Browse Articles

Abstract WE577: Associations of Occupational and Social Factors with Incident Kidney Stones in the Pro-Saude Study

Background: While occupational factors and social determinants of health (SDOH) are associated with kidney stone disease (KSD) risk in US cohorts, their role in other populations remains unexplored. We investigated the extent to which these factors are associated with KSD incidence in a Brazilian cohort. Hypothesis: Occupational and social factors are associated with KSD risk in a Brazilian working population. Methods: The Pro-Saude study followed employees of Universidade do Estado do Rio de Janeiro from 1999 to 2012. Baseline exposures included occupation (International Standard Classification of Occupations skill level), work hours/week, years worked, household income, education, and supplementary health insurance status. Incident KSD was defined as a first self-reported kidney stone between baseline and follow-up visits (2001, 2012). Multivariable Cox proportional hazards models estimated the risk of KSD across exposures, adjusting for known KSD risk factors. Results: Among 2,986 participants (mean age 40.4 years; 43.3% male), 148 developed KSD over 13 years. Participants without supplementary health insurance had significantly lower reported KSD incidence than those with supplementary health insurance (adjusted HR 0.66 [95% CI 0.44-0.97]; Figure 1). Other occupational and social factors showed no statistically significant associations with KSD risk. Conclusion: No supplementary health insurance was paradoxically associated with lower reported kidney stone incidence, a finding likely driven by detection bias rather than a protective effect. This suggests that individuals with more limited access to healthcare have lower rates of kidney stone diagnosis and reporting.

The utility of aqueous and serum apolipoprotein E and galectin-3 as biomarkers of neuroinflammation in glaucoma

Abstract TH884: Pulse Pressure as a Mediator of the Association Between Cognition and Bone Health in Older Women: Findings from the Study of Muscle, Mobility and Aging- Bone Ancillary Study (SOMMA Bone)

Background: Stiffening arteries, a risk factor of cognitive impairment, leads to increased pulse pressure (PP, difference between systolic and diastolic blood pressure). PP directly relates to bone metabolism by microvascular perfusion and mechanotransduction. We hypothesized that PP may mediate the known association between performance on episodic memory and bone health. Methods: Participants in the Study of Muscle, Mobility and Aging (SOMMA) study were > 70 years, able to complete a 400-meter walk at baseline, and free of advanced chronic disease. At the baseline SOMMA visit, participants completed a California Verbal Learning Test II short form (CVLT-II), a test of episodic memory. The SOMMA-Bone Study at the Pittsburgh site measured bone structure/microarchitecture using High-Resolution peripheral Quantitative Computed Tomography (HR-pQCT) at the distal radius and tibia after the 12-month SOMMA visit (N= 327; aged 76.2± 4.6 years; 60.5% women; 87.2% White). Total BMD (Tt.BMD, mg HA/cm 3 ), total area (Tt.Ar, mm 2 ), and failure load (F.ult, N) from micro-finite element analysis (µFEA) measurements were estimated and standardized by sex. A causal mediation analysis method was used to examine if PP mediated the association of CVLT-II performance and HR-pQCT measurements in women using the mediation package in R, adjusting for relevant confounders. To estimate the indirect (Average Causal Mediation Effect, ACME) and direct (Average Direct Effect, ADE) effects, we used nonparametric bootstrapping with 5000 simulations, assuming no unmeasured confounding. Results: There was no association between episodic memory and bone parameters in men. Of the women in SOMMA-Bone (n=198, 76.2 ± 4.7 years, 83.8% White), mean PP was 59.1±13.8 mmHg. Better performance on the immediate (but not short or long) recall was associated with higher F.ult in the tibia. Better performance on short and long recall tests (but not immediate) were associated with higher Tt. BMD (Table 1). At the radius, better performance on the long recall test was associated with lower Tt.Ar only. In all models, PP was not a significant mediator. Conclusions: In associations between better episodic memory and better skeletal parameters, there was no evidence of mediation through PP. This suggests that cognitive and skeletal health may share underlying biological mechanisms independent of PP in older women. Serum proteomic analysis is underway to identify the biology of this relationship.

