Associations of Early-Life Adversity With Later-Life Epigenetic Aging Profiles in the Multi-Ethnic Study of Atherosclerosis.

Epigenetic biomarkers of accelerated aging have been widely used to predict disease risk and may enhance our understanding of biological mechanisms between early-life adversity and disparities in aging. With respect to childhood adversity, most studies have used parental education or childhood disadvantage and/or have not examined the role played by socioemotional or physical abuse and trauma in epigenetic profiles at older ages. This study leveraged data from the Multi-Ethnic Study of Atherosclerosis (MESA) on experiences of threat and deprivation in participants' early lives (i.e., before the age of 18 years) to examine whether exposure to specific dimensions of early-life adversity is associated with epigenetic profiles at older ages that are indicative of accelerated biological aging. The sample included 842 MESA respondents with DNA methylation data collected between 2010 and 2012 who answered questions on early-life adversities in a 2018-2019 telephone follow-up. We found that experiences of deprivation, but not threat, were associated with later-life GrimAge epigenetic aging signatures that were developed to predict mortality risk. Results indicated that smoking behavior partially mediates this association, which suggests that lifestyle behaviors may act as downstream mechanisms between parental deprivation in early life and accelerated epigenetic aging in later life.

The Great Recession worsened blood pressure and blood glucose levels in American adults.

Longitudinal, individual-specific data from the Multi-Ethnic Study of Atherosclerosis (MESA) provide support for the hypothesis that the 2008 to 2010 Great Recession (GR) negatively impacted the health of US adults. Results further advance understanding of the relationship by (i) illuminating hypothesized greater negative impacts in population subgroups exposed to more severe impacts of the GR and (ii) explicitly controlling for confounding by individual differences in age-related changes in health over time. Analyses overcome limitations of prior work by (i) employing individual-level data that avoid concerns about ecological fallacy associated with prior reliance on group-level data, (ii) using four waves of data before the GR to estimate and control for underlying individual-level age-related trends, (iii) focusing on objective, temporally appropriate health outcomes rather than mortality, and (iv) leveraging a diverse cohort to investigate subgroup differences in the GR's impact. Innovative individual fixed-effects modeling controlling for individual-level age-related trajectories yielded substantively important insights: (i) significant elevations post-GR for blood pressure and fasting glucose, especially among those on medication pre-GR, and (ii) reductions in prevalence and intensity of medication use post-GR. Important differences in the effects of the GR are seen across subgroups, with larger effects among younger adults (who are likely still in the labor force) and older homeowners (whose declining home wealth likely reduced financial security, with less scope for recouping losses during their lifetime); least affected were older adults without a college degree (whose greater reliance on Medicare and Social Security likely provided more protection from the recession).

On the Biopsychosocial Costs of Alienated Labor.

Data from the national, longitudinal Mid-Life in the US (MIDUS) study were used to examine work alienation and its relationship to biological health as well as psychological and social functioning. The alienation measure focuses on the autonomy and creativity the work provides. We hypothesized that alienated work would have negative associations with each of the three domains: in biology, higher 'allostatic load' (biological dysregulation); in psychology, poorer cognitive performance; and socially, negative impacts on family life. The outcomes are generally as predicted, though there are notable differences for men and women.

Recommendations for epidemiologic and phenotypic research in polycystic ovary syndrome: an androgen excess and PCOS society resource.

