Browse Articles

Abstract P3122: Pericardial Adipose Tissue Outperforms BMI in Predicting Adverse Cardiac Outcomes in Severe Obesity

Introduction: Non-invasive cardiac imaging for assessing cardiovascular risk is challenging in obese patients. Intrathoracic adipose tissue, encompassing mediastinal adipose tissue (MAT) and pericardial adipose tissue (PAT), has emerged as a promising marker for cardiovascular risk. However, standard measurement methods for MAT and PAT and their diagnostic utility in the severe obese population remain unknown. Methods: We retrospectively analyzed the stress cardiovascular magnetic resonance (CMR) imaging of 790 consecutive patients between 2018-2021, including 199 with severe obesity (BMI ≧ 40 kg/m 2 ). Using the scout images (HASTE sequence), PAT and MAT were assessed as linear thickness of adipose on single axial slices. PAT was measured at the anterior mid right ventricle between the myocardium and parietal pericardium. MAT was measured at two levels: between the sternum and 1) pulmonary artery bifurcation and 2) aortic arch, respectively. Multivariable competing risk survival analysis was performed for the composite outcome of cardiac death or cardiac hospitalizations, adjusted for BMI, traditional cardiac risk factors, the presence of late gadolinium enhancement (LGE) and inducible ischemia. Results: Survival analysis showed PAT, but not MAT, was a significant predictor of adverse cardiac events for all subjects across a BMI range of 13.4-66.7 kg/m 2 with a sub-hazard ratio (SHR) of 1.087, along with LGE and inducible ischemia (Table 1). Among the severe obese group (BMI ≧ 40 kg/m 2 ), PAT, LGE and inducible ischemia remain significant predictors for cardiac events with similar SHR. BMI or the traditional cardiac risk factors were not significant predictors in either the full cohort or the severe obesity. Conclusions: PAT predicts adverse cardiac outcomes across BMI strata, including severe obesity, and can be readily attained from CMR by simple linear measurements.

Abstract P3083: Characterization of the Course of Heart Disease using Multimorbidity-adjusted Life Year (MALY): A Multi-state Non-Markov Framework

Background: In cardiovascular epidemiology, heart disease has been largely investigated by focusing on a single (or composite) endpoint. A few studies examined the disease course using multi-state Markov models, assuming the current disease state is independent of past states. Markov models are unsuitable to heart disease due to three reasons: First, risk factors interplay and affect future disease risk; second, Markov assumption does not allow for multimorbidity, a common condition for heart disease; and third, the estimated transition probabilities are time-specific and indirect for public health use. Methods: We have developed a multi-state non-Markov framework that splits disease state into substates by conditioning on past states (Ding et al. BMC Medical Research Methodology. 2024. In revision. doi: https://doi.org/10.1101/2024.09.18.24313882). As the substates track history of past states, transition rates between substates can be synthesized into a summary estimate, multimorbidity-adjusted life year (MALY) that represents the adjusted life year in full health. The derivation of MALY can be found in our second paper (Ding et al. medRxiv. 2024.doi: https://doi.org/10.1101/2024.09.18.24313882). In this study, we applied our framework to characterize the course of heart disease among participants enrolled in the Atherosclerosis Risk in Communities Study (ARIC). ARIC data was obtained from NHLBI BioLINCC. Results: We modeled the course of heart disease in five states: healthy, at metabolic risk, coronary heart disease (CHD), heart failure, and mortality ( Figure 1 ). The disability weights assigned to each disease state is shown in Figure 2 . In this mid- to old-age population, the estimated MALY was 24.13 (95% CI: 16.55, 32.06) years ( Figure 3 ). The multimorbidity-adjusted life expectancy was higher among women (79.29 [95% CI: 77.42, 81.57] years) than men (77.07 [95% CI: 74.37, 80.05] years), and was higher among Whites (79.04 [95% CI: 77.05, 81.31] years) than Blacks (75.49 [95% CI: 73.19, 79.30] years). Impact: MALY summarizes the course of heart disease into one estimate and can be used in comparative effectiveness of disease intervention in the near future.

