tbuckley/cabot-search huggingface dataset:
Abstract P1122: Reducing Sedentary Behavior and Cardiometabolic Biomarkers: Results from the RESET BP Trial
Authors: Bethany Barone Gibbs, Subashan Perera, Molly Conroy, John Jakicic, Matthew Muldoon
Journal: Circulation (2025)

Introduction: Sedentary behavior is associated with cardiovascular disease and diabetes, yet evidence from randomized controlled trials (RCT) demonstrating a causal effect of sedentary behavior on cardiometabolic biomarkers is scarce. Hypothesis: A 3-month sedentary behavior reduction intervention will improve cardiometabolic biomarkers compared to controls. Methods: The Reducing Sedentary Behavior on Blood Pressure (RESET BP) RCT tested the effect of a multi-component sedentary behavior reduction intervention on blood pressure (primary outcome) and other cardiometabolic risk factors after 3 months among 271 desk workers with high blood pressure. Primary findings revealed no evidence of a blood pressure reduction despite a 1.2 hours/day greater reduction in sedentary behavior. Here we considered secondary/exploratory outcomes including aldosterone, plasma renin activity (PRA), lipids, insulin and glucose, and HOMA-IR. Blood samples were obtained at baseline and 3-month follow-up, after an overnight fast and a 30-minute seated rest, stored at -80°F until the end of the study, and analyzed by a central laboratory using standardized assays. We performed analysis of covariance with adjustment for baseline values for comparing groups. Results: RESET BP participants had mean age 45 years, mean blood pressure 129/83 mmHg, were 60% female, and 83% White. Among those with cardiometabolic biomarkers (n=173-188), intervention participants had a 14.97 ng/mL greater reduction in aldosterone (p=0.037) and 0.23 ng/mL/hour in PRA (p=0.046) over follow-up compared to controls, indicating a favorable change. Changes in other biomarkers showed no evidence of an intervention vs. control difference: LDL cholesterol (-2.35 mg/dL; p=0.443); HDL cholesterol (-0.72 mg/dL; p=0.543); triglycerides (3.52 mg/dL, p=0.627); glucose (-1.98 mg/dL; p=0.225); insulin (0.44 IU; p=0.723); and HOMA-IR (-0.10; p=0.808) Conclusions: Despite no evidence of improvement in resting blood pressure or other biomarkers, intervention-related decreases in aldosterone and PRA may suggest a novel mechanism of benefit to the renin-angiotensin-aldosterone system with sedentary behavior reduction.
Abstract P3119: Increased Trunk Fat and Decreased Limb Fat Correlate with Adverse Blood Lipid Profiles: Evidence From the MECH-HK Cohort
Authors: Yao Jie Xie, Qingling Yang, Lin Yang, Harry H.X. Wang, Jing Qin
Journal: Circulation (2025)

Introduction: The associations between different regional body fat composition and blood lipids remain unclear, especially in Chinese population. The aim of this study was to investigate the associations of trunk, arm and leg body fat composition with blood lipids. Hypothesis: We hypothesized that trunk, arm and leg body fat percentages (BFP) would be differentially associated with blood lipid levels. Method: The baseline data of the MECH-HK (Migraine Exposures and Cardiovascular Health in Hong Kong Chinese Women) cohort were used for this study. The participants were recruited between October 2019 and October 2021. InBody 270 bioelectrical impedance analysis device was used for body fat composition measurement. Fingerstick capillary blood samples were collected for blood lipid measurements using point-of-care testing devices. Multivariable linear regression models were used to investigate the associations between regional body fat composition and blood lipids. Results: We included 3616 women participants (age: 56.12±8.51) in this analysis. The mean regional arm, trunk and leg BFP were 4.59%, 15.38% and 10.76%, respectively. The mean levels of total cholesterol, HDL cholesterol, LDL cholesterol and triglyceride were 198.42 mg/dL, 65.39 mg/dL, 102.39 mg/dL, and 158.42 mg/dL, respectively. After adjusting for age, education level, monthly family income, smoking and drinking status, physical activity levels, family history of hyperlipidemia and BMI, higher trunk BFP was associated with increased total cholesterol (β: 1.15, 95% CI: 0.25 to 2.04, P = 0.01), LDL cholesterol (β:1.62, 95% CI: 0.83 to 2.41, P &lt; 0.001), and triglyceride (β: 7.85, 95% CI: 5.80 to 9.90, P &lt; 0.001) and decreased HDL cholesterol (β: -1.74, 95% CI: -2.12 to -1.37, P &lt; 0.001). In contrast, higher arm and leg BFP were associated with decreased triglyceride (β for arm BFP: -25.62, 95% CI: -32.49 to -18.74, P &lt; 0.001; β for leg BFP: -8.10, 95% CI: -11.16 to -5.04, P &lt; 0.001) and increased HDL cholesterol (β for arm BFP: 5.34, 95% CI: 4.09 to 9.59, P &lt; 0.001; β for leg BFP: 1.95, 95% CI: 1.39 to 2.50, P &lt; 0.001). Conclusions: Higher trunk BFP was associated with an adverse blood lipid profile, while higher arm and leg BFP was associated with a favorable blood lipid profile. Regional body fat composition may differentially impact blood lipid metabolism.
Abstract P2033: Cumulative Lifetime Estimated Lead Exposure Estimated From DNA Methylation at Midlife and Risk of Incident Cardiovascular Disease: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Rob Walker, Jennifer Weuve, John Warren, Sanaz Sedaghat, Weihua Guan, Ana Navas-Acien, Srishti Shrestha, Myriam Fornage, Rebecca Gottesman, Jim Pankow, Pamela Lutsey
Journal: Circulation (2025)

