Social Susceptibility to Multiple Air Pollutants in Cardiovascular Disease.

INTRODUCTION: Cardiovascular disease (CVD) is the leading cause of death in the United States, and substantial research has linked ambient air pollution to elevated rates of CVD etiology and events. Much of this research identified increased effects of air pollution in lower socioeconomic position (SEP) communities, where pollution exposures are also often higher. The complex spatial confounding between air pollution and SEP makes it very challenging, however, to disentangle the impacts of these very different exposure types and to accurately assess their interactions. The specific causal components (i.e., specific social stressors) underlying this SEP-related susceptibility remain unknown, because there are myriad pathways through which poverty and/or lower-SEP conditions may influence pollution susceptibility - including diet, smoking, coexposures in the home and occupational environments, health behaviors, and healthcare access. Growing evidence suggests that a substantial portion of SEP-related susceptibility may be due to chronic psychosocial stress - given the known wide-ranging impacts of chronic stress on immune, endocrine, and metabolic function - and to a higher prevalence of unpredictable chronic stressors in many lower-SEP communities, including violence, job insecurity, and housing instability. As such, elucidating susceptibility to pollution in the etiology of CVD, and in the risk of CVD events, has been identified as a research priority. This interplay among social and environmental conditions may be particularly relevant for CVD, because pollution and chronic stress both impact inflammation, metabolic function, oxidative stress, hypertension, atherosclerosis, and other processes relevant to CVD etiology. Because pollution exposures are often spatially patterned by SEP, disentangling their effects - and quantifying any interplay - is especially challenging. Doing so, however, would help to improve our ability to identify and characterize susceptible populations and to improve our understanding of how community stressors may alter responses to multiple air pollutants. More clearly characterizing susceptible populations will improve our ability to design and target interventions more effectively (and cost-effectively) and may reveal greater benefits of pollution reduction in susceptible communities, strengthening cost-benefit and accountability analyses, ultimately reducing the disproportionate burden of CVD and reducing health disparities. METHODS: In the current study, we aimed to quantify combined effects of multiple pollutants and stressor exposures on CVD events, using a number of unique datasets we have compiled and verified, including the following. 1. Poverty metrics, violent crime rates, a composite socioeconomic deprivation index (SDI), an index of racial and economic segregation, noise disturbance metrics, and three composite spatial factors produced from a factor analysis of 27 community stressors. All indicators have citywide coverage and were verified against individual reports of stress and stressor exposure, in citywide focus groups and surveys. 2. Spatial surfaces for multiple pollutants from the New York City (NYC) Community Air Survey (NYCCAS), which monitored multiple pollutants year-round at 150 sites and used land use regression (LUR) modeling to estimate fine-scale (100-m) intra-urban spatial variance in fine particles (PM2.5), nitrogen dioxide (NO2), sulfur dioxide (SO2), and ozone (O3). 3. Daily data and time-trends derived from all U.S. Environmental Protection Agency (EPA) Air Quality System (AQS) monitors in NYC for 2005-2011, which we combined with NYCCAS surfaces to create residence- and day-specific spatiotemporal exposure estimates. 4. Complete data on in- and out-patient unscheduled CVD events presented in NYC hospitals for 2005-2011 (n = 1,113,185) from the New York State (NYS) Department of Health's Statewide Planning and Research Cooperative System (SPARCS). In the study, we quantified relationships between multiple pollutant exposures and both community CVD event rates and individual risk of CVD events in NYC and tested whether pollution-CVD associations varied by community SEP and social stressor exposures. We hypothesized (1) that greater chronic community-level SEP, stressor, and pollution exposures would be associated with higher community CVD rates; (2) that spatiotemporal variations in multiple pollutants would be associated with excess risk of CVD events; and (3) that pollution-CVD associations would be stronger in communities of lower SEP or higher stressor exposures. RESULTS: To first understand the separate and combined associations with CVD for both stressors and pollutants measured at the same spatial and temporal scale of resolution, we used ecological cross-sectional models to examine spatial relationships between multiple chronic pollutant and stressor exposures and age-adjusted community CVD rates. Using census-tract-level annual averages (n = 2,167), we compared associations with CVD rates for multiple pollutant concentrations and social stressors. We found that associations with community CVD rates were consistently stronger for social stressors than for pollutants, in terms of both magnitude and significance. We note, however, that this result may be driven by the relatively greater variation (on a proportional basis) for stressors than for pollutants in NYC. We also tested effect modification of pollutant-CVD associations by each social stressor and found evidence of stronger associations for NO2, PM2.5, and wintertime SO2 with CVD rates, particularly across quintiles of increasing community violence or assault rates (P trend < 0.0001). To examine individual-level associations between spatiotemporal exposures to multiple pollutants and the risk of CVD events, across multiple lag days, we examined the combined effects of multiple pollutant exposures, using spatiotemporal (day- and residence-specific) pollution exposure estimates and hospital data on individual CVD events in case-crossover models, which inherently adjust for nontime-varying individual confounders (e.g., sex and race) and comorbidities. We found consistent significant relationships only for same-day pollutant exposures and the risk of CVD events, suggesting very acute impacts of pollution on CVD risk. Associations with CVD were positive for NO2, PM2.5, and SO2, as hypothesized, and we found inverse associations for O3 (a secondary pollutant chemically decreased ["scavenged"] by fresh emissions that, in NYC, displays spatial and temporal patterns opposite those of NO2). Finally, to test effect modification by chronic community social stressors on the relationships between spatiotemporal pollution measures and the risk of CVD events, we used individual-level case-crossover models, adding interaction terms with categorical versions of each social stressor. We found that associations between NO2 and the risk of CVD events were significantly elevated only in communities with the highest exposures to social stressors (i.e., in the highest quintiles of poverty, socioeconomic deprivation, violence, or assault). The largest positive associations for PM2.5 and winter SO2 were generally found in the highest-stressor communities but were not significant in any quintile. We again found inverse associations for O3, which were likewise stronger for individuals living in communities with greater stressor exposures. CONCLUSIONS: In ecological models, we found stronger relationships with community CVD rates for social stressors than for pollutant exposures. In case-crossover analyses, higher exposures to NO2, PM2.5, and SO2 were associated with greater excess risk of CVD events but only on the case day (there were no consistent significant lagged-day effects). In effect-modification analyses at both the community and individual level, we found evidence of stronger pollution-CVD associations in communities with higher stressor exposures. Given substantial spatial confounding across multiple social stressors, further research is needed to disentangle these effects in order to identify the predominant social stressors driving this observed differential susceptibility.