Publisher Correction: The antibacterial capabilities of alginate encapsulated lemon essential oil nanocapsules against multi-drug-resistant Acinetobacter baumannii

Abstract P3110: Objective overeating by chronic stress level among men and women in the Hispanic Community Health Study/Study of Latinos

Background: Dysfunctional eating behaviors, including overeating, may serve as coping strategies against chronic stress (CS). US-residing Latinos face disproportionate exposure to CS, but overeating remains understudied in this population. Furthermore, overeating is usually measured using subjective scales, with little data on objective measures of overall excessive intake. This study estimated the distribution of objective overeating (OO) among US Latino men and women by CS. Methods: Data from adult participants of the Sociocultural Ancillary Study of the Hispanic Community Health Study/Study of Latinos (n=4,940; mean ± SD age 42.2 ± 0.37; 55.3% female) were used. CS was measured using a scale that assessed stressors across eight life domains, present for at least six months, and rated as moderately/very stressful, and was categorized into 0, 1, 2, or 3+ stressors. Dietary intake was assessed using two 24-hour recalls. Usual dietary intake was estimated accounting for within- to between-person variance, demographic, and clinical covariates using the National Cancer Institute method and bootstrap weights for variance estimation. Objective overeating was quantified with the following equation: Total energy intake > Basal Metabolic Rate x Physical activity factor + 500 due to the hypothesis that consuming 500 calories over the daily caloric needs every day for one week can lead to an increase of one pound. The physical activity factor was assessed with the Global Physical Activity Questionnaire. All analyses used appropriate sample weight and complex survey procedures. Results: The survey-weighted prevalence of 0, 1, 2, and 3+ CS, was 44.7%, 22.0%, 14.9% and 18.4%, respectively. The overall prevalence of OO was 21.7% (SE 2.7). Sex was significantly associated with OO (B = 1.05, p = 0.002), indicating the distribution of OO is significantly different among men and women. Among men, estimated OO prevalence by CS were as follows: 28.3% (SE 6.62) for 0 CS, 28.0% (SE 12.5) for 1 CS, 26.3% (SE 8.7) for 2 CS, and 33.6% (SE 9.9) for 3+ CS. Among women results were: 16.9% (SE 3.7) for 0 CS, 13.9% (SE 4.5) for 1 CS, 18.2% (SE 4.8) for 2 CS, and 17.0% (SE 6.9) for 3+ CS. Conclusion: Among US-residing Latinos, there are patterns of elevated overeating, measured objectively, across higher CS categories, as well as sex-based differences. Men had higher OO at higher categories of stress compared to women. Longitudinal studies are needed to confirm our findings.

Abstract P3097: Cardiometabolic Changes by Presence of Lipid Lowering Medications when Following a Vegan Diet High or Low in Extra Virgin Olive Oil

Introduction: Lipid levels are influenced by diet composition, pharmacotherapy, and severity of cardiovascular disease (CVD) risk both alone and in combination. Objective: To compare changes in apolipoprotein B (apoB), low-density lipoprotein cholesterol (LDL-C), and additional lipid biomarkers by treatment with lipid lowering medications (LLM) when following a vegan diet high or low in extra virgin olive oil (EVOO). We hypothesized greater lipid reduction among those not taking LLM compared to those taking LLM. Methods: In a secondary analysis from a 9-week randomized crossover trial in which adults at >5% risk for atherosclerotic CVD followed a high or low EVOO vegan diet for 4 weeks each (comprised of 48% and 32% dietary fat, respectively), we evaluated changes in blood lipids/lipoproteins from baseline by medication status. Independent t-tests compared levels between those taking and not taking LLM. Results: Of 40 participants (75% female, BMI 32 + 7 kg/m 2 , age 64 + 9 years mean + SD), 53% reported taking an LLM. Among those taking an LLM, apoB decreased -13.7 + 3.5 (mean + SEM) vs -2.8 + 3.2 mg/dl in absence of LLM during the low EVOO (p=0.03) and -3.2 + 3.7 vs -7.1 + 3.3 mg/dl during the high EVOO (p=0.4) diets. LDL-C reductions were comparable during the low EVOO diet (-13.6 + 4.9 with LLM vs -10.8 + 4.8 mg/dl without LLM, p=0.7). During the high EVOO diet, LDL-C decreased -8.4 + 3.9 with LLM vs -14 + 5.4 mg/dl without LLM, p=0.4. Minimal differences were observed in total cholesterol, high density lipoprotein cholesterol, and triglycerides between LLM and no LLM. Conclusions: A combination of a low EVOO vegan diet with LLM yielded the greatest lipid lowering effects, while the most potentially meaningful lipid reduction during a high EVOO vegan diet occurred without LLM. These differences may reflect individuals’ ability to effectively manage dietary fat intake that can occur with more severe lipid dysregulation warranting an LLM.