STUDY QUESTION: What are the best practices for undertaking epidemiologic and phenotypic studies in polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: Best practices for the undertaking of epidemiologic and phenotypic studies in PCOS are outlined. WHAT IS KNOWN ALREADY: Currently methodologies used for studies of PCOS epidemiology and phenotypes vary widely, and the comparability of studies is low, reducing the ability to harmonize studies. STUDY DESIGN, SIZE, DURATION: The Androgen Excess and PCOS (AE-PCOS) Society established a Task Force to draft a research resource for epidemiologic and phenotypic studies in PCOS, with the aim of providing guidelines on study design and execution, insights into the limitations and alternatives and protocols to be used, taking into consideration a global perspective. PARTICIPANTS/MATERIALS, SETTING, METHODS: A targeted review of the literature was carried out as necessary. MAIN RESULTS AND THE ROLE OF CHANCE: High level recommendations include the following: (i) Before initiating the study, a number of critical factors should be addressed including selecting the population and diagnostic criteria (which should ideally align with the recommendations of the International Guidelines), the type of observational study to be undertaken and the primary and secondary endpoint(s) of the study.(ii) To assess the 'natural' or true phenotype and epidemiology of PCOS, the least medically biased, broadest and most generalizable population, and the broadest definition of PCOS, should be used.(iii) Four PCOS phenotypes (Phenotypes A through D), based on the presence or absence of three general features (oligo-anovulation, hyperandrogenism and polycystic ovarian morphology), should be ascertained.(iv) In epidemiologic and phenotypic studies, the detection of PCOS rests on the accuracy and sensitivity of the methods used for assessing the individual features of the disorder, and how 'normal' is defined.(v) Although an assessment algorithm that minimizes the use of certain measures (e.g. androgen levels and/or ovarian ultrasonography) can be devised, when possible it is preferable to uniformly assess all subjects for all parameters of interest.(vi) The inclusion of subjects in epidemiologic studies who do not appear to have PCOS (i.e. 'non-PCOS') will provide the necessary cohort to establish population-specific normative ranges for the various features of PCOS. (vii) Epidemiologic studies of PCOS in unselected populations will yield relatively limited numbers of PCOS subjects available for genetic study; alternatively, large population-based epidemiologic studies of PCOS will potentially generate large numbers of unaffected individuals that may serve as genetic controls. (viii) Epidemiologic studies of PCOS will benefit from a clear governance structure and should begin by informing, educating and engaging both the formal and informal leaders of the populations targeted for study. (ix) In designing their study investigators should, in advance, establish statistical power and recognize, manage and account for inherent biases. (x) Subjects suspected of having PCOS but who do not/cannot complete their evaluation (i.e. have 'possible PCOS') can be included by imputation, assigning them a 'diagnostic weight' based on those subjects of similar clinical phenotype that have completed the study. (xi) In obtaining, storing and retrieving subject data, subjects should be assessed consecutively using a uniform data collection form; providing as complete and in depth data as possible. (xii) Maintenance of both paper and electronic medical records should focus on ensuring data quality, accuracy and institutional ethical compliance, and familiarity with country-dependent laws, including biobanking-specific laws, tissue laws and research laws. (xiii) In obtaining and biobanking study samples, these should be ideally collected at the time of the first assessment. (xiv) Access to stored data sets should ideally be granted to other bona fide researchers conducting research in the public interest. (xv) SOPs detailing the exact method of each of the activities for handling the data and the samples are necessary to ensure that all methods are performed uniformly. (xvi) Epidemiologic studies of PCOS must be resourced adequately. LIMITATIONS, REASONS FOR CAUTION: As with all reports involving expert interpretation of experiential and published data, inherent individual biases are possible. This risk is minimized in the present study by including experts from varying fields of study, aligning with recent international evidence-based guidelines and obtaining consensus approval of the recommendations from the Task Force and the board of the AE-PCOS. WIDER IMPLICATIONS OF THE FINDINGS: These guidelines should encourage investigators worldwide to undertake much needed epidemiologic studies of PCOS, increasing the validity, integrity and comparability of the data. STUDY FUNDING/COMPETING INTEREST(S): The study received no funding. R.A. serves as consultant for Medtronic, Spruce Biosciences and Ansh Labs; has received research funding from Ferring Pharmaceuticals; and is on the advisory board of Martin Imaging; R.L. has received research funding from MSD Pharmaceuticals; J.L. has received fees and/or grant support from the Dutch Heart Association, The Netherlands Organisation for Health Research and Development (ZonMw), Ferring Pharmaceuticals, Danone, Euroscreen/Ogeda and Titus Health Care; H.T. receives grant funding from the National Health and Medical Research Council; K.K., L.M.-P., S.S.M. and B.O.Y. have no potential conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Trends in Racial/Ethnic and Nativity Disparities in Cardiovascular Health Among Adults Without Prevalent Cardiovascular Disease in the United States, 1988 to 2014.