Dietary patterns and risk of systemic lupus erythematosus in women.

OBJECTIVE: Dietary intake is a complex exposure and a potential risk factor for systemic lupus erythematosus (SLE) due to its impact on lipid and glucose metabolism, oxidative stress, and the intestinal microbiome. We aimed to test whether a prudent dietary pattern is associated with a lower risk of SLE, and whether a Western dietary pattern is associated with a higher risk of SLE. METHODS: We prospectively investigated two dietary patterns and SLE risk among women in the Nurses' Health Study (NHS, 1984-2014) and Nurses' Health Study II (NHSII, 1991-2015). Food frequency questionnaires were completed every four years. Congruent with prior work in NHS and NHSII, we derived two separate dietary patterns (prudent and Western) using principal component analysis within each cohort. Incident SLE was confirmed by the American College of Rheumatology's 1997 criteria. We estimated hazard ratios (HR) and 95% confidence intervals (CI) for SLE by dietary pattern quartiles using Cox models adjusted for time-varying covariates. Models were performed separately in each cohort and results were meta-analyzed. Stratified analyses tested the association of dietary patterns with anti-dsDNA positive SLE and anti-dsDNA negative SLE. RESULTS: We confirmed 82 NHS incident SLE cases and 98 NHSII SLE cases during 3,833,054 person-years of follow-up. A higher (healthier) prudent dietary pattern score was not associated with SLE risk (meta-analyzed HRQ4 versus Q1 0.84 [95% CI 0.51, 1.38]). Women with higher (less healthy) Western dietary pattern scores did not have a significantly increased risk for SLE (meta-analyzed HRQ4 versus Q1 1.35 [95% CI 0.77, 2.35]). Results were similar after further adjustment for body mass index. Incident anti-dsDNA positive SLE and anti-dsDNA negative SLE were not associated with either dietary pattern. CONCLUSION: We did not observe a relationship between prudent or Western dietary pattern score and risk of SLE.

