Chronic stress may be a risk factor for coronary heart disease and is associated with dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. We tested the hypotheses that two markers of HPA ...axis dysregulation, elevated average level (area under the curve, adjusted for time awake) and diurnal decline of salivary cortisol, were associated with presence of coronary calcification (CaC).
Seven hundred eighteen black and white middle-aged adults enrolled in an ancillary study of Coronary Artery Risk Development in Young Adults provided six salivary cortisol samples throughout one full day and had measurements of CaC.
The prevalence of any calcification was low, 8.1% in the participants of the ancillary study, with white men having the highest proportion. Average cortisol did not differentiate groups, means = 2.15 and 2.08. Those with any CaC declined approximately 6% per hour in cortisol over the course of the day, whereas those with no CaC declined more than 8% per hour (p < .003). Those persons with slope scores in the flattest quartile had a greater likelihood of any CaC than did those in the remaining quartiles adjusted for sex-race group, age, smoking, treatment for diabetes, systolic blood pressure, logged triglycerides, average cortisol, and educational attainment (odds ratio = 2.58; 95% confidence interval = 1.26-5.30).
Our results are consistent with the hypothesis that HPA axis dysregulation may affect risk for atherosclerosis.
It is widely recognized that social relationships and affiliation have powerful effects on physical and mental health. When investigators write about the impact of social relationships on health, ...many terms are used loosely and interchangeably including social networks, social ties and social integration. The aim of this paper is to clarify these terms using a single framework. We discuss: (1) theoretical orientations from diverse disciplines which we believe are fundamental to advancing research in this area; (2) a set of definitions accompanied by major assessment tools; and (3) an overarching model which integrates multilevel phenomena.
Theoretical orientations that we draw upon were developed by Durkheim whose work on social integration and suicide are seminal and John Bowlby, a psychiatrist who developed attachment theory in relation to child development and contemporary social network theorists.
We present a conceptual model of how social networks impact health. We envision a cascading causal process beginning with the macro-social to psychobiological processes that are dynamically linked together to form the processes by which social integration effects health. We start by embedding social networks in a larger social and cultural context in which upstream forces are seen to condition network structure. Serious consideration of the larger macro-social context in which networks form and are sustained has been lacking in all but a small number of studies and is almost completely absent in studies of social network influences on health.
We then move downstream to understand the influences network structure and function have on social and interpersonal behavior. We argue that networks operate at the behavioral level through four primary pathways: (1) provision of social support; (2) social influence; (3) on social engagement and attachment; and (4) access to resources and material goods.
Low socioeconomic status (SES) early in life is one of the most well-established social predictors of poor health. However, little is understood about why some adults who grew up in low-SES ...environments do not have poor health outcomes. This study examined whether the psychological characteristic of "shift-and-persist" protects adults from the physiological risks of growing up in low-SES households. Shift-and-persist consists of reframing appraisals of current stressors more positively (shifting), while simultaneously persisting with a focus on the future. We hypothesized that this characteristic would be associated with reduced physiological risk in low-childhood SES individuals.
A national sample of 1207 adults (aged 25-74 years) from the Survey of Midlife Development in the United States completed psychological questionnaires and were queried about parent education. Biologic assessments consisted of 24 different measures across seven physiological systems, from which a composite measure representing cumulative physiological risk (allostatic load) was derived.
Among adults who grew up in low-SES households, those who engaged in high-shift-and-high-persist strategies had the lowest allostatic load (b = -0.15, p = .04). No benefit of shift-and-persist was found for those from higher-childhood SES backgrounds (p = .36).
Identifying the health-related protective qualities that naturally occur in some low-SES individuals represents one important approach for developing future health improvement interventions for those who start out life low in SES. Moreover, the psychological qualities that are protective from future disease risk for those from low-SES backgrounds are different from those beneficial to high-SES individuals.
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.
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.
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.
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.
: Stress is a condition of human existence and a factor in the expression of disease. A broader view of stress is that it is not just the dramatic stressful events that exact their toll but rather ...the many events of daily life that elevate activities of physiological systems to cause some measure of wear and tear. We call this wear and tear “allostatic load,” and it reflects not only the impact of life experiences but also of genetic load; individual habits reflecting items such as diet, exercise, and substance abuse; and developmental experiences that set life‐long patterns of behavior and physiological reactivity (see McEwen 1). Hormones associated with stress and allostatic load protect the body in the short run and promote adaptation, but in the long run allostatic load causes changes in the body that lead to disease. This will be illustrated for the immune system and brain. Among the most potent of stressors are those arising from competitive interactions between animals of the same species, leading to the formation of dominance hierarchies. Psychosocial stress of this type not only impairs cognitive function of lower ranking animals, but it can also promote disease (e.g. atherosclerosis) among those vying for the dominant position. Social ordering in human society is also associated with gradients of disease, with an increasing frequency of mortality and morbidity as one descends the scale of socioeconomic status that reflects both income and education. Although the causes of these gradients of health are very complex, they are likely to reflect, with increasing frequency at the lower end of the scale, the cumulative burden of coping with limited resources and negative life events and the allostatic load that this burden places on the physiological systems involved in coping and adaptation.
Gene expression may be an important biological mediator in associations between social factors and health. However, previous studies were limited by small sample sizes and use of differing cell types ...with heterogeneous expression patterns. We use a large population-based cohort with gene expression measured solely in monocytes to investigate associations between seven social factors and expression of genes previously found to be sensitive to social factors.
We employ three methodological approaches: 1) omnibus test for the entire gene set (Global ANCOVA), 2) assessment of each association individually (linear regression), and 3) machine learning method that performs variable selection with correlated predictors (elastic net).
