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1.  Air Pollution and Percent Emphysema Identified by Computed Tomography in the Multi-Ethnic Study of Atherosclerosis 
Environmental Health Perspectives  2014;123(2):144-151.
Background: Air pollution is linked to low lung function and to respiratory events, yet little is known of associations with lung structure.
Objectives: We examined associations of particulate matter (PM2.5, PM10) and nitrogen oxides (NOx) with percent emphysema-like lung on computed tomography (CT).
Methods: The Multi-Ethnic Study of Atherosclerosis (MESA) recruited participants (45–84 years of age) in six U.S. states. Percent emphysema was defined as lung regions < –910 Hounsfield Units on cardiac CT scans acquired following a highly standardized protocol. Spirometry was also conducted on a subset. Individual-level 1- and 20-year average air pollution exposures were estimated using spatiotemporal models that included cohort-specific measurements. Multivariable regression was conducted to adjust for traditional risk factors and study location.
Results: Among 6,515 participants, we found evidence of an association between percent emphysema and long-term pollution concentrations in an analysis leveraging between-city exposure contrasts. Higher concentrations of PM2.5 (5 μg/m3) and NOx (25 ppb) over the previous year were associated with 0.6 (95% CI: 0.1, 1.2%) and 0.5 (95% CI: 0.1, 0.9%) higher average percent emphysema, respectively. However, after adjustment for study site the associations were –0.6% (95% CI: –1.5, 0.3%) for PM2.5 and –0.5% (95% CI: –1.1, 0.02%) for NOx. Lower lung function measures (FEV1 and FVC) were associated with higher PM2.5 and NOx levels in 3,791 participants before and after adjustment for study site, though most associations were not statistically significant.
Conclusions: Associations between ambient air pollution and percentage of emphysema-like lung were inconclusive in this cross-sectional study, thus longitudinal analyses may better clarify these associations with percent emphysema.
Citation: Adar SD, Kaufman JD, Diez-Roux AV, Hoffman EA, D’Souza J, Stukovsky KH, Rich SS, Rotter JI, Guo X, Raffel LJ, Sampson PD, Oron AP, Raghunathan T, Barr RG. 2015. Air pollution and percent emphysema identified by computed tomography in the Multi-Ethnic Study of Atherosclerosis. Environ Health Perspect 123:144–151; http://dx.doi.org/10.1289/ehp.1307951
doi:10.1289/ehp.1307951
PMCID: PMC4314244  PMID: 25302408
2.  Testing Departure from Additivity in Tukey’s Model using Shrinkage: Application to a Longitudinal Setting 
Statistics in medicine  2014;33(29):5177-5191.
While there has been extensive research developing gene-environment interaction (GEI) methods in case-control studies, little attention has been given to sparse and efficient modeling of GEI in longitudinal studies. In a two-way table for GEI with rows and columns as categorical variables, a conventional saturated interaction model involves estimation of a specific parameter for each cell, with constraints ensuring identifiability. The estimates are unbiased but are potentially inefficient because the number of parameters to be estimated can grow quickly with increasing categories of row/column factors. On the other hand, Tukey’s one degree of freedom (df) model for non-additivity treats the interaction term as a scaled product of row and column main effects. Due to the parsimonious form of interaction, the interaction estimate leads to enhanced efficiency and the corresponding test could lead to increased power. Unfortunately, Tukey’s model gives biased estimates and low power if the model is misspecified. When screening multiple GEIs where each genetic and environmental marker may exhibit a distinct interaction pattern, a robust estimator for interaction is important for GEI detection. We propose a shrinkage estimator for interaction effects that combines estimates from both Tukey’s and saturated interaction models and use the corresponding Wald test for testing interaction in a longitudinal setting. The proposed estimator is robust to misspecification of interaction structure. We illustrate the proposed methods using two longitudinal studies — the Normative Aging Study and the Multi-Ethnic Study of Atherosclerosis.
doi:10.1002/sim.6281
PMCID: PMC4227925  PMID: 25112650
adaptive shrinkage estimation; gene-environment interaction; longitudinal data; Tukey’s one df test for non-additivity
3.  Do Psychosocial Stress and Social Disadvantage Modify the Association Between Air Pollution and Blood Pressure? 
American Journal of Epidemiology  2013;178(10):1550-1562.
Researchers have theorized that social and psychosocial factors increase vulnerability to the deleterious health effects of environmental hazards. We used baseline examination data (2000–2002) from the Multi-Ethnic Study of Atherosclerosis. Participants were 45–84 years of age and free of clinical cardiovascular disease at enrollment (n = 6814). The modifying role of social and psychosocial factors on the association between exposure to air pollution comprising particulate matter less than 2.5 µm in aerodynamic diameter (PM2.5) and blood pressure measures were examined using linear regression models. There was no evidence of synergistic effects of higher PM2.5 and adverse social/psychosocial factors on blood pressure. In contrast, there was weak evidence of stronger associations of PM2.5 with blood pressure in higher socioeconomic status groups. For example, those in the 10th percentile of the income distribution (i.e., low income) showed no association between PM2.5 and diastolic blood pressure (b = −0.41 mmHg; 95% confidence interval: −1.40, 0.61), whereas those in the 90th percentile of the income distribution (i.e., high income) showed a 1.52-mmHg increase in diastolic blood pressure for each 10-µg/m3 increase in PM2.5 (95% confidence interval: 0.22, 2.83). Our results are not consistent with the hypothesis that there are stronger associations between PM2.5 exposures and blood pressure in persons of lower socioeconomic status or those with greater psychosocial adversity.
doi:10.1093/aje/kwt190
PMCID: PMC3888274  PMID: 24064742
air pollution; blood pressure; population groups; social environment; social medicine; social psychology
4.  Relationship between the cortisol awakening response and other features of the diurnal cortisol rhythm: The Multi-Ethnic Study of Atherosclerosis 
Psychoneuroendocrinology  2013;38(11):10.1016/j.psyneuen.2013.06.032.