Advancing sepsis diagnosis and immunotherapy machine learning-driven identification of stable molecular biomarkers and therapeutic targets

Abstract P2092: The Association of Change in Circulating Biomarkers of Brain Injury with Cognitive Change and MRI Findings in the Cardiovascular Health Study

Background: Understanding how circulating biomarkers of brain injury correlate with cognitive function and magnetic resonance imaging. (MRI) findings of vascular brain injury is critical for developing early interventions. We aimed to elucidate the associations of change in circulating blood-based biomarkers of brain injury with change in cognitive measures and MRI findings in a cohort of older adults from the Cardiovascular Health Study. Methods: Four biomarkers (glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), total tau, and ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1)) were measured twice over 4 years in up to 780 participants. Biomarkers were log-transformed, and multiple linear regression was applied, adjusting for age and eGFR. Changes in residuals from year 5 to year 9 were the primary exposure variable. Cognitive changes (DSST and 3MSE) were calculated over the same period. MRI at the second biomarker measurement assessed cerebrovascular markers (WMH, lacunar/non-lacunar infarcts). Multivariable regression, adjusting for key covariates, examined associations between biomarker changes, cognitive outcomes, and MRI findings. Results: Rising NfL levels were associated with a decline in processing speed and executive function (DSST change: β = -0.63 points per standard deviation (SD) increase, 95% CI [-1.24, -0.02]). Changes in GFAP, total tau, and UCH-L1 were not significantly associated with cognitive change. A direct association was observed between change in total tau and WMH grade (β = 0.17 points per SD increase, 95% CI [0.00, 0.35]). In logistic regression models, NfL change was marginally associated with lacunar infarcts (OR = 0.82, 95% CI [0.68, 1.00]), but not with non-lacunar infarcts. Conclusion: Our findings suggest that changes in circulating NfL may serve as a biomarker for predicting decline in processing speed and executive function, whereas NfL and total tau appears to be linked to the burden cerebrovascular disease. Further research should investigate how these biomarkers can inform early risk stratification and personalized interventions to maximize brain health and cognition in older adults.

Abstract P3064: Socioeconomic adversity is associated with type 2 diabetes in a Mexican American border population

Introduction: Hispanic/Latino (H/L) populations, particularly Mexican Americans, face a disproportionately high prevalence of type II diabetes mellitus (T2D) in the United States, yet remain underrepresented in epidemiological research. While genetic predisposition and health behavior factors contribute to this disparity, the role of key social determinants of health (SDoH), particularly socioeconomic status (SES), in T2D prevalence is understudied. Methods: This study utilized data from the Cameron County Hispanic Cohort (CCHC), an ongoing population-based longitudinal study of Mexican American adults (n=3,916). T2D status was defined by self-reported diagnoses, medication use, fasting blood glucose ≥126 mg/dL, or hemoglobin A1c ≥6.5%. Socioeconomic status was measured using a socioeconomic adversity (SEA) score, which incorporated education, income, and occupation. Each component was scored from 0 to 1, and the cumulative SEA score ranged from 0 to 3. Descriptive statistics and binary logistic regression models were employed to assess associations between SEA components and T2D prevalence, adjusting for confounders such as age, gender, body mass index (BMI), fruit/vegetable intake, and insurance status. Results: Of the 3,916 participants, 1,053 (26.9%) met the criteria for T2D. Participants with lower education levels, especially those with less than a high school education, had significantly higher odds of T2D (OR=2.43, 95% CI [1.84, 3.22]). Additionally, those employed in blue-collar occupations had elevated odds of T2D (OR=1.33, 95% CI [1.11, 1.58]). In adjusted models, education remained the strongest predictor, with individuals who had less than a high school education being twice as likely to have T2D (OR=2.08, 95% CI [1.52, 2.84]), compared to participants with college degrees or higher. Conclusion: This study underscores the significant association between socioeconomic adversity and the prevalence of T2D in a predominantly Mexican American population. While other SES factors, such as income and occupation, were relevant, education emerged as the most significant predictor of T2D. These findings highlight the need for targeted interventions to improve educational opportunities and mitigate the impact of T2D in underserved H/L communities.

