Ambient air pollution and clinical dementia: systematic review and meta-analysis.

OBJECTIVE: To investigate the role of air pollutants in risk of dementia, considering differences by study factors that could influence findings. DESIGN: Systematic review and meta-analysis. DATA SOURCES: EMBASE, PubMed, Web of Science, Psycinfo, and OVID Medline from database inception through July 2022. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Studies that included adults (≥18 years), a longitudinal follow-up, considered US Environmental Protection Agency criteria air pollutants and proxies of traffic pollution, averaged exposure over a year or more, and reported associations between ambient pollutants and clinical dementia. Two authors independently extracted data using a predefined data extraction form and assessed risk of bias using the Risk of Bias In Non-randomised Studies of Exposures (ROBINS-E) tool. A meta-analysis with Knapp-Hartung standard errors was done when at least three studies for a given pollutant used comparable approaches. RESULTS: 2080 records identified 51 studies for inclusion. Most studies were at high risk of bias, although in many cases bias was towards the null. 14 studies could be meta-analysed for particulate matter <2.5 µm in diameter (PM2.5). The overall hazard ratio per 2 µg/m3 PM2.5 was 1.04 (95% confidence interval 0.99 to 1.09). The hazard ratio among seven studies that used active case ascertainment was 1.42 (1.00 to 2.02) and among seven studies that used passive case ascertainment was 1.03 (0.98 to 1.07). The overall hazard ratio per 10 µg/m3 nitrogen dioxide was 1.02 ((0.98 to 1.06); nine studies) and per 10 µg/m3 nitrogen oxide was 1.05 ((0.98 to 1.13); five studies). Ozone had no clear association with dementia (hazard ratio per 5 µg/m3 was 1.00 (0.98 to 1.05); four studies). CONCLUSION: PM2.5 might be a risk factor for dementia, as well as nitrogen dioxide and nitrogen oxide, although with more limited data. The meta-analysed hazard ratios are subject to limitations that require interpretation with caution. Outcome ascertainment approaches differ across studies and each exposure assessment approach likely is only a proxy for causally relevant exposure in relation to clinical dementia outcomes. Studies that evaluate critical periods of exposure and pollutants other than PM2.5, and studies that actively assess all participants for outcomes are needed. Nonetheless, our results can provide current best estimates for use in burden of disease and regulatory setting efforts. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021277083.

Emergency physicians' active patient queues over the course of a shift.

OBJECTIVES: When emergency physicians see new patients in an ad libitum system, they see fewer patients as the shift progresses. However, it is unclear if this reflects a decreasing workload, as patient assessments often span many hours. We sought to investigate whether the size of a physician's queue of active patients similarly declines over a shift. METHODS: Retrospective cohort study, conducted over two years in three community hospitals in the Northeastern United States, with 8 and 9-h shifts. Timestamps of all encounters were recorded electronically. Generalized estimating equations were constructed to predict the number of active patients a physician concurrently managed per hour. RESULTS: We evaluated 64 physicians over a two-year period, with 9822 physician-shifts. Across all sites, physicians managed an increasing queue of active patients in the first several hours. This queue plateaued in the middle of the shift, declining in the final hours, independently of other factors. Physicians' queues of active patients increased slightly with greater volume and acuity, but did not affect the overall pattern of work. Similarly, working alone or with colleagues had little effect on the number of active patients managed. CONCLUSIONS: Emergency physicians in an ad libitum system tend to see new patients until reaching a stable roster of active patients. This pattern may help explain why physicians see fewer new patients over the course of a shift, should be factored into models of throughput, and suggests new avenues for evaluating relationships between physician workload, patient safety, physicians' well-being, and the quality of care.

Synthesis of Harvard Environmental Protection Agency (EPA) Center studies on traffic-related particulate pollution and cardiovascular outcomes in the Greater Boston Area.

