The Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air) was initiated in 2004 to investigate the relation between individual-level estimates of long-term air pollution exposure and the progression of subclinical atherosclerosis and the incidence of cardiovascular disease (CVD). MESA Air builds on a multicenter, community-based US study of CVD, supplementing that study with additional participants, outcome measurements, and state-of-the-art air pollution exposure assessments of fine particulate matter, oxides of nitrogen, and black carbon. More than 7,000 participants aged 45–84 years are being followed for over 10 years for the identification and characterization of CVD events, including acute myocardial infarction and other coronary artery disease, stroke, peripheral artery disease, and congestive heart failure; cardiac procedures; and mortality. Subcohorts undergo baseline and follow-up measurements of coronary artery calcium using computed tomography and carotid artery intima-medial wall thickness using ultrasonography. This cohort provides vast exposure heterogeneity in ranges currently experienced and permitted in most developed nations, and the air monitoring and modeling methods employed will provide individual estimates of exposure that incorporate residence-specific infiltration characteristics and participant-specific time-activity patterns. The overarching study aim is to understand and reduce uncertainty in health effect estimation regarding long-term exposure to air pollution and CVD.
air pollution; atherosclerosis; cardiovascular diseases; environmental exposure; epidemiologic methods; particulate matter
Concentrations of outdoor fine particulate matter (PM2.5) have been associated with cardiovascular disease. PM2.5 chemical composition may be responsible for effects of exposure to PM2.5.
Using data from the Multi-Ethnic Study of Atherosclerosis (MESA) collected in 2000–2002 on 6,256 US adults without clinical cardiovascular disease in six U.S. metropolitan areas, we investigated cross-sectional associations of estimated long-term exposure to total PM2.5 mass and PM2.5 components (elemental carbon [EC], organic carbon [OC], silicon and sulfur) with measures of subclinical atherosclerosis (coronary artery calcium [CAC] and right common carotid intima-media thickness [CIMT]). Community monitors deployed for this study from 2007 to 2008 were used to estimate exposures at baseline addresses using three commonly-used approaches: (1) nearest monitor (the primary approach), (2) inverse-distance monitor weighting and (3) city-wide average.
Using the exposure estimate based on nearest monitor, in single-pollutant models, increased OC (effect estimate [95% CI] per IQR: 35.1 μm [26.8, 43.3]), EC (9.6 μm [3.6,15.7]), sulfur (22.7 μm [15.0,30.4]) and total PM2.5 (14.7 μm [9.0,20.5]) but not silicon (5.2 μm [−9.8,20.1]), were associated with increased CIMT; in two-pollutant models, only the association with OC was robust to control for the other pollutants. Findings were generally consistent across the three exposure estimation approaches. None of the PM measures were positively associated with either the presence or extent of CAC. In sensitivity analyses, effect estimates for OC and silicon were particularly sensitive to control for metropolitan area.
Employing commonly-used exposure estimation approaches, all of the PM2.5 components considered, except silicon, were associated with increased CIMT, with the evidence being strongest for OC; no component was associated with increased CAC. PM2.5 chemical components, or other features of the sources that produced them, may be important in determining the effect of PM exposure on atherosclerosis. These cross-sectional findings await confirmation in future work employing longitudinal outcome measures and using more sophisticated approaches to estimating exposure.
Atherosclerosis; Cardiovascular diseases; Coronary artery disease; Air pollution; Particulate matter
This study evaluated the association of long- and short-term air pollutant exposures with flow-mediated dilation (FMD) and baseline arterial diameter (BAD) of the brachial artery using ultrasound in a large multicity cohort.
Exposures to ambient air pollution, especially long-term exposure to particulate matter <2.5 μm in aerodynamic diameter (PM2.5), are linked with cardiovascular mortality. Short-term exposure to PM2.5 has been associated with decreased FMD and vasoconstriction, suggesting that adverse effects of PM2.5 may involve endothelial dysfunction. However, long-term effects of PM2.5 on endothelial dysfunction have not been investigated.
FMD and BAD were measured by brachial artery ultrasound at the initial examination of the Multi-Ethnic Study of Atherosclerosis. Long-term PM2.5 concentrations were estimated for the year 2000 at each participant’s residence (n = 3,040) using a spatio-temporal model informed by cohort-specific monitoring. Short-term PM2.5 concentrations were based on daily central-site monitoring in each of the 6 cities.
An interquartile increase in long-term PM2.5 concentration (3 μg/m3) was associated with a 0.3% decrease in FMD (95% confidence interval [CI] of difference: −0.6 to −0.03; p = 0.03), adjusting for demographic characteristics, traditional risk factors, sonographers, and 1/BAD. Women, nonsmokers, younger participants, and those with hypertension seemed to show a greater association of PM2.5 with FMD. FMD was not significantly associated with short-term variation in PM2.5 (−0.1% per 12 μg/m3 daily increase [95% CI: −0.2 to 0.04] on the day before examination).
