Browse Articles

Abstract P3140: Association Between Social Support and Health Status Among Adults After Myocardial Infarction

Background: Social support has been associated with morbidity and mortality among adults with coronary artery disease, but its relationship to health status among adults with recent myocardial infarction (MI) is less well understood. Objective: We examined the association between social support (ENRICHD Social Support Inventory [ESSI]) and health status (Seattle Angina Questionnaire [SAQ-7]) among a cohort of adults post-MI, overall and by sex. We hypothesized that higher social support would be associated with better health status and that the strength of association would differ by sex. Methods: This was a cross-sectional analysis of baseline data from an ongoing study examining the role of stress among adults with MI. Participants were ≥ 18 years old and had a MI within the last 3 months, defined by the Universal Definition. We conducted multivariate linear regression analyses to examine associations between ESSI score and SAQ-7 summary score, as well as SAQ domain scores for Physical Limitation (SAQ-PL), Angina Frequency (SAQ-AF), and Quality of Life (SAQ-QoL). We controlled for demographics (age, race, ethnicity, sex), clinical history (history of prior MI), and psychosocial covariates (Perceived Stress Scale 4 scores). Results: The sample (n=156) comprised 37% women, and 67% identified as non-Hispanic White. Mean age was 59 years (standard deviation 13 years). Median [interquartile range] ESSI score was 28 [22.5; 32] and SAQ-7 score was 76 [56; 89], which did not differ by sex (p=0.25). After adjustment, ESSI was positively associated with SAQ-7 (β 0.6 [increase in SAQ-7 score per unit increase in ESSI score], 95% confidence interval (CI) [0.1-1.1], p=0.03) and SAQ-AF (β 0.5, 95% CI [0.5-1.0], p=0.03), but not SAQ-PL (p=0.07) nor SAQ-QoL (p=0.15). In adjusted analyses stratified by sex, ESSI was more strongly associated with SAQ-7 in women than men (β 1.0, 95% CI [0.2-1.9], p=0.02 versus β 0.6, 95% CI [-0.1-1.2], p=0.08). Associations with SAQ-AF and SAQ-QoL were also stronger in women than men (β 0.9, 95% CI [0.1-1.7], p=0.03 versus β 0.4, 95% CI [-0.2-1.0], p=0.19 and β 1.3, 95% CI [0.2-2.5], p=0.02 versus β 0.5, 95% CI [-0.6-1.5], p=0.38, respectively). Conclusions: We found that higher social support is associated with better health status in adults post-MI, and this relationship is stronger in women compared to men. Results suggest that screening for low social support and identifying strategies to bolster it may benefit recovery post-MI.

Abstract MP17: Sex Disparities In Circadian Misalignment And Its Impact On Cardiovascular Health In Adolescents

Introduction: Prior research has reported sex differences in sleep and cardiovascular health. Most studies focused on disturbed sleep, sleep duration, and night-to-night sleep variability; however, sex differences in circadian misalignment and its impact on obesity-related cardiovascular outcomes remain elusive. Hypothesis: We hypothesize that male adolescents will show greater circadian misalignment and that its impact on cardiovascular outcomes will vary by sex. Methods: We analyzed 303 adolescents from the Penn State Child Cohort (median 16y; 144 females; 21% racial/ethnic minority) who had at least 5 nights of actigraphy (ACT), in-lab dual-energy X-ray absorptiometry (DEXA) scan, and polysomnography (PSG) data. ACT-measured sleep midpoint (SM) was calculated as the intra-individual average of the 7-night midpoint (zeroed to midnight) of the sleep period. ACT-measured sleep irregularity (SI) was calculated as the intra-individual standard deviation of the 7-night sleep midpoint. Social jetlag (SJL) was calculated as the absolute difference between weekends and weekdays SM. DEXA-measured visceral adipose tissue (VAT) was the primary predictor. Systolic (SBP) and diastolic (DBP) blood pressure, measured three times in the seated position, were the primary outcomes. Multivariable-adjusted means of SM, SI, and SJL for males and females were calculated. Thereafter, multivariable linear regression models stratified by sex tested the main effects and interaction effects of SM, SI, and SJL on VAT with SBP/DBP levels, while adjusting for race/ethnicity, age, ACT-sleep duration, ACT-sleep variability and PSG-apnea/hypopnea index. Results: Male adolescents had a SM 22 minutes later (p=0.010) than females. No significant sex differences in SI and SJL were observed. In males, a significant positive main effect was found between SM and SBP (p=0.030). In females, significant positive interactions were found between SI and VAT on SBP and DBP (p-interactions=0.002 and 0.030, respectively) and between SJL and VAT on SBP (p-interaction=0.002). Conclusions: The role of circadian misalignment in cardiovascular health does vary by sex. Females appear more vulnerable to its impact on the association between visceral adiposity and elevated blood pressure. Future studies should examine the underlying pathways, whether circadian, biological or behavioral, that may explain the observed sex differences. Support: AHA (23PRE1011962), NIH (R01HL136587, R01MH136472, UL1TR000127)