Summary
Cumulative cortisol burden is known to influence neuropsychiatric and metabolic disorders. To better understand the relationship between daily cortisol exposure and measures of the diurnal circadian cortisol rhythm, we examined the cross-sectional association of the cortisol awakening response (CAR) with wake-up cortisol, bedtime cortisol, diurnal slope, and total cortisol area under the curve (AUC). Up to 18 salivary cortisol samples were collected over 3 days from 935 White, Hispanic, and Black individuals (mean age 65 ± 9.8 years) in the Multi-Ethnic Study of Atherosclerosis. Outcome measures included awakening cortisol, CAR (awakening to 30 min post-awakening), early decline (30 min to 2 h post-awakening), late decline (2 h post-awakening to bedtime), and the corresponding AUCs. Total cortisol AUC was a summary measure of cumulative cortisol exposure. Higher CAR was associated with significantly lower wake-up cortisol (β = −0.56; 95% CI: −0.59 to −0.53) and a higher early decline AUC (β = 0.38; 95% CI: 0.34–0.42) but was not associated with total cortisol AUC (β = 0.04; 95% CI: −0.01 to 0.09), or other diurnal cortisol curve components following multivariable adjustment. Total cortisol AUC was significantly and positively associated with wake-up cortisol (β = 0.36; 95% CI: 0.32–0.40), bedtime cortisol (β = 0.61; 95% CI: 0.58–0.64), and other AUC measures, following multivariable adjustment. Associations were similar by sex, race/ethnicity, and age categories. We conclude that bedtime cortisol showed the strongest correlation with total cortisol AUC, suggesting it may be a marker of daily cortisol exposure.
doi:10.1016/j.psyneuen.2013.06.032
PMCID: PMC3812410  PMID: 23890985
Cortisol awakening response (CAR); Hypothalamic–pituitary–adrenal (HPA) axis; Diurnal cortisol; Correlation; Population-based study
5.  Discrete Land Uses and Transportation Walking in Two U.S. Cities: The Multi-Ethnic Study of Atherosclerosis 
Health & place  2013;24:10.1016/j.healthplace.2013.09.007.
This study examines associations of disaggregate land uses with self-reported walking for transportation among participants of the Multi-Ethnic Study of Atherosclerosis (MESA) in Forsyth County, NC and New York, NY. Network distance to each use (in miles), intensity (number of uses per ½-mile network buffer) of each use and diversity (number of different uses per ½-mile network buffer) of uses were calculated using Geographic Information Systems (GIS). Associations with odds of meeting recommended physical activity levels (150 min/week) were examined after controlling for individual- and census-tract-level covariates. Greater distance to and lower intensity of pedestrian-oriented uses, specifically those for social interactions, were associated with lower odds of meeting recommendations in NY. Results suggest that land uses linked to social interactions may be useful for encouraging increased transportation walking.
doi:10.1016/j.healthplace.2013.09.007
PMCID: PMC3851044  PMID: 24148201
Land use; Walking; Transportation; Geographic Information Systems (GIS)
6.  Associations between neighborhood characteristics and self-rated health: A cross-sectional investigation in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort 
Health & place  2013;24:10.1016/j.healthplace.2013.10.001.
Quantifying the effects of specific neighborhood features on self-reported health is important to understanding the global health impact of neighborhood context. We investigated associations of neighborhood poverty, sociability and walkability with self-rated physical and mental health in the Multi-Ethnic Study of Atherosclerosis (MESA). In separate models, each neighborhood variable was associated with physical health but associations with sociability and walkability were stronger than those for poverty. Only walkability remained significant after adjusting for the other neighborhood variables. There was no evidence that self-rated mental health as assessed by the SF12 was associated with neighborhood poverty, walkability or sociability. This study provides information on how neighborhood context is associated with global health in diverse midlife and older persons.
doi:10.1016/j.healthplace.2013.10.001
PMCID: PMC3874143  PMID: 24211514
Neighborhood; self-rated health; income; education; employment
7.  Socioeconomic Position Is Positively Associated With Blood Pressure Dipping Among African-American Adults: The Jackson Heart Study 
American journal of hypertension  2011;24(9):1015-1021.
BACKGROUND
Blunted nocturnal blood pressure (NBP) dipping is a significant predictor of cardiovascular events. Lower socioeconomic position (SEP) may be an important predictor of NBP dipping, especially in African Americans (AA). However, the determinants of NBP dipping are not fully understood.
METHODS
The cross-sectional associations of individual and neighborhood SEP with NBP dipping, assessed by 24-h ambulatory BP monitoring, were examined among 837 AA adults (Mean age: 59.2 ± 10.7 years; 69.2% women), after adjustment for age, sex, hypertension status, body mass index (BMI), health behaviors, office, and 24-h systolic BP (SBP).
RESULTS
The mean hourly SBP was consistently lower among participants in the highest category of individual income compared to those in the lowest category, and these differences were most pronounced during sleeping hours. The odds of NBP dipping (defined as >10% decline in the mean asleep SBP compared to the mean awake SBP) increased by 31% (95% confidence interval: 13–53%) and 18% (95% confidence interval: 0–39%) for each s.d. increase in income and years of education, respectively, after multivariable adjustment.
