Browse Articles
Discover research articles across all indexed journals
Abstract 32: Sleep Characteristics and Plasma Biomarkers of Alzheimer’s Disease Pathology, Neurodegeneration, and Neuroinflammation: The Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS)
Introduction: Abnormal sleep has been linked to increased dementia risk, but the pathophysiological processes driving this connection are unclear. To provide insight into the biological pathways underlying the relationship between sleep and brain health, we tested the hypothesis that increased obstructive sleep apnea (OSA) severity and shorter habitual sleep duration are associated with a higher burden of Alzheimer’s disease (AD) pathology, neurodegeneration, and neuroinflammation measured through plasma biomarkers. Methods: ARIC participants who took part in the Sleep Heart Health Study at Visit 4 (1996-98) with stored plasma samples at Visit 3 (1993-95) and Visit 5 (2011-13) were examined (n=261; mean age 61.3 years; 43.3% male). OSA severity, categorized based on the number of apneas and hypopneas per hour of sleep (<5 events/hour [Normal], 5 to <15 events/hour [Mild OSA], or ≥15 events/hour [Moderate/Severe OSA]) was assessed via in-home polysomnography, and average habitual sleep duration (<7 hours, 7 to <8 hours, or ≥8 hours) was self-reported. Plasma biomarkers of amyloid beta (Aβ) 42 and 40, phosphorylated Tau 181 (p-Tau181), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) were measured using Quanterix Simoa immunoassays. Covariate-adjusted linear regression models estimated associations of sleep indices in 1996-98 with standardized plasma biomarker measurements in 1993-95 (3 years earlier) and in 2011-13 (15 years later). Covariate-adjusted linear mixed effects models quantified associations of sleep measures with the 5-year rates of change in standardized biomarker levels (1993-2013). Results: Compared to a habitual sleep duration of 8 hours or more, sleeping less than 7 hours per night was associated with higher NfL, a biomarker of neurodegeneration, 15 years later (β = 0.252; 95% confidence interval [CI]: 0.003, 0.501). Sleep indices were not associated with biomarker levels 3 years earlier. Counter to our hypothesis, Moderate/Severe OSA was associated with slower increases in p-Tau181 (β = -0.102; 95% CI: -0.198, -0.006), a biomarker of AD pathology, over a median of 17.9 years. Conclusions: Short habitual sleep duration may impact dementia outcomes through neurodegenerative and other processes rather than through pathways specific to AD pathology or neuroinflammation. Longitudinal studies with sleep measurements in larger, more diverse samples are needed to further distinguish the pathways linking sleep to dementia.
Abstract WE562: Community-engaged Intervention Improves Cardiovascular Health Literacy
Background: Cardiovascular complication accounts for 26.7% of maternal deaths in the United States. Women residing in maternity care deserts (MCDs) face higher risks from cardiac complications. People with limited health literacy have fewer health-promoting behaviors, report poorer health status, and underuse preventive services. Hypotheses: Reproductive aged women residing in maternity desserts who access Pre-pregnancy and Interpregnancy Engagement for Alabama’s Cardiovascular Health (PEACH) intervention will show higher comprehensive knowledge about the American Heart Association’s (AHA) Life’s Essential 8 on a pre and post assessment. Methods: We adopted the Intervention Mapping (IM) Framework to develop the Pre-pregnancy and Interpregnancy Engagement for Alabama’s Cardiovascular Health (PEACH) intervention to improve cardiovascular health (CVH) literacy among reproductive-aged women residing in two MCDs in Alabama. The six steps of the IM framework include: 1) A needs assessment to determine CVH literacy needs in the target population. 2) Using the AHA’s Life’s Essential 8, we 3) identified the change objectives for the intervention. 4) We established an Expert Panel comprising lived experiences experts, community leaders/members, community health workers (CHWs), and health professionals to validate the design and development of the intervention materials including CHW training curriculum and facilitation guide, videos, interactive games and workbook. 5) We engaged key community stakeholders in the two MCDs to determine the best delivery strategies. 6) We delivered the intervention through in-person and virtual workshops. Enrolled participants were paired with CHWs for three months of community-based support. We used the Acceptability of Intervention Measure (AIM) scale to assess acceptability and the CVH literacy scale to assess knowledge gain between pre- and post-workshop. Results: Thirty-four (34) women participated in the in-person and virtual workshops; 24 completed the pre- and post-workshop surveys. Participants reported the workshops as engaging and informative. The mean acceptability (AIM) score was 4.6 (SD = 0.68) on a 1-5 scale and the mean CVH literacy improvement score was 1.1 points. Conclusion: The PEACH intervention was acceptable to participants and improved their CVH literacy.
