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Abstract 059: Longitudinal associations of accelerometer-determined sedentary and physical activity behaviors with heart failure biomarkers during the midlife transition: Coronary Artery Risk Development in Young Adults (CARDIA)

Circulation Kelley Gabriel, Bjoern Hornikel, Erin Dooley et al. Mar 11, 2025 DOI: 10.1161/cir.151.suppl_1.059

Introduction: Few studies have examined the longitudinal associations of accelerometry-based measures of sedentary and physical activity behaviors with subclinical heart failure (HF) in midlife. This is a key gap given an improved understanding of modifiable factors associated with HF risk may better inform prevention strategies. Hypothesis: More time in light intensity physical activity and/or moderate or vigorous intensity physical activity and less sedentary time will be related to lower levels of clinical HF biomarkers (NT-proBNP and hscTnT) across midlife . Methods: Data are from 2,844 CARDIA participants [57.9% women, 45.0% Black persons, aged 45.3 ± 3.6 years at the Year 20 exam (baseline for this analysis; 2005-06)] with at least one available timepoint of valid accelerometer (ActiGraph) wear (≥4 of 7 days with ≥10 hours per day of wear) and HF biomarkers at baseline and 10- and/or 15-years later. Linear mixed effects models, adjusted simultaneously for time spent sedentary and in light- or moderate or vigorous- intensity physical activity (partition model), sex, race, age, center, education, difficulty paying for basics, alcohol and tobacco use, obesity, diabetes, hypertension and hypercholesterolemia, were used to estimate the associations. Results: From baseline to 15-year follow-up, mean (± SD) time spent sedentary increased (488.1 ± 104.3 to 537.5 ± 112.0 min/d) and time spent in light intensity physical activity and moderate or vigorous intensity physical activity decreased (360.1 ± 86.7 to 312.1 ± 87.2 min/d and 37.3 ± 51.7 to 22.1 ± 22.4 min/d, respectively). Over this same period, mean (± SD) HF biomarkers increased (NT-proBNP: 61.6 ± 91.8 to 145.8 ± 1,111.9 pg/mL and hscTnT: 7.8 ± 4.7 to 11.0 ± 28.7 ng/L)). After adjustment, every 5-minute higher moderate or vigorous intensity physical activity was associated with lower NT-proBNP and hscTnT over 15 years ( Table ). Conclusions: Findings highlight the importance of moderate or vigorous intensity physical activity during the midlife transition for subclinical HF prevention, demonstrating this association before the onset of overt signs or symptoms.

Abstract P2022: The Use of Pod-Type Electronic Cigarettes and Recent Asthma Diagnosis in Adolescents

Circulation Ju-Mi Lee, Ji-Hyeon Kim, Hae-Sung Nam Mar 11, 2025 DOI: 10.1161/cir.151.suppl_1.p2022

Introduction: Recently, the rate of electronic cigarette (e-cig) use in Korea has steadily increased. The use of e-cigs in adolescents related to various diseases, and asthma, in particular, harms their quality of life. Research on e-cig use and asthma is insufficient compared to research on the relationship between regular cigarettes and asthma. In addition, research on e-cigs is focused on liquid-type, and there is a dearth of papers on other pod-type. Aim: The purpose was to identify the association between pod-type e-cigs and recent asthma diagnoses in adolescents. Methods: This study used the 19th Korean Youth Risk Behavior Survey, conducted in 2023. Out of 52,880 individuals, after excluding missing values for the age and economic status variables, 52,797 individuals were analyzed. The Rao-Scott chi-square test accessed the general characteristics. Logistic regression accessed the association between pod-type e-cigs and recent asthma. Results: Adolescents who are using the pod-type e-cig are likely to have asthma with a 4.0 higher odds (95% CI, 3.27-4.90) compared with nonpod-type users. The association was slightly weaker (OR 2.2, 95%CI 1.7-2.8) after adjusting gender, age, household income, stress, drinking alcohol, allergy, atopy, substance abuse, and the amount of pod-type electronic cigarettes smoked over a month. Conclusion: This study showed that adolescents who used pod-type e-cigarettes had a higher prevalence of asthma than those who did not. E-cigs are often advertised as a solution to the negative aspects of traditional cigarettes; however, from the perspective of asthma prevalence, they appear to have equally or even more harmful effects than regular cigarettes.

