tbuckley/cabot-search huggingface dataset:
Abstract P1129: Physical Activity Types, Variety, and Mortality: Results from Two Prospective Cohort Studies
Authors: Jinbo Hu, Han Han, Dong Hoon Lee, Yiwen Zhang, Edward Giovannucci, Meir Stampfer, Frank Hu, Yang Hu, Qi Sun
Journal: Circulation (2025)

Introduction: Different physical activities (PAs) may exert distinct physiological effects, yet associations of PA types and variety with mortality were unclear. Methods: We prospectively followed 98,117 participants in the Nurses’ Health Study (1986-2018) and the Health Professionals Follow-up Study (1986-2020) who were free of chronic diseases at baseline. Leisure-time PA was assessed biennially with validated questionnaires and was expressed as MET-hr/week. PA variety was measured as the total number of PAs that participants consistently engaged in. Cox regression was used to examine the association between PA and mortality. Results: During 2,180,153 person-years of follow-up, 32,665 deaths were recorded, with 8,314 from CVD, 8,932 from cancer, and 2,424 from respiratory disease [RD]. Total PA was inversely associated with mortality from any cause, CVD, cancer, RD, or other causes. Individual PAs, except for bicycling and swimming, were associated with lower mortality. The pooled multivariable-adjusted hazard ratios (95% CIs) of total mortality (highest vs. lowest group) were 0.85 (0.82, 0.88) for walking, 0.91 (0.87, 0.96) for jogging, 0.89 (0.82, 0.96) for running, 0.98 (0.95,1.01) for bicycling, 1.04 (1.00,1.09) for swimming, 0.86 (0.81, 0.91) for tennis, 0.90 (0.88, 0.93) for climbing stairs, 0.89 (0.86, 0.92) for rowing, and 0.90 (0.85, 0.95) for weight training. Non-linear relationships were found for total PA and most individual PAs: the risk reduction plateaued after reaching certain levels. Higher PA variety was significantly associated with lower mortality. After adjustment of total PA levels, participants in the highest quintile of PA variety score (vs. the lowest) had 15-32% lower mortality from any cause, CVD, cancer, RD, and other causes (all P -trend &lt;0.001). Conclusions: Most types of PA were associated with lower mortality. PA variety was inversely associated with mortality independent of total PA level. Our data suggest that long-term engagement of multiple types of PAs may benefit longevity.
Abstract MP77: Achieving Guidelines within a 24-Hour Movement Paradigm and Risk of Cardiovascular Disease and All-Cause Mortality in United States Adults
Authors: Benjamin Boudreaux, Chang Xu, Erin Dooley, Bjoern Hornikel, Alexandra Munson, Ari Shechter, Priya Palta, Kelley Gabriel, Keith Diaz
Journal: Circulation (2025)

Introduction: Lifestyle factors such as achieving recommended levels of aerobic moderate to vigorous physical activity (MVPA) intensity ( &gt; 150 min/wk), sedentary behavior (SB) ( &lt; 8h/d), and sleep duration (7-9h/d) comprise the 24-hour movement paradigm and are independently linked to mortality risk. Limited evidence exists on whether adherence to the 24-Hour Movement Guidelines (24H-MG) in combination is associated with mortality risk. Purpose: Examine the association of meeting the 24H-MG and risk of cardiovascular disease mortality (CVD) and all-cause mortality and estimate the number of deaths that could be prevented by meeting all components of the 24H-MG in a national representative sample of US adults. Methods: Participants enrolled in the 2005 and 2010 National Health Interview Survey were analyzed. MVPA, SB, and sleep were self-reported. Mortality was ascertained from National Death Index through December 31, 2019. Meeting a 24H-MG was classified by meeting following criteria sleep 7-9h/d, SB &lt; 8h/d, and MVPA &gt; 150 min/wk. Results: Among US adults, 4.9% (95% CI 4.6- 5.2), 23.9% (23.4-24.5), 44.6% (44.0-45.2), 26.6% (26.0-27.2) met 0,1, 2, or all 3 24H-MG respectively. After adjusting for covariates and excluding deaths in the first two years, meeting a greater number of 24H-MG was associated with lower risk of all-cause mortality in a dose-dependent fashion over a median follow-up of 9.9 years (Figure, Panel A). Hazard ratios (HR [95% CI]) comparing US adults meeting 1, 2 or 3 guidelines versus meeting 0 guidelines were 0.71 (0.59-0.85), 0.61 (0.51-0.73), and 0.52 (0.43-0.64), respectively (p-trend &lt;0.001). Meeting a greater number of 24H-MG was also associated with a reduced risk of CVD (Figure, Panel B): HRs=0.85 (0.60, 1.21), 0.75 (0.53, 1.06), 0.42 (0.28, 0.63) for meeting 1, 2 or 3 guidelines, respectively, versus meeting 0 guidelines (p-trend &lt;0.001). By targeting all but those who meet all 3 movement guidelines, 16.8% (95% CI: 13.7-19.0) of total deaths and 38.7% (95% CI: 31.0-41.4) of CVD deaths could be prevented by shifting US adults to meet all 3 guidelines. Conclusions: In a national representative sample of US adults, there is a dose-response association between meeting 24-hour movement guidelines and mortality risk. Meeting all three guidelines was associated with a 48% reduced risk of all-cause mortality and 58% reduced risk of CVD. These findings support the need to promote a healthy 24-hours to reduce mortality risk in US adults.
Abstract P3025: Evaluating the Correlation Between Urinary Microalbumin (ACR), Serum C-Reactive Protein (CRP), and Cardiovascular Risk Markers in Type 2 Diabetes Mellitus
Authors: Manvitha Thalamati
Journal: Circulation (2025)

