STUDY OBJECTIVES: Given the unknown immediate impact of migraine on nighttime sleep, we prospectively examined whether migraine headaches were associated with subsequent shorter sleep duration, higher fragmentation and poorer quality in a cohort of 98 adults with episodic migraine. METHODS: Participants completed twice-daily electronic diaries and wore actigraphs continuously for 6 weeks. We examined whether days with headaches were associated with changes in that night's sleep characteristics compared to non-headache days, using adjusted multivariable linear mixed models with subject-specific intercepts. RESULTS: Participants were 35 ± 12 years old, 88% women, with an average of five migraine headaches/month. Over 4406 days, we observed 1077 headache days, representing 823 discrete headaches. Average nightly objective sleep duration was 7.3 ± 1.2 hours, efficiency 89.5 ± 3.3% and wake after sleep onset (WASO) 44.8 ± 17.0 minutes. Objective sleep duration was 7.3 minutes (95% CI:1.5, 13.0) longer on nights following a headache day compared to nights on a headache-free day. Objective sleep efficiency, WASO, and reported sleep quality were not significantly different on headache days compared to headache-free days (sleep efficiency: -0.06 min. CONCLUSIONS: Sleep periods immediately following migraine headaches are not associated with shorter sleep duration, higher sleep disruption, or poorer sleep quality in patients with episodic migraine. These results suggest that clinical evaluation of sleep disturbance in patients with episodic migraine should be approached independently of their migraine status.

OBJECTIVE: To test the hypotheses that insufficient duration, high fragmentation, and poor sleep quality are temporally associated with migraine onset on the day immediately following the sleep period (day 0) and the following day (day 1). METHODS: In this prospective cohort study of 98 adults with episodic migraine, participants completed twice-daily electronic diaries on sleep, headaches, and other health habits, and wore wrist actigraphs for 6 weeks. We estimated the incidence of migraine following nights with short sleep duration, high fragmentation, or low quality compared to nights with adequate sleep with conditional logistic regression models stratified by participant and adjusted for caffeine intake, alcohol intake, physical activity, stress, and day of week. RESULTS: Participants were a mean age of 35.1 ± 12.1 years. We collected 4,406 days of data, with 870 headaches reported. Sleep duration ≤6.5 hours and poor sleep quality were not associated with migraine on day 0 or day 1. Diary-reported low efficiency was associated with 39% higher odds of headache on day 1 (odds ratio [OR] 1.39, 95% confidence interval [CI] 1.06-1.81). Actigraphic-assessed high fragmentation was associated with lower odds of migraine on day 0 (wake after sleep onset >53 minutes, OR 0.64, 95% CI 0.48-0.86; efficiency ≤88%, OR 0.74, 95% CI 0.56-0.99). CONCLUSION: Short sleep duration and low sleep quality were not temporally associated with migraine. Sleep fragmentation, defined by low sleep efficiency, was associated with higher odds of migraine on day 1. Further research is needed to understand the clinical and neurobiologic implications of sleep fragmentation and risk of migraine.

Whether critical care improvements over the last 10 years extend to all hospitals has not been described. To examine the temporal trends of critical care outcomes in minority and non-minority-serving hospitals using an inception cohort of critically ill patients. Using the Philips Health Care electronic ICU Research Institute Database, we identified minority-serving hospitals as those with an African American or Hispanic ICU census more than twice its regional mean. We examined almost 1.1 million critical illness admissions among 208 ICUs from across the United States admitted between 2006 and 2016. Adjusted hospital mortality (primary) and length of hospitalization (secondary) were the main outcomes. Large pluralities of African American (25%,  = 27,242) and Hispanic individuals (48%,  = 26,743) were cared for in minority-serving hospitals, compared with only 5.2% ( = 42,941) of white individuals. Over the last 10 years, although the risk of critical illness mortality steadily decreased by 2% per year (95% confidence interval [CI], 0.97-0.98) in non-minority-serving hospitals, outcomes within minority-serving hospitals did not improve comparably. This disparity in temporal trends was particularly noticeable among African American individuals, where each additional calendar year was associated with a 3% (95% CI, 0.96-0.97) lower adjusted critical illness mortality within a non-minority-serving hospital, but no change within minority-serving hospitals (hazard ratio, 0.99; 95% CI, 0.97-1.01). Similarly, although ICU and hospital lengths of stay decreased by 0.08 (95% CI, -0.08 to -0.07) and 0.16 (95% CI, -0.16 to -0.15) days per additional calendar year, respectively, in non-minority-serving hospitals, there was little temporal change for African American individuals in minority-serving hospitals. Critically ill African American individuals are disproportionately cared for in minority-serving hospitals, which have shown significantly less improvement than non-minority-serving hospitals over the last 10 years.

