tbuckley/cabot-search huggingface dataset:
Abstract P1030: Role of Hypertension in the Cardiovascular-Kidney-Metabolic Syndrome among Black Adults: The Jackson Heart Study
Authors: Medha Dubal, Lama Ghazi, Alain Bertoni, April Carson, Cora Lewis, Chibuike Alanaeme, Dayna Johnson, Daichi Shimbo, Kathryn Foti, Lisandro Colantonio, Milla Arabadjian, Rikki Tanner, Paul Muntner
Journal: Circulation (2025)

Introduction: CKM consists of obesity, metabolic risk factors, chronic kidney disease (CKD) and cardiovascular disease (CVD). Hypertension is a key factor for stage 2 CKM and it is most common among Black adults. A better understanding of the role of hypertension in CKM progression is needed. Aim: To estimate the risk of progression to stage 4 CKM in Black adults, overall and among those with hypertension, in the Jackson Heart Study (JHS). Methods: We included 2,118 Black adults in the JHS without clinical CVD at baseline. Participants were categorized into: Stage 1 CKM: overweight/obesity, abdominal obesity or dysfunctional adipose tissue with no metabolic risk factors including hypertension; Stage 2 CKM: metabolic risk factors including hypertension, diabetes, hypertriglyceridemia, metabolic syndrome or CKD; Stage 3 CKM: subclinical CVD; or Stage 4 CKM: Clinical CVD. The incidence rate of stage 4 CKM for participants in stages 1, 2 and 3 CKM were estimated. We used Cox proportional hazards regression to estimate hazard ratios (HRs) for incident stage 4 CKM. Results: At baseline, 20%, 69%, and 11% of participants were in stages 1, 2 and 3 CKM. The prevalence of hypertension in stage 2 CKM and stage 3 CKM were 80% and 95%, respectively. The incidence rate per 1,000 person-years of stage 4 CKM for participants with stage 2 CKM and hypertension was 7.5 (95% CI 6.1, 8.9), and for stage 3 CKM and hypertension was 26.6 (95% CI 19.8, 33.3) ( Table ). The adjusted HRs of developing stage 4 CKM were 3.25 (95%CI: 1.56-6.80) and 5.11 (95% CI 2.05-12.78) for participants with stage 2 and 3 CKM with hypertension versus stage 1 CKM, respectively. Conclusion: The majority of JHS participants with stages 2 and 3 CKM had hypertension, which was associated with an increased risk for progressing to stage 4 CKM when compared to stage 1 CKM participants.
Abstract P1045: Relationship Between Cardiovascular Risk Factors and All-Cause and Cancer-Specific Mortality Among Cancer Survivors in the United States
Authors: Reed Mszar, Danish Iltaf Satti, Tarang Parekh, Sarah Hull, Lauren Baldassarre, Garima Sharma, Erica Spatz, Khurram Nasir, Leah Ferrucci, Melinda Irwin, Suparna Clasen
Journal: Circulation (2025)

Background: To address the growing burden of cardiovascular disease among cancer survivors, prior studies have assessed the association between cardiometabolic risk factors and mortality among individuals with cancer but have largely focused on specific cancer types or been limited by small sample sizes. We used nationally representative data to examine the relationship between cardiovascular risk factors and mortality among US cancer survivors. Methods: We analyzed data from the National Health Interview Survey (2012-2018), linked to National Death Index, for adults aged ≥18 years with a self-reported cancer history (excluding non-melanoma skin cancer) and cardiovascular risk factors. Cardiovascular risk factors included hypertension, diabetes, hypercholesterolemia, obesity, smoking, and physical inactivity, categorized as low risk (0 factors), intermediate (1-2), or high (3+). Multivariable Cox proportional hazards regression was used to calculate hazard ratios (HRs) and 95% CI for all-cause and cancer-specific mortality. Results: Among 15,690 cancer survivors (median age 68.0 years; 60.4% female), representing 14.8 million survivors annually, 5.3%, 38.8%, and 55.9% were at low, intermediate, and high cardiovascular risk, respectively. Cancer survivors at intermediate and high risk had a 3.1-fold (HR: 3.11, 95% CI: 2.09-4.64) and 3.6-fold (HR: 3.60, 95% CI: 2.42-5.35) increased risk of all-cause mortality compared to survivors at low risk, respectively. A similar relationship was present for cancer-specific mortality (intermediate vs. low HR: 2.53, 95% CI: 1.50-4.24; high vs. low HR: 2.44, 95% CI: 1.45-4.09). Conclusions: In a sample of cancer survivors, most individuals were at high cardiovascular risk, which in turn was associated with an increased risk of all-cause and cancer-specific mortality. Identifying those at the highest risk as part of oncology survivorship care could impact survival among this vulnerable population.
Abstract P2122: Occupational Physical Activity and Mortality Risk: Evidence from a Nationally Representative U.S. Sample (NHANES 1999-2006)
Authors: Tyler Quinn, William Boyer
Journal: Circulation (2025)