Dynamic anticounterfeiting and tunable lasing with screen-printed cholesteric liquid crystal elastomers
Structural colors hold significant application value in anticounterfeiting, displays, and smart coatings due to their high stability, eco-friendliness, and dynamic optical response potential. However, conventional fabrication strategies for photonic crystals—such as photolithography and inkjet printing—suffer from limitations including high mask costs, nozzle clogging, lattice defects, and difficulties in scaling production. This study introduces an innovative screen-printing technique to achieve high-fidelity and multicolor structural color patterning based on cholesteric liquid crystal elastomers (CLCEs), overcoming key challenges in controlling the alignment of mesoscopic helical structures and ensuring spatial homogeneity of the photonic bandgap. Crucially, the chiral helical superstructure of CLCEs was investigated, revealing its decisive role in governing the circular polarization properties of the reflected light. The printed patterns exhibit dynamic optical behaviors, including viewing-angle-dependent color shifts, inherent selective circularly polarized reflection dictated by the handedness of the helix, and reversible mechanochromic responses under strain. Furthermore, integration of photochromic spiropyran enables multistimulus-responsive color and fluorescence switching under light and thermal stimuli, as well as ultraviolet-tunable (645 to 685 nm) random lasing emission. This work demonstrates that screen-printed CLCEs, with their excellent substrate compatibility and scalability, constitute a promising platform for next-generation anticounterfeiting labels, smart packaging, and flexible photonic devices.
Abstract WE448: Escalating Cardiovascular Mortality in Inflammatory Bowel Disease: A 22-Year National Analysis Revealing Alarming Geographic, Rural-Urban, and Racial Disparities in the United States, 1999-2020
Background: Inflammatory bowel disease (IBD), encompassing Crohn’s disease and ulcerative colitis, is increasingly linked to cardiovascular disease (CVD) through systemic inflammation, endothelial dysfunction, and treatment-related metabolic effects. Yet, long-term population-level trends and disparities in IBD-related cardiovascular mortality remain underexplored. Methods: We analyzed national mortality data from CDC WONDER (1999–2020), identifying deaths with IBD (ICD-10 K50–K51) as a contributing cause and CVD (I00–I99) as the underlying cause. Age-adjusted mortality rates (AAMRs) per 100,000 population were calculated, and temporal trends were quantified using Joinpoint regression to estimate Average Annual Percent Change (AAPC). Trends were stratified by region, urbanization, age, sex, race, and Hispanic origin. Results: A total of 11,891 deaths were recorded nationally, with mortality rising from 0.21 to 0.22 per 100,000 (AAPC +1.0%, 95% CI 0.3–1.7; p<0.05). A 22.5% spike occurred in 2020 (723 vs 590 deaths in 2019). Regionally, the South recorded 3,660 deaths (30.8%) and the steepest rise (AAPC +1.9%), while the Northeast declined (AAPC –0.8%). Rurality showed a strong inverse gradient: large central metros declined (AAPC –1.2%), but rural noncore counties rose +2.8%, representing a 4-fold disparity. Age-specific trends showed increasing mortality in 55–64 years (1,427 deaths; 0.19/100,000) despite declines in older cohorts. Females accounted for 6,409 deaths (53.9%) with AAPC +0.4%, whereas males (5,482 deaths) had AAPC +1.2%, tripling the female growth rate. Racial gaps widened: White 11,069 (93.1%, AAPC +1.8%), Black 684 (5.8%, AAPC +5.2%), Asian/Pacific Islander 95 (0.8%, +3.1%), and American Indian/Alaska Native 43 (0.4%). Black Americans had 2.9-fold higher AAPC than Whites. Hispanic populations (276 deaths; AAPC +2.4%) showed 2.7-fold faster increases than non-Hispanics. Conclusions: From 1999–2020, IBD-related CVD mortality increased +1.0% annually, with three intersecting disparities: geographic (South +1.9%), rural–urban (+2.8% vs –1.2%), and racial (Black +5.2%). The 2020 surge highlights vulnerability during systemic crises. Rising deaths among 55–64-year-olds suggest premature cardiovascular aging in IBD. These findings call for integrated IBD–cardiology care, rural and minority-focused interventions, and mechanistic studies into inflammation-accelerated atherosclerosis.
