Search

Objectives/background: Despite the high prevalence of sleep disturbance, stress, and depressive symptoms among patients with episodic migraine, there has been limited prospective research examining how these comorbid symptoms relate to future headache risk., Methods: We conducted an a priori secondary analysis of a prospective cohort study of 98 adults with episodic migraine recruited through Harvard-affiliated medical centers and local college student clinics in Boston, MA. At baseline, participants completed validated questionnaires on sleep quality, stress, and depressive symptoms. Over the next 6 weeks, they recorded headaches on twice-daily diaries. We conducted time-to-event analyses to evaluate whether these baseline symptoms were associated with headache recurrence., Results: At baseline, 45/98 (46%) participants had poor sleep quality, 51/98 (52%) reported moderate/high stress levels, and 18/98 (18%) had high depressive symptom scores. Over 4,406 person-days, we observed 823 discrete headaches. In multivariable models, the hazard ratios for headache recurrence were: 1.22 (95% CI 1.02, 1.46) for people with baseline poor sleep, 1.12 (95% CI 0.93, 1.35) for those with baseline moderate/high stress compared to lower levels, and 1.31 (95% CI 1.05, 1.65) for the combination of poor sleep and moderate/high stress compared to the combination of good sleep and low stress. There was no association between depression scores and headache risk., Conclusion: Among patients with episodic migraine, poor sleep was associated with a higher rate of headache recurrence over the next 6 weeks, especially among those with coexisting moderate/high stress., (© 2021 American Headache Society.)

Background: Individuals are exposed to air pollution and ionizing radiation from natural sources through inhalation of particles. This study investigates the association between cardiac arrhythmias and short-term exposures to fine particulate matter (particulate matter ≤2.5 µm aerodynamic diameter; PM 2.5 ) and particle radioactivity., Methods: Ventricular arrhythmic events were identified among 176 patients with dual-chamber implanted cardioverter-defibrillators in Boston, Massachusetts between September 2006 and June 2010. Patients were assigned exposures based on residential addresses. Daily PM 2.5 levels were estimated at 1-km×1-km grid cells from a previously validated prediction model. Particle gross β activity was used as a surrogate for particle radioactivity and was measured from several monitoring sites by the US Environmental Protection Agency's monitoring network. The association of the onset of ventricular arrhythmias (VA) with 0- to 21-day moving averages of PM 2.5 and particle radioactivity (2 single-pollutant models and a 2-pollutant model) before the event was examined using time-stratified case-crossover analyses, adjusted for dew point and air temperatures., Results: A total of 1,050 VA were recorded among 91 patients, including 123 sustained VA among 25 of these patients. In the single-pollutant model of PM 2.5 , each interquartile range increase in daily PM 2.5 levels for a 21-day moving average was associated with 39% higher odds of a VA event (95% CI, 12%-72%). In the single-pollutant model of particle radioactivity, each interquartile range increase in particle radioactivity for a 2-day moving average was associated with 13% higher odds of a VA event (95% CI, 1%-26%). In the 2-pollutant model, for the same averaging window of 21 days, each interquartile range increase in daily PM 2.5 was associated with an 48% higher odds of a VA event (95% CI, 15%-90%), and each interquartile range increase of particle radioactivity with a 10% lower odds of a VA event (95% CI, -29% to 14%). We found that with higher levels of particle radioactivity, the effect of PM 2.5 on VAs is reduced., Conclusions: In this high-risk population, intermediate (21-day) PM 2.5 exposure was associated with higher odds of a VA event onset among patients with known cardiac disease and indication for implanted cardioverter-defibrillator implantation independently of particle radioactivity.

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 2.5 ), 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 PM 2.5 (2003 average from a spatiotemporal model using satellite data) and proximity to roadway in addition to short-term averages of PM 2.5 , 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 2.5 or short-term levels of PM 2.5 , 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 PM 2.5 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 PM 2.5 , may affect arterial stiffness. Furthermore, short-term air pollution exposures were not associated with higher arterial stiffness., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: The few previous studies on the onset of paroxysmal atrial fibrillation and meteorologic conditions have focused on outdoor temperature and hospital admissions, but hospital admissions are a crude indicator of atrial fibrillation incidence, and studies have found other weather measures in addition to temperature to be associated with cardiovascular outcomes., Methods: Two hundred patients with dual chamber implantable cardioverter-defibrillators were enrolled and followed prospectively from 2006 to 2010 for new onset episodes of atrial fibrillation. The date and time of arrhythmia episodes documented by the implanted cardioverter-defibrillators were linked to meteorologic data and examined using a case-crossover analysis. We evaluated associations with outdoor temperature, apparent temperature, air pressure, and three measures of humidity (relative humidity, dew point, and absolute humidity)., Results: Of the 200 enrolled patients, 49 patients experienced 328 atrial fibrillation episodes lasting ≥30 seconds. Lower temperatures in the prior 48 hours were positively associated with atrial fibrillation. Lower absolute humidity (ie, drier air) had the strongest and most consistent association: each 0.5 g/m decrease in the prior 24 hours increased the odds of atrial fibrillation by 4% (95% confidence interval [CI]: 0%, 7%) and by 5% (95% CI: 2%, 8%) for exposure in the prior 2 hours. Results were similar for dew point but slightly weaker., Conclusions: Recent exposure to drier air and lower temperatures were associated with the onset of atrial fibrillation among patients with known cardiac disease, supporting the hypothesis that meteorologic conditions trigger acute cardiovascular episodes.

