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Urban noise is a common environmental exposure that may increase the burden of hypertension in communities, yet it is largely unstudied in the United States, and it has not been studied in relation to blood pressure (BP) control. We investigated associations of urban noise with BP levels and control in the United States. We used repeated BP and medication data from Chicago-based participants of the Chicago Health and Aging Project (≥65 years) and MESA (Multi-Ethnic Study of Atherosclerosis; ≥45 years). Using a spatial prediction model with project-specific measurements, we estimated noise at participant homes. We imputed BP levels for those on medication and used mixed-effects models to evaluate associations with noise. Logistic regression was used for uncontrolled and apparent treatment-resistant hypertension. Models were run separately by cohort and altogether, all with adjustment for age, sex, sociodemographic factors, and other plausible sources of confounding. We evaluated 16 462 BP measurements from 6764 participants (6073 Chicago Health and Aging Project and 691 MESA) over an average of 4 years. For both cohorts, we found that greater levels of noise were associated with higher BP levels and greater risk of apparent treatment-resistant hypertension. In our pooled models, 10-dBA higher residential noise levels corresponded to 1.2 (95% CI, 0.1–2.2) and 1.1 mm Hg greater (95% CI, 0.6–1.7) systolic and diastolic BPs as well as a 20% increased odds of apparent treatment-resistant hypertension (odds ratio per 10 dBA: 1.2 [95% CI, 1.0–1.4], P =0.04). Urban noise may increase BP levels and complicate hypertension treatment in the United States.

Rationale: Racial residential segregation has been associated with worse health outcomes, but the link with chronic obstructive pulmonary disease (COPD) morbidity has not been established.Objective...

Retinopathy is a microvascular complication of diabetes mellitus (DM); however, it is also increasingly recognized in persons without DM. The microvascular diseases may play a prominent role in coronary heart disease (CHD) development in individuals with DM. We performed the study to evaluate the relation between non-DM retinopathy and CHD and also the association between baseline retinopathy and incidence and progression of CHD in individuals with and without DM. We included 5709 subjects with and without DM from the Multi-Ethnic Study of Atherosclerosis, who had retinal photos and coronary artery calcium score (CACS) available. We studied the association between baseline retinopathy and incidence and progression of coronary artery calcification (CAC) in subjects with and without DM. In DM group, the presence of retinopathy was significantly associated with an increased rate of CAC (RR 1.3 (95% CI [1.02, 1.66]) after adjusting for age, sex, race, follow-up time, and CHD risk factors. In non-DM group, the presence of retinopathy was not significantly associated with increased risk of CAC, however, the interaction between presence of retinopathy and DM status was not statistically significant. Within the DM group with CAC present at baseline, the presence of retinopathy was significantly associated with greater CAC progression (113 Agatson units (AU) greater, (95% CI [51-174]). In the non-DM group with present CAC at baseline; the presence of retinopathy was associated with 24 (95% CI [-0.69, 48.76]) AU higher CAC progression. All findings were adjusted for CHD risk factors. In conclusion, after adjustment for major CHD risk factors, retinopathy was associated with progression of CAC in both DM and non-DM individuals. However, the association was stronger in those with DM.

BACKGROUND: Evidence links fine particulate matter (PM(2.5)) to Alzheimer’s Disease (AD), but no community-based prospective cohort studies in older adults have evaluated the association between long-term exposure to PM(2.5) and markers of AD neuropathology at autopsy. OBJECTIVE: Using a well-established autopsy cohort and new spatiotemporal predictions of air pollution, we evaluated associations of 10-year PM(2.5) exposure prior to death with Braak stage, Consortium to Establish a Registry for AD (CERAD) score, and combined AD neuropathologic change (ABC score). METHODS: We used autopsy specimens (N=832) from the Adult Changes in Thought (ACT) study, with enrollment ongoing since 1994. We assigned long-term exposure at residential address based on two-week average concentrations from a newly developed spatiotemporal model. To account for potential selection bias, we conducted inverse probability weighting (IPW). Adjusting for covariates with tiered models, we performed ordinal regression for Braak and CERAD and logistic regression for dichotomized ABC score. RESULTS: 10-year average (SD) PM(2.5) from death across the autopsy cohort was 8.2 (1.9) μg/m(3). Average (SD) age at death was 89 (7) years. Each 1 μg/m(3) increase in 10-year average PM(2.5) prior to death was associated with a suggestive increase in the odds of worse neuropathology as indicated by CERAD score (OR: 1.35 (0.90, 1.90)) but a suggestive decreased odds of neuropathology as defined by the ABC score (OR: 0.79 (0.49, 1.19)). There was no association with Braak stage (OR: 0.99 (0.64, 1.47)). CONCLUSIONS: We report inconclusive associations between PM(2.5) and AD neuropathology at autopsy among a cohort where 94% of individuals experienced 10-year exposures below the current EPA standard. Prior studies of AD risk factors and AD neuropathology are similarly inconclusive, suggesting alternative mechanistic pathways for disease or residual confounding.

Fine particulate air pollution

[Extract] After years of intensive research and deliberations with experts across the globe, the World Health Organization (WHO) updated its 2005 Global Air Quality Guidelines (AQG) in September 2021 [1, 2]. The new air quality guidelines (WHO AQG) are ambitious and reflect the large impact that air pollution has on global health. They recommend aiming for annual mean concentrations of PM2.5 not exceeding 5 µg/m3 and NO2 not exceeding 10 µg/m3, and the peak season mean 8-hr ozone concentration not exceeding 60 µg/m3 [1]. For reference, the corresponding 2005 WHO guideline values for PM2.5 and NO2 were, respectively, 10 µg/m3 and 40 µg/m3 with no recommendation issued for long-term ozone concentrations [3]. While the guidelines are not legally binding, we hope they will influence air quality policy across the globe for many years to come.

Background: Atrial fibrillation (AF) is associated with substantial morbidity and mortality. Short-term exposures to air pollution have been associated with AF triggering; less is known regarding associations between long-term air pollution exposures and AF incidence. Objectives: Our objective was to assess the association between long-term exposures to air pollution and distance to road on incidence of AF in a cohort of U.S. women. Methods: We assessed the association of high resolution spatiotemporal model predictions of long-term exposures to particulate matter (PM10 and PM2.5), sulfur dioxide (SO2), nitrogen dioxide (NO2), and distance to major roads with incidence of AF diagnosis, identified through Medicare linkage, among 83,117 women in the prospective Women’s Health Initiative cohort, followed from enrollment in Medicare through December 2012, incidence of AF, or death. Using time-varying Cox proportional hazards models adjusted for age, race/ethnicity, study component, body mass index, physical activity, menopausal hormone therapy, smoking, diet quality, alcohol consumption, educational attainment, and neighborhood socioeconomic status, we estimated the relative risk of incident AF in association with each pollutant. Results: A total of 16,348 incident AF cases were observed over 660,236 person-years of follow-up. Most exposure–response associations were nonlinear. NO2 was associated with risk of AF in multivariable adjusted models [Hazard Ratio (HR)=1.18; 95% confidence interval (CI): 1.13, 1.24, comparing the top to bottom quartile, p-for-trend=

BACKGROUND AND AIM: Age-related cognitive decline is a growing public health issue as increases in life expectancy and the aging of the population are expected to raise the prevalence of cognitive ...

