogram (ECG) data were obtained using a high-resolution 12-lead Holter system. After visually identifying and removing artifacts and arrhythmic beats, we summarized normal beat-to-beat QTs from each 30-min segment as heart rate (HR)-corrected QT measures: QT prolongation index (QTI), Bazett’s HR-corrected QT (QTcB), and Fridericia’s HR-corrected QT (QTcF). A personal PM2.5 monitor was used to measure individual-level real-time PM2.5 exposures for 24 hr. We averaged these data and used 30-min time-specific average PM2.5 exposures.
Results: The mean age of the participants was 56 ± 8 years, with 41% male and 74% white. The means ± SDs for QTI, QTcB, and QTcF were 111 ± 6.6, 438 ± 23 msec, and 422 ± 22 msec, respectively; and for PM2.5, the mean ± SD was 14 ± 22 μg/m. We used distributed lag models under a framework of linear mixed-effects models to assess the autocorrelation-corrected regression coefficients (β) between 30-min PM2.5 and the HR-corrected QT measures. Most of the adverse ventricular repolarization effects from PM2.5 exposure occurred within 3–4 hr. The multivariable adjusted β (SE, p-value) due to a 10-μg/m increase in lag 7 PM2.5 on QTI, QTcB, and QTcF were 0.08 (0.04, p < 0.05), 0.22 (0.08, p < 0.01), and 0.09 (0.05, p < 0.05), respectively.
Conclusions: Our results suggest a significant adverse effect of PM2.5 on ventricular repolarization. The time course of the effect is within 3–4 hr of elevated PM2.5.
Background: Recent analysis has demonstrated a remarkably consistent, nonlinear relationship between estimated inhaled dose of combustion particles measured as PM2.5 (particulate matter with aerodynamic diameter ≤ 2.5 μm) and cardiovascular disease mortality over several orders of magnitude of dose—from cigarette smoking, environmental tobacco smoke (ETS) exposure, and ambient air pollution exposure.
Objectives: Here we discuss the implications of this relationship and point out the gaps in our knowledge that it reveals.
Discussion: The nonlinear exposure–response relationship that is revealed—much steeper at lower than at higher doses—explains the seemingly inconsistent risks observed from ambient air pollution and cigarette smoking but also raises important questions about the relative benefits of control at different points along the curve. This analysis also reveals a gap in the evidence base along the dose–response curve between ETS and active smoking, which is the dose range experienced by half the world’s population from indoor biomass and coal burning for cooking and heating.
Conclusions: The shape of the exposure–response relationship implies much larger public health benefits of reductions at the lower end of the dose spectrum (e.g., from reductions in outdoor air pollution) than from reducing the rate of active smoking, which seems counterintuitive and deserving of further study because of its importance for control policies. In addition, given the potential risks and consequent global disease burden, epidemiologic studies are urgently needed to quantify the cardiovascular risks of particulate matter exposures from indoor biomass burning in developing countries, which lie in the dose gap of current evidence.
Background: The mechanisms underlying the relationship between particulate matter (PM) air pollution and cardiac disease are not fully understood.
Objectives: We examined the effects and time course of exposure to fine PM [aerodynamic diameter ≤ 2.5 μm (PM2.5)] on cardiac arrhythmia in 105 middle-age community-dwelling healthy nonsmokers in central Pennsylvania.
Methods: The 24-hr beat-to-beat electrocardiography data were obtained using a high-resolution Holter system. After visually identifying and removing artifacts, we summarized the total number of premature ventricular contractions (PVCs) and premature atrial contractions (PACs) for each 30-min segment. A personal PM2.5 nephelometer was used to measure individual-level real-time PM2.5 exposures for 24 hr. We averaged these data to obtain 30-min average time–specific PM2.5 exposures. Distributed lag models under the framework of negative binomial regression and generalized estimating equations were used to estimate the rate ratio between 10-μg/m increases in average PM2.5 over 30-min intervals and ectopy counts.