Abstract WE538: Sex Differences in Actigraphy-Measured Physical Activity Among Young Survivors of Acute Myocardial Infarction

Introduction: Light and moderate-to-vigorous physical activity (LPA and MVPA) are critical for secondary prevention in individuals with recent myocardial infarction (MI). Examining sex differences in physical activity (PA) patterns may inform the development of sex-specific post-MI health promotion strategies. Because women in community samples typically engage in lower levels of PA than men, we hypothesized that, among post-MI individuals, female sex would be associated with lower objectively measured LPA and MVPA. Methods: We recruited individuals aged ≤ 61 years within 8 months of an MI in metropolitan Atlanta. Participants wore a wrist accelerometer for 7 days to track PA and sleep. We constructed linear mixed-effect models to estimate the association between sex and minutes of total, daily PA. We adjusted sequentially for sleep minutes, demographics (age, race, income, marital status, education), physical factors (heart failure, functional capacity, Gensini score), cardiac rehabilitation participation, and psychosocial factors (stress, depression). Results: Our sample included 276 participants (43% women, 53% Black) with mean age 51 years (SD: 7) from the third wave of the Myocardial Ischemia and Mental Stress (MIMS3) study. On average, women had 19 greater minutes of LPA compared to men per day (119 vs.100 minutes), while no sex differences were found for MVPA (2 minutes/day for each). In models adjusting for a minimum of sleep, sociodemographic, and health factors, women engaged in a statistically significantly higher amount of overall PA compared to men ( Table ). In the fully adjusted model, women, vs. men, performed 116 (95% CI: 94-138) minutes vs. 88 (66-109) minutes of total PA/day on average. Results remained similar when patients with poor functional capacity were excluded. Discussion: On average, women engaged in more PA compared to men. Our results contradict the notion that women perform less PA compared to men, although previous studies mostly focused on self-reported, leisure MVPA. More research is needed to evaluate whether women spend more time performing gender-specific tasks that would contribute to LPA than men such as caregiving and house work. Whether these differences help protect post-MI women from mortality similar to leisure MVPA warrants more research, given the concern for burnout and vital exhaustion in this population.

Abstract TU188: Association of the IgG and Plasma Glycomes with Cardiometabolic Risk Factors

Background: The immunoglobulin G (IgG) and plasma N-glycomes represent biomarkers of cardiovascular disease. However, few studies have examined relationships between glycomic profiles and an extensive list of cardiometabolic risk factors in healthy adults. Hypothesis: Specific subsets of IgG and plasma glycans will associate with specific cardiometabolic traits. Methods: Plasma and IgG glycans were analyzed using HILIC-UPLC and MALDI-TOF-MS (25 IgG N-glycans and 39 plasma N-glycans) in samples from 652 HERITAGE Family Study participants (57% female, 44% Black, 17-65 years old). Spearman correlations adjusted for age, sex, and race were performed between glycans and 68 cardiometabolic traits. Sparse multiple canonical correlation analysis (SMCCA) was used to identify a parsimonious set of glycans maximally related to cardiometabolic risk factors. Results: Most (29/39) plasma glycans were associated with 10 or more traits ( Fig 1A ), while four IgG glycans were associated with 10 or more traits ( Fig 1B ). The SMCCA identified two canonical variates (CV) of groups of IgG and plasma glycans correlated with groups of phenotypes. CV1 was comprised of six IgG glycans, 12 plasma glycans, and 18 traits mostly related to body composition and indicative of worse cardiometabolic profiles (e.g., higher glycan abundance related to lower VO 2 max and insulin sensitivity, higher visceral fat and BMI; Fig 2A ). Conversely, CV2 was comprised of six IgG glycans, 13 plasma glycans, and 17 traits related to mostly body composition and lipids and indicative of better cardiometabolic profiles (e.g., higher glycan abundance related to lower triglycerides, total cholesterol, visceral fat, and BMI; Fig 2B ). Seven plasma and four IgG glycans were found in both CVs, while five and six plasma glycans and two IgG glycans each were unique to CV1 and CV2, respectively. Although eight traits mainly related to body composition overlapped between CVs, traits related to insulin sensitivity and cardiorespiratory fitness were uniquely included in CV1 and lipoprotein-related traits in CV2. Conclusions: We identified subsets of IgG and plasma glycans related to better or worse cardiometabolic profiles. Within the CVs, some associations between glycans and body composition traits overlapped. However, each CV is also related to a unique set of cardiometabolic traits. Future studies should investigate how changes in glycans relate to changes in cardiometabolic health.