The association between particulate pollution and cardiovascular morbidity and mortality is well established. While the cardiovascular effects of nationally regulated criteria pollutants (e.g., fine particulate matter [PM2.5] and nitrogen dioxide) have been well documented, there are fewer studies on particulate pollutants that are more specific for traffic, such as black carbon (BC) and particle number (PN). In this paper, we synthesized studies conducted in the Greater Boston Area on cardiovascular health effects of traffic exposure, specifically defined by BC or PN exposure or proximity to major roadways. Large cohort studies demonstrate that exposure to traffic-related particles adversely affect cardiac autonomic function, increase systemic cytokine-mediated inflammation and pro-thrombotic activity, and elevate the risk of hypertension and ischemic stroke. Key patterns emerged when directly comparing studies with overlapping exposure metrics and population cohorts. Most notably, cardiovascular risk estimates of PN and BC exposures were larger in magnitude or more often statistically significant compared to those of PM2.5 exposures. Across multiple exposure metrics (e.g., short-term vs. long-term; observed vs. modeled) and different population cohorts (e.g., elderly, individuals with co-morbidities, young healthy individuals), there is compelling evidence that BC and PN represent traffic-related particles that are especially harmful to cardiovascular health. Further research is needed to validate these findings in other geographic locations, characterize exposure errors associated with using monitored and modeled traffic pollutant levels, and elucidate pathophysiological mechanisms underlying the cardiovascular effects of traffic-related particulate pollutants. Implications: Traffic emissions are an important source of particles harmful to cardiovascular health. Traffic-related particles, specifically BC and PN, adversely affect cardiac autonomic function, increase systemic inflammation and thrombotic activity, elevate BP, and increase the risk of ischemic stroke. There is evidence that BC and PN are associated with greater cardiovascular risk compared to PM2.5. Further research is needed to elucidate other health effects of traffic-related particles and assess the feasibility of regulating BC and PN or their regional and local sources.

Short-term exposure to ambient air pollution and circulating biomarkers of endothelial cell activation: The Framingham Heart Study.

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 (PM2.5), black carbon (BC), sulfate (SO42-), nitrogen oxides (NOx), 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 PM2.5 and BC with P-selectin, of ozone with MCP-1, and of SO42- and NOx with osteoprotegerin. At the 5-day moving average, a 5 µg/m3 higher PM2.5 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 NOx 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.

Association of outdoor temperature with lung function in a temperate climate.

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.

Ambient Pollutants and Spontaneous Intracerebral Hemorrhage in Greater Boston.

Background and Purpose- Associations between exposures to ambient air pollution and spontaneous intracerebral hemorrhage (ICH) have been inconsistent, and data on stroke subtypes are currently limited. Methods- We obtained information on all cases of deep or lobar hematomas from ICH patients who were admitted to the Massachusetts General Hospital in Boston, MA, between 2006 and 2011. We linked the date of admission with 1- to 7-day moving averages of fine particulate matter (PM2.5), black carbon, nitrogen dioxide, and ozone from area monitors. We conducted time-stratified bidirectional case-crossover analyses to assess associations between pollutants and stroke. We also investigated whether associations differed by hemorrhage location and type. Results- There were 577 cases of ICH (295 deep, 282 lobar). Overall, there was no evidence of elevated ICH risk after increases in PM2.5, black carbon, or nitrogen dioxide in the whole population. However, there was suggestion of heightened risk with higher levels of ozone for averages longer than 1 day although CIs were wide. In models stratified by ICH location, associations with ozone remained positive for patients with lobar (3-day moving average odds ratio, 1.62; 95% CI, 1.18-2.22) but not deep ICH (odds ratio, 0.88; 95% CI, 0.65-1.20). Larger estimates were observed among participants with a probable diagnosis of cerebral amyloid angiopathy (odds ratio, 2.23; 95% CI, 1.25-3.96). Conclusions- Exposure to ozone may be associated with incidence of lobar ICH, especially among those who have confirmed or probable cerebral amyloid angiopathy.

Recent exposure to particle radioactivity and biomarkers of oxidative stress and inflammation: The Framingham Heart Study.