Results: The mean ± SD age of participants was 56 ± 8 years, with 40% male and 73% non-Hispanic white. The 30-min mean ± SD for PM2.5 exposure was 13 ± 22 μg/m, and PAC and PVC counts were 0.92 ± 4.94 and 1.22 ± 7.18. Increases of 10 μg/m in average PM2.5 concentrations during the same 30 min or the previous 30 min were associated with 8% and 3% increases in average PVC counts, respectively. PM2.5 was not significantly associated with PAC count.
Conclusion: PM2.5 exposure within approximately 60 min was associated with increased PVC counts in healthy individuals.
Background: A large body of evidence suggests that fine particulate matter (PM) air pollution is a cause of cardiovascular disease, but little is known in particular about the cardiovascular effects of indoor air pollution from household use of solid fuels in developing countries. RESPIRE (Randomized Exposure Study of Pollution Indoors and Respiratory Effects) was a randomized trial of a chimney woodstove that reduces wood smoke exposure.
Objectives: We tested the hypotheses that the stove intervention, compared with open fire use, would reduce ST-segment depression and increase heart rate variability (HRV).
Methods: We used two complementary study designs: a) between-groups comparisons based on randomized stove assignment, and b) before-and-after comparisons within control subjects who used open fires during the trial and received chimney stoves after the trial. Electrocardiogram sessions that lasted 20 hr were repeated up to three times among 49 intervention and 70 control women 38–84 years of age, and 55 control subjects were also assessed after receiving stoves. HRV and ST-segment values were assessed for each 30-min period. ST-segment depression was defined as an average value below –1.00 mm. Personal fine PM [aerodynamic diameter ≤ 2.5 μm (PM2.5)] exposures were measured for 24 hr before each electrocardiogram.
Results: PM2.5 exposure means were 266 and 102 μg/m during the trial period in the control and intervention groups, respectively. During the trial, the stove intervention was associated with an odds ratio of 0.26 (95% confidence interval, 0.08–0.90) for ST-segment depression. We found similar associations with the before-and-after comparison. The intervention was not significantly associated with HRV.
Conclusions: The stove intervention was associated with reduced occurrence of nonspecific ST-segment depression, suggesting that household wood smoke exposures affect ventricular repolarization and potentially cardiovascular health.
Background: The association of all-cause mortality and cardiovascular outcomes with air pollution exposures has been well established in the literature. The number of studies examining chronic exposures in cohorts is growing, with more recent studies conducted among women finding risk estimates of greater magnitude. Questions remain regarding sex differences in the relationship of chronic particulate matter (PM) exposures with mortality and cardiovascular outcomes.
Objectives: In this study we explored these associations in the all-male Health Professionals Follow-Up Study prospective cohort.
Methods: The same spatiotemporal exposure estimation models, similar outcomes, and biennially updated covariates were used as those previously applied in the female Nurses’ Health Study cohort.
Results: Among 17,545 men residing in the northeastern and midwestern United States, there were 2,813 deaths, including 746 cases of fatal coronary heart disease (CHD). An interquartile range change (4 µg/m) in average exposure to PM ≤ 2.5 µm in diameter in the 12 previous months was not associated with all-cause mortality [hazard ratio (HR) = 0.94; 95% confidence interval (CI), 0.87–1.00] or fatal CHD (HR = 0.99; 95% CI, 0.87–1.13) in fully adjusted models. Findings were similar for separate models of exposure to PM ≤ 10 µm in diameter and PM between 2.5 and 10 µm in diameter and for copollutant models.
Conclusions: Among this cohort of men with high socioeconomic status living in the midwestern and northeastern United States, the results did not support an association of chronic PM exposures with all-cause mortality and cardiovascular outcomes in models with time-varying covariates. Whether these findings suggest sex differences in susceptibility or the protective impact of healthier lifestyles and higher socioeconomic status requires additional investigation.