Effect of pH on niacinamide skin permeation

Abstract Niacinamide (NIA) is a widely used skincare ingredient with established benefits for skin barrier support, inflammation reduction, and dermal health. However, the mechanisms governing its transdermal delivery remain insufficiently understood, particularly regarding how formulation pH influences its permeation through the stratum corneum (SC). This study investigates how donor phase pH (5.0 vs. 7.4) modulates NIA skin permeation and how these effects relate to pH induced changes in SC electrical properties. Franz cell diffusion experiments were combined with electrical impedance spectroscopy (EIS) using full‑thickness human skin and 3D reconstructed epidermal tissue models. Permeation was quantified over 24 h and in pH switch experiments, while EIS characterized pH dependent changes in membrane resistance ( R mem ) and effective capacitance ( C eff ). Additional analyses assessed microbial conversion of NIA to nicotinic acid during prolonged exposure. Neutral donor pH (7.4) increased NIA permeation by roughly twofold compared with acidic pH (5.0) in both membrane types. Correspondingly, pH 7.4 decreased R mem and increased C eff , indicating pH driven changes in SC lipid organization and dielectric behavior. These effects were reversible and likely stem from alterations in SC lipid domains, including pH dependent partial deprotonation of free fatty acids that modifies the continuous lipid regions and introduce localized structural microdefects. Such changes enhance NIA and ion permeability and increase SC dielectric properties at neutral pH. Although microbial conversion of NIA to nicotinic acid was negligible within the first 24 h, it became clearly detectable upon prolonged experiments. In conclusion, donor phase pH is a critical determinant of NIA skin permeation, primarily through reversible modulation of SC lipid structure and transport pathways. These findings highlight the importance of pH control in topical formulations and underscore the need to consider microbiota‑mediated transformations when evaluating the efficacy and safety of skin care products containing NIA.

Abstract TU129: Stress, Sleep, and the Heart: Identifying Early Biomarkers of Cardiovascular Risk in Puerto Rican Children

Background: Psychological stress during childhood can disrupt vascular homeostasis and increase long-term cardiovascular disease (CVD) risk. Endothelin-1 (ET-1), a potent vasoconstrictor involved in endothelial dysfunction, oxidative stress, and vascular inflammation, has been proposed as a biomarker of cardiovascular risk. While adult populations show a link between stress and elevated ET-1, evidence in pediatric populations is scarce. Objective: To determine the relationship between psychosocial stress, sleep quality, and ET-1 levels in a pediatric population in Puerto Rico. Methods: Children were recruited from the Puerto Rico Health Justice Center and pediatric community clinics. Participants completed PROMIS Pediatric measures (stress, sleep, and family relations), self-reported trauma history, and clinical evaluations for BMI, blood pressure, and lipid profiles. Plasma ET-1 concentrations were quantified from blood samples. Thirty-eight Hispanic participants (mean age = 12.1 ± 2.3 years; 73% female) were analyzed. Results: Eleven participants (29%) exhibited elevated ET-1 levels. Higher PROMIS stress scores correlated with higher ET-1 concentrations (p < 0.05). Children with poor sleep quality showed significantly higher ET-1 levels (median = 1.7 vs. 0.8 pg/mL, p < 0.01). The coexistence of poor sleep and high stress further amplified ET-1 elevation, suggesting cumulative vascular effects. Participants with high ET-1, high stress, and poor sleep also had a greater frequency of dyslipidemia. Conclusion: Psychological stress and poor sleep are biologically linked to endothelial dysfunction in Hispanic children, as reflected by elevated ET-1 levels. ET-1 may serve as an early biomarker of stress-related cardiovascular vulnerability, underscoring the need for integrated behavioral and physiological interventions in pediatric populations.

Abstract WE511: Reduced Blood Pressure and Improved Survival in Patients with Normal Blood Pressure to Severe Hypertension Treated with the Very Low Sodium Rice Diet

Introduction: High sodium intake increases risks of hypertension (HTN) and mortality, but the impact of very low sodium intake is uncertain. No studies have examined dietary sodium as low as those in the original Rice Diet (RD: ~200 mg/d sodium, ~5% calories each from protein and fat). We retrospectively assessed factors associated with systolic blood pressure (SBP) change and survival of RD-treated patients across BP categories. Methods: We identified 12,312 adults (1942-1994) who consumed the RD for ≥7 days. Urinary chloride (UCl≤42mg/dl) indicated diet adherence. Multivariable linear regression examined factors linked with SBP change. Actuarial survival analysis compared survival by BP groups. Cox proportional hazards model assessed factors influencing survival. Observed and predicted life expectancy was compared using US Social Security Administration (SSA) life-tables. Significance was defined as p<0.05. Results: Patients were mostly female (64.8%), median age 48 [34,57] years, BMI 32.9 [0.1, 38.5] kg/m 2 . SBP declined rapidly during the first 4 weeks (Figure 1) and remained stable to week 52. Greater 12-week SBP reduction was associated with higher baseline SBP (β[95%CI]:-0.57[-0.59,-0.55]), better diet adherence(-0.05[-0.07,-0.04]), and greater weight loss(-0.42[-0.53,-0.31]); smaller reductions were linked to older age(0.1[0.07,0.14]) and worse kidney function(0.13[0.08,0.19]). Across BP groups, baseline SBP consistently predicted SBP decline. Survival (Figure 2) was longest in the normal BP group, followed by elevated and stage 1 HTN, which were similar, and markedly less in stage 2 and severe HTN. A larger first-month SBP reduction was strongly and progressively associated with improved survival (Table). Older age, male sex, worse kidney function, and higher baseline SBP increased mortality risk; higher BMI and better diet adherence were protective. Mortality risk was most influenced by male sex and early SBP reduction. Compared with SSA life tables, RD patients with normal, elevated, stage 1 and stage 2 HTN lived 4.1, 5.0, 3.7 and 1.0 yrs longer, respectively, whereas those with severe HTN lived 11 yrs less. Conclusions: The RD was associated with lowered SBP and improved survival. SBP reduction and survival benefits were comparable in elevated and stage 1 HTN, with benefit even in the normal BP group. Survival improved proportionally to the magnitude of SBP reduction, underscoring the strong impact of intensive diet intervention on BP and mortality.