Background: Leisure-time physical activity (LTPA) is associated with health benefits, but emerging evidence suggests occupational physical activity (OPA) may have paradoxically negative health associations. Limited U.S. data hinders understanding of this phenomenon in the American workforce. This study examined associations between OPA and mortality in a representative U.S. sample. Methods: Data from 8,041 working adults (baseline age 41.4±0.2, 55.9% female, 80.5% non-Hispanic White) in the 1999-2006 National Health and Nutrition Examination Survey, linked to 2019 National Death Index, were analyzed. Participants worked ≥35 hours/week and had complete data on all included variables. Self-reported jobs were classified into standard occupational classifications and categorized as low, intermediate, or high OPA. Cox proportional hazards models estimated hazard ratios (HR) for all-cause and cardiovascular disease (CVD) mortality across OPA categories, adjusting for age, sex, race-ethnicity, education, smoking status, alcohol consumption, body mass index, self-reported CVD, and LTPA. Effect modification by sex, race-ethnicity, smoking, and LTPA was examined. Results: In fully adjusted models, intermediate OPA was associated with higher all-cause mortality (HR 1.24, 95% CI 1.00-1.53) compared to low OPA. For CVD mortality, both intermediate (HR 1.79, 95% CI 1.16-2.75) and high OPA (HR 1.71, 95% CI 1.00-2.92) showed increased risk compared to low OPA. Associations varied by subgroups: females with high OPA had higher all-cause mortality risk (HR 1.59, 95% CI 1.05-2.41) compared to low OPA. Among never smokers, high OPA was associated with increased CVD mortality (HR 3.44, 95% CI 1.26-9.37). Surprisingly, among those meeting LTPA guidelines, high OPA was associated with the highest CVD mortality risk (HR 6.21, 95% CI 2.10-18.39). Conclusion: This analysis supports the OPA health paradox in a U.S. population, with higher OPA levels associated with increased mortality risk, particularly from CVD. Associations varied across subgroups, highlighting the complexity of the OPA-health relationship and potential implications for health disparities. The unexpected finding of heightened risk among those meeting LTPA guidelines warrants further investigation. Results underscore the need for targeted interventions and workplace policies to mitigate health risks for workers in high-OPA occupations, especially among vulnerable populations.
Abstract P1060: Examining the Impact of Adverse Childhood Experiences and Cardiovascular Health: A Propensity Score Matched Analysis in the Young Hearts Study
Authors: Yaojie Wang, Lucia Petito, Rachel Zmora, Aashima Chopra, Darci Phillips, Ileah Spain Rios, Amy Yu, Amanda Perak, Donald Lloyd-Jones, Sarah Deferranti, Holly Gooding, Stephen Daniels, Darwin Labarthe, Matthew Davis, Marc Rosenman, Rashmi Narayan, Mark Pletcher, Francis Alenghat, Rupali Gandhi, Cheryl Lefaiver, Amanda Luff, Huma Khan, Brad Appelhans, Karen Lui, Rachel Caskey, Norrina Allen
Journal: Circulation (2025)

