tbuckley/cabot-search huggingface dataset:
Abstract P1172: From adverse pregnancy outcome to preventive care: insights from patient interviews on barriers to primary care after adverse pregnancy outcomes, and how to overcome them
Authors: Mara Murray Horwitz, Grayce Bredy, Lillian Rupert, Jaylen Wright, Lois McCloskey
Journal: Circulation (2025)

Introduction: Primary care is needed to assess and address cardiovascular risk after adverse pregnancy outcomes (APOs) like preeclampsia and gestational diabetes. Yet 40% of individuals with APOs do not connect with primary care post-pregnancy, a gap that is pronounced among individuals who identify as Black or have low incomes. Understanding barriers and facilitators to primary care after APOs can inform interventions to improve women’s cardiovascular health and health equity. Hypothesis: We hypothesize that patient and health system factors impede access to primary care after APOs. Methods: We conducted semi-structured interviews with individuals who experienced APOs and delivered at our urban safety-net hospital 1-2 years prior. Purposive sampling was based on patient language (English, Spanish, Haitian Creole) and linkage to primary care (yes/no) to achieve a diverse sample (goal n=30). Two researchers independently coded the transcripts using an inductive-deductive approach, informed by the Patient-Centered Access to Health Care model. Results: Recruitment was challenging; from 9/2023-8/2024 we completed 15 interviews (9 in English, 3 in Spanish, 3 in Haitian Creole) with individuals with recent APOs, all of whom had linked to primary care in the first postpartum year. Despite universal linkage, every interviewee expressed confusion or frustration with the transition from pregnancy-based care to primary care. They cited numerous patient-level barriers (e.g., competing priorities) and system-level barriers (e.g., scheduling difficulties). Figure summarizes their suggestions for improving postpartum care transitions. Conclusions: In conclusion, individuals with APOs note an abrupt and unsupported transition to primary care after pregnancy, with barriers at multiple levels. They provide concrete and actionable recommendations for health system changes to improve linkage to primary care after APOs.
Abstract 050: Diet quality, pathway-specific polygenic risk scores, and risk of type 2 diabetes among US men and women
Authors: Zhendong Mei, Xingyan Wang, Huan Yun, Magdalena Sevilla-Gonzalez, Jie Hu, Shilpa Bhupathiraju, Qi Sun, Meir Stampfer, Walter Willett, Liming Liang, Frank Hu, Jun Li
Journal: Circulation (2025)

Background: Healthy diets are associated with lower risk of type 2 diabetes (T2D) risk, but it is unclear if individuals with different genetic risks benefit from specific dietary strategies. Hypothesis: The associations between healthy dietary patterns and lower T2D risk may be modified by global and pathway-specific polygenic risk scores (PRS). Methods: We conducted prospective analyses in 40,609 participants from the Nurses’ Health Studies and Health Professionals Follow-Up Study, who were free of baseline diabetes, cardiovascular disease, and cancer, with up to 36 years of follow-up. Diet was assessed every 4 years via a food frequency questionnaire. We examined 6 recommendation-based and 2 mechanistic-based dietary patterns. A global PRS and 12 pathway-specific PRS denoting distinct T2D mechanisms were calculated. Cox regression was used to examine diet, PRS, and their interactions with T2D risk. Results: We identified a total of 4,760 T2D cases during the follow-up. Higher global PRS and 11 pathway-specific PRS, except the one related to bilirubin metabolism, significantly predicted higher T2D risk. In multivariable-adjusted analyses, all dietary indices indicating a lower dietary quality were associated with higher T2D risk (hazard ratios comparing extreme quintiles 1.06-2.21, P-trend &lt;0.05/8). We found additive interactions between the Global PRS and the alternate Healthy Eating Index, healthy plant-based diet index, and proinflammatory and hyper-insulinemic diets, in relation to T2D risk (relative excess risk due to interaction 0.09 to 0.32, P-interaction ≤0.004; Figure ). PRS for beta-cell dysfunction and fat deposition-mediated insulin resistance also showed interactions with proinflammatory and hyper-insulinemic diets ( P-interaction ≤0.004; Figure ). Conclusions Healthy dietary patterns are associated with lower T2D risk across a wide genetic risk spectrum. Diets targeting inflammation and insulinemia may be particularly beneficial for those genetically predisposed to beta-cell dysfunction and fat deposition-mediated insulin resistance.