Abstract MPTH63: Effects Of Exercise Training On Predicted ASCVD Risk: Meta-Analysis Across Eight Exercise Training Studies

Background: Atherosclerotic cardiovascular disease (ASCVD) risk scores are commonly used to inform therapeutic strategies in the clinical setting. Although previous studies have shown that individual risk score components, such as HDL-C and total cholesterol, can be improved with regular exercise, few studies have investigated the effect of exercise interventions on composite measures of predicted ASCVD risk. Methods: Data from eight exercise trials (INFLAME; HART-D; CardioRACE; Queen’s; STRRIDEs 1, 2, and PD; HERITAGE) with 21 different interventions varying in exercise mode, amount, and/or intensity were analyzed. ASCVD risk scores were calculated for each participant (n=2,074) at baseline and after exercise training using the pooled cohort equations and Framingham Heart Study algorithm for 10- and 30-year risk, respectively ( Table 1 ). Meta-analysis of study group-specific mean changes in ASCVD risk with training was performed. When available, changes in exercise groups were compared against changes in the respective control group for each study. Since age is the strongest predictor of risk in the equations, additional meta-analysis was performed to examine changes in risk due to age only (phenotype levels held constant between time points), with all groups analyzed individually with no comparison to controls. Results: Exercise training resulted in an absolute decrease in 10-year ASCVD risk of -0.2% (95% CI: -0.3 to -0.1) and -1.2% (95% CI: -1.8 to -0.5) in 30-year risk, with low and high heterogeneity, respectively ( Figure 1 ). An increase in age only would have significantly increased 10- and 30-year risk across all exercise intervention groups by 0.3% (95% CI: 0.2 to 0.3), and 0.6% (95% CI: 0.5 to 0.7), respectively ( Figure 1 ). However, this age-related increase was abolished in all exercise groups except for the resistance training groups in STRRIDE 2 and CardioRACE. Conclusions: We found that a relatively short period of endurance exercise training of differing amounts and/or intensity performed alone or in combination with resistance training can prevent and even reverse the age-related increases in both short- and long-term ASCVD risk.

Mathematical modeling of sequential Dengue–Zika infections: dynamic insights into antibody-dependent enhancement and neutralization effects

Abstract TH984: Adverse gestational outcomes elevate risk of cardiac and vascular dysfunction in pre-menopausal women

Introduction: Pregnancy is considered the ultimate stress test on the body, as it may reveal or accelerate underlying cardiovascular risks in women. Existing studies have focused on the postmenopausal phase linking adverse pregnancy outcomes and menopausal symptoms to cardiovascular risk. However, the pre-menopausal phase is crucial for early signs of cardiovascular dysfunction. This study aims to evaluate the association between adverse pregnancy outcomes and cardiac structure and vascular function in pre or peri menopausal women. Methods: This study leverages data from a longstanding study of Black and White women enrolled in childhood and followed to their mid-40s. Women self-reported adverse pregnancy outcomes in one or more pregnancies, including preterm birth and hypertensive disorders of pregnancy (HDPs: gestational hypertension and pre-eclampsia/eclampsia). Women who never gave birth were included in the ‘no’ group. Left ventricular mass indexed to height 2.7 (LVMI), from echocardiography and pulse wave velocity (PWV) were used as measures of cardiac structure and vascular function. Linear regression analysis was used to determine relationships between cardiac and vascular assessments and each adverse pregnancy outcome, adjusting for lean mass index (LMI) and current systolic blood pressure (SBP). Results: Data from a total of 147 women (45.5 ± 3.9 years) were analyzed, where 30 (25.6%) reported preterm birth and 21 (19.7%) HDPs in one or more pregnancies. LMI and SBP were significantly associated with both LVMI and PWV (p<0.001) but race and overall parity were not. In unadjusted analyses, women with a history of preterm birth or HDP had significantly higher LVMI (mean difference ± SE: 4.36 ± 2.08 g/m 2.7 , p=0.04 and 4.70 ± 2.12 g/m 2.7 , p=0.03, respectively) and higher current SBP (difference: 6.84 ± 3.15 mmHg, p=0.03 and 11.8 ± 3.07 mmHg, p=0.0002, respectively) compared to those who did not. Adjusting for LMI and SBP, the relationships between preterm birth and HDP with LVMI were attenuated (both p=0.07). PWV was not associated with history of HDP or preterm birth. Conclusions: Pre or peri menopausal women with histories of preterm birth or HDPs may be at risk for increased left ventricular mass. Closer post-pregnancy monitoring of women with a history of preterm birth or HDP may help prevent later cardiovascular outcomes.