Background: Trends in cardiovascular disparities are poorly understood, even as diversity increases in the United States. Objective: To examine U.S. trends in racial/ethnic and nativity disparities in cardiovascular health. Design: Repeated cross-sectional study. Setting: NHANES (National Health and Nutrition Examination Survey), 1988 to 2014. Participants: Adults aged 25 years or older who did not report cardiovascular disease. Measurements: Racial/ethnic, nativity, and period differences in Life's Simple 7 (LS7) health factors and behaviors (blood pressure, cholesterol, hemoglobin A1c, body mass index, physical activity, diet, and smoking) and optimal composite scores for cardiovascular health (LS7 score ≥10). Results: Rates of optimal cardiovascular health remain below 40% among whites, 25% among Mexican Americans, and 15% among African Americans. Disparities in optimal cardiovascular health between whites and African Americans persisted but decreased over time. In 1988 to 1994, the percentage of African Americans with optimal LS7 scores was 22.8 percentage points (95% CI, 19.3 to 26.4 percentage points) lower than that of whites in persons aged 25 to 44 years and 8.0 percentage points (CI, 6.4 to 9.7 percentage points) lower in those aged 65 years or older. By 2011 to 2014, differences decreased to 10.6 percentage points (CI, 7.4 to 13.9 percentage points) and 3.8 percentage points (CI, 2.5 to 5.0 percentage points), respectively. Disparities in optimal LS7 scores between whites and Mexican Americans were smaller but also decreased. These decreases were due to reductions in optimal cardiovascular health among whites over all age groups and periods: Between 1988 to 1994 and 2011 to 2014, the percentage of whites with optimal cardiovascular health decreased 15.3 percentage points (CI, 11.1 to 19.4 percentage points) for those aged 25 to 44 years and 4.6 percentage points (CI, 2.7 to 6.5 percentage points) for those aged 65 years or older. Limitation: Only whites, African Americans, and Mexican Americans were studied. Conclusion: Cardiovascular health has declined in the United States, racial/ethnic and nativity disparities persist, and decreased disparities seem to be due to worsening cardiovascular health among whites rather than gains among African Americans and Mexican Americans. Multifaceted interventions are needed to address declining population health and persistent health disparities. Primary Funding Source: National Institute of Neurological Disorders and Stroke and National Center for Advancing Translational Sciences of the National Institutes of Health.

Neighborhood Characteristics are Associated with Racial and Gender Variation in Walking among Older Adults: the Cardiovascular Health Study.

OBJECTIVE: To examine variation by race and gender in the association between neighborhood socioeconomic status and walking among community-dwelling older adults. DESIGN: Cross-sectional. SETTING: Cardiovascular Health Study, a longitudinal population-based cohort. PARTICIPANTS: 4,849 adults, aged > 65 years. MEASUREMENTS: Participants reported the number of city blocks walked in the prior week. Neighborhood socioeconomic status (NSES) was measured at the level of the census tract. Negative binominal regression models were constructed to test the association between NSES and blocks walked. In the fully adjusted models, we included two-way and three-way interaction terms among race, gender, and NSES. RESULTS: In adjusted analyses, among White residents in the lowest NSES quartile (most disadvantaged), men walked 64% more than women (P<.001), while in the highest NSES (most advantaged), men walked 43% more than women (P<.001). Among African American residents in the lowest NSES quartile, men walked 196% more blocks than women (P<.001). CONCLUSIONS: Female gender is more strongly associated with walking for African Americans than for Whites in low SES neighborhoods but had a similar association with walking for both African Americans and Whites in high SES neighborhoods.

Life course socioeconomic status and longitudinal accumulation of allostatic load in adulthood: multi-ethnic study of atherosclerosis.