Method for reconstructing safety and arming motion process by integrating Kalman filter and KCF

Scientific Reports Yinhuan Zhang, Qinkun Xiao, Xing Liu et al. Mar 11, 2025 DOI: 10.1038/s41598-025-92957-y

Abstract P1135: Evidence Lacking for Association Between two Variants of the <i>CRP</i> Gene and Pre-eclampsia: Strong Heart Study

Circulation Lyle Best, Jessica Reese, Saroja Voruganti et al. Mar 11, 2025 DOI: 10.1161/cir.151.suppl_1.p1135

Introduction: Pre-eclampsia (PE) and other hypertensive disorders of pregnancy (HDP) constitute serious threats to maternal and fetal well-being. While the definitive cause (or causes) of PE has been sought since the time of Hippocrates, maternal immune dysfunction is one of many hypotheses that remain popular. A key component of the innate immune system, C-reactive protein (CRP), is elevated during pregnancies complicated by PE, but it is typically considered a secondary marker of inflammation initiated by other factors. None the less, genetic variants increasing the expression of CRP have been found associated with PE in multiple populations, suggesting a more primary role. Methods: Through a combination of self-report, medical record review and birth certificate information, the Strong Heart Study was able to assemble a dataset of 59 cases and 1080 women without similar indications of PE or gestational hypertension. Genotypes related to two CRP variants (rs1341665 and rs1205) were available and additive/dominant models evaluated using Chi-square and logistic regression methods for association with HDP. A p-value of 0.05 was considered statistically significant. Results: Neither variant, nor any of the genetic models showed significant association with HDP using either statistical test. Further analysis adjusting for body mass index or a more stringently defined outcome excluding gestational hypertension was similarly uninformative. Conclusion: Although previous investigation has demonstrated association between one of these variants (and other CRP variants unable to be tested in this cohort) in an American Indian population, this analysis was unable to replicate this finding. Possible reasons include difficulty comprehensively ascertaining cases and inclusion of other American Indian populations.

Abstract 058: Accelerometer-Measured Physical Activity and Sedentary Behavior and Risks of All-Cause and Cardiovascular Disease Mortality Among Postmenopausal Cancer Survivors: The Women’s Health Accelerometry Collaboration

Circulation Eric Hyde, Gretchen Bandoli, Jingjing Zou et al. Mar 11, 2025 DOI: 10.1161/cir.151.suppl_1.058

Introduction: The relationship between physical activity (PA) and sedentary behavior (SB) with mortality among women after a cancer diagnosis is understudied. We examined accelerometer-measured daily PA and SB in relation to all-cause and cardiovascular disease (CVD) mortality among postmenopausal cancer survivors in the Women’s Health Accelerometry Collaboration (WHAC). Methods: This study included 2,616 WHAC participants who reported a cancer diagnosis prior to baseline. From 2011–2015, WHAC participants wore an ActiGraph GT3X+ on the hip for ≥10 hours per day for ≥4 of 7 days. Daily accelerometer PA measures included light PA, moderate-to-vigorous PA (MVPA), total PA, and steps. SB measures were total sitting time and mean sitting bout duration. Mortality outcomes were ascertained through 2022. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable stratified Cox regression for each PA and SB measure in association with all-cause and CVD mortality. Models were adjusted for age, race/ethnicity, education, smoking status, alcohol use, general health, postmenopausal hormone use, diabetes, CVD, BMI, physical function, cancer type, and years since cancer diagnosis. Evidence of non-linearity was explored using restricted cubic splines. Results: Overall, the 2,616 cancer survivors (mean [Standard Deviation, SD] age, 74.3 [6.7] years) were followed for a mean of 8.2 years. For all-cause mortality (n=646 cases), 1-SD increments in light PA (78.3 min/day), total PA (96.7 min/day) sitting time (102.3 min/day) and sitting bout duration (4.7 min/bout) were associated with adjusted HRs (95% CIs) of 0.92 (0.84, 1.00), 0.89 (0.80, 0.98), 1.12 (1.02, 1.23), and 1.05 (0.97, 1.13), respectively. Statistically significant nonlinear associations were observed for MVPA and steps ( Figure ). The dose-response curve for steps shows the maximal benefit occurs around 5,000 steps/day before leveling off. The maximal mortality benefit for MVPA was near 50 min/day. For CVD mortality (n=119 cases), 1-SD increments in MVPA (32.9 min/day) and steps (2470 steps/day) were associated with adjusted HRs (95% CIs) of 0.59 (0.41, 0.84) and 0.64 (0.45, 0.93), respectively, while associations for light PA, total PA, and SBs were not significant. Conclusions: Among postmenopausal cancer survivors, higher PA and lower sitting time are associated with reduced risk of all-cause mortality, while more MVPA and steps were associated with reduced CVD mortality risk.

