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Objective: Prior work suggests that psychological resilience to trauma may protect not only mental but also physical health. This study examined the relationship of prepandemic psychological resilience to lifetime trauma with self-reported COVID-19 infection and symptoms during the early years of the COVID-19 pandemic., Methods: Data are from 18,670 longitudinal cohort participants in the Nurses' Health Study II. Based on prior evidence that trauma and subsequent distress can increase infection risk and severity, and that psychological assets may offset this risk, we hypothesized higher versus lower psychological resilience to prior trauma would be associated with lower risk for COVID-19 infection. Prepandemic resilience was assessed via self-report between 2017 and 2019 based on self-reported lifetime trauma exposure and psychological health. COVID-19 infection and symptoms were self-reported on seven questionnaires administered between May 2020 and October 2021, from which we derived a composite outcome measure of probable COVID-19 infection, defined as having 3+ COVID-19 symptoms (out of 9) and/or a positive COVID-19 test result at any single assessment., Results: Multivariable regression revealed significant associations between higher prepandemic resilience scores and lower risk for probable COVID-19 infection, adjusting for sociodemographic and COVID-19-related risk factors (risk ratio [RR] = 0.90 [95% confidence interval {CI}, 0.87-0.93]). Considering subcomponents of the composite COVID-19 infection measure separately, prepandemic resilience was significantly associated with lower risk of reported symptoms (RR = 0.83 [95% CI, 0.79-0.88]), but not with a positive test result alone (RR = 0.96 [95% CI, 0.91-1.01])., Conclusion: Identifying protective factors for infection risk may help inform psychosocial interventions to improve health outcomes., (Copyright © 2024 by the American Psychosomatic Society.)

Objective: Eudaimonic facets of psychological well-being (PWB), like purpose in life and sense of mastery, are associated with healthy aging. Variation in the gut microbiome may be one pathway by which mental health influences age-related health outcomes. However, associations between eudaimonic PWB and the gut microbiome are understudied. We examined whether purpose in life and sense of mastery, separately, were associated with features of the gut microbiome in older women., Methods: Participants were from the Mind-Body Study ( N = 206, mean age = 61 years), a substudy of the Nurses' Health Study II cohort. In 2013, participants completed the Life Engagement Test and the Pearlin Mastery Scale. Three months later, up to two pairs of stool samples were collected, 6 months apart. Covariates included sociodemographics, depression, health status, and health behaviors. Analyses examined associations of PWB with gut microbiome taxonomic diversity, overall community structure, and specific species/pathways. To account for multiple testing, statistical significance was established using Benjamini-Hochberg adjusted p values (i.e., q values ≤0.25)., Results: We found no evidence of an association between PWB and gut microbiome alpha diversity. In multivariate analysis, higher purpose levels were significantly associated with lower abundance of species previously linked with poorer health outcomes, notably Blautia hydrogenotrophica and Eubacterium ventriosum ( q values ≤0.25). No significant associations were found between PWB and metabolic pathways., Conclusions: These findings offer early evidence suggesting that eudaimonic PWB is linked with variation in the gut microbiome, and this might be one pathway by which PWB promotes healthy aging., (Copyright © 2024 by the American Psychosomatic Society.)

Objective: Higher optimism is associated with reduced mortality and a lower risk of age-related chronic diseases. DNA methylation (DNAm) may provide insight into mechanisms underlying these relationships. We hypothesized that DNAm would differ among older individuals who are more versus less optimistic., Methods: Using cross-sectional data from two population-based cohorts of women with diverse races/ethnicities ( n = 3816) and men (only White, n = 667), we investigated the associations of optimism with epigenome-wide leukocyte DNAm. Random-effects meta-analyses were subsequently used to pool the individual results. Significantly differentially methylated cytosine-phosphate-guanines (CpGs) were identified by the "number of independent degrees of freedom" approach: effective degrees of freedom correction using the number of principal components (PCs), explaining >95% of the variation of the DNAm data (PC-correction). We performed regional analyses using comb-p and pathway analyses using the Ingenuity Pathway Analysis software., Results: We found that essentially all CpGs (total probe N = 359,862) were homogeneous across sex and race/ethnicity in the DNAm-optimism association. In the single CpG site analyses based on homogeneous CpGs, we identified 13 significantly differentially methylated probes using PC-correction. We found four significantly differentially methylated regions and two significantly differentially methylated pathways. The annotated genes from the single CpG site and regional analyses are involved in psychiatric disorders, cardiovascular disease, cognitive impairment, and cancer. Identified pathways were related to cancer, and neurodevelopmental and neurodegenerative disorders., Conclusion: Our findings provide new insights into possible mechanisms underlying optimism and health., (Copyright © 2022 by the American Psychosomatic Society.)