Background: Air pollution contributes to cardiovascular morbidity, including heart failure. Exposure to pollutants has been associated with hypertension and inflammation, which contribute to cardiac remodeling. Few studies have investigated long-term air pollution concentrations and measures of cardiac structure, and no large longitudinal analyses have investigated this association. Hypothesis: Long-term air pollution concentrations are associated with magnetic resonance imaging-derived measures of left ventricular structure and function. Methods: In the Multi-Ethnic Study of Atherosclerosis (MESA), we investigated cross-sectional and longitudinal associations between modeled fine particulate matter (PM2.5), oxides of nitrogen (NOX) and ozone (O3) concentrations and left ventricular mass index (LVMI), mass to volume ratio, ejection fraction, and circumferential strain by cardiac magnetic resonance imaging (CMR) at two time points roughly 10 years apart. Multivariable linear regression was used to estimate the association between pollutants and both cross-sectional and longitudinal CMR measures. Results: At MESA Exam 1 (2000-2002), 4,825 participants in our cross-sectional analysis sample had a mean age of 61 years (standard deviation: 10), 53% were women, 40% were white, 13% were Chinese-American, 25% were African-American, and 21% were Hispanic. At Exam 1, Higher concentrations of PM2.5 and NOX in the year prior to Exam 1 were associated with higher LVMI at Exam 1 (1.6% per 5ug/m3 higher PM2.5, 95% CI: 0.3, 2.9; 1.8% per 40 parts per billion [ppb] NOX, 95% CI: 0.3, 3.3) and higher O3 was associated with lower LVMI (-3.5% per 10ppb, 95% CI: -6.0, -1.0). In longitudinal analyses, higher NOX was associated with a worsening of LV circumferential strain (-0.87% per 40ppb, 95% CI: -1.69, -0.05). Conclusions: Our study offers mixed evidence of a cross-sectional association between higher PM2.5 and NOx concentrations and greater LVMI. We also found associations between greater O3 concentration and lower cross-sectional LVMI, though this association may be confounded by other pollutants. These findings suggest a role for NOX, PM2.5, and O3 in cardiac remodeling. Additional work is needed to clarify that role and better understand the biological underpinnings of these associations.

Study Objectives To quantify the gender-specific associations between insomnia symptoms and subclinical atherosclerosis, measured by coronary artery calcium (CAC) scores, which has strong predictive value for incident cardiovascular disease. Methods We analyzed data from 1,429 participants in the Multi-Ethnic Study of Atherosclerosis (MESA). Participants completed standardized questionnaires and underwent polysomnography (PSG) and 7-day actigraphy. Insomnia symptoms were defined as: self-reported trouble falling, staying or returning to sleep, early-morning awakenings, or hypnotic use, for ≥5 nights/week. MESA assessed CAC using computed tomography. We employed multivariable linear regression to model the probability of CAC >0 overall and to model the linear continuous effect among those with nonzero CAC. Results Our sample was a mean age of 68.1 ± 9.1 years, 53.9% female, and 36.2% white, 28.0% black, 24.2% Hispanic, and 11.5% Chinese-American. Insomnia symptoms were present in 49.7% of men and 47.2% of women. In multivariable-adjusted analyses, insomnia symptoms was associated with an 18% higher prevalence of CAC (PR 1.18, 95% CI 1.04, 1.33) among females, but no association was observed among males (PR 1.00, 95% CI 0.91, 1.08). There was no evidence that the association between insomnia symptoms and prevalence of CAC >0 differed by objective sleep duration status (by single-night PSG or multi-night actigraphy) in females or males. Conclusions We found that among women, insomnia symptoms were associated with an 18% higher prevalence of CAC compared to no insomnia. Insomnia symptoms were not associated with CAC prevalence in men. Additionally, there was no evidence that the association between insomnia symptoms and CAC score >0 differed by objective short sleep duration status.

Introduction Exposure to noise might influence risk of Alzheimer's disease (AD) dementia. Methods Participants of the Chicago Health and Aging Project (≥65 years) underwent triennial cognitive assessments. For the 5 years preceding each assessment, we estimated 5227 participants' residential level of noise from the community using a spatial prediction model, and estimated associations of noise level with prevalent mild cognitive impairment (MCI) and AD, cognitive performance, and rate of cognitive decline. Results Among these participants, an increment of 10 A-weighted decibels (dBA) in noise corresponded to 36% and 29% higher odds of prevalent MCI (odds ratio [OR] = 1.36; 95% confidence interval [CI], 1.15 to 1.62) and AD (OR = 1.29, 95% CI, 1.08 to 1.55). Noise level was associated with worse global cognitive performance, principally in perceptual speed (-0.09 standard deviation per 10 dBA, 95% CI: -0.16 to -0.03), but not consistently associated with cognitive decline. Discussion These results join emerging evidence suggesting that noise may influence late-life cognition and risk of dementia.

Background: Exposure to household air pollution (HAP) from cooking with biomass fuel affects billions of people. We hypothesized that HAP from woodsmoke, compared to other household fuels, was associated with adverse cardiovascular outcomes, of which there have been few studies. Methods: A cross-sectional study was completed in 299 females aged 40–70 years in Kaski District, Nepal, during 2017–18. All participants underwent a standard 12-lead ECG, ankle and brachial systolic blood pressure measurement, and 2D color and Doppler echocardiography. Current stove type was confirmed by inspection. Blood pressure, height, and weight were measured using a standardized protocol. Hypertension was defined as ≥140/90 mmHg or prior diagnosis. Hemoglobin A1c (HbA1c) was obtained, with diabetes mellitus defined as a prior diagnosis or HbA1C ≥ 6.5%. We used adjusted linear and logistic multivariable regressions to examine the relationship of stove type with cardiac structure and function. Results: The majority of women primarily used liquified petroleum gas (LPG) stoves (65%), while 12% used biogas, and 23% used wood-burning cook-stoves. Prevalence of major cardiovascular risk factors was 35% with hypertension, 19% with diabetes mellitus, and 15% current smokers. After adjustment, compared to LPG, wood stove use was associated with increased indexed left atrial volume (β = 3.15, 95% CI 1.22 to 5.09) and increased indexed left ventricular end diastolic volume (β = 7.97, 95% CI 3.11 to 12.83). There was no association between stove type and systemic hypertension, left ventricular mass, systolic dysfunction, diastolic dysfunction, pulmonary hypertension, abnormal ankle-brachial index, or clinically significant ECG abnormalities. Conclusion: Biomass fuel use was associated with increased indexed left atrial volume and increased indexed left ventricular diastolic volume in Nepali women, suggesting subclinical adverse cardiac remodeling from HAP in this cross-sectional study. We did not find evidence of an association with hypertension or typical cardiac sequelae of hypertension. Future studies to confirm these results are needed.