BACKGROUND: Ambient air pollution accelerates lung function decline among adults, however, there are limited data about its role in the development and progression of early stages of interstitial lung disease. AIMS: To evaluate associations of long-term exposure to traffic and ambient pollutants with odds of interstitial lung abnormalities (ILA) and progression of ILA on repeated imaging. METHODS: We ascertained ILA on chest CT obtained from 2618 Framingham participants from 2008 to 2011. Among 1846 participants who also completed a cardiac CT from 2002 to 2005, we determined interval ILA progression. We assigned distance from home address to major roadway, and the 5-year average of fine particulate matter (PM), elemental carbon (EC, a traffic-related PM constituent) and ozone using spatio-temporal prediction models. Logistic regression models were adjusted for age, sex, body mass index, smoking status, packyears of smoking, household tobacco exposure, neighbourhood household value, primary occupation, cohort and date. RESULTS: Among 2618 participants with a chest CT, 176 (6.7%) had ILA, 1361 (52.0%) had no ILA, and the remainder were indeterminate. Among 1846 with a preceding cardiac CT, 118 (6.4%) had ILA with interval progression. In adjusted logistic regression models, an IQR difference in 5-year EC exposure of 0.14 µg/m was associated with a 1.27 (95% CI 1.04 to 1.55) times greater odds of ILA, and a 1.33 (95% CI 1.00 to 1.76) times greater odds of ILA progression. PM and O were not associated with ILA or ILA progression. CONCLUSIONS: Exposure to EC may increase risk of progressive ILA, however, associations with other measures of ambient pollution were inconclusive.

Acute exposure to cold dry air is a trigger of bronchoconstriction, but little is known about how daily outdoor temperature influences lung function.We investigated associations of temperature from a model using satellite remote sensing data with repeated measures of lung function among 5896 participants of the Framingham Heart Study Offspring and Third Generation cohorts residing in the Northeastern US. We further tested if temperature modified previously reported associations between pollution and lung function. We constructed linear mixed-effects models, and assessed departures from linearity using penalised splines.In fully adjusted linear models, 1-, 2- and 7-day average temperatures were all associated with lower lung function: each 5°C higher previous-week temperature was associated with a 20 mL lower (95% CI -34---6) forced expiratory volume in 1 s. There was significant effect modification by season: negative associations of temperature and lung function were present in winter and spring only. Negative associations between previous-day fine particulate matter and lung function were present during unseasonably warm but not unseasonably cool days, with a similar pattern for other pollutants.We speculate that temperature-related differences in lung function may be explained by behavioural changes on relatively warm days, which may increase outdoor exposures.

