tbuckley/cabot-search huggingface dataset:
Abstract P2029: Objectively Measured Daytime, Evening, and Nighttime Ambient Light Exposure and Mortality Risk: Findings from a US Nationally Representative Cohort
Authors: Jin Dai, Minghao Kou, Yoriko Heianza, JoAnn Manson, Lu Qi
Journal: Circulation (2025)

Introduction: Light is the strongest zeitgeber (time cue) for the human central circadian clock, and its effects on health may vary depending on the time of day by either strengthening or dampening circadian rhythms. However, the relations between various light exposures and human health remain largely unknown, partly due to the lack of available measurements. Hypothesis: We hypothesized that greater nighttime and evening light exposure would be associated with a higher mortality risk, while greater daytime light exposure would be associated with a lower mortality risk. Methods: This population-based prospective cohort study included 7,909 participants aged ≥20 years, with ≥4 days of data from wrist-worn accelerometers with light sensors measuring ambient light (lux) at 1 Hz from the U.S National Health and Nutrition Examination Survey 2011-2014. Mortality data through 2019 were obtained via linkage to the National Death Index. The average intensity of ambient light exposure during daytime (6:00 AM-7:59 PM), evening (8:00-11:59 PM), and nighttime (0:00-5:59 AM) were calculated. Cox models were used to estimate hazard ratios (HRs) for mortality. Results: During a median (IQR) follow-up of 6.8 (5.7-7.8) years, 803 deaths were documented, including 255 from cardiovascular disease and 192 from cancer. The multivariable-adjusted HRs (95% CIs) for all-cause mortality were 0.82 (0.66-1.03) for the second quartile of daytime light exposure, 0.83 (0.67-1.04) for the third quartile, and 0.67 (0.51-0. 89) for the highest quartile, compared to the lowest quartile ( P for trend &lt;0.001). Conversely, there was no association between nighttime ( P for trend = 0.14; HR for the highest vs lowest quartile: 0.94 [0.75-1.19]) or evening light exposure ( P for trend = 0.46; HR for the highest vs lowest quartile: 0.85 [0.71-1.03]) and all-cause mortality risk. Similar inverse associations of daytime light exposure were observed for cardiovascular disease mortality ( P for trend = 0.04; HR for highest vs lowest quartile: 0.65 [0.36-1.20]) but not for cancer mortality ( P for trend = 0.27; HR for highest vs lowest quartile: 0.89 [0.54-1.48]). Conclusions: In this nationally representative sample of U.S. adults, greater objectively measured ambient light exposure during daytime was inversely associated with all-cause and cardiovascular disease mortality risk. These findings may have significant public health implications given the reduced exposure to daytime light in modern society.
Abstract P2025: Incident stroke in unstably housed women: the role of cocaine and alcohol co-use
Authors: Akanksha Vaidya, Torsten Neilands, Felicia Chow, Andy Josephson, Jared Yuan, Samantha Dilworth, Alan Wu, Elise Riley
Journal: Circulation (2025)

Background: Sex and social determinants of health predict stroke, yet few studies focus exclusively on women at high social risk. Understanding associations between stroke and modifiable risk factors that are disproportionately common in high-risk populations may aid in tailoring primary and secondary prevention services. We sought a better understanding of the association between polysubstance use, with an emphasis on stimulant use, and stroke in women who experience homelessness and unstable housing (WEHUH). Methods: We recruited WEHUH from San Francisco community-based venues to participate in a cohort study. We identified incident stroke from electronic health records during the 2.5-year study period and up to two years following study completion. We then assessed associations with baseline study factors, including social determinants of health, toxicology-confirmed use of multiple substances, and traditional stroke risk factors. We used multiple logistic regression to determine independent relationships between study factors and incident stroke. Results: Among 243 participants, health records showed that nine (3.7%) had incident strokes. After adjusting for BMI, hyperlipidemia, and opioid use, cocaethylene--a biomarker signaling alcohol and cocaine concurrent co-use-- had a particularly strong association with incident stroke (OR 4.37; 95% CI 1.05-18.13). Conclusion: Stroke risk factors such as age and race were not strongly associated with incident stroke among WEHUH, but cocaethylene and opioids were. This suggests two possible opportunities for prevention in an environment where opioid use is already closely monitored. First, women reporting cocaine and alcohol co-use should be counseled about the especially harmful effects of this substance combination on their cerebrovascular health. Second, the utility of cocaethylene to assess stroke risk in high-risk populations may be currently underestimated.
Abstract P3021: Inflammatory Metabolomic Profiles are Associated with Increased Cardiovascular Disease Risk in Women
Authors: Kevin Sanchez, Jie Hu, Oana Zeleznik, Raji Balasubramanian, Dong Hoon Lee, Jun Li, Fred Tabung, A Eliassen, Kathryn Rexrode
Journal: Circulation (2025)