Long-term PM2.5 exposure was significantly associated with decreased endothelial function according to brachial ultrasound results. These findings may elucidate an important pathway linking air pollution and cardiovascular mortality.
air pollution; atherosclerosis; cardiovascular mortality; endothelial function; flow-mediated dilation; traffic
Background: Epidemiologic studies of fine particulate matter [aerodynamic diameter ≤ 2.5 μm (PM2.5)] typically use outdoor concentrations as exposure surrogates. Failure to account for variation in residential infiltration efficiencies (Finf) will affect epidemiologic study results.
Objective: We aimed to develop models to predict Finf for > 6,000 homes in the Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air), a prospective cohort study of PM2.5 exposure, subclinical cardiovascular disease, and clinical outcomes.
Methods: We collected 526 two-week, paired indoor–outdoor PM2.5 filter samples from a subset of study homes. PM2.5 elemental composition was measured by X-ray fluorescence, and Finf was estimated as the indoor/outdoor sulfur ratio. We regressed Finf on meteorologic variables and questionnaire-based predictors in season-specific models. Models were evaluated using the R2 and root mean square error (RMSE) from a 10-fold cross-validation.
Results: The mean ± SD Finf across all communities and seasons was 0.62 ± 0.21, and community-specific means ranged from 0.47 ± 0.15 in Winston-Salem, North Carolina, to 0.82 ± 0.14 in New York, New York. Finf was generally greater during the warm (> 18°C) season. Central air conditioning (AC) use, frequency of AC use, and window opening frequency were the most important predictors during the warm season; outdoor temperature and forced-air heat were the best cold-season predictors. The models predicted 60% of the variance in 2-week Finf, with an RMSE of 0.13.
Conclusions: We developed intuitive models that can predict Finf using easily obtained variables. Using these models, MESA Air will be the first large epidemiologic study to incorporate variation in residential Finf into an exposure assessment.
air exchange; attenuation; deposition; exposure misclassification; penetration; ventilation
Associations have been found between long-term exposure to ambient air pollution and cardiovascular morbidity and mortality. The contribution of air pollution to atherosclerosis that underlies many cardiovascular diseases has not been investigated. Animal data suggest that ambient particulate matter (PM) may contribute to atherogenesis. We used data on 798 participants from two clinical trials to investigate the association between atherosclerosis and long-term exposure to ambient PM up to 2.5 μm in aerodynamic diameter (PM2.5). Baseline data included assessment of the carotid intima-media thickness (CIMT), a measure of subclinical atherosclerosis. We geocoded subjects’ residential areas to assign annual mean concentrations of ambient PM2.5. Exposure values were assigned from a PM2.5 surface derived from a geostatistical model. Individually assigned annual mean PM2.5 concentrations ranged from 5.2 to 26.9 μg/m3 (mean, 20.3). For a cross-sectional exposure contrast of 10 μg/m3 PM2.5, CIMT increased by 5.9% (95% confidence interval, 1–11%). Adjustment for age reduced the coefficients, but further adjustment for covariates indicated robust estimates in the range of 3.9–4.3% (p-values, 0.05–0.1). Among older subjects (≥60 years of age), women, never smokers, and those reporting lipid-lowering treatment at baseline, the associations of PM2.5 and CIMT were larger with the strongest associations in women ≥60 years of age (15.7%, 5.7–26.6%). These results represent the first epidemiologic evidence of an association between atherosclerosis and ambient air pollution. Given the leading role of cardiovascular disease as a cause of death and the large populations exposed to ambient PM2.5, these findings may be important and need further confirmation.
air pollution; atherosclerosis; particulate matter
Most published epidemiology studies of long-term air pollution health effects have relied on central site monitoring to investigate regional-scale differences in exposure. Few cohort studies have had sufficient data to characterize localized variations in pollution, despite the fact that large gradients can exist over small spatial scales. Similarly, previous data have generally been limited to measurements of particle mass or several of the criteria gases. The Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air) is an innovative investigation undertaken to link subclinical and clinical cardiovascular health effects with individual-level estimates of personal exposure to ambient-origin pollution. This project improves on prior work by implementing an extensive exposure assessment program to characterize long-term average concentrations of ambient-generated PM2.5, specific PM2.5 chemical components, and co-pollutants, with particular emphasis on capturing concentration gradients within cities.
This paper describes exposure assessment in MESA Air, including questionnaires, community sampling, home monitoring, and personal sampling. Summary statistics describing the performance of the sampling methods are presented along with descriptive statistics of the air pollution concentrations by city.
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).
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 from linear regression found PP and SBP positively associated with PM2.5. For example, a 10-μg/m3 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.