CONCLUSIONS
NBP dipping is patterned by income and education in AA adults even after accounting for known risk factors. These results suggest that low SEP is a risk factor for insufficient NBP dipping in AA.
doi:10.1038/ajh.2011.98
PMCID: PMC4206938  PMID: 21654853
ambulatory blood pressure monitoring; blood pressure; hypertension; Jackson Heart Study; nocturnal dipping; socioeconomic position; systole
8.  Neighborhood socioeconomic characteristics and differences in the availability of healthy food stores and restaurants in Sao Paulo, Brazil 
Health & place  2013;23:39-47.
Differential access to healthy foods has been hypothesized to contribute to health disparities, but evidence from low and middle-income countries is still scarce. This study examines whether the access of healthy foods varies across store types and neighborhoods of different socioeconomic statuses (SES) in a large Brazilian city. A cross-sectional study was conducted in 2010–2011 across 52 census tracts. Healthy food access was measured by a comprehensive in-store data collection, summarized into two indexes developed for retail food stores (HFSI) and restaurants (HMRI). Descriptive analyses and multilevel models were used to examine associations of store type and neighborhood SES with healthy food access. Fast food restaurants were more likely to be located in low SES neighborhoods whereas supermarkets and full service restaurants were more likely to be found in higher SES neighborhoods. Multilevel analyses showed that both store type and neighborhood SES were independently associated with in-store food measures. We found differences in the availability of healthy food stores and restaurants in Sao Paulo city favoring middle and high SES neighborhoods.
doi:10.1016/j.healthplace.2013.05.001
PMCID: PMC3758426  PMID: 23747923
Neighborhood; Food environment; Socioeconomic factors; Disparities; Food stores
9.  Socioeconomic status, John Henrysim and blood pressure among African-Americans in the Jackson Heart Study 
John Henryism connotes a strong behavioral predisposition to engage in effortful, active coping with difficult social and economic stressors. This behavioral predisposition is measured by the 12 item John Henryism Scale for Active Coping (JHAC). The John Henry hypothesis predicts that the well-known inverse socioeconomic status (SES)-blood pressure association will be stronger among persons who score high rather than low on the JHAC. We tested this hypothesis in a large African American cohort using baseline data from the Jackson Heart Study. Unlike previous studies, we used multiple indicators of SES: income, education, occupation, childhood SES and cumulative SES. Because the hypothesis is most relevant for adults still in the labor force, we excluded retired participants, yielding a sample size of 3,978. Gender-specific Poisson regression models for hypertension adjusting for age, John Henryism, SES, and a John Henryism-SES interaction term, were fit to examine associations. Separate models were fit for each SES indicator. We found some evidence that John Henryism modified the association between income and hypertension in men: low income was associated with higher prevalence of hypertension in men who scored high on John Henryism (prevalence ratio (PR) for low vs. high income tertile 1.12), but with lower hypertension prevalence among men who scored low on John Henryism (PR 0.85, one sided P value for multiplicative interaction <0.05). For women, the association of low income with higher hypertension prevalence was stronger at lower than higher levels of John Henryism (PR 1.27 and 1.06 at low and high levels of John Henryism respectively, P value<0.05). There was no evidence that John Henryism modified the associations of hypertension with other SES indicators in men or women. The modest support of the John Henryism Hypothesis in men only, adds to the literature on this subject, but underscores questions regarding the gender, spatial, socioeconomic and historical contexts in which the hypothesis is valid.
doi:10.1016/j.socscimed.2013.06.016
PMCID: PMC4149751  PMID: 23906131
United States; John Henryism; socioeconomic status; hypertension; African American
10.  Walk Score® and Transit Score® and Walking in the Multi-Ethnic Study of Atherosclerosis 
Background
Walk Score® and Transit Score® are open-source measures of the neighborhood built environment to support walking (“walkability”) and access to transportation.
Purpose
To investigate associations of Street Smart Walk Score and Transit Score with self-reported transport and leisure walking using data from a large multi-city and diverse population-based sample of adults.
Methods
Data from a sample of 4552 residents of Baltimore MD; Chicago IL; Forsyth County NC; Los Angeles CA; New York NY; and St. Paul MN from the Multi-Ethnic Study of Atherosclerosis (2010–2012) were linked to Walk Score and Transit Score (collected in 2012). Logistic and linear regression models estimated ORs of not walking and mean differences in minutes walked, respectively, associated with continuous and categoric Walk Score and Transit Score. All analyses were conducted in 2012.
Results
After adjustment for site, key sociodemographic, and health variables, a higher Walk Score was associated with lower odds of not walking for transport and more minutes/week of transport walking. Compared to those in a “walker’s paradise,” lower categories of Walk Score were associated with a linear increase in odds of not transport walking and a decline in minutes of leisure walking. An increase in Transit Score was associated with lower odds of not transport walking or leisure walking, and additional minutes/week of leisure walking.
Conclusions
Walk Score and Transit Score appear to be useful as measures of walkability in analyses of neighborhood effects.
doi:10.1016/j.amepre.2013.03.018
PMCID: PMC3769092  PMID: 23867022
11.  Secular trends in the association between nativity/length of US residence with body mass index and waist circumference among Mexican-Americans, 1988–2008 
Objectives
We investigated whether associations between nativity/length of US residence and body mass index (BMI) and waist circumference (WC) varied over the past two decades.