Background: There is mounting evidence that long-term exposure to air pollution is related to accelerated cognitive decline in aging populations. Factors that influence individual susceptibility remain largely unknown, but may involve the apolipoprotein E genotype E4 (APOE-ε4) allele. Objectives: We assessed whether the association between long-term exposure to ambient air pollution and cognitive decline differed by APOE-ε4 status and cognitive risk factors. Methods: The Washington Heights Inwood Community Aging Project (WHICAP) is a prospective study of aging and dementia. Neuropsychological testing and medical examinations occur every 18–24 months. We used mixed-effects models to evaluate whether the association between markers of ambient air pollution (nitrogen dioxide [NO2]), fine [PM2.5], and coarse [PM10] particulate matter) and the rate of decline in global and domain-specific cognition differed across strata defined by APOE-ε4 genotypes and cognitive risk factors, adjusting for sociodemographic factors and temporal trends. Results: Among 4821 participants with an average of 6 years follow-up, higher concentrations of ambient air pollution were associated with more rapid cognitive decline. This association was more pronounced among APOE-ε4 carriers (p

Background and aims It is not known if ultrasound carotid plaque features are associated with cardiovascular disease (CVD) risk factors or if they predict future CVD events. Methods We measured total carotid plaque area (TPA) and grayscale plaque features (grayscale median, black areas, and discrete white areas) by B-mode carotid ultrasound among 2205 participants who participated in the first (baseline) visit of the Multi-Ethnic Study of Atherosclerosis. Multivariable linear regression was used to examine relationships between ultrasound plaque features and CVD risk factors at baseline. Cox proportional hazards models were used to assess if TPA, grayscale features, and carotid plaque score (number of arterial segments with a plaque) could predict incident coronary heart disease and cerebrovascular disease events over a mean follow-up of 13.3 years. Results Participants were mean (standard deviation [SD]) 65.4 (9.6) years, 49% male, 39% White, 11% Chinese, 28% Black, and 22% Hispanic. Mean TPA 27.7 (24.7) mm2, but no grayscale plaque features, was associated with CVD risk factors. In fully adjusted models, TPA but no grayscale features predicted incident coronary heart disease (CHD) events (HR 1.23; 95%CI 1.11–1.36; p Conclusions In middle-aged adults free of known cardiovascular disease, TPA but not grayscale plaque features was associated with CVD risk factors and predicted incident CHD events. For CHD, prediction indices for TPA were similar to carotid plaque score but less than for CAC.

Importance Few studies have investigated the association of long-term ambient ozone exposures with respiratory morbidity among individuals with a heavy smoking history. Objective To investigate the association of historical ozone exposure with risk of chronic obstructive pulmonary disease (COPD), computed tomography (CT) scan measures of respiratory disease, patient-reported outcomes, disease severity, and exacerbations in smokers with or at risk for COPD. Design, Setting, and Participants This multicenter cross-sectional study, conducted from November 1, 2010, to July 31, 2018, obtained data from the Air Pollution Study, an ancillary study of SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study). Data analyzed were from participants enrolled at 7 (New York City, New York; Baltimore, Maryland; Los Angeles, California; Ann Arbor, Michigan; San Francisco, California; Salt Lake City, Utah; and Winston-Salem, North Carolina) of the 12 SPIROMICS clinical sites. Included participants had historical ozone exposure data (n = 1874), were either current or former smokers (≥20 pack-years), were with or without COPD, and were aged 40 to 80 years at baseline. Healthy persons with a smoking history of 1 or more pack-years were excluded from the present analysis. Exposures The 10-year mean historical ambient ozone concentration at participants’ residences estimated by cohort-specific spatiotemporal modeling. Main Outcomes and Measures Spirometry-confirmed COPD, chronic bronchitis diagnosis, CT scan measures (emphysema, air trapping, and airway wall thickness), 6-minute walk test, modified Medical Research Council (mMRC) Dyspnea Scale, COPD Assessment Test (CAT), St. George’s Respiratory Questionnaire (SGRQ), postbronchodilator forced expiratory volume in the first second of expiration (FEV1) % predicted, and self-report of exacerbations in the 12 months before SPIROMICS enrollment, adjusted for demographics, smoking, and job exposure. Results A total of 1874 SPIROMICS participants were analyzed (mean [SD] age, 64.5 [8.8] years; 1479 [78.9%] white; and 1013 [54.1%] male). In adjusted analysis, a 5-ppb (parts per billion) increase in ozone concentration was associated with a greater percentage of emphysema (β = 0.94; 95% CI, 0.25-1.64;P = .007) and percentage of air trapping (β = 1.60; 95% CI, 0.16-3.04;P = .03); worse scores for the mMRC Dyspnea Scale (β = 0.10; 95% CI, 0.03-0.17;P = .008), CAT (β = 0.65; 95% CI, 0.05-1.26;P = .04), and SGRQ (β = 1.47; 95% CI, 0.01-2.93;P = .048); lower FEV1% predicted value (β = −2.50; 95% CI, −4.42 to −0.59;P = .01); and higher odds of any exacerbation (odds ratio [OR], 1.37; 95% CI, 1.12-1.66;P = .002) and severe exacerbation (OR, 1.37; 95% CI, 1.07-1.76;P = .01). No association was found between historical ozone exposure and chronic bronchitis, COPD, airway wall thickness, or 6-minute walk test result. Conclusions and Relevance This study found that long-term historical ozone exposure was associated with reduced lung function, greater emphysema and air trapping on CT scan, worse patient-reported outcomes, and increased respiratory exacerbations for individuals with a history of heavy smoking. The association between ozone exposure and adverse respiratory outcomes suggests the need for continued reevaluation of ambient pollution standards that are designed to protect the most vulnerable members of the US population.