Microstructure and properties of electroless Ni–P/Sn2.5Ag0.7Cu0.1RE micro-joints during thermomigration

Scientific Reports Ruiqing Hou, Keke Zhang, Wenjia Zhao et al. Mar 11, 2025 DOI: 10.1038/s41598-025-89492-1

Abstract P1088: The Association of Kidney Function Trajectories with Atrial Fibrillation, Heart Failure, and Mortality over a 19-Year Follow-up: Results from CRIC study

Circulation XUANYI JIN, L Hamm, Hua He et al. Mar 11, 2025 DOI: 10.1161/cir.151.suppl_1.p1088

Background: The long-term trajectories of estimated glomerular filtration rate (eGFR) in patients with chronic kidney disease (CKD) have not yet been well investigated. Objectives: The current study aims to compare eGFR trajectory patterns over 19-years follow-up, and their association of atrial fibrillation (AF), heart failure (HF), and all-cause mortality. Methods: Using data from the Chronic Renal Insufficiency Cohort (CRIC) where eGFR (creatine-based: CKD-Epi equation) was measured annually, group-base trajectory models were used to identify latent groups. Multivariable Cox proportional hazard models were used to examine the association of eGFR trajectory groups with the incident events of HF and AF based on records of hospitalization, and death from any cause. Results: Three eGFR trajectories were identified among 3,939 subjects (Figure 1). The largest was Group 1 (52.0%) with steeper declines both early and late in follow-up. Group 2 (32.7%) displayed a stable declining pattern, and Group 3 (15.3%) was predominantly stable with minimal decline. Group 1 were more likely to be the black (50.6%,) and have a higher BMI (32.3±7.8), hypertension (95%), diabetes (58.4%), and elevated NTproBNP (median 245.2pg/ml), at the baseline (all p &lt;0.0001). Group 3 were younger (54.1 year) compared to Groups 1 and 2 (59.3 and 60.5 years). Compared to Groups 2 and 3, Group 1 had greater hazard ratio (HR) of incident AF (HR, 3.14 [95% CI: 2.40, 4.11]), HF (HR, 9.13 [95% CI: 6.15, 13.6]), and mortality (HR, 3.95[95% CI: 3.29, 4.74]), adjusted for age, sex, race, BMI, hypertension, diabetes, eGFR, and NTproBNP. Conclusion: This study identified a group of CKD patients with steeper decline in eGFR data over 19-years of follow-up and a significantly higher risk of AF, HF, and all-cause mortality.

Abstract P2018: Re-evaluating the Effect of Pravastatin on Mortality and Cardiovascular Events Using G-methods to Adjust for Adherence in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial – Lipid Lowering Trial

Circulation Rienna Russo, Anna Siefkas, Barry Davis et al. Mar 11, 2025 DOI: 10.1161/cir.151.suppl_1.p2018