Background: Air pollution exposure has been associated with increased blood pressure in adults., Objective: We examined associations of antenatal exposure to ambient air pollution with newborn systolic blood pressure (SBP)., Methods: We studied 1,131 mother-infant pairs in a Boston, Massachusetts, area pre-birth cohort. We calculated average exposures by trimester and during the 2 to 90 days before birth for temporally resolved fine particulate matter (≤ 2.5 μm; PM2.5), black carbon (BC), nitrogen oxides, nitrogen dioxide, ozone (O3), and carbon monoxide measured at stationary monitoring sites, and for spatiotemporally resolved estimates of PM2.5 and BC at the residence level. We measured SBP at a mean age of 30 ± 18 hr with an automated device. We used mixed-effects models to examine associations between air pollutant exposures and SBP, taking into account measurement circumstances; child's birth weight; mother's age, race/ethnicity, socioeconomic position, and third-trimester BP; and time trend. Estimates represent differences in SBP associated with an interquartile range (IQR) increase in each pollutant., Results: Higher mean PM2.5 and BC exposures during the third trimester were associated with higher SBP (e.g., 1.0 mmHg; 95% CI: 0.1, 1.8 for a 0.32-μg/m3 increase in mean 90-day residential BC). In contrast, O3 was negatively associated with SBP (e.g., -2.3 mmHg; 95% CI: -4.4, -0.2 for a 13.5-ppb increase during the 90 days before birth)., Conclusions: Exposures to PM2.5 and BC in late pregnancy were positively associated with newborn SBP, whereas O3 was negatively associated with SBP. Longitudinal follow-up will enable us to assess the implications of these findings for health during later childhood and adulthood.

Objective: Long-term exposure to traffic-related air pollution has been linked to increased risk of obesity and diabetes and may be associated with higher serum levels of the adipokine leptin, but this hypothesis has not been previously evaluated in humans., Methods: In a cohort of older adults, we estimated the association between serum leptin concentrations and two markers of long-term exposure to traffic pollution, adjusting for participant characteristics, temporal trends, socioeconomic factors, and medical history., Results: An interquartile range increase (0.11 μg/m) in annual mean residential black carbon was associated with 12% (95% confidence interval: 3%, 22%) higher leptin levels. Leptin levels were not associated with residential distance to major roadway., Conclusions: If confirmed, these findings support the emerging evidence suggesting that certain sources of traffic pollution may be associated with adverse cardiometabolic effects.

Background: Residential proximity to green space has been associated with physical and mental health benefits, but whether green space is associated with post-stroke survival has not been studied., Methods: Patients ≥ 21 years of age admitted to the Beth Israel Deaconess Medical Center (BIDMC) between 1999 and 2008 with acute ischemic stroke were identified. Demographics, presenting symptoms, medical history and imaging results were abstracted from medical records at the time of hospitalization for stroke onset. Addresses were linked to average Normalized Difference Vegetation Index, distance to roadways with more than 10,000 cars/day, and US census block group. Deaths were identified through June 2012 using the Social Security Death Index., Results: There were 929 deaths among 1645 patients with complete data (median follow up: 5 years). In multivariable Cox models adjusted for indicators of medical history, demographic and socioeconomic factors, the hazard ratio for patients living in locations in the highest quartile of green space compared to the lowest quartile was 0.78 (95% Confidence Interval: 0.63-0.97) (p-trend = 0.009). This association remained statistically significant after adjustment for residential proximity to a high traffic road., Conclusions: Residential proximity to green space is associated with higher survival rates after ischemic stroke in multivariable adjusted models. Further work is necessary to elucidate the underlying mechanisms for this association, and to better understand the exposure-response relationships and susceptibility factors that may contribute to higher mortality in low green space areas., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Exposure to ambient air pollution, particularly from traffic, has been associated with adverse cognitive outcomes, but the association with depressive symptoms remains unclear., Objectives: We investigated the association between exposure to ambient air and traffic pollution and the presence of depressive symptoms among 732 Boston-area adults ≥ 65 years of age (78.1 ± 5.5 years, mean ± SD)., Methods: We assessed depressive symptoms during home interviews using the Revised Center for Epidemiological Studies Depression Scale (CESD-R). We estimated residential distance to the nearest major roadway as a marker of long-term exposure to traffic pollution and assessed short-term exposure to ambient fine particulate matter (PM2.5), sulfates, black carbon (BC), ultrafine particles, and gaseous pollutants, averaged over the 2 weeks preceding each assessment. We used generalized estimating equations to estimate the odds ratio (OR) of a CESD-R score ≥ 16 associated with exposure, adjusting for potential confounders. In sensitivity analyses, we considered CESD-R score as a continuous outcome and mean annual residential BC as an alternate marker of long-term exposure to traffic pollution., Results: We found no evidence of a positive association between depressive symptoms and long-term exposure to traffic pollution or short-term changes in pollutant levels. For example, we found an OR of CESD-R score ≥ 16 of 0.67 (95% CI: 0.46, 0.98) per interquartile range (3.4 μg/m(3)) increase in PM2.5 over the 2 weeks preceding assessment., Conclusions: We found no evidence suggesting that ambient air pollution is associated with depressive symptoms among older adults living in a metropolitan area in attainment of current U.S. regulatory standards.