Background: Cardiovascular disease (CVD) is the leading cause of death worldwide; ischemic stroke (IS) and coronary heart disease (CHD) are the two leading causes of CVD. The burden of CVD is particularly pronounced in women, who have a 20% higher lifetime risk of stroke than men and have worse outcomes for CHD and IS. Inflammation is a risk factor for CVD, yet the mechanisms through which chronic inflammation increases this risk remain uncertain. Methods: Metabolomic data from 11 case-control studies in the Nurses’ Health Study (NHS) focusing on chronic inflammatory disease outcomes were used. In this cohort, 1,734 women also had data on inflammatory biomarkers (i.e., hs-CRP, IL6, TNFaR2, adiponectin). A composite inflammatory score was created based on these four biomarkers, and elastic net regression was used to identify metabolites associated with the inflammatory score. A metabolomic signature index of inflammation (i-MSI) was subsequently calculated as the sum of retained metabolites with weights equal to their regression coefficients. In an independent NHS IS case-control study ( n = 405 cases and 405 controls), conditional logistic regression was used to determine the odds ratios (OR) for the i-MSI and IS risk, controlling for standard CVD risk factors. Additionally, the association between the i-MSI and CHD risk was assessed in a case-control dataset from the Women’s Health Initiative (WHI; n = 793 cases and 795 controls). Results: The i-MSI comprised 92 metabolites in the NHS and 87 overlapping metabolites in the WHI, showing enrichment in branched-chain amino acid biosynthesis and degradation pathways. Moreover, weighted coexpression network analysis revealed distinct pro- and anti-inflammatory metabolite clusters, identifying diacylglycerides in the pro-inflammatory cluster and cholesteryl esters in the anti-inflammatory cluster. Every standard deviation (SD) increase in the i-MSI was associated with an OR for IS of 1.31 (95% CI: 1.06 – 1.62), and women in the highest i-MSI quartile had an OR of 1.96 (95% CI: 1.12 – 3.42). These findings were consistent in the CHD case-control cohort from the WHI, where the OR for CHD was 1.27 (95% CI: 1.07 – 1.51) per SD of the i-MSI. Conclusions: These data identify an association between metabolites linked with inflammation and CVD risk. These findings may aid in identifying novel metabolic targets that can be utilized to develop therapies for mitigating IS and CHD risk in women.
Abstract 060: Associations of Neighborhood Walkability with Baseline Physical Activity and Sedentary Time among US South Asian Adults from the SAHELI Randomized Clinical Trial
Authors: Neela Thangada, Nicola Lancki, Namratha Kandula, Juned Siddique
Journal: Circulation (2025)

