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Generally, fasting and refeeding confer anti- and proinflammatory effects, respectively. In humans, these caloric-load interventions function, in part, via regulation of CD4+T cell biology. However, mechanisms orchestrating this regulation remain incomplete. We employed integrative bioinformatics of RNA sequencing and high-performance liquid chromatography–mass spectrometry data to measure serum metabolites and gene expression of peripheral blood mononuclear cells isolated from fasting and refeeding in volunteers to identify nutrient-load metabolite-driven immunoregulation. Propionate, a short chain fatty acid (SCFA), and the SCFA-sensing G protein–coupled receptor 43 (ffar2) were coordinately and inversely regulated by fasting and refeeding. Propionate and free fatty acid receptor agonists decreased interferon-γ and interleukin-17 and significantly blunted histone deacetylase activity in CD4+T cells. Furthermore, propionate blunted nuclear factor κB activity and diminished interleukin-6 release. In parallel, propionate reduced phosphorylation of canonical T helper 1 (TH1) and TH17 regulators, STAT1 and STAT3, respectively. Conversely, knockdown of free fatty acid receptors significantly attenuated the anti-inflammatory role of propionate. Interestingly, propionate recapitulated the blunting of CD4+THcell activation in primary cells from obese individuals, extending the role of this metabolite to a disease associated with low-grade inflammation. Together, these data identify a nutrient-load responsive SCFA–G protein–coupled receptor linked pathway to regulate CD4+THcell immune responsiveness.Propionate blunts T helper cell responsiveness.

Cardiovascular-kidney-metabolic health reflects the interplay among metabolic risk factors, chronic kidney disease, and the cardiovascular system and has profound impacts on morbidity and mortality. There are multisystem consequences of poor cardiovascular-kidney-metabolic health, with the most significant clinical impact being the high associated incidence of cardiovascular disease events and cardiovascular mortality. There is a high prevalence of poor cardiovascular-kidney-metabolic health in the population, with a disproportionate burden seen among those with adverse social determinants of health. However, there is also a growing number of therapeutic options that favorably affect metabolic risk factors, kidney function, or both that also have cardioprotective effects. To improve cardiovascular-kidney-metabolic health and related outcomes in the population, there is a critical need for (1) more clarity on the definition of cardiovascular-kidney-metabolic syndrome; (2) an approach to cardiovascular-kidney-metabolic staging that promotes prevention across the life course; (3) prediction algorithms that include the exposures and outcomes most relevant to cardiovascular-kidney-metabolic health; and (4) strategies for the prevention and management of cardiovascular disease in relation to cardiovascular-kidney-metabolic health that reflect harmonization across major subspecialty guidelines and emerging scientific evidence. It is also critical to incorporate considerations of social determinants of health into care models for cardiovascular-kidney-metabolic syndrome and to reduce care fragmentation by facilitating approaches for patient-centered interdisciplinary care. This presidential advisory provides guidance on the definition, staging, prediction paradigms, and holistic approaches to care for patients with cardiovascular-kidney-metabolic syndrome and details a multicomponent vision for effectively and equitably enhancing cardiovascular-kidney-metabolic health in the population.

A growing appreciation of the pathophysiological interrelatedness of metabolic risk factors such as obesity and diabetes, chronic kidney disease, and cardiovascular disease has led to the conceptualization of cardiovascular-kidney-metabolic syndrome. The confluence of metabolic risk factors and chronic kidney disease within cardiovascular-kidney-metabolic syndrome is strongly linked to risk for adverse cardiovascular and kidney outcomes. In addition, there are unique management considerations for individuals with established cardiovascular disease and coexisting metabolic risk factors, chronic kidney disease, or both. An extensive body of literature supports our scientific understanding of, and approach to, prevention and management for individuals with cardiovascular-kidney-metabolic syndrome. However, there are critical gaps in knowledge related to cardiovascular-kidney-metabolic syndrome in terms of mechanisms of disease development, heterogeneity within clinical phenotypes, interplay between social determinants of health and biological risk factors, and accurate assessments of disease incidence in the context of competing risks. There are also key limitations in the data supporting the clinical care for cardiovascular-kidney-metabolic syndrome, particularly in terms of early-life prevention, screening for risk factors, interdisciplinary care models, optimal strategies for supporting lifestyle modification and weight loss, targeting of emerging cardioprotective and kidney-protective therapies, management of patients with both cardiovascular disease and chronic kidney disease, and the impact of systematically assessing and addressing social determinants of health. This scientific statement uses a crosswalk of major guidelines, in addition to a review of the scientific literature, to summarize the evidence and fundamental gaps related to the science, screening, prevention, and management of cardiovascular-kidney-metabolic syndrome.

African-Americans have an increased risk for diet-related diseases. Cooking is a dietary behavior that increases self-efficacy and social support, factors shown to be efficacious in optimizing diet. However, the overall inclusion of African-Americans within dietary interventions remains a key gap area for addressing diet-related disparities. The use of implementation frameworks, such as RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) for planning interventions may assist in improving inclusion of African-American predominate communities in dietary interventions.

