Introduction: Chronic stress is a cardiovascular disease (CVD) risk factor but the mechanisms by which it promotes CVD are unclear. Chronic stress can affect amygdalar activity (AmygA), leading to increased levels of activity. We evaluated mediators of the relationship between chronic stress-related amygdalar activity (AmygA) and trimethylamine n-oxide (TMAO), a cardiovascular risk marker. Hypothesis: IL-1 β mediates the association between amygdalar activity and TMAO. Methods: 60 African American adults (93% female, mean age 61±11 years) at risk for CVD living in the Washington DC area participated in a cross-sectional, community-focused study. Participants had a 18 FDG PET/CT to assess chronic stress-related AmygA, phenotyping, and ELISA-based techniques to measure serum cytokines and TMAO. Multivariable regression analyses adjusted for atherosclerotic cardiovascular disease (ASCVD) 10-year risk score and body mass index (BMI) identified associations between AmygA and TMAO. IL-1 β, TNF-α, IL-6, IL-8, IL-17 and IFN-γ were evaluated as mediators of indirect associations between AmygA and TMAO. Results: Multivariable regression modeling revealed significant associations between AmygA and TMAO (β=0.32, p=0.02), AmygA and IL-1 β (β=0.36, p=0.003), and IL-1 β and TMAO (β=0.39, p=<0.001) in the fully adjusted model. IL-1 β mediated the AmygA and TMAO relationship (mediation effect = 43.51%). Conclusions: Chronic stress measured by AmygA directly associates with TMAO, a CVD risk biomarker. This relationship is mediated by IL-1 β, suggesting the potential for chronic stress-related inflammation in the brain-gut axis potentially influencing CVD in underserved communities. These hypothesis-generating results should be studied further in the future by including large, diverse populations.
Background: Increased self-efficacy facilitates health promoting behaviors such as physical activity (PA). Perceived discrimination may limit PA among minoritized populations, but little is known about the relationship between PA and nutrition self-efficacy (PANSE) and perceived discrimination (PD) among African American (AA) women with overweight/obesity. Methods: We examined the associations between PANSE and PD in 106 AA women in the Step It Up, a community-engaged, digital health intervention. All completed the PANSE (higher scores = higher self-efficacy), the everyday discrimination scale (higher scores = higher frequency of everyday discrimination), and a sociodemographic survey. We used linear regression to assess the associations between PANSE and PD adjusting for covariates and the interaction effects of discrimination and income. Results: The participants had a mean age of 55.9 (SD±12.7) years with mean BMI 36.3 (SD±6.9) kg/m2. PD was negative and significantly associated with PANSE in both our unadjusted model and after adjusting for age and educational level (Table 1). The association trended marginally significant in the third model when we adjusted for income. We found no interaction effect between PD and income. Conclusion: PD is associated with PANSE among this AA women cohort. This suggests an urgent need for future research to better extricate the relationship between PD and PANSE to inform interventions that addresses everyday discrimination among diverse population groups; particularly in AA women with overweight/obesity.
Background: Loneliness is a public health crisis and recent reports suggest that people suffering from loneliness have increased cardiovascular disease (CVD) risk. A potential link between loneliness and CVD is an atherogenic shift in the lipoprotein profile. We investigated associations between loneliness and lipoproteins in African American (AA) women residing in resource-limited neighborhoods of Washington, DC. Methods: Participants were enrolled in Step It Up, a technology-based, community-engaged PA intervention. Fasting blood samples were drawn at baseline to measure lipoproteins using nuclear magnetic resonance (NMR) technology. The Lipoprotein Insulin Resistance Index (LP-IR), a diabetes risk marker, was calculated. Loneliness was measured using the UCLA Loneliness scale. Associations between loneliness, lipoprotein particles and LP-IR were analyzed using multivariable regression adjusted for BMI, ASCVD 10-year risk score, and lipid-lowering therapy. Results: 106 AA women with CVD risk (Age 55.9±13, BMI 36.3±6.7) were enrolled into Step It Up. We found that higher loneliness at baseline was associated with higher Apo-B, LDL concentration (LDL-c), and LDL particle number (LDL-p) but not with LDL particle size (LDL-z, Table). We observed that higher loneliness associated with increased triglyceride rich lipoprotein size (TRL-z). This relationship seems to be due to very large and large TRL particles (TRL-p, Table). No significant associations were found with the HDL-related measures. Lastly, loneliness significantly associated with LP-IR, a new diabetes risk marker (Table). Conclusions: Thus, our data show that higher loneliness in AA women from under resourced neighborhoods is associated with increased hyperlipidemia and diabetes risk. This highlights a potential mechanism by which loneliness may accelerate CVD risk and support the urgent need for multilevel interventions to reduce loneliness and CVD risk in at-risk populations.