Abstract TH819: Association between adherence to the Dietary Approaches to Stop Hypertension and cognitive performance in individuals with and without diabetes: data from a large population-based study from Germany

Background: Diabetes is a known risk factor for impaired cognitive function. Higher adherence to healthy dietary patterns, such as the Dietary Approaches to Stop Hypertension (DASH), is associated with lower risk of cognitive impairment in healthy individuals. Whether the association of DASH with cognitive function differs by diabetes status is not well known. Objectives: In the German National Cohort (NAKO), we assessed the cross-sectional association of adherence to DASH with cognitive performance in individuals with and without diabetes. Methods: The study sample comprised n=5,986 individuals with diabetes and n=93,128 individuals without diabetes from the NAKO baseline examination (51.3% women, age 48.7 (±12.2) years). Dietary intake was assessed with a multiple source method combining up to four 24h dietary recalls with a self-administered, validated Food Frequency Questionnaire. Cognitive performance was assessed by a brief cognitive test battery (semantic fluency, 12-word list recall task (verbal memory), Stroop test (cognitive interference), and digit span backwards (working memory capacity)). Linear regression models stratified by diabetes status were used to relate DASH (effects per 5-point increment) to cognitive performance (as 1-point increments), adjusting for age, sex, body mass index, smoking, socioeconomic status, physical activity, alcohol, daily energy intake, German language ability, and prevalence of neurological or psychiatric diseases. Results: In multivariable-adjusted models, better adherence to DASH was associated with better performance in semantic fluency (ß Diabetes : 0.38 [95% CI: 0.21; 0.54], ß No Diabetes : 0.34 [95% CI: 0.31; 0.38]) and verbal memory (ß Diabetes : 0.06 [95% CI: 0.02; 0.11]; ß No Diabetes : 0.05 [95% CI: 0.04; 0.06]) irrespective of diabetes status. By contrast, better performance in cognitive interference with better adherence to DASH was only observed in individuals without diabetes (ß Diabetes : 0.01 [95% CI: -0.36; 0.38], ß No Diabetes : -0.28 [95% CI: -0.34; -0.22], p Interaction > 0.05 ). For working memory capacity, no clear association with DASH adherence was observed (ß Diabetes : 0.01 [95% CI: -0.02; 0.04], ß No Diabetes : 0.01 [95% CI: 0.00; 0.02]). Conclusion: Better adherence to the DASH diet was associated with better semantic fluency and verbal memory in individuals irrespective of diabetes status, while the protective association of DASH with cognitive interference was only seen in individuals without diabetes.

Abstract MPTH74: Metabolomic Responses to Diets Varying in Carbohydrate and Glycemic Index Are Linked to Improved Glucose Metabolism and Insulin Sensitivity: OmniCarb and POUNDS Lost

Background: The effects of reducing dietary carbohydrate intake and glycemic index (GI) levels on temporal changes in blood metabolomic profiles and their impact on improving glucose tolerance remain unclear. Aim: We examined temporal changes in circulating metabolites induced by lowering dietary carbohydrate content and GI levels and aimed to identify specific metabolites associated with improved glucose tolerance and insulin sensitivity. Methods: We analyzed data from 162 adults in the OmniCarb trial, a crossover feeding study of diets varying in carbohydrate amount and GI levels. Each diet was consumed for 5 weeks, with at least a 2-week washout period. Global metabolomics was repeatedly performed to calculate temporal changes. Oral glucose tolerance tests (OGTTs) were conducted for all participants; 12-hour meal tests were performed in a subsample (n=59). To validate and explore long-term associations in an independent study (n=670), we analyzed 6-month changes in metabolites in response to weight-loss diets varying in macronutrient composition among participants in the POUNDS Lost trial. Results: At baseline, 189 of 906 analyzed metabolites showed suggestive associations (crude p <0.05) for the area under the curve of glucose during the OGTT, and 51 metabolites remained significant after correcting for multiple testing (P-FDR <0.05). We found that 170 metabolites (19%) after overnight fasting were significantly modified by lowering carbohydrate amount and GI. In addition, at 30 minutes post-meal (after breakfast), 101 metabolites changed significantly, indicating that the low-carbohydrate, low-GI diet altered postprandial metabolite responses. Particularly, changes in gut microbiota-related metabolites, including 3-hydroxybutyrate, 3-aminoisobutyrate, kynurenate, N-acetylglycine, and hippurate, were associated with improved 12-hour postprandial glucose responses following the low-carbohydrate, low-GI diet. In the POUNDS Lost trial, 6-month increases in 3-hydroxybutyrate, 3-aminoisobutyrate, and N-acetylglycine were associated with greater reductions in fasting glucose and insulin resistance at 6 months. These initial (6-month) metabolite changes were associated with 2-year improvements in glucose metabolism and insulin sensitivity. Conclusions: Dietary interventions focusing on carbohydrate amount and GI altered circulating metabolites, including gut microbiota-related metabolites, which were linked to improved glucose tolerance and insulin sensitivity.