Background: Previous research has shown adverse childhood experiences (ACEs) – traumatic events such as witnessing domestic violence and experiencing physical abuse before age 18 – are associated with poorer cardiovascular health (CVH) in childhood. However, this association may be confounded by childhood home environment and other social determinants of health (SDOH). We explored this relationship using propensity score matching to control for selection bias. Methods: We conducted a propensity score (PS)-matched analysis in the Young Hearts study, a Chicago-based pediatric cohort study. We included participants aged 1-17y (N = 6,487) with available ACEs and behavioral CVH (bCVH) data (diet, exercise, nicotine exposure, sleep, and BMI). Participants self-reported whether the child was exposed to any of 17 possible ACEs. We calculated bCVH scores (0-100) using an age-appropriate adaptation of the Life’s Essential 8 framework. PS matching balanced the sample on key SDOH, including parental education, child sex, child race and ethnicity, birth year, and number of adults and children at home. Then, linear regression assessed the association of ACEs with bCVH scores. Results: The PS-matched sample included 3263 children without ACEs and 3078 children with at least 1 ACE. Individuals with &gt;=1 ACE had significantly lower bCVH scores than those without ACEs (-4.72; 95% CI -5.36, -4.09) ( Figure ). Among individual CVH metrics, ACEs were most strongly associated with diet (-8.40, 95% CI = -9.65, -7.15) and physical activity (-5.48, 95% CI = -6.91, -4.05). Conclusion: This study highlights the significant impact of ACEs on children’s CVH. The use of propensity score matching to reduce SDOH-related confounding suggests that efforts to prevent the ACEs themselves would likely be complementary to important efforts to improve adverse SDOH. These findings underscore the need for early identification of and intervention for children experiencing ACEs to improve and preserve CVH.
Abstract P1044: External validation of a novel cancer-associated venous thromboembolism risk assessment score in a safety-net hospital
Authors: Saran Lotfollahzadeh, Karlynn N. Dulberger, Jennifer La, Katya Ravid, Nhan Do, Mary Brophy, Michael Gaziano, Ang Li, Vipul Chitalia, Nathanael Fillmore
Journal: Circulation (2025)

Background: Cancer-associated VTE (CAT) is the second leading cause of death in patients diagnosed with cancer. However, pharmacologic thromboprophylaxis use in cancer patients must be tightly regulated due to a two-fold increased risk of experiencing a major bleeding event within this population. A cancer-associated venous thromboembolism (CAT) risk assessment model (RAM) has recently been developed utilizing patient electronic health records (EHR) that reports improved performance over the prior state-of-the-art Khorana score. Objective: To externally validate a recently published RAM using EHR data from 2,103 cancer patients at Boston Medical Center, New England’s largest safety-net hospital, and to compare this RAM to the Khorana score. Methods: We conducted a retrospective study of Boston Medical Center (BMC) cancer patients diagnosed between January 2014 and December 2022 using data from the BMC tumor registry and electronic health record system. We validated the risk assessment model using measures of discrimination and calibration. Results: The recently published score exhibited a strong ability to discriminate risk of CAT (C statistic, 0.67) substantially higher than the classic Khorana score (C statistic, 0.58). This increased discrimination power reflects the 20% of patients correctly reclassified into high or low risk by the expanded score. Model calibration was also strong in this dataset. Conclusion: In our external validation, the recently published CAT score clearly and improvedly separated patients at high and low risk for CAT. This expanded CAT score could facilitate improved selection of prophylactic therapy among cancer patients.
Abstract P3127: Loneliness and Social Isolation from Reduced Activities Increase Ischemic Heart Disease Risk via Metabolic and Behavioral Mediators: Evidence from Mendelian Randomization Study
Authors: Shuyao Su, Wanyue Wang, Chenxi Yuan, Zhennan Lin, Xiangfeng Lu, fangchao liu
Journal: Circulation (2025)