Background: Physical activity (PA) reduces cardiovascular disease (CVD) risk; those living in lower-resourced neighborhoods have higher CVD risk in part due to limited PA access. Monocyte subsets (classical, intermediate, and non-classical) with their platelet aggregates (PlAgg) are key in CVD, but less is known about relationships between PA and monocytes. We investigated associations between PA and monocyte subsets with PlAgg in African American (AA) women at risk for CVD living in resource-limited Washington, DC areas. Methods: Participants were enrolled in Step It Up, a technology-enabled, community-engaged PA intervention. Baseline PA was measured as daily step counts using a FitBit Charge 2. Monocyte subsets and PlAgg were measured in fasting blood samples by flow cytometry. Multivariable linear regression was used to determine relationships between PA and monocytes adjusting for BMI and ASCVD 10-year risk score. We examined neighborhood deprivation index (NDI), a 2018 Census-tract based measure of neighborhood socioeconomic deprivation, as a moderator of associations between PA and monocytes. Results: The study cohort was a sample of AA women with overweight/obesity enrolled in Step It Up (N=106, age=57±12 y, BMI=34.8±6.3kg/m2). Higher baseline PA associated with monocyte subsets, but not overall monocyte presence (Table). Furthermore, higher baseline PA negatively associated with PlAgg on all monocytes. PA and monocyte subsets were most associated among those residing in higher deprivation neighborhoods (Table). Conclusion: Baseline PA was associated with monocyte subsets and lower monocyte-PlAgg formation among AA women living in lower-resourced conditions. Future work should examine the relationship between PA changes and changes in monocyte subsets in community engaged PA interventions like Step It Up, particularly among those residing in limited resource communities.
Importance There are considerable socioeconomic status (SES) disparities in youth physical activity (PA) levels. For example, studies show that lower-SES youth are less active, have lower participation in organized sports and physical education classes, and have more limited access to PA equipment. Objective To determine the potential public health and economic effects of eliminating disparities in PA levels among US youth SES groups. Design and Setting An agent-based model representing all 6- to 17-year-old children in the US was used to simulate the epidemiological, clinical, and economic effects of disparities in PA levels among different SES groups and the effect of reducing these disparities. Main Outcomes and Measures Anthropometric measures (eg, body mass index) and the presence and severity of risk factors associated with weight (stroke, coronary heart disease, type 2 diabetes, or cancer), as well as direct and indirect cost savings. Results This model, representing all 50 million US children and adolescents 6 to 17 years old, found that if the US eliminates the disparity in youth PA levels across SES groups, absolute overweight and obesity prevalence would decrease by 0.826% (95% CI, 0.821%-0.832%), resulting in approximately 383 000 (95% CI, 368 000-399 000) fewer cases of overweight and obesity and 101 000 (95% CI, 98 000-105 000) fewer cases of weight-related diseases (stroke and coronary heart disease events, type 2 diabetes, or cancer). This would result in more than $15.60 (95% CI, $15.01-$16.10) billion in cost savings over the youth cohort’s lifetime. There are meaningful benefits even when reducing the disparity by just 25%, which would result in $1.85 (95% CI, $1.70-$2.00) billion in direct medical costs averted and $2.48 (95% CI, $2.04-$2.92) billion in productivity losses averted. For every 1% in disparity reduction, total productivity losses would decrease by about $83.8 million, and total direct medical costs would decrease by about $68.7 million. Conclusions and Relevance This study quantified the potential savings from eliminating or reducing PA disparities, which can help policymakers, health care systems, schools, funders, sports organizations, and other businesses better prioritize investments toward addressing these disparities.
Abstract While it is well known from numerous epidemiologic investigations that social determinants (socioeconomic, environmental, and psychosocial factors exposed to over the life-course) can dramatically impact cardiovascular health, the molecular mechanisms by which social determinants lead to poor cardiometabolic outcomes are not well understood. This review comprehensively summarizes a variety of current topics surrounding the biological effects of adverse social determinants (i.e., the biology of adversity), linking translational and laboratory studies with epidemiologic findings. With a strong focus on the biological effects of chronic stress, we highlight an array of studies on molecular and immunological signaling in the context of social determinants of health (SDoH). The main topics covered include biomarkers of sympathetic nervous system and hypothalamic–pituitary–adrenal axis activation, and the role of inflammation in the biology of adversity focusing on glucocorticoid resistance and key inflammatory cytokines linked to psychosocial and environmental stressors (PSES). We then further discuss the effect of SDoH on immune cell distribution and characterization by subset, receptor expression, and function. Lastly, we describe epigenetic regulation of the chronic stress response and effects of SDoH on telomere length and aging. Ultimately, we highlight critical knowledge gaps for future research as we strive to develop more targeted interventions that account for SDoH to improve cardiometabolic health for at-risk, vulnerable populations.