Introduction: High neighborhood walkability, defined as presence of crosswalks, sidewalks, and parks, is associated with higher physical activity (PA) and lower sedentary time (ST) among United States (US) adults. The associations between neighborhood walkability, PA, and ST have not been studied among US South Asians adults, a group which experiences significantly higher cardiovascular disease (CVD) mortality compared to other race-ethnic groups. Methods: The SAHELI clinical trial randomized South Asian adults from the Chicago, IL metro area (18-65 years with CVD risk factors) to a 16-week lifestyle intervention versus a control group between 2018-2023. Baseline PA and ST were measured by an Actigraph worn by participants for 7 consecutive days. Moderate-to-vigorous physical activity (MVPA), light physical activity (LPA), and ST were defined by Troiano cut points. Neighborhood was defined by a 500-meter radius around participants’ home address. Neighborhood walkability measures included: the National Walkability Index (measured at the US Census block level), total number of crosswalks, total number of sidewalks, and percentage of neighborhood which contained a park, all measured by Google Street View. In separate models, multivariate linear regression evaluated the association between each neighborhood walkability measure and baseline MVPA, LPA, and ST, adjusting for age, sex, country-of-origin, years in US, and Actigraph wear time. Results: Participants from SAHELI with valid Actigraph data (defined as at least 600 min/day of wear time for &gt;3 days) and geocoded neighborhood walkability data were included (N=432; 59% female, 98% immigrant, 79% Indian origin). Mean±SD MVPA was 24±19 min/day, LPA was 299±95 min/day, and ST was 564±136 min/day. Distribution of neighborhood walkability variables are shown in Figure . Neighborhood walkability exposures were not associated with MVPA. The National Walkability Index, total number of crosswalks, and total number of sidewalks were significantly associated with higher LPA and lower ST in maximally-adjusted models ( Figure ). The percentage of neighborhood containing a park was not associated with LPA or ST. Conclusion: National Walkability Index, number of neighborhood crosswalks and sidewalks were significantly associated with higher LPA and lower ST, but not with MVPA. Neighborhood walkability may be important to consider when designing CVD prevention interventions that promote PA and minimize ST among US South Asians.
Abstract P3020: A prognostic molecular signature of hepatic steatosis is spatially heterogeneous and dynamic in human liver
Authors: Andrew Perry, Niran Hadad, Emeli Chatterjee, Maria Jimenez Ramos, Eric Farber-Eger, Rashedeh Roshani, Lindsey Stolze, Michael Betti, SHilin Zhao, Shi Huang, Liesbet Martens, Timothy Kendall, Tinne Thone, Kaushik Amancherla, Samuel Bailin, Curtis Gabriel, John Koethe, John Carr, James Terry, Nataraja Sarma Vaitinadin, Jane Freedman, Kahraman Tanriverdi, Eric Alsop, kendall Van Keuren-Jensen, John Sauld, Gautam Mahajan, Sadiya Khan, Laura Colangelo, Matthew Nayor, Susan Fisher-hoch, Joseph B McCormick, Kari North, Jennifer Below, Quinn Wells, Dale Abel, Ravi Kalhan, Charlotte Scott, Martin Guilliams, Eric Gamazon, Jonathan Fallowfield, Nicholas Banovich, Saumya Das, Ravi Shah
Journal: Circulation (2025)

Introduction: The prevalence of hepatic steatosis—a central and early phenotype in multi-system metabolic dysfunction—is increasing in parallel with the obesity pandemic, calling for novel approaches for prevention and treatment. Hypothesis: We hypothesized that the circulating proteome may reflect cell specific mechanisms of hepatic steatosis. Methods: Using multi-modality hepatic imaging and broad circulating proteomics in approximately 5,000 individuals across 3 diverse cohorts (CARDIA, Cameron County Hispanic Cohort, UK Biobank), we identified proteins implicated in the progression of hepatic steatosis. We tested for a relationship with these proteomic markers of hepatic steatosis with metabolic-related clinical outcomes in UK Biobank. We translated these findings from the circulating proteome to several tissue-based datasets including bulk RNA sequencing, single-cell RNA sequencing, and spatial transcriptomics. To further prove the hepatocyte origin of prioritized proteins, we used a humanized “liver-on-a-chip” model. Results: We observed proteins implicated in the progression of hepatic steatosis—such as those related to central carbon and amino acid metabolism, hepatocyte regeneration, inflammation, fibrosis, insulin sensitivity—are largely encoded by genes enriched at the transcriptional level in human liver. Circulating multi-protein signatures of hepatic steatosis were strongly associated with a fatty liver disease phenotype and multi-system metabolic outcomes in &gt;26,000 free-living individuals. Moreover, we observed increased activity of transcripts encoding proteins prioritized in clinical studies spatially in areas of steatosis via spatial transcriptomics in human liver, with several top candidates dynamic during progression of steatosis in human liver. Finally, using a humanized “liver-on-a-chip” model, we induced hepatic steatosis, confirming cell-specific expression of targets implicated across tissue and clinical studies at a transcriptional and proteomic level. Conclusions: These results underscore the utility of a unified approach that combines human studies, multi-omics, and dynamic tissue-on-a-chip experiments to identify a prognostic, functional, dynamic “liquid biopsy” of human liver, with relevance for clinical biomarker discovery and mechanistic research applications.
Abstract 037: Proteo-Transcriptional Characterization of Aortic Stenosis Prioritizes Novel Targets Relevant to Heart Failure
Authors: Kaushik Amancherla, Brian Lindman, Andrew Perry, Michelle Lance, Quanhu Sheng, Ryan Pfeiffer, Eric Farber-Eger, William Fearon, Samir Kapadia, Dharam Kumbhani, Linda Gillam, Ravinder Mallugari, Deepak Gupta, Francis Miller, Anna Vatterott, Natalie Jackson, Yanru Su, Kelsey Tomasek, Tarek Absi, Jane Freedman, Matthew Nayor, Saumya Das, Quinn Wells, marc dweck, Robert Gerszten, Nathan Tucker, Sammy Elmariah, Ravi Shah
Journal: Circulation (2025)