Background: Evidence suggests a link between depressive symptoms and risk of subsequent stroke. However, most studies assess depressive symptoms at only one timepoint, with few examining this relationship using repeatedly measured depressive symptoms. This study aimed to examine the relationship between depressive symptom trajectories and risk of incident stroke., Methods: This prospective cohort included 12 520 US individuals aged ≥50 years enrolled in the Health and Retirement Study, free of stroke at study baseline (1998). We used the 8-item Center for Epidemiologic Studies Depression scale to assess depressive symptoms (high defined as ≥3 symptoms; low <3 symptoms) at 4 consecutive, biennial timepoints from 1998 to 2004. We assigned individuals to 5 predefined trajectories based on their scores at each timepoint (consistently low, decreasing, fluctuating, increasing, and consistently high). Using self-reported doctors' diagnoses, we assessed incident stroke over a subsequent 10-year period from 2006 to 2016. Cox regression models estimated the association of depressive symptom trajectories with risk of incident stroke, adjusting for demographics, health behaviors, and health conditions., Results: During follow-up, 1434 incident strokes occurred. Compared with individuals with consistently low symptoms, individuals with consistently high depressive symptoms (adjusted hazard ratio, 1.18 [95% CI, 1.02-1.36]), increasing symptoms (adjusted hazard ratio, 1.31 [95% CI, 1.10-1.57]), and fluctuating symptoms (adjusted hazard ratio, 1.21 [95% CI, 1.01-1.46]) all had higher hazards of stroke onset. Individuals in the decreasing symptom trajectory group did not show increased stroke risk., Conclusions: Depressive symptom trajectories characterized by high symptoms at multiple timepoints were associated with increased stroke risk. However, a trajectory with depressive symptoms that started high but decreased over time was not associated with higher stroke risk. Given the remitting-relapsing nature of depressive symptoms, it is important to understand the relationship between depressive symptoms and stroke risk over time through repeated assessments.

Objective: Metabolomic profiling may provide insights into biological mechanisms underlying the strong epidemiologic links observed between early abuse and cardiometabolic disorders in later life., Methods: We examined the associations between early abuse and midlife plasma metabolites in two nonoverlapping subsamples from the Nurses' Health Study II, comprising 803 (mean age = 40 years) and 211 women (mean age = 61 years). Liquid chromatography-tandem mass spectrometry assays were used to measure metabolomic profiles, with 283 metabolites consistently measured in both subsamples. Physical and sexual abuse before age 18 years was retrospectively assessed by validated questions integrating type/frequency of abuse. Analyses were conducted in each sample and pooled using meta-analysis, with multiple testing adjustment using the q value approach for controlling the positive false discovery rate., Results: After adjusting for age, race, menopausal status, body size at age 5 years, and childhood socioeconomic indicators, more severe early abuse was consistently associated with five metabolites at midlife (q value < 0.20 in both samples), including lower levels of serotonin and C38:3 phosphatidylethanolamine plasmalogen and higher levels of alanine, proline, and C40:6 phosphatidylethanolamine. Other metabolites potentially associated with early abuse (q value < 0.05 in the meta-analysis) included triglycerides, phosphatidylcholine plasmalogens, bile acids, tyrosine, glutamate, and cotinine. The association between early abuse and midlife metabolomic profiles was partly mediated by adulthood body mass index (32% mediated) and psychosocial distress (13%-26% mediated), but not by other life-style factors., Conclusions: Early abuse was associated with distinct metabolomic profiles of multiple amino acids and lipids in middle-aged women. Body mass index and psychosocial factors in adulthood may be important intermediates for the observed association., (Copyright © 2022 by the American Psychosomatic Society.)

Objective: Although evidence has linked anger and hostility with all-cause mortality risk, less research has examined whether anger frequency and expression (outwardly expressing angry feelings) are linked to all-cause and cause-specific mortality., Methods: In 1996, men (n = 17,352) free of medical conditions from the Health Professionals Follow-Up Study reported anger frequency and aggressive expression levels. Deaths were ascertained from participants' families, postal authorities, and death registries. Cox proportional hazards regression models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) of mortality risk until 2016 with a 2-year lag, adjusting for a range of relevant covariates., Results: There were 4881 deaths throughout follow-up. After adjustment for sociodemographics and health status, moderate and higher (versus lower) levels of anger frequency and aggressive expression were generally unrelated to the risk of death from all-cause, neurological, or respiratory diseases. However, cardiovascular mortality risk was greater with higher anger frequency (HR = 1.17, 95% CI = 1.01-1.34), whereas cancer mortality risk was greater with higher anger expression (HR = 1.14, 95% CI = 0.98-1.33). Results were similar after including all covariates and stronger when considering anger expression's interaction with frequency., Conclusions: In this cohort of men, experiencing angry feelings and expressing them aggressively were related to an increased risk of dying from cardiovascular disease and cancer but not from other specific causes, over two decades. These results suggest that not only the experience of negative emotions but also how they are managed may be critical for some but not all health outcomes, highlighting the importance of considering causes of death separately when investigating psychosocial determinants of mortality., (Copyright © 2021 by the American Psychosomatic Society.)