Background: Extreme weather and air pollution are associated with increased cardiovascular risk in people with diabetes., Objectives: In a population with diabetes, we conducted a novel assessment of vascular brachial artery responses both to ambient pollution and to weather (temperature and water vapor pressure, a measure of humidity)., Methods: Sixty-four 49- to 85-year-old Boston residents with type 2 diabetes completed up to five study visits (279 repeated measures). Brachial artery diameter (BAD) was measured by ultrasound before and after brachial artery occlusion [i.e., flow-mediated dilation (FMD)] and before and after nitroglycerin-mediated dilation (NMD). Ambient concentrations of fine particulate mass (PM2.5), black carbon (BC), organic carbon (OC), elemental carbon, particle number, and sulfate were measured at our monitoring site; ambient concentrations of carbon monoxide, nitrogen dioxide, and ozone were obtained from state monitors. Particle exposure in the home and during each trip to the clinic (home/trip exposure) was measured continuously and as a 5-day integrated sample. We used linear models with fixed effects for participants, adjusting for date, season, temperature, and water vapor pressure on the day of each visit, to estimate associations between our outcomes and interquartile range increases in exposure., Results: Baseline BAD was negatively associated with particle pollution, including home/trip-integrated BC (-0.02 mm; 95% CI: -0.04, -0.003, for a 0.28 μg/m3 increase in BC), OC (-0.08 mm; 95% CI: -0.14, -0.03, for a 1.61 μg/m3 increase) as well as PM2.5, 5-day average ambient PM2.5, and BC. BAD was positively associated with ambient temperature and water vapor pressure. However, exposures were not consistently associated with FMD or NMD., Conclusion: Brachial artery diameter, a predictor of cardiovascular risk, decreased in association with particle pollution and increased in association with ambient temperature in our study population of adults with type 2 diabetes., Citation: Zanobetti A, Luttmann-Gibson H, Horton ES, Cohen A, Coull BA, Hoffmann B, Schwartz JD, Mittleman MA, Li Y, Stone PH, de Souza C, Lamparello B, Koutrakis P, Gold DR. 2014. Brachial artery responses to ambient pollution, temperature, and humidity in people with type 2 diabetes: a repeated-measures study. Environ Health Perspect 122:242-248; http://dx.doi.org/10.1289/ehp.1206136.

We investigated associations between short-term exposure to air pollution and central augmentation index and augmentation pressure, correlates of arterial stiffness, in a cohort of elderly men in the Boston, Massachusetts, metropolitan area. This longitudinal analysis included 370 participants from the Veterans Affairs Normative Aging Study with up to 2 visits between 2007 and 2011 (n = 445). Augmentation index (as %) and augmentation pressure (in mmHg) were measured at each visit by using radial artery applanation tonometry for pulse wave analysis and modeled in a mixed effects regression model as continuous functions of moving averages of air pollution exposures (over 4 hours and 1, 3, 7, and 14 days). The results suggest that short-term changes in air pollution were associated with augmentation index and augmentation pressure at several moving averages. Interquartile range (IQR) increases in 3-day average exposure to particles with aerodynamic diameter less than 2.5 μm (3.6-μg/m(3) IQR increase) and sulfate (1.4-μg/m(3) IQR increase) and 1-day average exposure to particle number counts (8,741-counts/cm(3) IQR increase) were associated with augmentation index values that were 0.8% (95% confidence interval (CI): 0.2, 1.4), 0.6% (95% CI: 0.1, 1.2), and 1.7% (95% CI: 0.4, 2.9) higher, respectively. Overall, the findings were similar for augmentation pressure. The findings support the hypothesis that exposure to air pollution may affect vascular function.

