tbuckley/cabot-search huggingface dataset:
Abstract 005: Plasma Senescence-Associated Secretory Phenotype (SASP) Proteins are Associated with the Development of Cognitive Impairment in Late Life: the ARIC study
Authors: Fernando Giugni, Yimin Yang, Victoria Lamberson, Arshama Dehghan, Brian Claggett, Bing Yu, Myriam Fornage, Chiara Giannarelli, Morgan Grams, B Gwen Windham, Thomas Mosley, Richey Sharrett, Priya Palta, Amil Shah
Journal: Circulation (2025)

Introduction: The senescence-associated secretory phenotype (SASP) consists of paracrine signaling molecules with deleterious effects secreted by senescent cells. However, little human data exist linking circulating SASP proteins to cognitive decline. Hypothesis: Plasma levels of SASP proteins will be associated with the development of mild cognitive impairment (MCI) or dementia and with subclinical neurodegenerative disease. Methods: Among participants in the Atherosclerosis Risk in Communities (ARIC) cohort study 5 th visit (2011-2013), we measured 26 SASP plasma proteins using an aptamer-based platform (SomaScan). Participants underwent protocol cognitive evaluations at Visit 5, Visit 6 (2016-2017) and Visit 7 (2018-2019), and a subset underwent brain magnetic resonance imaging at Visit 5. Among MCI/dementia-free individuals at Visit 5, we assessed associations of SASP proteins with incident MCI or dementia at Visit 6 (median interval 4.9 years) or Visit 7 (median interval 6.6 years) using multivariable logistic regression. We further assessed the associations of cognitive decline-related SASP proteins with total brain volume, temporal lobe meta-ROI volume, and volume of white matter hyperintensities using multivariable linear regression. All models were adjusted for age, sex, race and visit center. Two-sample cis-Mendelian randomization (MR) was performed to evaluate potential causal effects of proteins on overall dementia and specific dementia etiologies. Results: Among 2,024 participants included, mean age was 74±5 years, 59% were female, and 18% reported Black race. Between study Visit 5 and Visits 6 or 7, 639 (32%) participants developed MCI or dementia. Of the 26 SASP proteins, higher levels of 5 (GDF15, IGFBP7, CTSD, CST3 and HSPA8) were associated with higher risk of incident MCI or dementia (FDR-corrected p&lt;0.05; Figure 1). Among these proteins, GFD15, CST3 and HSPA8 were associated with lower total brain volume and lower temporal lobe meta-ROI volume, and GDF 15, CST3, IGFBP7, and CTSD were associated with greater volume of white matter hyperintensities (Figure 2). Two-sample MR identified a potential causal effect of GDF15 on Alzheimer’s Disease (p&lt;0.001). Conclusions: Higher plasma levels of a subset of the SASP proteins are associated with higher risk of developing MCI or dementia, and with greater subclinical alterations on neuroimaging. These findings support the potential role of cellular senescence in cognitive impairment.
Abstract P3080: Factor IX and Incident Hypertension in Black and White Adults: The REasons for Geographic and Racial Differences in Stroke (REGARDS) Cohort
Authors: Eric Stoutenburg, Maria Cristina Bravo, Virginia Howard, Suzanne Judd, Leann Long, Timothy Plante
Journal: Circulation (2025)

Background: A significant fraction of Americans are diagnosed with hypertension. Prior studies have shown Black adults experience a disproportionate amount of this burden. Certain biomarkers of thrombosis are associated with a greater risk of hypertension. Factor IX is a marker of thrombosis. Whether higher factor IX correlates with an increased risk of incident hypertension or explains some of the disproportionate burden faced by Black adults is not fully known. Methods: We included Black and White participants from the REasons for Geographic and Racial Difference in Stroke (REGARDS) study, excluding those with prevalent hypertension, missing factor IX level, or covariates of interest. Modified Poisson regression estimated risk ratios (RR) for incident hypertension by higher factor IX tertiles. A mediation analysis was performed using inverse odds ratio weighting to assess whether racial differences in hypertension risk could be attributed to factor IX levels. Results: A total of 1,824 participants were included, (55% female and 24% Black race), with 36% of participants developed incident hypertension. Higher factor IX levels were seen in Black participants with a mean of 110% vs 105% for White participants (p=0.0018). As shown in the Table, there was a greater risk of incident hypertension by higher factor IX tertile in all models. Mediation analysis did not demonstrate factor IX level mediated hypertension risk in any model. Conclusions: In this prospective study of Black and White adults without prevalent hypertension, higher factor IX was associated with a greater risk of developing hypertension, after adjusting for known confounders. A mediation analysis did not indicate that the excess burden of hypertension experienced by Black adults could be explained by factor IX level.
Abstract P3173: Stroke Risk Associated with Atrial Fibrillation in the General Population: A Systematic Review and Bayesian Meta-Analysis
Authors: Md Rezaul Hossain, Christian Razo Garcia, Judd Walson, Stephen Hawes, Gregory Roth
Journal: Circulation (2025)