Abstract 055: Gestational Diabetes and Risk of Type 2 Diabetes: Exploring the Role of Gut microbiome and Blood Metabolome in the Hispanic Community Health Study / Study of Latinos (HCHS/SOL)
Authors: Yi Wang, Carmen Isasi, Alison Stuebe, Adetola Louis-Jacques, Martha Daviglus, Eric Boerwinkle, Robert Burk, Robert Kaplan, Qibin Qi, Brandilyn Peters-Samuelson
Journal: Circulation (2025)

Introduction: Women with a history of gestational diabetes mellitus (GDM) have a higher risk of type 2 diabetes (T2D), but the underlying mechanisms, particularly the roles of gut microbiota and blood metabolites, remain unclear. Hypothesis: Women with history of GDM have an altered gut microbiota and blood metabolites, which may lead to a higher T2D risk. Methods: Among parous women from HCHS/SOL, gut microbiome was assessed by shotgun sequencing (visit 2, 2014-17). We identified microbial species associated with presence vs. absence of history of GDM (visit 2, n=1525), and serum metabolites associated with both history of GDM (baseline, 2008-11, n=2968) and GDM-related microbiota (visit 2, n=391). We also examined prospective associations of the GDM-related microbiome (visit 2, n=798) with incident T2D over 6 years follow-up, and of microbial-related metabolites (baseline, n=2341) with incident T2D over 12 years. Results: Seven species showed differential abundance between women with and without history of GDM, including higher abundance of 4 species (e.g., Parabacteroides merdae CAG:48 ), and lower abundance of 3 species (e.g., Dialister sp. CAG:588 ). A GDM-related microbiome score, generated via linear combination of 7 species, was associated with higher T2D risk (RR=1.08 [95% CI: 1.00, 1.18] per SD). Fifteen metabolites (e.g., saturated sphingomyelins) were associated with both history of GDM and the microbiome score in consistent direction, 9 of which were prospectively associated with incident T2D (Fig. 1A). Proxy association analysis based on these metabolites suggested a positive relationship between the GDM-related microbiome and T2D (Fig. 1B). A metabolite score derived from the 9 microbial-related metabolites partially mediated the relationship between GDM and T2D risk (21.8%, 95% CI: 8.1%, 54%). Conclusion: Among U.S. Hispanic/Latino women, history of GDM is associated with an unfavorable gut microbiota and related metabolites, suggesting a potential role of gut microbiota in GDM-T2D relationship.
Abstract P1082: Estimating the Burden of Undiagnosis HFpEF in the Community
Authors: Ryan Demmer, Alanna Chamberlain, Ruoxiang Jiang, Lisa Vaughan, Barry Borlaug
Journal: Circulation (2025)

Objective: Over 3 million Americans have heart failure with preserved ejection fraction (HFpEF). Effective guideline directed medical treatments (GDMT) are increasingly available but patients with HFpEF are likely under-detected (particularly women) and not receiving GDMT. Limited data are available informing the extent of HFpEF under-detection in the community. Hypothesis: Among patients with undifferentiated dyspnea and a high risk for unrecognized HFpEF, fewer than 50% will receive a HFpEF diagnosis during two years of follow-up; underrecognition will be greater among women. Methods: We identified 22,134 patients aged ≥30 in the Rochester Epidemiology Project (a medical records linkage system comprising a 27-county region of southeastern Minnesota and western Wisconsin) with evidence of unexplained dyspnea (≥2 ICD codes for dyspnea separated by &gt;1 day) without prior documented etiology including HF or lung disease, during the time period 2018-2022. We calculated the recently validated HFpEF-Age-BMI-Atrial Fibrillation (HFpEF-ABA) score to estimate the probability of underlying HFpEF. Cox proportional hazards models regressed risk for incident HFpEF diagnosis on HFpEF-ABA score (dichotomized as ≥80% vs. &lt;80%) with multivariable adjustment for sex, race and ethnicity. HRs(95%CIs) are presented. Results: Patients were 59±16 yrs, 50.8% women, 88.6% white, 3.1% Black, 3.7% other race, 4.6% Hispanic. Atrial fibrillation prevalence was 9.4% and mean BMI=31.4±7.8. Prevalence of HFpEF-ABA≥80% was 22.4%(n=4,958): 22.7% among women and 22.1% among men. The cumulative incidence of clinically-recognized HFpEF diagnosis at two years follow-up was 9.7% among women and 12.8% among men (log-rank p&lt;0.01). HFpEF incidence was elevated with high HFpEF-ABA scores(≥80%): HR(95%CI) among women=3.72 (3.35, 4.14), and men=3.42 (3.11, 3.76). Among those with clinically diagnosed HFpEF during follow-up, mean time from date of first dyspnea ICD code to HFpEF diagnosis was 1.26 years overall: 1.31 and 1.21 years in women and men, respectively (p=0.05). Conclusions: One in five patients with undifferentiated dyspnea have probable undiagnosed HFpEF, and of that group, only 30% receive a clinical diagnosis, requiring an average of over 1 year to be recognized. The rate of diagnosis is even lower among women than men. Further study is warranted to implement evidence-based algorithms supporting detection of undiagnosed HFpEF in the community, especially in women.