Impact of formal and informal finance on environmental sustainability in developing countries

Abstract TU238: Cumulative cardiovascular health over two decades and subclinical target organ damage in the Framingham Heart Study

Introduction: Single measures of cardiovascular health (CVH) have been related to risk of numerous outcomes beyond cardiovascular diseases (CVD). However, data are sparse regarding associations of cumulative CVH exposure across the life course with subclinical target organ damage (TOD) throughout the body. Methods: We included Framingham Heart Study (FHS) Offspring participants who had data to calculate repeated Life’s Essential 8 (LE8) scores (range, 0-100; higher scores = better CVH) and were free of CVD at Exams 1-5 (1971-1995). Cumulative LE8 scores over time were estimated using a nonparametric cubic spline-based mixed effects model to compute the participant-specific cumulative area under the curve (AUC) of LE8 score from Exams 1-5, expressed as point-years (i.e., LE8 score of 60 points for 20 years ≈ 1200 point-years). Lower cumulative LE8 scores (e.g., lower point-years) indicate less favorable cumulative CVH exposure. Sixteen markers of cardiac, renal, pulmonary, and metabolic TOD were assessed at Exam 6 or later (1995-onwards). Nonlinear associations between cumulative LE8 scores and these 16 markers of subclinical TOD were examined using generalized additive models with a restricted cubic spline function, adjusted for age and maximal education, separately by sex. Results: Among 2546 FHS participants, mean (SD) age at baseline was 35 (9) years, 1422 (56%) were female, and the mean (SD) cumulative LE8 score was 1215 (194) point-years over a 20-year period. In female participants (Figure) , lower cumulative LE8 scores were associated with evidence of more adverse cardiac and vascular remodeling/injury (carotid intima-medial thickness, coronary artery calcium [CAC] score, high CAC burden, left ventricular mass index), renal dysfunction (urine albumin-creatinine ratio), worse pulmonary function (forced expiratory volume to forced vital capacity ratio, diffusion capacity), and metabolic dysfunction (hemoglobin A1c, total fat mass, subcutaneous adipose tissue). Cumulative LE8 scores were weakly associated with left ventricular ejection fraction, estimated glomerular filtration rate, high-sensitivity troponin I, and total lean mass. Similar patterns were observed among male participants. Conclusion: Higher cumulative CVH across the life course was associated with lower cardiac, renal, pulmonary, and metabolic TOD. Public health strategies are needed to promote and maintain high LE8 scores at all ages to prevent TOD and progression to clinical events.

Abstract 12: Phthalate Exposure as a Second Hit for APOL1-Associated Chronic Kidney Disease Progression

Introduction: Carrying two risk alleles in the apolipoprotein L1 ( APOL1 ) gene is a well-established risk factor for chronic kidney disease (CKD) and its progression among African Americans. However, many high-risk individuals do not develop CKD or experience rapid progression, suggesting that environmental “second hits” may be required to trigger the adverse effects. We tested the hypothesis that phthalates, ubiquitous environmental pollutants linked to podocyte injury, act as a “second hit” that exacerbates APOL1 -associated CKD progression. Methods: We examined APOL1 -phthalate interactions among 1,347 African American patients with CKD from the Chronic Renal Insufficiency Cohort (CRIC) and replicated findings in 289 African American CKD patients from the Atherosclerosis Risk in Communities (ARIC) study (Table). APOL1 genotypes were classified as high-risk (2 risk alleles) or low-risk (0/1 risk alleles). Phthalate exposure was assessed by monobutyl phthalate acyl-β-glucuronide (MBPAG) and monoethyl phthalate O-β-glucuronide (MEPOG) measured from 24-hour urine samples at baseline and dichotomized at cohort-specific medians. CKD progression was defined as incident end-stage kidney disease (ESKD) or ≥50% estimated glomerular filtration rate (eGFR) decline in CRIC and as ESKD or ≥30% eGFR decline in ARIC. Multivariable Cox models adjusted for age, sex, study sites, BMI, smoking, drinking, blood pressure, diabetes, and cardiovascular disease in the base model, and additionally for eGFR and proteinuria in the full model. Results: Over a mean 6.5 years of follow-up in both CRIC and ARIC, MBPAG significantly modified the association between APOL1 genotypes and CKD progression (P for interaction=5.3×10 -5 in CRIC and 0.04 in ARIC, Figure). In CRIC, the APOL1 high-risk genotype was associated with increased risk only among participants with high MBPAG levels (Hazard ratio [HR]=1.97; 95% confidence interval [CI]: 1.49–2.62; P=2.3×10 -6 ), but not in those with low MBPAG (HR=1.03; 95% CI: 0.79–1.35; P=0.80). Similar findings were observed in ARIC, where high MBPAG levels amplified the effect of APOL1 high-risk genotypes on CKD progression (HR=2.62; 95% CI: 1.26–5.47; P=0.01), but not at low MBPAG levels (HR=0.19; 95% CI: 0.02–1.51; P=0.12). The interactions remained significant in fully adjusted models, with consistent results for MEPOG. Conclusions: Phthalate exposure amplified the adverse effect of APOL1 high-risk genotypes on CKD progression among African Americans.