Abstract TU169: Healthy Dietary Patterns Are Associated With Lower Cardiovascular Risk and All-Cause Mortality Among Hypertensive Adults
Introduction: Healthy dietary patterns have been consistently linked to lower risks of cardiovascular disease (CVD) and mortality in the general population. However, evidence among individuals with established hypertension remains limited. Hypothesis: We hypothesized that higher adherence to healthy dietary patterns are associated with lower risks of incident CVD and all-cause death among adults with hypertension. Methods: We analyzed participants with hypertension and no prior CVD from the UK Biobank. Diet quality was assessed using 24-hour dietary recall questionnaires. Five versions of dietary indices were calculated: the Dietary Approaches to Stop Hypertension (DASH) score, the Alternative Healthy Eating Index-2010 (AHEI-2010), the Alternate Mediterranean Diet (AMED) score, the healthful Plant-Based Diet Index (hPDI), and the Empirical Dietary Inflammatory Pattern (EDIP) index. Multivariable-adjusted Cox models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between each index and outcomes. Results: During 1,230,983 person-years of follow-up in 83,248 participants with hypertension, 4,889 CVD events and 8,276 deaths occurred. Compared with the lowest quintile, the highest quintile of DASH adherence was associated with lower CVD risk (HR 0.85, 95% CI 0.77–0.93, p for trend = 0.003), as was a lower inflammatory diet (reversed EDIP; HR 0.89, 0.81–0.97 , p for trend = 0.009). AHEI-2010 showed a borderline association (HR 0.91, 0.83–1.00, p for trend = 0.062), while AMED and hPDI were not significant. All five dietary scores were inversely associated with all-cause mortality (HRs 0.77–0.85; all P for trend < 0.01). The foods that were associated with lower mortality include vegetables, whole grains, nuts and legumes, fruits, and vegetable oil, while foods associated with increased CVD risk or mortality include sugar sweetened beverage and red meat. Conclusions: Among adults with hypertension, adherence to healthy dietary patterns—especially the DASH and low-inflammatory diets—was associated with lower risks of CVD and all-cause mortality.
Abstract TU115: Cardiovascular-Kidney-Metabolic Stage Three Prevalence in the Community: A Comparison of Different Criteria
Background: The American Heart Association’s Cardiovascular-Kidney-Metabolic (CKM) Stages, introduced in 2023, highlight the progressive and interrelated nature of metabolic risk factors, chronic kidney disease (CKD), and cardiovascular disease (CVD). Stage 4 is defined by clinical CVD or CKD, while stage 3 represents subclinical disease or a high-risk profile. Increasingly, studies are investigating the epidemiology of CKM stages in the community. However, few have utilized all proposed stage 3 criteria, potentially leading to misclassification. Methods: We compared CKM stage 3 classification using different criteria in Framingham Heart Study (FHS) participants. We classified participants as stage 4 if they had a history of coronary heart disease (CHD), heart failure (HF), stroke, peripheral artery disease (PAD), atrial fibrillation (AF), or CKD stage 4a/4b. From the remaining sample, we compared the prevalence of stage 3 CKM with the commonly used “epidemiologic criteria” (PREVENT CVD risk score ≥20% or very high-risk CKD) versus complete stage 3 criteria, which additionally include coronary artery calcium score (CAC) ≥100, elevated left ventricular (LV) mass, high cardiac biomarkers, or very-high risk CKD. Results: Among 3424 participants (mean age 60±9 years, 53% female, with body mass index 28±5 kg/m 2 ), 371 met criteria for CKM stage 4, including CHD (157), HF (40), stroke (87), PAD (107), AF (100), or CKD stage 4a/4b (17). Of the remaining 3053 participants , 1160 (38%) were classified as stage 3, using the complete criteria, compared with 304 (10%) using the “epidemiologic criteria.” In a subsample of 780 individuals with complete subclinical data, 361 (46%) met complete stage 3 criteria, compared with only 38 (5%) using the epidemiologic criteria. Most individuals with elevated CAC (90%), LV mass (87%), cardiac biomarkers (85%), or high-risk CKD (67%) do not have PREVENT scores of ≥20% and most have a single abnormal subclinical measure ( Figure 1A ). We then explored proportions of individuals identified by lower PREVENT thresholds ( Figure 1B ). Conclusions: Categorization of stage 3 CKM in the absence of comprehensive subclinical disease domains is challenging and leads to misclassifying individuals’ true risk. Future studies should evaluate whether lowering the PREVENT score threshold would improve the classification of subclinical risk for stage 3 CKM in the absence of comprehensive subclinical CVD phenotypes.