Objective: The contribution of atrial fibrillation (AF) to global stroke burden is not well described. This study synthesized available evidence using the Burden of Proof (BoP) methodology and a Meta-regression-Bayesian, Regularized, trimmed (MR-BRT) model, to provide a robust stroke risk estimate for the general population while accounting for multiple potential biases. Methods: We conducted a systematic review and Bayesian meta-analysis of population-based observational studies of AF and stroke, sourced from PubMed and EMBASE (1970-2024). To adequately capture potential global burden, all (paroxysmal, persistent/sustained, chronic and, unspecified) types of AF were considered as exposure and the study outcome was any types of incident (ischemic, hemorrhagic, or total) stroke. Relative risk (RR) assessments - hazard ratio, risk ratio, and odds ratio were extracted from published observational studies. Binary covariates were generated to identify potential systematic bias, including the representativeness, precision in exposure and outcome status determination, variations in definitions, and adjustment was made for confounders - age, sex, education, lifestyle factors, study design, and comorbidities. We used the MR-BRT model to estimate a conservative mean AF-stroke dichotomous risk function and the overall pooled mean RR, adjusting for study heterogeneity and publication bias. Results: Of 6,447 articles reviewed, 49 studies were included, with participants aged 18 to 99 and sample sizes ranging from 250 to 4.3 million. Individuals with AF had a 99% higher risk of stroke (RR 1.99, 95% uncertainty interval [UI]: 1.91, 2.08), with an increasing range of 92% to 108%, indicating a significant association despite study heterogeneity (γ). The most conservative estimate was 1.92 (95% UI: 1.90, 1.99). No publication bias was found based on the funnel plot analysis. Conclusion: This study quantifies the risk of all strokes in the general population due to any type of AF. Differences in age, comorbidities, and medication use (especially anticoagulants) across populations and the level of confounder adjustment may influence the observed risk. The BoP framework highlights the importance of synthesizing high-quality evidence to guide targeted interventions and health policy decisions aimed at reducing stroke globally. These findings support more aggressive AF management, particularly in lower-resource settings, as part of stroke prevention strategies to reduce stroke incidence.
Abstract P2116: Peripheral Artery Disease Identified by Multi-Modalities and Accelerometry-Derived Physical Activity in the community: the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)
Authors: Pablo Martinez-Amezcua, Robert Kaplan, Matthew Allison, Maya Salameh, Franklyn Gonzalez, Daniela Sotres-Alvarez, Yimin Ding, Yejin Mok, Jennifer Schrack, Kuni Matsushita
Journal: Circulation (2025)

Introduction: Lower extremity peripheral artery disease (PAD) causes pain and discomfort with exertion, possibly leading to reduced physical activity (PA). Resting ankle-brachial index (ABI), the standard method for diagnosing PAD, has low sensitivity in the general population. Aim: To examine the association between PAD, identified using two definitions (ABI only and several different modalities), and accelerometry-derived PA in HCHS/SOL. Methods: Using interim data from 2,901 participants (mean age = 63 years; 67% female) from four U.S. sites, PAD was defined as (a) a resting ABI ≤0.90 or (b) if there was a significant drop in post-exercise ABI or at least 2 of the following conditions: 1) toe-brachial index ≤0.6, 2) abnormal Doppler waveforms, or 3) abnormal pulse-wave recordings. PA was measured 24 hours a day over 7 days using wrist-worn accelerometers and summarized as total activity counts/day (TAC), active time (min/day), and activity fragmentation (active-to-sedentary transition probability [ASTP], [higher=more fragmented]). We fitted linear regression models, adjusted for age, sex, smoking, adiposity, diabetes, and hypertension, and accounted for sampling weights. Results: PAD was identified in 104 participants (3.6%) by low resting ABI and 386 (13.3%) via the other modalities. When compared to those without PAD, those with an ABI ≤0.90 had lower and more fragmented daily PA (beta for TAC -227.9 [95% CI: -437.4, -18.4], active time -39.3 min [-76.5, -2.2], ASTP 1.8% [-0.2, 3.9]). Those with PAD identified by the other tests (vs. no PAD) also showed lower activity and more fragmented PA, but these associations were not statistically significant (Figure). Conclusion: PAD identified by a resting ABI ≤0.90 was significantly associated with lower and more fragmented PA, while PAD identified through other methods showed weaker associations with PA, suggesting that further research is needed to clarify how PAD with resting ABI &gt;0.90 may affect PA.
Abstract P3092: Improvements in Hemoglobin A1c among Diabetic and Prediabetic Participants of a Mobile Health Cardiovascular Program
Authors: Walter Roberts, Helena Lyson, Yehuda Paz
Journal: Circulation (2025)