Objectives We aim to characterize the qualities of estimation approaches for individual exposure to ambient-origin fine particulate matter (PM2.5), for use in epidemiological studies. Methods The analysis incorporates personal, home indoor, and home outdoor air monitoring data and spatio-temporal model predictions for 60 participants from the Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air). We compared measurement-based personal PM2.5 exposure with several measured or predicted estimates of outdoor, indoor, and personal exposures. Results The mean personal 2-week exposure was 7.6 (standard deviation 3.7) µg/m3. Outdoor model predictions performed far better than outdoor concentrations estimated using a nearest-monitor approach (R = 0.63 versus R = 0.43). Incorporating infiltration indoors of ambient-derived PM2.5 provided better estimates of the measurement-based personal exposures than outdoor concentration predictions (R = 0.81 versus R = 0.63) and better scaling of estimated exposure (mean difference 0.4 versus 5.4 µg/m3 higher than measurements), suggesting there is value to collecting data regarding home infiltration. Incorporating individual-level time-location information into exposure predictions did not increase correlations with measurement-based personal exposures (R = 0.80) in our sample consisting primarily of retired persons. Conclusions This analysis demonstrates the importance of incorporating infiltration when estimating individual exposure to ambient air pollution. Spatio-temporal models provide substantial improvement in exposure estimation over a nearest monitor approach.

Rationale: Rural residence is associated with poor outcomes in several chronic diseases. The association between rural residence and chronic obstructive pulmonary disease (COPD) exacerbations remains unclear.Objectives: In this work, we sought to determine the independent association between rural residence and COPD-related outcomes, including COPD exacerbations, airflow obstruction, and symptom burden.Methods: A total of 1,684 SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study) participants with forced expiratory volume in 1 second/forced vital capacity < 0.70 had geocoding-defined rural-urban residence status determined (N = 204 rural and N = 1,480 urban). Univariate and multivariate logistic and negative binomial regressions were performed to assess the independent association between rurality and COPD outcomes, including exacerbations, lung function, and symptom burden. The primary exposure of interest was rural residence, determined by geocoding of the home address to the block level at the time of study enrollment. Additional covariates of interest included demographic and clinical characteristics, occupation, and occupational exposures. The primary outcome measures were exacerbations determined over a 1-year course after enrollment by quarterly telephone calls and at an annual research clinic visit. The odds ratio (OR) and incidence rate ratio (IRR) of exacerbations that required treatment with medications, including steroids or antibiotics (total exacerbations), and exacerbations leading to hospitalization (severe exacerbations) were determined after adjusting for relevant covariates.Results: Rural residence was independently associated with a 70% increase in the odds of total exacerbations (OR, 1.70 [95% confidence interval (CI), 1.13-2.56]; P = 0.012) and a 46% higher incidence rate of total exacerbations (IRR 1.46 [95% CI, 1.02-2.10]; P = 0.039). There was no association between rural residence and severe exacerbations. Agricultural occupation was independently associated with increased odds and incidence of total and severe exacerbations. Inclusion of agricultural occupation in the analysis attenuated the association between rural residence and the odds and incidence rate of total exacerbations (OR, 1.52 [95% CI, 1.00-2.32]; P = 0.05 and IRR 1.39 [95% CI, 0.97-1.99]; P = 0.07). There was no difference in symptoms or airflow obstruction between rural and urban participants.Conclusions: Rural residence is independently associated with increased odds and incidence of total, but not severe, COPD exacerbations. These associations are not fully explained by agriculture-related exposures, highlighting the need for future research into potential mechanisms of the increased risk of COPD exacerbations in the rural population.

Differences in residential location as well as race/ethnicity and dietary habits may result in differences in inorganic arsenic (iAs) exposure. We investigated the association of exposure to iAs with race/ethnicity, geography, and dietary intake in a random sample of 310 White, Black, Hispanic, and Chinese adults in the Multi-Ethnic Study of Atherosclerosis from 6 US cities with inorganic and methylated arsenic (ΣAs) measured in urine. Dietary intake was assessed by food-frequency questionnaire. Chinese and Hispanic race/ethnicity was associated with 82% (95% CI: 46%, 126%) and 37% (95% CI: 10%, 70%) higher urine arsenic concentrations, respectively, compared to White participants. No differences were observed for Black participants compared to Whites. Urine arsenic concentrations were higher for participants in Los Angeles, Chicago, and New York compared to other sites. Participants that ate rice ≥2 times/week had 31% higher urine arsenic compared to those that rarely/never consumed rice. Participants that drank wine ≥2 times/week had 23% higher urine arsenic compared to rare/never wine drinkers. Intake of poultry or non-rice grains was not associated with urinary arsenic concentrations. At the low-moderate levels typical of the US population, exposure to iAs differed by race/ethnicity, geographic location, and frequency of rice and wine intake.

The receptor for advanced glycation end products (RAGE) is underexpressed in idiopathic pulmonary fibrosis (IPF) lung, but the role of RAGE in human lung fibrosis remains uncertain.To examine (1) the association between IPF risk and variation at rs2070600, a functional missense variant in AGER (the gene that codes for RAGE), and (2) the associations between plasma-soluble RAGE (sRAGE) levels with disease severity and time to death or lung transplant in IPF.We genotyped the rs2070600 single-nucleotide polymorphism in 108 adults with IPF and 324 race-/ethnicity-matched control subjects. We measured plasma sRAGE by ELISA in 103 adults with IPF. We used generalized linear and additive models as well as Cox models to control for potential confounders. We repeated our analyses in 168 (genetic analyses) and 177 (sRAGE analyses) adults with other forms of interstitial lung disease (ILD).There was no association between rs2070600 variation among adults with IPF (P = 0.31). Plasma sRAGE levels were lower among adults with IPF and other forms of ILD than in control subjects (P 0.001). The rs2070600 allele A was associated with a 49% lower sRAGE level (95% confidence interval [CI], 11 to 71%; P = 0.02) among adults with IPF. In adjusted analyses, lower sRAGE levels were associated with greater disease severity (14% sRAGE decrement per 10% FVC decrement; 95% CI, 5 to 22%) and a higher rate of death or lung transplant at 1 year (adjusted hazard ratio, 1.9 per logarithmic unit of sRAGE decrement; 95% CI, 1.2-3.3) in IPF. Similar findings were observed in a heterogeneous group of adults with other forms of ILD.Lower plasma sRAGE levels may be a biological measure of disease severity in IPF. Variation at the rs2070600 single-nucleotide polymorphism was not associated with IPF risk.