Abstract P3081: Evaluation of Blood Pressure Management Practices Among Non-Cardiovascular Physicians in Zhejiang Province, China

Introduction: In clinical practice, we observed suboptimal blood pressure (BP) control prior to admission. Due to the need for treatment of other conditions, many patients are managed by non-cardiovascular specialists, resulting in discrepancies in BP control levels during hospitalization between specialist and non-specialist care. Hypothesis: By reviewing clinical data, we analyzed BP management before and after treatment by cardiovascular specialists versus non-specialists, validating the hypothesis that non-specialist physicians demonstrate inadequate BP management during hospitalization. Methods: We employed simple random sampling to select 500 adults with essential hypertension (EH) admitted to Zhejiang Provincial People's Hospital in January 2022. Clinical records were collected; comparisons were made regarding antihypertensive medication usage and BP control status before and after admission, along with an evaluation of management practices by non-specialist physicians. Results: A total of 500 adults with EH participated in this study. Compared to pre-admission BP control, there was a significant increase in treatment rates, BP control, and combination therapy following admission (100.0% vs 83.0%, 67.0% vs 36.2%, 63.5% vs 40.6%, P<0.05). Approximately 62.4% of patients were admitted under non-specialty care, with only 37.5% achieving adequate BP control at admission time. The discharge BP control rate (63.0 % vs 72.9%), long-term monitoring adherence and discharge monitoring rates (81.1% vs 100.0%, 90.1% vs 100.0%), medication adjustment rate (20.2% vs 72.9%), and combined treatment rate (49.8% vs 84.0%) were all significantly lower than those seen in specialty care settings (all P <0 .05). Conclusions: The treatment rate and control rate of patients prior to admission in Zhejiang Province were higher than those in other regions of China. However, over 60% of patients had inadequate BP control and require referral to hospitals with cardiovascular departments for further management. The core principles governing medication use before and after admission remained consistent, suggesting that differences in BP control may be linked to the use of combination medications. Over 60% of patients received care from non-cardiovascular departments, where rates of BP control, monitoring adherence, and medication adjustment were notably low—indicating a persistent gap in hypertension management knowledge among non-cardiovascular physicians.

Retraction Note: Experimental design and analysis of advanced three phase converter for PV application with WCO-P&O MPPT controller

A data-driven generative strategy to avoid reward hacking in multi-objective molecular design

Abstract Molecular design using data-driven generative models has emerged as a promising technology, impacting various fields such as drug discovery and the development of functional materials. However, this approach is often susceptible to optimization failure due to reward hacking, where prediction models fail to extrapolate, i.e., fail to accurately predict properties for designed molecules that considerably deviate from the training data. While methods for estimating prediction reliability, such as the applicability domain (AD), have been used for mitigating reward hacking, multi-objective optimization makes it challenging. The difficulty arises from the need to determine in advance whether the multiple ADs with some reliability levels overlap in chemical space, and to appropriately adjust the reliability levels for each property prediction. Herein, we propose a reliable design framework to perform multi-objective optimization using generative models while preventing reward hacking. To demonstrate the effectiveness of the proposed framework, we designed candidates for anticancer drugs as a typical example of multi-objective optimization. We successfully designed molecules with high predicted values and reliabilities, including an approved drug. In addition, the reliability levels can be automatically adjusted according to the property prioritization specified by the user without any detailed settings.