Background: Lead (Pb) may increase risk of cardiovascular disease (CVD) through several pathways such as endothelial injury, inflammation, oxidative stress, lipid metabolism, and hypertension. Epigenetic biomarkers can be used to estimate cumulative Pb exposure. We tested the hypothesis that greater cumulative Pb exposure estimated through DNA methylation (DNAm)-based biomarkers would be associated with higher risk of CVD. Methods: We included 3,372 ARIC study participants who had Illumina 450K BeadChip DNAm data and were free of prevalent CVD in 1990-1995. We calculated two DNAm-based biomarkers of estimated cumulative Pb exposure that have been validated against measured tibia and patella bone Pb concentrations in an external sample of men. The tibia score was a weighted average of 138 CpG sites while the patella score used 59 CpG sites. ARIC participants were followed through 2021 for incident coronary heart disease (CHD), stroke, heart failure (HF), and a CVD composite. Cox regression was used. Results: Participants were an average of 57±5.9 years old, 62% were female and 70% self-identified as Black and 30% as White. There were 1,342 CVD events and 523 CHD events over a median of 22.0 years. For tibia Pb estimates, interactions (p&lt;0.05) with sex were observed ( Table ). Men in the highest versus lowest quintile of estimated tibia Pb had a hazard ratio (95% CI) of 1.38 (1.03-1.85) for incident CVD and 1.93 (1.24-2.99) for incident CHD, after model 2 adjustments. Magnitudes of association were smaller for HF, and null for stroke. There was no evidence of an association in women. In both sexes, estimated patella Pb was unrelated to both outcomes. Discussion: Epigenetic estimates of cumulative tibia Pb exposure were associated with risk of incident CVD and CHD in this sample of men from the ARIC cohort. DNAm estimates were derived from a sample of men and may not be generalizable to women. There is a longer half-life of Pb in the tibia (a cortical bone) than in the patella (a trabecular bone). Our findings with estimated tibia Pb may reflect longer-term exposure. Additional research is needed to understand the role of cumulative Pb exposure on CVD risk.
Abstract P1171: Spanish-Language Health Promotion Education Does Not Reduce Carotid-Femoral Pulse Wave Velocity in Cohort of Midlife Latinas
Authors: Valentina Marginean, Latesha Harris, Andrea Cazales, Yamnia Cortes
Journal: Circulation (2025)