A two stage blood cell detection and classification algorithm based on improved YOLOv7 and EfficientNetv2

Abstract 061: Joint Associations of Objectively Measured Physical Activity and Cardiovascular-Kidney-Metabolic Syndrome with All-Cause Mortality in US Adults

Introduction: Physical activity is recommended for slowing the progression of Cardiovascular-Kidney-Metabolic (CKM) syndrome. Guidelines suggest lifestyle modification may be most beneficial for those with advanced CKM (stages 3-4), but few studies have compared the impact of physical activity across the CKM spectrum. Objective: We examined associations between physical activity (PA) patterns and risk of all-cause mortality across CKM stages. Methods: We conducted a weighted, prospective cohort analysis of the 2003-2006 National Health and Nutritional Examination Survey (NHANES), with follow-up until December 31, 2019. We restricted analyses to those adults who were ≥ 20 years old, not pregnant, and able to walk. We classified participants according to CKM stage. We calculated average daily moderate-to-vigorous physical activity (MVPA) using up to 7 days of actigraphy data and the standard cut-point of 2000 activity counts per minute. We visualized the MVPA distributions by CKM stage and calculated the proportion of adults meeting the recommended MVPA target of ≥ 150 minutes a week (≥ 21.4 minutes per day). We fit Cox regression models to estimate relative and absolute mortality risk using a polynomial B-spline of log-MVPA with a single knot at the midpoint. We stratified all analyses by CKM stage and adjusted models for demographics. Results: We included 7,246 adults (weighted mean age 47.6 yrs, 51.5% female). Over a median follow up of 14.4 years, there were 1676 deaths. The percentage of US adults achieving the AHA-recommended MVPA target ranged from 7.3% (CKM stage 3) to 43.1% (CKM stage 0 to 1) ( Fig. 1A ). Greater MVPA was associated with lower hazard of mortality across CKM stages. Hazard ratios of reaching the AHA recommendation, as opposed to being sedentary, ranged from 0.93 (CKM stage 0/1) to 0.52 (CKM stage 4). The minimum MVPA associated with lower mortality ranged from 4.1 minutes per day (CKM stage 3) to 19.9 minutes/day (CKM stage 0/1) ( Fig. 1B ). The associations between greater MVPA and lower absolute mortality risk were more pronounced in later stage CKM ( Fig. 1C ). Conclusion: MVPA is associated with lower mortality along the full spectrum of CKM syndrome. The benefits of MVPA appeared largest in advanced CKM (stages 3-4), where even modest activity potentially confers cardioprotection.

Abstract P1067: Impact of Health Literacy, Numeracy, and Social Determinants on Readmission and Outpatient Adherence in Heart Failure Patients at an Urban Safety-Net Hospital