Abstract P3134: Semaglutide Versus Liraglutide and Incidence of Diabetes and Cardiovascular Disease: an Analysis of Real-World Data

Introduction: Semaglutide (2.4 mg) and liraglutide (3.0 mg) are glucagon-like peptide-1 receptor agonist (GLP-1 RA) drugs used to promote weight loss, with evidence indicating a greater effect for semaglutide. In the SELECT trial, semaglutide reduced the risk of major adverse cardiovascular disease (CVD) events compared to placebo among overweight or obese individuals without diabetes. Both semaglutide and liraglutide are effective at improving glycemic control, though no clinical trials have assessed incident diabetes as a primary endpoint. Hypothesis: Among patients without diabetes, semaglutide is associated with lower risk of incident CVD and diabetes compared with liraglutide. Methods: Using the MarketScan insurance claims database from 2020-22, we matched diabetes-free patients prescribed semaglutide with up to 2 controls prescribed liraglutide by age, sex, enrollment date and prescription date. We used Cox regression to assess the association of semaglutide versus liraglutide use with incident 1) diabetes, 2) hard CVD (myocardial infarction, stroke and heart failure), and 3) a composite outcome of hard CVD plus unstable angina and coronary revascularization. Models adjusted for age, sex, and a propensity score determined by comorbidities and the use of other medications. Results: Our sample included 15,017 semaglutide users and 21,431 matched liraglutide users who initiated treatment during 2021 or 2022 (mean age 45 years; 83% female). Follow-up concluded at the end of 2022 or insurance disenrollment. Over a mean of 0.7 years, there were 631 diabetes, 30 hard CVD, and 64 composite CVD events. Comparing semaglutide with liraglutide, the hazard ratio (95% confidence interval) was 0.60 (0.35-1.02) for the composite CVD outcome and 0.57 (0.26-1.25) for hard CVD. The proportional hazards assumption was violated in the analysis of diabetes (p=0.01). Semaglutide use was associated with higher risk of diabetes during the first six months of follow-up (2.07 [1.70-2.53]) and lower risk thereafter (0.70 [0.54-0.92]). Conclusions: In this real-world study of GLP-1 RAs and CVD outcomes, results directionally favored semaglutide over liraglutide. The change in directionality of the association with incident diabetes may be supported by the results of the SUSTAIN 10 and PIONEER 4 trials, which showed a greater improvement in measures of glycemic control for liraglutide during early follow-up visits, but a superior effect of semaglutide by the end of the trial.

Abstract P1040: Characterizing Metabolically Unhealthy Normal Weight In Hispanic / Latino adults: Results from HCHS/SOL

Introduction: Metabolically unhealthy normal weight (MUNW) individuals exhibit metabolic abnormalities linked to obesity, increasing their risk of cardiometabolic diseases. MUNW is often overlooked in clinical practice, as guidelines generally focus on overweight or obesity. Additionally, the long-term stability of MUNW and its potential role in future weight gain remain unclear. This study aimed to identify factors associated with prevalent and incident MUNW and examine its stability over time. Hypothesis: MUNW evolves into excess weight phenotypes, and among those with stable MUNW over time, the number of cardiometabolic risk factors (CRFs) increases. Methods: We examined 2,343 individuals with normal weight (BMI ≥18.5, <25 Kg/m 2 ) free of diabetes and cardiovascular disease (baseline) from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) [18-74 years old], a community-based cohort of Hispanic/Latino adults living in the U.S. MUNW was defined as having a normal weight with at least one of the following CRFs: elevated fasting glucose, triglycerides, blood pressure, or low HDL cholesterol. Survey multivariable models were used to explain prevalent and incident MUNW at baseline and after 7 years of follow-up. The stability of MUNW was assessed by tracking transitions to other weight phenotypes. Results: At baseline, 69% of individuals had MUNW. In a multivariable model, older age [Odds Ratio (OR): 1.05, 95%CI: 1.03-1.06], being foreign-born with ≥10 years in the U.S. (vs. U.S.-born) [OR: 1.65, 95%CI: 1.17-2.33], and a household income over $40,000 (vs.<$20,000) [OR: 0.56, 95%CI: 0.39-0.81] were associated with prevalent MUNW. Waist circumference (continuous) was also associated [OR: 1.06, 95%CI: 1.03-1.08]. Among 264 individuals free of metabolic abnormalities at baseline who maintained normal weight over 7 years, 33.3% developed MUNW. Age [Relative Risk (RR): 1.04, 95%CI: 1.02-1.06] and male sex [RR: 1.76, 95%CI: 1.13-2.73] were predictors of incident MUNW. Among individuals with MUNW at baseline, 30.6% progressed to metabolically unhealthy overweight/obesity (MUO) and 3.7% to metabolically healthy overweight/obesity. Stable MUNW individuals (57.3%) showed an increase in the number of CRFs over time (p<0.05). Conclusion: MUNW is not stable, as many individuals transition to MUO, and those remaining MUNW accumulate more CRFs over time. Metabolic health needs to be assessed in normal-weight adults, particularly those with high waist circumference.