IMPORTANCE: Rural populations experience an increased burden of heart failure (HF) mortality compared with urban populations. Whether HF incidence is greater among rural individuals is less known. Additionally, the intersection between racial and rural health inequities is understudied. OBJECTIVE: To determine whether rurality is associated with increased risk of HF, independent of cardiovascular (CV) disease and socioeconomic status (SES), and whether rurality-associated HF risk varies by race and sex. DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study analyzed data for Black and White participants of the Southern Community Cohort Study (SCCS) without HF at enrollment who receive care via Centers for Medicare & Medicaid Services (CMS). The SCCS is a population-based cohort of low-income, underserved participants from 12 states across the southeastern United States. Participants were enrolled between 2002 and 2009 and followed up until December 31, 2016. Data were analyzed from October 2021 to November 2022. EXPOSURES: Rurality as defined by Rural-Urban Commuting Area codes at the census-tract level. MAIN OUTCOMES AND MEASURES: Heart failure was defined using diagnosis codes via CMS linkage through 2016. Incidence of HF was calculated by person-years of follow-up and age-standardized. Sequentially adjusted Cox proportional hazards regression models tested the association between rurality and incident HF. RESULTS: Among 27 115 participants, the median (IQR) age was 54 years (47-65), 18 647 (68.8%) were Black, and 8468 (32.3%) were White; 5556 participants (20%) resided in rural areas. Over a median 13-year follow-up, age-adjusted HF incidence was 29.6 (95% CI, 28.9-30.5) per 1000 person-years for urban participants and 36.5 (95% CI, 34.9-38.3) per 1000 person-years for rural participants (P < .001). After adjustment for demographic information, CV risk factors, health behaviors, and SES, rural participants had a 19% greater risk of incident HF (hazard ratio [HR], 1.19; 95% CI, 1.13-1.26) compared with their urban counterparts. The rurality-associated risk of HF varied across race and sex and was greatest among Black men (HR, 1.34; 95% CI, 1.19-1.51), followed by White women (HR, 1.22; 95% CI, 1.07-1.39) and Black women (HR, 1.18; 95% CI, 1.08-1.28). Among White men, rurality was not associated with greater risk of incident HF (HR, 0.97; 95% CI, 0.81-1.16). CONCLUSIONS AND RELEVANCE: Among predominantly low-income individuals in the southeastern United States, rurality was associated with an increased risk of HF among women and Black men, which persisted after adjustment for CV risk factors and SES. This inequity points to a need for additional emphasis on primary prevention of HF among rural populations.

Mechanisms explaining the link between psoriasis, a proinflammatory condition, and cardiovascular disease are not fully known. PCSK9 is predominantly expressed in hepatocytes as a critical regulator of lipid metabolism, and clinical trials targeting PCSK9 reduce cardiovascular disease. Independent of its role in lipid metabolism, PCSK9 levels associate with endothelial dysfunction and predict cardiovascular events. We used two separate human psoriasis cohorts and the K14-Rac1V12−/+murine model of psoriasis to investigate PCSK9 and cardiovascular risk in psoriasis. In both psoriasis cohorts (n = 88 and n = 20), PCSK9 levels were 20% and 13% higher than in age-, sex-, and cholesterol-matched controls, respectively (P< 0.05 for each comparison) and correlated with PASI (r = 0.43, P< 0.05). Despite no difference in hepatocyte expression, K14-Rac1V12−/+mice demonstrated skin-specific PCSK9 staining, which was confirmed in human psoriatic lesional skin. In patients with psoriasis, PCSK9 levels correlated with impaired endothelial vascular health (e.g., early atherosclerosis, β = 4.5, P< 0.01) and log converted coronary artery calcium score (β = 0.30, P = 0.01), which remained significant after adjustment for Framingham risk, body mass index, and active biologic use. Taken together, these findings suggest, independent of cholesterol, an association between circulating PCSK9 and early as well as advanced stages of atherosclerosis in psoriasis.

Supplemental Digital Content is available in the text.

IMPORTANCE: Cardiovascular disease (CVD) is a leading cause of morbidity and mortality in the United States. Despite substantial declines in CVD mortality rates during past decades, progress against cardiovascular deaths in midlife has stagnated, with rates increased in some US racial/ethnic groups. OBJECTIVE: To examine the trends in premature (ages 25-64 years) mortality from CVD from 2000 to 2015 by demographics and county-level factors, including education, rurality, and the prevalence of smoking, obesity, and diabetes. DESIGN, SETTING, AND PARTICIPANTS: This descriptive study used US national mortality data from the Surveillance, Epidemiology, and End Results data set and included all CVD deaths among individuals ages 25 to 64 years from January 2000 to December 2015. The data analysis began in February 2018. EXPOSURES: Age, sex, race/ethnicity, and county-level factors. MAIN OUTCOMES AND MEASURES: Age-standardized mortality rates and average annual percent change (AAPC) in rates by age, sex, race/ethnicity, and county-level factors (in quintiles) and relative risks of CVD mortality across quintiles of each county-level factor. RESULTS: In 2000 to 2015, 2.3 million CVD deaths occurred among individuals age 25 to 64 years in the United States. There were significant declines in CVD mortality for black, Latinx, and Asian and Pacific Islander individuals (AAPC: range, −1.7 to −3.2%), although black people continued to have the highest CVD mortality rates. Mortality rates were second highest for American Indian/Alaskan Native individuals and increased significantly among those aged 25 to 49 years (AAPC: women, 2.1%; men, 1.3%). For white individuals, mortality rates plateaued among women age 25 to 49 years (AAPC, 0.05%). Declines in mortality rates were observed for most major CVD subtypes except for ischemic heart disease, which was stable in white women and increased in American Indian/Alaska Native women, hypertensive heart disease, for which significant increases in rates were observed in most racial/ethnic groups, and endocarditis, for which rates increased in white individuals and American Indian/Alaska Native men. Counties with the highest prevalence of diabetes (quintile 5 vs quintile 1: relative risk range 1.6-1.8 for white individuals and 1.4-1.6 for black individuals) had the most risk of CVD mortality. CONCLUSIONS AND RELEVANCE: There have been substantial declines in premature CVD mortality in much of the US population. However, increases in CVD mortality before age 50 years among American Indian/Alaska Native individuals, flattening rates in white people, and overall increases in deaths from hypertensive disease suggest that targeted public health interventions are needed to prevent these premature deaths.