Introduction: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack – Lipid-Lowering Trial (ALLHAT-LLT) was a large-scale, pragmatic clinical trial comparing pravastatin to usual care. In contrast to placebo-controlled statin trials, ALLHAT-LLT did not find an effect on all-cause mortality when data were analyzed under the intention-to-treat (ITT) principle. Objective: We replicated the ITT analysis and estimated the per-protocol effect of pravastatin on the 5-year risk of all-cause mortality and major adverse cardiovascular events (MACE). Methods: To replicate the ITT analysis, we used discrete time methods (pooled logistic regression). To estimate the per-protocol effect, we censored individuals when they deviated from protocol, i.e., in the pravastatin arm when they discontinued the study drug in the absence of adverse events. In the usual care arm, following the trial’s protocol, we considered the initiation of lipid-lowering therapy to be clinically indicated and not a deviation from protocol. We adjusted for baseline and time-varying factors associated with adherence using inverse probability weighting. Our outcomes of interest were all-cause mortality and a composite endpoint of MACE (myocardial infarction, stroke, heart failure, and cardiovascular mortality). Results: Of 10,355 individuals randomized, we included 9,741 individuals who had complete baseline data. This restriction did not result in an imbalance between the randomization groups, nor substantial changes in the distribution of characteristics compared to the original trial. The ITT findings were consistent with the original trial, (hazard ratio 1.00; 95% confidence interval (CI) 0.88, 1.13). Over one-third (35%) of individuals in the pravastatin arm were nonadherent to protocol at year 5. After adjusting for this, we found a 5-year risk difference of -2.99 (-4.94, -1.46) and risk ratio of 0.79 (0.68, 0.89) for all-cause mortality and -3.56 (-7.06, 0.18) and 0.82 (0.66, 1.01) for MACE, comparing pravastatin to usual care. Findings were consistent across sensitivity analyses modifying definitions of adherence and missing data methods. Conclusion: We found that use of pravastatin was protective against all-cause mortality and cardiovascular events after adjusting for adherence to protocol. Results support the use of g-methods to adjust for adherence when interested in understanding the effect of dynamic, sustained treatments in pragmatic trials.

Sr-doping effects on piezoelectric and dielectric properties of lead-free barium titanate via molecular dynamics approach

Scientific Reports Shadi Esmaeili, M. H. Ehsani, Davood Toghraie et al. Mar 11, 2025 DOI: 10.1038/s41598-025-92959-w

Abstract P2072: Lipoprotein(a) Levels in Premature Versus Non-Premature Atherosclerotic Cardiovascular Disease: The Atherosclerosis Risk in Communities (ARIC) Study

Circulation Matthew Belanger, Jelani Grant, Sui Zhang et al. Mar 11, 2025 DOI: 10.1161/cir.151.suppl_1.p2072

Background: Lipoprotein(a) [Lp(a)] is a causal, predominantly genetically determined risk factor for atherosclerotic cardiovascular disease (ASCVD). Approximately 20-30% of the global population have Lp(a) levels in the atherogenic range, with prospective data demonstrating a dose-response association of Lp(a) levels with ASCVD risk. However, there are relatively limited data characterizing the relationship between Lp(a) and premature ASCVD in epidemiologic cohort studies. Methods: We evaluated participants in the ARIC study with available Lp(a) measurements, collected at ARIC Visit 4 (1996-98). We used continuous follow-up and adjudication for ASCVD events (nonfatal myocardial infarction, fatal coronary heart disease, or ischemic stroke) from 1987 through 2021 to categorize participants as having had premature ASCVD events (events by age &lt;55 for men, &lt;65 for women), non-premature ASCVD events (age ≥55 for men, ≥65 for women), or no ASCVD events. Lp(a) levels were categorized according to previously established cutpoints: &lt;30, ≥30 to &lt;50, ≥50 to &lt;100, and ≥100 mg/dL and compared across those with non-premature ASCVD, premature ASCVD, and no ASCVD. Elevated Lp(a) was defined as ≥30 mg/dL, and multivariable-adjusted logistic regression models were used to assess the association of elevated Lp(a) with ASCVD status. Results: Among 8,236 participants (mean age 58 yrs, 71% female, 24% Black adults), those with premature ASCVD had the highest median Lp(a) levels (17.7 mg/dL), followed by non-premature ASCVD (14.4 mg/dL), and no ASCVD (13.6 mg/dL) (p = 0.002) ( Table ). Elevated Lp(a) levels were found in 40.8% of participants with premature ASCVD, compared with 34.1% in non-premature ASCVD, and 30.8% without ASCVD (p &lt;0.001). Participants with premature ASCVD had the highest odds of elevated Lp(a) relative to those with no ASCVD (OR: 1.39 [95% CI: 1.09-1.77]), while participants with non-premature ASCVD had a lesser, but still significantly higher odds of elevated Lp(a), compared to those with no ASCVD (OR: 1.16 [1.02-1.31]). Conclusion: Among ARIC study participants, premature ASCVD is associated with the highest prevalence and odds of elevated Lp(a). These findings reinforce the importance of the broader adoption of current guidelines that recommend systematic screening for elevated Lp(a) among individuals with premature ASCVD.