Abstract P3060: A Measure of Residential Segregation and Thrombo-inflammation in Black and White Americans

Introduction: Development of hypertension is linked to thrombo-inflammation. In the U.S., Black women have the highest hypertension prevalence of any race-gender group, and Black people have higher thrombo-inflammatory responses than White people. Evidence on residential segregation— a manifestation of structural racism and a key driver of health inequities— and thrombo-inflammation is limited. This study examined race and/or gender differences in the association of a measure of residential segregation and hypertension-related thrombo-inflammatory biomarkers. Methods: We included 4,362 Black and White participants of the REasons for Geographic And Racial Differences in Stroke study. Residential segregation was measured with the delta index (the proportion of Black people that would need to move across census tracts to achieve a uniform density in a county). Regression models assessed associations of the delta index with 8 thrombo-inflammatory biomarkers: C-reactive Protein, D-dimer, E-selectin, factor IX, interferon-γ, interleukin (IL)-6, and tumor necrosis factor-α, and IL-1β. Racial and/or gender differences in associations were tested. Results: The delta index was only associated with IL-1β. The figure shows that each SD higher delta index was associated with 39% lower odds of being in the top versus the bottom tertile of IL-1β (odds ratio: 0.61, 95% confidence interval: 0.38, 0.95). There were no significant racial and/or gender differences in associations. Discussion: A measure of residential segregation, the delta index, was associated with lower IL-1β in Black and White Americans. This suggests that aspects of living in majority Black counties may buffer thrombo-inflammatory responses associated with IL-1β.

Relating the molecular phenotype of ulcerative colitis to the clinical course

Abstract The expanding portfolio of targeted therapies for ulcerative colitis (UC) suggests that a more precise approach to defining disease activity will aid clinical decision-making. This prospective study used genome-wide microarrays to characterize gene expression in biopsies from the most inflamed colon segments from patients with UC and analyzed associations between molecular changes and short-term outcomes while on standard-of-care treatment. We analyzed 141 biopsies—128 biopsies from 112 UC patients and 13 biopsies from eight inflammatory bowel disease unclassified (IBDU) patients. Endoscopic disease was associated with expression of innate immunity transcripts, e.g. complement factor B (CFB); inflammasome genes (ZBP1 and PIM2); calprotectin (S100A8 and S100A9); and inflammation-, injury-, and innate immunity-associated pathway analysis terms. A cross-validated molecular machine learning classifier trained on the endoscopic Mayo subscore predicted the endoscopic Mayo subscore with area-under-the-curve of 0.85. A molecular calprotectin transcript score showed strong associations with fecal calprotectin and the endoscopic Mayo subscore. Logistic regression models showed that molecular features (e.g. molecular classifier and molecular calprotectin scores) improved the prediction of disease progression over conventional, clinical features alone (e.g. total Mayo score, fecal calprotectin, physician global assessment). The molecular features of UC showed strong correlations with disease activity and permitted development of machine-learning predictive disease classifiers that can be applied to expanded testing in diverse cohorts.

Correction for Patel et al., Aspirin binds to PPARα to stimulate hippocampal plasticity and protect memory

Bicomponent nano- and microfiber aerogels for effective management of junctional hemorrhage

Abstract Managing junctional hemorrhage is challenging due to ineffective existing techniques, with the groin being the most common site, accounting for approximately 19.2% of potentially survivable field deaths. Here, we report a bicomponent nano- and microfiber aerogel (NMA) for injection into deep, narrow junctional wounds to effectively halt bleeding. The aerogel comprises intertwined poly(lactic acid) nanofibers and poly(ε-caprolactone) microfibers, with mechanical properties tunable through crosslinking. Optimized aerogels demonstrate improved resilience, toughness, and elasticity, enabling rapid re-expansion upon blood contact. They demonstrate superior blood absorption and clotting efficacy compared to commercial products (i.e., QuikClot® Combat Gauze and XStat®). Most importantly, in a lethal swine junctional wound model (Yorkshire swine, both male and female, n = 5), aerogel treatment achieved immediate hemostasis, a 100% survival rate, no rebleeding, hemodynamic stability, and stable coagulation, hematologic, and arterial blood gas testing.