Key Points Question Are long-term exposure to ambient air pollution and proximity to traffic associated with subclinical atherosclerosis? Findings In this population-based cross-sectional study of 8867 Chinese participants, long-term exposure to ambient nitrogen dioxide and fine particulate matter with aerodynamic diameter less than 2.5 μm was independently associated with a higher coronary artery calcium score, a key atherosclerotic marker. Associations with ozone and proximity to traffic were less consistent. Meaning Long-term exposure to ambient air pollution may be an important risk factor for coronary atherosclerosis., This population-based cross-sectional study of 8867 Chinese participants examines the association of long-term exposure to air pollution and proximity to traffic with the coronary artery calcium score, a marker for coronary atherosclerosis., Importance Epidemiologic evidence of the mechanisms of the association between long-term exposure to air pollution and coronary heart disease (CHD) is limited and relies heavily on studies performed in Europe and the United States, where air pollution levels are relatively low. In particular, the association between air pollution and CHD in patients with underlying risks for CHD is understudied. Objective To determine whether air pollution and proximity to traffic are associated with the coronary artery calcium (CAC) score, a key atherosclerotic marker. Design, Setting, and Participants In this prospective, population-based cross-sectional study in a large-scale setting in China, 8867 consecutive patients aged 25 to 92 years with suspected CHD were recruited between November 17, 2015, and September 13, 2017. Participants were excluded if they had previous myocardial infarction, stenting, or coronary artery bypass grafting or incomplete risk factors and exposure data. Each participant underwent assessment of CAC and CHD risk factors at baseline. Data were analyzed from December 2017 to November 2018. Exposures Annual means of fine particulate matter with aerodynamic diameter less than 2.5 μm (PM2.5), nitrogen dioxide (NO2), and ozone (O3) were estimated at the participants’ residences using a validated geostatistical prediction model. Exposure to a nearby roadway was also estimated. Main Outcomes and Measures Computed tomography measurement of CAC score. Results The mean (SD) age of the 8867 participants was 56.9 (10.4) years; 4378 (53.6%) were men. Annual mean (SD) PM2.5, NO2, and O3 measurements were 70.1 (20.0), 41.4 (14.7), and 93.9 (10.5) μg/m3, respectively. The mean (SD) CAC score was 91.4 (322.2) Agatston units. Exposure to PM2.5 and NO2, adjusting for CHD risk factors and multiple pollutants, were independently associated with increases in CAC scores of 27.2% (95% CI, 10.8% to 46.1%) per 30 μg/m3 PM2.5 and 24.5% (95% CI, 3.6% to 49.7%) per 20 μg/m3 NO2. For PM2.5, odds of both detectable CAC (Agatston score >0; odds ratio, 1.28; 95% CI, 1.13 to 1.45) and severe CAC (Agatston score >400; odds ratio, 1.59; 95% CI, 1.20 to 2.12) were increased. Associations of CAC with PM2.5 and NO2 were greater among male participants (PM2.5: 42.2%; 95% CI, 24.3% to 62.7%; NO2: 45.7%; 95% CI, 25.3% to 69.5%) and elderly participants (PM2.5: 50.1%; 95% CI, 28.8% to 75.0%; NO2: 55.5%; 95% CI, 31.8% to 83.6%) and those with diabetes (PM2.5: 62.2%; 95% CI, 30.9% to 101.0%; NO2: 31.2%; 95% CI, 13.9% to 51.0%). Independent association with CAC score was 9.0% (95% CI, −1.4% to 20.4%) for O3 per 15 μg/m3 and 2.4% (95% CI, −0.6% to 5.4%) for distance near roadway per 50% decrease. Conclusions and Relevance In this large Chinese study, long-term exposures to PM2.5 and NO2 were independently associated with severity of CAC. This finding may provide support for the pathophysiological role of coronary atherosclerosis through which air pollution exposure may be associated with CHD.

BACKGROUND: Limited research suggests ambient air pollution impairs fecundity but groups most susceptible have not been identified. We studied whether long-term ambient air pollution exposure prior to an in vitro fertilization (IVF) cycle was associated with successful livebirth, and whether associations were modified by underlying infertility diagnosis. METHODS: Data on women initiating their 1(st) autologous IVF cycle in 2012-13 were obtained from four U.S. clinics. Outcomes included pregnancy, pregnancy loss, and livebirth. Annual average exposure to fine particulate matter (PM(2.5)), PM(10), and nitrogen dioxide (NO(2)) prior to IVF start were estimated at residential address using a validated national spatial model incorporating land-use regression and universal kriging. We also assessed residential distance to major roadway. We calculated risk ratios (RR) using modified Poisson regression and evaluated effect modification (EM) by infertility diagnosis on additive and multiplicative scales. RESULTS: Among 7,463 eligible participants, 36% had a livebirth. There was a non-significant indication of an association between PM(2.5) or NO(2) and decreased livebirth and increased pregnancy loss. Near roadway residence was associated with decreased livebirth (RR: 0.96, 95% CI: 0.82, 0.99. There was evidence for EM between high exposure to air pollutants and a diagnosis of diminished ovarian reserve (DOR) or male infertility and decreased livebirth. CONCLUSIONS: Despite suggestive but uncertain findings for the overall effect of air pollution on fecundity, we found a suggestive indication that there may be synergistic effects of air pollution and DOR or male infertility diagnosis on livebirth. This suggests two possible targets for future research and intervention.

Novel technology permits quantification of common carotid artery (CCA) displacement, which is traditionally ignored. We evaluated associations with CCA displacement and cardiovascular disease (CVD) risk and events in a large, multi-ethnic cohort. Right CCA longitudinal displacement (LD), transverse displacement (TD), and grayscale median (GSM) were evaluated using ultrasound speckle-tracking and texture analysis software in 2050 participants. Regression analyses were used to define relationships between CCA LD, TD, GSM, and CVD risk factors. Cox proportional hazards models were used to assess relationships between LD, TD, and incident CVD events. Participants were mean (SD) 64 (10) years old. There were 791 cases with a CVD event over a 12-year median follow-up. The mean LD was 0.29 (0.20) mm. In multivariable models including age, sex, race/ethnicity, heart rate, and CVD risk factors, LD was associated positively with active smoking (β = 0.08, p < 0.001) and inversely with black (β = −0.08, p < 0.001), Chinese (β = −0.05, p < 0.001), and Hispanic (β = −0.04, p < 0.05) race/ethnicities relative to white individuals, heart rate (β = −0.03/10 beats/min, p < 0.001), and diastolic blood pressure (β = −0.01/5 mmHg, p < 0.05). In fully adjusted models, LD and TD were associated with GSM ( p < 0.01), but neither predicted incident CVD events (LD: hazard ratio (HR) 0.77 [0.48 to 1.24], p = 0.3; TD: HR 1.12 [0.8 to 1.57], p = 0.5). CCA LD and TD are associated with race/ethnicity and CVD risk factors but not incident CVD events. LD and TD are not measures of arterial stiffness but their association with GSM suggests that lower LD and TD may be related to structural changes within the carotid arterial wall.