Background: Aortic stenosis (AS) initiates a series of molecular alterations that predate cardiac remodeling and development of heart failure (HF). We hypothesized that integrating circulating mediators (proteome) from large-scale epidemiological cohorts with their cell-specific gene expression in the heart (transcriptome) may prioritize novel targets in human AS. Methods: Among individuals with severe AS, we measured the circulating proteome (Olink) and examined associations with myocardial structure/function (N=519), cardiac MRI-based tissue fibrosis (N=145), and clinical outcomes (N=802). We constructed proteomic signatures of cardiac remodeling and tested their association with mortality and HF in the UK Biobank (UKBB; N=36,668). We then examined a "remodeling proteome” prioritized by proteome-phenotype relations at the transcriptional level via single nuclear RNA-sequencing in 20 human hearts (11 with AS at the time of SAVR and 9 donor hearts unused for transplant). Results: We identified three principal components (PCs) of cardiac remodeling (across 12 echocardiographic measures in 503 patients with severe AS) loaded on cardiac morphology, systolic, and diastolic function traits. Proteins associated with these PCs specified both known and novel mediators of fibrosis, LVH, and oxidative stress. Proteomic signatures were strongly linked to mortality (AS cohort, UKBB) and incident HF (UKBB). At a myocardial level, we observed cell-specific differential gene expression, particularly prominent in fibroblasts, cardiomyocytes, and endothelial cells, featuring convergent fibrosis pathways ( WNT9A , ITGA6 , AGRN , CRIM1 , SEMA4C , LAYN, PTX3 , HMOX1 ) and metabolic-inflammatory signaling ( ENPP2/ATX, TNF), among others. Conclusions: Proteo-transcriptional prioritization in human AS identifies both known and novel targets that are mechanistically relevant to HF pathogenesis. Future integrative studies that link longitudinal circulating biomarkers in large-scale cohorts directly to myocardial tissue are warranted to inform pathways of HF progression.
Abstract MP60: Associations between Chronic Stress, Resilience Factors and Cardiovascular Health among Young Adults in Puerto Rico
Authors: Milagros Rosal, Sharina PERSON, Catarina Kiefe, Katherine Tucker, Jose Rodriguez, Miredys Sanchez, Polaris Torres, Claudia Boneu, Christine Frisard, Cynthia Perez
Journal: Circulation (2025)

Introduction: The association between stress, resilience and cardiovascular health (CVH), as defined by the American Heart Association Life’s Essential 8 (LE8) metric, has not been well studied. We studied these associations among young adults in PR. Hypothesis: Chronic stress is associated with suboptimal CVH among young adults in PR; however, culture-relevant resilience factors, including optimism, spirituality, religiosity, and social support, help mitigate this association. Methods: Participants, aged 18-29 y and living in PR, completed assessments between September 2020 and November 2023 (60.8% female, n= 2,179). Participants completed measures of chronic stress (Chronic Burden scale, score dichotomized: low=0-1, high: &gt; 2), optimism (LOT-R; score range: 0-24), spirituality (DSES; scores: 1-80), religiosity (1 item; score: 0-2), and social support from family and friends (Walen&amp;Lachman; score: 1-8). Resilience scores were treated as continuous variables. CVH (LE8) scores were derived from surveys, laboratory assays, and physical exams (scores:0-100, suboptimal = &lt;80). Multivariable logistic regression was used to assess the association between chronic stress and CVH, followed by mediation analysis to determine whether resilience factors mitigated this association. Bias-corrected and accelerated 95% confidence intervals (CI) for the mediated proportions were estimated using bootstrapping with 1,000 replications. All models controlled for sex, age, subjective social standing, and mother’s education. Results: Overall, 36% of participants had high scores for chronic stress. The mean and standard deviations for the resilient factors were 14.7 (4.3) for optimism, 35.4 (18.1) spirituality, 1.3 (0.7) religiosity, and 6.5 (1.1) social support, and 72.5% of participants had suboptimal CVH. In the adjusted analysis, chronic stress was significantly associated with suboptimal CVH (OR=1.42; 95%CI:1.16-1.75). Mediation analyses showed that 19% (95%CI:4.58-55.9) of this association was mediated by optimism and 13.7% (95% CI: 4.0-45.8) by social support. Conclusion: The experience of chronic stress is associated with suboptimal CVH among young adults in PR. However, this association is mitigated by optimism and social support from friends and family. To increase the evidence base for preventive interventions, future research should assess longitudinal trajectories of these associations and pathways by which chronic stress and resilience factors may impact CVH.
Abstract P1167: Racism-Related Stress Related to Carotid-Femoral Pulse Wave Velocity in Cohort of Midlife Latinas
Authors: Maria Martinez Rangel, Valentina Marginean, Karla Halverson, Cynthia Doyle, Jennie Embree, Maria Hein, Yelena Perkhounkova, Yamnia Cortes
Journal: Circulation (2025)