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.
air pollution; blood pressure; cardiovascular disease; epidemiology; particulate matter
Background: Studies estimating health effects of long-term air pollution exposure often use a two-stage approach: building exposure models to assign individual-level exposures, which are then used in regression analyses. This requires accurate exposure modeling and careful treatment of exposure measurement error.
Objective: To illustrate the importance of accounting for exposure model characteristics in two-stage air pollution studies, we considered a case study based on data from the Multi-Ethnic Study of Atherosclerosis (MESA).
Methods: We built national spatial exposure models that used partial least squares and universal kriging to estimate annual average concentrations of four PM2.5 components: elemental carbon (EC), organic carbon (OC), silicon (Si), and sulfur (S). We predicted PM2.5 component exposures for the MESA cohort and estimated cross-sectional associations with carotid intima-media thickness (CIMT), adjusting for subject-specific covariates. We corrected for measurement error using recently developed methods that account for the spatial structure of predicted exposures.
Results: Our models performed well, with cross-validated R2 values ranging from 0.62 to 0.95. Naïve analyses that did not account for measurement error indicated statistically significant associations between CIMT and exposure to OC, Si, and S. EC and OC exhibited little spatial correlation, and the corrected inference was unchanged from the naïve analysis. The Si and S exposure surfaces displayed notable spatial correlation, resulting in corrected confidence intervals (CIs) that were 50% wider than the naïve CIs, but that were still statistically significant.
Conclusion: The impact of correcting for measurement error on health effect inference is concordant with the degree of spatial correlation in the exposure surfaces. Exposure model characteristics must be considered when performing two-stage air pollution epidemiologic analyses because naïve health effect inference may be inappropriate.
Citation: Bergen S, Sheppard L, Sampson PD, Kim SY, Richards M, Vedal S, Kaufman JD, Szpiro AA. 2013. A national prediction model for PM2.5 component exposures and measurement error–corrected health effect inference. Environ Health Perspect 121:1017–1025; http://dx.doi.org/10.1289/ehp.1206010
Rationale: Ambient air pollution has been associated with heart failure morbidity and mortality. The mechanisms responsible for these associations are unknown but may include the effects of traffic-related pollutants on vascular or autonomic function.
Objectives: We assessed the cross-sectional relation between long-term air pollution, traffic exposures, and important end-organ measures of alterations in cardiac function—left ventricular mass index (LVMI) and ejection fraction—in the Multi-Ethnic Study of Atherosclerosis, a multicenter study of adults without previous clinical cardiovascular disease.
Methods: A total of 3,827 eligible participants (aged 45–84 yr) underwent cardiac magnetic resonance imaging between 2000 and 2002. We estimated air pollution exposures using residential proximity to major roadways and interpolated concentrations of fine particulate matter (less than 2.5 microns in diameter). We examined adjusted associations between these exposures and left ventricular mass and function.
Measurements and Main Results: Relative to participants living more than 150 m from a major roadway, participants living within 50 m of a major roadway showed an adjusted 1.4 g/m2 (95% CI, 0.3–2.5) higher LVMI, a difference in mass corresponding to a 5.6 mm Hg greater systolic blood pressure. Ejection fraction was not associated with proximity to major roadways. Limited variability in estimates of fine particulate matter was observed within cities, and no associations with particulate matter were found for either outcome after adjustment for center.
Conclusions: Living in close proximity to major roadways is associated with higher LVMI, suggesting chronic vascular end-organ damage from a traffic-related environmental exposure. Air pollutants or another component of roadway proximity, such as noise, could be responsible.
epidemiology; particulate matter; hypertrophy; heart failure; magnetic resonance imaging
Short-term exposure to air pollution may affect ventricular repolarization, but there is limited information on how long-term exposures might affect the surface ventricular electrocardiographic (ECG) abnormalities associated with cardiovascular events. We carried out a study to determine whether long-term air pollution exposure is associated with abnormalities of ventricular repolarization and conduction in adults without known cardiovascular disease.
A total of 4783 participants free of clinical cardiovascular disease in the Multi-Ethnic Study of Atherosclerosis underwent 12-lead ECG examinations, cardiac-computed tomography and calcium scoring, as well as estimation of air pollution exposure using a finely resolved spatio-temporal model to determine long-term average individual exposure to fine particulate matter (PM2.5) and proximity to major roadways. We assessed ventricular electrical abnormalities including presence of QT prolongation (Rautaharju QTrr criteria) and intraventricular conduction delay (QRS duration > 120 msec). We used logistic regression to determine the adjusted relationship between air pollution exposures and ECG abnormalities.
A 10 µg/m3-increase in estimated residential PM2.5 was associated with an increased odds of prevalent QT prolongation (adjusted odds ratio [OR]= 1.6 [95% confidence interval (CI)= 1.2 to 2.2]) and intraventricular conduction delay (OR 1.7, 95% CI: 1.0 to 2.6, independent of coronary-artery calcium score. Living near major roadways was not associated with ventricular electrical abnormalities. No significant evidence of effect modification by traditional risk factors or study site was observed.