BackgroundAir pollution alters small pulmonary vessels in animal models. We hypothesised that long-term ambient air pollution exposure would be associated with differences in pulmonary vascular volumes in a population-based study.MethodsThe Multi-Ethnic Study of Atherosclerosis recruited adults in six US cities. Personalised long-term exposures to ambient black carbon, nitrogen dioxide (NO2), oxides of nitrogen (NOx), particulate matter with a 50% cut-off aerodynamic diameter of 2.5) and ozone were estimated using spatiotemporal models. In 2010–2012, total pulmonary vascular volume was measured as the volume of detectable pulmonary arteries and veins, including vessel walls and luminal blood volume, on noncontrast chest computed tomography (TPVVCT). Peripheral TPVVCTwas limited to the peripheral 2 cm to isolate smaller vessels. Linear regression adjusted for demographics, anthropometrics, smoking, second-hand smoke, renal function and scanner manufacturer.ResultsThe mean±sdage of the 3023 participants was 69.3±9.3 years; 46% were never-smokers. Mean exposures were 0.80 μg·m−3black carbon, 14.6 ppb NO2and 11.0 μg·m−3ambient PM2.5. Mean±sdperipheral TPVVCTwas 79.2±18.2 cm3and TPVVCTwas 129.3±35.1 cm3. Greater black carbon exposure was associated with a larger peripheral TPVVCT, including after adjustment for city (mean difference 0.41 (95% CI 0.03–0.79) cm3per interquartile range; p=0.036). Associations for peripheral TPVVCTwith NO2were similar but nonsignificant after city adjustment, while those for PM2.5were of similar magnitude but nonsignificant after full adjustment. There were no associations for NOxor ozone, or between any pollutant and TPVVCT.ConclusionsLong-term black carbon exposure was associated with a larger peripheral TPVVCT, suggesting diesel exhaust may contribute to remodelling of small pulmonary vessels in the general population.

Background: Long-term ozone (O3) exposure is associated with cardiovascular mortality, but little is known about the associations between O3 and subclinical arterial disease. Objectives: We studied...

Objective— Lp(a) [lipoprotein(a)] is a well-described risk factor for atherosclerosis, but Lp(a)-associated risk may vary by race/ethnicity. We aimed to determine whether race/ethnicity modifies Lp(a)-related risk of carotid atherosclerotic plaque outcomes among black, white, Chinese, and Hispanic individuals. Approach and Results— Carotid plaque presence and score were assessed by ultrasonography at baseline (n=5155) and following a median 9.4 year period (n=3380) in MESA (Multi-Ethnic Study of Atherosclerosis) participants. Lp(a) concentrations were measured by immunoassay and examined as a continuous and categorical variable using clinically-based cutoffs, 30 and 50 mg/dL. Lp(a) was related to greater risk of prevalent carotid plaque at baseline in whites alone (all P P P =0.04). In prospective analyses, whites with Lp(a) ≥50 mg/dL were found to have greater risk of plaque progression (relative risk, 1.12; P =0.03) and higher plaque scores (all P Conclusions— Race was found to be a modifying variable in Lp(a)-related risk of carotid plaque, and Lp(a) levels may have greater influence on plaque burden in whites than in black individuals. Borderline results in Hispanics suggest that elevated Lp(a) may increase the risk of carotid plaque, but follow-up studies are needed.

Rationale: Air pollution may influence sleep through airway inflammation or autonomic nervous system pathway alterations. Epidemiological studies may provide evidence of relationships between chronic air pollution exposure and sleep apnea. Objectives: To determine whether ambient-derived pollution exposure is associated with obstructive sleep apnea and objective sleep disruption. Methods: We analyzed data from a sample of participants in MESA (Multi-Ethnic Study of Atherosclerosis) who participated in both the Sleep and Air studies. Mean annual and 5-year exposure levels to nitrogen dioxide (NO(2)) and particulate matter ≤ 2.5 μm in aerodynamic diameter (PM(2.5)) were estimated at participants’ homes using spatiotemporal models based on cohort-specific monitoring. Participants completed in-home full polysomnography and 7 days of wrist actigraphy. We used multivariate models, adjusted for demographics, comorbidities, socioeconomic factors, and site, to assess whether air pollution was associated with sleep apnea (apnea–hypopnea index ≥ 15) and actigraphy-measured sleep efficiency. Results: The participants (n = 1,974) were an average age of 68 (±9) years, 46% male, 36% white, 24% Hispanic, 28% black, and 12% Asian; 48% had sleep apnea and 25% had a sleep efficiency of ≤88%. A 10 ppb annual increase in NO(2) exposure was associated with 39% greater adjusted odds of sleep apnea (95% confidence interval [CI], 1.03–1.87). A 5 μg/m(3) greater annual PM(2.5) exposure was also associated with 60% greater odds of sleep apnea (95% CI, 0.98–2.62). Sleep efficiency was not associated with air pollution levels in fully adjusted models. Conclusions: Individuals with higher annual NO(2) and PM(2.5) exposure levels had a greater odds of sleep apnea. These data suggest that in addition to individual risk factors, environmental factors also contribute to the variation of sleep disorders across groups, possibly contributing to health disparities.

Background We hypothesized that measures of common carotid artery echolucency and grayscale texture features were associated with cardiovascular disease ( CVD ) risk factors and could predict CVD events. Methods and Results Using a case‐cohort design, we measured common carotid artery ultrasound images from 1788 participants in Exam 1 of the MESA study (Multi‐Ethnic Study of Atherosclerosis) to derive 4 grayscale features: grayscale median, entropy, gray level difference statistic‐contrast, and spatial gray level dependence matrices‐angular second moment. CVD risk factor associations were determined by linear regression. Cox proportional hazard models with inverse selection probability weighting and adjustments for age, sex, race/ethnicity, CVD risk factors, and C‐reactive protein were used to determine if standardized values for grayscale median, entropy, gray level difference statistic‐contrast, and spatial gray level dependence matrices‐angular second moment could predict incident coronary heart disease, stroke, and total CVD events over a median 13 years follow‐up. Participants were mean ( SD ) 63.1 (10.3) years of age, 52.6% female, 32.1% white, 27.8% black, 23.3% Hispanic, and 16.8% Chinese. There were 283 coronary heart disease, 120 stroke, and 416 CVD events. Several associations of grayscale features with CVD risk factors were identified. In fully adjusted models, higher gray level difference statistic‐contrast was associated with a lower risk of incident coronary heart disease (hazard ratio 0.82, 95% CI 0.71–0.94, p adj =0.005) and CVD events (hazard ratio 0.87, 95% CI 0.77–0.98, p adj =0.018); higher spatial gray level dependence matrices‐angular second moment was associated with a higher risk of CVD events (hazard ratio 1.09, 95% CI 1.00–1.19, p adj =0.044). Conclusions Gray level difference statistic‐contrast and spatial gray level dependence matrices‐angular second moment predicted CVD events independent of risk factors, indicating their potential use as biomarkers to assess future CVD risk.