Methods
Mexican-Americans aged 20–64 years from the National Health and Nutrition Survey (NHANES) III (1988–1994), and NHANES (1999–2008). Sex-stratified multivariable linear regression models further adjusted for age, education, and NHANES period.
Results
We found no evidence of secular variation in the nativity/length of US residence gradient for men or women. Foreign-born Mexican-Americans, irrespective of residence length, had lower mean BMI and WC than their US-born counterparts. However among women, education modified secular trends in nativity differentials: notably, in less-educated women, nativity gradients widened over time due to alarming increases in BMI among the US-born and little increase in the foreign-born.
Conclusions
Associations between nativity/length of US residence and BMI/WC did not vary over this 20-year period, but we noted important modifications by education in women. Understanding these trends is important for identifying vulnerable subpopulations among Mexican-Americans and for the development of effective health promotion strategies in this fast-growing segment of the population.
doi:10.1007/s00038-012-0414-5
PMCID: PMC3570586  PMID: 23052250
Obesity; Trends; Mexican; Immigrants; Socioeconomic status
12.  Examining the association between salivary cortisol levels and subclinical measures of atherosclerosis: the Multi-Ethnic Study of Atherosclerosis 
Psychoneuroendocrinology  2012;38(7):1036-1046.
Objective
To investigate the association between salivary cortisol and two markers of subclinical cardiovascular disease (CVD), coronary calcification (CAC), and ankle-brachial index (ABI).
Methods
Data from an ancillary study to the Multi-Ethnic Study of Atherosclerosis (MESA), the MESA Stress Study, were used to analyze associations of salivary cortisol data collected six times per day over three days with CAC and ABI. The authors used mixed models with repeat cortisol measures nested within persons to determine if specific features of the cortisol profile were associated with CAC and ABI.
Results
total of 464 participants were included in the CAC analysis and 610 in the ABI analysis. The mean age of participants was 65.6 years. A 1-unit increase in log coronary calcium was associated with a 1.77% flatter early decline in cortisol (95% CI: 0.23, 3.34) among men and women combined. Among women low ABI was associated with a steeper early decline (−13.95% CI:−25.58, −3.39) and a marginally statistically significant flatter late decline (1.39% CI: −0.009, 2.81). The cortisol area under the curve and wake to bedtime slope were not associated with subclinical CVD.
Conclusions
This study provides weak support for the link between cortisol and measures of subclinical atherosclerosis. We found an association between some features of the diurnal cortisol profile and coronary calcification and ABI but associations were not consistent across subclinical measures. There are methodological challenges in detecting associations of cortisol measures at a point in time with health outcomes that develop over a lifetime. Studies of short-term mechanisms linking stress to physiological processes related to the development of early atherosclerosis may be more informative.
doi:10.1016/j.psyneuen.2012.10.007
PMCID: PMC4020284  PMID: 23146655
salivary cortisol; ankle brachial index; coronary calcification; atherosclerosis; stress; cortisol awakening response; cortisol diurnal pattern; Multi-Ethnic Study of Atherosclerosis
13.  Current employment status, occupational category, occupational hazard exposure, and job stress in relation to telomere length: The Multiethnic Study of Atherosclerosis (MESA) 
Objective
Telomere length has been proposed as a biomarker of cell senescence, which is associated with a wide array of adverse health outcomes. While work is a major determinant of health, few studies have investigated the association of telomere length with various dimensions of occupation. Accelerated cellular aging could be a common pathway linking occupational exposure to several health outcomes.
Methods
Leukocyte telomere length was assessed using quantitative polymerase chain reaction (Q-PCR) in a community-based sample of 981 individuals (age: 45–84 years old). Questionnaires were used to collect information on current employment status, current or main occupation before retirement, and job strain. The O*NET (Occupational Resource Network) database was linked to the questionnaire data to create 5 exposure measures: physical activity on the job, physical hazard exposure, interpersonal stressors, job control, and job demands. Linear regression was used to estimate associations of occupational characteristics with telomere lengths after adjustment for age, sex, race, socioeconomic position, and several behavioral risk factors.
Results
There were no mean differences in telomere lengths across current employment status, occupational category, job strain categories or levels of most O*NET exposure measures. There was also no evidence that being in lower status occupational categories or being exposed to higher levels of adverse physical or psychosocial exposures accelerated the association between age and telomere shortening.
Conclusions
Cellular aging as reflected by shorter telomeres does not appear to be an important pathway linking occupation to various health outcomes.
doi:10.1136/oemed-2012-101296
PMCID: PMC4068015  PMID: 23686115
14.  Complex systems thinking and current impasses in health disparities research 
American Journal of Public Health  2011;101(9):1627-1634.
Complex systems approaches have received increasing attention in public health because reductionist approaches yield limited insights in the context of dynamic systems. Most discussions to date have been highly abstract. There is a need to consider the application of complex systems approaches to specific research questions. After briefly reviewing the features of population health problems for which complex systems approaches are most likely to yield new insights, this commentary discusses possible applications of complex systems to health disparities research. It provides illustrative examples of how complex systems approaches may help address unanswered and persistent questions regarding genetic factors, life course processes, place effects, and the impact of upstream policies. It is argued that the concepts and methods of complex systems may help researchers move beyond current impasse points in health disparities research.
doi:10.2105/AJPH.2011.300149
PMCID: PMC3154209  PMID: 21778505
15.  Racial discrimination, racial/ethnic segregation and health behaviors in the CARDIA Study 
Ethnicity & health  2012;18(3):227-243.