This study demonstrates an association between long-term exposure to air pollution and ventricular repolarization and conduction abnormalities in adults without clinical cardiovascular disease, independent of subclinical coronary arterial calcification.
Genetic variants associated with fasting glucose in European ancestry populations are increasingly well understood. However, the nature of the associations between these SNPs and fasting glucose in other racial and ethnic groups is unclear. We sought to examine regions previously identified to be associated with fasting glucose in Caucasian GWAS across multiple ethnicities in the Multi-Ethnic Study of Atherosclerosis (MESA). Non-diabetic MESA participants with fasting glucose measured at the baseline exam and with GWAS genotyping were included; 2349 Caucasians, 664 individuals of Chinese descent, 1366 African Americans, and 1171 Hispanics. Genotype data was generated from the Affymetrix 6.0 array and imputation in IMPUTE. Fasting glucose was regressed on SNP dosage data in each ethnic group adjusting for age, gender, MESA study center, and ethnic-specific principal components. SNPs from the three gene regions with the strongest associations to fasting glucose in previous Caucasian GWAS (MTNR1B / GCK / G6PC2) were examined in depth. There was limited power to replicate associations in other ethnic groups due to smaller allele frequencies and limited sample size; SNP associations may also have differed across ethnic groups due to differing LD patterns with causal variants. rs10830963 in MTNR1B and rs4607517 in GCK demonstrated consistent magnitude and direction of association with fasting glucose across ethnic groups, although the associations were often not nominally significant. In conclusion, certain SNPs in MTNR1B and GCK demonstrate consistent effects across four racial and ethnic groups, narrowing the putative region for these causal variants.
GWAS; fasting glucose; SNP
Common carotid artery inter-adventitial diameter (IAD) and intima-media thickness (IMT) are measurable by ultrasound. IAD may be associated with left ventricular mass (LV mass) while IMT is a marker of subclinical atherosclerosis. It is not clear if IAD is associated with LV mass after accounting for IMT and traditional cardiovascular risk factors.
IAD and IMT were measured on participants of the Multi-Ethnic Study of Atherosclerosis (MESA) IMT progression study. A total of 5641 of the originally enrolled 6814 MESA participants were studied. LV mass was measured by magnetic resonance imaging. Multivariable linear regression was used with IAD as the outcome and adjustment for risk factors, as well as IMT and LV mass.
Traditional cardiovascular risk factors, height, weight and ethnicity were significantly associated with IAD. After adjustment for risk factors, a one mm difference in IMT was associated with a 1.802 mm (95% CI: 1.553, 2.051) higher mean IAD. A one gm difference in LV mass was associated with a 0.006 mm (95% CI: 0.005, 0.007) higher mean IAD. LV mass was independently associated with IAD after adjusting for cardiovascular risk factors and IMT. These associations were slightly different for men and women.
Inter-adventitial diameters are associated with left ventricular mass after adjusting for cardiovascular risk factors and IMT. IAD might serve as a surrogate for left ventricular mass and have predictive value for cardiovascular outcomes.
carotid arteries; ultrasonics; hypertrophy; magnetic resonance imaging; remodeling; risk factors; left ventricle
Modern imaging technology allows us the visualization of coronary artery calcification (CAC), a marker of subclinical coronary atherosclerosis. The prevalence, quantity, and risk factors for CAC were compared between two studies with similar imaging protocols but different source populations: the Multi-Ethnic Study of Atherosclerosis (MESA) and the Heinz Nixdorf Recall Study (HNR).
Methods and results
The measured CAC in 2220 MESA participants were compared with those in 3126 HNR participants with the inclusion criteria such as age 45–75 years, Caucasian race, and free of baseline cardiovascular disease. Despite similar mean levels of CAC of 244.6 among participants in MESA and of 240.3 in HNR (P = 0.91), the prevalence of CAC > 0 was lower in MESA (52.6%) compared with HNR (67.0%) with a prevalence rate ratio of CAC > 0 of 0.78 [95% confidence interval (CI): 0.72–0.85] after adjustment for known risk factors. Consequently, among participants with CAC > 0, the participants in MESA tended to have higher levels of CAC than those in HNR (ratio of CAC levels: 1.39; 95% CI: 1.19–1.63), since many HNR participants have small (near zero) CAC values.
The CAC prevalence was lower in the United States (MESA) cohort than in the German (HNR) cohort, which may be explained by more favourable risk factor levels among the MESA participants. The predictors for increased levels of CAC were, however, similar in both cohorts with the exception that male gender, blood pressure, and body mass index were more strongly associated in the HNR cohort.