Introduction: Diabetes mellitus (DM) is a common endocrine disorder characterized by hyperglycemia due to insulin deficiency. Over the past 35 years, the incidence of DM has nearly quadrupled, contributing to around 1 million deaths in 2019, with cardiovascular complications as a leading cause. Current management strategies in type 2 DM patients focus on early detection of cardiovascular risk markers, such as urinary microalbumin and serum C-reactive protein (CRP), both of which are cost-effective and minimally invasive. Objectives: To determine the correlation between urinary microalbumin, serum CRP, and albumin-to-creatinine ratio (ACR) with traditional cardiovascular risk markers in patients with type 2 diabetes mellitus. Methods: The study included 87 clinically diagnosed type 2 diabetes mellitus patients on oral antidiabetic medication, aged 35 to 60 years, and with normal serum creatinine levels. After obtaining informed consent, blood and urine samples were collected to assess blood glucose, serum CRP, renal profile, lipid profile, liver function tests, and urinary microalbumin. Albumin creatinine ratio (ACR) and atherogenic index of plasma (AIP) were calculated. Results: Comparison of profiles in the study revealed a significant decrease in serum HDL levels, a higher TG: HDL ratio, elevated glycated hemoglobin (HbA1c), and a raised atherogenic index of plasma (AIP) in cases with CRP ≥ 0.3 mg/dL compared to those with CRP &lt; 0.3 mg/dL. Conversely, serum albumin (p&lt;0.01), ALT, and A:G ratio were decreased in cases with CRP ≥ 0.3 mg/dL. MAU and blood urea nitrogen (BUN) were elevated in cases with ACR ≥ 30 mg/g (p&lt;0.01) compared to those with ACR &lt; 30 mg/g. Pearson’s correlation with CRP showed a negative correlation with total protein, albumin (p=0.01), A:G ratio, and hemoglobin, while BUN and serum ALP showed a positive correlation with CRP. ACR correlated positively with MAU (p=0.01) and negatively with albumin (p=0.05), with both correlations being statistically significant. These results demonstrate an association between urinary microalbumin (ACR), serum CRP, atherogenic index of plasma, and cardiovascular risk markers in type 2 DM. Conclusion: The study suggests that spot microalbuminuria and serum CRP are correlate well with traditional cardiovascular risk markers and can be used as screening tools for cardiovascular disease in DM patients. These markers are inexpensive, minimally invasive and can warrant for timely intervention's.
Abstract P3146: Racial Disparities in the Association of Adiposity Measures with Cardiovascular Disease Mortality
Authors: King Sum Tong, Jeff Leung, Seth Tivakaran, Julia Raghu, Nicholas Panyanouvong, Lester Uy, Armaan Jamal, Malathi Srinivasan, Nitya Rajeshuni, Gloria Kim, Robert Huang, Latha Palaniappan, Adrian Bacong
Journal: Circulation (2025)