Objective
Racial discrimination has been associated with unhealthy behaviors, but the mechanisms responsible for these associations are not understood and may be related to residential racial segregation. We investigated associations between self-reported racial discrimination and health behaviors before and after controlling for individual- and neighborhood-level characteristics; and potential effect modification of these associations by segregation.
Design
We used data from the longitudinal Coronary Artery Risk Development in Young Adults study (CARDIA) for 1,169 African-Americans and 1,322 whites. To assess racial discrimination, we used a 4 category variable to capture the extent and persistence of self-reported discrimination between years 7 (1992–93) and 15 (2000–2001). We assessed smoking status, alcohol consumption, and physical activity at year 20 (2005–2006). Segregation was examined as the racial/ethnic composition of the Census tract level.
Results
Discrimination was more common in African-Americans (89.1%) than in whites (40.0%). Living in areas with high percentage of blacks was associated with less reports of discrimination in African-Americans but more reports in whites. After adjustment for selected characteristics including individual and neighborhood-level socioeconomic conditions and segregation, we found significant positive associations of discrimination with smoking and alcohol consumption in African-Americans and with smoking in whites. African-Americans experiencing moderate or high discrimination were more physically active than those reporting no discrimination. Whites reporting some discrimination were also more physically active than those reporting no discrimination. We observed no interactions between discrimination and segregation measures in African-Americans or whites for any of the three health behaviors.
Conclusions
Racial discrimination may impact individuals’ adoption of healthy and unhealthy behaviors independent of racial/ethnic segregation. These behaviors may help individuals buffer or reduce the stress of discrimination.
doi:10.1080/13557858.2012.713092
PMCID: PMC3523091  PMID: 22913715
United States; discrimination; segregation; health behaviors; race/ethnicity; neighborhood characteristics
16.  The associations of fast food restaurant availability with dietary intake and weight among African Americans in the Jackson Heart Study, 2000–2004 
American Journal of Public Health  2011;101(Suppl 1):S301-S309.
Objectives
The purpose of this study was to examine the associations of fast food restaurant (FFR) availability with dietary intake and weight among African Americans in the Southeastern United States.
Methods
Cross-sectional associations of 0.5, 1, 2, and 5 mile FFR availability with energy, fat, carbohydrates, fiber, and fruit and vegetable intakes, and body mass index (BMI) and waist circumference were investigated in 4,740 African American Jackson Heart Study participants (55.2±12.6 years, 63.3% women).
Results
No consistent associations between FFR availability and BMI or waist circumference were observed. Greater FFR availability was associated with higher energy intake among persons <55 years after adjustment for individual socioeconomic status mean difference in energy intake per standard deviation increase in 5-mile FFR 138 KCal (Confidence interval (CI): 70.53, 204.75) and 58 Kcal (CI: 8.55, 105.97) in men and women, respectively. Similar associations were also observed for the 2-mile windows in men. FFR availability was positively associated with total fiber intake among men and women <55 years.
Conclusions
FFR availability may contribute to greater energy intake in younger African Americans.
doi:10.2105/AJPH.2010.300006
PMCID: PMC3222494  PMID: 21551382
17.  Assessing the Psychometric and Ecometric Properties of Neighborhood Scales in Developing Countries: Saúde em Beagá Study, Belo Horizonte, Brazil, 2008–2009 
Although specific measurement instruments are necessary to better understand the relationship between features of neighborhoods and health, very few studies have developed instruments to measure neighborhood features in developing countries. The objective of the study was to develop valid and reliable measures of neighborhood context useful in a Latin American urban context, assess their psychometric and ecometric properties, and examine individual and neighborhood-level predictors of these measures. We analyzed data from a multistage household survey (2008–2009) conducted in Belo Horizonte City by the Observatory for Urban Health. One adult in each household was selected to answer a questionnaire that included scales to measure neighborhood domains. Census tracts were used to proxy neighborhoods. Internal consistency was evaluated by Cronbach’s alpha, and multilevel models were used to estimate ecometric properties and to estimate associations of neighborhood measures with socioeconomic indicators. The final sample comprised 4048 survey respondents representing 149 census tracts. We assessed ten neighborhood environment dimensions: public services, aesthetic quality, walking environment, safety, violence, social cohesion, neighborhood participation, neighborhood physical disorder, neighborhood social disorder, and neighborhood problems. Cronbach’s alpha coefficients ranged from 0.53 to 0.83; intraneighborhood correlations ranged from 0.02 to 0.53, and neighborhood reliability varied from 0.76 to 0.99. Most scales were associated with individual and neighborhood socioeconomic predictors. Questionnaires can be used to reliably measure neighborhood contexts in developing countries.