OBJECTIVES: We examined the association of childhood and adult socioeconomic status with longitudinal change in allostatic load (AL), a measure of biological dysfunction. METHODS: The study sample included 6135 participants from the Multi-Ethnic Study of Atherosclerosis, aged 45 to 84 years, recruited in 2000 from 6 US counties; 3 follow-up examinations took place through September 2011. We calculated standardized scores for several metabolic and cardiovascular components relative to accepted clinical cut points for "higher risk" and then summed them to create an overall index of AL. We used mixed effects growth curve models to assess the relationship between socioeconomic status and AL as a linear function of time passed since the baseline examination; we included random effects for the intercept and slope. RESULTS: Among those with lower baseline AL (< median), high adult education was associated with a significantly slower increase in AL over time, whereas there was no significant association among those with higher baseline AL. CONCLUSIONS: The relationship between socioeconomic status and patterns of change in health parameters may vary over time and with the accumulation of biological risk.

Exploring psychosocial pathways between neighbourhood characteristics and stroke in older adults: the cardiovascular health study.

OBJECTIVES: to investigate whether psychosocial pathways mediate the association between neighbourhood socioeconomic disadvantage and stroke. METHODS: prospective cohort study with a follow-up of 11.5 years. SETTING: the Cardiovascular Health Study, a longitudinal population-based cohort study of older adults ≥65 years. MEASUREMENTS: the primary outcome was adjudicated incident ischaemic stroke. Neighbourhood socioeconomic status (NSES) was measured using a composite of six census-tract variables. Psychosocial factors were assessed with standard measures for depression, social support and social networks. RESULTS: of the 3,834 white participants with no prior stroke, 548 had an incident ischaemic stroke over the 11.5-year follow-up. Among whites, the incident stroke hazard ratio (HR) associated with living in the lowest relative to highest NSES quartile was 1.32 (95% CI = 1.01-1.73), in models adjusted for individual SES. Additional adjustment for psychosocial factors had a minimal effect on hazard of incident stroke (HR = 1.31, CI = 1.00-1.71). Associations between NSES and stroke incidence were not found among African-Americans (n = 785) in either partially or fully adjusted models. CONCLUSIONS: psychosocial factors played a minimal role in mediating the effect of NSES on stroke incidence among white older adults.

Personal Health Literacy and Life Simple 7: The Multi-Ethnic Study of Atherosclerosis.

Background: Personal Health literacy (PHL) is essential in cardiovascular risk management. Hindrances in PHL can lead to poor cardiovascular outcomes. Purpose: To investigate whether limited PHL is associated with lower likelihoods of i) overall cardiovascular health and ii) individual cardiovascular health components as defined by the American Heart Association's Life Simple (LS7). Methods: Multi-Ethnic Study of Atherosclerosis participants (N=3719; median age[range]: 59[45-84]) completed a PHL questionnaire in 2016-2018. PHL was classified as limited (score ≥10) or adequate (score <10). LS7 components were measured in 2000-2002. Robust Poisson regression was employed to compute prevalence ratios and 95% confidence intervals (PR[95%CI]) of LS7 measures. Results: 14.7% of participants had limited PHL. Limited PHL was associated with lower likelihoods of optimal LS7 (0.69[0.50, 0.95], p=0.02) and average LS7 (0.95[0.88, 1.02], p=0.15) after adjustment. Limited PHL was significantly associated with a 7% lower likelihood of ideal fasting blood glucose level after adjustment (0.93[0.89, 0.98], p<0.01). Discussion: Limited PHL was modestly associated with suboptimal cardiovascular health and elevated blood glucose, independent of income and education. Translation to Health Education Practice: Health educators and providers should equitably address PHL barriers to improve cardiovascular management and quality of care for patients and communities.

Diurnal dynamic range as index of dysregulation of system dynamics. A cortisol examplar using data from the Study of Midlife in the United States.