ASCVD/CVD Risk Assessment

Heart Failure

This study sought to evaluate the influence of race/ethnicity on the relationship between body mass index (BMI) and mortality in heart failure with preserved ejection fraction (HFpEF) and HF with reduced EF (HFrEF) patients.

Social determinants of health (SDoH) include socioeconomic, environmental, and psychological factors that impact health. Neighborhood socioeconomic deprivation (NSD) and low individual-level socioeconomic status (SES) are SDoH that associate with incident heart failure, stroke, and cardiovascular mortality, but the underlying biological mechanisms are not well understood. Previous research has demonstrated an association between NSD, in particular, and key components of the neural-hematopoietic-axis including amygdala activity as a marker of chronic stress, bone marrow activity, and arterial inflammation. Our study further characterizes the role of NSD and SES as potential sources of chronic stress related to downstream immunological factors in this stress-associated biologic pathway. We investigated how NSD, SES, and catecholamine levels (as proxy for sympathetic nervous system activation) may influence monocytes which are known to play a significant role in atherogenesis. First, in an ex vivoapproach, we treated healthy donor monocytes with biobanked serum from a community cohort of African Americans at risk for CVD. Subsequently, the treated monocytes were subjected to flow cytometry for characterization of monocyte subsets and receptor expression. We determined that NSD and serum catecholamines (namely dopamine [DA] and norepinephrine [NE]) associated with monocyte C–C chemokine receptor type 2 (CCR2) expression (p < 0.05), a receptor known to facilitate recruitment of monocytes towards arterial plaques. Additionally, NSD associated with catecholamine levels, especially DA in individuals of low SES. To further explore the potential role of NSD and the effects of catecholamines on monocytes, monocytes were treated in vitrowith epinephrine [EPI], NE, or DA. Only DA increased CCR2 expression in a dose-dependent manner (p < 0.01), especially on non-classical monocytes (NCM). Furthermore, linear regression analysis between D2-like receptor surface expression and surface CCR2 expression suggested D2-like receptor signaling in NCM. Indicative of D2-signaling, cAMP levels were found to be lower in DA-treated monocytes compared to untreated controls (control 29.78 pmol/ml vs DA 22.97 pmol/ml; p = 0.038) and the impact of DA on NCM CCR2 expression was abrogated by co-treatment with 8-CPT, a cAMP analog. Furthermore, Filamin A (FLNA), a prominent actin-crosslinking protein, that is known to regulate CCR2 recycling, significantly decreased in DA-treated NCM (p < 0.05), indicating a reduction of CCR2 recycling. Overall, we provide a novel immunological mechanism, driven by DA signaling and CCR2, for how NSD may contribute to atherogenesis. Future studies should investigate the importance of DA in CVD development and progression in populations disproportionately experiencing chronic stress due to SDoH.

Supplemental Digital Content is available in the text.Meta-analyses are becoming increasingly popular, especially in the fields of cardiovascular disease prevention and treatment. They are often considered to be a reliable source of evidence for making healthcare decisions. Unfortunately, problems among meta-analyses such as the misapplication and misinterpretation of statistical methods and tests are long-standing and widespread. The purposes of this statement are to review key steps in the development of a meta-analysis and to provide recommendations that will be useful for carrying out meta-analyses and for readers and journal editors, who must interpret the findings and gauge methodological quality. To make the statement practical and accessible, detailed descriptions of statistical methods have been omitted. Based on a survey of cardiovascular meta-analyses, published literature on methodology, expert consultation, and consensus among the writing group, key recommendations are provided. Recommendations reinforce several current practices, including protocol registration; comprehensive search strategies; methods for data extraction and abstraction; methods for identifying, measuring, and dealing with heterogeneity; and statistical methods for pooling results. Other practices should be discontinued, including the use of levels of evidence and evidence hierarchies to gauge the value and impact of different study designs (including meta-analyses) and the use of structured tools to assess the quality of studies to be included in a meta-analysis. We also recommend choosing a pooling model for conventional meta-analyses (fixed effect or random effects) on the basis of clinical and methodological similarities among studies to be included, rather than the results of a test for statistical heterogeneity.