Objective: Poor mental health in childhood is associated with a greater risk of cardiometabolic disease in adulthood, but less is known about when these associations begin to emerge. This study tests whether poor mental health (indexed by emotional and behavioral problems) in early childhood predicts increases in cardiometabolic dysregulation over 4 years of follow-up., Methods: Data are from 4327 participants in the Generation R Study. Problem behaviors were reported by mothers using the Child Behavior Checklist at age 6 years. Repeated measurements of six cardiometabolic parameters were collected at ages 6 and 10 years: high-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, systolic and diastolic blood pressures, C-reactive protein, and body mass index. Standardized measures were used to create continuous cardiometabolic dysregulation scores at ages 6 and 10 years. Change in dysregulation was defined as the difference in dysregulation scores over time. Cross-sectional and prospective associations were tested using linear regression, sequentially adjusting for relevant confounders. Additional analyses examined whether prospective relationships were robust to adjustment for baseline levels of dysregulation., Results: There was no association between child problem behaviors and cardiometabolic dysregulation at age 6 years. However, higher levels of problem behaviors predicted increases in cardiometabolic dysregulation (β = 0.12, 95% confidence interval = 0.00-0.23) from ages 6 to 10 years., Conclusions: Worse child mental health may be associated with increases in cardiometabolic dysregulation by preadolescence. To our knowledge, this is the first study to demonstrate that adverse physiologic effects of psychological distress identified in adult populations may be observed as early as childhood., (Copyright © 2021 by the American Psychosomatic Society.)

As clinicians delivering health care, we are very good at treating disease but often not as good at treating the person. The focus of our attention has been on the specific physical condition rather than the patient as a whole. Less attention has been given to psychological health and how that can contribute to physical health and disease. However, there is now an increasing appreciation of how psychological health can contribute not only in a negative way to cardiovascular disease (CVD) but also in a positive way to better cardiovascular health and reduced cardiovascular risk. This American Heart Association scientific statement was commissioned to evaluate, synthesize, and summarize for the health care community knowledge to date on the relationship between psychological health and cardiovascular health and disease and to suggest simple steps to screen for, and ultimately improve, the psychological health of patients with and at risk for CVD. Based on current study data, the following statements can be made: There are good data showing clear associations between psychological health and CVD and risk; there is increasing evidence that psychological health may be causally linked to biological processes and behaviors that contribute to and cause CVD; the preponderance of data suggest that interventions to improve psychological health can have a beneficial impact on cardiovascular health; simple screening measures can be used by health care providers for patients with or at risk for CVD to assess psychological health status; and consideration of psychological health is advisable in the evaluation and management of patients with or at risk for CVD.

Objective: Favorable cardiovascular health is associated with greater longevity free of cardiovascular disease. Although the prevalence of cardiovascular health decreases with age, less is known about protective factors that promote and preserve it over time. We investigated whether optimism was associated with better cardiovascular health over a 10-year period., Methods: Participants included 3188 Black and White men and women from the Coronary Artery Risk Development in Young Adults study. Self-reported optimism was assessed in 2000 (this study's baseline) with the revised Life Orientation Test. Favorable cardiovascular health was defined by healthy status on five components of cardiovascular functioning that were repeatedly assessed through 2010 either clinically or via self-report (blood pressure, lipids, body mass index, diabetes, and smoking status). Linear mixed-effects models examined whether optimism predicted cardiovascular health over time, adjusting for covariates such as sociodemographic characteristics, health behaviors, health status, and depression diagnosis., Results: In models adjusting for sociodemographic characteristics, optimism was associated with better cardiovascular health across all time points (β = 0.08, 95% confidence interval = 0.04-0.11, p ≤ .001) but not with rate of change in cardiovascular health. Findings were similar when adjusting for additional covariates. Optimism did not interact significantly with race (p = .85) but did with sex, such that associations seemed stronger for women than for men (p = .03)., Conclusions: Optimism may contribute to establishing future patterns of cardiovascular health in adulthood, but other factors may be more strongly related to how slowly or quickly cardiovascular health deteriorates over time.

Objective: Mounting evidence suggests that higher optimism is associated with reduced risk of age-related morbidities and premature mortality. However, possible biological mechanisms underlying these associations remain understudied. One hypothesized mechanism is a slower rate of cellular aging, which in turn delays age-related declines in health., Methods: We used data from two large cohort studies to test the hypothesis that higher optimism is associated with longer leukocyte telomere length. With cross-sectional data from the Health and Retirement Study (HRS; n = 6417; mean age = 70 years) and the Women's Health Initiative (WHI; N = 3582; mean age = 63 years), we used linear regression models to examine the association of optimism with relative telomere length (assessed in leukocytes from saliva [HRS] or plasma [WHI]). Models adjusted for sociodemographics, depression, health status, and health behaviors., Results: Considering both optimism and telomere length as continuous variables, we found consistently null associations in both cohorts, regardless of which covariates were included in the models. In models adjusting for demographics, depression, comorbidities, and health behaviors, optimism was not associated with mean relative telomere length (HRS: β = -0.002, 95% confidence interval = -0.014 to 0.011; WHI: β = -0.004, 95% confidence interval = -0.017 to 0.009)., Conclusions: Findings do not support mean telomere length as a mechanism that explains observed relations of optimism with reduced risk of chronic disease in older adults. Future research is needed to evaluate other potential biological markers and pathways.