We discuss the importance of including measures of dysregulated system dynamics in the operationalization of allostatic load. The concept of allostatic load, as originally proposed by McEwen and Stellar, included dysregulation not only in the resting state of physiological systems, but also in system dynamics. We describe previous work on cortisol diurnal dynamic range (peak to nadir spread) as an index of the health of the hypothalamic-pituitary-adrenal axis, with compression of dynamic range being a marker of dysregulation. In particular, we review the evidence for a) diurnal dynamic range compression in people from disadvantaged backgrounds, b) cross-sectional association of cortisol diurnal dynamic range compression with dysregulation in other systems' resting states, and c) cross-sectional association of cortisol diurnal dynamic range compression with lower scores on cognitive testing. Then, we present new data from the Study of Midlife in the United States (MIDUS) on longitudinal associations of cortisol dynamic range compression with subsequent cognitive decline and all-cause mortality. Briefly, each standard deviation decrement in cortisol diurnal dynamic range is associated with adjusted mortality hazard ratio of 1.35 (95% confidence interval: 1.19, 1.54). Among those who scored at median or lower in executive functioning at baseline and survive, each standard deviation decrement in cortisol dynamic range is associated with 1% greater decline in executive functioning over a decade (95% confidence interval: 0.4%, 2.0%). We conclude that including measures of system dynamics like diurnal dynamic range in the next generation of allostatic load measurement will likely advance understanding of the cumulative physiological burden of chronic stress and life experiences, and improve the prediction of future health consequences.

Association of Exposure to Abuse, Nurture, and Household Organization in Childhood With 4 Cardiovascular Disease Risks Factors Among Participants in the CARDIA Study.

Background We investigated associations of childhood abuse with 4 cardiovascular disease risk factors in adulthood, and whether exposure to nurturing and household organization in childhood mitigated these associations. Methods and Results The CARDIA (Coronary Artery Risk Development in Young Adults) study (baseline examination, 1985-1986) was used to examine associations of childhood exposures (measured retrospectively at the year 15 examination) with incident obesity, type 2 diabetes, hypertension, and hyperlipidemia (assessed from baseline to year 30). Race- and sex-stratified Cox proportional hazards models were used to examine associations of exposure to childhood abuse with incident cardiovascular disease risk factors. Interaction terms between exposure to abuse and exposure to nurturing relationship and household organization were included to test for effect modifications. Exposure to occasional/frequent abuse (versus no abuse) was associated with incident type 2 diabetes among White men (hazard ratio [HR], 1.81; 95% CI, 1.06-3.08). Exposure to low versus no abuse was associated with incident hyperlipidemia among White men (HR, 1.35; 95% CI, 1.09-1.67) and White women (HR, 1.26; 95% CI, 1.01-1.56). Risks of incident hyperlipidemia were higher for White women who experienced abuse and lived in dysfunctional households (HR, 3.61; 95% CI, 1.62-8.05) or households with low levels of organization (HR, 2.05; 95% CI, 1.25-3.36) compared with White women who experienced abuse but lived in well-organized households (HR, 0.66; 95% CI, 0.41-1.06). Similar patterns were seen for Black men who lived in dysfunctional households (HR, 3.62; 95% CI, 1.29-10.12) or households with low organization (HR, 2.01; 95% CI, 1.08-3.72). Conclusions We identified race- and sex-specific associations of childhood exposures with incident cardiovascular disease risk factors. The associations of household organization and dysfunction with cardiovascular disease risks merits further investigation.

Major Lipids and Future Risk of Pneumonia: 20-Year Observation of the Atherosclerosis Risk in Communities (ARIC) Study Cohort.

BACKGROUND: Circulating lipids have been implicated as important modulators of immune response, and altered lipid levels correlate with the severity of infection. However, long-term prognostic implications of lipid levels regarding future infection risk remain unclear. The current project aims to explore whether baseline lipid levels are associated with risk of future serious infection, measured by hospitalization for pneumonia. METHODS: A retrospective analysis was performed in 13,478 participants selected from the Atherosclerosis Risk in Communities (ARIC) study, a large community-based longitudinal cohort in the United States with a median follow-up time of >20 years. First incident of hospitalization for pneumonia was identified through hospital discharge records. Cox proportional hazard models were used to assess the association of baseline major lipid levels (total cholesterol, low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], triglycerides) with time to first pneumonia hospitalization. RESULTS: A total of 1969 (14.61%) participants had a pneumonia hospitalization during a median follow-up time of 21.5 years. The hazard ratio (HR) for pneumonia hospitalization was 0.90 (95% confidence interval, 0.87-0.92) for every 10-mg/dL increase in baseline HDL-C, and 1.02 (95% confidence interval, 1.02-1.03) for every 10-mg/dL increase in baseline triglycerides. HDL-C and triglycerides both remained significant predictors of pneumonia hospitalization after multivariable adjustment. Such associations were not seen with baseline LDL-C or total cholesterol levels. CONCLUSION: Lower baseline HDL-C and higher triglyceride levels were strongly associated with increased risk of long-term pneumonia hospitalization in a large longitudinal US cohort.