Abstract WE523: Prevalence of Clinical Obesity in Brazilians: Cross-Sectional Results from the Health Survey of São Paulo with a Focus on Nutrition

Introduction: Obesity has traditionally been defined using BMI thresholds. While BMI is useful for population screening, it sometimes misclassifies individuals. Considering this, Lancet Diabetes&Endocrinology Commission introduced a new clinical obesity definition in January 2025, shifting the focus from body size to obesity-related pathophysiology and functional impairment. It remains uncertain whether this approach identifies a group distinct from that classified by classical tools. We examined the prevalence of clinical obesity in São Paulo. Hypothesis: We hypothesized that prevalence varies by sociodemographic and lifestyle factors, with distinct patterns by sex and age. Methods: This representative cross-sectional population-based study included 610 adults and older adults from the 2015 Health Survey of São Paulo with focus on Nutrition. BMI and waist circumference (WC) were measured using standardized procedures and categorized by validated cut-offs. Clinical manifestations were identified using ICD codes and self-reported conditions, following Lancet Diabetes&Endocrinology Commission criteria. Weighted means, prevalence estimates, and 95% confidence intervals accounted for the complex survey design. Analyses were performed in RStudio. Results: Overall, 24.9% (95% CI: 21.5, 28.8) had BMI ≥30 kg/m2. Preclinical obesity occurred in 6.6% (95% CI: 4.6, 9.2), and clinical obesity in 19.1% (95% CI: 15.9, 22.8). BMI ≥30 kg/m2 and preclinical obesity were more frequent among women than men (31.8%, 95% CI: 26.4, 37.2 vs. 9.6%, 95% CI: 5.9, 13.2). Preclinical obesity was higher among adults (8.6%, 95% CI: 5.4, 11.8), and clinical obesity among older adults (26.8%, 95% CI: 20.6, 33.1). Prevalence of clinical obesity among adults was higher for those living with a partner, ≥10 years of schooling, and never smokers; among older adults, for White or Asian individuals, and never smokers. Among women, prevalence was higher among never smokers, whereas among men, it was higher among White or Asian individuals, those living with a partner, and with ≥10 years of schooling. Across all groups, prevalence was higher among those not meeting physical activity recommendations. Conclusion: The new clinical definition identifies a group with distinct sociodemographic and lifestyle patterns. Further studies are needed to determine whether this classification offers advantages over BMI alone in identifying individuals at higher risk and guiding public health actions.

The effects of social media addiction on depression and anxiety among university students: The mediating role of family environment

Abstract The significant mental health concerns have been highlighted by the rising incidence of social media addiction among university students. This research examined the relationship between social media addiction (SMA) and both depression and anxiety, while exploring the mediating effect of the family environment (FE) among Saudi university students. A cross-sectional survey was conducted between January and February 2025 among 627 students from four Saudi public universities (376 men and 251 women). Using SPSS 25.0 and AMOS 25.0, descriptive, correlational, and mediation analyses were conducted. Significant positive relationships were seen between SMA and anxiety ( r  = 0.41, p  < 0.001) and depression ( r  = 0.37, p  < 0.001). Additionally, there was a strong correlation between the family environment and anxiety ( r  = 0.42, p  < 0.001) and depression ( r  = 0.31, p  < 0.001). The indirect effects were statistically significant (bootstrapped 95% CI not containing zero), and mediation analysis showed that FE fully mediated the connections between SMA and both anxiety and depression. These results highlight the need for early treatments that address students’ social media-related discomfort while creating a nurturing home setting to mitigate the psychological effects of excessive social media use.

