Error and bias geocoding school and student's home addresses

Zandbergen and Green (2007) recently described the effect of positional error on the distance between geocoded addresses and major roads, an often-used proxy for traffic-related exposures. They found a 200–500 m range of mean positional errors in their study of 126 Orange County, Florida, public school addresses, a somewhat higher range than that associated with geocodes assigned by four commercial vendors to a larger variety and number of street addresses in the 48 contiguous U.S. states (Whitsel et al. 2006). In both studies, however, the ranges exceeded commonly used thresholds for identifying those at greatest potential risk of traffic-related exposures, raising due cause for concern

The environmental epidemiology of atrial Arrhythmogenesis

Atrial fibrillation (AF) is the most common cardiac arrhythmia seen in clinical practice, and makes an important contribution to cardiovascular disease (CVD) and all-cause mortality. The focus of AF research has recently shifted, from concentrating on treatments and complications, to the evaluation of putative risk factors including ambient air pollution. Although the present study pertains specifically to AF, much of its content is drawn from, and therefore is applicable to, the study of other arrhythmias, the conduct of which is confronted by many of the same challenges. Meeting these challenges involves recognising the collective importance of 1. large, ethnically and geographically diverse, clinically well-characterised populations; 2. methods for reducing uncertainty in outcome ascertainment, distinguishing effects of pervasive environmental exposures and improving their estimation; 3. approaches to evaluation of susceptibility; and 4. strategies for informing regulatory policies designed to help control population-level risks for CVD

Accuracy of QT(c) and QTI for detection of autonomic dysfunction

Background: Correlates of QT interval duration have been described although their effects on its ability to identify autonomic neuropathy have not. Methods: We examined the ability of QT(c) and QTI to detect pharmacologically simulated autonomic dysfunction (PSAD) in persons without bundle branch block, U waves, or long QT syndrome by reviewing 249 articles published through 1996 describing the influence of adrenergic beta antagonists or atropine on QT duration. Six of the articles described effects of intravenous drug administration on the ECG among 94 individuals in sinus rhythm. Autonomic dysfunction was pharmacologically simulated in a subset of 30 men and women via coadministration of both drugs. We used logistic regression to estimate accuracy of QT(c) and QTI for PSAD, reported as area under summary receiver operating characteristic curves (AUC [95% CI]) and sensitivity (95% CI) of test thresholds with specificity of 0.80. Results: Sensitivity of QT(c) > 436 ms(1/2) was 0.20 (0.09-0.38) and AUC(QTc), 0.54 (0.41-0.66). A QTI < 95% was similarly insensitive, 0.30 (0.16-0.48), and AUC(QTI) equally low. However, stratum-specific AUC(QTI) was higher than overall AUC(QTI), 0.69 (0.64-0.74) when age ≤ mean (37.7 years), 0.77 (0.73- 0.81) in males, and 0.87 (0.77-0.97) in participants without history of arrhythmia. Sensitivity of QTI thresholds in these strata, range 0.41 to 0.62, was 2.2 to 7.8 times greater than sensitivity, range 0.08 to 0.19, of equally specific QT(c) thresholds. In a model combining age (y), gender, and arrhythmia, AUC(QTI) was 0.88 (0.86-0.90). Conclusions: In isolation, QT(c) and QTI inaccurately detect PSAD. When confounding is taken into consideration, low QTI identifies PSAD with greater sensitivity and accuracy than high QT(c)

Social relationships, inflammation markers, and breast cancer incidence in the Women's Health Initiative

Objectives: Previous research has reported associations between social relationships and carcinogenesis. Inflammation is a potential mediator of these associations. To clarify these links for one tumor site, we examined associations between social relationships, circulating inflammation markers, and breast cancer incidence. Materials and Methods: Among 132,262 participants from the prospective Women's Health Initiative, we used linear and logistic regression to evaluate associations between social relationship characteristics (social support, social strain, social network size) and inflammation markers of C-reactive protein (CRP) and white blood cell count (WBC). Cox regression was used to evaluate associations between inflammation markers and breast cancer incidence, as well as associations between social relationship characteristics and breast cancer incidence with and without adjustment for inflammation markers. Results: Larger social networks were associated with lower continuous CRP (beta = −0.22, 95% CI -0.36, −0.08) and WBC (beta = −0.23, 95% CI -0.31, −0.16). Greater social strain was associated with higher continuous CRP (beta = 0.24, 95% CI 0.14, 0.33) and WBC (beta = 0.09, 95% CI 0.04, 0.14). When WBC was dichotomized at 10,000 cells/uL, high WBC was associated with greater hazards of in situ breast cancer (HR = 1.65, 95% CI 1.17, 2.33) but not invasive breast cancer. Social relationship characteristics were not associated with incidence of invasive or in situ breast cancer. Conclusion: Larger social networks were associated with lower inflammation and greater social strain was associated with higher inflammation. Higher inflammation might be associated with development of in situ breast cancer, but this appeared to be due to factors other than social relationships

Racial differences in blood pressure response to calcium channel blocker monotherapy: A meta-analysis