Introduction: Observational studies have linked loneliness or social isolation (SI) to ischemic heart disease (IHD), but results are inconsistent. Moreover, modifiable risk factors mediating the causal effects remain unclear. Hypothesis: loneliness and SI causally increase IHD risk, with metabolic and behavioral factors acting as key mediators. Methods: Using genetic instruments derived from summary-level Genome-Wide Association Studies data of European ancestry, we performed a bidirectional two-sample Mendelian Randomization (MR) study to estimate causal effects between loneliness (N=487,647) or SI and IHD (60,801 cases and 123,504 controls). SI traits included living alone (N=459,988), fewer social activities (N=459,830), and fewer contact with friends or family (N=461,369). Five subtypes of social activities were further analyzed, including sports club or gym, pub or social club, religious group, adult education class, or other group activities. Subsequently, a network MR study was conducted to evaluate the potential mediating effects of 20 candidate mediators and calculate their mediated proportions. Results: Loneliness was causally associated with IHD (OR 2.129; 95% CI, 1.380 to 3.285), mediated by body fat percentage, waist-hip ratio, total cholesterol and LDL-C. Regarding SI traits, fewer social activities increased IHD risk (OR, 1.815; 95%CI, 1.189 to 2.772), and only sports club or gym had protected against IHD (OR, 0.333; 95%CI, 0.204 to 0.542). No evidence showed causality between living alone or contact frequency and IHD. Smoking cessation, HDL-C, triglycerides, hypertension and fasting insulin mediated the causal pathway from fewer social activities to IHD. Moreover, no evidence indicated the reverse causality of IHD with loneliness or SI. Results were robust in sensitivity analyses. Conclusions: More attention should be paid to individuals who feel lonely or have fewer social activities for prevention of IHD, with several modifiable mediators as prioritized targets.
Abstract P2102: Enhancing Ischemic Stroke Risk Prediction: Functional Genomic Insights in Black and White Participants from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study
Authors: Nicole Armstrong, vinodh srinivasasainagendra, Amit Patki, Chad Aldridge, Alana Jones, Ulrich Broeckel, Ethan Lange, Leslie Lange, Pankaj Arora, Nita Limdi, Keith Keene, Bradford Worrall, Hemant Tiwari, Ryan Irvin
Journal: Circulation (2025)

Genome-wide association studies (GWAS) have advanced our understanding of the polygenic basis of complex human diseases. Although translating GWAS findings into clinical application remains difficult, polygenic risk scores (PRS) offer a potential approach. PRS methods aim to improve prediction, with Bayesian approaches like PRS-CS and functional-based methods such as SBayesRC. This study compares these two methods for incident ischemic stroke (IS) in Black and White participants from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study. We hypothesize that including functional annotations using SBayesRC will (1) improve IS polygenic prediction compared to PRS-CS and (2) outperform previous scores. Using summary statistics from the GIGASTROKE consortium (African ancestry n=20,924 [894 cases]; European ancestry n=1,296,908 [62,100 cases]), we developed IS PRS using SBayesRC and PRS-CS (four parameterizations, phi) for 6,569 Black (436 cases) and 1,544 White (368 cases) REGARDS participants. We applied the effect weights of two published IS PRS (Abraham and Mishra) in REGARDS. Performance was evaluated by the (1) proportion of variation in IS explained by the PRS on the liability scale (Nagelkerke’s R 2 ), (2) odds ratio (OR) per standard deviation (SD), and (3) the area under the curve (AUC), adjusting for age, sex, and genetic similarity. In REGARDS Black participants, the PRS constructed by SBayesRC explained 2.47% of the IS variation, with OR of 1.32 (1.18-1.48). While this score had stronger prediction compared to the Abraham (R 2 =0.13%, OR=1.08 [0.94, 1.23]) and Mishra (R 2 =0.59%, OR=1.16 [1.03, 1.32]) scores, PRS-CS (phi=0.01) explained 14.77% of the variation in IS, with OR of 1.69 (1.55-1.85). Among White participants, the best performing PRS was also from PRS-CS (phi=0.01) (R 2 =3.93%, OR=1.78 [1.54-2.07]). SBayesRC (R 2 =1.66%, OR=1.41 [1.24-1.61]) had stronger prediction compared to the Mishra score (R 2 =0.52%, OR=1.22 [1.07-1.39]) but was similar to the Abraham score (R 2 =2.19%, OR=1.48 [1.30-1.69]) ( Table 1) . In Black and White participants from REGARDS, adding functional annotation improved PRS prediction for IS compared to prior scores, although not as effectively as PRS-CS using large, single ancestry summary statistics. Additional validation is ongoing using data available in All of Us. In conclusion, this study underscores the need for large ancestry-specific summary statistics for PRS development.
Abstract P2017: Baseline Androgenic State Modifies the Effect of Intensive Lifestyle Intervention on Triglyceride Levels in Males with Diabetes: The Look AHEAD Trial Sex Hormone Study
Authors: Jianqiao Ma, Jiahuan Helen He, Mark Woodward, Erin Michos, Chigolum Oyeka, Rita Kalyani, Jeanne Clark, Wendy Bennett, Dhananjay Vaidya
Journal: Circulation (2025)