Introduction: Body Mass Index (BMI) has been generally used to measure adiposity, but it can be inaccurate when examining diverse race groups. We examined how the association between cardiovascular disease (CVD) mortality and adiposity – as measured by BMI, Waist-to-Height Ratio (WHtR), and Body Roundness Index (BRI) – differed by race. Hypothesis: We hypothesized that BRI would have the strongest association with obesity-related mortality risk with the association being more pronounced among Non-White race groups. Methods: We use 2019 National Death Index Linked Mortality data combined with the pooled adult sample of the 2007-2018 National Health and Nutrition Examination Survey (N = 31,244). We examined four race groups: Non-Hispanic White (n=12,684), Hispanic (n=8,043), Non-Hispanic Black (n=6,669), and Other Races (n=3,848). BMI, WHtR, and BRI were calculated using established equations and scaled by 0.05 increments to improve interpretability for regression analyses. We examined the association between each adiposity measure and CVD-related morality by race using Cox Regression. Results: Each race group had increased risk of CVD-related mortality for increasing adiposity for all measures (Figure). For BMI, people of “Other Race” had the highest risk (HR = 1.04). Non-Hispanic Black people had the lowest risk (HR = 1.01). For WHtR, Hispanic people had the highest risk (HR = 1.16), while Non-Hispanic Black people had the lowest risk (HR = 1.08). Finally, for BRI, Hispanic people had the highest risk (HR = 1.16) while Non-Hispanic Black people had the lowest risk (HR = 1.06). Conclusions: While increased adiposity is associated with heighted risk of mortality for all race groups, the association may be stronger for Hispanic people. Further investigation is needed into which adiposity measure is best for assessing CVD risk and mortality.
Abstract P1119: Model-based Replacement of Sedentary Time with Light Intensity Physical Activity is Associated with Improved Cardiometabolic Risk Score over 15 Years of Midlife in the CARDIA Study
Authors: Sylvia Badon, Alex Asera, Erin Dooley, Kara Whitaker, Bjoern Hornikel, Ankeet Bhatt, Robert Booker, Barbara Sternfeld, Kelley Gabriel
Journal: Circulation (2025)

Introduction: Current physical activity (PA) recommendations support replacing time spent sedentary with PA of any intensity. Replacing sedentary time with light intensity PA (LPA) may be a more accessible behavior change for many individuals compared with increasing moderate/vigorous intensity PA (MVPA). However, the longitudinal associations of replacing sedentary behavior with LPA and cardiometabolic health are not clear. Hypothesis: We hypothesized that replacing time spent sedentary with LPA is associated with improvement in cardiometabolic risk across midlife. Methods: Participants in the CARDIA study with accelerometer and cardiometabolic biomarker data at Year 20 (2005-06) and Year 35 (2020-22) study visits (n=996) were included in this analysis. Waist circumference, mean arterial pressure, fasting glucose, fasting insulin, triglycerides, and HDL cholesterol were standardized and averaged to create a z-score, where higher scores represent worse cardiometabolic health. We used compositional isotemporal substitution models to estimate changes in cardiometabolic risk score resulting from replacement of sedentary time with LPA and whether associations varied by initial sedentary time or MVPA level. Results: Across midlife (mean 45±SD 3.5 [Y20] to mean 60±SD 3.6 [Y35] years old), mean cardiometabolic risk score increased by 0.03 SD. In those with initially low sedentary time, replacing 1 hour of sedentary time with LPA from Y20 to Y35 was associated with a -0.03 SD change in cardiometabolic risk score (95% CI: -0.06, -0.004; Figure) across the same time period. In those with initially high sedentary time, associations were attenuated and not statistically significant (-0.02; 95% CI: -0.04, 0.004). Associations were stronger with more time reallocated (up to 3 hours) and similar in those with low and high MVPA. Conclusions: Model-based replacement of sedentary time with LPA was associated with attenuation of age-related decline in cardiometabolic health across midlife.
Abstract 075: Diurnal postprandial glucose responses to meals with different carbohydrate content and glycemic index and their effects on lipid metabolomics: The OmniCarb trial
Authors: Yoriko Heianza, Difei Liu, Qi Sun, Rebholz Casey, Edgar Miller, Lawrence Appel, Frank Sacks, Lu Qi
Journal: Circulation (2025)