Abstract P2144: The Duration of Expectant Management During Hypertensive Disorders of Pregnancy and Blood Pressure 2-7 Years After Delivery
Authors: Raj Shree, Mindy Pike, Hyagriv Simhan, Lynn Yee, Lisa Levine, Robert Silver, Matthew Hoffman, Philip Greenland, George Saade, C Noel Bairey Merz, William Grobman, Janet Catov
Journal: Circulation (2025)

Expectant management of preterm pregnancies with hypertensive disorders (HDP), such as preeclampsia (PE), is standard practice for neonatal benefit, although the effects on the maternal cardiovascular (CV) system from longer exposure to endothelial inflammation is uncertain. Latency of expectant management is the time from HDP diagnosis to delivery. Studies from administrative databases suggest a higher rate of adverse CV outcomes several years post-pregnancy with latency &gt;7 days. Using the nuMoM2b-HHS (Nulliparous Pregnancy Outcomes Heart Health Study) cohort, we evaluated the relation between latency in nulliparas expectantly managed with HDP and mean systolic and diastolic blood pressure (BP) 2-7 years post-pregnancy. In the primary study (nuMoM2b), pregnancy diagnoses and outcomes were prospectively ascertained and biospecimens were obtained. We included those with HDP (PE with or without severe features, and gestational HTN) diagnosed &lt;37 weeks. Latency was defined as short (2-7 days) or long (&gt;7 days). We excluded those with chronic hypertension (HTN) or pregestational diabetes at index pregnancy, if exposure or outcome data were missing from the index pregnancy or HHS visit, or if latencies were implausible based on timing of diagnosis and delivery. We used linear regression models to examine the association between latency with BP and markers of CV risk (high-sensitivity CRP (hs-CRP), lipids, HgbA1C, NTproBNP, and ACC/AHA CV risk score) obtained 2-7 years post-pregnancy. We planned a sensitivity analysis of those with early-onset HDP (diagnosis &lt;34 weeks). 150 participants, 32 with short and 118 with long latency, met inclusion criteria (Table 1). BP at HHS follow-up was not different by latency duration (Table 1, Fig 1). hs-CRP was significantly higher in those with long latency, including after adjustment for confounders (age, race, BMI, baseline CV markers, gestational diabetes, small for gestational age infant, and smoking [Fig 2]). The other markers of CV risk were not statistically different between groups [Table 1]. In sensitivity analysis, BP was not different between groups; however, hs-CRP was significantly higher in the longer latency group. In this cohort of prospectively adjudicated pregnancy outcomes, longer latency in those with expectantly managed preterm HDP was not associated with overall differences in CV risk, including BP 2-7 years after a first delivery. The finding of elevated hs-CRP warrants follow-up in a larger cohort.