Background:Coronary heart disease (CHD) is the leading cause of death in the United States (US). Evidence supports adverse neighborhood conditions as a contributor to CHD. However, the impact of discriminatory housing practices, including historic redlining, on CHD across US cities remains understudied.Methods:Data on CHD for US cities were downloaded from the 500 Cities Project. We merged this data with census tract historic redlining data from the Mapping Inequality Project and census tract level demographic data from the American Community Survey. We used linear regressions to examine relationships between historic redlining scores and CHD adjusting for census tract level covariates.Results:12 cities from the US were included in the analyses. After controlling for covariates, these relationships' strength and significance varied by city and region. In the Northeast/Mid-Atlantic region (Boston, Baltimore, and New York), increases in redlining scores were associated with increases in the proportion of people with CHD (Table). In the Midwest, increases in redlining scores were associated with increases in the proportion of people with CHD in Detroit and Cleveland; this relationship was significant in Detroit and marginally significant in Cleveland. There were no significant associations in Chicago. In the South, census tracts with higher redlining scores were associated with higher CHD prevalence in Miami. Paradoxical relationships were seen in Atlanta where higher redlining scores were associated with a lower proportion of people with CHD; there were no significant associations in Dallas. In the West, increases in redlining scores were associated with increases in the proportion of people with CHD in Los Angeles; relationships were not statistically significant in San Francisco or Seattle.Discussion:This is one of the first studies to suggest differential impact of historic redlining on CHD across US cities. Additional research is needed to examine potential mechanisms that explain these associations.

Introduction:Chronic psychosocial stressors are associated with inflammation and cardiovascular (CV) risk, including insulin resistance (IR); however, potential DNA methylation (DNAm) mediators between stress-related inflammation and IR are not known.Hypothesis:DNAm biomarkers mediate the relationship between stress-related inflammation and IR.Methods:Participants from the DC Cardiovascular Health and Needs Assessment (DC-CHNA) underwent phenotyping at the NIH Clinical Center. Homeostatic Model Assessment for Insulin Resistance was calculated using insulin and glucose values. Social isolation, loneliness, and depression were determined using validated surveys. IL-8 was measured using an ELISA-based method. Principal component DNAm-based surrogate markers of leptin, cystatin C, and plasminogen activator inhibitor-1 were calculated from DNAm data obtained from participants' buffy coat samples. We examined relationships of interest with regression models adjusted for atherosclerotic cardiovascular disease (ASCVD) risk score and body mass index (BMI). Mediation analysis was used to evaluate DNAm measures as possible mediators.Results:The DC-CHNA consisted of 60 African American participants (mean age 61±11 years, 93% female) with ASCVD risk. Social isolation (β=0.34, p=0.009) and depression (β=0.30, p=0.04) associated with IL-8. IL-8 then inversely associated with DNAm-based surrogate leptin levels and directly associated with IR; leptin DNAm mediated the IL-8-IR relationship (Figure).Conclusions:We show a relationship between stress-associated IL-8 and IR mediated by DNAm-based surrogate leptin levels. While relationships between inflammation, serum leptin, and IR are documented, the impact of chronic stress on leptin DNAm in the context of CV risk requires further investigation in larger, diverse cohorts. DNAm-based surrogate markers of plasma proteins, such as leptin, could serve as a marker for increased CV risk in populations disproportionately exposed to chronic stress.

Introduction:Metabolic syndrome (MetS) can lead to harmful effects on cardiovascular health. Assessing whether links between perceived neighborhood social environment (PNSE) and MetS are mediated by physical activity (PA) levels will inform interventions to reduce population-level mortality attributed to MetS.Hypothesis:PNSE will be both directly and indirectly related to MetS severity via PA.Methods:This study utilized baseline data from the Jackson Heart Study, a prospective, community-based cohort of African American adults in Jackson, MS (total sample=3082; mean age 53.3 years; 64% female). PNSE variables included neighborhood violence, problems (higher value=more violence or problems), and social cohesion (higher value=more cohesion). MetS severity Z-score was the outcome (higher score indicates worse MetS). Validated self-reported total PA, based on active living, sports, and home/yard indices, was tested as the mediator. Linear regressions with bootstrap-generated 95% bias-corrected confidence intervals (BC CIs) were estimated to test for significant unstandardized indirect effects, controlling for covariates (age, education, smoking status, alcohol consumption, and diet). All analyses were stratified by sex.Results:In women, neighborhood violence, problems, and social cohesion were indirectly related to MetS via PA (B for indirect effects=.04, 95% BC CI=.01, .08; .03, 95% BC CI=.01, .06; and -.03, 95% BC CI=-.07, -.01, respectively). That is, higher violence and problems were related to lower PA (B=-1.06, 95%CI=-1.76, -.36; B=-.79, 95%CI=-1.26, -.32, respectively), while higher social cohesion was associated with higher PA (B=.86, 95%CI=.15, 1.58). In turn, higher PA was associated with lower MetS. All PNSE factors were directly related to MetS (p<.05). In men, neighborhood violence, problems, and social cohesion were indirectly related to MetS via PA (B for indirect effects=.06, 95% BC CI=.02, .12; .04, 95% BC CI=.01, .08; and -.06, 95% BC CI=-.11, -.02, respectively). Again, higher violence and problems were related to lower PA (B=-1.65, 95%CI=-2.58, -.71; B=-1.02, 95%CI=-1.64, -.40, respectively), while higher social cohesion was associated with higher PA (B=1.58, 95%CI=.64, 2.52). In turn, higher PA was associated with lower MetS. No PNSEs were directly related to MetS.Conclusions:Consistent with what we expected, higher perceived neighborhood violence and problems were positively related to MetS, and vice versa for social cohesion. These associations may be explained in part by PA levels. The data showed that indirect effects by PA were more pronounced in men than women. Future interventions to reduce MetS attributed to neighborhood issues should consider PA promotion tailored to women and men in conjunction with community efforts to reduce neighborhood violence and problems and encourage cohesive neighborhoods.