Childhood Psychological Distress and Healthy Cardiovascular Lifestyle 17-35 Years Later: The Potential Role of Mental Health in Primordial Prevention.

Background: Maintaining a healthy lifestyle in adulthood has been shown to significantly reduce cardiovascular disease risk. Increasing evidence suggests that behavioral risk factors for cardiovascular disease are established in childhood; however, limited research has evaluated whether childhood psychological factors play a role. Purpose: To evaluate the association between childhood psychological distress and young to mid adulthood healthy lifestyle. Methods: Using prospective data from the 1958 British Birth Cohort, we assessed whether psychological distress in childhood (captured by internalizing and externalizing symptoms at ages 7, 11, and 16 years) predicted healthy lifestyle at ages 33 (N = 10,748) and 42 (N = 9,581) years. Healthy lifestyle was measured using an index previously demonstrated to predict cardiovascular disease, consisting of five components: absence of smoking, moderate alcohol consumption, regular physical activity, healthy diet, and ideal body weight. Results: Few participants (3.8% at age 33 years and 2.8% at age 42 years) endorsed all five healthy lifestyle components. Linear regression models, adjusting for potential child- and family-level confounders, revealed that higher distress levels in childhood were negatively associated with healthy lifestyle at age 33 years (ß = -0.11, SE = 0.01, p < .001) and 42 years (ß = -0.13, SE = 0.01, p < .001). Higher distress was also associated with significantly lower odds of endorsing each lifestyle component, except physical activity, at both ages. Additional analyses indicated that childhood distress levels were highest among those whose lifestyle scores were low at age 33 and further declined between ages 33 and 42. Conclusions: Psychological distress in childhood may indicate children at risk of less healthy lifestyle practices later in life. Although our findings are preliminary, psychological distress may also provide an important target for public health interventions aimed at preventing cardiovascular disease.

Post-traumatic stress disorder and cardiometabolic disease: improving causal inference to inform practice.

Post-traumatic stress disorder (PTSD) has been declared 'a life sentence' based on evidence that the disorder leads to a host of physical health problems. Some of the strongest empirical research - in terms of methodology and findings - has shown that PTSD predicts higher risk of cardiometabolic diseases, specifically cardiovascular disease (CVD) and type 2 diabetes (T2D). Despite mounting evidence, PTSD is not currently acknowledged as a risk factor by cardiovascular or endocrinological medicine. This view is unlikely to change absent compelling evidence that PTSD causally contributes to cardiometabolic disease. This review suggests that with developments in methods for epidemiological research and the rapidly expanding knowledge of the behavioral and biological effects of PTSD the field is poised to provide more definitive answers to questions of causality. First, we discuss methods to improve causal inference using the observational data most often used in studies of PTSD and health, with particular reference to issues of temporality and confounding. Second, we consider recent work linking PTSD with specific behaviors and biological processes, and evaluate whether these may plausibly serve as mechanisms by which PTSD leads to cardiometabolic disease. Third, we evaluate how looking more comprehensively into the PTSD phenotype provides insight into whether specific aspects of PTSD phenomenology are particularly relevant to cardiometabolic disease. Finally, we discuss new areas of research that are feasible and could enhance understanding of the PTSD-cardiometabolic relationship, such as testing whether treatment of PTSD can halt or even reverse the cardiometabolic risk factors causally related to CVD and T2D.

Post-traumatic stress disorder symptom duration and remission in relation to cardiovascular disease risk among a large cohort of women.

