tbuckley/cabot-search huggingface dataset:
Abstract P3034: Plasma branched-chain amino acid levels and cardiovascular disease risk factors: a longitudinal analysis of a lifestyle trial
Authors: Mahya Mehrihajmir
Journal: Circulation (2025)

Purpose: Branched-chain amino acid (BCAAs) levels have been associated with a higher risk of cardiovascular diseases (CVD), but studies of CVD risk factors have mainly been cross-sectional. We examined the longitudinal association between changes in BCAA levels and CVD risk factors in a lifestyle trial. Method: We used data on 708 male and female participants, aged 25-78, of the U.S. PREMIER study. Data and biospecimens were from the NHLBI Biologic Specimen and Data Repository Information Coordinating Center. Participants were divided into control, lifestyle intervention, or lifestyle plus DASH diet groups. Biomarkers were measured with NMR spectroscopy. Multiple linear regression models assessed changes in BCAA levels in relation to changes in cardiometabolic risk factors over 6 months. Estimates were expressed per SD change in BCAA levels and adjusted for age, sex, race, marital status, region, and body mass index changes. Results: Increases in BCAA levels were associated with increases in insulin resistance (HOMA-IR) (Beta = 0.22, SE = 0.07, p = 0.005), inflammation (GlycA) (Beta = 0.03 mmol/l, SE = 0.004, p &lt;0.001), Apolipoprotein B (Beta = 0.02 g/l, SE = 0.006, p &lt;0.001), and VLDL-cholesterol levels (Beta = 0.03 mmol/l, SE = 0.007, p &lt;0.001).. Associations for other lipoprotein measures differed for individual BCAAs. Increases in valine were associated with LDL-cholesterol (Beta = 0.07 mmol/l, SE = 0.01, p &lt;0.001), with no significant association for leucine and isoleucine. Isoleucine was inversely associated with HDL-C (Beta = -0.03 mmol/l, SE = 0.01, p &lt;0.001) and Apolipoprotein A (Beta = -0.02 g/l, SE = 0.009, p = 0.004). Also, leucine was inversely associated with HDL-C (Beta = -0.04, SE = 0.01, p &lt;0.001), Apolipoprotein A (Beta = -0.03, SE = 0.009, p &lt;0.001) and triglyceride (Beta = -0.05 (mmol/l), SE = 0.01, p = 0.004) while valine had a direct association with HDL-C (Beta = 0.03, SE = 0.01, p &lt;0.001), Apolipoprotein A (Beta = 0.04, SE 0.009, p &lt;0.001) and triglyceride (Beta = 0.06, SE = 0.01, p = 0.001). BCAA levels were not significantly associated with fasting glucose and blood pressure. Conclusion: Increases in BCAA levels were associated with insulin resistance, inflammation, and unfavorable lipid profiles. These findings support BCAA levels as a target for CVD prevention. Further research is warranted to elucidate possible differences in the effects of individual BCAAs on lipid metabolism.
Abstract P2094: Atrial Fibrillation and Risk of Incident Cognitive Impairment: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study
Authors: Vinh Le, Katherine Wilkinson, Suzanne Judd, Elsayed Soliman, Hyacinth I. Hyacinth, Nels Olson, Melissa Smith, Mary Cushman
Journal: Circulation (2025)