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 18FDG 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.

•We examine the burden of lifetime healthcare expenses among disadvantaged individuals•Black men have higher lifetime healthcare expenses compared to other demographic groups•Lifetime healthcare expenditure tends to increase with higher cardiovascular risk factor prevalence

Introduction:Identification of factors associated with preservation of cardiovascular health (CVH) during adolescence may inform strategies to reduce CV disease burden in adulthood.Hypothesis:CVH status is worse in later (16-18 years) vs early (13-15 years) adolescence and is influenced by socioeconomic factors.Methods:National Health and Nutrition Examination Survey (NHANES) 2007 to 2018 data (6 most recent complete survey cycles) analyzed. CVH status was characterized by AHA Life Simple 7 score (AHAS7). A representative sample (N=5874) of the US adolescent population was analyzed and weights used to estimate trends for the entire US adolescent population. The proportion of US adolescents with ideal (AHAS7 score 12-14), intermediate (8-11), and poor (0-7) CVH status calculated. Consecutive 2-year NHANES cycles were rescaled to consecutive integers to assess change in CVH score over time. Regression models were used to assess trend in CVH score over time and separately by age. Nonlinearity of secular trend was tested by assessing the significance of adding a quadratic term to the regression model (significance, p<0.01). CVH status by early vs late adolescence was assessed via categorical analysis as was the association between CVH status in early vs late adolescence and social determinants such as insurance status, poverty status (above and below 5x’s the national poverty level) and household reference (e.g., parent) education level.Results:CVH scores improved from 2007 to 2018 (p<0.0001), however, the proportion of youth with ideal CVH status declined with age and was highest in early and lowest in later adolescence (early 59% vs later 41%) (p<0.0001). The proportion of adolescents with ideal physical activity, smoking status, blood pressure, and cholesterol was lowest among older adolescents. Older adolescents are more likely to have no insurance (early 44% vs later 56%, p<0.0001). Other social determinants were not significantly different.Conclusions:Efforts to improve CVH status should begin no later than adolescence. Greater focus on preserved physical activity, BP and cholesterol management, reduced smoking and maintenance of health insurance coverage may lead to sustained CVH status throughout adolescence.

Background:Increased self-efficacy may improve health behavior, but little is known about the relationship between physical activity (PA) and nutrition self-efficacy and cardiovascular health behaviors associated with weight loss among African Americans (AAs).Methods:Examined the associations between PA and nutrition self-efficacy and self-reported PA and nutrition behaviors using AA data from the Washington DC CV Health and Needs Assessment, a community-based participatory research study. All completed the PA and Nutrition Self-Efficacy (PANSE) scale with sub-scores measuring participants’ self-efficacy for engaging in PA and nutrition behaviors (higher scores= greater self-efficacy). PA types (moderate-leisure PA, vigorous-leisure PA, and strength training) and dietary (red meat, fast foods, sodas, and vegetables) behavior scores were calculated using the International Physical Activity Questionnaire (IPAQ) for self-report PA or the National Health and Nutrition Examination Survey (NHANES) dietary screener for consumption of specific food products. Linear regression models were used to assess the associations between PANSE sub-scores and corresponding PA or dietary behavior adjusting for covariates.Results:Participants (N=117) were predominantly women (82.1%), mean age=59.4 (SD±12.3) years with mean BMI 32.6 (SD±7.0) kg/m2. While PA self-efficacy remained significantly and positively associated with self-reported moderate leisure PA and strength training, nutrition self-efficacy remained significantly and negatively associated with consumption of fast foods and sodas after adjusting for covariates (Table 1).Conclusion:PA and nutrition self-efficacy are associated with self-reported PA and nutrition behaviors among AAs. Interventions that augment self-efficacy may be particularly important in improving cardiovascular health behaviors by enhancing PA and nutrition behaviors aimed at weight loss among AAs.

Introduction:Neighborhood disadvantage is associated with a higher risk of sudden cardiac death. However, autopsy findings have never been investigated in this context. Here, we sought to explore associations between neighborhood disadvantage and cardiovascular findings at autopsy in cases of sudden death in the State of Maryland.Methods:State of Maryland investigation reports from 2,278 subjects within the CVPath Sudden Death Registry were screened for street addresses and 9-digit zip-codes. Area Deprivation Index (ADI), used as metric for neighborhood disadvantage, was available for 1,464 subjects; 650 of whom self-identified as Black and 814 as White. The primary study outcome measurements were causes of death and gross and histopathologic findings of the heart.Results:Subjects from most disadvantaged neighborhoods (i.e., ADI ≥ 8; n = 607) died at younger age compared with subjects from less disadvantaged neighborhoods (i.e., ADI ≤ 7; n = 857; 46.07 ± 14.10 versus 47.78 ± 13.86 years; p = 0.02) and were more likely Black or women. They were, however, less likely to die from cardiac causes of death (61.8% versus 67.7%; p = 0.02) and had less severe atherosclerotic plaque features, including plaque burden, calcification, intraplaque hemorrhage, and thin-cap fibroatheromas. In addition, subjects from most disadvantaged neighborhoods had lower frequencies of plaque rupture (18.8% versus 25.1%, p = 0.004). However, these associations were omitted after adjustment for traditional risk factors and race.Conclusion:Neighborhood disadvantage did not associate with cause of death or coronary histopathology after adjustment for cardiovascular risk factors and race, implying that social determinants of health other than neighborhood disadvantage play a more prominent role in cardiovascular pathology.