BACKGROUND: Prior studies suggest that post-traumatic stress disorder (PTSD) is associated with elevated cardiovascular disease (CVD) risk, but effects of duration and remission of PTSD symptoms have rarely been evaluated. METHOD: We examined the association of time-updated PTSD symptom severity, remission and duration with incident CVD risk (552 confirmed myocardial infarctions or strokes) over 20 years in 49 859 women in the Nurses' Health Study II. Among women who reported trauma on the Brief Trauma Questionnaire, PTSD symptoms, assessed by a screener, were classified by symptom severity and chronicity: (a) no symptoms, (b) 1-3 ongoing, (c) 4-5 ongoing, (d) 6-7 ongoing, (e) 1-3 remitted, (f) 4-7 remitted symptoms. Inverse probability weighting was used to estimate marginal structural logistic regression models, adjusting for time-varying and time-invariant confounders. RESULTS: Compared with women with no trauma exposure, women with trauma/no PTSD [odds ratio (OR) 1.30, 95% confidence interval (CI) 1.03-1.65] and women with trauma/6-7 symptoms (OR 1.69, 95% CI 1.08-2.63) had elevated risk of CVD; women with remitted symptoms did not have elevated CVD risk. Among women exposed to trauma, every 5 additional years of PTSD symptomology was associated with 9% higher CVD incidence compared with women with trauma/no PTSD. CONCLUSIONS: The findings suggest that alleviating PTSD symptoms shortly after onset may attenuate CVD risk.

Post-traumatic stress disorder symptoms and risk of hypertension over 22 years in a large cohort of younger and middle-aged women.

BACKGROUND: Post-traumatic stress disorder (PTSD) has been linked to hypertension, but most research on PTSD and hypertension is cross-sectional, and potential mediators have not been clearly identified. Moreover, PTSD is twice as common in women as in men, but understanding of the PTSD-hypertension relationship in women is limited. We examined trauma exposure and PTSD symptoms in relation to incident hypertension over 22 years in 47 514 civilian women in the Nurses' Health Study II. METHOD: We used proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for new-onset hypertension (N = 15 837). RESULTS: PTSD symptoms assessed with a screen were modestly associated with incident hypertension in a dose-response fashion after adjusting for potential confounders. Compared to women with no trauma exposure, women with 6-7 PTSD symptoms had the highest risk of developing hypertension (HR 1.20, 95% CI 1.12-1.30), followed by women with 4-5 symptoms (HR 1.17, 95% CI 1.10-1.25), women with 1-3 symptoms (HR 1.12, 95% CI 1.06-1.18), and trauma-exposed women with no symptoms (HR 1.04, 95% CI 1.00-1.09). Findings were maintained, although attenuated, adjusting for hypertension-relevant medications, medical risk factors, and health behaviors. Higher body mass index and antidepressant use accounted for 30% and 21% of the PTSD symptom-hypertension association, respectively. CONCLUSIONS: Screening for hypertension and reducing unhealthy lifestyle factors, particularly obesity, in women with PTSD may hold promise for offsetting cardiovascular risk.

Do genetic risk scores for body mass index predict risk of phobic anxiety? Evidence for a shared genetic risk factor.

BACKGROUND: Obesity and anxiety are often linked but the direction of effects is not clear. METHOD: Using genetic instrumental variable (IV) analyses in 5911 female participants from the Nurses' Health Study (NHS, initiated 1976) and 3697 male participants from the Health Professional Follow-up Study (HPFS, initiated 1986), we aimed to determine whether obesity increases symptoms of phobic anxiety. As instrumental variables we used the fat mass and obesity-associated (FTO) gene, the melanocortin 4 receptor (MC4R) gene and a genetic risk score (GRS) based on 32 single nucleotide polymorphisms (SNPs) that significantly predict body mass index (BMI). 'Functional' GRSs corresponding with specific biological pathways that shape BMI (adipogenesis, appetite and cardiopulmonary) were considered. The main outcome was phobic anxiety measured by the Crown Crisp Index (CCI) in 2004 in the NHS and in 2000 in the HPFS. RESULTS: In observational analysis, a 1-unit higher BMI was associated with higher phobic anxiety symptoms [women: ß = 0.05, 95% confidence interval (CI) 0.030-0.068; men: ß = 0.04, 95% CI 0.016-0.071). IV analyses showed that BMI was associated with higher phobic anxiety symptoms in the FTO-instrumented analysis (p = 0.005) but not in the GRS-instrumented analysis (p = 0.256). Functional GRSs showed heterogeneous, non-significant effects of BMI on phobic anxiety symptoms. CONCLUSIONS: Our findings do not provide conclusive evidence in favor of the hypothesis that higher BMI leads to higher levels of phobic anxiety, but rather suggest that genes that influence obesity, in particular FTO, may have direct effects on phobic anxiety, and hence that obesity and phobic anxiety may share common genetic determinants.