Introduction: Atrial fibrillation (AF) and cognitive impairment are expected to double in prevalence over the next 20 years. While most literature on AF and risk of cognitive disorders is focused on dementia, there is little evidence on cognitive impairment or non-stroke populations. We addressed this question in the REGARDS cohort. Hypothesis: Baseline AF is associated with increased risk of incident cognitive impairment (ICI) in REGARDS participants with and without prevalent stroke. We tested for differences in this association by prevalent stroke, race (Black and White), and oral anticoagulant use, and for the attenuating effect of selected biomarkers on associations. Methods: REGARDS enrolled 30,239 persons &gt; 45 years old in 2003-07. AF was defined by self-report or ECG. ICI was defined during follow-up by robust cognitive norms based on the Montreal Cognitive Assessment and Six-Item Screener. HRs of time to ICI with AF were calculated by Cox proportional hazards models (Table footnote), with censoring at death or last follow-up. Considered individually, interaction terms for prevalent stroke, race, and oral anticoagulant use with AF were assessed. Results: Among 23,638 participants with mean follow-up 12.8 years (mean age 64.3 years, 56.3% women, 37.6% Black), the association of AF with ICI was modest (HR 1.21; see Table). The adjusted HR was greater in those with prevalent stroke than without stroke (1.69 vs. 1.05). Among those with prevalent stroke, there was little impact of added adjustment for anticoagulant use; with added adjustment for each biomarker individually, there was small-modest attenuation by each biomarker. HRs did not differ by race or oral anticoagulant use (both p interactions &gt;0.4). Conclusion: Independent of other factors including anticoagulant use, AF was associated with ICI in those with prevalent stroke, but not in those without prevalent stroke. Biomarkers had modest attenuating effects on the association among those with prevalent stroke. Results underscore the importance of considering cognitive impairment after stroke in those with AF and identifying underlying causes, which could involve inflammation.
Abstract P1090: Inhibition of Inositol 1,4,5-trisphosphate receptors (ITP3Rs) in Cardiac Myofibroblasts Attenuates Post-Ischemic Cardiac Fibrosis
Authors: Urna Kansakar, Fahimeh Varzideh, Xujun Wang, Gaetano Santulli, Stanislovas Jankauskas
Journal: Circulation (2025)

Introduction: Cardiac fibrosis is one of the major pathophysiologic features of ischemic cardiac disorders and substantial evidence has shown that cardiac fibroblasts and their activated form (myofibroblasts) are key players in heart failure progression. Inositol 1,4,5-trisphosphate receptors (ITP3Rs a.k.a. IP3Rs) are intracellular calcium release channels that play a critical role in calcium signaling, influencing cardiac remodeling and fibrosis. In both human and mouse fibroblasts, all three isoforms of ITP3Rs (ITP3R1, ITP3R2, and ITP3R3) are expressed, exhibiting redundant features. There is a lack of functional studies investigating the precise role of ITP3Rs in post-ischemic cardiac fibrosis in vivo . We assessed the hypothesis that after ischemia/reperfusion (I/R), ITP3Rs mediate the activation of cardiac fibroblasts and their persistence. Our data indicates that all three isoforms of ITP3Rs are increased in cardiac fibroblasts after myocardial infarction. Methods: Using a Cre/lox recombination strategy, we developed a novel mouse model (ITP3RKO) in which all isoforms of ITP3R are specifically deleted in cardiac myofibroblasts. This ITP3RKO model offers a unique opportunity to dissect the specific contributions of ITP3R to the progression of cardiac fibrosis, providing insights that were previously obscured by the compensatory mechanisms observed in models targeting individual isoforms. By selectively deleting all ITP3R isoforms in cardiac myofibroblasts, we can more accurately assess the role of ITP3R signaling in fibrosis, inflammation, and cardiac remodeling post-ischemia. This approach lays the foundation for more precise therapeutic strategies aimed at modulating ITP3R function in the context of heart disease. Results: Our data show that ITP3RKO mice exhibit reduced fibrosis and attenuated myocardial dysfunction compared to ITP3Rflox littermates after I/R. We further assessed the functional relationships between ITP3Rs and cardiac fibrosis in primary isolated fibroblasts at different time points and in response to established stimuli, to assess their survival, proliferative, migratory, and contractile capacity. Conclusion: Our studies are highly significant and innovative as they identify potential innovative therapeutic strategies to target excessive post-ischemic cardiac fibrosis and provide the first assessment of the role of ITP3R in activated myofibroblasts using a specific Cre/lox recombination model.
Abstract P3165: Summary Measure of Social Determinants of Health/Health Equity and Stroke Burden among Mississippi Adults
Authors: Vincent Mendy, Tawandra Rowell-Cunsolo, Enkhmaa Byambaa
Journal: Circulation (2025)