Cigarette smoke exposure is a risk factor for many lung diseases, and histologic studies suggest that tobacco-related vasoconstriction and vessel loss plays a role in the development of emphysema. However, it remains unclear how tobacco affects the pulmonary vasculature in general populations with a typical range of tobacco exposure, and whether these changes are detectable by radiographic methods. To determine whether tobacco exposure in a generally healthy population manifests as lower pulmonary blood vessel volumes and vascular pruning on imaging. A total of 2,410 Framingham Heart Study participants with demographic data and smoking history underwent volumetric whole-lung computed tomography from 2008 to 2011. Automated algorithms calculated the total blood volume of all intrapulmonary vessels (TBV), smaller peripheral vessels (defined as cross-sectional area <5 mm [BV5]), and the relative fraction of small vessels (BV5/TBV). Tobacco exposure was assessed as smoking status, cumulative pack-years, and second-hand exposure. We constructed multivariable linear regression models to evaluate associations of cigarette exposure and pulmonary blood vessel volume measures, adjusting for demographic covariates, including age, sex, height, weight, education, occupation, and median neighborhood income. All metrics of tobacco exposure (including smoking status, pack-years, and second-hand exposure) were consistently associated with higher absolute pulmonary blood vessel volume, higher small vessel volume, and/or higher small vessel fraction. For example, ever-smokers had a 4.6 ml higher TBV (95% confidence interval [CI] = 2.9-6.3,  < 0.001), 2.1 ml higher BV5 (95% CI = 1.3-2.9,  < 0.001), and 0.28 percentage-point-higher BV5/TBV (95% CI = 0.03-0.52,  = 0.03) compared with never-smokers. These associations remained significant after adjustment for percent predicted forced expiratory volume in 1 second, cardiovascular comorbidities, and did not differ based on presence or absence of airflow obstruction. Using computed tomographic imaging, we found that cigarette exposure was associated with higher pulmonary blood vessel volumes, especially in the smaller peripheral vessels. Although, histologically, tobacco-related vasculopathy is characterized by vessel narrowing and loss, our results suggest that radiographic vascular pruning may not be a surrogate of these pathologic changes.

BACKGROUND: Whether cognitive decline is related to a higher risk of death independent of the initial cognitive function is inconclusive. Evidence of the association between cognitive decline and mortality among Chinese older people is limited. We aimed to examine whether cognitive decline, assessed by the rate of decrease in the Mini-Mental State Examination (MMSE) score, was associated with mortality independent of initial cognitive function (baseline MMSE score) among Chinese older people. METHODS: We established two successive and non-overlapping cohorts of older adults nested within the Chinese Longitudinal Healthy Longevity Survey (CLHLS), an ongoing, open, community-based cohort survey conducted every 2-3 years. Cognitive function was measured using the Chinese version of the MMSE. A total of 11,732 older adults who completed two consecutive cognitive function examinations were included and followed for 3 years. A Cox proportional hazards model was used to examine the association of cognitive decline with mortality after adjusting for sociodemographic characteristics, health behaviours, comorbidities and initial cognitive function. RESULTS: The mean age was 82.5 years old, and 44.9% (5264/11732) of participants were men. After adjusting for baseline MMSE scores and other covariates, the rate of change in MMSE scores over 3 years was monotonically and positively associated with subsequent 3-year mortality. Compared to those with stable cognitive function, participants with rapid cognitive decline (decline faster than average, a reduction of MMSE scores > 1.62 points/year) had a 75% higher risk of death (hazard ratio = 1.75, 95% confidence interval 1.57-1.95). The association between cognitive decline and mortality was stronger among relatively younger Chinese older people (aged 65-79 years versus 80 years and over) and those with normal cognitive function at baseline (MMSE scores ≥ 24 versus < 24 points), respectively, but did not differ by cohort and sex. CONCLUSION: Faster cognitive decline was associated with higher mortality independent of initial cognitive function, especially among those aged 65-79 years and those with normal cognitive function at baseline. The association was consistent across two successive cohorts. Our findings indicate the practical significance of monitoring cognitive change in older adults.