Objective: Low social integration and divorce/widowhood are chronic psychosocial stressors that may affect health. When assessed after cancer diagnosis, they have been associated with poorer survival, but their role in cancer development, particularly ovarian cancer (OvCA), is less understood. We investigated whether social integration and marital status were related to OvCA risk in a large population-based study., Methods: Women from the Nurses' Health Study completed the Berkman-Syme Social Network Index and reported their marital status every 4 years starting in 1992 (N = 72,206), and were followed up until 2012 (20-year follow-up period). Multivariate Cox regression models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) of OvCA risk, considering relevant potential confounders, in lagged analyses whereby psychosocial indicators were assessed 4 to 8 years (n = 436 cases) and 8 to 12 years (n = 306 cases) before diagnosis to account for the effects of prediagnostic symptoms on social measures. Secondary analyses evaluated the stability of and cumulative exposure to these social factors on OvCA risk., Results: Being socially isolated versus integrated was related to an increased OvCA risk 8 to 12 years later (HR = 1.51, 95% CI = 1.07-2.13), but not 4 to 8 years later. Compared with married women, OvCA risk was significantly higher in widowed but not in separated/divorced individuals, with both time periods (e.g., 8-12 years later: HRwidowed = 1.57 [95% CI = 1.15-2.14] versus HRseparated/divorced = 1.13 [95% CI = 0.74-1.72]). Estimates were comparable or stronger when investigating stability in and cumulative effects of social indicators., Conclusions: Results suggest higher OvCA risk among socially isolated and widowed women, particularly when such psychosocial stressors were experienced a decade before diagnosis or were sustained over time.

Objective: The aim of the study was to examine the association of lifetime maternal depression with regulation of immune responses in the infant, measured by cytokine levels and lymphocyte proliferation (LP) in cord blood mononuclear cells collected at delivery., Methods: We studied women recruited in early pregnancy into the Project Viva longitudinal cohort who had cord blood assayed after delivery (N = 463). Women reported about depressive symptoms in midpregnancy (Edinburgh Postnatal Depression Scale) and depression history by questionnaire. Immune responses were assayed by an index of LP, and concentrations of five cytokines (interleukin [IL]-6, IL-10, IL-13, tumor necrosis tumor necrosis factor factor α, and interferon γ) after incubation of cord blood mononuclear cells either in medium alone or stimulated with phytohemagglutinin (PHA), cockroach extract, or house dust mite extract. We examined associations of maternal depression with these sets of cytokine measures using multivariable linear or tobit regression analyses., Results: After adjustment for confounders (mother's age, race/ethnicity, education, household income, season of birth, and child sex), levels of IL-10 after stimulation with cockroach or dust mite allergen were lower in cord blood from ever versus never depressed women, and a similar trend was evident in IL-10 stimulated with PHA (percentage difference: cockroach extract = -41.4, p = .027; house dust mite extract = 1-36.0, p = .071; PHA = -24.2, p = .333). No significant differences were seen in levels of other cytokines or LP., Conclusions: Maternal depression is associated with offspring immune responses at birth, which may have implications for later life atopic risk or immune function.

Optimistic people have reduced risk for cardiovascular disease and cardiovascular-related mortality compared with their less optimistic peers. One explanation for this is that optimistic people may be more likely to engage in healthy behavior like exercising frequently, eating fruits and vegetables, and avoiding cigarette smoking. However, researchers have not formally determined the extent or direction of optimism's association with health behaviors. Moreover, it is unclear whether optimism temporally precedes health behaviors or whether the relationship is because of shared common causes. We conducted random effects meta-analyses examining optimism's association with 3 health behaviors relevant for the prevention of cardiovascular disease. PubMed and PsycINFO databases were searched for studies published through November 2017 reporting on optimism's relationship with physical activity, diet, and cigarette smoking. We identified 34 effect sizes for physical activity (n=90 845), 15 effect sizes for diet (n=47 931), and 15 effect sizes for cigarette smoking (n=15 052). Findings suggested that more optimistic individuals tended to engage in healthier behaviors compared with less optimistic individuals, but effect sizes were modest ( r activity =0.07, P <0.0001; r diet =0.12, P <0.0001; and r smoking =0.07, P =0.001). Most evidence was cross-sectional (≥53% of effect sizes) and did not consider sociodemographic characteristics (<53% of effect sizes) or psychological distress (<27% of effect sizes) as potential confounders. Optimism is associated with healthier behaviors that protect against cardiovascular disease, although most evidence was relatively low quality. Additional longitudinal and experimental research is required to determine whether optimism causally contributes to healthy behaviors and whether optimism could be an effective target for preventing cardiovascular disease., (© 2018 American Heart Association, Inc.)

Objective: Ovarian cancer (OvCA) is a leading cause of cancer death for women. Depression and social isolation have been associated with a higher OvCA risk and poorer survival, but other forms of chronic psychosocial stress, including work-related characteristics, remain understudied., Methods: Women from three prospective cohorts (Nurses' Health Study: n = 31,754; Nurses' Health Study II: n = 74,260; Northern Sweden Health and Disease Study: nnested case-control study = 196) completed a job questionnaire, assessing demand and control at work, social support provided by coworkers and supervisor, and job security. Multivariate Cox and conditional logistic regression models estimated hazard ratios (Nurses' Health Study/Nurses' Health Study II) and odd ratios (Northern Sweden Health and Disease Study) of OvCA risk and mortality among cases. Random coefficient models were used for meta-analyses., Results: There were 396 OvCA cases and 186 deaths during follow-up. Overall, job strain, strain chronicity, social support, and job security were not significantly associated with OvCA risk (e.g., pooled relative risk [RR]high demand/low control = 1.06, confidence interval [CI] = 0.72-1.55) or mortality (e.g., pooled RRhigh demand/low control = 1.08, CI = 0.64-1.82). When considered individually, compared with low levels, only moderate levels of demand were associated with a reduced OvCA risk (pooled RR = 0.66, CI = 0.49-0.90). Social support provided by the coworker or the supervisor did not moderate the association of job strain with either OvCA risk or overall mortality., Conclusions: We did not observe clear associations between work characteristics and OvCA incidence or mortality, but further research with diverse populations is warranted.