Background: The risk of cardiovascular disease (CVD), the leading cause of death among women, increases after menopause. Latinas have a more adverse CVD risk profile than non-Latina White women but remain underrepresented in research; additionally, CVD and menopause-related education offered in Spanish is sparse. Carotid-femoral pulse wave velocity (cfWPV), a non-invasive measure of arterial stiffening, has been extensively validated for the prediction of CVD events. In healthy perimenopausal Latinas, this study determined changes in cfPWV following Spanish-language health promotion education. Hypothesis: Participants receiving virtual group education from Su Vida, Su Corazón will develop lower CVD risk, including cfPWV, than their wait-list control counterparts. Methods: A two-arm pilot study was designed to reduce CVD risk in perimenopausal Latinas aged 40-60 years. Participants reported no hormone therapy use in the prior three months and were free of CVD. Participants received weekly virtual sessions from Su Vida, Su Corazón , a health promotion curriculum designed in Spanish with wait-listed participants receiving the same materials one year following randomization. Physical and anthropometric measures (e.g., weight, waist circumference, blood pressure, lipid profile) were collected during a clinical exam at baseline and 12 months. Sociodemographic factors and medical history were self-reported using an interviewer-administered questionnaire. cfPWV was assessed using the Vicorder® device. Statistical analysis was conducted using standardized t-test with two-tailed variance (α=0.10). Results: Participants mean age was 47.7 ± 4.7 years (n=27). Among participants who received the weekly virtual sessions (n=15), cfPWV declined from baseline to 12-month follow-up by a mean 0.2 ± 0.9 m/s. Waitlisted participants (n=12) showed an average decrease of 0.1 ± 1.0 m/s across the same window. This change did not differ significantly between groups (p=0.6). Conclusions: Health promotion with Su Vida, Su Corazón did not significantly impact cfPWV. However, this pilot study demonstrated that it was feasible to collect cfPWV data in a sample of midlife Latinas across clinical and community settings. Future work is necessary to modify the intervention for greater impact.
Abstract P3002: Hypoalbuminemia genetic variants are associated with higher cholesterol levels but not atherosclerotic heart disease
Authors: Alexander Berry, Dylan Cawley, Andrea Hattenberger, Samuel Gidding, Matthew Oetjens
Journal: Circulation (2025)

Introduction: Secondary hypoalbuminemia is associated with many clinical conditions including hypercholesterolemia, liver disease, kidney disease, and diabetes. These clinical conditions are often associated with atherosclerotic cardiovascular disease (ASCVD). It is unknown if primary hypoalbuminemia from genetic causes (rare monogenic variants or polygenic score [PGS]) is associated with hypercholesterolemia and ASCVD risk similar to secondary hypoalbuminemia. Here, we tested the hypothesis that primary hypoalbuminemia has the same association with cholesterol and incident ASCVD as secondary hypoalbuminemia. Methods: Geisinger’s MyCode cohort is a US-based healthcare cohort with linked genomic and electronic health record data for all participants. Among 146,030 MyCode participants with serum albumin measurements, a rare loss-of-function ALB variant was identified in 30 subjects. An albumin level PGS was calculated for each participant. Regression coefficients were calculated using linear models and hazard ratios (HR) were calculated using Cox proportional hazard models controlling for age at first serum albumin measurement, sex, diabetes, and principal components of ancestry. Results: With regard to LDL-C level, across the entire cohort, each standard deviation (SD) reduction in serum albumin was associated with a 3.4mg/dL (95% confidence interval [CI], 3.2-3.6) decrease in LDL-C. The relationship between the albumin PGS and LDL-C followed the same pattern. Each SD reduction in albumin PGS was associated with a 0.7mg/dL decrease in LDL-C (95% CI, 0.5-0.9). In contrast, ALB variant carriers had 0.69g/dL (95% CI, 0.57-0.81) lower albumin, but 37.7mg/dL (95% CI, 23.3-52.1) higher LDL relative to non-carriers. Contradictory results were observed with regard to ASCVD. Across the entire cohort, a reduction in serum albumin was associated with increased incident ASCVD (HR, 1.13 per SD reduction in albumin; 95% CI, 1.12-1.14; p=3.1x10 -90 ). However, neither the albumin PGS (HR, 0.99 per SD reduction in albumin PGS; 95% CI, 0.98-1.00; p=0.19) nor ALB variants (HR, 0.6; 95% CI, 0.19-1.85; p=0.37) were associated with incident ASCVD. Conclusions: The association of hypoalbuminemia with ASCVD is likely related to secondary causes as no association of albumin with incident ASCVD was seen with genetic causes. ALB variants are novel in that they are associated with higher LDL-C but are unrelated to incident ASCVD. Further investigation of the ALB gene is warranted.
Abstract P1064: Central Vascular Implication in Neurocognitive Functioning among Men Living with and without HIV
Authors: Ray Jones, Jessica Blair, Zenoria Causey Pruitt, Michael Hankes, David Vance, Amanda Willig, Daniel Huck, Wendy Post, Mary Masters, Frank Palella, Matthew Mimiaga, Mallory Witt, Jamie Peven, Sabina Haberlen, Mariam Aziz, Roland Thorpe, Emily Levitan, Thomas Buford
Journal: Circulation (2025)