Background and aims: Meal timing has been suggested as a circadian disruptor that may be linked cardiovascular disease by influencing fatty acid metabolism and specific metabolomic pathways. We aimed to test associations of diurnal postprandial glucose responses (PPGRs) after consuming diets varying in carbohydrate amount (Carb) and glycemic index (GI) with comprehensive lipid subtypes and lipidomic signatures. Materials and methods: This ancillary analysis included 61 adults from the OmniCarb trial, a randomized crossover, controlled feeding trial of 4 diets that differed in Carb and GI levels. Each diet was based on a healthful DASH-type diet and was provided for 5 weeks, with a 2-week washout. Twelve-hour meal tests were conducted at the end of each intervention. Participants were given the same diet type for that diet period for breakfast, lunch, and dinner, which had a mean 486, 610, 618 kcal, respectively, for a typical 2000-kcal diet. The area under the curve (AUC) of glucose after each meal was calculated and analyses were performed per 1 SD higher of AUC-glucose. Lipid subtypes considering the presence of apolipoprotein C-III (apoC-III) were measured in fasting samples collected at the end of the intervention. Serum lipid metabolites were analyzed using Metabolon's complex lipids targeted panel. Results: At the end of high-carb and high-GI diet interventions, PPGRs after dinner, but not after lunch, were associated with higher levels of atherogenic apoC-III (β [SE]: 0.3 [0.1]; p=0.035), apoB (β 0.2 [0.1]; p=0.04), and cholesterol (β 1.2 [0.5]; p=0.018) in LDL with apoC-III. PPGRs after breakfast were not significantly related to cholesterol in LDL with apoC-III. When analyzing effects on lipid class concentrations, a low-carb and low-GI diet compared to high-carb and high-GI diet lowered triacylglycerol (TAG) and phosphatidylcholines but slightly increased phosphatidylethanolamines (PE) and lactosylceramides ( p &lt;0.05 for all). At the end of low-carb and low-GI diet interventions, greater AUC-glucose after dinner and AUC-glucose differences between lunch and dinner showed significant associations with higher levels of cholesteryl esters, dihydroceramides, TAG, and PE. Conclusion: Greater PPGRs were associated with atherogenic lipid subtypes and lipidomic pathways after evening meals but not after daytime meals. The atherogenic lipid pathways associated with PPGRs in the evening may vary depending on Carb content and dietary GI of the meals.
Abstract MP58: Left ventricular hypertrophy among Black adults in a low-income country: the Haiti Cardiovascular Disease Cohort Study
Authors: Anju Ogyu, Vanessa Rouzier, Rodney Sufra, Reichling St Sauveur, Marie Christine Jean Pierre, Joanna Lin, Victor Davila-Roman, Altaf Pirmohamed, Parag Goyal, Richard Devereux, Wheytnie Alexandre, Nour Mourra, Marie Marcelle Hippolyte, Jean William Pape, Margaret Mcnairy, Lily Yan
Journal: Circulation (2025)

Cardiovascular disease (CVD) is the leading cause of death globally and disproportionately affects low-and-middle income countries like Haiti. Left ventricular hypertrophy (LVH) is an important predictor of CVD incidence and mortality, but rarely measured in resource-constrained settings due to limited availability of echocardiograms (ECHO). Electrocardiograms (EKGs) may be a more accessible method to detect LVH. To address this gap, we determined the prevalence of LVH using echocardiography (LVH-ECHO), using EKGs (LVH-EKG), and compared diagnostic performance of EKGs versus ECHOs in detection of LVH in Haiti. We used enrollment data from the Haiti CVD Cohort study. Adults (≥18 years) living in Port-au-Prince were recruited using multistage random sampling between March 2019 and August 2021. All participants underwent standardized questionnaires to capture CVD risk factors, vital signs, physical exams, and EKGs. ECHOs were performed on participants with signs and symptoms of CVD or hypertension. Left ventricular mass was derived using 2D measurements with Devereux’s formula and indexed against body surface area (LVMI). LVH-ECHO was defined as LVMI &gt;95 g/m 2 (female) and &gt;115 g/m 2 (male), and defined by Sokolow-Lyon, Cornell Criteria and Limb-Lead Voltage criteria on EKGs. We compared risk factors for LVH-ECHO using univariate analysis and diagnostic performance of EKGs vs echocardiograms using sensitivity, specificity, likelihood ratio (LR) and accuracy. Among the 3,005 enrolled participants, 1,040 (34.6%) had both EKG and ECHO. Majority were female (67.0%) with mean age of 48.5 years (SD=15.3). Prevalence of LVH-ECHO was 39.0% (95%CI: 36.6%-41.5%), and associated with older age, having arrhythmia and lower education level attainment on univariate analysis. Prevalence of LVH-EKG ranged from 1.9%-5.0%. In comparing LVH-EKG to LVH-ECHO, all criteria had low sensitivity (&lt;10%), high specificity (&gt;90%) and moderate accuracy (62-64%). Limb-Lead voltage and Cornell criteria performed better in females (LR+ = 10.7) and males (LR+ = 8.2), respectively. Our findings show high prevalence of LVH-ECHO amongst a cohort of young Haitian adults with hypertension or CVD symptoms. All LVH-EKG criteria performed well on “ruling-in” LVH but missed cases of LVH due to poor sensitivity highlighting the need and capacity for ECHOs. Further research is needed to understand the utility of LVH diagnosis as a clinical tool to reduce CVD risk in low-resource settings.
Abstract P1009: Epigenetic age acceleration as a hallmark of premature mortality in US adults
Authors: Minghao Kou, Hao Ma, Xuan Wang, Yoriko Heianza, JoAnn Manson, Lu Qi
Journal: Circulation (2025)