Background A systematic literature review was conducted to determine whether US blacks and whites have differential blood pressure (BP) response to calcium channel blocker (CCB) monotherapy.MethodsSix published studies made up the final cohort of eligible articles. Multiple treatment groups within some studies led to a total of eight sets of estimates for BP reduction with a total of 6,851 white or nonblack participants and 3,371 black participants.ResultsThe pooled difference in systolic blood pressure (SBP) change between blacks and whites was 2.7 mm Hg (95% confidence interval (CI): 4.0, 1.3) with blacks having greater response. The difference in diastolic blood pressure (DBP) between blacks and whites was 0.4 mm Hg (95% CI: 1.0, 0.3) with blacks having greater response. Using a dichotomous outcome measure, whites were found to be just as likely as blacks to attain the DBP goal of 90 mm Hg or a 10 mm Hg or greater change (relative risk: 1.00 95% CI: 0.91, 1.11). In addition, examination of the continuous distribution of BP responses of whites and blacks showed over 90% overlap in treatment response.ConclusionAssessment of differential response to CCB monotherapy by race in published data depends on choice of outcome metric. Nonetheless, the results of this systematic review indicate that BP response is qualitatively similar in US blacks and whites, suggesting that patient race is not likely to offer any clinical utility for decisions about the likely effect of this antihypertensive therapy

Use of prescription medications with cardiovascular adverse effects among older adults in the United States

Background: Many commonly used prescription medications have cardiovascular adverse effects, yet the cumulative risk of cardiovascular events associated with the concurrent use of these medications is unknown. We examined the association between the concurrent use of prescription medications with known risk of a major adverse cardiovascular event (MACE) (“MACE medications”) and the risk of such events among older adults. Methods: A multi-center, population-based study from the Atherosclerosis Risk in Communities (ARIC) study of a cohort of 3669 community-dwelling adults aged 61–86 years with no history of cardiovascular disease who reported the use of at least one medication between September 2006 and August 2013 were followed up until August 2015. Exposure defined as time-varying and time-fixed use of 1, 2 or ≥3 MACE medications with non-MACE medications serving as negative control. Primary outcome was incident MACE defined as coronary artery revascularization, myocardial infarction, fatal coronary heart disease, stroke, cardiac arrest, or death. Results: In fully adjusted models, there was an increased risk of MACE associated with use of 1, 2, or ≥3 MACE medications (1 MACE: hazards ratio [HR], 1.21; 95% confidence interval [CI], 0.94–1.57); 2 MACE: HR 1.89, CI 1.42–2.53; ≥3 MACE: HR 2.22, CI 1.61–3.07) compared to use of non-MACE medications. These associations persisted in propensity score-matched analyses and among new users of MACE medications, never users of cardiovascular medications and subgroups of participants with increased risk of MACE. There was no association between the number of non-MACE medications used and MACE. Conclusions and Relevance: In this community-based cohort of older adults with no prior cardiovascular disease, the use of MACE medications was independently and consistently associated with an increased risk of such events in a dose–response fashion

Estimating Associations Between Annual Concentrations of Particulate Matter and Mortality in the United States, Using Data Linkage and Bayesian Maximum Entropy

Background: Exposure to fine particulate matter (PM2.5) is an established risk factor for human mortality. However, previous US studies have been limited to select cities or regions or to population subsets (e.g., older adults). Methods: Here, we demonstrate how to use the novel geostatistical method Bayesian maximum entropy to obtain estimates of PM2.5 concentrations in all contiguous US counties, 2000–2016. We then demonstrate how one could use these estimates in a traditional epidemiologic analysis examining the association between PM2.5 and rates of all-cause, cardiovascular, respiratory, and (as a negative control outcome) accidental mortality. Results: We estimated that, for a 1 log(μg/m3) increase in PM2.5 concentration, the conditional all-cause mortality incidence rate ratio (IRR) was 1.029 (95% confidence interval [CI]: 1.006, 1.053). This implies that the rate of all-cause mortality at 10 µg/m3 would be 1.020 times the rate at 5 µg/m3. IRRs were larger for cardiovascular mortality than for all-cause mortality in all gender and race–ethnicity groups. We observed larger IRRs for all-cause, nonaccidental, and respiratory mortality in Black non-Hispanic Americans than White non-Hispanic Americans. However, our negative control analysis indicated the possibility for unmeasured confounding. Conclusion: We used a novel method that allowed us to estimate PM2.5 concentrations in all contiguous US counties and obtained estimates of the association between PM2.5 and mortality comparable to previous studies. Our analysis provides one example of how Bayesian maximum entropy could be used in epidemiologic analyses; future work could explore other ways to use this approach to inform important public health questions

Using animations of risk functions to visualize trends in US all-cause and cause-specific mortality, 1968-2016