Rationale: Short-term exposure to ambient air pollution has been associated with lower lung function. Few studies have examined whether these associations are detectable at relatively low levels of pollution within current U.S. Environmental Protection Agency (EPA) standards., Objectives: To examine exposure to ambient air pollutants within EPA standards and lung function in a large cohort study., Methods: We included 3,262 participants of the Framingham Offspring and Third Generation cohorts living within 40 km of the Harvard Supersite monitor in Boston, Massachusetts (5,358 examinations, 1995-2011) who were not current smokers, with previous-day pollutant levels in compliance with EPA standards. We compared lung function (FEV1 and FVC) after previous-day exposure to particulate matter less than 2.5 μm in diameter (PM2.5), nitrogen dioxide (NO2), and ozone (O3) in the "moderate" range of the EPA Air Quality Index to exposure in the "good" range. We also examined linear relationships between moving averages of pollutant concentrations 1, 2, 3, 5, and 7 days before spirometry and lung function., Measurements and Main Results: Exposure to pollutant concentrations in the "moderate" range of the EPA Air Quality Index was associated with a 20.1-ml lower FEV1 for PM2.5 (95% confidence interval [CI], -33.4, -6.9), a 30.6-ml lower FEV1 for NO2 (95% CI, -60.9, -0.2), and a 55.7-ml lower FEV1 for O3 (95% CI, -100.7, -10.8) compared with the "good" range. The 1- and 2-day moving averages of PM2.5, NO2, and O3 before testing were negatively associated with FEV1 and FVC., Conclusions: Short-term exposure to PM2.5, NO2, and O3 within current EPA standards was associated with lower lung function in this cohort of adults.

Background: Living in areas with higher levels of ambient air pollution has been associated with a higher incidence of ischemic stroke and all-cause mortality but less is known about the relationship between traffic-related pollution and long-term survival after stroke., Methods: We identified consecutive patients admitted to Beth Israel Deaconess Medical Center with ischemic stroke between 1999 and 2008 and determined the distance to the nearest roadway with an average daily traffic count of more than 10,000 vehicles/day. Categories of residential proximity were defined as 100 m or less, 100-200 m, 200-400 m or less, or more than 400 m from a busy roadway. We identified deaths through June 2012 using the Social Security Death Index and used Cox proportional hazards models adjusted for medical history and socioeconomic factors to calculate hazard ratios for the association between residential proximity to a high-traffic roadway and all-cause mortality., Results: Among 1683 stroke patients with complete data, there were 950 deaths (median follow-up=4.6 years). We observed higher poststroke mortality among people living closer to high-traffic roadways. Patients living 100 m or less from high-traffic roadways had a 20% (95% confidence interval: 1%, 43%) higher rate of poststroke mortality than patients living more than 400 m away (P trend=.02)., Conclusions: In this study, living close to a high-traffic roadway was associated with an elevated mortality rate. This relationship remained statistically significant after adjustment for individual- and neighborhood-level factors, providing evidence that traffic-related pollution is associated with a higher mortality rate among stroke survivors., (Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background: Evidence suggests that air pollution is associated with atherosclerosis and that traffic-related particles are a particularly important contributor to the association., Objectives: We investigated the association between long-term exposure to black carbon, a correlate of traffic particles, and intima-media thickness of the common carotid artery (CIMT) in elderly men residing in the greater Boston, Massachusetts, area., Methods: We estimated 1-year average exposures to black carbon at the home addresses of Normative Aging Study participants before their first CIMT measurement. The association between estimated black carbon levels and CIMT was estimated using mixed effects models to account for repeated outcome measures. In secondary analyses, we examined whether living close to a major road or average daily traffic within 100 m of residence was associated with CIMT., Results: There were 380 participants (97% self-reported white race) with an initial visit between 2004 and 2008. Two or three follow-up CIMT measurements 1.5 years apart were available for 340 (89%) and 260 (68%) men, respectively. At first examination, the average ± SD age was 76 ± 6.4 years and the mean ± SD CIMT was 0.99 ± 0.18 mm. A one-interquartile range increase in 1-year average black carbon (0.26 µg/m3) was associated with a 1.1% higher CIMT (95% CI: 0.4, 1.7%) based on a fully adjusted model., Conclusions: Annual mean black carbon concentration based on spatially resolved exposure estimates was associated with CIMT in a population of elderly men. These findings support an association between long-term air pollution exposure and atherosclerosis.

Background: Living near major roadways has been associated with increased risk of cardiovascular events, but little is known about its impact on renal function., Methods: We calculated the estimated glomerular filtration rate (eGFR) for 1103 consecutive Boston-area patients hospitalised with confirmed acute ischaemic stroke between 1999 and 2004. We used linear regression to evaluate the association between eGFR and categories of residential distance to major roadway (0 to ≤50, >50 to ≤100, >100 to ≤200, >200 to ≤400, >400 to ≤1000 and >1000 m) adjusting for age, sex, race, smoking, comorbid conditions, treatment with ACE inhibitor and neighbourhood-level socioeconomic characteristics. In a second analysis, we considered the log of distance to major roadway as a continuous variable., Results: Patients living closer to a major roadway had lower eGFR than patients living farther away (Ptrend=0.01). Comparing patients living 50 m versus 1000 m from a major roadway was associated with a 3.9 ml/min/1.73 m(2) lower eGFR (95% CI 1.0 to 6.7; p=0.007): a difference comparable in magnitude to the reduction in eGFR observed for a 4-year increase in age in population-based studies. The magnitude of this association did not differ significantly across categories of age, sex, race, history of hypertension, diabetes or socioeconomic status., Conclusions: Living near a major roadway is associated with lower eGFR in a cohort of patients presenting with acute ischaemic stroke. If causal, these results imply that exposures associated with living near a major roadway contribute to reduced renal function, an important risk factor for cardiovascular events.