Genetic vulnerability to diabetes and obesity: does education offset the risk?

The prevalence of type 2 diabetes (T2D) and obesity has recently increased dramatically. These common diseases are likely to arise from the interaction of multiple genetic, socio-demographic and environmental risk factors. While previous research has found genetic risk and education to be strong predictors of these diseases, few studies to date have examined their joint effects. This study investigates whether education modifies the association between genetic background and risk for type 2 diabetes (T2D) and obesity. Using data from non-Hispanic Whites in the Health and Retirement Study (HRS, n = 8398), we tested whether education modifies genetic risk for obesity and T2D, offsetting genetic effects; whether this effect is larger for individuals who have high risk for other (unobserved) reasons, i.e., at higher quantiles of HbA1c and BMI; and whether effects differ by gender. We measured T2D risk using Hemoglobin A1c (HbA1c) level, and obesity risk using body-mass index (BMI). We constructed separate genetic risk scores (GRS) for obesity and diabetes respectively based on the most current available information on the single nucleotide polymorphism (SNPs) confirmed as genome-wide significant predictors for BMI (29 SNPs) and diabetes risk (39 SNPs). Linear regression models with years of schooling indicate that the effect of genetic risk on HbA1c is smaller among people with more years of schooling and larger among those with less than a high school (HS) degree compared to HS degree-holders. Quantile regression models show that the GRS × education effect systematically increased along the HbA1c outcome distribution; for example the GRS × years of education interaction coefficient was -0.01 (95% CI = -0.03, 0.00) at the 10th percentile compared to -0.03 (95% CI = -0.07, 0.00) at the 90th percentile. These results suggest that education may be an important socioeconomic source of heterogeneity in responses to genetic vulnerability to T2D.

A prospective study of dominance and coronary heart disease in the Normative Aging Study.

The purpose of this study was to examine the prospective relation between dominance, as assessed by a Minnesota Multiphasic Personality Inventory (MMPI-2)-derived dominance scale, and incidence of coronary heart disease (CHD), independent of participants' anger level. The study was performed in the VA Normative Aging Study, an ongoing cohort of older (mean age 61 years) men. A total of 1,225 men who were free of CHD in 1986 completed the MMPI-2. A factor analysis of selected MMPI items provided the basis for the construction of a dominance scale and an anger scale. During an average of 8 years of follow-up, 158 cases of incident CHD occurred, including 29 cases of fatal CHD, 69 cases of nonfatal myocardial infarction (MI), and 60 cases of angina pectoris (AP). Compared with men reporting the lowest levels of dominance (lower tertile), the multivariate-adjusted relative risk among men reporting the highest levels of dominance (upper tertile) was 1.80 (95% confidence interval [CI] 1.21 to 3.24) for combined nonfatal MI and fatal CHD. Additional adjustment for anger scores did not significantly alter this relation. There was no significant relation between dominance and AP. Our data suggest that dominance is an independent risk factor for CHD in older men.

Going to the heart of the matter: do negative emotions cause coronary heart disease?

OBJECTIVE: Negative emotions, such as anger, anxiety, and depression, have emerged as potentially important risk factors for coronary heart disease. The purpose of this article is to consider the nature and function of emotions, to review epidemiological evidence for an association between the three negative emotions and coronary heart disease (CHD), to discuss briefly the mechanisms by which emotions may be linked to CHD, and to consider this evidence in light of theoretical insights provided by mainstream psychological research on emotions. METHODS: We collected articles published between 1980 and 1998 on the relationship between each negative emotion and CHD. We also collected review articles or chapters published during the same time period that considered mechanisms by which emotions may increase CHD risk. We used a qualitative approach to review the published literature. RESULTS: Evidence that anxiety is involved in the onset of CHD is strongest, whereas evidence for an association between anger and CHD is limited but suggestive. Although depression has consistently been linked to mortality following a myocardial infarction, evidence for its role in the onset of coronary disease is quite mixed. Numerous unresolved issues leave our current understanding of the emotion-health relationship incomplete. Psychological theories of emotion are considered to help address gaps in our knowledge. CONCLUSION: Growing evidence indicates that negative emotions may influence the development of CHD. The focused and specific consideration of negative emotions and their possible role in the etiology of CHD gives insight into current knowledge and suggests important directions for future research.