Epidemiology; Atherosclerosis; Coronary artery calcium; Risk factors; Screening
Epidemiological studies that assess the health effects of long-term exposure to ambient air pollution are used to inform public policy. These studies rely on exposure models that use data collected from pollution monitoring sites to predict exposures at subject locations. Land use regression (LUR) and universal kriging (UK) have been suggested as potential prediction methods. We evaluate these approaches on a dataset including measurements from three seasons in Los Angeles, CA.
The measurements of gaseous oxides of nitrogen (NOx) used in this study are from a “snapshot” sampling campaign that is part of the Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air). The measurements in Los Angeles were collected during three two-week periods in the summer, autumn, and winter, each with about 150 sites. The design included clusters of monitors on either side of busy roads to capture near-field gradients of traffic-related pollution.
LUR and UK prediction models were created using geographic information system (GIS)-based covariates. Selection of covariates was based on 10-fold cross-validated (CV) R2 and root mean square error (RMSE). Since UK requires specialized software, a computationally simpler two-step procedure was also employed to approximate fitting the UK model using readily available regression and GIS software.
UK models consistently performed as well as or better than the analogous LUR models. The best CV R2 values for season-specific UK models predicting log(NOx) were 0.75, 0.72, and 0.74 (CV RMSE 0.20, 0.17, and 0.15) for summer, autumn, and winter, respectively. The best CV R2 values for season-specific LUR models predicting log(NOx) were 0.74, 0.60, and 0.67 (CV RMSE 0.20, 0.20, and 0.17). The two-stage approximation to UK also performed better than LUR and nearly as well as the full UK model with CV R2 values 0.75, 0.70, and 0.70 (CV RMSE 0.20, 0.17, and 0.17) for summer, autumn, and winter, respectively.
High quality LUR and UK prediction models for NOx in Los Angeles were developed for the three seasons based on data collected for MESA Air. In our study, UK consistently outperformed LUR. Similarly, the 2-step approach was more effective than the LUR models, with performance equal to or slightly worse than UK.
Universal kriging; land use regression; spatial modeling; air pollution; exposure assessment; Los Angeles
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.
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.
In the adjusted analysis, a cross-sectional exposure difference of 3.91 μg/m3 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.
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.
air quality; cardiovascular disease; epidemiology; inflammation; roadway proximity
The initiation and acceleration of atherosclerosis is hypothesized as a physiologic mechanism underlying associations between air pollution and cardiovascular effects. Despite toxicologic evidence, epidemiologic data are limited.
In this cross-sectional analysis we investigated exposure to fine particulate matter (PM2.5) and residential proximity to major roads in relation to abdominal aortic calcification a sensitive indicator of systemic atherosclerosis. Aortic calcification was measured by computed tomography among 1147 persons, in 5 U.S. metropolitan areas, enrolled in the Multi-Ethnic Study of Atherosclerosis (MESA). The presence and quantity of aortic calcification were modeled using relative risk regression and linear regression, respectively, with adjustment for potential confounders.
We observed a slightly elevated risk of aortic calcification (RR = 1.06; 95% confidence interval = 0.96–1.16) with a 10-μg/m3 contrast in PM2.5. The PM2.5-associated risk of aortic calcification was stronger among participants with long-term residence near a PM2.5 monitor (RR = 1.11; 1.00–1.24) and among participants not recently employed outside the home (RR = 1.10; 1.00–1.22). PM2.5 was not associated with an increase in the quantity of aortic calcification (Agatston score) and no roadway proximity effects were noted. There was indication of PM2.5 effect modification by lipid-lowering medication use, with greater effects among users, and PM2.5 associations were observed most consistently among Hispanics.
Although we did not find persuasive associations across our full study population, associations were stronger among participants with less exposure misclassification. These findings support the hypothesis of a relationship between particulate air pollution and systemic atherosclerosis.
Rationale and Objectives
Higher socioeconomic status (SES) has been associated with lower respiratory mortality and better lung function, but whether a similar gradient exists for computed tomography (CT) measures of subclinical emphysema is unknown.
Materials and Methods
The Multi-Ethnic Study of Atherosclerosis (MESA) recruited African American, Chinese, Hispanic, and white participants, ages 45–84 years, without clinical cardiovascular disease, from 6 US sites in 2000–2002. The MESA Lung Study assessed percent emphysema, defined based on the proportion of pixels below an attenuation threshold of 910 HU from lung windows of cardiac CT scans. Generalized linear models were adjusted for demographic characteristics, height, body mass index, history of respiratory illness, occupational and residential exposures, tobacco use, and CT scanner type.
Among 3,706 participants with a mean age of 61 (±10), the median value for percent emphysema was 18 (interquartile range=20). Compared with those who did not complete high school, participants with a graduate degree had a higher percent emphysema (difference of 4; p < 0.001). Income and wealth were also positively associated with percent emphysema. In contrast, higher SES was associated with better lung function. Descriptive and subgroup analyses were used to explore potential explanations for divergent results, including the possibility that suboptimal inspiration during CT scanning would decrease percent emphysema, making the lungs appear healthier when effort is relatively poor.