Background: A number of studies have shown associations between chronic exposure to particulate air pollution and increased mortality, particularly from cardiovascular disease, but fewer studies have examined the association between long-term exposure to fine particulate air pollution and specific cardiovascular events, such as acute myocardial infarction (AMI)., Objective: We examined how long-term exposure to area particulate matter affects the onset of AMI, and we distinguished between area and local pollutants., Methods: Building on the Worcester Heart Attack Study, an ongoing community-wide investigation examining changes over time in myocardial infarction incidence in greater Worcester, Massachusetts, we conducted a case-control study of 4,467 confirmed cases of AMI diagnosed between 1995 and 2003 and 9,072 matched controls selected from Massachusetts resident lists. We used a prediction model based on satellite aerosol optical depth (AOD) measurements to generate both exposure to particulate matter ≤ 2.5 μm in diameter (PM2.5) at the area level (10 × 10 km) and the local level (100 m) based on local land use variables. We then examined the association between area and local particulate pollution and occurrence of AMI., Results: An interquartile range (IQR) increase in area PM2.5 (0.59 μg/m3) was associated with a 16% increase in the odds of AMI (95% CI: 1.04, 1.29). An IQR increase in total PM2.5 (area + local, 1.05 μg/m3) was weakly associated with a 4% increase in the odds of AMI (95% CI: 0.96, 1.11)., Conclusions: Residential exposure to PM2.5 may best be represented by a combination of area and local PM2.5, and it is important to consider spatial gradients within a single metropolitan area when examining the relationship between particulate matter exposure and cardiovascular events.

There is increasing interest in evaluating the association between specific fine-particle (particles with aerodynamic diameters less than 2.5 µm; PM2.5) constituents and adverse health outcomes rather than focusing solely on the impact of total PM2.5. Because PM2.5 may be related to both constituent concentration and health outcomes, constituents that are more strongly correlated with PM2.5 may appear more closely related to adverse health outcomes than other constituents even if they are not inherently more toxic. Therefore, it is important to properly account for potential confounding by PM2.5 in these analyses. Usually, confounding is due to a factor that is distinct from the exposure and outcome. However, because constituents are a component of PM2.5, standard covariate adjustment is not appropriate. Similar considerations apply to source-apportioned concentrations and studies assessing either short-term or long-term impacts of constituents. Using data on 18 constituents and data from 1,060 patients admitted to a Boston medical center with ischemic stroke in 2003-2008, the authors illustrate several options for modeling the association between constituents and health outcomes that account for the impact of PM2.5. Although the different methods yield results with different interpretations, the relative rankings of the association between constituents and ischemic stroke were fairly consistent across models.

DNA methylation is a potential pathway linking air pollution to disease. Studies indicate that psychological functioning modifies the association between pollution and morbidity. The authors estimated the association of DNA methylation with ambient particulate matter less than 2.5 µm in diameter (PM(2.5)) and black carbon, using mixed models. DNA methylation of the inducible nitric oxide synthase gene, iNOS, and the glucocorticoid receptor gene, GCR, was measured by quantitative polymerase chain reaction pyrosequencing of 1,377 blood samples from 699 elderly male participants in the VA Normative Aging Study (1999-2009). The authors also investigated whether this association was modified by psychological factors including optimism or pessimism, anxiety, and depression. iNOS methylation was decreased after acute exposure to both black carbon and PM(2.5). A 1-μg/m(3) increase in exposure to black carbon in the 4 hours preceding the clinical examination was associated with a 0.9% decrease in 5-methylcytosine (95% CI: 0.4, 1.4) in iNOS, and a 10-μg/m(3) increase in exposure to PM(2.5) was associated with a 0.6% decrease in 5-methylcytosine (95% CI: 0.03, 1.1) in iNOS. Participants with low optimism and high anxiety had associations that were 3-4 times larger than those with high optimism or low anxiety. GCR methylation was not associated with particulate air pollution exposure.

Background: Extreme temperatures have been associated with hospitalization and death among individuals with heart failure, but few studies have explored the underlying mechanisms., Objectives: We hypothesized that outdoor temperature in the Boston, Massachusetts, area (1- to 4-day moving averages) would be associated with higher levels of biomarkers of inflammation and myocyte injury in a repeated-measures study of individuals with stable heart failure., Methods: We analyzed data from a completed clinical trial that randomized 100 patients to 12 weeks of tai chi classes or to time-matched education control. B-type natriuretic peptide (BNP), C-reactive protein (CRP), and tumor necrosis factor (TNF) were measured at baseline, 6 weeks, and 12 weeks. Endothelin-1 was measured at baseline and 12 weeks. We used fixed effects models to evaluate associations with measures of temperature that were adjusted for time-varying covariates., Results: Higher apparent temperature was associated with higher levels of BNP beginning with 2-day moving averages and reached statistical significance for 3- and 4-day moving averages. CRP results followed a similar pattern but were delayed by 1 day. A 5°C change in 3- and 4-day moving averages of apparent temperature was associated with 11.3% [95% confidence interval (CI): 1.1, 22.5; p = 0.03) and 11.4% (95% CI: 1.2, 22.5; p = 0.03) higher BNP. A 5°C change in the 4-day moving average of apparent temperature was associated with 21.6% (95% CI: 2.5, 44.2; p = 0.03) higher CRP. No clear associations with TNF or endothelin-1 were observed., Conclusions: Among patients undergoing treatment for heart failure, we observed positive associations between temperature and both BNP and CRP-predictors of heart failure prognosis and severity.