Background: Few studies have directly assessed the association of secondhand smoke (SHS) with cardiovascular disease–related inflammatory markers, and the findings are inconsistent.
Objectives: We assessed the association between SHS exposure and the inflammatory markers high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and soluble intercellular adhesion molecule-1 (sICAM-1) in 199 nonsmoking U.S. trucking industry workers.
Methods: Participants provided blood samples either by mail (blood drawn at local health care provider near home) or at the work site (blood drawn by research staff on-site) and completed a health and work history questionnaire at the time of blood draw. Exposure to SHS was measured by plasma cotinine concentrations. We used multivariate regression analyses to assess the associations between levels of cotinine and inflammatory markers.
Results: The median cotinine level was 0.10 ng/mL (interquartile range, 0.04–0.23 ng/mL). The odds ratios of elevated hs-CRP (above highest CRP tertile, 1.5 mg/L) were 2.85 [95% confidence interval (CI), 1.03–7.89] for the high-cotinine group (> 0.215 ng/mL) and 2.80 (95% CI, 1.11–7.10) for the moderate-cotinine group (0.05–0.215 ng/mL), compared with the low-cotinine group (< 0.05 ng/mL), adjusting for age, sex, race, educational level, obesity, previous smoking history, job title, and medical history. Plasma cotinine levels were not associated with IL-6 or sICAM-1.
Conclusions: SHS exposure, as assessed by plasma cotinine, was positively associated with hs-CRP in this group of blue-collar workers. The strength of the association with hs-CRP depended on the cut points selected for analysis.
Background: Epidemiologic studies of cardiovascular disease risk factors and appropriate biomarkers in populations exposed to a wide range of arsenic levels are a public health research priority.
Objective: We investigated the relationship between inorganic arsenic exposure from drinking water and plasma levels of soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular adhesion molecule-1 (sVCAM-1), both markers of endothelial dysfunction and vascular inflammation, in an arsenic-exposed population in Araihazar, Bangladesh.
Methods: The study participants included 115 individuals with arsenic-related skin lesions participating in a 2 × 2 randomized, placebo-controlled, double-blind trial of vitamin E and selenium supplementation. Arsenic exposure status and plasma levels of sICAM-1 and sVCAM-1 were assessed at baseline and after 6 months of follow-up.
Results: Baseline well arsenic, a long-term measure of arsenic exposure, was positively associated with baseline levels of both sICAM-1 and sVCAM-1 and with changes in the two markers over time. At baseline, for every 1-μg/L increase in well arsenic there was an increase of 0.10 ng/mL [95% confidence interval (CI), 0.00–0.20] and 0.33 ng/mL (95% CI, 0.15–0.51) in plasma sICAM-1 and sVCAM-1, respectively. Every 1-μg/L increase in well arsenic was associated with a rise of 0.11 ng/mL (95% CI, 0.01–0.22) and 0.17 ng/mL (95% CI, 0.00–0.35) in sICAM-1 and sVCAM-1 from baseline to follow-up, respectively, in spite of recent changes in urinary arsenic as well as vitamin E and selenium supplementation during the study period.
Conclusions: The findings indicate an effect of chronic arsenic exposure from drinking water on vascular inflammation that persists over time and also suggest a potential mechanism underlying the association between arsenic exposure and cardiovascular disease.
Background: Blood pressure (BP) may be implicated in associations observed between ambient particulate matter and cardiovascular morbidity and mortality. This study examined cross-sectional associations between short-term ambient fine particles (particulate matter ≤ 2.5 μm in aerodynamic diameter; PM2.5) and BP: systolic (SBP), diastolic (DBP), mean arterial (MAP), and pulse pressure (PP).