Abstract P1156: Associations Between Absolute Blood Eosinophil Count and Subclinical Atherosclerotic Plaque in the Multi-Ethnic Study of Atherosclerosis

Circulation Nyla Mathis, Matthew Tattersall, Spencer Hansen et al. Mar 11, 2025 DOI: 10.1161/cir.151.suppl_1.p1156

Background: Prior studies have demonstrated associations between eosinophil activation products and incident stroke. We sought to investigate associations between blood eosinophil count and imaging markers of atherosclerosis (carotid artery plaque [CAP] and coronary artery calcium [CAC]) in the Multi-Ethnic Study of Atherosclerosis (MESA). Methods: The MESA enrolled adults aged 45-84 years, free of atherosclerotic cardiovascular disease (ASCVD) at baseline. ASCVD risk factors, blood eosinophils, CAP presence and score (0-12) and CAC presence and Agatston score were measured at exam 5. Logistic and linear regression models were employed to test the association of blood eosinophils, CAP and CAC presence and score (log[score+1]) adjusted for biologic confounders. Results: The 2,166 participants were a mean (standard deviation [SD]) 69.6 (9.3) years old, 53% female, 29% Hispanic, 28% Black, 1% Chinese. The median (interquartile range) eosinophil count was 0.1 (0.1, 0.2)x10E3/uL, CAP score= 2 (0,4) and CAC score= 45 (0, 292) Agatston units. In risk-factor adjusted models (Table 1; model 5), increased blood eosinophil count (per 1 SD [0.15 x10E3/uL]) was associated with CAP (β = 0.05 [95% CI 0.02-0.08, p = 0.001) and CAC (β = 0.11, [95% CI: 0.01-0.21], p = 0.03) score. Similar associations were seen with eosinophils and CAP (Odds ratio [OR] = 1.12, [95% CI: 1.01-1.25], p = 0.03) and CAC (OR = 1.15, [95% CI: 1.02-1.30], p = 0.02) presence. Conclusions: In a large, contemporary, multiethnic, U.S. cohort, blood eosinophils were strongly associated with imaging measures of atherosclerosis even after adjustment for ASCVD risk factors. These data suggest potential roles of T2/eosinophilic inflammation in atherosclerosis.

Thermal properties of sands and their dependence on physical and environmental factors

Scientific Reports Manuela Campanale, Lorenzo Moro, Cristina Siligardi Mar 11, 2025 DOI: 10.1038/s41598-025-93054-w

Abstract P3020: A prognostic molecular signature of hepatic steatosis is spatially heterogeneous and dynamic in human liver

Circulation Andrew Perry, Niran Hadad, Emeli Chatterjee et al. Mar 11, 2025 DOI: 10.1161/cir.151.suppl_1.p3020

Introduction: The prevalence of hepatic steatosis—a central and early phenotype in multi-system metabolic dysfunction—is increasing in parallel with the obesity pandemic, calling for novel approaches for prevention and treatment. Hypothesis: We hypothesized that the circulating proteome may reflect cell specific mechanisms of hepatic steatosis. Methods: Using multi-modality hepatic imaging and broad circulating proteomics in approximately 5,000 individuals across 3 diverse cohorts (CARDIA, Cameron County Hispanic Cohort, UK Biobank), we identified proteins implicated in the progression of hepatic steatosis. We tested for a relationship with these proteomic markers of hepatic steatosis with metabolic-related clinical outcomes in UK Biobank. We translated these findings from the circulating proteome to several tissue-based datasets including bulk RNA sequencing, single-cell RNA sequencing, and spatial transcriptomics. To further prove the hepatocyte origin of prioritized proteins, we used a humanized “liver-on-a-chip” model. Results: We observed proteins implicated in the progression of hepatic steatosis—such as those related to central carbon and amino acid metabolism, hepatocyte regeneration, inflammation, fibrosis, insulin sensitivity—are largely encoded by genes enriched at the transcriptional level in human liver. Circulating multi-protein signatures of hepatic steatosis were strongly associated with a fatty liver disease phenotype and multi-system metabolic outcomes in &gt;26,000 free-living individuals. Moreover, we observed increased activity of transcripts encoding proteins prioritized in clinical studies spatially in areas of steatosis via spatial transcriptomics in human liver, with several top candidates dynamic during progression of steatosis in human liver. Finally, using a humanized “liver-on-a-chip” model, we induced hepatic steatosis, confirming cell-specific expression of targets implicated across tissue and clinical studies at a transcriptional and proteomic level. Conclusions: These results underscore the utility of a unified approach that combines human studies, multi-omics, and dynamic tissue-on-a-chip experiments to identify a prognostic, functional, dynamic “liquid biopsy” of human liver, with relevance for clinical biomarker discovery and mechanistic research applications.