Background and Aims: Low health literacy and numeracy are associated with increased mortality and rehospitalization in heart failure (HF) patients. However, their combined effect on long-term readmission rates and outpatient visit-adherence remains unclear, particularly in underserved populations. This study aimed to evaluate the association of health literacy and numeracy with 3-month post-discharge readmission rates and outpatient visits in a large, urban, safety-net county hospital. Methods: We conducted a prospective, observational cohort study of 169 English or Spanish-speaking patients hospitalized with HF in Dallas, TX, from 11/2022 to 06/2023. Patients were stratified into two groups based on validated health literacy (SAHL-E) and numeracy (NUMi) scores: (1) Low Numeracy or Literacy (LNL) and (2) High Numeracy and Literacy (HNL). The primary outcome was a composite rate of emergency department (ED) visits and hospital re-admission rate at 3-months post-discharge, expressed per 100 patient-months. Clinic attendance at 3 months was a secondary outcome. We used univariate analyses and multivariate linear regressions adjusted for age, sex, race, ethnicity, and Charlson comorbidity score. Results: Among participants (mean age 54 years; 73.3% male, 66.9 % Black, 20.1 % Hispanic), 47.8% were in the LNL group and 52.2% in the HNL group. In univariate analyses, the LNL group showed a significantly higher composite ED/hospitalization rate at 3 months (81.33 vs 50.67 per 100 patient-months; β = 30.66, 95% CI: 3.47 to 57.85, P = 0.03). No significant difference was observed in 3-month clinic attendance (43% vs 48%, P = 0.36). After adjustment, both associations were not statistically significant (adjusted β = 11.09, 95% CI: -18.14 to 40.33, P = 0.45 for ED/hospitalization rate). Conclusions: Low numeracy or literacy was associated with worse clinical outcomes at 3 months in univariate analyses. However, these associations were not significant after adjustment, suggesting that broader social determinants of health may play a more substantial role in healthcare outcomes among underserved patients with HF.

The effect of slow breathing in regulating anxiety

Abstract Anxiety is an interactive disorder of the mind and body, characterized by excessive worry about uncertain future events and a dysfunction of the autonomic nervous system. Previous studies have shown that slow, deep breathing can reduce physical tension, and anxiety. Although we know that slow and deep breathing techniques can effectively regulate anxiety and other emotions, the psychological and neurophysiological mechanisms of slow breathing on anxiety have not been systematically explored. In the study, we combined the paced breathing task with the threat uncertainty task for the first time to investigate the role of slow breathing in regulating anxiety. Here we investigated this question, using Spectral analysis and Time-frequency domain of EEG to assess brain activity relating respiratory rate and the mechanism of respiratory rate impact on the anxious. Twenty-seven individuals participated in the experiment, which followed a 2 (respiratory rate: fast breathing, slow breathing) × 2 (certainty: certain, uncertain) within-subjects design. The results of showed that: (1) Slow breathing effectively reduced anxiety, the valence and arousal are lower under the slow breathing. (2) The EEG of fast and slow breathing showed different characteristics. There is an overall increase in power during slow breathing in the delta, theta, alpha and beta bands.(3) The interaction of respiratory rate and certainty were closely related to beta. In the uncertain, beta power decreased with slow breathing but increased with fast breathing.

Abstract MP19: Indoor Radon Concentrations Are Associated With Incident Myocardial Infarction in the Women’s Health Initiative

Background: Radon is an emerging risk factor for stroke, but its relationship with common forms of coronary heart disease (CHD) is unclear. Methods: We studied the radon-myocardial infarction (MI) association among US women without a history of MI or coronary revascularization at the 1993-1998 screening visit of the Women’s Health Initiative Clinical Trials (CT) and Observational Study (OS). We paired their geocoded addresses with county-level, indoor, screening radon gas concentrations predicted by the US Environmental Protection Agency and classified as Zone 3 (<2 pCi/L), Zone 2 (2-4 pCi/L), or Zone 1 (>4 pCi/L). We used medical records to identify incident, physician-reviewed, classified, and adjudicated MI through 02/17/24 based on acute onset of cardiac pain, electrocardiographic abnormalities, and/or elevated cardiac biomarkers. We estimated the radon-MI association as a hazard ratio (HR) and 95% confidence interval (CI) using a Cox proportional hazards model on an attained-age scale adjusting for CT/OS membership, race/ethnicity, education, homemaker status, US Census region, neighborhood socioeconomic status, annual mean concentration of ambient particulate matter <2.5 um in diameter (PM 2.5 , ug/m 3 ), smoking, alcohol intake, sodium intake (g/day), Healthy Eating Index, recreational physical activity (metabolic equivalent-hr/wk), body mass index (kg/m 2 ), systolic blood pressure (mm Hg), as well as history of diabetes and hypercholesterolemia. Results: Among 153,701 postmenopausal women examined at 40 US centers (mean age = 63.1 years; 83% white; 9% Black; 4% Hispanic/Latina; 4% other), we identified 5,925 incident MIs over a mean follow-up of 13.2 years. Incidence proportions and corresponding rates in Radon Zones 3, 2, and 1 were 36, 38, and 43 MIs per 10 3 women at risk and 278, 287, and 314 MIs per 10 5 woman-years, respectively. Relative to women in Zone 3, those in Zones 2 and 1 had higher hazards of incident MI: HR (95% CI) = 1.04 (0.97-1.11) and 1.18 (1.09-1.28). The association was robust after adjusting for center-level confounding, multiply imputing missing data, stratifying by smoking or PM 2.5 , and substituting related radon exposures and CHD outcomes. In contrast, it was attenuated after replacing MI with a negative outcome control, coronary revascularization. Conclusion: Exposure to radon gas—a residentially ubiquitous carcinogen previously associated with risk of stroke—may also be associated with risk of MI among postmenopausal women.