The cross-linking activity of transglutaminase 2 drives α-Synuclein pathology in synucleinopathy models
Transglutaminase 2 (TG2) is implicated in synucleinopathies including Parkinson’s disease (PD) and dementia with Lewy bodies, as it promotes α-Synuclein (α-Syn) aggregation in vitro, and evidence for its activity is detected in Lewy bodies in human postmortem brains. Additionally, TG2 overexpression exacerbates α-Syn toxicity in double transgenic mice, while TG2 deletion mitigates the phenotype of α-Syn transgenic mice. Considering that TG2 is a multidomain and multifunctional protein, the present study was carried out to confirm that the transamidase activity of TG2 specifically drives its pathogenetic role in synucleinopathies. We generated transgenic mice expressing a catalytically inactive W241A mutant TG2 and compared them with TG2-overexpressing and TG2 knockout mice using the α-Syn preformed fibril (PFF) model. We also examined double transgenic mice coexpressing human α-Syn with either wild-type TG2 or mutant TG2, alongside α-Syn single transgenic controls. 6 mo post–PFF injection, or at 6 mo of age in the double transgenic lines, the exacerbation of the behavioral and neuropathological phenotype seen with TG2 overexpression was lost with mutant TG2 overexpression in both models. Parallel findings were replicated in PD patient induced pluripotent stem cell-derived dopaminergic neurons. These findings indicate that the cross-linking activity of TG2 plays a pivotal role in α-Syn aggregation and toxicity, underscoring its significance as a therapeutic target in synucleinopathies.
Abstract 41: Accumulation of Skeletal Muscle Adiposity over 18-years is Associated with Lower Cognitive Functioning: The Tobago Health Study
Background: Skeletal muscle adiposity (i.e. myosteatosis) increases with age and is a risk factor for cardiometabolic diseases. Recent studies suggest that myosteatosis may play a role in cognitive functioning. Prospective studies in African ancestry populations are sparse, yet this population has higher risks of myosteatosis and Alzheimer’s disease and related dementias than Whites. Aim: To investigate the association between changes in myosteatosis over an 18-year follow-up period and cognitive functioning among middle-aged and older African Caribbean men. Method: Two hundred ninety-two (292) men participating in the Tobago Health Study were analyzed. Calf muscle density (MD) was measured at baseline, follow-up visit (FV) 1 (6.2±0.4 years after baseline), and FV2 (12.0±0.8 years after FV1) using peripheral quantitative computed tomography, where lower density reflects greater myosteatosis. Neurocognitive functioning was assessed using validated tests at FV2 across 6 domains (global cognition (MoCA), executive function (Trails B), psychomotor speed (Digit Symbol, Trails A), language (Animals&Vegetables), memory (Word List Recall), and visual-spatial skills (Benson Figure Copy)). Individual slopes of MD change over time from linear regression were used as predictors in linear and Poisson regression models to test the association between cognition and longitudinal changes in MD. Results: At FV2, men were 69.5 ± 5.8 years old, with high prevalences of obesity (23.2%), hypertension (82.0%), and diabetes (25.0%). MD decreased over the 18-year follow-up period (-0.17 ± 0.24 mg/cm3 per year). After adjusting for demographics, baseline MD, muscle area, comorbidities, lifestyle factors, and medication use, a 0.1 mg/cm3 per year faster decline in MD was associated with a 0.286-point lower MoCA score (p=0.03). Similarly, a 0.1 mg/cm3 per year faster decline in MD was associated with a 1.71 second slower psychomotor speed (p=0.032). Yearly decreases in MD were also associated with worse semantic verbal fluency (β: -1.73, p=0.02). Conclusion: Faster declines in muscle density are associated with poor domain-specific cognitive performance and may signal early cognitive impairment. Future research should include women and focus on mechanisms to understand the role of myosteatosis in cognitive impairment.
Abstract TU279: Neighborhood as a Window to Women’s Health 15 Years After Pregnancy: Do Income and Food Access Play a Role?
Introduction: Food environment is directly related to food choice, diet quality, and health outcomes. Access, availability, and food cost are all factors in a food environment. Purpose: To determine if neighborhood factors can provide insight into women’s health in the years after pregnancy and examine if income and food accessibility relate to diet quality. Hypothesis: Women in low-income (LI), low-access (LA) areas in the Pittsburgh area will have lower Cardiovascular health (CVH) diet scores (less ideal diet quality). Methods: CVH was evaluated in the first 149 women (mean age 44 years; 15 years after pregnancy) recruited into the Window Brain Study with completed diet surveys (MEPA), using the American Heart Association’s Life’s Essential 8 (LE8). CVH scores (0-100, higher is healthier) were generated using LE8 components, including diet. Neighborhoods (census tracts) were assigned GeoIDs and matched with the USDA’s Food Access Research Atlas to assess access to food-stores (within ½-mile in urban areas or 10-miles in rural areas). It also identifies LI areas based on the Department of Treasury’s Markets Tax Credit program (tract poverty rate of 20+%; or a tract median family income is < 80% of their area’s median family income). Results: Women classified as LILA (N=35, 23%) had significantly lower CVH diet scores (25(25,50) vs 50(25,50) P=0.001) compared to not LILA (N=114) and scored significantly lower on the MEPA questionnaire ((7(6,9) vs 8(7, 10) P=0.005), as seen in Table 1. LILA also had higher HbA1C levels (5.55(5.20, 5.95) vs 5.40(5.10,5.50)) P= 0.021) and a history of gestational diabetes (17% vs 8% P=0.103). Overall CVH scores of the LILA group tended to be less healthy (63.3 ±12.7 vs 68.4 ± 13.6 P=0.108). Of the health behaviors, diet and physical activity (PA) had the lowest mean CVH scores in both groups. Conclusion: Enhanced nutrition education and awareness of food accessibility are critical to improve CVH. Diet quality and PA posit opportunities to improve overall CVH among women residing in LILA neighborhoods.