Background Exposure to traffic-related air pollution is associated with an increased risk of cardiovascular and respiratory disease. Evidence suggests that inhaled pollutants precipitate these effects via multiple pathways involving oxidative stress. Objective Postulating that a decrease in circulating antioxidant levels reflect an oxidative response, we investigated the effect of inhaled diesel exhaust (DE) on the ratio of reduced to oxidized glutathione (GSH/GSSG) in healthy adults, and whether pre-exposure antioxidant supplementation blunted this response. We also examined exposure-related changes in antioxidant/stress response leukocyte gene expression (GCLc, HMOX-1, IL-6, TGFβ) and plasma IL-6 levels. Methods Nineteen nonsmoking adults participated in a double-blind, randomized, four-way crossover study. Each subject completed 120-min exposures to filtered air and DE (200 μg/m3), with and without antioxidant pretreatment. Antioxidant comprised 1000 mg ascorbate for 7 days and 1200 mg N-acetylcysteine 1 day prior to exposure, with 1000 mg and 600 mg, respectively, administered 2 h prior to exposure. Whole blood glutathione was measured pre- and post-exposure; plasma IL-6 and mRNA expression were quantified pre, during and post exposure. Results Diesel exhaust exposure was associated with significantly decreased GSH/GSSG (p = 0.001) and a 4-fold increase in IL-6 mRNA (p = 0.01) post exposure. Antioxidant pretreatment did not significantly mediate the effect of DE exposure on GSH/GSSG, though appeared to decrease the effect of exposure on IL-6 mRNA expression. Conclusions Acute DE inhalation induced detectable oxidative effects in healthy adults, which were not significantly attenuated by the selected antioxidant pre-treatment. This finding supports the premise that oxidative stress is one mechanism underlying the adverse effects of traffic-related air pollution.

Evidence suggests that lung injury, inflammation and extracellular matrix remodelling precede lung fibrosis in interstitial lung disease (ILD). We examined whether a quantitative measure of increased lung attenuation on computed tomography (CT) detects lung injury, inflammation and extracellular matrix remodelling in community-dwelling adults sampled without regard to respiratory symptoms or smoking.We measured high attenuation areas (HAA; percentage of lung voxels between −600 and −250 Hounsfield Units) on cardiac CT scans of adults enrolled in the Multi-Ethnic Study of Atherosclerosis.HAA was associated with higher serum matrix metalloproteinase-7 (mean adjusted difference 6.3% per HAA doubling, 95% CI 1.3–11.5), higher interleukin-6 (mean adjusted difference 8.8%, 95% CI 4.8–13.0), lower forced vital capacity (FVC) (mean adjusted difference −82 mL, 95% CI −119–−44), lower 6-min walk distance (mean adjusted difference −40 m, 95% CI −1–−80), higher odds of interstitial lung abnormalities at 9.5 years (adjusted OR 1.95, 95% CI 1.43–2.65), and higher all cause-mortality rate over 12.2 years (HR 1.58, 95% CI 1.39–1.79).High attenuation areas are associated with biomarkers of inflammation and extracellular matrix remodelling, reduced lung function, interstitial lung abnormalities, and a higher risk of death among community-dwelling adults.

Summary Air pollution epidemiology studies are trending towards a multipollutant approach. In these studies, exposures at subject locations are unobserved and must be predicted by using observed exposures at misaligned monitoring locations. This induces measurement error, which can bias the estimated health effects and affect standard error estimates. We characterize this measurement error and develop an analytic bias correction when using penalized regression splines to predict exposure. Our simulations show that bias from multipollutant measurement error can be severe, and in opposite directions or simultaneously positive or negative. Our analytic bias correction combined with a non-parametric bootstrap yields accurate coverage of 95% confidence intervals. We apply our methodology to analyse the association of systolic blood pressure with PM2.5 and NO2 levels in the National Institute of Environmental Health Sciences Sister Study. We find that NO2 confounds the association of systolic blood pressure with PM2.5 levels and vice versa. Elevated systolic blood pressure was significantly associated with increased PM2.5 and decreased NO2 levels. Correcting for measurement error bias strengthened these associations and widened 95% confidence intervals.

Objective: To determine the value of neurologist ambulatory care in chronic neurologic diseases in a large administrative claims dataset detailing costs, adverse events, and health care utilization. Methods: The Optum proprietary claims dataset (2010–2012) was examined to describe direct health care costs, as well as specific outcome metrics for a large population of persons with chronic neurologic illnesses. In phase I of the study, we detail neurologist involvement and differences in annualized allowed third--party payments within episode treatment groups (ETGs) for 10 neurologic illnesses. For phase II, we examined health care utilization for ETGs of epilepsy, Parkinson disease (PD), stroke, and multiple sclerosis (MS) with and without neurologist involvement. Reported outcomes were unadjusted differences and odds ratios between treatment groups. Results: For phase I, a total of 1,913,605 ETGs for 10 neurologic conditions were identified, 30.1% meeting criteria for neurologist involvement. All conditions had higher direct costs when neurologists were involved with care, ranging from a 25% increase for Alzheimer dementia to 100% more for MS care. In phase II, fractures, infections, emergent care, and inpatient admission were less with neurologist ambulatory care, while neurologist care was associated with greater utilization of disease-specific treatments (immunotherapies in MS anticoagulation in atrial fibrillation–associated stroke, deep brain stimulation and dopaminergic therapies in PD). Conclusion: Neurologist involvement with care is associated with greater unadjusted allowed payments, but fewer adverse events and less acute care utilization.

Emphysema on CT is associated with accelerated lung function decline in heavy smokers and patients with COPD; however, in the general population, it is not known whether greater emphysema-like lung on CT is associated with incident COPD. We used data from 2045 adult participants without initial prebronchodilator airflow limitation, classified by FEV1/FVC>upper limit of normal, was associated with increased odds of incident airflow limitation at 5-year follow-up on both prebronchodilator (adjusted OR 2.62, 95% CI 1.47 to 4.67) and postbronchodilator (adjusted OR 4.38, 95% CI 1.63 to 11.74) spirometry, independent of smoking history. These results support investigation into whether emphysema-like lung could be informative for COPD risk stratification.