While SES indicators were positively associated with subclinical emphysema detectable on CT scan, this unexpected association may highlight potential bias due to effort-dependence of both CT measures and spirometry.
Chronic Obstructive Pulmonary Disease; Emphysema; Socioeconomic Status; Epidemiology
Older women have a higher prevalence of systolic hypertension than do men; however, whether or not this relates to arterial properties, such as distensibility coefficient (DC), is not known. We examined whether the association of carotid artery DC with age differed by sex in the Multi-Ethnic Study of Atherosclerosis (MESA).
B-mode ultrasound-measured carotid diameters and brachial pressures were obtained from 6359 participants (53% female, 38% white, 12% Chinese, 27% black, 22% Hispanic, aged 45–85 years) of the MESA baseline examination. The within-individual slopes of 2log(diameter) vs. blood pressure fit using mixed models (MM) are interpreted as the DC, and interaction terms are interpreted as differences in DC. The MM calculation allows for correction of the confounding caused by the association of age, sex, and race with blood pressure, the denominator in the calculation of DC.
DC was associated with age, sex, and race (all p<0.001). Women had a greater age-related lowering of DC compared to men (2.52×10−5 vs. 2.16×10−5/mm Hg lower DC per year of age, p=0.006). Mean diameter of carotid arteries was greater with age (p<0.001); this association also was significantly stronger in women compared to men (0.24% vs. 0.14% larger mean carotid diameter per year of age, p<0.001).
Greater stiffening and enlargement of arteries are seen in older women compared to older men. This implies that the afterload on the heart of older women is likely to be greater than that among older men.
Several studies have reported associations between long-term exposure to ambient fine particulate matter (PM) and cardiovascular mortality. However, the health impacts of long-term exposure to specific constituents of PM2.5 (PM with aerodynamic diameter ≤ 2.5 μm) have not been explored.
We used data from the California Teachers Study, a prospective cohort of active and former female public school professionals. We developed estimates of long-term exposures to PM2.5 and several of its constituents, including elemental carbon, organic carbon (OC), sulfates, nitrates, iron, potassium, silicon, and zinc. Monthly averages of exposure were created using pollution data from June 2002 through July 2007. We included participants whose residential addresses were within 8 and 30 km of a monitor collecting PM2.5 constituent data. Hazard ratios (HRs) were estimated for long-term exposure for mortality from all nontraumatic causes, cardiopulmonary disease, ischemic heart disease (IHD), and pulmonary disease.
Approximately 45,000 women with 2,600 deaths lived within 30 km of a monitor. We observed associations of all-cause, cardiopulmonary, and IHD mortality with PM2.5 mass and each of its measured constituents, and between pulmonary mortality and several constituents. For example, for cardiopulmonary mortality, HRs for interquartile ranges of PM2.5, OC, and sulfates were 1.55 [95% confidence interval (CI), 1.43–1.69], 1.80 (95% CI, 1.68–1.93), and 1.79 (95% CI, 1.58–2.03), respectively. Subsequent analyses indicated that, of the constituents analyzed, OC and sulfates had the strongest associations with all four outcomes.
Long-term exposures to PM2.5 and several of its constituents were associated with increased risks of all-cause and cardiopulmonary mortality in this cohort. Constituents derived from combustion of fossil fuel (including diesel), as well as those of crustal origin, were associated with some of the greatest risks. These results provide additional evidence that reduction of ambient PM2.5 may provide significant public health benefits.
cardiopulmonary mortality; chronic exposure; cohort study; elemental carbon; fine particles; organic carbon; PM2.5; species; sulfates
The purpose of this study was to assess coronary arterial remodeling as a marker of subclinical atherosclerosis using coronary wall MRI in an asymptomatic population-based cohort.
In early atherosclerosis, compensatory enlargement of both the outer wall of the vessel as well as the lumen, termed compensatory enlargement or positive remodeling, occurs before luminal narrowing.
179 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) were evaluated using black-blood coronary wall MRI. Coronary cross-sectional area (vessel size), lumen area, and mean wall thickness of the proximal coronary arteries were measured.
Men had a greater vessel size, lumen area, and mean wall thickness than women (38.3±11.3 versus 32.6±9.4 mm2, 6.7±3.2 versus 5.3±2.4 mm2, and 2.0±0.3 versus 1.9±0.3 mm, respectively, p<0.05). No significant coronary artery narrowing was present by magnetic resonance angiography. Overall, coronary vessel size increased 25.9 mm2 per millimeter increase in coronary wall thickness, while lumen area increased only slightly at 3.1 mm2 for every millimeter increase in wall thickness (difference in slopes, p<0.0001). Adjusting for age and gender, participants with Agatston score greater than zero were more likely to have wall thickness greater than 2.0 mm (odds ratio 2.0, 95% CI 1.01–3.84).