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 (PM2.5)-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 F2α, 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 PM2.5. We also examined whether the associations differed by median age, sex, diabetes status, PM2.5 levels, and black carbon levels. RESULTS: The mean age was 54 years and 54% were women. An interquartile range (3 × 10-3 pCi/m3) 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 F2α 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 F2α among our study participants.

Long- and short-term air pollution exposure and measures of arterial stiffness in the Framingham Heart Study.

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 (PM2.5), 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 PM2.5 (2003 average from a spatiotemporal model using satellite data) and proximity to roadway in addition to short-term averages of PM2.5, black carbon, particle number, sulfate, nitrogen oxides, and ozone from stationary monitors. RESULTS: We examined 5842 participants (mean age 51 ±â€¯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 PM2.5 or short-term levels of PM2.5, 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 PM2.5 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 PM2.5, may affect arterial stiffness. Furthermore, short-term air pollution exposures were not associated with higher arterial stiffness.

Acute Kidney Injury in Sugarcane Workers at Risk for Mesoamerican Nephropathy.

RATIONALE & OBJECTIVE: Mesoamerican nephropathy (MeN), a form of chronic kidney disease (CKD) of unknown cause in Central America, affects young individuals working in physically strenuous occupations. Repeated episodes of work-related kidney injury may lead to CKD in this setting. We aimed to better understand the burden and natural history of acute kidney injury (AKI) in workers at risk for MeN. STUDY DESIGN: Cross-sectional study of active sugarcane workers, followed by prospective follow-up of individuals with AKI. SETTING & PARTICIPANTS: 326 sugarcane workers with normal preharvest serum creatinine (Scr) values and no history of CKD in an MeN hotspot in Nicaragua near the end of the harvest, and prospective follow-up of workers with AKI. PREDICTOR: AKI during the harvest, as defined by Scr level increase ≥ 0.3mg/dL over baseline to a level ≥ 1.3mg/dL. OUTCOMES: Kidney function trajectory and development of CKD over 12 months. ANALYTICAL APPROACH: Linear regression models were used to analyze the association between job category and kidney function. For workers with AKI, the effect of time on Scr level was evaluated using linear mixed effects. RESULTS: 34 of 326 participants were found to have AKI, with a median late-harvest Scr level of 1.64mg/dL in the AKI group. Workers without AKI had a median Scr level of 0.88mg/dL. AKI was more common among cane cutters compared with other field workers. Participants with AKI had variable degrees of kidney function recovery, with median 6- and 12-month Scr values of 1.25 and 1.27mg/dL, respectively (P < 0.001 for each follow-up value compared to late-harvest Scr). When we compared workers' kidney function before the AKI episode to their kidney function at last follow-up, 10 participants with AKI developed de novo estimated glomerular filtration rate < 60mL/min/1.73m2 and 11 had a >30% decrease in estimated glomerular filtration rate. LIMITATIONS: Follow-up limited to 1 year and some loss to follow-up in the prospective component of the study. Broad definition of AKI that includes both acute and subacute kidney injury. CONCLUSIONS: In a group of sugarcane workers with normal preharvest kidney function, newly decreased kidney function developing during the harvest season was common. Of those with kidney injury, nearly half had established CKD 12 months later.

Modelling attending physician productivity in the emergency department: a multicentre study.

OBJECTIVES: Emergency physician productivity, often defined as new patients evaluated per hour, is essential to planning clinical operations. Prior research in this area considered this a static quantity; however, our group's study of resident physicians demonstrated significant decreases in hourly productivity throughout shifts. We now examine attending physicians' productivity to determine if it is also dynamic. METHODS: This is a retrospective cohort study, conducted from 2014 to 2016 across three community hospitals in the north-eastern USA, with different schedules and coverage. Timestamps of all patient encounters were automatically logged by the sites' electronic health record. Generalised estimating equations were constructed to predict productivity in terms of new patients per shift hour. RESULTS: 207 169 patients were seen by 64 physicians over 2 years, comprising 9822 physician shifts. Physicians saw an average of 15.0 (SD 4.7), 20.9 (SD 6.4) and 13.2 (SD 3.8) patients per shift at the three sites, with 2.97 (SD 0.22), 2.95 (SD 0.24) and 2.17 (SD 0.09) in the first hour. Across all sites, physicians saw significantly fewer new patients after the first hour, with more gradual decreases subsequently. Additional patient arrivals were associated with greater productivity; however, this attenuates substantially late in the shift. The presence of other physicians was also associated with slightly decreased productivity. CONCLUSIONS: Physician productivity over a single shift follows a predictable pattern that decreases significantly on an hourly basis, even if there are new patients to be seen. Estimating productivity as a simple average substantially underestimates physicians' capacity early in a shift and overestimates it later. This pattern of productivity should be factored into hospitals' staffing plans, with shifts aligned to start with the greatest volumes of patient arrivals.