Abstract 22: Cooking Oil Choice and Cardiometabolic Risk Among Asian Indians: Evidence from the Indian Council of Medical Research-India Diabetes (ICMR-INDIAB) National Study
Background: The type of cooking oil used is an under recognized dietary factor influencing cardiometabolic disease in India. Little is known about how commonly used oils relate to cardiometabolic risk in Asian Indians. Methods: We analyzed data from 18,090 adults (mean age=42y, 51% female) in the nationally representative ICMR-INDIAB study. Diet was assessed by a validated food frequency questionnaire where participants reported their top 3 cooking oils. Dyslipidemia was defined as high LDL-C (≥130 mg/dl), high triglycerides (≥150 mg/dl), and low HDL-C (men <40mg/dl, women <50 mg/dl) per NCEP ATP III guidelines. Logistic regression using sampling weights evaluated associations between main cooking oil, dyslipidemia, general (BMI≥25 kg/m 2 ) and abdominal obesity (waist >90cm men or >80cm women), adjusting for sociodemographic, lifestyle, and dietary factors. Results: Cooking oil preferences showed distinct regional patterns: mustard oil was predominant in North, East, Northeast, and Central regions; peanut (groundnut) oil in the West; palm, sunflower, and peanut oils in South, coconut oil in the state of Kerala (South); and soybean oil in states of Maharashtra (West), Madhya Pradesh (Central), and Mizoram (Northeast). Across India, users of coconut oil [OR=2.89 (2.03-4.11)], butter/ghee [OR=3.45 (1.48-8.03)] sunflower [OR=1.49 (1.12-1.97)], soybean [OR=1.81 (1.32-2.48)], or palm oil [OR=1.77 (1.27-2.46)] had a significantly higher odds of high LDL-C than those using peanut oil. Conversely, compared to peanut oil users, users of mustard oil [OR=0.68 (0.55-0.86)], sunflower oil [OR=0.80 (0.64-0.99)], and soybean oil [OR=0.72 (0.57-0.91)] had lower odds of low HDL-C. The likelihood of general obesity was higher among those using coconut oil [OR=1.45 (1.08-1.96)], sunflower oil [OR=1.45 (1.17-1.80)], or butter/ghee [OR=2.34 (1.12-4.89)] when compared to peanut oil users. No associations were observed with abdominal obesity. When examining fatty acid subtypes from cooking oils, each 2%E from saturated fat was associated with 6% higher odds of high LDL-C and abdominal obesity, while each 2%E from PUFA was linked to 3% lower odds of abdominal obesity. Conclusions: In this nationally representative sample of Indian adults, cooking oil choice was significantly associated with cardiometabolic risk. Promoting healthier oils, such as peanut and mustard oil, via dietary guidelines and the Public Distribution System, may help reduce dyslipidemia and obesity in India.
Phosphorus enrichment does not enlarge the predicted CO <sub>2</sub> fertilization effect on forest carbon sequestration
The capacity of nutrient-limited forests to enhance carbon (C) sequestration under elevated CO 2 (eCO 2 ) remains a critical uncertainty in C cycle modeling. While existing evidence suggests that low phosphorus (P) bioavailability may constrain CO 2 fertilization effects on plant growth, the extent to which this limitation modulates ecosystem responses to eCO 2 in forests adapted to P-deficient soils remains poorly understood. Here, using eight P-enabled models, we simulated the magnitudes and mechanisms through which P bioavailability interacts with eCO 2 , emulating an ecosystem-scale P enrichment experiment at a P-limited Eucalyptus forest undergoing long-term Free-Air CO 2 Enrichment. While models predicted pronounced P effects on tree growth, P enrichment unexpectedly did not increase the CO 2 effects on tree growth and ecosystem C sequestration. Models prioritized either CO 2 -driven or P-driven growth, but rarely both. This tradeoff emerged due to model-specific assumptions on 1) partitioning of the extra P in soil labile versus nonlabile pools; 2) plant photosynthetic acclimation to P deficiency; 3) C and nutrient use strategies regulating plant size and allocation; and 4) microbial-driven soil decomposition processes. By generating divergent yet biologically plausible outcomes, these predictions establish critical testable hypotheses for empirical research and highlight multiple P-related pathways that may influence the future land C sink.