In global analyses, significant associations with the a priori defined socially sensitive gene set were detected for major or lifetime discrimination and chronic burden (p = 0.019 and p = 0.047, respectively). Marginally significant associations were detected for loneliness and adult socioeconomic status (p = 0.066, p = 0.093, respectively). No associations were significant in linear regression analyses after accounting for multiple testing. However, a small percentage of gene expressions (up to 11%) were associated with at least one social factor using elastic net.
The Global ANCOVA and elastic net findings suggest that a small percentage of genes may be "socially sensitive," (i.e. demonstrate differential expression by social factor), yet single gene approaches such as linear regression may be ill powered to capture this relationship. Future research should further investigate the biological mechanisms through which social factors act to influence gene expression and how systemic changes in gene expression affect overall health.
Short sleep and insomnia are each associated with a greater risk of age-related disease, which suggests that insufficient sleep may accelerate biological aging. We examine whether short sleep and ...insomnia alone or together relates to epigenetic age among older adults.
A total of 3795 men (46.3%) and women aged 56 to 100 years from the Health and Retirement Study were included. Insomnia was defined as reporting at least one insomnia symptom (difficulty falling asleep, waking up at night, or waking up too early in the morning) and feeling unrested when waking up most of the time. Those reporting <6 hours of bedtime were categorized as short sleepers. Three second- or third-generation epigenetic age acceleration clocks were derived from the 2016 Health and Retirement Study Venous Blood Study. The linear regression analysis was adjusted for age, sex, race/ethnicity, education, and obesity status.
Insomnia and short sleep were associated with acceleration of GrimAge of 0.49 (95% confidence interval CI = 0.03-0.94 years; p = .04) and 1.29 (95% CI = 0.52-2.07 years; p = .002) years, respectively, as well as a faster pace of aging (DunedinPACE; 0.018 95% CI = 0.004-0.033; p = .02 and 0.022 95% CI = -0.004 to 0.048; p = .11). Compared with healthy sleepers, individuals with the combination of short sleep and insomnia had an accelerated GrimAge (0.97 years; 95% CI = 0.07-1.87 years, p = .04) and a greater DunedinPACE (0.032; 95% CI = 0.003-0.060, p = .04).
Our findings indicate that short sleep, insomnia, and the combination of the two are linked to epigenetic age acceleration, suggesting that these individuals have an older biological age that may contribute to risk of comorbidity and mortality.
Low socioeconomic status (SES) and a harsh family environment in childhood have been linked to mental and physical health disorders in adulthood. The objective of the present investigation was to ...evaluate a developmental model of pathways that may help explain these links and to relate them to C-reactive protein (CRP) in the Coronary Artery Risk Development in Young Adults (CARDIA) dataset.
Participants (
n = 3248) in the CARDIA study, age 32 to 47 years, completed measures of childhood SES (CSES), early family environment (risky families RF), adult psychosocial functioning (PsyF, a latent factor measured by depression, mastery, and positive and negative social contacts), body mass index (BMI), and C-reactive protein.
Structural equation modeling indicated that CSES and RF are associated with C-reactive protein via their association with PsyF (standardized path coefficients: CSES to RF, RF to PsyF, PsyF to CRP, CSES to CRP, all
p < .05), with good overall model fit. The association between PsyF and CRP was partially mediated by BMI (PsyF to BMI, BMI to CRP, both
p < .05).
Low childhood SES and a harsh early family environment appear to be related to elevated C-reactive protein in adulthood through pathways involving psychosocial dysfunction and high body mass index.
To examine whether perceptions of generativity predict the likelihood of increases in levels of impairment in activities of daily living (ADLs) or of dying over a 10-year period in older adults aged ...60-75 from the Study of Midlife in the United States (MIDUS).
Perceptions of generativity and current generative contributions as well as select sociodemographic, health status, health behavior, and psychosocial factors, assessed at a baseline exam, were examined as predictors of change in ADL disability level or mortality over the 10-year period between the baseline and follow-up waves of the MIDUS Study.
Greater levels of generativity and generative contributions at baseline predicted lower odds of experiencing increases in ADL disability (2 or more new domains of impairment; generativity odds ratio OR = 0.93 and generative contributions OR = 0.87), or of dying (generativity OR = 0.94 and generative contributions OR = 0.88), over the 10-year follow-up in models adjusted for sociodemographics and baseline health and disability. Associations remained relatively unchanged with the inclusion of different sets of health behavior and psychosocial variables in analytic models.
Findings indicate that greater perceptions of generativity are associated with more favorable trajectories of physical functioning and longevity over time in older adults.
To identify genetic factors that interact with social environments to impact human health, we used a bioinformatic strategy that couples expression array-based detection of environmentally responsive ...transcription factors with in silico discovery of regulatory polymorphisms to predict genetic loci that modulate transcriptional responses to stressful environments. Tests of one predicted interaction locus in the human IL6 promoter (SNP rs1800795) verified that it modulates transcriptional response to β-adrenergic activation of the GATA1 transcription factor in vitro. In vivo validation studies confirmed links between adverse social conditions and increased transcription of GATA1 target genes in primary neural, immune, and cancer cells. Epidemiologic analyses verified the health significance of those molecular interactions by documenting increased 10-year mortality risk associated with late-life depressive symptoms that occurred solely for homozygous carriers of the GATA1-sensitive G allele of rs1800795. Gating of depression-related mortality risk by IL6 genotype pertained only to inflammation-related causes of death and was associated with increased chronic inflammation as indexed by plasma C-reactive protein. Computational modeling of molecular interactions, in vitro biochemical analyses, in vivo animal modeling, and human molecular epidemiologic analyses thus converge in identifying β-adrenergic activation of GATA1 as a molecular pathway by which social adversity can alter human health risk selectively depending on individual genetic status at the IL6 locus.
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