Exposure to Traffic Emissions and Fine Particulate Matter and Computed Tomography Measures of the Lung and Airways.

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.

Ambient air pollution, adipokines, and glucose homeostasis: The Framingham Heart Study.

OBJECTIVE: To examine associations of proximity to major roadways, sustained exposure to fine particulate matter (PM2.5), 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 PM2.5 at participants' home address, residential distance to the nearest major roadway, and daily PM2.5, black carbon (BC), sulfate, nitrogen oxides (NOx), 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 NOx 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.

Short-term rehospitalization across the spectrum of age and insurance types in the United States.

Few studies have examined rates and causes of short-term readmissions among adults across age and insurance types. We compared rates, characteristics, and costs of 30-day readmission after all-cause hospitalizations across insurance types in the US. We retrospectively evaluated alive patients ≥18 years old, discharged for any cause, 1/1/13-11/31/13, 2006 non-federal hospitals in 21 states in the Nationwide Readmissions Database. The primary stratification variable of interest was primary insurance. Comorbid conditions were assessed based on Elixhauser comorbidities, as defined by administrative billing codes. Additional measures included diagnoses for index hospitalizations leading to rehospitalization. Hierarchical multivariable logistic regression models, with hospital site as a random effect, were used to calculate the adjusted odds of 30-day readmissions by age group and insurance categories. Cost and discharge estimates were weighted per NRD procedures to reflect a nationally representative sample. Diagnoses for index hospitalizations leading to rehospitalization were determined. Among 12,533,551 discharges, 1,818,093 (14.5%) resulted in readmission within 30 days. Medicaid insurance was associated with the highest adjusted odds ratio (AOR) for readmission both in those ≥65 years old (AOR 1.12, 95%CI 1.10-1.14; p <0.001), and 45-64 (AOR 1.67, 95% CI 1.66-1.69; p < 0.001), and Medicare in the 18-44 group (Medicare vs. private insurance: AOR 1.99, 95% CI 1.96-2.01; p <0.001). Discharges for psychiatric or substance abuse disorders, septicemia, and heart failure accounted for the largest numbers of readmissions, with readmission rates of 24.0%, 17.9%, 22.9% respectively. Total costs for readmissions were 50.7 billion USD, highest for Medicare (29.6 billion USD), with non-Medicare costs exceeding 21 billion USD. While Medicare readmissions account for more than half of the total burden of readmissions, costs of non-Medicare readmissions are nonetheless substantial. Medicaid patients have the highest odds of readmission in individuals older than age 44, commonly due to hospitalizations for psychiatric illness and substance abuse disorders. Medicaid patients represent a population at uniquely high risk for readmission.

Short-Term Exposure to Ambient Air Pollution and Biomarkers of Systemic Inflammation: The Framingham Heart Study.

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/m3 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.

Residential Proximity to Major Roadways, Fine Particulate Matter, and Hepatic Steatosis: The Framingham Heart Study.

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 (ß = -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.

Residential proximity to major roads, exposure to fine particulate matter and aortic calcium: the Framingham Heart Study, a cohort study.

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 (PM2.5) 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 PM2.5 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 PM2.5, there were no strong associations of proximity to a major road or PM2.5 with the presence or extent of aortic calcification, or with AAC progression.

Aß Amyloid Pathology Affects the Hearts of Patients With Alzheimer's Disease: Mind the Heart.