Background: Cardiovascular-kidney metabolic (CKM) syndrome is exacerbated among individuals experiencing chronic exposure to both environmental and psychosocial stressors. Both neighborhood and individual-level stressors increase chronic inflammation resulting in worsened CKM factors, such as hypertension, diabetes, and dys/hyperlipidemia. However, associations between neighborhood perceptions (NP) and lipid profiles remain understudied. Therefore, we examined associations between NP domains and lipid profiles among African-American (AA) women with ≥Stage 1 CKM syndrome (overweight/obesity) residing in resource-limited neighborhoods within the Washington, DC area. Methods: Participants were enrolled in Step It Up, a technology-enabled, community-engaged physical activity (PA) intervention. Fasting blood samples were drawn at baseline to measure lipoproteins using Nuclear Magnetic Resonance (NMR) spectroscopy. Factor analysis of overall NP identified four perception sub-scores: disorder, social cohesion, violence, and safety (higher score=favorable perception). Associations between NP domains and lipoprotein particles were analyzed using multivariable regression adjusting for BMI, ASCVD 10-year risk score, and lipid-lowering therapy. Results: Participants (n=169) had mean age=57.16 ± 12.00 and BMI 35.99 ± 6.57. Perceptions of safety were positively associated with LDL concentrations (LDLc) and large LDL particles (L-LDLp) (β=4.70 [SD=2.41], p=0.05, β= 43.75 [17.70], p= 0.01), respectively). Perceptions about neighborhood violence were positively associated with L-LDLp (marginally) and very-low-density lipoprotein size (VLDLz) (β= 7.10 [3.96], p=0.08, β= 0.31 [0.14], p= 0.02, respectively). No associations were found between disorder and social cohesion with lipid biomarkers. Conclusions: After adjusting for BMI, ASCVD risk, and lipid-lowering therapy, there were significant associations between neighborhood perceptions of safety and violence with lipid profiles among AA women with CKM syndrome. Greater perceived safety was associated with higher LDLc and L-LDLp while more favorable perception about neighborhood violence was associated with higher L-LDLp. Future work should examine whether improving neighborhood resources and perceptions may improve CKM health among urban AA women.
Neighborhood socioeconomic deprivation is associated with increased cardiovascular risk factors, including inflammation. Inflammation plays an important role in modifying the cardioprotective function of high-density lipoprotein (HDL). Moreover, recent studies suggest that very high HDL is associated with adverse cardiovascular disease (CVD) outcomes. Thus, we sought to explore the relationships between neighborhood socioeconomic deprivation as a marker of chronic stress, inflammation, proprotein convertase subtilisin/kexin type 9 (PCSK9) (a core component of the HDL proteome), HDL subspecies, and biological aging as a predictor of CVD and all-cause mortality. Sixty African American subjects were recruited to the NIH Clinical Center as part of a community-based participatory research-designed observational study. Neighborhood deprivation index (NDI), a marker of neighborhood socioeconomic deprivation, was measured using US Census data. HDL characteristics (cholesterol, particle number, size, subspecies) were determined from NMR lipoprotein profiling, and plasma cytokines (IL-1β, IL-6, IL-8, TNFα, IFNγ) were measured using an ELISA-based multiplex technique. Epigenetic clock biomarkers of aging were measured using DNA methylation data obtained from participants' buffy coat samples. We used linear regression modeling adjusted for atherosclerotic cardiovascular disease (ASCVD) risk score, body mass index (BMI), and lipid-lowering medication use to investigate relationships of interest. NDI directly associated with large HDL particle count (H7P) and IFNγ and trended toward significance with HDL-C and PCSK9. IFNγ and PCSK9 then directly associated with H7P. H7P also directly associated with higher DNA methylation phenotypic age (PhenoAge). We highlight associations between neighborhood socioeconomic deprivation, IFNγ, PCSK9, HDL subspecies, and epigenetic biomarkers of aging. Taken together, our findings suggest indirect pathways linking neighborhood deprivation-related stress and inflammation to HDL and immune epigenetic changes. Moreover, these results add to recent work showing the pathogenicity of high HDL levels and underscore the need to understand how chronic stress-related inflammation and lipoprotein subspecies relate to CVD risk across diverse populations.