Social conditions and distress in elderly persons: findings from the MacArthur Studies of Successful Aging.

The purpose of this study was to determine separate and joint associations of race/ethnicity and socioeconomic status (SES) with psychological distress among older high-functioning adults and to examine 2 psychosocial resources that may explain these associations. Participants were 70-79-year-old individuals (n = 1,189) participating in the MacArthur Studies of Successful Aging program, a 3-site study of community-dwelling men and women. Participants represented the top third of their peers in terms of functional ability in 1988. Additive and interactive models were used to examine cross-sectional associations among race/ethnicity, SES, and distress. Although decreases in distress generally occur with aging, findings suggest that social structural factors can influence distress even among elderly people. Blacks were less distressed than Whites when SES was controlled. There was a gradient between education and distress among Whites but not among Blacks. Measures of social support and control did not mediate effects of race/ethnicity on distress. These results differ from those of previous studies and indicate that age and functional status should be considered in examinations of relationships among race/ethnicity, SES, and distress.

Challenges in modelling the random structure correctly in growth mixture models and the impact this has on model mixtures.

Lifecourse trajectories of clinical or anthropological attributes are useful for identifying how our early-life experiences influence later-life morbidity and mortality. Researchers often use growth mixture models (GMMs) to estimate such phenomena. It is common to place constrains on the random part of the GMM to improve parsimony or to aid convergence, but this can lead to an autoregressive structure that distorts the nature of the mixtures and subsequent model interpretation. This is especially true if changes in the outcome within individuals are gradual compared with the magnitude of differences between individuals. This is not widely appreciated, nor is its impact well understood. Using repeat measures of body mass index (BMI) for 1528 US adolescents, we estimated GMMs that required variance-covariance constraints to attain convergence. We contrasted constrained models with and without an autocorrelation structure to assess the impact this had on the ideal number of latent classes, their size and composition. We also contrasted model options using simulations. When the GMM variance-covariance structure was constrained, a within-class autocorrelation structure emerged. When not modelled explicitly, this led to poorer model fit and models that differed substantially in the ideal number of latent classes, as well as class size and composition. Failure to carefully consider the random structure of data within a GMM framework may lead to erroneous model inferences, especially for outcomes with greater within-person than between-person homogeneity, such as BMI. It is crucial to reflect on the underlying data generation processes when building such models.

DNA methylation of stress-related genes and LINE-1 repetitive elements across the healthy human placenta.

OBJECTIVES: DNA methylation is known to play a critical role in regulating development of placental morphology and physiology. The methylation of genes mediated by glucocorticoid hormones may be particularly vulnerable to intrauterine stress in the placenta. However little is known about DNA methylation of stress-related genes within a healthy placenta, and particularly whether methylation occurs uniformly across different regions of the placenta, which is a critical question for researchers seeking to analyze methylation patterns. We examined DNA methylation across four regions of the placenta to evaluate methylation levels of stress-related genes within a healthy placenta, and to evaluate whether methylation patterns vary by sampling location. STUDY DESIGN: We evaluated levels of DNA methylation of three stress-related genes: NR3C1, BDNF, and 11B-HSD2 and of the repetitive element, LINE-1, in four different sample locations of 20 healthy placentas. MAIN OUTCOME MEASURES: Pyrosequencing was used to quantify levels of methylation at CpG sites within the promoter regions of each of the three stress-related genes, and global methylation of LINE-1. RESULTS: Very low levels of methylation were found across all three stress-related genes; no gene showed a median methylation level greater than 4.20% across placental regions. Variation in methylation between placental regions for stress-related genes and for LINE-1 was minimal. CONCLUSIONS: Our data suggest that these frequently studied stress-related genes have low levels of methylation in healthy placenta tissue. Minimal variation between sites suggests that sampling location does not affect DNA methylation analyses of these genes or of LINE-1 repetitive elements.

Angry breathing: A prospective study of hostility and lung function in the Normative Aging Study.