doi:10.1007/s11524-012-9737-z
PMCID: PMC3675718  PMID: 22692842
Epidemiologic methods; Psychometrics; Residence characteristics; Data collection; Self-report; Environment design; Censuses
18.  A Genome-Wide Association Study of Depressive Symptoms 
Hek, Karin | Demirkan, Ayse | Lahti, Jari | Terracciano, Antonio | Teumer, Alexander | Cornelis, Marilyn C. | Amin, Najaf | Bakshis, Erin | Baumert, Jens | Ding, Jingzhong | Liu, Yongmei | Marciante, Kristin | Meirelles, Osorio | Nalls, Michael A. | Sun, Yan V. | Vogelzangs, Nicole | Yu, Lei | Bandinelli, Stefania | Benjamin, Emelia J. | Bennett, David A. | Boomsma, Dorret | Cannas, Alessandra | Coker, Laura H. | de Geus, Eco | De Jager, Philip L. | Diez-Roux, Ana V. | Purcell, Shaun | Hu, Frank B. | Rimma, Eric B. | Hunter, David J. | Jensen, Majken K. | Curhan, Gary | Rice, Kenneth | Penman, Alan D. | Rotter, Jerome I. | Sotoodehnia, Nona | Emeny, Rebecca | Eriksson, Johan G. | Evans, Denis A. | Ferrucci, Luigi | Fornage, Myriam | Gudnason, Vilmundur | Hofman, Albert | Illig, Thomas | Kardia, Sharon | Kelly-Hayes, Margaret | Koenen, Karestan | Kraft, Peter | Kuningas, Maris | Massaro, Joseph M. | Melzer, David | Mulas, Antonella | Mulder, Cornelis L. | Murray, Anna | Oostra, Ben A. | Palotie, Aarno | Penninx, Brenda | Petersmann, Astrid | Pilling, Luke C. | Psaty, Bruce | Rawal, Rajesh | Reiman, Eric M. | Schulz, Andrea | Shulman, Joshua M. | Singleton, Andrew B. | Smith, Albert V. | Sutin, Angelina R. | Uitterlinden, André G. | Völzke, Henry | Widen, Elisabeth | Yaffe, Kristine | Zonderman, Alan B. | Cucca, Francesco | Harris, Tamara | Ladwig, Karl-Heinz | Llewellyn, David J. | Räikkönen, Katri | Tanaka, Toshiko | van Duijn, Cornelia M. | Grabe, Hans J. | Launer, Lenore J. | Lunetta, Kathryn L. | Mosley, Thomas H. | Newman, Anne B. | Tiemeier, Henning | Murabito, Joanne
Biological psychiatry  2013;73(7):10.1016/j.biopsych.2012.09.033.
Background
Depression is a heritable trait that exists on a continuum of varying severity and duration. Yet, the search for genetic variants associated with depression has had few successes. We exploit the entire continuum of depression to find common variants for depressive symptoms.
Methods
In this genome-wide association study, we combined the results of 17 population-based studies assessing depressive symptoms with the Center for Epidemiological Studies Depression Scale. Replication of the independent top hits (p < 1 × 10−5) was performed in five studies assessing depressive symptoms with other instruments. In addition, we performed a combined meta-analysis of all 22 discovery and replication studies.
Results
The discovery sample comprised 34,549 individuals (mean age of 66.5) and no loci reached genome-wide significance (lowest p = 1.05 × 10−7). Seven independent single nucleotide polymorphisms were considered for replication. In the replication set (n = 16,709), we found suggestive association of one single nucleotide polymorphism with depressive symptoms (rs161645, 5q21, p = 9.19 × 10−3). This 5q21 region reached genome-wide significance (p = 4.78 × 10−8) in the overall meta-analysis combining discovery and replication studies (n = 51,258).
Conclusions
The results suggest that only a large sample comprising more than 50,000 subjects may be sufficiently powered to detect genes for depressive symptoms.
doi:10.1016/j.biopsych.2012.09.033
PMCID: PMC3845085  PMID: 23290196
Center for Epidemiologic Studies Depression Scale; CHARGE consortium; depression; depressive symptoms; genetics; genome-wide association study; meta-analysis
19.  The association of optimism and pessimism with inflammation and hemostasis in the Multi-Ethnic Study of Atherosclerosis (MESA) 
Psychosomatic medicine  2010;72(2):134-140.
Objective
Optimism and pessimism are associated with cardiovascular disease mortality and progression, however the biological mechanism remains unclear. This study investigates the association between optimism/pessimism and concentrations of seven inflammation and hemostasis markers.
Methods
This cross-sectional study used data from the Multi-Ethnic Study of Atherosclerosis (MESA), a study of 6814 persons aged 45–84 with no history of clinical cardiovascular disease. The Life-Orientation Test—Revised (LOT-R) was used to measure dispositional optimism and pessimism. Regression analyses were used to estimate associations of optimism and pessimism with interleukin-6 (IL-6), C-reactive protein (CRP), fibrinogen, homocysteine, factor VIII, D-dimer, and plasmin-antiplasmin, before and after adjustment for sociodemographics, depression, cynicism, health behaviors, BMI, hypertension, and diabetes.
Results
Higher scores on the LOT-R (positive disposition) were related to lower concentrations of IL-6 (p=0.001), fibrinogen (p<0.001) and homocysteine (p=0.031). Associations were stronger for the pessimism subscale. After adjustment for demographics, the percentage differences in inflammatory markers corresponding to a 2-standard deviation increase in pessimism were 6.01% (p=0.001) for IL-6; 10.31% (p=0.001) for CRP; 2.47% (p<0.0001) for fibrinogen, and 1.36% (p=0.07) for homocysteine. Associations were attenuated but significant after adjustment for sociodemographics, depression, cynical distrust, and behaviors. Further adjustment for hypertension, BMI and diabetes reduced associations for CRP and IL-6. Pessimism remained associated with a 1.36% (p=0.02) increase in fibrinogen in the fully adjusted model. Factor VIII, D-dimer and plasmin-antiplasmin were not associated with the LOT-R or subscales.