Abstract TH977: Endometriosis and Early-Onset Cardiovascular Disease: Effect Modification by Systemic Inflammation and Age at Menarche
Introduction: Endometriosis, a chronic gynecological condition, has been increasingly associated with increased cardiovascular disease (CVD) risk. However, the mechanisms underlying this relationship remain poorly understood. Identifying biological factors that modify this relationship may help clarify underlying pathways and highlight women at higher cardiovascular risk. Hypothesis: We hypothesized that systemic inflammation and age at menarche will modify the association between endometriosis and early-onset CVD through shared hormonal and inflammatory pathways. Methods: We analyzed data from 5,546 women aged 20–54 years in the National Health and Nutrition Examination Survey (1999–2006). Endometriosis and early-onset cardiovascular disease (i.e., CVD before age 55) were based on self-reported physician diagnoses. Early-onset CVD included congestive heart failure, coronary heart disease, angina, myocardial infarction, or stroke. Systemic inflammation was defined using laboratory measures for serum C-reactive protein (CRP, mg/dL), and categorized as low/moderate (≤0.3 mg/dL) or elevated (>0.3 mg/dL). Age at menarche (mean 12.6 ± 0.03 years) was classified as early (≤11 years), normal (12–13 years), or late (≥14 years). Multivariable survey-weighted logistic regression were used to assess associations and effect modification by CRP and age at menarche, adjusting for age, race/ethnicity, smoking status, education, hypertension, diabetes, body mass index, and insurance status. Results: Of the 5,546 women, 379 (9.0%) reported endometriosis diagnosis, 170 (3.1%) early-onset CVD and 2665 (41.7%) had elevated CRP (≥3 mg/L). Endometriosis was associated with approximately two-fold higher odds of early-onset CVD (aOR = 2.1, 95% CI: 1.3-3.4). The association was stronger among women with elevated CRP (aOR = 2.9, 95% CI: 1.7-5.0) than among those with low/moderate CRP (aOR 1.1, 95% CI: 0.5-2.3; interaction P = 0.03). Similarly, the association between endometriosis and early-onset CVD was strongest among women with early menarche (aOR = 2.9, 95% CI: 1.2-6.8) but was not significant among those with normal (aOR = 1.8, 95% CI: 0.8-4.1) and late menarche (aOR = 1.4, 95% CI: 0.5-4.0; interaction P = 0.66). Conclusion: In this nationally representative sample of U.S. women, endometriosis was associated with higher odds of early-onset CVD, with stronger effects among women with elevated CRP and earlier menarche, underscoring their potential mechanistic role.
Abstract MPTH69: Metabolic Dysfunction-Associated Steatotic Liver Disease Across the Cardiovascular-Kidney-Metabolic Spectrum: Insights from the CARDIA Study
Background: The prevalence and prognostic impact of metabolic dysfunction-associated steatotic liver disease (MASLD), overall and across the cardiovascular-kidney-metabolic (CKM) spectrum, is uncertain. Methods: In the prospective Coronary Artery Risk Development in Young Adults (CARDIA) study, abdominal computed tomography was performed at a follow-up examination in 2010. MASLD was defined as hepatic steatosis (≤51 Hounsfield units) and ≥1 cardiometabolic criteria, without other causes of hepatic steatosis. The association between MASLD (vs. no MASLD) and clinical outcomes was evaluated. Subgroup analyses were repeated by CKM stage. Results: Among 2,600 participants with sufficient data (mean age, 50±10 years), 89% had CKM syndrome stage ≥1 ( Figure, A ); 24% had MASLD, with higher prevalence at higher CKM syndrome stages ( Figure, B ). After covariate adjustment, MASLD was associated with a higher rate of all-cause death (aHR, 1.90; 95% CI, 1.22-2.98), without heterogeneity across CKM stages ( P interaction =0.78) ( Figure, C ). MASLD was associated with a higher rate of incident cardiovascular events (aHR, 1.81; 95% CI, 1.23-2.65), observed primarily in those with CKM stages 0-1 ( P interaction =0.032) ( Figure, C ). Conclusions: MASLD impacted 1 in 4 middle-aged adults and was associated with cardiovascular and mortality events, particularly at earlier CKM stages. These findings suggest early MASLD recognition and intervention across the CKM spectrum may reduce long-term adverse outcomes.