Abstract P1162: Cardiac Magnetic Resonance Imaging Measures of Atrial Cardiomyopathy and Adverse Clinical Outcomes in the UK Biobank

Introduction: Atrial cardiomyopathy precedes atrial fibrillation (AF) and is a strong risk factor for downstream adverse clinical outcomes, but there is no census about the optimal method for assessing it. Cardiac magnetic resonance imaging (CMR) is the most accurate tool to assess atrial function and structure. Our objective was to evaluate the association between CMR measures of atrial cardiomyopathy, incident AF, and AF-related clinical complications. Hypothesis: We hypothesized that CMR measures of atrial cardiomyopathy are associated with AF, ischemic stroke, heart failure, and dementia, independent of established risk factors. Methods: In 44,591 participants who underwent CMR as part of UK Biobank Imaging Study and had no history of AF, we assessed atrial minimal and maximal volumes (indexed to body surface area) and ejection fraction. Cox proportional hazard models were used to evaluate the association of these CMR measures with incident AF, ischemic stroke, heart failure, and dementia, adjusting for established risk factors. Results: During a median follow-up time of 4.0 [IQR 2.9-5.4] years, 834 (2%) participants developed AF, 197 (0.4%) developed ischemic stroke, 278 (0.6%) developed heart failure, and 61 (0.1%) developed dementia. The mean [standard deviation] age was 65 [8] years and 51% were female. When evaluated as continuous variables, left atrial ejection fraction (LAEF) was significantly associated with the risk of new-onset AF, ischemic stroke, and heart failure, while left atrial minimal volume (LAVI min ) and maximal volume (LAVI max ) were associated with these outcomes as well as the risk of dementia (Table). In comparison, right atrial measures were associated with only AF and heart failure, and the magnitude of the associations was generally smaller. After further adjustment for time-varying AF, these associations remained significant. When categorized by quintiles, participants in the highest LAVI min group had a HR of 3.67(95%CI 2.93-4.60) for AF, 1.51(95%CI 1.02-2.25) for ischemic stroke, 2.71(95%CI 1.86-3.96) for heart failure, and 2.43 (95%CI 1.11-5.31) for dementia, compared to those in the lowest. Conclusion: CMR measures of atrial structure and function were associated with AF-associated clinical outcomes independent of risk of AF. These findings suggest that atrial cardiomyopathy may be an important target of future research efforts, with potential implications for screening patients at high risk for cardiovascular disease.

Abstract P1069: Health Care Professional Perspectives on IMPLEMENT-HF: A Qualitative Study Examining Successes, Facilitators, and Barriers in a Quality Improvement Program for Patients with Heart Failure

Introduction: Heart failure (HF) leads to over 1 million hospitalizations and 450,000 related deaths annually, yet there are substantial quality gaps in care. In 2021, the American Heart Association launched IMPLEMENT-HF (I-HF), a 3-year national Quality Improvement (QI) initiative, to improve care and outcomes for patients with HF. Several QI strategies were used and evaluated over the course of this initiative. Purpose: Focus groups were conducted to gather health care professional (HCP) perspectives on I-HF implementation. Results will assist in determining overall program impact and to identify successes, barriers, and facilitators to inform implementation of future QI programs. Methods: This study involved virtual focus groups (n=8) with HCPs (n=25) recruited from the 111 sites enrolled in I-HF. A semi-structured focus group guide was developed to facilitate the 60-minute sessions. Focus groups were recorded and transcribed, and inductive and deductive thematic analyses conducted in NVivo identified key high-level themes and subthemes. Results: HCPs felt I-HF improved their care team’s knowledge of HF treatment options and their confidence in treating patients with HF. They reported improvements in prescribing guideline-directed medical therapy (GDMT), medication adherence, and follow-up appointment attendance during the program period. HCPs appreciated the flexibility and variety of I-HF’s educational offerings, opportunities to learn from other HCPs, and the benefits of the Get With The Guidelines® program on patient care. Commonly cited implementation barriers included high staff turnover, clinical roles taking precedence, and a lack of leadership and organization within their sites, which hindered full engagement with I-HF. The cost of and lack of insurance coverage for GDMT was frequently cited as a major burden for patients and a barrier to uptake. Conclusions: QI programs like I-HF can improve care and outcomes for patients with HF and increase HCP knowledge and confidence in providing appropriate treatments. Several cited implementation facilitators, such as flexible educational offerings, can be replicated in future programs. Some reported barriers, such as limited staff capacity, will be challenging to address. However, future initiatives can offer additional guidance on program implementation and recommend assigning a point person at each site to enhance internal organization and support more comprehensive adoption of program activities.