PURPOSE: We aimed to evaluate the role of caffeinated beverage intake as a potential trigger of migraine headaches on that day or on the following day. METHODS: In this prospective cohort study, 101 adults with episodic migraine completed electronic diaries every morning and evening. Ninety-eight participants completed at least 6 weeks of diaries in March 2016-October 2017. Every day, participants reported caffeinated beverage intake, other lifestyle factors, and the timing and characteristics of each migraine headache. We compared a participant's incidence of migraines on days with caffeinated beverage intake to the incidence of migraines among the same individual on days with no intake, accounting for day of week. We used conditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals. RESULTS: Among 98 participants (86 women, 12 men) with mean age 35.1 years, 83% white, and 10% Hispanic or Latino, the average age when headaches started was 16.3 years. In total, the participants reported 825 migraines during 4467 days of observation. There was a statistically significant nonlinear association between the number of caffeinated beverages and the odds of migraine headache occurrence on that day (P-quadratic trend = .024), though estimates for each level of intake were not statistically significant. The associations varied according to habitual intake and oral contraceptive use. CONCLUSIONS: There was a nonlinear association between caffeinated beverage intake and the odds of migraine headache occurrence on that day. This suggests that high levels of caffeinated beverage intake may be a trigger of migraine headaches on that day.

Radiographic abnormalities of the pulmonary vessels, such as vascular pruning, are common in advanced airways disease, but it is unknown if pulmonary vascular volumes are related to measures of lung health and airways disease in healthier populations.In 2388 participants of the Framingham Heart Study computed tomography (CT) sub-study, we calculated total vessel volumes and the small vessel fraction using automated CT image analysis. We evaluated associations with measures of lung function, airflow obstruction on spirometry and emphysema on CT. We further tested if associations of vascular volumes with lung function were present among those with normal forced expiratory volume in 1 s and forced vital capacity.In fully adjusted linear and logistic models, we found that lower total and small vessel volumes were consistently associated with worse measures of lung health, including lower spirometric volumes, lower diffusing capacity and/or higher odds of airflow obstruction. For example, each standard deviation lower small vessel fraction (indicating more severe pruning) was associated with a 37% greater odds of obstruction (OR 1.37, 95% CI 1.11-1.71, p=0.004). A similar pattern was observed in the subset of participants with normal spirometry.Lower total and small vessel pulmonary vascular volumes were associated with poorer measures of lung health and/or greater odds of airflow obstruction in this cohort of generally healthy adults without high burdens of smoking or airways disease. Our findings suggest that quantitative CT assessment may detect subtle pulmonary vasculopathy that occurs in the setting of subclinical and early pulmonary and airways pathology.

BACKGROUND: Short-term exposure to air pollution has been associated with cardiovascular events, potentially by promoting endothelial cell activation and inflammation. A few large-scale studies have examined the associations and have had mixed results. METHODS: We included 3820 non-current smoking participants (mean age 56 years, 54% women) from the Framingham Offspring cohort examinations 7 (1998-2001) and 8 (2005-2008), and Third Generation cohort examination 1 (2002-2005), who lived within 50 km of a central monitoring station. We calculated the 1- to 7-day moving averages of fine particulate matter (PM), black carbon (BC), sulfate (SO), nitrogen oxides (NO), and ozone before examination visits. We used linear mixed effect models for P-selectin, monocyte chemoattractant protein 1 (MCP-1), intercellular adhesion molecule 1, lipoprotein-associated phospholipase A2 activity and mass, and osteoprotegerin that were measured up to twice, and linear regression models for CD40 ligand and interleukin-18 that were measured once, adjusting for demographics, life style and clinical factors, socioeconomic position, time, and meteorology. RESULTS: We found negative associations of PM and BC with P-selectin, of ozone with MCP-1, and of SO and NO with osteoprotegerin. At the 5-day moving average, a 5 µg/m higher PM was associated with 1.6% (95% CI: - 2.8, - 0.3) lower levels of P-selectin; a 10 ppb higher ozone was associated with 1.7% (95% CI: - 3.2, - 0.1) lower levels of MCP-1; and a 20 ppb higher NO was associated with 2.0% (95% CI: - 3.6, - 0.4) lower levels of osteoprotegerin. CONCLUSIONS: We did not find evidence of positive associations between short-term air pollution exposure and endothelial cell activation. On the contrary, short-term exposure to higher levels of ambient pollutants were associated with lower levels of P-selectin, MCP-1, and osteoprotegerin in the Framingham Heart Study.