Health Literacy Within a Diverse Community-Based Cohort: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Health literacy has yet to be described in a non-clinical, racially diverse, community-based cohort. METHODS: Four questions assessing health literacy were asked during annual phone encounters with Multi-Ethnic Study of Atherosclerosis (MESA) participants between 2016 and 2018 (n = 3629). We used prevalence ratios (PRs) with 95% confidence intervals (CIs) to characterize how demographic and acculturation factors related to limited health literacy. Models adjusted for age, sex, and race/ethnicity, and race/ethnicity-stratified models were also examined. RESULTS: Limited health literacy was prevalent in 15.4% of the sample. Participants who were older, female, lower-income, or less acculturated were at greater risk for having limited health literacy. Chinese, Hispanic, and Black participants were more likely than White participants to have limited health literacy. Patterns were similar when stratified by race/ethnicity. DISCUSSION: Within MESA limited health literacy was common, particularly among Chinese and Hispanic participants, with some of the variance explained by differences in acculturation.

Intergenerational mentoring, eudaimonic well-being and gene regulation in older adults: A pilot study.

To clarify the biological mechanisms underlying the relationship between pro-social behavior and health, this pilot study examined the impact of a 9-month intergenerational helping intervention on conserved transcriptional response to adversity (CTRA) gene expression profiles, which are characterized by up-regulation of genes involved in inflammation and down-regulation of genes involved in antiviral defenses. The Generation Xchange program trains and places older (age 50+) volunteers in K-3rd grade classrooms to aid students' academic development (reading and math) and address behavioral issues (e.g., inability to focus during class, behaviors that disrupt class). Volunteers were predominately women (89%) and African American (94%) from the neighborhoods around the schools. Repeated measures planned contrast analysis of 53 CTRA indicator transcripts in 50 blood samples collected from 18 individuals on 2-3 occasions revealed a significant reduction in CTRA gene expression from baseline to the average of 3- and 9-month follow-up. The magnitude of individual decrease in CTRA gene expression correlated with the magnitude of individual increase in eudaimonic well-being over time (net of changes in hedonic well-being). In addition to clarifying biological pathways through which pro-social behavior might impact health, these pilot data suggest that the GenX program may have favorable effects on immune cell gene regulation.

Race/ethnicity, neighborhood socioeconomic status and cardio-metabolic risk.

OBJECTIVE: To determine the association between neighborhood socioeconomic status (NSES) and cardio-metabolic risk and whether this relationship differs by race/ethnicity. METHODS: Participants in the Multi-Ethnic Study of Atherosclerosis (n = 5750), ages 45-84 years, from 6 US counties, including 5 examinations from 2000 to 2012. We calculated a modified allostatic load (AL) index, indicating cardio-metabolic risk. NSES score included census-derived measures at census tract of residence. Mixed effects growth curve models were used to assess linear and non-linear associations between NSES and AL at baseline and over time. RESULTS: Higher NSES was associated with lower AL across race/ethnic groups; considering NSES quintiles, significant associations were found only for the highest NSES quintiles (difference of -0.86 and -1.15 for white and Hispanic participants) vs. the lowest. We found no significant association between NSES and change in AL over time. DISCUSSION: Our findings suggest that the relationship between NSES and AL reflects the health benefits of living in the most advantaged neighborhoods. PUBLIC HEALTH IMPLICATIONS: Understanding the impact of higher NSES on health effects may help identify interventions to effectively target high risk neighborhoods.

Association of Childhood Psychosocial Environment With 30-Year Cardiovascular Disease Incidence and Mortality in Middle Age.