Abstract P1094: Patient-Specific Barriers to Establishing Outpatient Heart Failure Care Following Hospitalization

Circulation Megan Nordberg, Sarah Bowman, Stephen Clarkson et al. Mar 11, 2025 DOI: 10.1161/cir.151.suppl_1.p1094

Background: Heart failure (HF) is a complex chronic disease that requires long-term outpatient care. Patients with a high burden of adverse social determinants of health have fewer opportunities for this care. When these patients attend an inter-professional HF clinic specifically designed to care for underserved patients they experience fewer hospital readmissions, however, about 30% of patients will be unable to present to clinic. Methods: Through qualitative interviews guided by the Health Belief Model, we sought to identify patient-specific barriers to successful linkage in outpatient care. We asked patients to describe perceived seriousness of HF, importance of their involvement in their care, barriers to attending appointments, and ways to mitigate barriers. Results: We interviewed 10 patients newly referred to the UAB HF clinic during an inpatient HF hospitalization at UAB Hospital. Participants were 53 years old, white, male, and residing in Jefferson County, AL ( Table ). Patients viewed HF as a serious condition due to the necessity of heart function. They valued information received from doctors, but most emphasized the importance of their involvement in their care, stressing patient responsibility to implement the doctor’s guidance. Barriers to attending appointments were transportation and monetary concerns. Patients reported that rides to and from their appointments would be helpful in addressing their reported barriers. Patients noted the importance of a welcoming environment while hospitalized to encourage appointment attendance following hospital discharge. Conclusion: Patients with HF perceive HF as serious and recognize the importance of their involvement in their care. Inadequate transportation and monetary concerns were reasons they might not attend outpatient appointments, highlighting potential barriers to be addressed. In addition to rides, experiencing a welcoming environment while hospitalized would most help them to attend appointments post-discharge.

Burden and trends of facial fractures in China and the United States based on GBD 2021 analysis

Scientific Reports Hao Chen, Zhi Jia, Xin He et al. Mar 11, 2025 DOI: 10.1038/s41598-025-92980-z

Abstract P3039: A New Biomarker of Aging Derived From Electrocardiogram Improves Risk Prediction of Incident Myocardial Infarction and Stroke.

Circulation Tom Wilsgaard, Wayne Rosamond, Henrik Schirmer et al. Mar 11, 2025 DOI: 10.1161/cir.151.suppl_1.p3039

Introduction: Deep neural networks are increasingly used to generate diagnostic algorithms in cardiovascular medicine. A biomarker of cardiovascular aging, derived from a deep-learning algorithm applied to digitized 12-lead electrocardiograms (ECGs), has recently been introduced. This biomarker, delta age (δ-age), is defined as the difference between predicted ECG age and chronological age. Hypthesis: We hypothesized that δ-age will improve the prediction of incident fatal and non-fatal myocardial infarction (MI) and stroke on top of what contemporary CVD prediction tools would do. Methods: In this cohort study, we included 7,111 men and women from the Norwegian Tromsø Study conducted in 2015-16, with follow-up through 2021 for incident fatal and non-fatal myocardial infarction (MI) and hemorrhagic or cerebral stroke. We used Cox proportional hazards regression models to assess the independent effect of δ-age on MI and stroke. Discrimination was evaluated using Harrell’s concordance statistic (C-index) and the net reclassification improvement (NRI). Results: During a median follow-up of 5.9 years, we observed 155 incident cases of MI, 141 cases stroke and 290 cases with either MI or stroke. δ-age was observed with a mean of 0 and standard deviation of 6.2 years. In men and women combined, hazard ratios (HRs) per standard deviation increase in δ-age, after adjustment for traditional risk factors, were 1.24 (95% confidence interval (CI) 1.09, 1.41) for the combined outcome, 1.26 (1.06, 1.49) for MI and 1.25 (1.03, 1.50) for stroke. In men, the corresponding HRs were 1.27 (1.09, 1.49), 1.46 (1.18, 1.79) and 1.02 (0.80, 1.31), respectively, and in women, 1.20 (0.97, 1.49), 0.87 (0.64, 1.20) and 1.58 (1.19, 2.11), respectively. The C-index increased modestly when δ-age was added to a model with traditional risk factors. The 95% CI for the C-index increase excluded zero for the combined outcome overall, and for MI in men and for stroke in women. The NRI was 26.0% (13.3%, 38.1%) for the combined outcome, 17.5% (0.6%, 33.5%) for MI and 37.2% (20.1%, 53.0%) for stroke. Conclusions: Incorporating δ-age into primary prevention risk prediction models significantly improved performance beyond traditional cardiovascular risk factors for the combined outcome and separately for MI and stroke.