OBJECTIVE: Migraine is a common recurrent headache disorder affecting 14% American adults. Although weather and air pollution are often reported by patients with migraine as precipitating factors, previous studies have had mixed results. METHODS: We prospectively collected migraine headache onset data using electronic questionnaires from 98 adults with episodic migraine in the Greater Boston area (2016-2017). Each participant was followed for an average of 45 days for a total of 4406 days of observation. Temperature, relative humidity, and barometric pressure data were obtained from local weather station. Daily average fine particulate matter, daily maximum 1-hour sulfur dioxide, daily maximum 1-hour nitrogen dioxide, daily maximum 8-hour ozone, and daily maximum 8-hour carbon monoxide from local air pollution monitors. We conducted a repeated measures analysis using fixed effects logistic regression models. In the models we adjusted for day of week, a natural cubic spline term of day of the year with 4 degrees of freedom, and a participant identifier. We additionally adjusted for linear terms of temperature and relative humidity in the air pollution analyses. We also applied logistic regression models with generalized estimating equation (GEE) and autoregressive correlation structure in the sensitivity analysis. RESULTS: The mean age was 35 years and 88% were women. Mean temperature was 56.9 °F, relative humidity 67.3%, and fine particulate matter 7.3 μg/m. Higher relative humidity was associated with higher odds of migraine headache, but the association was only observed in warm season (April-September). Higher levels of daily maximum 8-hour ozone and daily maximum 8-hour carbon monoxide appeared to be associated with higher odds of migraine headache onset in cold season (October-March). Although the associations for ozone and relative humidity were attenuated and no longer statistically significant in the overall GEE analysis, the differing associations by season remained. CONCLUSIONS: We found that higher relative humidity was associated with higher odds of migraine headache onset in warm season, and traffic-related gaseous pollutants may be associated with higher odds of migraine headache onset in cold season.

OBJECTIVE: To examine associations of proximity to major roadways, sustained exposure to fine particulate matter (PM), and acute exposure to ambient air pollutants with adipokines and measures of glucose homeostasis among participants living in the northeastern United States. METHODS: We included 5958 participants from the Framingham Offspring cohort examination cycle 7 (1998-2001) and 8 (2005-2008) and Third Generation cohort examination cycle 1 (2002-2005) and 2 (2008-2011), who did not have type 2 diabetes at the time of examination visit. We calculated 2003 annual average PM at participants' home address, residential distance to the nearest major roadway, and daily PM, black carbon (BC), sulfate, nitrogen oxides (NO), and ozone concentrations. We used linear mixed effects models for fasting glucose, insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) which were measured up to twice, and used linear regression models for adiponectin, resistin, leptin, and hemoglobin A1c (HbA1c) which were measured only once, adjusting for demographics, socioeconomic position, lifestyle, time, and seasonality. RESULTS: The mean age was 51years and 55% were women. Participants who lived 64m (25th percentile) from a major roadway had 0.28% (95% CI: 0.05%, 0.51%) higher fasting plasma glucose than participants who lived 413m (75th percentile) away, and the association appeared to be driven by participants who lived within 50m from a major roadway. Higher exposures to 3- to 7-day moving averages of BC and NO were associated with higher glucose whereas the associations for ozone were negative. The associations otherwise were generally null and did not differ by median age, sex, educational attainment, obesity status, or prediabetes status. CONCLUSIONS: Living closer to a major roadway or acute exposure to traffic-related air pollutants were associated with dysregulated glucose homeostasis but not with adipokines among participants from the Framingham Offspring and Third Generation cohorts.