Background Childhood adversity and trauma have been shown to be associated with poorer cardiovascular disease (CVD) outcomes in adulthood. However, longitudinal studies of this association are rare. Methods and Results Our study used the CARDIA (Coronary Artery Risk Development in Young Adults) Study, a longitudinal cohort that has followed participants from recruitment in 1985-1986 through 2018, to determine how childhood psychosocial environment relates to CVD incidence and all-cause mortality in middle age. Participants (n=3646) completed the Childhood Family Environment (CFE) questionnaire at the year 15 (2000-2001) CARDIA examination and were grouped by high, moderate, or low relative CFE adversity scores. We used sequential multivariable regression models to estimate hazard ratios of incident (CVD) and all-cause mortality. Participants were 25.1±3.6 years old, 47% black, and 56% female at baseline and 198 participants developed CVD (17.9 per 10 000 person-years) during follow-up. CVD incidence was >50% higher for those in the high CFE adversity group compared with those in the low CFE adversity group. In fully adjusted models, CVD hazard ratios (95% CI) for participants who reported high and moderate CFE adversity versus those reporting low CFE adversity were 1.40 (0.98-2.11) and 1.25 (0.89-1.75), respectively. The adjusted hazard ratios for all-cause mortality was 1.68 (1.17-2.41) for those with high CFE adversity scores and 1.55 (1.11-2.17) for those with moderate CFE adversity scores. Conclusions Adverse CFE was associated with CVD incidence and all-cause mortality later in life, even after controlling for CVD risk factors in young adulthood.

Compared to non-drinkers, individuals who drink alcohol have a more favorable multisystem physiologic risk score as measured by allostatic load.

AIMS: Alcohol use is associated with both positive and negative effects on individual cardiovascular risk factors, depending upon which risk factor is assessed. The present analysis uses a summative multisystem index of biologic risk, known as allostatic load (AL), to evaluate whether the overall balance of alcohol-associated positive and negative cardiovascular risk factors may be favorable or unfavorable. METHODS: This analysis included 1255 adults from the Midlife in the United States (MIDUS) biomarker substudy. Participants, average age 54.5 (±11) years, were divided into 6 alcohol-use categories based on self-reported drinking habits. Current non-drinkers were classified as lifelong abstainers and former light drinkers, former moderate drinkers, or former heavy drinkers. Current alcohol users were classified as light, moderate, or heavy drinkers. A total AL score was calculated using 24 biomarkers grouped into 7 physiologic systems including cardiovascular, inflammation, glucose metabolism, lipid metabolism, sympathetic and parasympathetic nervous systems, and the hypothalamic-pituitary-adrenal axis. Mixed-effects regression models were fit to determine the relationship between alcohol use categories and AL with controls for covariates that may influence the relationship between alcohol use and AL. RESULTS: 468 (37.6%) individuals were current non-drinkers while 776 (62.4%) were current drinkers. In adjusted mixed-effects regression models, all 3 groups of current drinkers had significantly lower average AL scores than the lifelong abstainer/former light drinker group (light: -0.23, 95% CI -0.40, -0.07, p < 0.01; moderate: -0.20, 95% CI -0.38, -0.02, p < 0.05; heavy: -0.30, 95% CI -0.57, -0.04, p < 0.05), while the average AL scores of former moderate and former heavy drinkers did not differ from the lifelong abstainer/former light drinker group. CONCLUSIONS: Current alcohol use is associated cross-sectionally with a favorable multisystem physiologic score known to be associated with better long-term health outcomes, providing evidence in support of long-term health benefits related to alcohol consumption.

Interleukin-10 as a predictor of major adverse cardiovascular events in a racially and ethnically diverse population: Multi-Ethnic Study of Atherosclerosis.