Rationale: Higher social integration is associated with lower cardiovascular mortality; however, whether it is associated with incident coronary heart disease (CHD), especially in women, and whether associations differ by case fatality are unclear., Objectives: This study sought to examine the associations between social integration and risk of incident CHD in a large female prospective cohort., Methods and Results: Seventy-six thousand three hundred and sixty-two women in the Nurses' Health Study, free of CHD and stroke at baseline (1992), were followed until 2014. Social integration was assessed by a simplified Berkman-Syme Social Network Index every 4 years. End points included nonfatal myocardial infarction and fatal CHD. Two thousand three hundred and seventy-two incident CHD events occurred throughout follow-up. Adjusting for demographic, health/medical risk factors, and depressive symptoms, being socially integrated was significantly associated with lower CHD risk, particularly fatal CHD. The most socially integrated women had a hazard ratio of 0.55 (95% confidence interval, 0.41-0.73) of developing fatal CHD compared with those least socially integrated ( P for trend <0.0001). When additionally adjusting for lifestyle behaviors, findings for fatal CHD were maintained but attenuated ( P for trend =0.02), whereas the significant associations no longer remained for nonfatal myocardial infarction. The inverse associations between social integration and nonfatal myocardial infarction risk were largely explained by health-promoting behaviors, particularly through differences in cigarette smoking; however, the association with fatal CHD risk remained after accounting for these behaviors and, thus, may involve more direct biological mechanisms., Conclusions: Social integration is inversely associated with CHD incidence in women, but is largely explained by lifestyle/behavioral pathways., (© 2017 American Heart Association, Inc.)

Background and Purpose: Depression is associated with stroke, but the effects of changes in depressive symptoms on stroke risk are not well understood. This study examined whether depressive symptom changes across 2 successive annual assessments were associated with incident stroke the following year., Methods: We used visit data from 4319 participants of the Cardiovascular Health Study who were stroke free at baseline to examine whether changes in depressive symptoms classified across 2 consecutive annual assessments predicted incident first stroke during the subsequent year. Depressive symptoms were assessed using the 10-item Center for Epidemiologic Studies Depression scale (high versus low at ≥10). Survival models were inverse probability weighted to adjust for demographics, health behaviors, medical conditions, past depressive symptoms, censoring, and survival., Results: During follow-up, 334 strokes occurred. Relative to stable low scores of depressive symptoms, improved depression symptoms were associated with almost no excess risk of stroke (adjusted hazards ratio, 1.02; 95% confidence interval, 0.66-1.58). New-onset symptoms were nonsignificantly associated with elevated stroke risk (adjusted hazards ratio, 1.44; 95% confidence interval, 0.97-2.14), whereas persistently high depressive symptoms were associated with elevated adjusted hazard of all-cause stroke (adjusted hazards ratio, 1.65; 95% confidence interval, 1.06-2.56). No evidence for effect modification by race, age, or sex was found., Conclusions: Persistently high symptoms of depression predicted elevated hazard of stroke. Participants with improved depressive symptoms had no elevation in stroke risk. Such findings suggest that strategies to reduce depressive symptoms may ameliorate stroke risk., (© 2016 American Heart Association, Inc.)

Objectives: Prior research on the relationship between early adversity and adult chronic disease has often relied on retrospective reports of a limited range of exposures and has not considered childhood psychological distress as a mediator. We investigate whether distress in childhood is one pathway by which early social disadvantage leads to greater cardiometabolic risk in middle adulthood., Methods: Data are from the 1958 British Birth Cohort study (sample n = 6027). We created an early social disadvantage index based on 16 exposures related to family and socioeconomic hardship from birth to age 7. Childhood psychological distress was ascertained from internalizing and externalizing symptoms at ages 7, 11, and 16 years. Cardiometabolic risk was assessed with a Z-standardized score derived from 9 immune, cardiovascular, and metabolic biomarkers measured at age 45. We used linear regression models and formal tests of mediation to assess relationships between disadvantage, distress, and subsequent cardiometabolic risk., Results: Higher social disadvantage predicted increased adult cardiometabolic risk (β = 0.05; 95% CI = 0.03-0.07). Mediation analyses revealed a significant direct (path c'; β = 0.03; 95% CI = 0.01-0.05) and indirect (path ab; β = 0.02; 95% CI = 0.01-0.02) effect of social disadvantage on cardiometabolic risk, adjusting for potential confounders. Child psychological distress accounted for 37% (95% CI = 34-46%) of the observed association., Conclusions: Results suggest childhood distress may be one factor on the pathway linking early disadvantage to higher risk of developing cardiometabolic diseases. Such results may point to the importance of blocking the translation of psychosocial to biological risk during a potentially sensitive developmental window.