Coronary wall MRI detected positive arterial remodeling, in asymptomatic men and women with subclinical atherosclerosis.
subclinical atherosclerosis; magnetic resonance imaging; coronary artery disease; plaque
We hypothesized that individuals with low 10-year but high lifetime cardiovascular disease (CVD) risk would have a greater burden of subclinical atherosclerosis than those with low 10-year but low lifetime risk.
Methods and Results
We included 2988 individuals age ≤50 at exam year 15 from the Coronary Artery Risk Development in Young Adults (CARDIA) study and 1076 individuals age ≤50 at study entry from the Multi-Ethnic Study of Atherosclerosis (MESA). The 10-year risk and lifetime risk for CVD were estimated for each participant, permitting stratification into three groups: low 10-year (<10%)/low lifetime (<39%) risk, low 10-year (<10%)/high lifetime risk (≥39%), and high 10-year risk (≥10%) or diagnosed diabetes. Baseline levels and change in levels of subclinical atherosclerosis (coronary artery calcium [CAC] or carotid intima-media thickness [IMT]) were compared across risk strata. Among participants with low 10-year risk (91% of all participants) in CARDIA, those with a high lifetime risk compared to low lifetime risk had significantly greater common (0.83 vs 0.80 mm in men; 0.79 vs 0.75 mm in women) and internal (0.85 vs 0.80 mm; 0.80 vs 0.76 mm) carotid IMT, higher CAC prevalence (16.6 vs 9.8%; 7.1 vs 2.3%), and significantly greater incidence of CAC progression (22.3 vs 15.4%; 8.7 vs 5.3%). Similar results were observed in MESA.
Individuals with low 10-year but high lifetime risk have a greater subclinical disease burden and greater incidence of atherosclerotic progression compared to individuals with low 10-year and low lifetime risk, even at younger ages.
epidemiology; risk estimation; prevention
Understanding mechanistic pathways linking airborne particle exposure to cardiovascular health is important for causal inference and setting environmental standards. We evaluated whether urinary albumin excretion, a subclinical marker of microvascular function which predicts cardiovascular events, was associated with ambient particle exposure.
Urinary albumin and creatinine were measured among members of the Multi-Ethnic Study of Atherosclerosis at three visits during 2000–2004. Exposure to PM2.5 and PM10 (µg/m3) was estimated from ambient monitors for 1 month, 2 months and two decades before visit one. We regressed recent and chronic (20 year) particulate matter (PM) exposure on urinary albumin/creatinine ratio (UACR, mg/g) and microalbuminuria at first examination, controlling for age, race/ethnicity, sex, smoking, second-hand smoke exposure, body mass index and dietary protein (n = 3901). We also evaluated UACR changes and development of microalbuminuria between the first, and second and third visits which took place at 1.5- to 2-year intervals in relation to chronic PM exposure prior to baseline using mixed models.
Chronic and recent particle exposures were not associated with current UACR or microalbuminuria (per 10 µg/m3 increment of chronic PM10 exposure, mean difference in log UACR = −0.02 (95% CI −0.07 to 0.03) and relative probability of having microalbuminuria = 0.92 (95% CI 0.77 to 1.08)) We found only weak evidence that albuminuria was accelerated among those chronically exposed to particles: each 10 µg/m3 increment in chronic PM10 exposure was associated with a 1.14 relative probability of developing microalbuminuria over 3–4 years, although 95% confidence intervals included the null (95% CI 0.96 to 1.36).
UACR is not a strong mechanistic marker for the possible influence of air pollution on cardiovascular health in this sample.
High plasma sphingomyelin level has been associated with subclinical atherosclerosis, coronary artery disease and worse prognosis in subjects with acute coronary syndromes. We assess the predictive value of plasma sphingomyelin levels for incident CHD events in the Multi Ethnic Study of atherosclerosis (MESA).