Conclusions
Pessimism is related to higher levels of inflammation. Health behaviors, BMI, hypertension and diabetes appear to play a mediating role.
doi:10.1097/PSY.0b013e3181cb981b
PMCID: PMC2842951  PMID: 20100888
Psychosocial factors; inflammation; coagulation; epidemiology; risk factors
20.  Socioeconomic Factors and Leukocyte Telomere Length In A Multi-Ethnic Sample: Findings From The Multi-Ethnic Study of Atherosclerosis (MESA) 
Brain, behavior, and immunity  2012;28:108-114.
Previous findings have linked lower socioeconomic status (SES) with elevated morbidity and mortality. Leukocyte telomere length (LTL), which also has been associated with age-related disease morbidity and mortality, is a marker of aging at the cellular level, making it a valuable early biomarker of risk and an indicator of biological age. It is hypothesized that SES will be associated with LTL, indicating that SES influences disease risk by accelerating biological aging. In the present sample we test for associations of childhood SES and adult SES (i.e. education, income, home ownership) with LTL, and examine whether these associations vary by racial/ethnic group. Analyses on 963 subjects (18.7% White, 53% Hispanics, and 28.5% African American) from the Stress ancillary study of the Multi-Ethnic Study of Atherosclerosis revealed a significant difference in LTL between home owners and renters in Hispanic and White participants (p < .05), but not amongst African Americans (p = .98). There were no linear associations of adult education or family income with LTL, however, there was an inverse association between father’s education and LTL (p = .03). These findings suggest that for Whites and Hispanics renting vs. owning a home is associated with an older biological age; however we did not replicate previous findings linking education with LTL.
doi:10.1016/j.bbi.2012.10.024
PMCID: PMC3544984  PMID: 23142704
Telomere length; childhood SES; socioeconomic status; home ownership; wealth; parental education; cellular aging; biological aging; ethnicity
21.  Low Social Support Is Associated With Shorter Leukocyte Telomere Length in Late Life: Multi-Ethnic Study of Atherosclerosis (MESA) 
Psychosomatic medicine  2013;75(2):10.1097/PSY.0b013e31828233bf.
Objective
The primary goal was to test the hypothesis that limited social support (SS) is related to shorter leukocyte telomere length (LTL), particularly in an older adult population.
Methods
Cross-sectional analyses were performed on 948 participants at Exam 1 of the Multi-Ethnic Study of Atherosclerosis (MESA), ages 45–84 years (18.4% White, 53.1% Hispanics, and 28.5% African-American). LTL was determined using qPCR and social support was measured with the ENRICHD social support inventory.
Results
Across the entire sample, SS was not associated with LTL (p = .87) after adjusting for demographic (age, gender, race/ethnicity, socioeconomic status), age X gender, age X race, health (body mass index, diabetes, pulse pressure), and lifestyle factors (smoking, physical activity, diet), however the interaction term Age (dichotomized) X SS was significant, p = .001. Stratification by age group revealed a positive association between SS (score range: 5–25) and LTL in the older (65–84 years) B(SE) = .005(.002), p = .007, but not younger participants (45–64 years), p = .12, after adjusting for covariates.
Conclusions
These results from a racially/ethnically diverse community sample of men and women provide initial evidence that low SS is associated with shorter LTL in adults aged 65 and older and is consistent with the hypothesis that social environment may contribute to rates of cellular aging, particularly in late life.
doi:10.1097/PSY.0b013e31828233bf
PMCID: PMC3881963  PMID: 23370895
telomere length; social support; cellular aging; loneliness; isolation; older adults
22.  The Relationship Between Neighborhood Poverty and Alcohol Use: Estimation by Marginal Structural Models 
Epidemiology (Cambridge, Mass.)  2010;21(4):482-489.
Background
Previous studies on the relationship of neighborhood disadvantage with alcohol use or misuse have often controlled for individual characteristics on the causal pathway, such as income—thus potentially underestimating the relationship between disadvantage and alcohol consumption.
Methods
We used data from the Coronary Artery Risk Development in Young Adults study of 5115 adults aged 18–30 years at baseline and interviewed 7 times between 1985 and 2006. We estimated marginal structural models using inverse probability-of-treatment and censoring weights to assess the association between point-in-time/cumulative exposure to neighborhood poverty (proportion of census tract residents living in poverty) and alcohol use/binging, after accounting for time-dependent confounders including income, education, and occupation.
Results
The log-normal model was used to estimate treatment weights while accounting for highly-skewed continuous neighborhood poverty data. In the weighted model, a one-unit increase in neighborhood poverty at the prior examination was associated with a 86% increase in the odds of binging (OR = 1.86 [95% confidence interval = 1.14–3.03]); the estimate from a standard generalized-estimating-equations model controlling for baseline and time-varying covariates was 1.47 (0.96–2.25). The inverse probability-of-treatment and censoring weighted estimate of the relative increase in the number of weekly drinks in the past year associated with cumulative neighborhood poverty was 1.53 (1.02–2.27); the estimate from a standard model was 1.16 (0.83–1.62).
Conclusions
Cumulative and point-in-time measures of neighborhood poverty are important predictors of alcohol consumption. Estimators that more closely approximate a causal effect of neighborhood poverty on alcohol provided a stronger estimate than estimators from traditional regression models.
doi:10.1097/EDE.0b013e3181e13539
PMCID: PMC3897210  PMID: 20498603
23.  The Neighborhood Energy Balance Equation: Does Neighborhood Food Retail Environment + Physical Activity Environment = Obesity? The CARDIA Study 
PLoS ONE  2013;8(12):e85141.