Background: The link between daily changes in level of ambient fine particulate matter (PM) air pollution (PM <2.5 μm in diameter [PM(2.5)]) and cardiovascular morbidity and mortality is well established. Whether PM(2.5) levels below current US National Ambient Air Quality Standards also increase the risk of ischemic stroke remains uncertain., Methods: We reviewed the medical records of 1705 Boston area patients hospitalized with neurologist-confirmed ischemic stroke and abstracted data on the time of symptom onset and clinical characteristics. The PM(2.5) concentrations were measured at a central monitoring station. We used the time-stratified case-crossover study design to assess the association between the risk of ischemic stroke onset and PM(2.5) levels in the hours and days preceding each event. We examined whether the association with PM(2.5) levels differed by presumed ischemic stroke pathophysiologic mechanism and patient characteristics., Results: The estimated odds ratio (OR) of ischemic stroke onset was 1.34 (95% CI, 1.13-1.58) (P < .001) following a 24-hour period classified as moderate (PM(2.5) 15-40 μg/m(3)) by the US Environmental Protection Agency's (EPA) Air Quality Index compared with a 24-hour period classified as good (≤15 μg/m(3)). Considering PM(2.5) levels as a continuous variable, we found the estimated odds ratio of ischemic stroke onset to be 1.11 (95% CI, 1.03-1.20) (P = .006) per interquartile range increase in PM(2.5) levels (6.4 μg/m(3)). The increase in risk was greatest within 12 to 14 hours of exposure to PM(2.5) and was most strongly associated with markers of traffic-related pollution., Conclusion: These results suggest that exposure to PM(2.5) levels considered generally safe by the US EPA increase the risk of ischemic stroke onset within hours of exposure.

Background: Diabetes increases the risk of hypertension and orthostatic hypotension and raises the risk of cardiovascular death during heat waves and high pollution episodes., Objective: We examined whether short-term exposures to air pollution (fine particles, ozone) and heat resulted in perturbation of arterial blood pressure (BP) in persons with type 2 diabetes mellitus (T2DM)., Methods: We conducted a panel study in 70 subjects with T2DM, measuring BP by automated oscillometric sphygmomanometer and pulse wave analysis every 2 weeks on up to five occasions (355 repeated measures). Hourly central site measurements of fine particles, ozone, and meteorology were conducted. We applied linear mixed models with random participant intercepts to investigate the association of fine particles, ozone, and ambient temperature with systolic, diastolic, and mean arterial BP in a multipollutant model, controlling for season, meteorological variables, and subject characteristics., Results: An interquartile increase in ambient fine particle mass [particulate matter (PM) with an aerodynamic diameter of ≤ 2.5 μm (PM2.5)] and in the traffic component black carbon in the previous 5 days (3.54 and 0.25 μg/m3, respectively) predicted increases of 1.4 mmHg [95% confidence interval (CI): 0.0, 2.9 mmHg] and 2.2 mmHg (95% CI: 0.4, 4.0 mmHg) in systolic BP (SBP) at the population geometric mean, respectively. In contrast, an interquartile increase in the 5-day mean of ozone (13.3 ppb) was associated with a 5.2 mmHg (95% CI: -8.6, -1.8 mmHg) decrease in SBP. Higher temperatures were associated with a marginal decrease in BP., Conclusions: In subjects with T2DM, PM was associated with increased BP, and ozone was associated with decreased BP. These effects may be clinically important in patients with already compromised autoregulatory function.

DNA methylation has been associated with age-related disease. Intra-individual changes in gene-specific DNA methylation over time in a community-based cohort has not been well described. We estimated the change in DNA methylation due to aging for nine genes in an elderly, community-dwelling cohort of men. Seven hundred and eighty four men from the Veterans Administration Normative Aging Study who were living in metropolitan Boston from 1999-2009 donated a blood sample for DNA methylation analysis at clinical examinations repeated at approximately 3-5 year intervals. We used mixed effects regression models. Aging was significantly associated with decreased methylation of GCR, iNOS and TLR2 and with increased methylation of IFNγ, F3, CRAT and OGG. Obstructive pulmonary disease at baseline modified the effect of aging on methylation of IFNγ (interaction p = 0.04). For participants who had obstructive pulmonary disease at their baseline visit, the rate of change of methylation of IFNγ was -0.05% 5-methyl-cytosine (5-mC) per year (95% CI: -0.22, 0.13), but was 0.14% 5-mC per year (95% CI: 0.05, 0.24) for those without this condition. Models with random slopes indicated significant heterogeneity in the effect of aging on methylation of GCR, iNOS and OGG. These findings suggest that DNA methylation may reflect differential biological aging.