BACKGROUND: Exposure to ambient air pollution has been associated with lower lung function in adults, but few studies have investigated associations with radiographic lung and airway measures. METHODS: We ascertained lung volume, mass, density, visual emphysema, airway size, and airway wall area by computed tomography (CT) among 2,545 nonsmoking Framingham CT substudy participants. We examined associations of home distance to major road and PM2.5 (2008 average from a spatiotemporal model using satellite data) with these outcomes using linear and logistic regression models adjusted for age, sex, height, weight, census tract median household value and population density, education, pack-years of smoking, household tobacco exposure, cohort, and date. We tested for differential susceptibility by sex, smoking status (former vs. never), and cohort. RESULTS: The mean participant age was 60.1 years (standard deviation 11.9 years). Median PM2.5 level was 9.7 µg/m (interquartile range, 1.6). Living <100 m from a major road was associated with a 108 ml (95% CI = 8, 207) higher lung volume compared with ≥400 m away. There was also a log-linear association between proximity to road and higher lung volume. There were no convincing associations of proximity to major road or PM2.5 with the other pulmonary CT measures. In subgroup analyses, road proximity was associated with lower lung density among men and higher odds of emphysema among former smokers. CONCLUSIONS: Living near a major road was associated with higher average lung volume, but otherwise, we found no association between ambient pollution and radiographic measures of emphysema or airway disease.

BACKGROUND: Studies of air pollution exposure and arterial stiffness have reported inconsistent results and large studies employing the reference standard of arterial stiffness, carotid-femoral pulse-wave velocity (CFPWV), have not been conducted. AIM: To study long-term exposure to ambient fine particles (PM), proximity to roadway, and short-term air pollution exposures in relation to multiple measures of arterial stiffness in the Framingham Heart Study. METHODS: We assessed central arterial stiffness using CFPWV, forward pressure wave amplitude, mean arterial pressure and augmentation index. We investigated long-and short-term air pollution exposure associations with arterial stiffness with linear regressions using long-term residential PM (2003 average from a spatiotemporal model using satellite data) and proximity to roadway in addition to short-term averages of PM, black carbon, particle number, sulfate, nitrogen oxides, and ozone from stationary monitors. RESULTS: We examined 5842 participants (mean age 51 ± 16, 54% women). Living closer to a major roadway was associated with higher arterial stiffness (0.11 m/s higher CFPWV [95% CI: 0.01, 0.22] living <50 m vs 400 ≤ 1000 m). We did not observe association between arterial stiffness measures and long-term PM or short-term levels of PM, particle number, sulfate or ozone. Higher levels of black carbon and nitrogen oxides in the previous days were unexpectedly associated with lower arterial stiffness. CONCLUSIONS: Long-term exposure to PM was not associated with arterial stiffness but positive associations with living close to a major road may suggest that pollutant mixtures very nearby major roads, rather than PM, may affect arterial stiffness. Furthermore, short-term air pollution exposures were not associated with higher arterial stiffness.

BACKGROUND: Decay products of radioactive materials may attach to ambient fine particles and form radioactive aerosol. Internal ionizing radiation source from inhaled radioactive aerosol may contribute to the fine particulate matter (PM)-inflammation pathway. However, few studies in humans have examined the associations. OBJECTIVES: To examine the associations between particle radioactivity and biomarkers of oxidative stress and inflammation among participants from the Framingham Offspring and Third Generation cohorts. METHODS: We included 3996 participants who were not current smokers and lived within 50 km from our central air pollution monitoring station. We estimated regional mean gross beta radioactivity from monitors in the northeastern U.S. as a surrogate for ambient radioactive particles, and calculated the 1- to 28-day moving averages. We used linear regression models for fibrinogen, tumor necrosis factor α, interleukin-6, and myeloperoxidase which were measured once, and linear mixed effect models for 8-epi-prostaglandin F, C-reactive protein, intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant protein-1 (MCP-1), P-selectin, and tumor necrosis factor receptor-2 that were measured up to twice, adjusting for demographics, individual- and area-level socioeconomic positions, time, meteorology, and PM. We also examined whether the associations differed by median age, sex, diabetes status, PM levels, and black carbon levels. RESULTS: The mean age was 54 years and 54% were women. An interquartile range (3 × 10 pCi/m) higher beta radioactivity level at the 7-day moving average was associated with 5.09% (95% CI: 0.92, 9.43), 2.65% (1.10, 4.22), and 4.71% (95% CI: 3.01, 6.44) higher levels of interleukin-6, MCP-1, and P-selectin, but with 7.01% (95% CI: -11.64, -2.15) and 2.70% (95% CI: -3.97, -1.42) lower levels of 8-epi-prostaglandin F and ICAM-1, respectively. CONCLUSIONS: Regional mean particle radioactivity was positively associated with interleukin-6, MCP-1, and P-selectin, but negatively with ICAM-1 and 8-epi-prostaglandin F among our study participants.