Objective: Higher levels of optimism have been linked with positive health behaviors, biological processes, and health conditions that are potentially protective against cognitive impairment in older adults. However, the association between optimism and cognitive impairment has not been directly investigated. We examined whether optimism is associated with incident cognitive impairment in older adults., Methods: Data are from the Health and Retirement Study. Optimism was measured by using the Life Orientation Test-R and cognitive impairment with a modified version of the Telephone Interview for Cognitive Status derived from the Mini-Mental State Examination. Using multiple logistic regression models, we prospectively assessed whether optimism was associated with incident cognitive impairment in 4624 adults 65 years and older during a 4-year period., Results: Among participants, 312 women and 190 men developed cognitive impairment during the 4-year follow-up. Higher optimism was associated with decreased risk of incident cognitive impairment. When adjusted for sociodemographic factors, each standard deviation increase in optimism was associated with reduced odds (odds ratio [OR] = 0.70, 95% confidence interval [CI] = 0.61-0.81) of becoming cognitively impaired. A dose-response relationship was observed. Compared with those with the lowest levels of optimism, people with moderate levels had somewhat reduced odds of cognitive impairment (OR = 0.78, 95% CI = 0.59-1.03), whereas people with the highest levels had the lowest odds of cognitive impairment (OR = 0.52, 95% CI = 0.36-0.74). These associations remained after adjusting for health behaviors, biological factors, and psychological covariates that could either confound the association of interest or serve on the pathway., Conclusions: Optimism was prospectively associated with a reduced likelihood of becoming cognitively impaired. If these results are replicated, the data suggest that potentially modifiable aspects of positive psychological functioning such as optimism play an important role in maintaining cognitive functioning.

Objective: Adverse experiences in childhood may influence cardiovascular risk in adulthood. We examined the prospective associations between types of psychosocial adversity and having multiple adversities (e.g., cumulative risk) with carotid intima-media thickness (IMT) and its progression among young adults. Higher cumulative risk score in childhood was expected to be associated with higher IMT and its progression., Methods: Participants were 2265 men and women (age range, 24-39 years in 2001) from the ongoing Cardiovascular Risk in Young Finns study whose carotid IMTs were measured in 2001 and 2007. A cumulative psychosocial risk score, assessed at the study baseline in 1980, was derived from four separate aspects of the childhood environment that may impose risk (childhood stressful life events, parental health behavior family, socioeconomic status, and childhood emotional environment)., Results: The cumulative risk score was associated with higher IMT in 2007 (b = 0.004, standard error [SE] = 0.001, p < .001) and increased IMT progression from 2001 to 2007 (b = 0.003, SE = 0.001, p = .001). The associations were robust to adjustment for conventional cardiovascular risk factors in childhood and adulthood, including adulthood health behavior, adulthood socioeconomic status, and depressive symptoms. Among the individual childhood psychosocial risk categories, having more stressful life events was associated with higher IMT in 2001 (b = 0.007, SE = 0.003, p = .016) and poorer parental health behavior predicted higher IMT in 2007 (b = 0.004, SE = 0.002, p = .031) after adjustment for age, sex, and childhood cardiovascular risk factors., Conclusions: Early life psychosocial environment influences cardiovascular risk later in life, and considering cumulative childhood risk factors may be more informative than individual factors in predicting progression of preclinical atherosclerosis in adulthood.

Background: Mendelian Randomization (MR) studies have reported that type 2 diabetes (T2D) was not associated with Alzheimer disease (AD). We adopted a modified, mechanism-specific MR design to explore this surprising result., Methods: Using inverse-variance weighted MR analysis, we evaluated the association between T2D and AD using data from 39 single nucleotide polymorphisms (SNPs) significantly associated with T2D in DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) and the corresponding associations of each SNP with AD risk obtained from the International Genomics of Alzheimer's Project (IGAP, n=17,008 AD cases and n=37,154 controls). We evaluated mechanism-specific genetic subscores, including β-cell function, insulin sensitivity, and adiposity, and repeated analyses in 8501 Health and Retirement Study participants for replication and model validation., Results: In IGAP, the overall T2D polygenic score did not predict AD [odds ratio (OR) for the T2D polygenic score=1.01; 95% confidence interval (CI), 0.96, 1.06] but the insulin sensitivity polygenic score predicted higher AD risk (OR=1.17; 95% CI, 1.02, 1.34). In the Health and Retirement Study, polygenic scores were associated with T2D risk; the associations between insulin sensitivity genetic polygenic score and cognitive phenotypes were not statistically significant., Conclusions: Evidence from polygenic scores suggests that insulin sensitivity specifically may affect AD risk, more than T2D overall.