Background: DNA methylation is a potential pathway linking environmental exposures to disease. Exposure to particulate air pollution has been associated with increased cardiovascular morbidity and mortality, and lower blood DNA methylation has been found in processes related to cardiovascular morbidity., Objective: We hypothesized that prolonged exposure to particulate pollution would be associated with hypomethylation of repetitive DNA elements and that this association would be modified by genes involved in glutathione metabolism and other host characteristics., Methods: DNA methylation of the long interspersed nucleotide element-1 (LINE-1) and the short interspersed nucleotide element Alu were measured by quantitative polymerase chain reaction pyrosequencing in 1,406 blood samples from 706 elderly participants in the Normative Aging Study. We estimated changes in repetitive element DNA methylation associated with ambient particles (particulate matter ≤ 2.5 µm in aerodynamic diameter), black carbon (BC), and sulfates (SO₄), with mixed models. We examined multiple exposure windows (1-6 months) before DNA methylation measurement. We investigated whether this association was modified by genotype and phenotype., Results: An interquartile range (IQR) increase in BC over a 90-day period was associated with a decrease of 0.31% 5-methylcytosine (5mC) (95% confidence interval, 0.12-0.50%) in Alu. An IQR increase in SO₄ over a 90-day period was associated with a decrease of 0.27% 5mC (0.02-0.52%) in LINE-1. The glutathione S-transferase mu-1-null genotype strengthened the association between BC and Alu hypomethylation., Conclusion: Prolonged exposure to BC and SO₄ particles was associated with hypomethylation of two types of repetitive elements.

Regular physical activity is known to decrease the risk of cardiovascular disease, but the risk of ischemic stroke immediately following moderate or vigorous physical activity remains unclear. The authors evaluated the risk of acute ischemic stroke immediately following physical activity and examined whether the risk was modified by regular physical activity. In a multicenter case-crossover study, the authors interviewed 390 ischemic stroke patients (209 men, 181 women) at 3 North American hospitals between January 2001 and November 2006. Physical activity during the hour before stroke symptoms arose was compared with usual frequency of physical activity over the prior year. Of the 390 subjects, 21 (5%) reported having engaged in moderate or vigorous physical activity during the hour before ischemic stroke onset, and 6 subjects had lifted an object weighing at least 50 pounds (≥23 kg) during that hour. The rate ratio for ischemic stroke was 2.3 (95% confidence interval (CI): 1.5, 3.7; P < 0.001) for moderate or vigorous physical activity in the previous hour and 2.6 (95% CI: 1.1, 5.9; P = 0.02) for lifting 50 pounds or more. People who reported engaging in moderate or vigorous physical activity at least 3 times per week experienced a 2-fold increased risk (95% CI: 1.2, 3.3) with each bout of physical activity, as compared with a 6.8-fold risk (95% CI: 2.5, 18.8) among more sedentary subjects (P for homogeneity = 0.03).

Background: Epidemiologic studies linking ambient air pollution to the onset of acute cardiovascular events often rely on date of hospital admission for exposure assessment., Methods: We investigated the extent of exposure misclassification resulting from assigning exposure to particulate matter based on (1) date of hospital admission, or (2) time of hospital presentation compared with particulate matter exposure based on time of stroke symptom onset. We performed computer simulations to evaluate the impact of this source of exposure misclassification on estimates of air pollution health effects in the context of a time-stratified case-crossover study., Results: Among 1101 patients admitted for a confirmed acute ischemic stroke to a Boston area hospital, symptom onset occurred a median of 1 calendar day before hospital admission (range = 0-30 days). The difference between ambient particulate matter exposure based on the calendar day of admission versus time of symptom onset ranged from -47 to 36 microg/m3 (-0.1 +/- 7.1 microg/m3; mean +/- SD). The simulation study indicated that for nonnull associations, exposure assessment based on hospitalization date led to estimates that were biased toward the null by 60%-66%, whereas assessment based on time of hospital presentation yielded estimates that were biased toward the null by 37%-42%., Conclusions: Epidemiologic studies of air pollution-related risk of acute cardiovascular events that assess exposure based on date of hospitalization likely underestimate the strength of associations. Using data on time of hospital presentation would marginally attenuate, but not eliminate, this important source of bias.

Background: Although welding fume exposure is associated with adverse cardiovascular outcomes, the mechanisms remain unclear. To investigate the role of vascular function, we assessed levels of the augmentation index (a correlate of arterial stiffness) after short-term exposure to welding-derived fine particulate matter (PM2.5)., Methods: In a panel study, we monitored 26 male welders over 24 hours on a welding day (n = 25), a non-welding day (n = 15), or both (n = 14). Augmentation index (expressed as a percent) was obtained in the morning before exposure (baseline) and after exposure in the afternoon and the following morning. Personal PM2.5 exposure was measured over 6 hours of welding or an equivalent non-welding period. We used linear mixed models adjusting for baseline augmentation index, smoking, age, and time to evaluate the effects of welding (binary) and PM2.5 (continuous) on augmentation index levels. We also assessed modification by welding exposure the day before monitoring (binary)., Results: Welding was associated with a 2.8% increase in afternoon augmentation index (95% confidence interval = -1.4 to 7.0) and a 2.4% decrease (-6.9 to 2.2) in next-morning augmentation index. Additional exposure the day prior to monitoring was associated with a greater afternoon increase (5.1%; 0.8 to 9.5). Using PM2.5 concentration, a positive association was observed in the afternoon and an inverse association the next morning; results differed by previous day's welding status after excluding outliers., Conclusions: Subsequent to welding fume exposure, there is an increase in afternoon augmentation index and a decrease in next-morning augmentation index, with greater changes after consecutive days of exposure. These results suggest that exposure to the PM2.5 component of welding fume elicits acute adverse vascular responses.