Background: Neurocognitive impairment is linked to aging, vascular stiffness, and HIV infection. The role of vascular stiffness in neurocognitive functioning among men with HIV (MWH) remains unclear. This study examined the relationship between carotid artery distensibility and neurocognitive decline in MWH and men without HIV (MWoH), while exploring whether HIV serostatus and age influenced the association. Methods: Baseline vascular and cognitive assessments (2004-2013) were measured in the Multicenter AIDS Cohort Study. Carotid distensibility was measured using B-mode ultrasound. Neurocognitive function was assessed via executive function (Trail Making B) and psychomotor/information processing speed (Trail Making A, Symbol Digit Modalities Test) over a 6.5-year follow-up. Mixed effects linear regression was used to evaluate the association between baseline stiffness and the progression of neurocognitive function, with time operationalized as participant age. Models were adjusted for demographic, behavioral, and cardiometabolic risk factors. Results: Among 717 men, (mean age 49.9 years, 62.9% non-Hispanic White), 459 (64%) were MWH. In MWH, lower distensibility (higher stiffness) at baseline was associated with greater neurocognitive decline with increasing age in Trail Making A (β=-0.03, p &lt;0.001) and Trail Making B (β=-0.02, p =0.02), but not in Symbol Digit Modalities Test. Among MWoH, lower distensibility at baseline was associated with greater neurocognitive decline with increasing age in Trail Making B (β=-0.03, p=0.002) only. The longitudinal association of distensibility with neurocognition only differed by HIV serostatus for Trail Making A ( p &lt;0.05), when assessing the three-way interaction of serostatus, age, and distensibility. Conclusions: Increased vascular stiffness was linked to significant neurocognitive decline in both MWH and MWoH after adjusting for confounding factors. Addressing cardiovascular risk factors may help prevent neurocognitive decline in this population.
Abstract MP75: Novel Heart Failure Stages Incorporating Cardiorespiratory Fitness are Differentially Associated with Heart Failure Risk in the Community
Authors: Danielle Davis, Priya Gajjar, Matthew Nayor
Journal: Circulation (2025)

Background: Heart failure (HF) progresses through stages as depicted by the AHA/ACC/HFSA guidelines. These stages advance from the presence of risk factors (stage A), to asymptomatic structural heart disease, elevated filling pressures, or abnormal biomarkers (stage B), to clinical HF (stage C). However, even among individuals classified as having the highest pre-clinical risk (stage B), the majority do not progress to clinical HF. This highlights the need to identify new risk factors to refine preclinical HF phenotypes. Impaired cardiorespiratory fitness (CRF) is a powerful predictor of HF risk but is not currently considered in HF staging. Accordingly, we hypothesized that HF substages incorporating CRF would be differentially associated with HF risk. Methods: We investigated Framingham Heart Study participants with submaximal exercise testing (up to Bruce protocol stage 2) at a routine exam. CRF was estimated based on stage 2 heart rate, weight, age, sex, treadmill grade, and velocity using the equation from Loe, et al. Due to the importance of HR for determining estimated CRF, we excluded individuals on atrioventricular nodal blocking agents. We evaluated the association of HF substages (categorized by CRF above vs. below sex-specific median) with incident HF using Cox models adjusted for age and sex. Results: Our sample included 1683 individuals, 55% women, mean age 58±8 yrs, with estimated CRF 35±3mL/kg/min in women and 40±4mL/kg/min in men. A total of 522 individuals (31%) were classified as having no HF risk factors (“healthy”; stage H), 693 (41%) as stage A, and 468 (28%) as stage B. Over a median follow up of 20 years, 99 incident HF events occurred. HF incidence was highest in individuals categorized as stage B with lower than median CRF (B2, Figure 1A). Stage B participants with estimated CRF above the median did not have a significantly higher risk of HF compared to stage H participants, but those with stage B and low CRF had an over 2.5-fold higher risk of HF (hazard ratio [HR] 2.75, 95% CI 1.50-5.07, P&lt;0.01; Figure 1B). Among stage B participants, every 1-SD higher CRF was associated with lower HF risk (HR 0.57, 95% CI 0.43-0.76, P&lt;0.001). We did not observe an association of CRF with incident HF among individuals categorized as stage A. Conclusion: Incorporating CRF into HF staging criteria may improve risk assessment and facilitate precision targeting of preventive therapies, especially among individuals classified as stage B HF.
Abstract P2142: Hypertensive disorders of pregnancy (HDP) and cardiovascular disease (CVD) in American Indians: The Strong Heart Family Study (SHFS)
Authors: Jessica Reese, Ying Zhang, Richard Devereux, Jason Umans, Emily Harville, Lyle Best
Journal: Circulation (2025)