Background: In people with type 2 diabetes (T2D), weight loss due to an intensive lifestyle intervention (ILI) reduces triglyceride (TG) levels, a risk factor for cardiovascular disease. However, efficacy of treatment varies between people. Both testosterone and estradiol are associated with TG level. We examined whether baseline androgenic state, i.e., the ratio of testosterone to estradiol (T/E), modifies the treatment effect and partially explains the TG variability. Methods: The Look AHEAD Study was a randomized control trial of 5145 individuals with T2D and overweight/obesity to evaluate the effect of ILI compared to the control group on cardiovascular outcomes. We selected a random sample of 1166 postmenopausal females and 1166 males (mean age 60 years [SD 6.2]) to examine heterogeneity of treatment effect by baseline T/E ratio on changes in TG at years 1 (weight loss nadir) and 4. We created longitudinal mixed models stratified by sex, and modeled the interaction between log-transformed baseline T/E ratio, ILI (vs control), and year, with log-transformed TG as the outcome. We plotted the estimated treatment effects over time for 25 th and 75 th percentile of baseline T/E ratio. Results: Figure, panel A, shows that males with T/E ratio at the 75 th percentile (vs 25 th percentile) had a larger reduction in TG due to ILI (vs control) at year 1 (p = 0.002), which is no longer statistically significant at year 4 (p = 0.14, overall heterogeneity for both years, p = 0.009). We did not detect any statistically significant heterogeneity in TG levels by T/E ratio for females (panel B, p = 0.87). Conclusion: Greater baseline androgenic state (T/E ratio) in males, but not females, was associated with a larger reduction in TG due to ILI, compared to the control at year 1 but not year 4. Males with lower T/E ratio might need more aggressive lipid treatment to achieve TG-reducing benefits of ILI.
Abstract P2134: Fatigue category, quality of life, and risk of incident clinical heart failure in those with stage B heart failure in the Atherosclerosis Risk in Communities (ARIC) Study.
Authors: Noelle Pavlovic, Martha Abshire Saylor, Cheryl Dennison Himmelfarb, Yvonne Commodore-Mensah, Christopher Lee, Amil Shah, Patricia Chang, Kunihiro Matsushita, Sabra Lewsey, Chiadi Ndumele
Journal: Circulation (2025)

Background: General and exertional fatigue are common in clinical heart failure (HF) and associated with worse quality of life (QOL) and increased risk of HF re-admission and mortality. However, little is known about general and exertional fatigue in those with pre-HF. Methods: We included 2,972 individuals at Visit 5 (2011-13) of the ARIC study without clinical HF but meeting criteria for pre-HF (stage B HF per ACC/AHA guidelines) by echocardiography or elevated cardiac biomarkers, and with complete fatigue data. Using previously defined PROMIS fatigue (general fatigue) and MRC Breathlessness (exertional fatigue) scale score thresholds, individuals were cross categorized into 4 groups: low/no fatigue, high general fatigue, high exertional fatigue, and the co-occurrence of high general and high exertional fatigue. Adjusting for sociodemographic and clinical characteristics, we determined the cross-sectional association of fatigue category with physical and mental QOL (SF-12 scale) using linear regression, and prospective associations with incident clinical HF using Cox regression. To reduce the contribution of indolent HF to results, we conducted a sensitivity analysis excluding individuals with an outpatient diagnosis of clinical HF from Centers for Medicare and Medicaid Services claims data. Results: Participants were 60% female, 18% Black, and had a mean age of 76 years. Compared to the low/no fatigue category, all individuals in higher fatigue categories had lower physical QOL scores. The co-occurrence of high general and exertional fatigue was associated with the lowest QOL [β (95% CI) = -11 (-13, -10)] (Table). More modest, but significant, associations were seen for fatigue categories with mental QOL. Compared to the low/no fatigue category, those with high exertional fatigue, and those with the co-occurrence of high general and high exertional fatigue, had higher risk of incident clinical HF [HRs (95% CI) = 1.9 (1.4, 2.5) and 2.2 (1.5, 3.2), respectively]. Associations were similar after excluding individuals with an outpatient clinical HF diagnosis. Conclusions: In those with pre-HF, worse fatigue category was associated with worse QOL and increased risk of incident clinical HF, independent of traditional risk factors. Assessment of general and exertional fatigue may provide prognostic information in individuals with pre-HF.