Background: In 2022, ~97,000 Mississippi adults self-reported receiving a stroke diagnosis. Social determinants of health (SDOH) contribute to stroke burden and associated disparities and mortality. We examined the association between a summary measure of SDOH and stroke burden among Mississippi adults. Methods: Using the SDOH and Health Equity (SDOH/HE) Module data from 3,994 respondents in the 2022 Mississippi Behavioral Risk Factor Surveillance System survey, we conducted multivariable logistic regression models to examine the association between a SDOH/HE summary measure and stroke. Results: Participants who received food stamps or were enrolled in the Supplemental Nutrition Assistance Program (adjusted odds ratio, AOR, 3.10), experienced food insecurity (AOR, 2.49) or mental distress (AOR, 2.20) had significantly higher odds of stroke. Mississippians experiencing three (AOR, 2.79) or more (AOR, 3.27) of SDOH/HE risk factors had higher odds of stroke compared to those experiencing no SDOH/HE risk factors. Conclusions: Mississippi adults with multiple SDOH/HE risk factors had significantly higher odds of stroke than those with no SDOH/HE risk factors. These findings highlight the importance of addressing multiple SDOH/HE factors in stroke burden and the need for targeted interventions among Mississippi adults experiencing multiple SDOH/HE risk factors.
Abstract P1099: A Daily Diary Examination of the Associations of Adverse Childhood Experiences, Anticipated Discrimination, and Blood Pressure among Sexual and Gender Minority Adults
Authors: Lisa Pardee, Lauren Bochicchio, Billy Caceres
Journal: Circulation (2025)

Background: Chronic psychosocial stressors, such as anticipated discrimination and adverse childhood experiences, have been shown to influence hypertension risk among stigmatized adults. Emerging research suggests that individuals exposed to adverse childhood experiences later report greater discrimination as adults. Researchers theorize that exposure to adverse childhood experiences likely moderate the association between discrimination and blood pressure (BP); however, this remains underexplored. Therefore, we sought to examine whether adverse childhood experiences moderated the associations of anticipated discrimination and BP in a diverse sample of adults. Methods: Data were obtained from a 30-day online diary study of sexual and gender minority (SGM; e.g., gay/lesbian, bisexual, transgender) adults in the United States. Participants completed daily electronic diaries that assessed anticipated discrimination every morning. Home BP was assessed every day at awakening and before bedtime. Adverse childhood experiences, including childhood physical, emotional, and sexual abuse, were assessed at baseline using a validated questionnaire. Mixed-effects linear models, adjusted for demographic factors, estimated the associations between daily anticipated discrimination and BP and the moderating role of adverse childhood experiences. Results: The sample included 31 SGM adults with a mean age of 27.1 years (±7.50). Approximately 83% of participants were Latinx and 49% were multiracial. We found that 39% of the sample reported exposure to 4 or more adverse childhood experiences. Results of mixed-effects linear models suggested that daily anticipated discrimination was not significantly associated with BP. However, we did find evidence that childhood physical abuse significantly strengthened the association between daily anticipated discrimination and morning diastolic BP (β(SE) = 2.36 (0.88), p = 0.01). Childhood emotional and sexual abuse were not significant moderators. Conclusions: Our findings highlight the importance of considering the moderating effects of adverse childhood experiences on the association between daily anticipated discrimination and BP among SGM people. Future research is needed with larger samples to understand the role that adverse childhood experiences (particularly childhood physical abuse) may play in sensitizing individuals to greater exposure to psychosocial stress and subsequent hypertension risk in adulthood.
Abstract P3033: Determining Decision Thresholds For Physicians And Parents For Instituting A Do-Not-Attempt-Resuscitation Order For Pediatric In-Hospital Cardiac Arrest Patients – A Cross-Sectional Study Of Parents And Physicians In The United States
Authors: Minaz Mawani, Ye Shen, Jessica Knight, Bryan McNally, Mark Ebell
Journal: Circulation (2025)