Introduction: American Indian populations have high risks of both hypertensive disorders of pregnancy (HDP) and cardiovascular disease (CVD) yet few studies have evaluated associations of HDP and CVD in these populations. Aim: To determine if the odds of hypertension outside of pregnancy (HTN), carotid artery plaque, left ventricular mass indexed to body surface area (LVM/BSA), ejection fraction (EF), or clinical CVD events are higher in HDP cases compared to controls from the SHFS. Methods: We included 66 cases of HDP (preeclampsia and gestational hypertension) confirmed by medical records and/or birth certificates, matched on date of delivery (±3 years) to 185 controls. We defined HTN as systolic blood pressure (BP) ≥140 mm HG, diastolic BP ≥ 90 mmHg, or taking HTN medication. We used ultrasounds to measure carotid artery plaque, echocardiograms to measure LVM/BSA and EF, and physician adjudication to determine CVD events. We used conditional logistic regression to determine if the odds of HTN, plaque, LVM/BSA, EF, or CVD were different in HDP cases compared to controls while controlling for maternal age, center (Arizona, Oklahoma, or Dakotas), body mass index, smoking, and diabetes. Results: Of the total sample (n=251), 44 had HTN outside of pregnancy (23 were HDP cases), 29 had plaque (9 were HDP cases), and 12 had CVD (4 were HDP cases). Mean LVM/BSA was 70.4 (std=12.8) and mean EF was 59.7% (std=4.3%). The odds of HTN and CVD were higher in HDP cases compared to controls, while controlling for covariates (HTN OR= 7.53, 95% CI=2.22-25.67; CVD OR=6.04, 95% CI=1.05-34.91, Table 1). The univariate odds of LVM/BSA were higher in HDP cases compared to controls (OR=1.024, 95% CI=1.001-1.048), but the association attenuated when controlling for covariates. Conclusions: These data suggest that HDP is associated with HTN outside of pregnancy and CVD events in American Indian populations, which has never been demonstrated. Thus, these analyses may provide a critical step toward reducing HTN or CVD in American Indians diagnosed with HDP.
Abstract P2014: Baseline Sex Hormone Binding Globulin Level Modifies Intensive Lifestyle Intervention Effect on Blood Pressure in Post-Menopausal Females
Authors: Jiahuan Helen He, Jianqiao Ma, Mark Woodward, Erin Michos, Chigolum Oyeka, Rita Kalyani, Jeanne Clark, Dhananjay Vaidya, Wendy Bennett
Journal: Circulation (2025)

Background: The Look AHEAD (Action for Health in Diabetes) randomized controlled trial showed that Intensive Lifestyle Intervention (ILI) targeting weight loss caused greater reductions in systolic and diastolic blood pressure (SBP and DBP) than Diabetes Support and Education (DSE) in patients with body mass index (BMI) 25 kg/m 2 and type 2 diabetes (T2D). Nonetheless, treatment assignment alone did not explain the individual variations in BP improvement. We hypothesize that baseline sex hormone binding globulin (SHBG), which is inversely associated with hypertension in both males and females, might modify the effect of ILI on BP. Methods: We selected a random sample of 1167 post-menopausal females and 1167 males from the Look AHEAD trial in our analysis. We retained the randomized design and created sex-stratified linear mixed models to examine whether log-transformed baseline SHBG levels modify the treatment effects (i.e., absolute difference between ILI and DSE) on SBP and DBP reduction after 1 year, adjusting for age, race, study site, baseline BMI and use of anti-hypertensive medications. Results: In our study sample (age: 60.0 [SD, 6.2] years; 14.8% black; 50% female), median [IQI] baseline SHBG levels were 32.9 [22.2-54.0] nmol/L in females and 29.0 [19.9-44.8] nmol/L in males. Mean (SD) baseline SBP and DBP were 130 (17.3) and 67.6 (9.2) mmHg for females, 128.6 (16.3) and 73.1 (8.9) mmHg for males. Females with 2-fold higher baseline SHBG had 3.0 (95%CI: 1.0, 5.0) mmHg and 1.3 (95%CI: 0.3, 2.2) mmHg greater reduction in SBP (Figure, panel A) and DBP (panel B), respectively, due to ILI compared to DSE. However, treatment effects in males did not vary significantly with baseline SHBG (heterogeneity p-values: 0.81 SBP, 0.98 DBP). Conclusion: Females with higher baseline SHBG had more BP lowering due to ILI, compared to DSE, but this effect was not seen in males. Future research is needed to confirm if baseline SHBG can identify female patients with T2D who benefit most from ILI, and to determine whether those with low SHBG levels need more aggressive BP management in combination with ILI.