Background: Cardiovascular disease (CVD) is the leading cause of death globally, and diabetes is a significant independent risk factor. Mobile health (mHealth) technology can enable effective self-management of CVD risk factors. This study evaluates the impact of an mHealth cardiovascular risk self-management program designed to promote behavioral and lifestyle changes on hemoglobin A1c (HbA1c) among participants with diabetes or prediabetes. Methods: We analyzed real-world data from participants of the mHealth program between January 2020 and April 2024. Participants were included in the analysis if they had an A1c of &gt; 5.7% or a previous diagnosis of diabetes, as well as at least two A1c values available from linked electronic health records. Change in A1c was evaluated from baseline (measured up to 6 months before program enrollment) to follow-up. Participants were stratified according to their baseline A1c values (well-controlled: &lt;7%; fairly-controlled: 7% to 9%; poorly-controlled: &gt;9%) to separately evaluate the effects of program membership on A1c outcomes among individuals with different levels of diabetes severity. Results: A total of 4,358 participants (mean age 56.2±11.2 years, 56.8% female, mean baseline A1c 6.8±1.4%) were included (Table 1). The mean follow-up period was 312.4 days. Pre- and post-enrollment A1c values are graphed in Figure 1. Participants with poorly-controlled baseline A1c (&gt;9%, n =352) showed a significant reduction of 2.1% (from 10.1±1.4% to 8.0±1.9%; t (351) = -18.0, p &lt; 0.001, d = -0.96). Those with fairly-controlled baseline A1c (7–9%, n =1,073) experienced a modest decrease of 0.2% (from 7.5±0.56% to 7.3±1.11%; t (1,072) = -7.2, p &lt; 0.001, d = -0.22). Participants with well-controlled baseline A1c (&lt;7%, n =2,933) remained well-controlled, with a clinically insignificant increase of 0.1% (from 6.0% to 6.1%; t (2,932) = 4.8, p &lt; 0.001, d = 0.09). Conclusion: Participants of an mHealth cardiovascular risk self-management program with poorly-controlled baseline A1c (&gt;9%) decreased A1c significantly, while those with well-controlled baseline A1c (&lt;7%) maintained A1c in this range. These findings highlight the potential of mHealth technology to support control of diabetes in the context of managing CVD risk.
Abstract P3082: Pregnancy heavy metal, essential element, and micronutrient mixtures and mid-life blood pressure and hypertension: findings from a prospective U.S. pregnancy cohort study with two decades of follow-up
Authors: Mingyu Zhang, Izzuddin Aris, Andres Cardenas, Sheryl Rifas-Shiman, Pi-i Lin, Long Ngo, Emily Oken, Marie-France Hivert, Stephen Juraschek
Journal: Circulation (2025)