Abstract P1072: Underutilization of Novel Guideline-Directed Medical Therapy in Patients with Heart Failure

Circulation Deepika Laddu, Manisha Cherupally, Raymond Kang et al. Mar 11, 2025 DOI: 10.1161/cir.151.suppl_1.p1072

Background: Guideline directed medical therapy (GDMT) for patients with heart failure (HF) now includes SGLT2i and ARNI regardless of ejection fraction. Despite strong evidence supporting these therapies, their utilization among HF patients remains unclear. This study used healthcare claims data to examine the utilization of GDMT in a contemporary cohort of newly diagnosed HF patients. Methods: We analyzed claims data from commercial and Medicare Advantage plans of a large national insurer to identify patients with incident HF, diagnosed in 2022. Patients were identified as having at least two outpatient claims or one inpatient HF claim, and 12 months of continuous enrollment prior to diagnosis. Pharmacy claims assessed prescription fill rates for novel and standard GDMT (including SGLT2i, ARNI, ACEI/ARB, BB, MRA, and GLP-1 RA). Results: The analytic cohort included 163,596 patients (49% male) diagnosed with new-onset HF, with two-thirds in the outpatient setting ( Table ). HF incidence was higher with older age, with over half of cases in adults aged ≥75 years. Comorbidities were prevalent, particularly hypertension (88%), diabetes (42%), and history of myocardial infarction (50%). Beta-blockers (55%) were most frequently used, while ACEi/ARB (24%) and MRAs (11%) were less commonly used. ARNI, SGLT2i and GLP-1 RA use remained low (5% each). Conclusion: In a privately insured sample with a new diagnosis of HF, use of novel GDMT was very low. Understanding treatment patterns by HF subtype and identifying gaps in GDMT utilization are critical for developing targeted strategies to improve HF management.

BWM analysis of online and offline learning effectiveness in Bangladesh

Scientific Reports Syeda Sharaban Tahura, Md. Abdus Shabur, Tasnuva Jahan Nuva Mar 11, 2025 DOI: 10.1038/s41598-025-92831-x

Abstract P3040: Associations between Triglyceride-glucose-obesity Indicators with Cardiovascular Disease Across Combination of Body Mass Index and Central Obesity Categories: The China Health and Retirement Longitudinal Study

Circulation Ruolin Zhang, Yaojie Wang, Huiyuan Zhou et al. Mar 11, 2025 DOI: 10.1161/cir.151.suppl_1.p3040