Abstract TH974: Left Ventricular Mass Index Changes across 20 Years of Follow-up Among Pre-Menopausal Women: The National Growth and Health Study

Introduction: Left ventricular mass index (LVMI) is a known risk factor for cardiovascular (CV) disease. However, little is known about changes in LVMI across the lifespan, especially in relation to reproductive history. Hypothesis: We hypothesized that LVMI would increase over time, particularly among women with higher parity or higher CV risk factors in young adulthood. Methods: Participants from the National Growth and Health Study were assessed for LVMI, body composition by DEXA, anthropometry, lab values and blood pressure in young adulthood and midlife using consistent protocols. LVM was assessed by echocardiography and indexed to height 2.7 . Fat free mass index (FFMI, kg/m 2 ) was calculated as FFM divided by height (m) 2 . Systolic and diastolic blood pressures (SBP and DBP) were measured seated using an automated device. Spearman correlations, paired t-tests and general linear models were used in analysis. Results: In 161 women (53% Black), LVMI was assessed at baseline at a mean age of 25.5 ± 1.6 years and at follow up at a mean age of 46.2 ± 0.9 years. Over the 20 year period, LVMI increased by a mean (±SE) of 3.6 ± 0.8 g/m 2.7 and FFMI decreased by a mean of -0.76 ± 0.16 kg/m 2 (both p<0.0001). Baseline LVMI was significantly higher with greater parity at baseline (range 0-6), adjusting for FFMI (p=0.002), but follow-up LVMI was not associated with total parity (range 0-8; p=0.87; Table). Change in LVMI across 20 years were significantly correlated with baseline measures of LVMI (-0.39, p<0.0001), glucose (0.19, p=0.049) and parity at baseline (-0.17, p=0.03), but not baseline lipids, BP or FFMI. Changes in LVMI were also significantly correlated with differences in age (0.20, p=0.009) and FFMI over time (0.40, p<0.0001) and with current measures of DBP (0.17, p=0.04), insulin (0.24, p=0.003), high sensitivity CRP (0.26, p=0.001), HDL-C (-0.19, p=0.02), and total parity at follow-up (-0.18, p=0.03). In adjusted models, increases in LVMI were independently associated with increases in FFMI (p<0.0001), greater current DBP (p=0.01) and lower total parity (p=0.004). Conclusions: Greater increases in LVMI over 20 years of follow-up were seen among women with lower parity but not baseline CV risk factors. However, this negative association is likely due to higher initial LVMI and FFMI among women with greater parity by baseline age 25. Women with early parity should be evaluated for increases in LVMI, which may increase CV risk across the lifespan.

Abstract WE454: Trends in Global Cardiovascular Disease Mortality from 1990 - 2022

Introduction: Heart disease remains the leading cause of mortality worldwide. We examined global heart disease mortality trends over the past three decades to assess progress made and to identify areas of need, including regional disparities. Methods: We used data from the Institute for Health Metrics and Evaluation (IHME) Global Burden of Disease program. We analyzed the age-adjusted mortality from 1990 to 2022 for overall heart disease, ischemic and non-ischemic heart disease, and by non-ischemic subtypes including atrial fibrillation and flutter, cardiomyopathy, endocarditis, hypertensive heart disease, myocarditis, non-rheumatic valvular heart disease, pulmonary arterial hypertension, rheumatic heart disease, and other cardiovascular and circulatory diseases. For 2022, we compared age-adjusted mortality of ischemic and non-ischemic subtypes by IHME socioeconomic and geographic regions. Results: From 1990 to 2022, overall global heart disease age-adjusted mortality decreased 35%, from 358 per 100,000 to 233 per 100,000. Ischemic heart disease mortality decreased 33%, from 160 per 100,000 to 108 per 100,000 (Figure 1). Mortality for all non-ischemic subtypes decreased except for atrial fibrillation and flutter, which increased 9.5% (Figure 2). Notably, cardiomyopathy mortality decreased 71% and rheumatic heart disease mortality decreased 57%. In 2022 there were notable disparities; Mortality for cardiomyopathy in Central&Eastern Europe / Central Asia was three times greater than the global mortality rate (Figure 3). Mortality for hypertensive heart disease in Sub-Saharan Africa and the Middle East&North Africa was over twice the global mortality rate. Mortality for rheumatic heart disease in South Asia was more than three times the global mortality rate. Interpretation: Significant progress has been made in heart disease mortality over the last three decades. However, disparities exist by geographic and socioeconomic region, particularly for cardiomyopathy, hypertensive heart disease, and rheumatic heart disease. Public health strategies addressing resource allocation and equitable access to prevention and treatment are needed. Conclusion: There have been substantial declines in global heart disease mortality. However, stark regional disparities underscore the urgent need for targeted prevention and treatment efforts.