Objectives: Racial and ethnic minorities are at increased risk for hypertension and hypercholesterolemia. Appropriate blood pressure and cholesterol monitoring is a critical first step in identification, treatment, and control of these conditions and the prevention of coronary artery disease. This study examines blood pressure and cholesterol monitoring among non-Hispanic Black, Hispanic, and non-Hispanic White subjects., Design: Data were drawn from the 1999 Massachusetts Behavioral Risk Factor Surveillance Survey (BRFSS) Boston oversample. Monitoring for hypertension and hypercholesterolemia were compared across 2515 respondents to the 1999 Boston BRFSS oversample, including (67.6% White non-Hispanic, 18% Black non-Hispanic, and 14.4% Hispanic, any race). Chi-square analyses were used to test unadjusted race- and ethnicity-specific differences, and logistic regression was used to estimate the odds of inadequate blood pressure and cholesterol monitoring by race/ ethnicity, adjusting for demographic characteristics, insurance, source of care, psychosocial factors, and neighborhood characteristics., Results: No significant differences were seen in the adequacy of blood pressure and cholesterol monitoring among the racial/ethnic groups of interest, despite significant differences in sociodemographic characteristics and morbidity., Conclusions: In this local dataset, non-Hispanic Blacks and Hispanics, as compared to non-Hispanic Whites, were not more likely to report inadequate blood pressure or cholesterol monitoring. The data suggest that safety net factors in place in Boston may have contributed to the observed parity in access to preventive care among the racial/ethnic groups of interest. The data also suggest that factors antecedent/subsequent to blood pressure and cholesterol monitoring may explain the observed disparities in blood pressure and cholesterol morbidity and control reported for racial/ethnic minorities.

Objectives: We reported previously that 24-hr moving average ambient air pollution concentrations were positively associated with ventricular arrhythmias detected by implantable cardioverter defibrillators (ICDs). ICDs also detect paroxysmal atrial fibrillation episodes (PAF) that result in rapid ventricular rates. In this same cohort of ICD patients, we assessed the association between ambient air pollution and episodes of PAF., Design: We performed a case-crossover study., Participants: Patients who lived in the Boston, Massachusetts, metropolitan area and who had ICDs implanted between June 1995 and December 1999 (n=203) were followed until July 2002., Evaluations/measurements: We used conditional logistic regression to explore the association between community air pollution and 91 electrophysiologist-confirmed episodes of PAF among 29 subjects., Results: We found a statistically significant positive association between episodes of PAF and increased ozone concentration (22 ppb) in the hour before the arrhythmia (odds ratio=2.08; 95% confidence interval=1.22, 3.54; p=0.001). The risk estimate for a longer (24-hr) moving average was smaller, thus suggesting an immediate effect. Positive but not statistically significant risks were associated with fine particles, nitrogen dioxide, and black carbon., Conclusions: Increased ambient O3 pollution was associated with increased risk of episodes of rapid ventricular response due to PAF, thereby suggesting that community air pollution may be a precipitant of these events.

Background: As part of the Worcester Heart Attack Study, a community-wide study examining changes over time in the incidence and long-term case-fatality rates of greater Worcester, Mass, residents hospitalized with confirmed acute myocardial infarction (AMI), we investigated the hypothesis that census tract-level socioeconomic position is an important predictor of survival after hospital discharge for AMI, after adjusting for demographic and clinical characteristics., Methods and Results: Data were available for 3423 confirmed cases of AMI among metropolitan Worcester residents during the 4 study years of 1995, 1997, 1999, and 2001 who were followed up through the end of 2002. The mean age among patients was 69 years, and 58% were men. Using a multilevel Cox proportional hazards regression model, we estimated a 30% higher death rate after AMI for patients living in census tracts with the most residents living below the poverty line compared with patients living in the wealthiest census tracts (relative risk=1.30; 95% CI, 1.08 to 1.56). Similarly, patients living in census tracts with the highest proportion of residents with less than a high school education experienced a 47% higher death rate than patients living in census tracts with the lowest proportion of residents with less than a high school education (relative risk=1.47; 95% CI, 1.15 to 1.88)., Conclusions: Within a medium-sized urban area, there are important variations in survival after hospital discharge for AMI that are associated with socioeconomic position. These associations persist after adjustment for demographic and clinical characteristics. Reasons for these differences warrant further investigation.