Introduction: Epigenetic (DNA methylation) clocks have been derived as hallmarks of biological age based on their ability to predict chronological age or aging-related phenotypes. However, studies comprehensively examining the associations between epigenetic age acceleration and premature mortality in nationally representative U.S. populations are lacking. Hypothesis: Epigenetic age acceleration will be associated with higher risks of premature mortality in the general US population. Methods: We included 2,191 participants aged 50-79 years from the 1999-2002 National Health and Nutrition Examination Survey (NHANES) who underwent DNA methylation measurement. We included five epigenetic clocks (Horvath’s, Hannum’s, PhenoAge, GrimAge, and DunedinPoAm), and calculated epigenetic age acceleration as the residual from regressing epigenetic age on chronological age (except for DunedinPoAm, which reflects aging rates). Premature mortality was defined as death before age 80, with a sensitivity analysis using a cutoff of 75 years. Cox proportional hazards models were used to assess the association between epigenetic age acceleration and premature mortality. Results: We found that faster epigenetic age acceleration was significantly associated with a 19% to 61% higher risk of premature mortality across the 5 clocks, adjusting for demographic, socioeconomic, and behavioral factors ( Table ). GrimAge age acceleration was the strongest predictor, while Horvath age acceleration was the weakest. The associations were consistent when premature mortality was defined as death before age 75. Conclusions: Our examination of epigenetic age acceleration measures in a representative U.S. population lends innovative evidence to support the potential application of epigenetic clocks as hallmarks for monitoring biological aging and a promising target for prevention of premature mortality and aging-related disorders in the broader US populations.
Proteomic-based stemness score measures oncogenic dedifferentiation and enables the identification of druggable targets
Authors: Iga Kołodziejczak-Guglas, Renan L S Simões, Emerson de Souza Santos, Elizabeth G Demicco, Rossana N Lazcano Segura, Weiping Ma, Pei Wang, Yifat Geffen, Erik Storrs, Francesca Petralia, Antonio Colaprico, Felipe da Veiga Leprevost, Pietro Pugliese, Michele Ceccarelli, Houtan Noushmehr, Alexey I Nesvizhskii, Bożena Kamińska, Waldemar Priebe, Jan Lubiński, Bing Zhang, Alexander J Lazar, Paweł Kurzawa, Mehdi Mesri, Ana I Robles, Li Ding, Tathiane M Malta, Maciej Wiznerowicz
Journal: Cell Genomics (2025)

Cancer progression and therapeutic resistance are closely linked to a stemness phenotype. Here, we introduce a protein-expression-based stemness index (PROTsi) to evaluate oncogenic dedifferentiation in relation to histopathology, molecular features, and clinical outcomes. Utilizing datasets from the Clinical Proteomic Tumor Analysis Consortium across 11 tumor types, we validate PROTsi's effectiveness in accurately quantifying stem-like features. Through integration of PROTsi with multi-omics, including protein post-translational modifications, we identify molecular features associated with stemness and proteins that act as active nodes within transcriptional networks, driving tumor aggressiveness. Proteins highly correlated with stemness were identified as potential drug targets, both shared and tumor specific. These stemness-associated proteins demonstrate predictive value for clinical outcomes, as confirmed by immunohistochemistry in multiple samples. The findings emphasize PROTsi's efficacy as a valuable tool for selecting predictive protein targets, a crucial step in customizing anti-cancer therapy and advancing the clinical development of cures for cancer patients.