Background
Recent obesity prevention initiatives focus on healthy neighborhood design, but most research examines neighborhood food retail and physical activity (PA) environments in isolation. We estimated joint, interactive, and cumulative impacts of neighborhood food retail and PA environment characteristics on body mass index (BMI) throughout early adulthood.
Methods and Findings
We used cohort data from the Coronary Artery Risk Development in Young Adults (CARDIA) Study [n=4,092; Year 7 (24-42 years, 1992-1993) followed over 5 exams through Year 25 (2010-2011); 12,921 person-exam observations], with linked time-varying geographic information system-derived neighborhood environment measures. Using regression with fixed effects for individuals, we modeled time-lagged BMI as a function of food and PA resource density (counts per population) and neighborhood development intensity (a composite density score). We controlled for neighborhood poverty, individual-level sociodemographics, and BMI in the prior exam; and included significant interactions between neighborhood measures and by sex. Using model coefficients, we simulated BMI reductions in response to single and combined neighborhood improvements. Simulated increase in supermarket density (from 25th to 75th percentile) predicted inter-exam reduction in BMI of 0.09 kg/m2 [estimate (95% CI): -0.09 (-0.16, -0.02)]. Increasing commercial PA facility density predicted BMI reductions up to 0.22 kg/m2 in men, with variation across other neighborhood features [estimate (95% CI) range: -0.14 (-0.29, 0.01) to -0.22 (-0.37, -0.08)]. Simultaneous increases in supermarket and commercial PA facility density predicted inter-exam BMI reductions up to 0.31 kg/m2 in men [estimate (95% CI) range: -0.23 (-0.39, -0.06) to -0.31 (-0.47, -0.15)] but not women. Reduced fast food restaurant and convenience store density and increased public PA facility density and neighborhood development intensity did not predict reductions in BMI.
Conclusions
Findings suggest that improvements in neighborhood food retail or PA environments may accumulate to reduce BMI, but some neighborhood changes may be less beneficial to women.
doi:10.1371/journal.pone.0085141
PMCID: PMC3874030  PMID: 24386458
24.  Cross-Sectional and Longitudinal Associations of Neighborhood Cohesion and Stressors with Depressive Symptoms in the Multiethnic Study of Atherosclerosis (MESA) 
Annals of epidemiology  2009;19(1):49-57.
Purpose
This study examined associations of neighborhood social cohesion, violence and aesthetic quality with depressive symptoms amongst 2619 healthy adults aged 45-84 years enrolled in the Multiethnic Study of Atherosclerosis.
Methods
Neighborhood characteristics were estimated by surveying a separate sample of area residents. Measures of aesthetic environment, social cohesion, and violence were combined into a summary score with increasing scores indicating more favorable environments. Depressive symptoms were measured using the Center for Epidemiologic Studies Depression (CES-D) scale. Marginal maximum likelihood estimation was used to assess associations of neighborhood characteristics with CES-D score at baseline and with the odds of developing incident depression (CES-D score ≥16 or use of antidepressants) over a 4-5 year follow-up among persons with CESD<16 at baseline. Models were adjusted for age, income, education, and race/ethnicity.
Results
Lower levels of social cohesion and aesthetic quality and higher levels of violence were associated with higher mean CES-D scores in men and women (p-value for trend <0.01, adjusted mean difference in CES-D per 1 SD increase in summary score -1.01 (95% CI: -1.85, -0.17) and -1.08 (-1.88, -0.28) in men and women respectively). Associations of neighborhood characteristics with incident depression were in the expected direction for women but confidence intervals were wide (OR of incident depression 0.89 (0.63, 1.26)). No association was seen for men (OR=0.96 (0.74, 1.25)). Conclusions: Neighborhood social cohesion, aesthetic quality and violence are associated with the presence of depressive symptoms in residents.
doi:10.1016/j.annepidem.2008.10.002
PMCID: PMC2763272  PMID: 19064189
mental health; depression; residence characteristics; epidemiology; social environment
25.  Associations of Acculturation and Socioeconomic Status with Subclinical CVD in the MultiEthnic Study of Atherosclerosis 
American journal of public health  2008;98(11):1963-1970.
Objective
To assess whether markers of acculturation (birthplace, number of U.S. generations) and socioeconomic status (SES) are associated with carotid artery plaque, internal carotid intima-media thickness (IMT), and albuminuria, in four racial/ethnic groups.
Methods
Using Multi-Ethnic Study of Atherosclerosis data (n = 6,716; age: 45-84) and race-specific binomial regression models, we computed prevalence ratios, adjusted for demographics and traditional cardiovascular risk factors.
Results
The adjusted U.S. to foreign-born prevalence ratio (99% CI) for carotid plaque was 1.20 (0.97, 1.39) in Whites, 1.91 (0.94, 2.94) in Chinese, 1.62 (1.28, 2.06) in Blacks, and 1.23 (1.15, 1.31) in Hispanics. Greater carotid plaque prevalence was also found among Whites, Blacks, and Hispanics with more generations of US residence (p<0.001). Lower educational attainment and/or income were associated with greater carotid plaque prevalence in Whites and Blacks. Similar associations were observed with IMT. There was also some evidence of an inverse association between albuminuria and SES, in Whites and Hispanics.
Conclusions
Greater U.S. acculturation and lower SES were associated with a higher prevalence of carotid plaque and IMT, while little association was found with albuminuria.
doi:10.2105/AJPH.2007.123844
PMCID: PMC2575668  PMID: 18511718

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