BACKGROUND: Individually, heart failure (HF) and Alzheimer's disease (AD) are severe threats to population health, and their potential coexistence is an alarming prospect. In addition to sharing analogous epidemiological and genetic profiles, biochemical characteristics, and common triggers, the authors recently recognized common molecular and pathological features between the 2 conditions. Whereas cognitive impairment has been linked to HF through perfusion defects, angiopathy, and inflammation, whether patients with AD present with myocardial dysfunction, and if the 2 conditions bear a common pathogenesis as neglected siblings are unknown. OBJECTIVES: Here, the authors investigated whether amyloid beta (Aß) protein aggregates are present in the hearts of patients with a primary diagnosis of AD, affecting myocardial function. METHODS: The authors examined myocardial function in a retrospective cross-sectional study from a cohort of AD patients and age-matched controls. Imaging and proteomics approaches were used to identify and quantify Aß deposits in AD heart and brain specimens compared with controls. Cell shortening and calcium transients were measured on isolated adult cardiomyocytes. RESULTS: Echocardiographic measurements of myocardial function suggest that patients with AD present with an anticipated diastolic dysfunction. As in the brain, Aß40 and Aß42 are present in the heart, and their expression is increased in AD. CONCLUSIONS: Here, the authors provide the first report of the presence of compromised myocardial function and intramyocardial deposits of Aß in AD patients. The findings depict a novel biological framework in which AD may be viewed either as a systemic disease or as a metastatic disorder leading to heart, and possibly multiorgan failure. AD and HF are both debilitating and life-threatening conditions, affecting enormous patient populations. Our findings underline a previously dismissed problem of a magnitude that will require new diagnostic approaches and treatments for brain and heart disease, and their combination.

Residential proximity to major roadways, fine particulate matter, and adiposity: The framingham heart study.

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 (PM2.5 ) 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/m2 ), 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/m2 higher BMI (95% CI: 0.10 to 0.65 kg/m2 ), 78.4 cm3 higher SAT (95% CI: 4.5 to 152.3 cm3 ), and 41.8 cm3 higher VAT (95% CI: -4.7 to 88.2 cm3 ) than those who lived 440 m away. CONCLUSIONS: Living closer to a major roadway was associated with higher overall and abdominal adiposity.

Fine Particulate Matter, Residential Proximity to Major Roads, and Markers of Small Vessel Disease in a Memory Study Population.

BACKGROUND: Long-term exposure to ambient air pollution has been associated with impaired cognitive function and vascular disease in older adults, but little is known about these associations among people with concerns about memory loss. OBJECTIVE: To examine associations between exposures to fine particulate matter and residential proximity to major roads and markers of small vessel disease. METHODS: From 2004-2010, 236 participants in the Massachusetts Alzheimer's Disease Research Center Longitudinal Cohort participated in neuroimaging studies. Residential proximity to major roads and estimated 2003 residential annual average of fine particulate air pollution (PM2.5) were linked to measures of brain parenchymal fraction (BPF), white matter hyperintensities (WMH), and cerebral microbleeds. Associations were modeled using linear and logistic regression and adjusted for clinical and lifestyle factors. RESULTS: In this population (median age [interquartile range] = 74 [12], 57% female) living in a region with median 2003 PM2.5 annual average below the current Environmental Protection Agency (EPA) standard, there were no associations between living closer to a major roadway or for a 2µg/m3 increment in PM2.5 and smaller BPF, greater WMH volume, or a higher odds of microbleeds. However, a 2µg/m3 increment in PM2.5 was associated with -0.19 (95% Confidence Interval (CI): -0.37, -0.005) lower natural log-transformed WMH volume. Other associations had wide confidence intervals. CONCLUSIONS: In this population, where median 2003 estimated PM2.5 levels were below the current EPA standard, we observed no pattern of association between residential proximity to major roads or 2003 average PM2.5 and greater burden of small vessel disease or neurodegeneration.

Residential Proximity to Major Roads, Exposure to Fine Particulate Matter, and Coronary Artery Calcium: The Framingham Heart Study.

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.