Abstract P1058: Parental Stress and Depression on Child Cardiovascular Health: The Young Hearts Study
Authors: Ileah Spain Rios, Yaojie Wang, Aashima Chopra, Darci Phillips, Rachel Zmora, Lucia Petito, Amy Yu, Amanda Perak, Donald Lloyd-Jones, Sarah de Ferranti, 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: The association of parental stress and depression with child behavioral cardiovascular health (bCVH) has received limited attention in the literature. Methods: We used data from the Young Hearts study, a cohort examining CVH in children and adolescents. Parental stress was assessed using the Perceived Stress Scale (PSS-4), which consisted of 4 questions rated on a Likert scale (0-16), with a higher score indicating greater levels of stress. Parental depression was evaluated using the 2-item Patient Health Questionnaire (PHQ-2), with responses rated on a Likert scale (0-6). bCVH scores were calculated from the mean of the four behavioral metrics of the American Heart Association’s Life’s Essential 8 (physical activity, diet, nicotine exposure, and sleep; 0-100 points each, with a higher score = better CVH) and self-reported body mass index (BMI). We examined the association of parental stress and depression with child bCVH score, using linear regression, adjusting for age, sex, race, ethnicity, household income, and parental education level. Results: Our sample consisted of 6,427 children with complete data, with an average age of 8.2 years [SD 5.1]. Of the participants, 53.5% were male, and 46.3% were Non-Hispanic White. In adjusted models, a 1-unit higher parental depression score was associated with 1.30 (95% CL = -1.54, -1.07) point lower children’s bCVH. Parental stress also showed an association with bCVH though the effect size was smaller (-0.44 points; -0.54, -0.34). Among the individual behavioral components for parental depression, there were significant associations with physical activity (-1.75 points; -2.29, -1.21) and sleep (-1.98 points; -2.52, -1.44). Conclusion: Parental stress and depression are inversely associated with child bCVH, highlighting the need for further investigation of potential mechanisms to inform targeted family interventions.
Abstract P1176: The Association of Urinary Incontinence, Physical Activity, and Cardiovascular Disease Risk in Women
Authors: Lisa VanWiel, Lucas Carr, Dale Bond, Yin Wu, elena tunitsky-bitton, Adam Steinberg, Paul Tulikangas, Kara Whitaker
Journal: Circulation (2025)

Introduction: Urinary incontinence (UI) is a common condition among women. Emerging evidence indicates UI might contribute to lower physical activity (PA) levels. Thus, women with UI may have increased risk for inactivity and related cardiovascular disease (CVD). Hypothesis: Women with UI, compared to women without UI, will 1) have higher odds of being inactive or insufficiently active, and 2) have higher odds of cardiovascular risk factors or diagnosed cardiovascular disease. Methods: This retrospective observational study used electronic medical records to capture data on UI diagnosis, self-reported moderate-to-vigorous PA using the Exercise Vital Sign, Atherosclerotic Cardiovascular Disease (ASCVD) risk factor components and the diagnosis or management of CVD using ICD-10 codes, and demographic information. Multinomial logistic regression assessed the association of UI and PA classification (inactive: 0 min/week, insufficiently active: 1-149 min/week, and active ≥150 min/week). Multiple variable logistic regression models assessed associations of UI with CVD risk calculator components and diagnosed CVD. All models adjusted for age, race, body mass index, and tobacco use. Results: Of 20,155 women who were included in analysis (mean age 50.36±16.42 years), 1,085 (5.4%) had a UI diagnosis. Women with UI were on average 11.4 years older than those without UI. A greater proportion of those with UI were current or former smokers compared to those without UI. Activity classification did not differ in those with and without UI. Those with UI had greater odds of type 2 diabetes (aOR 1.25, 95% CI: 1.06-1.48), dyslipidemia (aOR 1.37, 95% CI: 1.19-1.58), stroke (aOR 1.55, 95% CI: 1.06-2.25), and coronary artery bypass grafts (aOR 3.17, 95% CI: 1.45-6.95) than those without UI (Table 1). Conclusions: UI was not associated with PA classification; future studies should investigate whether increasing PA among women with UI can mitigate associations of UI and CVD risk. Women with UI also present with risk factors for CVD and the association should be further studied. Additionally, women with CVD should be screened for UI.