Abstract P3146: Racial Disparities in the Association of Adiposity Measures with Cardiovascular Disease Mortality

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.

Light-matter coupling via quantum pathways for spontaneous symmetry breaking in van der Waals antiferromagnetic semiconductors

Abstract P2014: Baseline Sex Hormone Binding Globulin Level Modifies Intensive Lifestyle Intervention Effect on Blood Pressure in Post-Menopausal Females

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.

Abstract P1160: Gut Microbiota, Circulating Inflammatory Markers, and Cardiac Dysfunction In Women Living With HIV

Introduction: The relationships among gut microbial alterations, host inflammation, and cardiac dysfunction remain understudied, particularly in the context of HIV. Hypothesis: We hypothesized that higher abundance of pro-inflammatory gut bacteria is associated with higher levels of host circulating inflammatory makers and cardiac dysfunction. Methods: We examined associations of gut microbial features (16S rRNA sequencing) with cardiac dysfunction (Echocardiography) in 973 women from the MACS/WIHS Combined Cohort Study. Cardiac dysfunction was defined as the presence of left ventricular systolic (LV ejection fraction<54%) or diastolic (ASE 2016 criteria) dysfunction. In a subset (n=397), we further integrated cardiac dysfunction-associated microbial features (Shotgun metagenomics sequencing) with serum proteomic inflammatory markers (Olink platform inflammation panel) in relation to cardiac dysfunction. Results: The potentially pathogenic bacteria Streptococcus, Eggerthella and Anaeroglobus , were positively associated with cardiac dysfunction, while the beneficial genera Roseburia and Alistipes were linked to lower odds of cardiac dysfunction ( Fig. 1A ). Results were consistent in women with and without HIV. These cardiac dysfunction-associated bacteria were associated with a number of circulating proteomic inflammatory markers ( Fig. 1B ). For example, the pathogenic Streptococcus was positively associated with the pro-inflammatory cytokines IL-8 and IL-6, the chemokine MCP-3 (linked to immune response and atherosclerosis), and the inflammatory mediator OSM (associated with vascular inflammation and heart failure). Proteomic inflammatory scores were generated for each genus based on their specific inflammatory marker profiles. The inflammatory score for Streptococcus was significantly associated with cardiac dysfunction ( Fig. 1C ). Associations between bacterial genera and cardiac dysfunction were attenuated after further adjustment for specific microbial associated inflammatory markers ( Fig. 1D ). Conclusion: Among women living with or at risk of HIV, we identified gut microbial features associated with cardiac dysfunction, with certain microbiota-related inflammatory markers partially explaining these associations.

Abstract 034: Proteomic Profiles of Obesity-Related Phenotypes are Independently Associated with Incident Cardiovascular Events