Background: Heavy metals are cardiovascular disease risk factors, while essential elements possess antioxidant and anti-inflammatory properties and are crucial for health at trace levels. Metals may also interact with elements, leading to synergistic or antagonistic health effects. The associations of a mixture of metals and elements during pregnancy with women’s mid-life blood pressure (BP) and hypertension are unclear. Objective: To examine the prospective associations of a mixture of 6 metals, 5 elements, and 2 micronutrients in early pregnancy with women’s BP and risk of hypertension in mid-life. Methods: Project Viva is a prospective pregnancy cohort that enrolled women between 1999-2002 from Eastern MA. We measured metals (As, Ba, Cd, Cs, Hg, Pb) and elements (Cu, Mg, Mn, Se, Zn) in red blood cells, along with folate and vitamin B12 in plasma, all collected during pregnancy (median: 9.9w gestation). We measured mid-life BP in 2017-2020 (median maternal age: 51.2y). We examined associations of individual metals and elements with BP using linear regression and with hypertension (BP ≥130/80 mmHg or use of anti-hypertensive medication) using modified Poisson regression. We used Bayesian kernel machine regression (BKMR) to examine the mixture effects of all exposures. Models were adjusted for confounders listed in the Figure footnote . Results: Of the 493 women, 72% were White, 78% were college graduates, and 65% had a household income &gt;$70K/y. The median (IQR) follow-up time was 18.1 (17.8-18.6)y. A doubling of Cu and Mn concentrations was associated with 0.75 (95% CI: 0.57, 0.99) and 0.80 (95% CI: 0.71, 0.91) times the risk of hypertension, respectively. A doubling of Cs and Se was respectively associated with 1.22 (95% CI: 0.94, 1.57) and 1.19 (95% CI: 0.77, 1.83) times the risk of hypertension, though the 95% CIs were wide. A doubling of vitamin B12 was associated with a 3.64 (95% CI: 1.23, 6.04) mmHg lower systolic BP and a 2.52 (95% CI: 0.72, 4.32) mmHg lower diastolic BP ( Figure 1 ). BKMR showed similar, linear associations for BP (results not shown) and hypertension ( Figure 2 ) and did not identify metal-element or metal-micronutrient interactions. The essential element mixture was monotonically associated with lower BP and risk of hypertension ( Figure 3 ). Conclusion: Optimizing essential element levels during pregnancy, particularly Cu and Mn, along with vitamin B12, may offer protective benefits against higher BP and hypertension in mid-life women.
Abstract P2086: Sex and Racial Differences in Prescription Patterns to Guideline-directed Medical Therapy Among STEMI Patients.
Authors: Mary Imboden, Jane Bryant, Adrienne Jones, Renee Swanson, Lori Tam, Kevin Woolf
Journal: Circulation (2025)

Background: ST-elevation myocardial infarction (STEMI) is associated with serious complications and mortality. Percutaneous coronary intervention (PCI) is the principal reperfusion strategy for STEMI patients, followed by pharmacologic therapy to prevent recurrent cardiovascular (CV) events. The American Heart Association (AHA) and American College of Cardiology (ACC) recommend the use of guideline directed medical therapy (GDMT) prescribed at hospital discharge following a STEMI. Given the well-described sex and racial differences in the adherence to pharmacologic therapies, this study aimed to assess whether sex and racial differences also exist in GDMT prescribing patterns in STEMI patients at hospital discharge. Methods: Analyses were performed on 734 STEMI patients (176 females, 558 males; 78.5% white) that presented to two urban emergency departments between January 1, 2022, and March 31, 2024 and underwent PCI during admission. Discharge prescriptions for GDMT based on AHA/ACC guidelines (Aspirin, P2Y12 inhibitors, β-blockers (BBs), angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), and statins) were compared by sex and race using chi-square tests of association. Given that physicians commonly only prescribe ACEIs/ARBS when ejection fraction (EF) is low, sub-analyses were run on patients with EF &lt;50%. Results: Table 1 shows differences in GDMT prescribed at discharge by sex and race categories. Among patients with successful PCI, 52.8% were prescribed all five GDMT and 70.0% were prescribed four secondary prevention medications (Aspirin, P2Y12 inhibitors, BBs, statins). Males were more likely to be prescribed all five GDMT at discharge compared to females (55.4 vs. 44.6%). The greatest difference in medication class prescribed between sexes was for BBs (80.1 vs. 72.2%). Racial disparities were also noted, as white patients were more likely to receive all five GDMT at discharge compared to non-white patients (53.7 vs. 47.7%). The greatest difference in medication class prescribed between white and non-white patients was for ACEI/ARBs (63.1 vs. 49.3%). Racial differences remained significant when only assessing patients with low EF (86.3 vs. 70.8% on ACEI/ARB). Conclusion: Optimal secondary prevention medications are effective in reducing the risk of repeat CV events. Strategies are needed to address sex and racial disparities in GDMT prescribing patterns to achieve AHA/ACC guidelines and improve patient outcomes.
Abstract MP37: Proteomics Of Prediabetes Progression And Remission: The Atherosclerosis Risk In Communities (ARIC) Study
Authors: Mary Rooney, Jingsha Chen, Keenan Walker, Justin Echouffo, Christie Ballantyne, Eric Boerwinkle, Chiadi Ndumele, Jim Pankow, Morgan Grams, Elizabeth Selvin, Joe Coresh
Journal: Circulation (2025)