Supplemental Digital Content is available in the text.

Neighborhood socioeconomic disadvantage may contribute to depression. This study examined associations between neighborhood socioeconomic disadvantage, measured as deprivation, and depression severity within a broadly representative sample of the U.S. adult population. The sample (n = 6308 U.S. adults) was from the 2011–2014 National Health and Nutrition Examination Survey. Neighborhood deprivation was calculated using the 2010 U.S. Census and shown in tertile form. Depression severity was calculated from responses to the Patient Health Questionnaire-9 (PHQ-9) as a continuous depression severity score and binary Clinically Relevant Depression (CRD). Multilevel modeling estimated the relationship between deprivation and depression (reference = low deprivation). Models were additionally stratified by gender and race/ethnicity. U.S. adults living in high deprivation neighborhoods were more likely to have a higher PHQ-9 score (p < 0.0001). In unadjusted models, living in high deprivation neighborhoods associated with higher PHQ-9 (β = 0.89, SE = 0.15, p < 0.0001) and higher odds of CRD (OR = 1.35, 95% CI = 1.20–1.51). Living in medium deprivation neighborhoods associated with higher PHQ-9 (β = 0.49, SE = 0.16, p = 0.0019). Associations between deprivation and depression severity lost significance after adjusting for individual-level SES. The results suggest that, for U.S. adults, the relationship between neighborhood-level disadvantage and depression may be attenuated by individual-level SES.

To evaluate the cardiometabolic outcomes associated with discordant visceral adipose tissue (VAT) and liver fat (LF) phenotypes in 2 cohorts.

The aim of this study was to test the mediating role of perceived discrimination and stress on associations between perceived neighborhood social environment (PNSE) and TV viewing.

Socioeconomically disadvantaged neighborhoods have been associated with poor health outcomes. Little is known about the biological mechanism by which deprived neighborhood conditions exert negative influences on health. Data from the 1999–2002 National Health and Nutrition Examination Surveys (NHANES) were used to assess the relationship between neighborhood deprivation index (NDI) and log-transformed leukocyte telomere length (LTL) via multilevel modeling to control for census tract level clustering. Models were constructed using tertiles of NDI (ref = low NDI). NDI was calculated using census tract level socioeconomic indicators from the 2000 U.S. Census. The sample (n = 5,106 adults) was 49.8% female and consisted of 82.9% non-Hispanic whites, 9.4% non-Hispanic blacks, and 7.6% Mexican Americans. Mean age was 45.8 years. Residents of neighborhoods with high NDI were younger, non-white, had lower educational attainment, and had a lower poverty to income ratio (all p < 0.0001). Neighborhood deprivation was inversely associated with LTL among individuals living in neighborhoods with medium NDI (β = −0.043, SE = 0.012, p = 0.0005) and high NDI (β = −0.039, SE = 0.013, p = 0.003). Among men, both medium (β = −0.042, SE = 0.015, p = 0.006) and high (β = −0.047, SE = 0.015, p = 0.001) NDI were associated with shorter LTL. Among women, only medium NDI (β = −0.020, SE = 0.016, p = 0.009) was associated with shorter LTL. After controlling for individual characteristics, including individual-level socioeconomic status, increasing neighborhood socioeconomic deprivation is associated with shorter LTL among a nationally representative sample of US adults. This suggests that telomere shortening may be a mechanism through which neighborhood deprivation results in poor health outcomes.

Introduction:Psoriasis is a chronic inflammatory skin disease associated with accelerated development of asymptomatic coronary artery disease (CAD) by coronary computed tomography angiography (CCTA). Allostatic load score is a multidimensional measure related to chronic stress which incorporates cardiovascular, metabolic and inflammatory indices. To better understand the physiologic impact of chronic stress in psoriasis, we studied the association between allostatic load score and subclinical CAD.Hypothesis:We hypothesized that allostatic load score would associate with coronary artery disease burden beyond traditional risk factors in an ongoing psoriasis cohort study.Methods:Consecutive psoriasis patients (n=275) underwent CCTA for assessment of coronary artery disease burden (QAngio, Medis). Allostatic load score was determined using established methods (see Table 1 footnote). The association between coronary artery disease burden and allostatic load score was characterized by multivariable regression (STATA 12).Results:Psoriasis patients were middle-aged, predominantly male and white, with low cardiovascular risk by Framingham risk score and moderate-severe psoriasis severity (Table 1). Allostatic load score associated with total coronary burden (β=0.39; p<0.001) and non-calcified coronary burden (β=0.40; p<0.001) in unadjusted analyses. In multivariable models, allostatic load score was still associated with total coronary burden (β=0.30; p<0.001) and non-calcified coronary burden (β=0.31; p<0.001) independent of race, Framingham risk score and waist-hip ratio.Conclusions:Allostatic load score positively associated with both total and non-calcified coronary artery burden beyond traditional risk factors, suggesting multisystem physiologic dysregulation related to chronic stress may drive subclinical atherosclerosis in psoriasis. Efforts to understand stress effects and its reduction are critical in this population at high-risk for cardiovascular disease.