Method and Results
Plasma sphingomyelin was measured in 6809 out of 6814 subjects with mean age 62.2 ± 10.2 years, participating in the MESA study, a population based cohort study of adults free of clinical CVD at baseline recruited at six clinic sites in USA. The subjects consisted of 52.8% females, 38.5% Caucasian, 11.8% Chinese, 27.8% African Americans and 21.9% Hispanics. Cox proportional hazard analysis was used to examine the association between plasma sphingomyelin and five years of adjudicated incident CHD events including MI, resuscitated cardiac arrest, angina, CHD death and revascularization (CABG or PTCA). Mean (SD) plasma sphingomyelin level was 48 mg/dl (16.0). One hundred and eighty-nine subjects had an adjudicated CHD event during the five years of follow up. In the Kaplan meier analysis, subjects with plasma sphingomyelin level above the sex specific median had similar event free survival rate compared with subjects with plasma sphingomyelin level below or equal to the sex specific median (97.16% vs 97.0%, log rank p= 0.713). In the univariate Cox proportional hazard analysis, plasma sphingomyelin was not a predictor of incident CHD event [hazard ratio 0.992(0.982 – 1.004), p=0.09]. In our multistage multivariable Cox models, higher plasma sphingomyelin had modest negative association with incident CHD events when total cholesterol, HDL and triglycerides were included in the model [hazard ratio 0.985 (0.973 – 0.996), p=0.008] and also in our full model after adjusting for age, gender, total cholesterol, HDL, triglycerides, diabetes, cigarette smoking, systolic BP, diastolic BP, BP medication use, HMG CoA use [hazard ratio 0.984 (0.973 – 0.996), p=0.002]. In other models, plasma sphingomyelin was not associated with incident CHD events.
High plasma sphingomyelin level is not associated with increased risk of incident coronary heart disease in population based adults free of clinical cardiovascular disease at baseline.
Plasma sphingomyelin; prognosis; coronary heart disease events; epidemiology
Particulate air pollution has been linked to heart disease and stroke, possibly resulting from enhanced coagulation and arterial thrombosis. Whether particulate air pollution exposure is related to venous thrombosis is unknown.
We examined the association of exposure to particulate matter of less than 10 µm in aerodynamic diameter (PM10) with DVT risk in 870 patients and 1210 controls from Lombardia Region, Italy examined between 1995–2005. We estimated exposure to particulate matter of less than 10 µm in aerodynamic diameter (PM10) in the year before DVT diagnosis (cases) or examination (controls) through area-specific average levels obtained from ambient monitors.
Higher average PM10 level in the year before the examination was associated with shortened Prothrombin Time (PT) in DVT cases (beta=−0.12; 95% CI −0.23, 0.00; p=0.04) and controls (beta=-0.06; 95% CI −0.11, 0.00, p=0.04). Each PM10 increase of 10 µg/m3 was associated with a 70% increase in DVT risk (OR=1.70; 95% CI, 1.30–2.23; p=0.0001) in models adjusting for clinical and environmental covariates. The exposure-response relationship was approximately linear over the observed PM10 range. The association between PM10 and DVT was weaker in women (OR=1.40; 95% CI, 1.02–1.92; p=0.02 for the interaction between PM10 and sex), particularly in those using oral contraceptives or hormone replacement therapy (OR=0.97; 95% CI 0.58–1.61; p=0.048 for the interaction between PM10 and hormone use).
Long-term exposure to particulate air pollution is associated with altered coagulation function and DVT risk. Other risk factors for DVT may modulate the effect of particulate air pollution.
Background. Changes in retinal microvascular caliber, which occur prior to onset of retinopathy, may indicate presence of kidney damage.
Methods. This study examined the association between retinal arteriolar [central retinal artery equivalent (CRAE)] and venular caliber [central retinal venule equivalent (CRVE)] and presence of albuminuria (micro- or macroalbuminuria) among participants of the Multi-Ethnic Study of Atherosclerosis (MESA), a cohort of adults aged 45–84 years without baseline clinical cardiovascular disease. During the second MESA exam, digital fundus photography was completed in 5897 participants who provided spot urine specimens. Albuminuria was defined by spot urine albumin/creatinine ratios ≥30 mg/g. Multivariable adjusted odds of albuminuria by quintiles of CRAE and CRVE were determined using logistic regression. Analyses were repeated after stratifying by presence of type 2 diabetes.
Results. Albuminuria was noted in 11.5% (n = 675) and included 584 subjects with microalbuminuria and 91 with macroalbuminuria. A significant U-shaped pattern was seen with higher prevalence of albuminuria across quintile extremes in CRAE (15.7, 8.8 and 10.6% in CRAE Quintiles 1, 3 and 5, respectively; P <0.0001). After adjustment for covariates, both narrower CRAE [odds ratios (OR) 1.55; 95% confidence interval (CI) 1.17–2.04, Quintile 1 versus 3) and wider CRAE (OR 1.44; 95% CI 1.07–1.93, Quintile 5 versus 3) were significantly associated with albuminuria. Associations appeared substantially stronger in adults with than without type 2 diabetes but the interaction term for diabetes and CRAE on presence of albuminuria did not meet statistical significance (P = 0.3). No association was noted between CRVE quintiles and albuminuria.
Conclusions. Albuminuria is associated with narrower and wider arteriolar caliber. Future studies should determine whether variation in arteriolar caliber predicts incident albuminuria and whether associations are mediated by hypertension and diabetes. Such information could further clarify early microvascular processes in the pathogenesis of kidney disease.
albuminuria; diabetic retinopathy; MESA (Multi-Ethnic Study of Atherosclerosis); retinal arteriolar; retinal venular