OBJECTIVES: Traffic and ambient air pollution exposure are positively associated with cardiovascular disease, potentially through atherosclerosis promotion. Few studies have assessed associations of these exposures with thoracic aortic calcium Agatston score (TAC) or abdominal aortic calcium Agatston score (AAC), systemic atherosclerosis correlates. We assessed whether living close to a major road and residential fine particulate matter (PM) exposure were associated with TAC and AAC in a Northeastern US cohort. DESIGN: Cohort study. SETTING: Framingham Offspring and Third Generation participants residing in the Northeastern USA. PARTICIPANTS AND OUTCOME MEASURES: Among 3506 participants, mean age was 55.8 years; 50% female. TAC was measured from 2002 to 2005 and AAC up to two times (2002-2005; 2008-2011) among participants from the Framingham Offspring or Third Generation cohorts. We first assessed associations with detectable TAC (logistic regression) and AAC (generalised estimating equation regression, logit link). As aortic calcium scores were right skewed, we used linear regression models and mixed-effects models to assess associations with natural log-transformed TAC and AAC, respectively, among participants with detectable aortic calcium. We also assessed associations with AAC progression. Models were adjusted for demographic variables, socioeconomic position indicators and time. RESULTS: There were no consistent associations of major roadway proximity or PM with the presence or extent of TAC or AAC, or with AAC progression. Some estimates were in the opposite direction than expected. CONCLUSIONS: In this cohort from a region with relatively low levels of and variation in PM, there were no strong associations of proximity to a major road or PM with the presence or extent of aortic calcification, or with AAC progression.

We examined associations between ambient air pollution and hepatic steatosis among 2,513 participants from the Framingham (Massachusetts) Offspring Study and Third Generation Cohort who underwent a computed tomography scan (2002-2005), after excluding men who reported >21 drinks/week and women who reported >14 drinks/week. We calculated each participant's residential-based distance to a major roadway and used a spatiotemporal model to estimate the annual mean concentrations of fine particulate matter. Liver attenuation was measured by computed tomography, and liver-to-phantom ratio (LPR) was calculated. Lower values of LPR represent more liver fat. We estimated differences in continuous LPR using linear regression models and prevalence ratios for presence of hepatic steatosis (LPR ≤ 0.33) using generalized linear models, adjusting for demographics, individual and area-level measures of socioeconomic position, and clinical and lifestyle factors. Participants who lived 58 m (25th percentile) from major roadways had lower LPR (β = -0.003, 95% confidence interval: -0.006, -0.001) and higher prevalence of hepatic steatosis (prevalence ratio = 1.16, 95% confidence interval: 1.05, 1.28) than those who lived 416 m (75th percentile) away. The 2003 annual average fine particulate matter concentration was not associated with liver-fat measurements. Our findings suggest that living closer to major roadways was associated with more liver fat.