Background: Obesity is a critical modifiable risk factor for adverse cardiovascular events, yet traditional measures like Body Mass Index (BMI) have limitations in capturing the complexities of adiposity and its associated cardiovascular disease risk. Proteomics may improve the understanding of the molecular underpinnings of obesity and its implications for cardiovascular health. Methods: Proteomic profiling was performed using the Olink Explore 3072 platform on blood plasma samples from a subset of the UK Biobank participants. The relative protein abundance was normalized using rank-based inverse normalization. A total of 15,652 healthy participants without prevalent or incident diabetes, cardiovascular disease, renal disease, and cancer were included for training and testing of the protein-predicted obesity phenotypes, including BMI, body fat percentage (BFP), and waist-hip ratio (WHR). An additional 24,999 participants without prevalent stroke or coronary artery disease were included in predicting major adverse cardiovascular events (MACE). Protein-predicted scores of BMI, BFP, and WHR were generated using the least absolute shrinkage and selection operator (LASSO) algorithm with cross-validation among the healthy participants. Associations between these protein-predicted scores and MACE were evaluated using Fine and Gray's competing risk model accounting for all-cause death as competing risk, adjusting for lipids, blood pressure, estimated glomerular filtration rate, diabetes, smoking, blood pressure-lowering medication, cholesterol-lowering medication, and the measured obesity-related phenotypes. Results: Strong correlations were observed between protein-predicted obesity phenotypes and their measured counterparts (R 2 : BMI = 0.78, BFP = 0.85, WHR = 0.63). A standard deviation of elevated protein-predicted scores for BFP and WHR, but not for BMI, was significantly associated with an increased risk of MACE (Hazard Ratio [HR] 1.25, 95% CI 1.14 - 1.38, p <0.0001; HR 1.15, 95% CI 1.06 - 1.24, p = 0.001, respectively), independent of established cardiovascular risk factors and outperformed the measured obesity-related phenotypes. Conclusion: Proteomic markers can improve the assessment of obesity-related risks for cardiovascular outcomes. Integrating proteomic data into clinical practice complements current metrics for adiposity and has the potential to facilitate personalized preventive strategies for adverse cardiovascular outcomes.

VDAC2 and Bak scarcity in liver mitochondria enables targeting hepatocarcinoma while sparing hepatocytes

Abstract P2078: Extreme Lipoprotein(a) Levels and the Hazard of Acute Myocardial Infarction Among Standard Modifiable Cardiovascular Risk Factors in the United States

Background: Lipoprotein(a) [Lp(a)] is a risk factor for atherosclerotic cardiovascular disease, including acute myocardial infarction (AMI). Currently, no Lp(a) targeted pharmaceutical treatments are available in the U.S. While Lp(a) has previously shown prognostic value among patients without standard modifiable risk factors (SMuRFs), data is limited among patients with SMuRFs. This study examined the variation in Lp(a) and AMI association by SMuRFs’ number. Hypothesis: We hypothesized that the association between extremely high Lp(a) (XHI) levels and AMI among U.S. adults would differ by SMuRFs’ number with an increased AMI hazard among those with more SMuRFs. Methods: This retrospective study included U.S. adults with ≥1Lp(a) lab result between 01/01/2016-01/31/2023 identified in the Veradigm Network Electronic Health Records (VNEHR) linked to closed claims. Patients had EHR/claims activity ≥13 months prior to and ≥12 months following the index date (30 days post-first Lp(a) test). Patients were stratified by Lp(a) value into low (LO, <50 th percentile) and XHI (>90 th percentile) cohorts. SMuRFs at baseline were defined as hypertension, dyslipidemia, diabetes, chronic kidney disease, current or former smoker, alcohol use disorder, and BMI <18.5 or ≥25. Descriptive analyses were completed in SQL and SAS. Multivariable analyses are ongoing to examine AMI’s association with XHI Lp(a) by the number of SMuRFs. Results: Among the 17,819 patients meeting the inclusion criteria, 1,776 and 8,999 were assigned to the XHI and LO cohorts. Patients overall were 52.9 years old, 59% female, and 59% white. The XHI cohort had a greater proportion of patients with 3 SMuRFs (23.4% vs. 19.0%) and > 4 SMuRFs (15.7% vs. 11.5%) and a lower proportion with 0 SMuRFs (6.6% vs. 11.0%) vs. the LO cohort (all p<0.001). Baseline dyslipidemia (84.0% vs. 74.2%), hypertension (42.1% vs. 35.3%), and diabetes (19.5% vs. 15.7%) were observed more commonly among XHI vs. LO patients (all p<0.001). During a mean follow-up of 3.9-years, AMI incidence was low (<1.5%) and did not differ between Lp(a) cohorts. Conclusions: Patients in the XHI cohort were more likely to have ≥3 SMuRFs and baseline risk factors vs. the LO cohort. Although few patients had an AMI during the follow-up period, the higher presence of SMuRFs and risk factors within the XHI cohort underscore a pressing public health need. Additionally, a longer follow-up period may help better understand SMuRFs’ contribution to AMI hazard.