Abstract P2004: Calibration of the Predicting Risk of CVD Events (PREVENT) equation among Hispanic/Latino adults of the HCHS/SOL.

Background: The Predicting Risk of CVD EVENTs (PREVENT) equations were developed with minimal representation from Hispanic/Latino adults. Objective: To describe the ten-year risk of total cardiovascular disease (CVD) using PREVENT and estimate the discordance rate in Hispanic/Latino adults. Methods: The Hispanic Community Health Study/Study of Latinos is a population-based cohort of 16,415 diverse Hispanic/Latino adults aged 18-74 from four urban communities (Bronx, NY; Chicago, IL; Miami, FL; and San Diego, CA). At baseline (2008-2011), participants underwent a comprehensive examination which included questionnaires, anthropometric measurements, and fasting blood draws. Among 4,829 participants 30-79 years of age, without a history of CVD, examined in 2008-2009 and followed through 2019 (at least ten years), we used baseline information on age, sex, blood lipids, systolic blood pressure, body mass index, estimated glomerular filtration rate, diabetes status, smoking status, and anti-hypertensive or lipid lowering medication use, to calculate ten-year risk of total CVD (heart disease, stroke, or heart failure) using the base model PREVENT equation. CVD events were adjudicated from hospital records by an independent panel of clinicians through Dec 2019. We calculated the ten-year risk of total CVD using the base PREVENT equation. These analyses were weighted and accounted for the complex survey design of the study. We then calculated the discordance rate by comparing the predicted to observed number of CVD events overall and according to sex. Results: In a diverse sub-population of HCHS/SOL, the mean age was 47.3 years, and 52.0% were female. Using the PREVENT equation, the mean ten-year CVD risk score was 5.2%; and 67.9% had a <5.0% risk of CVD; 9.0% had a 5 to <7.5% risk of CVD, 5.7% had a 7.5 to <10.0% risk of CVD, 8.6% had a 10.0 to <15.0%, 4.1% had a 15.0 to <20.0% risk of CVD, and 4.7% had a ≥20% risk of CVD. Over ten years, 224 CVD events were predicted, and 110 CVD events were observed (discordance rate: 103.6%). Men compared with women had higher risk of CVD (5.7% vs. 4.8%, p<0.05) and CVD was more likely to be overpredicted among males (discordance rate: 178.6%) than females (discordance rate: 55.9%). Conclusion: In this diverse sample of Hispanic/Latino adults, the base PREVENT equation for total CVD overestimated risk of CVD, especially among males. These data identify a potential limitation of the PREVENT equation for Hispanic/Latinos adults.

Correcting promoter and beta-lactamase ORF orientation in a widely-used retroviral plasmid to restore bacterial growth

Abstract The pBMN-I-GFP plasmid is a widely used retroviral vector for producing retroviral particles, utilized by thousands of laboratories worldwide. However, we observed that E. coli transformed with pBMN-I-GFP failed to grow on selective LB agar plates containing ampicillin or carbenicillin, in contrast to similar retroviral vectors. Multiple attempts to optimize growth conditions were unsuccessful. Sequencing, contrary to the available reference sequence, revealed an inversion of the beta-lactamase (bla) gene and part of its promoter, likely disrupting bla expression and, consequently, antibiotic resistance. To address this, we corrected the orientation of the ampicillin resistance gene and its promoter in a new plasmid, prBMN-I-EGFP. This modification restored robust growth of E. coli transformed with this plasmid on selective plates, confirming the essential role of an intact bla promoter for antibiotic resistance. Additionally, retroviral functionality tests in murine cell lines showed that prBMN-I-EGFP exhibited transfection and infection efficiencies comparable to the original pBMN-I-GFP. These findings underscore the importance of thorough sequence verification for commonly used plasmids and present an improved version of pBMN-I-GFP.