Background: Psychological stress is a proposed risk factor for cardiovascular disease (CVD), and posttraumatic stress disorder (PTSD), the sentinel stress-related mental disorder, occurs twice as frequently in women as men. However, whether PTSD contributes to CVD risk in women is not established., Methods and Results: We examined trauma exposure and PTSD symptoms in relation to incident CVD over a 20-year period in 49 978 women in the Nurses' Health Study II. Proportional hazards models estimated hazard ratios and 95% confidence intervals for CVD events confirmed by additional information or medical record review (n=548, including myocardial infarction [n=277] and stroke [n=271]). Trauma exposure and PTSD symptoms were assessed by using the Brief Trauma Questionnaire and a PTSD screen. In comparison with no trauma exposure, endorsing ≥4 PTSD symptoms was associated with increased CVD risk after adjusting for age, family history, and childhood factors (hazard ratio,1.60; 95% confidence interval, 1.20-2.13). Being trauma-exposed and endorsing no PTSD symptoms was associated with elevated CVD risk (hazard ratio, 1.45; 95% confidence interval, 1.15-1.83), although being trauma-exposed and endorsing 1 to 3 PTSD symptoms was not. After adjusting for adult health behaviors and medical risk factors, this pattern of findings was maintained. Health behaviors and medical risk factors accounted for 14% of the trauma/no symptoms-CVD association and 47% of the trauma/4+ symptoms-CVD association., Conclusion: Trauma exposure and elevated PTSD symptoms may increase the risk of CVD in this population of women. These findings suggest that screening for CVD risk and reducing health risk behaviors in trauma-exposed women may be promising avenues for prevention and intervention., (© 2015 American Heart Association, Inc.)

Background: Depression and anxiety have been inconsistently associated with diabetes. Sex differences in the biological and behavioral correlates of these forms of distress could partially explain these inconsistencies. We investigated sex-specific associations between depression/anxiety symptoms and diabetes in two separate samples., Methods: The First National Health and Nutrition Examination Survey enrolled 3233 participants aged 25 to 74 years from 1971 to 1974. Depression and anxiety symptoms were measured via General Well Being schedule subscales. Incident diabetes for 17 years was defined by the following: a) death certificate, b) participant self-report, or c) health care facility discharge. The Detroit Neighborhood Health Study enrolled 1054 participants 18 years or older from 2008 to 2010. The Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7 assessed depression and anxiety. Participants' self-reported physician-diagnosed prevalent diabetes., Results: In the First National Health and Nutrition Examination Survey, the risk ratio (RR; 95% confidence interval) for incident diabetes among men with high versus low anxiety symptoms was 0.85 (0.56-1.29) and that among women was 2.19 (1.17-4.09; p for interaction = .005). RRs comparing high versus low depressive symptoms for men and women were 0.69 (0.43-1.100) and 2.11 (1.06-4.19); p for interaction = .007. In the Detroit Neighborhood Health Study, the RRs for prevalent diabetes comparing those with high versus low anxiety symptoms were 0.24 (0.02-2.42) for men and 1.62 (0.61-4.32) for women (p for interaction = < .001), whereas RRs for depression were 1.30 (0.46-3.68) for men and 2.32 (1.10-4.89) for women (p for interaction = .16)., Conclusions: In two separate samples, depressive symptoms were related to increased diabetes risk among women but not men. Although less robust, findings for anxiety were differentially associated with diabetes by sex.

Background: The American Heart Association has defined a new metric of ideal cardiovascular health as part of its 2020 Impact Goals. We examined whether psychosocial factors in youth predict ideal cardiovascular health in adulthood., Methods and Results: Participants were 477 men and 612 women from the nationwide Cardiovascular Risk in Young Finns Study. Psychosocial factors were measured from cohorts 3 to 18 years of age at the baseline of the study, and ideal cardiovascular health was examined 27 years later in adulthood. The summary measure of psychosocial factors in youth comprised socioeconomic factors, emotional factors, parental health behaviors, stressful events, self-regulation of the child, and social adjustment of the child. There was a positive association between a higher number of favorable psychosocial factors in youth and greater ideal cardiovascular health index in adulthood (β=0.16; P<0.001) that persisted after adjustment for age, sex, medication use, and cardiovascular risk factors in childhood (β=0.15; P<0.001). The association was monotonic, suggesting that each increment in favorable psychosocial factors was associated with improvement in cardiovascular health. Of the specific psychosocial factors, a favorable socioeconomic environment (β=0.12; P<0.001) and participants' self-regulatory behavior (β=0.07; P=0.004) were the strongest predictors of ideal cardiovascular health in adulthood., Conclusions: The findings suggest a dose-response association between favorable psychosocial factors in youth and cardiovascular health in adulthood, as defined by the American Heart Association metrics. The effect seems to persist throughout the range of cardiovascular health, potentially shifting the population distribution of cardiovascular health rather than simply having effects in a high-risk population., (© 2015 American Heart Association, Inc.)