Abstract TH881: Demographic and Cardiovascular Risk Factors Influence Midlife Cognitive Function: Evidence from the i3C DECADE Study
Introduction: Age, sex, race, and education are known determinants of cognitive performance in traditional neuropsychological testing; however, their impact on novel digital measures remains less defined. Digital assessments offer scalable, precise evaluations of cognition, potentially revealing subtle demographic differences relevant to early risk detection. Leveraging three distinct cohorts from the Disparities and Equity in Childhood Cardiovascular Exposures and Alzheimer’s Dementia (DECADE) project, we examined demographic influences on two digital cognitive tools. Methods: Participants included 236 adults (age 38-69 years; 79.5% female; 68.3% White) from three midlife DECADE cohorts, each with distinct racial/ethnic and socioeconomic profiles. Demographic predictors included age, sex, and race; obesity and hypertension were included, given their cognitive relevance. Cognitive performance was measured using two tablet-based instruments: the Rowan Digital Cancellation Test (RDCT), including letter, symbol, and mixed cancellation with outcomes of accuracy and processing speed, and the Digital Clock Drawing Task (dCDT), including command and copy conditions with metrics of latency, stroke conformity, speed, and total completion time. Standardized protocols were used across sites. One-way ANOVA models tested differences between demographic variables and digital outcomes, with post hoc comparisons to delineate group differences. Results: Older participants showed slower processing across RDCT (letter speed F=36.5, p<0.001 ; mixed speed F=29.8, p<0.001 ) and clock tasks. Women outperformed men on RDCT speed (letter F=22.9, p<0.001 ; symbol F=9.6, p=0.002 ) and clock copy time (F=4.9, p=0.027 ). Black participants exhibited longer clock command latencies (F=22.7, p<0.001 ), more stroke errors (F=6.9, p<0.001 ), and slower cancellation performance (letter speed F=10.5, p=0.001 ). Obese participants showed slower digital processing on clock average speed (F = 4.83, p = 0.02 ) and symbol speed F = 4.82, p = 0.029 ), whereas those with hypertension did not show any significant differences. Conclusion: Significant group differences were observed across digital cognitive outcomes by age, sex, race, and obesity status, consistent with patterns previously reported in traditional neuropsychological testing. Both the RDCT and dCDT were sensitive to these differences, supporting their utility as scalable tools for characterizing demographic variation in midlife cognitive performance
SUN5 forms a regular protein lattice reinforcing the sperm head–tail junction
Spermatozoa strongly rely on their streamlined morphology to successfully fertilize an oocyte. A striking example of a morphological defect resulting in infertility is acephalic spermatozoa syndrome, a rare but severe condition leading to detachment of the sperm head and tail. Among the most common genetic causes for this syndrome are mutations in the linker of nucleo- and cytoskeleton (LINC) complex component SUN5. LINC complexes typically reside in the nuclear envelope, the double-membrane surrounding the nucleus, where they establish a physical bridge between nucleus and cytoplasm. This localization allows them to transduce mechanical signals from the cytoplasm to the nucleus and to regulate nuclear morphology. In sperm, LINC complexes are essential for a multitude of morphological changes during sperm development, including the reshaping of the nucleus and establishing a stable head–tail junction. Here, using superresolution fluorescence microscopy, we find that sperm-specific SUN5 localizes to the base of the head in human, mouse, and boar sperm. By applying in situ cryoelectron tomography, we find an extensive hexagonal lattice in the nuclear envelope in this region. This lattice appears to maintain a consistent close apposition between the inner and outer nuclear membranes (ONM). Further structural analysis supports a model in which LINC complexes form this lattice by laterally interacting at the ONM. Overall, this study sheds light on nuclear envelope organization in the highly streamlined sperm cell, providing a structural basis for uniform nuclear envelope spacing maintained by a LINC lattice and rationalizing the disruptive effects of SUN5 mutations.