OBJECTIVE: The objective of this study is to examine associations between short-term exposure to ambient air pollution and circulating biomarkers of systemic inflammation in participants from the Framingham Offspring and Third Generation cohorts in the greater Boston area. APPROACH AND RESULTS: We included 3996 noncurrent smoking participants (mean age, 53.6 years; 54% women) who lived within 50 km from a central air pollution monitoring site in Boston, MA, and calculated the 1- to 7-day moving averages of fine particulate matter (diameter<2.5 µm), black carbon, sulfate, nitrogen oxides, and ozone before the examination visits. We used linear mixed effects models for C-reactive protein and tumor necrosis factor receptor 2, which were measured up to twice for each participant; we used linear regression models for interleukin-6, fibrinogen, and tumor necrosis factor α, which were measured once. We adjusted for demographics, socioeconomic position, lifestyle, time, and weather. The 3- to 7-day moving averages of fine particulate matter (diameter<2.5 µm) and sulfate were positively associated with C-reactive protein concentrations. A 5 µg/m higher 5-day moving average fine particulate matter (diameter<2.5 µm) was associated with 4.2% (95% confidence interval: 0.8, 7.6) higher circulating C-reactive protein. Positive associations were also observed for nitrogen oxides with interleukin-6 and for black carbon, sulfate, and ozone with tumor necrosis factor receptor 2. However, black carbon, sulfate, and nitrogen oxides were negatively associated with fibrinogen, and sulfate was negatively associated with tumor necrosis factor α. CONCLUSIONS: Higher short-term exposure to relatively low levels of ambient air pollution was associated with higher levels of C-reactive protein, interleukin-6, and tumor necrosis factor receptor 2 but not fibrinogen or tumor necrosis factor α in individuals residing in the greater Boston area.

OBJECTIVE: Long-term exposure to traffic and particulate matter air pollution is associated with a higher risk of cardiovascular disease, potentially via atherosclerosis promotion. Prior research on associations of traffic and particulate matter with coronary artery calcium Agatston score (CAC), an atherosclerosis correlate, has yielded inconsistent findings. Given this background, we assessed whether residential proximity to major roadway or fine particulate matter were associated with CAC in a Northeastern US study. APPROACH AND RESULTS: We measured CAC ≤2 times from 2002 to 2005 and 2008 to 2011 among Framingham Offspring or Third-Generation Cohort participants. We assessed associations of residential distance to major roadway and residential fine particulate matter (2003 average; spatiotemporal model) with detectable CAC, using generalized estimating equation regression. We used linear mixed effects models to assess associations with loge(CAC). We also assessed associations with CAC progression. Models were adjusted for demographic variables, socioeconomic position markers, and time. Among 3399 participants, 51% had CAC measured twice. CAC was detectable in 47% of observations. At first scan, mean age was 52.2 years (standard deviation 11.7); 51% male. There were no consistent associations with detectable CAC, continuous CAC, or CAC progression. We observed heterogeneous associations of distance to major roadway with odds of detectable CAC by hypertensive status; interpretation of these findings is questionable. CONCLUSIONS: Our findings add to prior work and support evidence against strong associations of traffic or fine particulate matter with the presence, extent, or progression of CAC in a region with relatively low levels of and little variation in fine particulate matter.

OBJECTIVE: Higher traffic-related air pollution has been associated with higher body mass index (BMI) among children. However, few studies have assessed the associations among adults. METHODS: Participants (N = 2,372) from the Framingham Offspring and Third Generation cohorts who underwent multidetector-computed tomography scans (2002-2005) were included. Residential-based proximity to the nearest major roadway and 1-year average levels of fine particulate matter (PM ) air pollution were estimated. BMI was measured at Offspring examination 7 (1998-2001) and Third Generation examination 1 (2002-2005); subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) were measured using multidetector-computed tomography. Linear regression models were used for continuous BMI, SAT, and VAT and logistic models for the binary indicator of obesity (BMI ≥30 kg/m ), adjusting for demographic variables, individual- and area-level measures of socioeconomic position, and clinical and lifestyle factors. RESULTS: Participants who lived 60 m from a major roadway had 0.37 kg/m higher BMI (95% CI: 0.10 to 0.65 kg/m ), 78.4 cm higher SAT (95% CI: 4.5 to 152.3 cm ), and 41.8 cm higher VAT (95% CI: -4.7 to 88.2 cm ) than those who lived 440 m away. CONCLUSIONS: Living closer to a major roadway was associated with higher overall and abdominal adiposity.