An organ that stores red blood cells for emergencies

Abstract P1009: Epigenetic age acceleration as a hallmark of premature mortality in US adults

Introduction: Epigenetic (DNA methylation) clocks have been derived as hallmarks of biological age based on their ability to predict chronological age or aging-related phenotypes. However, studies comprehensively examining the associations between epigenetic age acceleration and premature mortality in nationally representative U.S. populations are lacking. Hypothesis: Epigenetic age acceleration will be associated with higher risks of premature mortality in the general US population. Methods: We included 2,191 participants aged 50-79 years from the 1999-2002 National Health and Nutrition Examination Survey (NHANES) who underwent DNA methylation measurement. We included five epigenetic clocks (Horvath’s, Hannum’s, PhenoAge, GrimAge, and DunedinPoAm), and calculated epigenetic age acceleration as the residual from regressing epigenetic age on chronological age (except for DunedinPoAm, which reflects aging rates). Premature mortality was defined as death before age 80, with a sensitivity analysis using a cutoff of 75 years. Cox proportional hazards models were used to assess the association between epigenetic age acceleration and premature mortality. Results: We found that faster epigenetic age acceleration was significantly associated with a 19% to 61% higher risk of premature mortality across the 5 clocks, adjusting for demographic, socioeconomic, and behavioral factors ( Table ). GrimAge age acceleration was the strongest predictor, while Horvath age acceleration was the weakest. The associations were consistent when premature mortality was defined as death before age 75. Conclusions: Our examination of epigenetic age acceleration measures in a representative U.S. population lends innovative evidence to support the potential application of epigenetic clocks as hallmarks for monitoring biological aging and a promising target for prevention of premature mortality and aging-related disorders in the broader US populations.

Abstract P2169: Salt and Potassium Intake Measured by 24-Hours Urine Collection in the Adult Population: the Italian Health Examination Survey 2023-2024 - CUORE Project

Introduction: The WHO recommends a 30% relative reduction in mean population intake of salt/sodium within 2025 (baseline 2010) and an adequate potassium intake. To these ends, the Italian Ministry of Health (MoH) has strengthened prevention/health promotion. To update the assessment of the habitual salt and potassium intake in the Italian general adult population, national health examination surveys (HESs) were implemented, technicallly and financially supported by the Ministry of Health - National Centre for Disease Prevention and Control, and conducted within the CUORE Project. Hypothesis: This analysis aims to assess if Italy can meet the WHO target on salt intake and to monitor the levels of potassium intake in the general adult population. Methods: In 2023 a new HES started including salt and potassium intake assessment by the use of 24h urine collection. Up to now, data from random samples of residents in 12 Regions (of 20 regions) distributed in North, Centre and South of Italy and aged 35-74 years are available (1334 men, 1317 women). Urinary excretion is assayed by a central lab. Persons with urinary volume < 500 ml and/or a urinary creatinine content referred to body weight outside the range of population mean ± 2 standard deviations are excluded. Results: Out of 1138 men and 1140 women, mean level of salt per day was 9,3 g (95% CI: 9,1-9.5 g) and 7,2 g (7,0-7,3 g) respectively, and mean level of potassium per day was 2,9 g (2,9-3,0 g) and 2,5 g (2,4-2,5 g) respectively. A salt intake level lower than the WHO recommended target of 5g/day was detected in 9,5 % (6,2 -12,8 %) of men and 23,6 % (18,8 -28,3 %) of women and a potassium intake level higher than the WHO recommended target of 3510 mg/day was detected in 23,8 % (19,0 -28,6 %) of men and 10,6 % (7,2 -14,0 %) of women. Conclusions: These preliminary data showed that in Italian adults the average salt intake is still higher and the average potassium intake is still lower than recommended. Compared to 2008, the habitual salt intake decreased of about 12% in 2018 and remained stable in 2023; the habitual potassium intake remained stable in 2008, 2018 and 2023.These results justify and encourage the ongoing preventive initiatives of MoH, facilitating the meeting of WHO targets.