Introduction: Decision-making about resuscitating a critically ill child is complex but common. We aimed to study the survival thresholds at which a physician, compared to parents, decides to treat or withhold resuscitating a child. Moreover, we aimed to compare physicians' estimates of survival with the estimates calculated using data from a nationwide registry. Methods: We conducted a cross-sectional survey-based study including parents and physicians in the United States. Clinical vignettes based on hypothetical survival probabilities were used to study and compare the decision thresholds for parents and physicians. Vignettes developed using the Get-With-The-Guidelines-Resuscitation registry were used to explore physicians’ decision thresholds and compare the physician-estimated survival with the survival from the data. Thresholds were determined for each vignette using mixed-effect logistic regression models. Results: A total of 167 parents and 43 physicians provided decisions for 501 and 257 vignettes respectively. The decision threshold for survival to discharge was 5.3% (95% CI: 3.7 to 7.0) for physicians and 1.2% (95% CI: -0.8 to 3.0) for parents. Whereas the decision threshold for survival to discharge with PCPC 1 or 2 was 3.5% (95% CI: 1.1 to 7.1) for physicians and 0.6% (95% CI: -1.2 to 1.8) for parents. Physicians overestimated the likelihood of survival. About 58% estimated a higher survival than that predicted by the multivariate model. The Do-Not-Attempt-Resuscitation threshold based on physician-estimated survival probability was 13% and the threshold based on model-based probability was 5.3%, the same as the one calculated using hypothetical survival probabilities. Conclusions: Using the model-based and hypothetical probability of survival, we estimated the decision threshold for physicians and parents to be 5.3% and 1.2% respectively. This illustrates that parents still want to attempt resuscitation at a survival probability where physicians would recommend withholding the resuscitation. These findings have implications for clinical practice and counseling the parents of critically ill hospitalized children.
Abstract P3161: Discrimination in Healthcare is Associated with Increased Stroke Risk among Older Adults in the United States
Authors: Michael Green, Ann Marie Navar, Emily Obrien, M. Brookhart, Roland Thorpe, Matthew Dupre
Journal: Circulation (2025)

Introduction: Discrimination in healthcare strains patient-provider relationships and may contribute to disparities in outcomes. When patients feel disrespected, they could be less likely to trust providers or seek follow-up care, which poses a challenge for cardiovascular risk management. We assessed the association between discrimination in healthcare and incidence of stroke. Methods: We used nationally-representative longitudinal data from the 2008-2020 Health and Retirement Study to examine the association between stroke and discrimination in healthcare. Participants were ages 50-80 at baseline, had no history of stroke, and were followed for up to 12 years (mean follow-up=6.9 years). First occurrence of stroke was ascertained from participant-reported diagnosis of stroke by a doctor during follow-up (month/year). Discrimination in healthcare was assessed at baseline by asking respondents how often they “receive poorer service or treatment than other people from doctors or hospitals.” Cox proportional hazards models were used to estimate the incidence of stroke during the follow-up period (n=518 events). Confounding was controlled through adjustment for baseline covariates that included sociodemographic factors (age, gender, race, ethnicity, education), health status (disease diagnoses [diabetes, hypertension, heart disease]), and prior healthcare utilization (doctor visits and hospitalizations in past 2 years). Results: Among study participants (n=14,215, median age 62, 41.01% male, 72.68% White, 19.63% Black, 7.69% Hispanic), 19.19% (n=2,728) reported experiencing discrimination in healthcare settings. Those who experienced discrimination were more likely to have a stroke during follow-up compared to participants who did not report discrimination (4.5% vs. 3.4%, P =.010). Unadjusted proportional hazard models showed that discrimination in healthcare was associated with an increased hazard of stroke (hazard ratio [HR]=1.33, 95% confidence interval [CI]= 1.08-1.62). The association persisted after adjusting for all covariates (HR= 1.29, CI=1.05-1.58). Conclusions: Discrimination in healthcare was associated with increased stroke risk after adjusting for factors which impact both exposure to discrimination and risk of stroke. Future research should consider how changes in health status and/or experiences of discrimination during the course of care may contribute to this association.
Abstract P3169: Significant Social Determinants of Health Disparities Exist Between Rural and Non-rural Residents with Elevated Blood Pressure: Findings from the LINKED-BP Study
Authors: Sarah Slone, Janice Dugbartey, Yuling Chen, Bunmi Ogungbe, Kathryn Foti, Bharat Poudel, Cheryl Dennison Himmelfarb, Yvonne Commodore-Mensah
Journal: Circulation (2025)