PURPOSE: To understand if baseline levels of the anti-inflammatory cytokine interleukin-10 (IL-10) are associated with either subclinical atherosclerosis or risk for adverse cardiovascular (CV) events. METHODS: The study included 930 adults from the Multi-Ethnic Study of Atherosclerosis (MESA) ancillary Stress Study. Participants, age 48-90 years at enrollment, were followed for an average of 10.2 years. IL-10 level was measured at the initial Stress Study visit. Cardiovascular outcomes were defined as composite CV death, myocardial infarction, stroke, stroke death, and resuscitated cardiac arrest. Coronary calcification was determined by Agatston coronary artery calcium (CAC) score. The association between IL-10 level and CV event risk was evaluated by Cox proportional hazard modeling, while that of IL-10 level and CAC presence and amount was determined with prevalence risk ratio (PRR) and linear regression modeling, respectively. Models were adjusted for CV risk factors and proinflammatory biomarkers. RESULTS: After full adjustment, IL-10 level did not predict CV events (HR 1.19, 95%CI 0.89, 1.60) and was not associated with CAC prevalence (PRR 1.00, 95%CI 0.94, 1.07), nor amount of CAC in those with nonzero CAC (ß -0.01, 95%CI -0.23, 0.21). CONCLUSION: In individuals without clinical heart disease, baseline IL-10 level appears unrelated to risk of CV events and is a poor marker of subclinical coronary atherosclerosis.

Early-Life Adversity and Dysregulation of Adult Diurnal Cortisol Rhythm.

Objectives: Exposure to life stresses can lead to diminution in the capacity of stress response systems to mount a robust response to new challenges, with blunting of dynamic range-the spread between maximal attainable and minimal resting levels. We investigate the association between early-life adversity and the dynamic range of adult diurnal cortisol secretion. Method: In 35- to 86-year-old adults, cortisol assayed from 16 saliva samples over 4 consecutive days was used to compute diurnal dynamic range and area under the curve (AUC). Economic adversity in childhood was indexed by recalled parental education, family welfare dependence, and perceived financial status; and childhood social adversity by parental separation, death, and abuse. Results: Adjusted for age, gender, and race/ethnicity, both childhood adversities were strongly associated with smaller adult cortisol diurnal dynamic range, but not with AUC. The association with cortisol dynamic range was explained by adult social and economic variables. Discussion: Early-life adversity appears to leave a long-term imprint on cortisol secretion dynamics, reducing diurnal dynamic range without increasing total secretion. This points to the importance of examining the adaptation capacity of physiological systems when studying the impact of early-life and chronic stresses on adult health.

The cross-sectional and longitudinal association between air pollution and salivary cortisol: Evidence from the Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Cortisol, a stress hormone released by the activation of the hypothalamic-pituitary-adrenal (HPA) axis, is critical to the body's adaptive response to physiological and psychological stress. Cortisol has also been implicated in the health effects of air pollution through the activation of the sympathetic nervous system. This study evaluates the cross-sectional and longitudinal association between several air pollutants and salivary cortisol. METHODS: We used data from the Multi-Ethnic Study of Atherosclerosis (MESA), a cohort of 45-85 years old participants from six US cities. Salivary cortisol was evaluated at two time points between 2004 and 2006 and then again from 2010 to 2012. Cortisol samples were taken several times per day on two or three consecutive days. Particulate matter <2.5 µm in diameter (PM2.5), nitrogen dioxide (NO2) and nitrogen oxides (NOx) in the year prior to cortisol sampling were examined. We used piecewise linear mixed models that were adjusted for demographics, socioeconomic status and cardiovascular risk factors to examine both cross-sectional and longitudinal associations. Longitudinal models evaluated change in cortisol over time. RESULTS: The pooled cross-sectional results revealed largely null results with the exception of a 9.7% higher wake-up cortisol associated with a 10 ppb higher NO2 (95% CI, -0.2%, 20.5%). Among all participants, the features of the cortisol curve became flatter over 5 years. The wake-to-bed slope showed a more pronounced flattening over time (0.014, 95% CI, 0.0, 0.03) with a 10 ppb higher NO2 level. Other air pollutants were not associated with change in cortisol over time. CONCLUSIONS: Our results suggest only a moderate association between traffic related air pollution and cortisol. Very few epidemiologic studies have examined the long-term impact of air pollution on the stress response systems, thus warranting further exploration of these findings.