BACKGROUND: Hostility and anger are risk factors for, or co-occur with, many health problems of older adults such as cardiovascular diseases, all-cause mortality, and asthma. Evidence that negative emotions are associated with chronic airways obstruction suggests a possible role for hostility in the maintenance and decline of pulmonary function. This study tests the hypothesis that hostility contributes to a faster rate of decline in lung function in older adults. METHODS: A prospective examination was undertaken of the effect of hostility on change in lung function over time. Data are from the VA Normative Aging Study, an ongoing cohort of older men. Hostility was measured in 1986 in 670 men who also had an average of three pulmonary function examinations obtained over an average of 8.2 years of follow up. Hostility was ascertained using the 50-item MMPI based Cook-Medley Hostility Scale. Pulmonary function was assessed using spirometric tests to obtain measures of forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC). RESULTS: Baseline pulmonary function differed between high and medium/low hostility groups (mean (SE) percent predicted FEV(1) 88.9 (18.5) v 95.3 (16.9) and FVC 92.5 (16.5) v 98.9 (15.9), respectively; p < 0.01 for both). This overall association between higher hostility and reduced lung function remained significant after adjusting for smoking and education, although the effect size was attenuated for both FEV1 and FVC. Higher hostility was associated with a more rapid decline in lung function, and this effect was unchanged and remained significant for FEV1)in multivariate models but was attenuated for FVC. Each standard deviation increase in hostility was associated with a loss in FEV1 of approximately 9 ml/year. CONCLUSIONS: This study is one of the first to show prospectively that hostility is associated with poorer pulmonary function and more rapid rates of decline among older men.

Socioeconomic status, hostility, and risk factor clustering in the Normative Aging Study: any help from the concept of allostatic load?

OBJECTIVE: To examine the relationships between socioeconomic status (SES), psychosocial vulnerability (hostility), and allostatic load. Allostatic load refers to the cumulative physiological cost of adaptation to stress. METHOD: We examined the relationships between SES (as measured by educational attainment), hostility, and allostatic load in the Normative Aging Study, a longitudinal study of community-dwelling men aged 21 to 80 years and free of known chronic medical conditions at entry in the 1960s. In 1986, the revised Minnesota Multiphasic Personality Inventory was administered by mail, from which a hostility measure was derived by summing the scores from three Cook-Medley subscales: Hostile Affect, Hostile Attribution, Aggressive Responding. An index of allostatic load was constructed from data collected during physical exams conducted between 1987 and 1990 (i.e. measures reflecting "wear and tear" on the cardiovascular, endocrine, and metabolic systems). Cross-sectional relationships between education, hostility, and allostatic load were examined in 818 men. RESULTS: Separate linear regression analyses indicated that lower levels of educational attainment and greater hostility were both associated with higher allostatic load scores (p < .05 and p < .01, respectively). Less education was also associated with higher hostility (p < .001). When allostatic load was regressed simultaneously on education and hostility, the effect of education was attenuated, while hostility (p < .05) maintained an independent effect. CONCLUSIONS: Our findings suggest that lower levels of education and greater hostility are associated with greater "wear and tear" on the body. The effects of education on allostatic load may be mediated by hostility.

Is the glass half empty or half full? A prospective study of optimism and coronary heart disease in the normative aging study.

OBJECTIVE: A sense of optimism, which derives from the ways individuals explain causes of daily events, has been shown to protect health, whereas pessimism has been linked to poor physical health. We examined prospectively the relationship of an optimistic or pessimistic explanatory style with coronary heart disease incidence in the Veterans Affairs Normative Aging Study, an ongoing cohort of older men. METHODS AND RESULTS: In 1986, 1306 men completed the revised Minnesota Multiphasic Personality Inventory, from which we derived the bipolar revised Optimism-Pessimism Scale. During an average of 10 years of follow-up, 162 cases of incident coronary heart disease occurred: 71 cases of incident nonfatal myocardial infarction, 31 cases of fatal coronary heart disease, and 60 cases of angina pectoris. Compared with men with high levels of pessimism, those reporting high levels of optimism had multivariate-adjusted relative risks of 0.44 (95% confidence interval = 0.26-0.74) for combined nonfatal myocardial infarction and coronary heart disease death and 0.45 (95% confidence interval = 0.29-0.68) for combined angina pectoris, nonfatal myocardial infarction, and coronary heart disease death. A dose-response relation was found between levels of optimism and each outcome (p value for trend,.002 and.0004, respectively). CONCLUSIONS: These results suggest that an optimistic explanatory style may protect against risk of coronary heart disease in older men.