Introduction: Proteomics could improve our understanding of the mechanisms underlying short-term prediabetes progression and remission, i.e., reverting to normoglycemia. Objective: To identify proteomic predictors of 3-year progression from prediabetes to diabetes and remission. Method: We used data from the Atherosclerosis Risk in Communities (ARIC) Study visit 2 (1990-2) and visit 3 (1993-5). We examined associations of 4,955 plasma proteins (SOMAScan v4.0) in participants with baseline prediabetes (fasting glucose [FG] 100-125 mg/dL without diabetes). We used multivariable logistic regressions to examine protein associations with 3-year progression from prediabetes to diabetes (physician diagnosis, medication, or FG ≥126 mg/dL) or remission (FG &lt;100 mg/dL). Analyses were adjusted for demographics, cardiometabolic risk factors, and baseline glucose. Statistical significance was based on p&lt;10 -5 . We explored biologic pathways enriched among top proteins and calculated the delta-AUC for models with (and without) the associated proteins. Results: The 3,788 participants with prediabetes were mean aged 57 years (SD:6), 52% were women, 18% self-identified as Black. The 3-year cumulative incidence of diabetes was 6% and was 40% for prediabetes remission. We identified 6 proteins associated with 3-year progression to diabetes (e.g., lower adiponectin [ADIPOQ]) and 8 proteins (e.g., higher insulin growth factor binding protein 2 [IGFBP2], lower complement C3 [C3]) associated with prediabetes remission. Adipogenesis and Jak/STAT signaling were among the pathways enriched in diabetes-associated proteins. Regulation of IGF transport and uptake by IGFBPs and C3/C5 activation were pathways for remission-associated proteins. The 6 proteins collectively improved diabetes progression prediction (covariate only AUC=0.798; delta-AUC=0.03 p&lt;0.001). The 8 proteins collectively improved remission prediction (covariate only AUC=0.722; delta-AUC=0.03 p&lt;0.001). Conclusions: In persons with prediabetes, we identified known and novel proteins that were associated with 3-year progression to diabetes and remission. Proteins associated with remission relate to reduced inflammation and improved insulin sensitivity.
Abstract MP12: Global Disparities of Hypertension Prevalence and Control: A Systematic Analysis of Population-Based Studies
Authors: Samantha O'Connell, Paul Whelton, Hua He, Fengxue Li, Farah Allouch, Lauren Shapiro, Megan Vandenburg, Mihir Patel, Akanksha Patel, Jiang He, Katherine Mills
Journal: Circulation (2025)

Background: Hypertension is the leading preventable risk factor for premature death and disability worldwide. Aims: We estimated global disparities in hypertension prevalence, awareness, treatment, and control in 2020 and compared secular changes from 2000 to 2020 worldwide. Methods: We searched MEDLINE from 1995 to June 2023 and supplemented with a manual review of retrieved article references. We applied sex- and age- specific prevalences from each country to population data to calculate the number of hypertensive adults in each region and worldwide. Proportions of awareness, treatment, and control from each country were applied to hypertensive populations to obtain regional and global estimates. Results: A total of 237 population-based surveys with 4,779,321 adults from 118 countries were included in analyses. We defined hypertension as SBP/DBP ≥140/90 mm Hg, or antihypertensive medication use and control of hypertension as SBP/DBP &lt;140/90 mm Hg. An estimated 30.6% (95% CI, 30.0-31.2%) of the world’s adult population had hypertension in 2020. The prevalence was higher in low- and middle-income countries compared to high-income (Table). In 2020 an estimated 1.59 (1.57-1.61) billion people had hypertension; 378 (376-381) million in high-income and 1.21 (1.19-1.23) billion in low- and middle-income countries. From 2000 to 2010 the age-standardized prevalence of hypertension increased by 3.5% among men and 3.3% among women; from 2010 to 2020, the age-standardized prevalence increased by 2.1% among men and decreased by 1.0% among women. From 2000 to 2010 to 2020, worldwide proportions of hypertension awareness (38.7% vs 45.8% vs 48.0%), treatment (29.2% vs 36.9% vs 40.6%), and control among hypertensives (11.3% vs 14.0% vs 19.1%) increased. During the same period, proportions of awareness in high-income countries (57.3% vs 68.9% vs 68.6%) remained higher than in low-and middle-income countries (30.2% vs 37.6% vs 41.6%). Similar trends were identified for treatment in high-income countries (41.9% vs 56.2% vs 62.2%) compared to low- and middle- income countries (23.4% vs 28.8% vs 33.8%). Finally, control among hypertensives remained higher in high-income countries (15.1% vs 28.3% vs. 33.4%) compared to low- and middle-income countries (9.6% vs 9.0% vs 14.6%) in the same timeframe. Conclusions: Collaborative efforts are needed to address the high burden of hypertension worldwide, particularly in low- and middle-income countries.