Abstract P2126: Physical Activity, Inflammation, and Cardiometabolic Risk in Diabetic Kidney Disease: A Population-Based Study
Authors: Wirampa Tanglai, Apichai Wattanapisit, Watanabe Osamu, Thanakrit Jeamjitvibool, Mark Lockwood, Mia Cajita
Journal: Circulation (2025)

Introduction: Diabetic kidney disease (DKD) increases morbidity and mortality in individuals with diabetes. This study aimed to examine the relationships between cardiometabolic factors, high-sensitivity C-reactive protein (hs-CRP), physical activity (PA) measured as total METs, and the risk of DKD in adults. Additionally, it explored moderators of the association between total PA METs-DKD. Hypothesis: We hypothesized that lower levels of cardiometabolic factors and hs-CRP, along with higher levels of total PA METs are associated with reduced DKD risk in adults. We also posited that age and race/ethnicity moderate the relationship between total PA METs and DKD. Methods: The study analyzed 5,856 adults aged ≥18 years (mean age = 49.89) from the 2017-2018 National Health and Nutrition Examination Survey. DKD was defined by diabetes with an estimated glomerular filtration rate of &lt;60 mL/min/1.73m2 or an albumin to creatinine ratio was ≥30 mg/g. The International Physical Activity Questionnaire was used to subjectively measure PA in the survey. Multiple imputations were conducted to address the missing data. Hierarchical logistic regression was used to assess the odds of DKD and identify moderators. Results: DKD was present in 13.32% of participants. Age strongly predicted DKD, with those aged 70-80 having an 18.13 times higher risk than those aged 20-29. Non-Hispanic Black participants had 1.51 times higher DKD risk than non-Hispanic Whites. Among metabolic and inflammatory markers, high systolic blood pressure, elevated fasting glucose level, and hs-CRP were associated with increased odds of DKD. Conversely, total cholesterol levels of 5.2-6.2 mmol/L and total PA METs ≥1,110 METs-minutes/week were linked to a 24% and 25% reduction in DKD odds, respectively. Age and race/ethnicity did not moderate the relationship between total PA METs and DKD. Conclusions: Most cardiometabolic markers and hs-CRP were associated with increased DKD risk, while total cholesterol and total PA METs were associated with reduced DKD risk. Contrary to our hypothesis, age and race/ethnicity did not moderate the relationship between total PA METs and DKD risk.
Abstract P1039: Inhibition Of Drug Metabolizing Enzyme Cytochrome P450 2C8 By Acyl-Glucuronide Metabolites Of Gemfibrozil And Clopidogrel.
Authors: Manish Shah
Journal: Circulation (2025)

Human cytochrome P450 (CYP) enzymes are a superfamily of heme-containing oxidoreductases essential in the metabolism of various xenobiotics. CYP2C8 is responsible for the oxidative metabolism of many important drugs including cerivastatin, repaglinide, pioglitazone, enzalutamide, dasabuvir, imatinib, etc. and has generated research interest due to its involvement in drug-drug interactions (DDI). The glucuronide metabolites of the antilipemic drug gemfibrozil and the antiplatelet drug clopidogrel are known as strong inhibitors of CYP2C8 leading to several DDIs. Most of the gemfibrozil dose is primarily metabolized as glucuronide conjugate or gemfibrozil acyl-glucuronide, which is a known mechanism-based inhibitor of CYP2C8 that leads to clinical DDIs with the substrates of CYP2C8. For example, the co-administration of gemfibrozil with the CYP2C8 substrate pioglitazone inhibited the metabolism and increased the concentration of pioglitazone leading to DDIs. In addition, the clopidogrel acyl-glucuronide metabolite is a known strong time-dependent inhibitor of CYP2C8 leading to marked clinical DDIs with the substrates of this enzyme. Patients on clopidogrel and concurrently taking cerivastatin, or the anti-diabetic repaglinide, are at increased risk of rhabdomyolysis. It is not clear how a glucuronide metabolite of these drugs binds in the active site of CYP2C8 and inhibit the enzyme. CYP2C8 enzyme was recombinantly expressed and purified. A biophysical method Surface Plasmon Resonance (SPR) was used to elucidate the binding of the acyl-glucuronide metabolites of gemfibrozil and clopidogrel with CYP2C8. The representative dissociation constant (K D ) of CYP2C8 binding with gemfibrozil acyl-glucuronide was 227.5 ± 38.5 µM, whereas the K D of CYP2C8 binding with clopidogrel acyl-glucuronide was ten-fold lower, in the range of 3 to 25 µM indicative of higher affinity. The purified protein was also used for crystallization with these acyl glucuronides of gemfibrozil and clopidogrel with an aim to determine the three-dimensional structure. Overall, the characterization of CYP2C8 with gemfibrozil acyl-glucuronide and clopidogrel acyl-glucuronide yielded insights into the binding and inhibition of an important drug metabolizing enzyme.