Background: Although higher optimism has been linked with an array of positive health behaviors, biological processes, and cardiovascular outcomes, the relationship between optimism and heart failure has not been examined. In the United States, 80% of heart failures occur in adults aged 65+ years. Therefore, we examined whether higher optimism was linked with a reduced incidence of heart failure among older adults., Methods and Results: Prospective data were from the Health and Retirement Study, a nationally representative study of older US adults. Our sample included 6808 participants who were followed for 4 years. Multiple logistic regression models were used to assess whether optimism was independently associated with incident heart failure. We adjusted for sociodemographic, behavioral, biological, and psychological covariates. Higher optimism was associated with a lower risk of incident heart failure during the follow-up period. In a model that adjusted for sociodemographic factors, each SD increase in optimism had an odds ratio of 0.74 (95% confidence interval, 0.63-0.85) for heart failure. Effects of optimism persisted even after adjusting for a wide range of covariates. There was also evidence of a dose-response relationship. As optimism increased, risk of developing heart failure decreased monotonically, with a 48% reduced odds among people with the highest versus lowest optimism., Conclusions: This is the first study to suggest that optimism is associated with a lower risk of heart failure. If future studies confirm these findings, they may be used to inform new strategies for preventing or delaying the onset of heart failure., (© 2014 American Heart Association, Inc.)

Background and Purpose: Higher levels of anxiety are associated with increased risk for coronary heart disease. However, few studies have investigated whether anxiety is associated with stroke risk. The purpose of this study was to examine the association between anxiety symptoms and incident stroke in a nationally representative longitudinal study of the US population., Methods: Participants (n=6019) in the First National Health and Nutrition Examination Survey were assessed at baseline and followed for 16.29±4.75 years. Multivariate Cox proportional hazards regression models were used to estimate hazard ratios and 95% confidence intervals of incident stroke associated with a 1 SD increase in anxiety symptoms. Models were adjusted for standard cardiovascular risk factors and additionally for depression., Results: A total of 419 incident stroke cases were identified from hospital/nursing home discharge reports and death certificates. Reporting more anxiety symptoms at baseline was associated with increased risk of incident stroke after adjusting for standard biological and behavioral cardiovascular risk factors (hazard ratio, 1.14; 95% confidence interval, 1.03-1.25). Findings persisted when additionally controlling for depression. Exploratory analyses considering the role of potential confounding versus pathway variables suggested that behavioral factors may be a key pathway linking anxiety to stroke risk., Conclusions: Higher anxiety symptom levels were associated prospectively with increased risk for incident stroke independent of other risk factors, including depression. Anxiety is a modifiable experience that is highly prevalent among the general population. Its assessment and treatment may contribute to developing more effective preventive and intervention strategies for improving overall cardiovascular health.

Background: The American Heart Association's national goals for cardiovascular health promotion emphasize that cardiovascular risk originates early in life, but little is known about childhood factors that may increase the likelihood of having a favorable cardiovascular risk (FCR) in adulthood. We examined the prospective association between positive childhood factors and the likelihood of midlife FCR. We also considered pathways through which childhood factors may influence FCR., Methods and Results: We studied 415 adults (mean age=42.2 years) of the Collaborative Perinatal Project, a national cohort initiated in 1959 to 1966. We examined 3 positive childhood factors assessed at age 7 years: attention regulation (ability to stay focused), cognitive ability, and positive home environment. Of these adults, 10.6% had FCR in midlife. Adjusting for demographics and childhood cardiovascular health, a 1-unit increase in childhood attention regulation, cognitive ability, and positive home environment was associated with 2.4 (95% confidence interval, 1.1-4.7), 1.8 (95% confidence interval, 1.1-2.9), and 1.3 (95% confidence interval, 1.1-1.6) higher respective odds of having midlife FCR. The association with childhood attention regulation was maintained when accounting for adulthood factors; education and diet in part explained the associations with childhood cognitive ability and home environment. The effect of each attribute was additive as those with high levels of each childhood factor had 4.3 higher odds (95% confidence interval, 1.01-18.2) of midlife FCR in comparison with those low in all factors., Conclusions: Positive childhood psychosocial factors may promote healthy adult cardiovascular functioning. Primordial prevention efforts aimed at preventing the development of cardiovascular risk should consider building on childhood psychosocial resources.

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.

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.

Background: Several methods exist by which to assess type A behavior (TAB). Although the videotaped clinical interview is regarded as the "gold standard," self-report measures have also proved useful in assessing TAB in large population studies. The purpose of this study was to examine prospectively the relationship of TAB to risk of coronary heart disease (CHD) incidence with the use of the revised Minnesota Multiphasic Personality Inventory (MMPI-2) Type A Scale. To the best of our knowledge, this is the first test of this scale in the context of predicting CHD incidence., Methods and Results: The study was performed in the VA Normative Aging Study, an ongoing cohort of older (mean age, 61 years) community-dwelling men. A total of 1305 men who were free of diagnosed CHD in 1986 completed the MMPI-2 Type A Scale. During an average 7.0 years of follow-up, 110 cases of incident CHD occurred. Compared with men in the lowest quartile of type A scores, men in the highest quartile had multivariate adjusted relative risks of 2.86 (95% CI, 1.19 to 6.89; P for trend=0.016) for combined CHD death and nonfatal myocardial infarction (MI) and 2.30 (95% CI, 1.32 to 4.01; P for trend=0.001) for combined CHD death/nonfatal MI plus angina pectoris. The relationship of TAB to CHD was independent of measures of anger and cynicism., Conclusions: The MMPI-2 Type A Scale predicts CHD incidence. Further research is warranted to examine the correlation, if any, between this scale and the videotaped clinical interview.

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.