Introduction: The triglyceride glucose-body mass index (TyG-BMI) and triglyceride glucose-waist circumference (TyG-WC) are fast and simple clinical indices with proven reliability in predicting heart diseases and stroke. Considering the obesity paradox, where body mass index (BMI) may fail to accurately predict cardiovascular outcomes in obese patients, assessing the effectiveness of TyG-BMI and TyG-WC across the combination categories of BMI and waist circumference (WC) becomes essential. Methods: We included individuals with complete data on TyG, fasting plasma glucose, BMI, and WC at 2011 wave. Incidence of heart disease and stroke was observed during the follow-up visits. All participants were classified into four groups at baseline: both BMI and WC normal, BMI obesity (BMI ≥ 24 kg/m 2 ) but WC normal, BMI normal but WC obesity (WC, male ≥ 90 cm, female ≥ 80 cm) and both BMI and WC obesity. TyG-BMI and TyG-WC were calculated as BMI * TyG index and WC * TyG index, where TyG index = ln[FPG (mg/dL) * TG (mg/dL)/2]. Multivariate Cox proportional hazards models were employed to assess the association between TyG-BMI and TyG-WC with the risk of incident cardiovascular disease within the four groups, adjusted for demographic characteristics, smoking, drinking, blood urea nitrogen, high-density lipoprotein cholesterol, low-density lipoproteins cholesterol, C-Reactive protein, hemoglobin, uric acid, serum creatinine, cystatin C, hypertension, diabetes and kidney disease. Results: Among 7,405 participants (mean age 57.8, 53.9% women), 479 stroke and 1141 heart disease incidents were recorded with average follow-up years of 6.55 and 6.35. The fully adjusted models in Figure 1 revealed that in the BMI and WC obesity group, every 10-unit increase in TyG-BMI and TyG-WC was associated with 4.2% and 1.3% higher risk of heart disease respectively (HR = 1.04, 95% CI = 1.01, 1.07; HR = 1.01, 95% CI = 1.002, 1.03). Additionally, among individuals with normal BMI but obese WC, each 10-unit rise in TyG-WC was associated with a 4.5% increase in stroke risk (HR = 1.05, 95% CI = 1.01, 1.08). Conclusions: The TyG-BMI and TyG-WC indices exhibit differential predictive capabilities for cardiovascular disease risk across diverse obesity phenotypes, where the applicability could not extend to populations characterized by both normal BMI and WC. Our findings stress the importance of applying TyG indices to tailored populations, enhancing the precision of cardiovascular risk assessment.

Abstract 042: Estimating the effect of menopausal hormone therapy on CVD risk among women with vasomotor symptoms: A target trial emulation within the SWAN Study

Circulation Ziyuan Wang, Rebecca Thurston, Sonja Swanson et al. Mar 11, 2025 DOI: 10.1161/cir.151.suppl_1.042

Introduction: Frequent and/or persistent vasomotor symptoms (VMS) are associated with cardiovascular disease (CVD) risk. Although menopausal hormone therapy (HT) is the standard treatment for VMS, no clinical trial data exist to assess its effects on CVD risk in women with VMS. This study uses observational data to emulate a target trial of HT initiation on CVD risks among women with VMS and to understand how the timing of HT initiation relative to menopause modifies this risk. Methods: SWAN is an ongoing longitudinal study of the menopause transition into early old age. Between SWAN’s visit 0 (1997) and visit 16 (2017), HT use (systemic estrogen with/without progestogens, including oral contraceptives for non-contraceptive use) since prior visits was self-reported and verified from pill bottles and coded according to the Iowa Drug Information Service system. VMS, assessed at each visit, was defined as the self-reported presence of hot flashes or night sweats over the past 2 weeks. CVD events (myocardial infarction, stroke, heart failure, and revascularization) were self-reported; a subset of CVD events was adjudicated via medical records. We emulated a series of sequential trials among women with VMS and no history of HT, with eligibility assessed at SWAN visits 0-15. Adjusting for baseline confounders (listed in Figure ) in pooled logistic regression models, we estimated the effect of initiating vs. not initiating HT on CVD events among women with VMS. Results: Among 2737 women who reported VMS (46% White, 34% Black, 8% Japanese, 7% Chinese, 4% Hispanic), 1181 initiated HT at some point during the SWAN follow-up at a mean±SD age of 55±5 years. Over 20 years of follow-up, 152 CVD events occurred (44% adjudicated). The adjusted hazard ratio of CVD for HT initiation vs. non-initiation was 0.73 (95% CI: 0.52-1.02), Figure . Stratified by HT initiation relative to the time since onset of menopause, the adjusted hazard ratio was 0.60 (0.36-0.99) and 1.03 (0.33, 3.20) among women initiating HT ≤ 10 years versus &gt; 10 years of the onset of menopause, respectively (interaction p value=0.48). Conclusions: HT initiation contributed an estimated 27% reduction in CVD risk, but wide confidence intervals included the null. The magnitude of the estimated protective effect was greater among women who initiated HT ≤10 years postmenopause. Given potential residual confounding and confidence intervals that included 1, our results should be interpreted cautiously.