Anxiety and coronary heart disease: a synthesis of epidemiological, psychological, and experimental evidence.

The purpose of this review is to examine the epidemiological, psychological, and experimental evidence for an association between anxiety and coronary heart disease (CHD). Papers published during the years 1980-1996 on anxiety and CHD and relevant publications from earlier years were selected for this review. Epidemiologic evidence suggests that anxiety may be a risk factor for the development of CHD. Chronic anxiety may increase the risk of CHD by: (a) influencing health behaviors (e.g. smoking); (b) promoting atherogenesis (e.g. via increased risk of hypertension); and (c) triggering fatal coronary events, either through arrhythmia, plaque rupture, coronary vasospasm, or thrombosis. Electrophysiologic evidence is particularly compelling: anxiety appears to be associated with abnormal cardiac autonomic control, which may indicate increased risk of fatal ventricular arrhythmias. The strength, consistency, and dose-response gradient of the association between anxiety and CHD, together with the biologic plausibility of the experimental evidence, suggest that anxiety may contribute to risk of CHD and that the relationship warrants further investigation.

Is educational attainment associated with shared determinants of health in the elderly? Findings from the MacArthur Studies of Successful Aging.

OBJECTIVE: To investigate the association of educational attainment with an array of risk factors for poor health among high-functioning older men and women. METHODS: Cross-sectional analyses of psychosocial, behavioral, and biological factors and educational attainment were conducted using data from a population-based cohort study of older men and women. Participants consisted of 70- to 79-year-old residents of communities of East Boston, MA; New Haven, CT; and Durham County, NC (N = 1192) participating in the Established Populations for Epidemiologic Studies of the Elderly programs, a three-site longitudinal study of community-dwelling men and women. Participants were selected on the basis of high physical and cognitive function, representing approximately the top third of their peers in terms of functional ability in 1988. In-home interviews were conducted. Associations among education and behavioral (e.g., cigarette smoking and physical activity), biological (e.g., pulmonary function, serum cholesterol), psychological (e.g., self-efficacy, anxiety), and social (e.g., networks and support) factors were examined. RESULTS: Low levels of education were associated with poorer psychological function (less mastery, efficacy, happiness), less optimal health behaviors (increased tobacco consumption and decreased levels of physical activity), poorer biological conditions (decreased pulmonary function, increased body mass index and waist-to-hip ratio), and larger social networks (increased number of contacts, decreased negative support). Several factors (alcohol consumption, high-density lipoprotein cholesterol) were nonlinearly related to educational attainment. CONCLUSIONS: Educational attainment is associated with a broad array of psychosocial and biological conditions among the elderly. That an education gradient functions over an array of factors that structure daily life, even in later life in a healthy population, may suggest how socioeconomic status influences health.

Is worrying bad for your heart? A prospective study of worry and coronary heart disease in the Normative Aging Study.

BACKGROUND: Worry is an important component of anxiety, which recent work suggests is related to increased incidence of coronary heart disease (CHD). Chronic worry has also been associated with decreased heart rate variability. We hypothesized that high levels of worry may increase CHD risk. METHOD AND RESULTS: We examined prospectively the relationship of worry with CHD incidence in the Normative Aging Study, an ongoing cohort of older men. In 1975, 1759 men free of diagnosed CHD completed a Worries Scale, indicating the extent to which they worried about each of five worry domains: social conditions, health, financial, self-definition, and aging. During 20 years of follow-up, 323 cases of incident CHD occurred: 113 cases of nonfatal myocardial infarction (MI); 86 cases of fatal CHD; and 124 cases of angina pectoris. Worry about social conditions was the domain most strongly associated with incident CHD. Compared with men reporting the lowest levels of social conditions worry, men reporting the highest levels had multivariate adjusted relative risks of 2.41 (95% CI, 1.40 to 4.13) for nonfatal MI and 1.48 (95% CI, 0.99 to 2.20) for total CHD (nonfatal MI and fatal CHD). A dose-response relation was found between level of worry and both nonfatal MI (P for trend, .002) and total CHD (P for trend, .04). CONCLUSIONS: These results suggest that high levels of worry in specific domains may increase the risk of CHD in older men.