Methods: The study sample included 5,112 persons 45–84 years of age, free of cardiovascular disease at the Multi-Ethnic Study of Atherosclerosis baseline examination (2000–2002). Data from U.S. Environmental Protection Agency monitors were used to estimate ambient PM2.5 exposures for the preceding 1, 2, 7, 30, and 60 days. Roadway data were used to estimate local exposures to traffic-related particles.
Results: Results from linear regression found PP and SBP positively associated with PM2.5. For example, a 10-μg/m increase in PM2.5 30-day mean was associated with 1.12 mmHg higher pulse pressure [95% confidence interval (CI), 0.28–1.97] and 0.99 mmHg higher systolic BP (95% CI, –0.15 to 2.13), adjusted for age, sex, race/ethnicity, income, education, body mass index, diabetes, cigarette smoking and environmental tobacco smoke, alcohol use, physical activity, medications, atmospheric pressure, and temperature. Results were much weaker and not statistically significant for MAP and DBP. Although traffic-related variables were not themselves associated with BP, the association between PM2.5 and BP was stronger in the presence of higher traffic exposure.
Conclusions: Higher SBP and PP were associated with ambient levels of PM2.5 and the association was stronger in the presence of roadway traffic, suggesting that impairment of blood pressure regulation may play a role in response to air pollution.
Background: Lung cancer and cardiovascular disease (CVD) mortality risks increase with smoking, secondhand smoke (SHS), and exposure to fine particulate matter < 2.5 μm in diameter (PM2.5) from ambient air pollution. Recent research indicates that the exposure–response relationship for CVD is nonlinear, with a steep increase in risk at low exposures and flattening out at higher exposures. Comparable estimates of the exposure–response relationship for lung cancer are required for disease burden estimates and related public health policy assessments.
Objectives: We compared exposure–response relationships of PM2.5 with lung cancer and cardiovascular mortality and considered the implications of the observed differences for efforts to estimate the disease burden of PM2.5.
Methods: Prospective cohort data for 1.2 million adults were collected by the American Cancer Society as part of the Cancer Prevention Study II. We estimated relative risks (RRs) for increments of cigarette smoking, adjusting for various individual risk factors. RRs were plotted against estimated daily dose of PM2.5 from smoking along with comparison estimates for ambient air pollution and SHS.
Results: For lung cancer mortality, excess risk rose nearly linearly, reaching maximum RRs > 40 among long-term heavy smokers. Excess risks for CVD mortality increased steeply at low exposure levels and leveled off at higher exposures, reaching RRs of approximately 2–3 for cigarette smoking.
Conclusions: The exposure–response relationship associated with PM2.5 is qualitatively different for lung cancer versus cardiovascular mortality. At low exposure levels, cardiovascular deaths are projected to account for most of the burden of disease, whereas at high levels of PM2.5, lung cancer becomes proportionately more important.
Background: Traffic-related particles (TRPs) are associated with adverse cardiovascular events. The exact mechanisms are unclear, but systemic inflammatory responses likely play a role.
Objectives: We conducted a repeated measures study among male participants of the Normative Aging Study in the greater Boston, Massachusetts, area to determine whether individual-level residential black carbon (BC), a marker of TRPs, is associated with systemic inflammation and whether coronary heart disease (CHD), diabetes, and obesity modify associations.
Methods: We quantified markers of inflammation in 1,163 serum samples from 580 men. Exposure to BC up to 4 weeks prior was predicted from a validated spatiotemporal land-use regression model. Linear mixed effects models estimated the effects of BC on each marker while adjusting for potential confounders.
Results: Associations between BC and blood markers were not observed in main effects models or when stratified by obesity status. However, BC was positively associated with markers of inflammation in men with CHD (particularly vascular endothelial growth factor) and in men with diabetes (particularly interleukin-1β and tumor necrosis factor-α). Significant exposure time windows varied by marker, although in general the strongest associations were observed with moving averages of 2–7 days after a lag of several days.
Conclusions: In an elderly male population, estimated BC exposures were positively associated with markers of systemic inflammation but only in men with CHD or diabetes.