Introduction:Little is known about whether links between perceived neighborhood social environment (PNSE) and depressive symptoms are mediated by physical activity (PA) levels.Hypothesis:We tested the hypotheses that total PA mediates relations between PNSE and depressive symptoms.Methods:We used Jackson Heart Study (JHS) baseline data. JHS is a prospective, community-based study of African Americans in the Jackson, MS (valid samples=2082; Mage 52.4 years; 64% female). PNSE variables included neighborhood violence, problems (higher value=more violence or problems), and social cohesion (higher value=more cohesion). Depressive symptoms were measured by the Center for Epidemiological Studies Depression (CES-D) scale. Validated total PA, based on active living, sport, and work indices, was tested as the mediator. Linear regressions with bootstrap-generated 95% bias-corrected confidence intervals (BC CIs) were estimated using SAS 9.4 to test for significant unstandardized indirect effects, controlling for all covariates.Results:Participants had a mean depressive symptoms score of 10.8 (SD=8.1). Neighborhood violence and problems were indirectly related to depressive symptoms via total PA (βfor indirect effects=.21, 95% BC CI=.02, .48 and .13, 95% BC CI=.01, .32, respectively). That is, higher violence and problems were related to lower total PA. In turn, higher total PA was associated with lower depressive symptoms (Figure 1). Neighborhood violence and problems also were directly related to depressive symptoms (p<.05). Yet, social cohesion was not indirectly or directly related to depressive symptoms.Conclusions:Higher perceived neighborhood violence and problems were positively related to depressive symptoms. These associations may be explained in part via lower total PA levels. Future interventions to reduce depressive symptoms attributed to neighborhood issues should consider PA promotion in conjunction with community efforts to reduce neighborhood violence and problems.

Introduction:A ?malignant? subphenotype of left ventricular hypertrophy (LVH) has been described, in which elevations in cardiac biomarkers identify individuals with LVH at high risk for developing heart failure (HF).Hypothesis:We hypothesized that a higher prevalence of malignant LVH among blacks may contribute to racial disparities in HF risk.Methods:15,710 participants without prevalent cardiovascular disease were pooled from 3 population-based cohort studies, the ARIC Study, DHS and MESA. Participants were classified into 3 groups: those without ECG-LVH, those with ECG-LVH and normal biomarkers (hs-cTnT < 6 ng/L and NT-proBNP < 100 pg/mL), and those with ECG-LVH and abnormal levels of either biomarker (malignant LVH). The outcome was incident HF.Results:Over the 10 year follow up period, HF occurred in 512 (3.3%) participants, with rates 5.2% among black men (BM), 3.8% in white men (WM), 3.2% in black women (BW), and 2.2% in white women (WW). The prevalence of malignant LVH was 3-fold higher among BM and BW vs WM and WW. Compared with participants without LVH, the adjusted hazard ratio for HF was 2.8 (95% CI 2.1-3.5) in those with malignant LVH and 0.9 (95% CI 0.6-1.5) in those with LVH and normal biomarkers, with similar findings in each race/sex subgroup. Mediation analyses indicated that 63% of excess hazard for HF among BM and 35% of the excess hazard among BW was explained by the higher prevalence of malignant LVH in blacks. Of BM who developed HF, 30.8% had malignant LVH at baseline, with a population attributable fraction (PAF) of 0.21. The proportion of HF cases occurring among those with malignant LVH, and corresponding PAF, were intermediate and similar among BW and WM and lowest among WW.Conclusions:A higher prevalence of malignant LVH may in part explain the higher risk of HF among blacks vs whites. Strategies to prevent development or attenuate risk associated with malignant LVH should be investigated as a strategy to lower HF risk and mitigate racial disparities.

Background:Cardiovascular disease (CVD) disproportionately affects minority populations; biologic mechanisms that promote higher CVD risk are understudied in diverse populations. We have previously shown that vascular inflammation correlates positively with total monocyte counts from clinical blood counts (CBC) in a community-based cohort of 42 African Americans (AA). CBC could not differentiate between monocyte subsets?information we thought to be of importance. Therefore, we took an ex vivoapproach.Methods and Results:PBMCs from a healthy blood bank donor were isolated and treated with 10% participant serum overnight followed by flow cytometry analysis of monocyte subsets and their chemokine receptor 2&5 expression (CCR2/CCR5). Linear regression analysis revealed that classical monocytes displayed a negative correlation with LDL levels (?=-0.38, p=0.02). Non-classical and intermediate monocytes displayed a positive correlation with LDL (?=0.38, p=0.02; ?=0.36, p=0.03, respectively). The expression of CCR2 on non-classical monocytes significantly correlated with total cholesterol levels (?=0.37, p=0.03) while a trend with LDL levels was observed (?=0.31, p=0.06). This prompted us to investigate LDL?s role in CCR2/5 expression in vitro. PBMC?s from five healthy blood bank donors were treated with LDL for 4h. We observed that LDL induced a significant decrease in classical monocytes while non-classical, pro-inflammatory monocytes doubled (Figure). A 20% increase in CCR2 expression was detected upon LDL treatment only in non-classical monocytes.Conclusions:Our data suggest that LDL initiates trans-differentiation of monocytes towards a pro-inflammatory phenotype while simultaneously increasing chemokine receptor CCR2 expression in an AA population. Larger studies are needed to examine potential mechanisms that promote these CCR2 expression changes and may be associated with increased CVD risk among African Americans.