Background: Cardiovascular disease (CVD) is one of the leading causes of death among women in the U.S, with an increased risk among Latinas. One-third of Latinas report experiences of racism and discrimination in the U.S. Psychological stress has been demonstrated to worsen CVD risk factors such as blood pressure, insulin resistance, and adverse lipid profile. However, there is limited consensus surrounding the relationship between racism-related stress and subclinical CVD in the Latina population. Thus, this study examines the relationship between sociocultural stress and carotid-femoral pulse wave velocity (cfPWV), a subclinical marker of CVD, in midlife Latinas. Methods: A cross-sectional analysis was conducted using baseline data from 31 women enrolled in an ongoing longitudinal study of midlife Latinas. Participants were eligible if they self-identified as Latinas between the ages of 40 and 60 years old and were perimenopausal. Women with a history of CVD, or moderate to major depression (PH9 &gt;10) were excluded. Racism-related stress was assessed using the Hispanic Women Social Stress Scale. Physical and anthropometric measures (e.g., weight, waist circumference, blood pressure, lipid profile) were collected during a clinical exam. Sociodemographic factors and medical history were self-reported using an interviewer-administered questionnaire. cfPWV was assessed using the Vicorder® device. Descriptive statistics and Pearson correlations were conducted (α = 0.1). Results: Participants were on average aged 47.1 ± 4.1 years, with 71% reporting having been born outside of the continental United States. At baseline, average cfPWV was 5.4 ± 0.7 m/s. Respondents had an average of 26.3 ± 25.1 on the Hispanic Social Stressor Scale (0-120) and over half (n=16) reported an experience of racism. When considering the total sample, cfPWV did not differ between women who reported at least one experience of racism (5.39 ± 0.73 m/s) compared to those who had no experience (5.75 ± 0.71 m/s). Among women who reported an experience of racism, greater severity of stress was positively correlated to cfPWV (r=0.58, p=0.02). Conclusions: In this cross-sectional analysis of midlife Latinas, the severity of racism-related stress was positively correlated to arterial stiffness. Findings support prior reports that greater exposure to racism worsens CVD risk. Additional data are necessary to further explore the impact of racism on CVD risk in this population.
Abstract MP62: Health Behaviors Among Nulliparas With Planned and Unplanned Pregnancies
Authors: Nadine Sunji, Melodee Liegl, Amy Pan, Ronald Anguzu, Anna Palatnik
Journal: Circulation (2025)

Introduction: The relationship between pregnancy planning and health behaviors in the preconception and antepartum periods remains unclear. This study aimed to compare health behaviors before and during pregnancy between nulliparous individuals with planned and unplanned pregnancies. Methods: This is a secondary analysis of the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be. The present study included nulliparas who indicated whether their pregnancy was planned or unplanned. Preconception and antepartum health behaviors were compared between planned and unplanned pregnancies using bivariate and multivariate analyses. Results: Among the 8,765 participants included, 5,202 (59.3%) had planned pregnancies, and 3,563 (40.7%) had unplanned pregnancies. Planned pregnancies were associated with older age, lower body mass index, white race, college education, higher income, and commercial insurance (p≤.001). Participants with unplanned pregnancies were more likely to have chronic hypertension and pregestational diabetes, and to be Hispanic or Latino, unmarried or unpartnered, and unemployed (p≤.001). In bivariate analysis, tobacco use, secondhand smoke exposure, and illicit drug use were more frequent among unplanned pregnancies three months preconception and throughout all three trimesters whereas engagement in physical activity was higher among planned pregnancies. Healthy Eating Index-2010 scores were also higher pre-pregnancy among planned pregnancies (Table). After adjusting for maternal age, education, marital status, income, commercial insurance, employment, chronic hypertension, and pregestational diabetes, these associations persisted (Table). Conclusion: Nulliparas with planned pregnancies demonstrated healthier behaviors that included less tobacco use, secondhand smoke exposure, and illicit drug use and greater engagement in physical activity and healthy eating. These associations persisted beyond the preconception period throughout pregnancy. This underscores the importance of preconception counseling and interventions as they not only improve health behaviors before pregnancy but also sustain these healthy practices throughout pregnancy.