Type of diet has no major influence on inflammatory response in a Saddleback pig model

Abstract Fermentable carbohydrates and resulting short-chain fatty acids (SCFAs) received attention via modifying potential on obesity-associated systemic low-grade inflammation. However, their effects on inflammation remain poorly understood. In this study, the anti-inflammatory properties of pectin or inulin supplementation were investigated in an atherogenic-fed pig obesity model. Pigs were divided into three atherogenic-fed groups with or without 5% pectin/inulin supplementation (AD, ADp, ADi, n = 10) and a conventional-fed group (CD, n = 10) for a 15-week feeding period. We demonstrated that faecal SCFA concentrations decreased and faecal pH increased in all groups over the feeding period (P < 0.05). SCFA concentrations were comparable between colon and faeces in all groups. Liver inflammatory-marker expressions were on average < 1 in all groups, except TNF-α (AD < CD and ADi; P < 0.01). Inflammatory-marker expressions in abdominal adipose tissue exceeded subcutaneous marker expressions in all groups. AD showed significantly lower IL-1β and CD68 mRNA levels than CD (P < 0.03). Comparing the atherogenic diet groups, the IL-1β mRNA levels were higher in ADi versus AD and ADp (P = 0.02). Our data indicated that fermentable carbohydrates added to an atherogenic diet cannot resolve low-grade adipose tissue inflammatory associated with obesity.

Abstract P3111: Healthcare Resource Utilization (HCRU) and Economic Burden of Obesity or Overweight with Comorbidities in the US: A Systematic Literature Review (SLR)

Introduction: The obesity epidemic is a growing public health challenge. Obesity-related morbidity and mortality rates in the US are rising, putting a substantial burden on the US healthcare system. This SLR identified publications reporting HCRU and costs associated with overweight and obesity in the US. Methods: A systematic search was conducted in January 2024, using Medline, Embase, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews. Eligible studies reported HCRU or costs in adults living with obesity (body mass index [BMI] ≥30 kg/m 2 ), or overweight (BMI ≥27 kg/m 2 ) and ≥1 obesity-related complication (ORC; diabetes, cardiovascular disease [including stroke], renal, liver, pancreas, or gallbladder disorders, sleep apnea, musculoskeletal condition, or mental health condition), published in English from 2019–present. Studies reporting other comorbidities, surgery (bariatric or musculoskeletal), or in patients with COVID-19 were excluded. Results: Of 6862 publications identified, 60 were included. Of these, 23 reported general costs and HCRU associated with obesity and 37 reported the impact of ORCs, including cardiovascular comorbidities (n=10; venous thromboembolism, atrial fibrillation, infective endocarditis, and acute myocardial infarction), diabetes-related comorbidities (n=7), stroke (n=5), metabolic dysfunction-associated steatotic liver disease (n=1), osteoarthritis (n=1), mental health disorders (n=1), or ≥2 comorbidities (n=7). Total medical costs per patient per year (PPPY) associated with obesity ranged from $4443–$45,683, which increased with higher BMI. Annual direct healthcare costs were higher for individuals with ORCs than those without and increased with the number of ORCs (no ORCs: $5149; ≥3 ORCs: $16,451). Among ORCs, the highest mean PPPY cost was in bipolar disorder-1 ($37,771) and the lowest was in type 2 diabetes ($8987). Job seekers with obesity experienced longer average spells of unemployment than those without obesity, and rates of absenteeism increased with BMI. People with BMI ≥25 kg/m 2 who lost weight had lower direct medical costs (excluding anti-obesity medications), with greater cost savings at 2 years. Discussion: Obesity and ORCs are significant drivers of HCRU and costs, which are expected to rise in the future. These results highlight an unmet need for effective prevention and treatments for obesity and ORCs to mitigate the economic burden of this chronic, complex disease.