Introduction:Increased psychosocial stress and obesity are both associated with elevated risk of cardiovascular disease (CVD). However, the effect of change in cumulative psychosocial stressors (stressors) on change in body mass index (BMI) over time is unknown, particularly among older women, a population in whom weight change characterization is complex.Methods and Results:We examined change in stressors in relation to change in BMI among 20,750 women without CVD or cancer at baseline (2012-13) participating in the Women?s Health Study (WHS) follow-up cohort. Stressors and BMI were collected at two time points 2012-13 (Baseline: T1; mean age=71.8 ? 5.8 years) and 2014-15 (Follow-up: T2; mean age=73.8 ? 5.8 years). Our measures of stressors were comprised of a composite of 8 domains, including acute (e.g. negative life events) and chronic (e.g., financial) stressors. We defined stressors over 3 years of follow-up into four categories: chronically low, delayed, acutely high, and chronically high; and BMI change was grouped into three categories (BMI: loss >3%, gain >3%, and maintenance ? 3%). Women with chronically high stress and delayed stress were younger, current smokers and reported more anxiety/depressive symptoms compared to other women. Women with chronically high stress were more likely to have diabetes, hypertension and hypercholesterolemia than their counterparts. Compared to women who maintained both their BMI and had low stress over time, women with delayed stress or chronically high stress had higher odds of decreased BMI [Delayed: Odds Ratio (OR) 1.16,95% Confidence Interval (CI): 1.03-1.30; Chronically High: OR=1.12, 95% CI 1.01-1.24] (Table 1).Conclusion:Chronically high and delayed cumulative stress were associated with higher odds of weight loss in older women over 3 years. Future studies are needed to test associations between stressors and metabolic, hormonal and autonomic factors resulting in adiposity or musculoskeletal changes.

Background:Despite well-documented evidence that one’s neighborhood environment and resource access are associated with cardiovascular (CV) risk, little is known about how physical activity (PA) resource access availability and type are related to vigorous PA (VPA) in urban communities.Methods:Using cross-sectional data from the Washington DC CV Health and Needs Assessment, a sample of 37 black adults living in low-income, limited-resource DC communities, we created one outcome: self-reported VPA hours/week. We used Geographic Information Systems to create three exposure variables: counts of parks, recreation facilities, and private gyms within 800 and 1600-meter (m) line-based road network buffers around homes. We examined the relationship between the three exposures and VPA in models adjusted for demographics (age, sex, and income) and neighborhood factors, including neighborhood deprivation index (NDI), neighborhood environment perception (NEP), or walk score (WS), separately.Results:Participants (mean age=57.65 years) reported a mean VPA hr/wk of 3.46. After separately adjusting for neighborhood factors, greater availability of parks within 800m and 1600m positively associated with VPA (p<0.01) (Table). Positive associations between recreation facilities and VPA were found with 1600m buffer (p<0.05), but not 800m. Private gyms had the weakest relationship with VPA. When considering WS, only the relationship with parks remained significant.Conclusions:Increased availability of parks was positively related to VPA, even after adjusting for NDI, NEP or WS. However, relationships were not as robust for recreation facilities and private gyms, perhaps due to higher likelihood of barriers to use or limited availability in these communities. Our findings suggest that DC public health professionals should consider prioritizing increased availability of PA resources, especially parks, to promote PA and ultimately improve CV health outcomes for residents within limited-resource communities.

Background:Although evidence suggests that extremes of sleep (i.e. long and short) are associated with cardiovascular disease-related risk factors in the general population, research examining the association between the extremes of sleep and obesity in older women is limited.Methods and Results:We used the Women’s Health Study (WHS) 2012-2013 follow-up cohort of 21,726 older women (mean age = 72.1 ± 6.0 years old) to examine the cross-sectional association between extremes of sleep and obesity. Women with cancer or missing body mass index (BMI) data were excluded. Long sleep was defined as > 9 hours/day, short sleep as < 6 hours/day, and sleep of 6-9 hours/day was the reference. Sleep duration and BMI were self-reported measures. Approximately 23.3% of women were obese (BMI ≥ 30 kg/m2).Overall, women who were obese and had either long or short sleep were less likely to exercise, and more likely to have history of diabetes, depression symptoms, and lower education and income levels. Women who were obese and long sleepers were more likely to use alcohol and have history of hypertension, while short sleepers were more likely to be current smokers. Logistic regression analyses revealed that older women with long sleep and short sleep had 30% higher odds of obesity, respectively, compared to women who slept 6-9 hours, adjusting for age and race/ethnicity. These relationships were attenuated and lost significance when controlling for potential important confounders (Table 1).Conclusion:Older women reporting extremes of sleep had higher odds of obesity compared to women who sleep 6-9 hours, after control for age and race/ethnicity. Further adjustment for traditional cardiovascular risk factors and socioeconomic parameters resulted in loss of significance.