Background: Surface-available iron (Fe) is proposed to contribute to asbestos-induced toxicity through the production of reactive oxygen species.
Objective: Our goal was to evaluate the hypothesis that rat models of cardiovascular disease with coexistent Fe overload would be increasingly sensitive to Libby amphibole (LA)-induced subchronic lung injury.
Methods: Male healthy Wistar Kyoto (WKY), spontaneously hypertensive (SH), and SH heart failure (SHHF) rats were intratracheally instilled with 0.0, 0.25, or 1.0 mg LA (with saline as the vehicle). We examined bronchoalveolar lavage fluid (BALF) and histological lung sections after 1 week, 1 month, or 3 months for pulmonary biomarkers and pathology. SHHF rats were also assessed at 6 months for pathological changes.
Results: All animals developed concentration- and time-dependent interstitial fibrosis. Time-dependent Fe accumulation occurred in LA-laden macrophages in all strains but was exacerbated in SHHF rats. LA-exposed SHHF rats developed atypical hyperplastic lesions of bronchiolar epithelial cell origin at 3 and 6 months. Strain-related baseline differences existed in gene expression at 3 months, with persistent LA effects in WKY but not SH or SHHF rats. LA exposure altered genes for a number of pathways, including inflammation, immune regulation, and cell-cycle control. Cell-cycle control genes were inhibited after LA exposure in SH and SHHF but not WKY rats, whereas tumor suppressor genes were induced only in WKY rats. The inflammatory gene expression also was apparent only in WKY rats.
Conclusion: These data show that in Fe-overload conditions, progressive Fe accumulation occurs in fiber-laden macrophages within LA-induced lesions. Fe overload does not appear to contribute to chronic inflammation, and its role in hyperplastic lesion development requires further examination.
Background: Exposure to ambient fine particulate matter air pollution (PM2.5; < 2.5 µm in aerodynamic diameter) induces endothelial dysfunction and increases the risk for cardiovascular disease. Endothelial progenitor cells (EPCs) contribute to postnatal endothelial repair and regeneration. In humans and mice, EPC levels are decreased upon exposure to elevated levels of PM2.5.
Objective: We examined the mechanism by which PM2.5 exposure suppresses circulating levels of EPCs.
Methods: Mice were exposed to HEPA-filtered air or concentrated ambient fine particulate matter (CAP, 30–100 µg/m) from downtown Louisville (Kentucky) air, and progenitor cells from peripheral blood or bone marrow were analyzed by flow cytometry or by culture ex vivo.
Results: Exposure of the mice to CAP (6 hr/day) for 4–30 days progressively decreased circulating levels of EPCs positive for both Flk-1 and Sca-1 (Flk-1/Sca-1) without affecting stem cells positive for Sca-1 alone (Sca-1). After 9 days of exposure, a 7-day exposure-free period led to complete recovery of the circulating levels of Flk-1/Sca-1 cells. CAP exposure decreased circulating levels of EPCs independent of apoptosis while simultaneously increasing Flk-1/Sca-1 cells in the bone marrow. We observed no change in tissue deposition of these cells. CAP exposure suppressed vascular endothelial growth factor (VEGF)-induced Akt and endothelial nitric oxide synthase (eNOS) phosphorylation in the aorta, and it prevented VEGF/AMD3100-induced mobilization of Flk-1/Sca-1 cells into the peripheral blood. Treatment with stem cell factor/AMD3100 led to a greater increase in circulating Flk-1/Sca-1 cells in CAP-exposed mice than in mice breathing filtered air.
Conclusion: Exposure to PM2.5 increases EPC levels in the bone marrow by preventing their mobilization to the peripheral blood via inhibition of signaling events triggered by VEGF-receptor stimulation that are upstream of c-kit activation. Suppression of EPC mobilization by PM2.5 could induce deficits in vascular repair or regeneration.