Objectives. To use dynamic visualizations of mortality risk functions over both calendar year and age as a way to estimate and visualize patterns in US life spans. Methods. We built 49 synthetic cohorts, 1 per year 1968 to 2016, using National Center for Health Statistics (NCHS) mortality and population data. Within each cohort, we estimated age-specific probabilities of dying from any cause (all-cause analysis) or from a particular cause (cause-specific analysis). We then used Kaplan–Meier (all-cause) or Aalen–Johansen (cause-specific) estimators to obtain risk functions. We illustrated risk functions using time-lapse animations. Results. Median age at death increased from 75 years in 1970 to 83 years in 2015. Risk by age 100 years of cardiovascular mortality decreased (from a risk of 55% in 1970 to 32% in 2015), whereas risk attributable to other (i.e., nonrespiratory and noncardiovascular) causes increased in compensation. Conclusions. Our findings were consistent with the trends published in the NCHS 2015 mortality report, and our dynamic animations added an efficient, interpretable tool for visualizing US mortality trends over age and calendar time

Association of psychosocial factors with short-term resting heart rate variability: The atherosclerosis risk in communities study

BACKGROUND: Psychosocial factors predict heart disease risk, but our understanding of underlying mechanisms is limited. We sought to evaluate the physiologic correlates of psychosocial factors by measuring their relationships with heart rate variability (HRV), a measure of autonomic health, in the ARIC (Atherosclerosis Risk in Communities) study. We hypothesize that increased psychosocial stress associates with lower HRV. METHODS AND RESULTS: We studied 9331 participants in ARIC with short-term HRV data at visits 2 and 4. The mean (SD) age was 54.4 (5.7) years, 55% were women, and 25% were Black. Psychosocial factors included: (1) vital exhaustion (VE), (2) anger proneness, a personality trait, and (3) perceived social support. Linear models adjusted for sociodemographic and cardiovascular risk factors. Low frequency HRV (ln ms2) was significantly lower in the highest versus lowest quartiles of VE (B=−0.14, 95% CI, −0.24 to −0.05). When comparing this effect to age (B=−0.04, 95% CI, −0.05 to −0.04), the difference was equivalent to 3.8 years of accelerated aging. Perceived social support associated with lower time-domain HRV. High VE (versus low VE) also associated with greater decreases in low frequency over time, and both anger and VE associated with greater increases in resting heart rate over time. Survival analyses were performed with Cox models, and no evidence was found that HRV ex-plains the excess risk found with high VE and low perceived social support. CONCLUSIONS: Vital exhaustion, and to a lesser extent anger and social support, were associated with worse autonomic function and greater adverse changes over time

Association Between Long-term Ambient PM2.5 Exposure and Cardiovascular Outcomes Among US Hemodialysis Patients

Rationale &amp; Objective: Ambient PM2.5 (particulate matter with a diameter of 2.5 microns) is a ubiquitous air pollutant with established adverse cardiovascular (CV) effects. However, quantitative estimates of the association between PM2.5 exposure and CV outcomes in the setting of kidney disease are limited. This study assessed the association of long-term PM2.5 exposure with CV events and cardiovascular disease (CVD)–specific mortality among patients receiving maintenance in-center hemodialysis (HD). Study Design: Retrospective cohort study. Settings &amp; Participants: 314,079 adult kidney failure patients initiating HD between 2011 and 2016 identified from the US Renal Data System. Exposure: Estimated daily ZIP code–level PM2.5 concentrations were used to calculate each participant's annual average PM2.5 exposure based on the dialysis clinics visited during the 365 days before the outcome. Outcome: CV event and CVD-specific mortality were ascertained based on ICD-9/ICD-10 diagnostic codes and recorded cause of death from Centers for Medicare &amp; Medicaid Services form 2746. Analytical Approach: Discrete time hazards models were used to estimate hazards ratios per 1 μg/m3 greater annual average PM2.5, adjusting for temperature, humidity, day of the week, season, age at baseline, race, employment status, and geographic region. Effect measure modification was assessed for age, sex, race, and baseline comorbidities. Results: Each 1 μg/m3 greater annual average PM2.5 was associated with a greater rate of CV events (HR, 1.02 [95% CI, 1.01-1.02]) and CVD-specific mortality (HR, 1.02 [95% CI, 1.02-1.03]). The association was more pronounced for people who initiated dialysis at an older age, had chronic obstructive pulmonary disease (COPD) at baseline, or were Asian. Evidence of effect modification was also observed across strata of race, and other baseline comorbidities. Limitations: Potential exposure misclassification and unmeasured confounding. Conclusions: Long-term ambient PM2.5 exposure was associated with CVD outcomes among patients receiving maintenance in-center HD. Stronger associations between long-term PM2.5 exposure and adverse effects were observed among patients who were of advanced age, had COPD, or were Asian. Plain-Language Summary: Long-term exposure to air pollution, also called PM2.5, has been linked to adverse cardiovascular outcomes. However, little is known about the association of PM2.5 and outcomes among patients receiving dialysis, who are individuals with high cardiovascular disease burdens. We conducted an epidemiological study to assess the association between the annual PM2.5 exposure and cardiovascular events and death among patients receiving regular outpatient hemodialysis in the United States between 2011 and 2016. We found a higher risk of heart attacks, strokes, and related events in patients exposed to higher levels of air pollution. Stronger associations between air pollution and adverse health events were observed among patients who were older at the start of dialysis, had chronic obstructive pulmonary disease, or were Asian. These findings bolster the evidence base linking air pollution and adverse health outcomes and may inform policy makers and clinicians