Background: Rural populations face multiple challenges related to social determinants of health (SDOH). However, the extent of these disparities between rural and non-rural residing people with elevated blood pressure or untreated stage 1 hypertension is not well described. Further understanding of these disparities in the context of a hypertension prevention program focused on addressing SDOH that may contribute to the development of hypertension may inform targeted interventions. Objective: To examine differences in SDOH between rural and non-rural residents with elevated blood pressure or untreated stage 1 hypertension and identify areas for targeted interventions within the context of a blood pressure management program. Methods: This cross-sectional study analyzed baseline data from the LINKED-BP (Home Blood Pressure Telemonitoring Linked with Community Health Workers to Improve Blood Pressure) Program. SDOH were assessed using standardized questionnaires covering education, income, housing, food security, transportation, utilities, and social support. Rurality was determined based on zip code. Chi-square tests for categorical variables and Kruskal-Wallis tests for continuous variables were used for comparisons between rural and non-rural groups. Results: The study included 308 adults (127 rural, 181 non-rural) with known ZIP codes. People residing in rural areas had lower educational attainment (25.2% vs 1.1% with less than high school education, P&lt;0.001) and lower income (40.2% vs 6.1% earning ≤$39,999 annually, P&lt;0.001) compared to non-rural residents. Food insecurity (24.4% vs 5.0%, P&lt;0.001) and transportation needs (19.7% vs 3.9%, P&lt;0.001) were more prevalent in rural areas. Housing insecurity was higher in rural areas but was not statistically significant (5.5% vs 1.7%, P=0.060). No differences were found in housing conditions, utility needs, or social/emotional support. Conclusions: Significant SDOH disparities exist between rural and non-rural populations particularly in education, income, food security, and transportation access. These findings highlight potential challenges in implementing home blood pressure telemonitoring programs in rural areas. Targeted interventions addressing these SDOH factors could enhance the effectiveness of blood pressure management programs in rural communities. Future research should explore whether proactively addressing SDOH disparities in rural communities prevents hypertension and cardiovascular disease.
Abstract P3060: A Measure of Residential Segregation and Thrombo-inflammation in Black and White Americans
Authors: Erin Manogaran, Andrew Sparks, Ryan Packer, Paige Brochu, Suzanne Judd, Virginia Howard, Timothy Plante, Leann Long, Katherine Cheung, Mary Cushman, Debora Kamin Mukaz
Journal: Circulation (2025)

Introduction: Development of hypertension is linked to thrombo-inflammation. In the U.S., Black women have the highest hypertension prevalence of any race-gender group, and Black people have higher thrombo-inflammatory responses than White people. Evidence on residential segregation— a manifestation of structural racism and a key driver of health inequities— and thrombo-inflammation is limited. This study examined race and/or gender differences in the association of a measure of residential segregation and hypertension-related thrombo-inflammatory biomarkers. Methods: We included 4,362 Black and White participants of the REasons for Geographic And Racial Differences in Stroke study. Residential segregation was measured with the delta index (the proportion of Black people that would need to move across census tracts to achieve a uniform density in a county). Regression models assessed associations of the delta index with 8 thrombo-inflammatory biomarkers: C-reactive Protein, D-dimer, E-selectin, factor IX, interferon-γ, interleukin (IL)-6, and tumor necrosis factor-α, and IL-1β. Racial and/or gender differences in associations were tested. Results: The delta index was only associated with IL-1β. The figure shows that each SD higher delta index was associated with 39% lower odds of being in the top versus the bottom tertile of IL-1β (odds ratio: 0.61, 95% confidence interval: 0.38, 0.95). There were no significant racial and/or gender differences in associations. Discussion: A measure of residential segregation, the delta index, was associated with lower IL-1β in Black and White Americans. This suggests that aspects of living in majority Black counties may buffer thrombo-inflammatory responses associated with IL-1β.