Background and Purpose— Long-term exposure to ambient air pollution is associated with higher risk of cardiovascular disease and stroke. We hypothesized that long-term exposure to air pollution would be associated with magnetic resonance imaging markers of subclinical cerebrovascular disease. Methods— Participants were 1075 stroke-free individuals aged ≥50 years drawn from the magnetic resonance imaging subcohort of the Northern Manhattan Study who had lived at the same residence for at least 2 years before magnetic resonance imaging. Cross-sectional associations between ambient air pollution and subclinical cerebrovascular disease were analyzed. Results— We found an association between distance to roadway, a proxy for residential exposure to traffic pollution, and white matter hyperintensity volume; however, after adjusting for risk factors, this relationship was no longer present. All other associations between pollutant measures and white matter hyperintensity volume were null. There was no clear association between exposure to air pollutants and subclinical brain infarcts or total cerebral brain volume. Conclusions— We found no evidence that long-term exposure to ambient air pollution is independently associated with subclinical cerebrovascular disease in an urban population-based cohort.

IMPORTANCE: Smoking is a major risk factor for chronic obstructive pulmonary disease (COPD), yet much of COPD risk remains unexplained. OBJECTIVE: To determine whether dysanapsis, a mismatch of airway tree caliber to lung size, assessed by computed tomography (CT), is associated with incident COPD among older adults and lung function decline in COPD. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study of 2 community-based samples: the Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study, which involved 2531 participants (6 US sites, 2010-2018) and the Canadian Cohort of Obstructive Lung Disease (CanCOLD), which involved 1272 participants (9 Canadian sites, 2010-2018), and a case-control study of COPD: the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS), which involved 2726 participants (12 US sites, 2011-2016). EXPOSURES: Dysanapsis was quantified on CT as the geometric mean of airway lumen diameters measured at 19 standard anatomic locations divided by the cube root of lung volume (airway to lung ratio). MAIN OUTCOMES AND MEASURES: Primary outcome was COPD defined by postbronchodilator ratio of forced expired volume in the first second to vital capacity (FEV(1):FVC) less than 0.70 with respiratory symptoms. Secondary outcome was longitudinal lung function. All analyses were adjusted for demographics and standard COPD risk factors (primary and secondhand tobacco smoke exposures, occupational and environmental pollutants, and asthma). RESULTS: In the MESA Lung sample (mean [SD] age, 69 years [9 years]; 1334 women [52.7%]), 237 of 2531 participants (9.4%) had prevalent COPD, the mean (SD) airway to lung ratio was 0.033 (0.004), and the mean (SD) FEV(1) decline was −33 mL/y (31 mL/y). Of 2294 MESA Lung participants without prevalent COPD, 98 (4.3%) had incident COPD at a median of 6.2 years. Compared with participants in the highest quartile of airway to lung ratio, those in the lowest had a significantly higher COPD incidence (9.8 vs 1.2 cases per 1000 person-years; rate ratio [RR], 8.12; 95% CI, 3.81 to 17.27; rate difference, 8.6 cases per 1000 person-years; 95% CI, 7.1 to 9.2; P

Background: Grayscale ultrasound atherosclerotic plaque characteristics may predict cardiovascular disease (CVD) events, though they have not been investigated in a large primary prevention cohort. This study determined if CVD risk factors were associated with carotid plaque ultrasound characteristics and if these characteristics could predict future coronary heart disease (CHD) and stroke/transient ischemic attack (TIA) events in a multi-ethnic cohort free of known CVD at baseline. Methods: We measured carotid artery total plaque area (TPA) and grayscale carotid plaque features (grayscale median, black areas, and discrete white areas) at baseline in participants of the Multi-Ethnic Study of Atherosclerosis that had B-mode carotid ultrasound examinations. There were 2205 participants with images available for TPA analyses and 1703 with images available for grayscale analyses. Multivariable linear regression analysis was used to examine relationships between baseline ultrasound carotid plaque features and CVD risk factors. Cox proportional hazards models were used to assess their ability to predict incident CHD and stroke/TIA events over an average follow-up of 13.3 years. The predictive characteristics of TPA and carotid plaque features were compared to carotid plaque score and coronary artery calcification (CAC) score. Results: Participants were mean (standard deviation) 65.4 (9.6) years old, 49% male, 39% White, 28% Black, 22% Hispanic, and 11% Chinese. Mean TPA (27.7 [24.7] mm 2 ), but not grayscale plaque features, were associated with several CVD risk factors. In risk factor-adjusted models, TPA was the only plaque feature that predicted incident CHD events (HR 1.23; 95% CI 1.11-1.36; p Conclusions: In middle-aged individuals free of known CVD, carotid TPA was associated with CVD risk factors and predicted incident CHD events while grayscale plaque features did not. For CHD, predictive characteristics of TPA were similar to carotid plaque score but lower than CAC score.

Rationale: Large airway dimensions on computed tomography (CT) have been associated with lung function, symptoms, and exacerbations in chronic obstructive pulmonary disease (COPD), as well as with symptoms in smokers with preserved spirometry. Their prognostic significance in persons without lung disease remains undefined. Objectives: To examine associations between large airway dimensions on CT and respiratory outcomes in a population-based cohort of adults without prevalent lung disease. Methods: The Multi-Ethnic Study of Atherosclerosis recruited participants ages 45–84 years without cardiovascular disease in 2000–2002; we excluded participants with prevalent chronic lower respiratory disease (CLRD). Spirometry was measured in 2004–2006 and 2010–2012. CLRD hospitalizations and deaths were classified by validated criteria through 2014. The average wall thickness for a hypothetical airway of 10-mm lumen perimeter on CT (Pi10) was calculated using measures of airway wall thickness and lumen diameter. Models were adjusted for age, sex, principal components of ancestry, body mass index, smoking, pack-years, scanner, percent emphysema, genetic risk score, and initial forced expiratory volume in 1 second (FEV(1)) percent predicted. Results: Greater Pi10 was associated with 9% faster FEV(1) decline (95% confidence interval [CI], 2 to 15%; P = 0.012) and increased incident COPD (odds ratio, 2.22; 95% CI, 1.43–3.45; P = 0.0004) per standard deviation among 1,830 participants. Over 78,147 person-years, higher Pi10 was associated with a 57% higher risk of first CLRD hospitalization or mortality (P = 0.0496) per standard deviation. Of Pi10’s component measures, both greater airway wall thickness and narrower lumen predicted incident COPD and CLRD clinical events. Conclusions: In adults without CLRD, large airway dimensions on CT were prospectively associated with accelerated lung function decline and increased risks of COPD and CLRD hospitalization and mortality.