Abstract TH927: Validity of Ankle-Brachial Index and Other Modalities to Identify Peripheral Artery Disease in the Community
Background: Resting ankle-brachial index (ABI) is the first-line diagnostic test for lower extremity peripheral artery disease (PAD). Previous studies that reported high sensitivity and specificity (often >90%) of ABI included only clinically diagnosed PAD cases and non-PAD controls, overestimating measurement accuracy of ABI relative to unselected populations. A community-based study observed sensitivity of ~20%, but only included older adults aged around 70 years. Objective: To assess the validity of resting ABI to detect PAD among community-based adults and evaluate whether the addition of other tests (post-exercise ABI, toe-brachial index [TBI], and two types of waveforms [pulse volume recordings (PVR) and continuous Doppler]) can improve the diagnostic accuracy. Methods: We used data from the PAD Study of Study of Latinos (PASOS; 2020-24). Resting ABI and TBI were measured on each side. PVR waveforms were recorded using air plethysmography with ankle cuffs; continuous Doppler waveforms were assessed at the ankle and dorsum of the foot using a Doppler probe. Then, post-exercise ABI was measured after heel raises, performed 50 times or up to 2 minutes. We compared the validity of resting ABI ≤0.9, ≤1.0, and a comprehensive multi-modal definition: (1) resting ABI ≤0.9, (2) a post-exercise ABI drop ≥20% or an ankle blood pressure drop ≥30 mmHg, or (3) at least two abnormalities of TBI, abnormal PVR, and abnormal continuous Doppler waveforms. We considered arterial diameter reduction ≥50% or systolic peak velocity ≥200 cm/s in Duplex ultrasound as stenosis. Results: Among 405 participants (mean age 63.4 [SD 8.1] years; 64.2% female), there were 70 cases of PAD based on ultrasound detection of leg artery stenosis. ABI ≤0.9 alone showed a sensitivity of 17.1% and specificity of 96.7%, with Youden’s index of 0.14 ( Figure ). Using ABI ≤1.0 as the threshold for PAD, sensitivity reached 48.6% but specificity went down to 66.8%, with an unchanged Youden’s index of 0.15. The multi-modal approach had a sensitivity of 50.0% and specificity of 84.1%, with Youden’s index of 0.34. The results were largely consistent in the subset of high-risk group (n = 312). Conclusions: ABI ≤0.9 alone had a sensitivity of <20% for detecting PAD among middle-aged and older adults in the community, whereas additional modalities markedly improved the overall diagnostic accuracy. Our results have implications on strategies for PAD screening in the community.
Abstract TH839: Barriers to Enrollment and Attendance in Outpatient Cardiac Rehabilitation Access after TAVI in Tennessee
Background: Outpatient cardiac rehabilitation (OCR) is a recognized key component of secondary prevention of cardiovascular disease, particularly after procedures such as transcatheter aortic valve implantation (TAVI). Limited research has examined barriers among patients who have undergone TAVI, even as the number of these procedures continues to rise. Recognizing these barriers enables hospital and policy level strategies to provide targeted support and improve patient participation in OCR after TAVI. Objective: To identify key OCR barriers among patients who underwent TAVI at the University of Tennessee Medical Center using a nurse-designed survey and see whether barriers varied by age and sex. Methods: We identified individuals who underwent TAVI between 1/1/2021-5/31/2025 and contacted them to complete an online survey. Participants rated OCR barriers as “present”, “not present”, or “prefer not to answer”. For barriers without "prefer not to answer" responses and where there was participant response variation, Chi squared tests or Fisher’s exact tests were used to assess whether barriers differed by age (55-64, 65-74, 75-84, ≥85 years(y)) and sex. Results: Thirty-five individuals participated in the survey, and n=24 (95.8% > 65y, 54.2% female) completed the demographic and OCR sections. The most reported barriers were lack of transportation (58.3%) and physical limitations/health (25.0%). About 12.5% of survey participants cited other barriers such as OCR distance, financial constraints, lack of awareness, emotional or psychological challenges, and lack of family/friend support. Where sample size allowed for statistical testing, we observed that barriers such as lack of transportation, OCR distance, financial constraints, physical limitations/health, lack of family/friend support, and difficulty understanding OCR program materials did not vary significantly by age categories or sex. Conclusion: While many barriers did not differ by age or sex, nurse-led identification of transportation as a major barrier for >50% of participants to undergo OCR post TAVI is notable. This finding highlights the need for targeted clinical and policy solutions to improve OCR access in this Tennessee patient population.
Abstract TU195: Comparison of Large-Scale Proteomics Platforms: The Dallas Heart Study
Introduction: Large-scale proteomic profiling plays an important role in the identification of novel biomarkers. We compared the performance of three proteomics platforms in a multi-ethnic cohort in terms of cross platform agreement and technical variability. Methods: Among community-based participants in the multi-ethnic Dallas Heart Study who participated in the third study phase (2020-2024), we measured proteomics using two affinity-based platforms (SomaLogic 7k; Olink Explore HT) and a mass spectrometry platform (SEER Proteograph) in 186 participants. Eighteen samples were also randomly selected to be run as blind duplicates, which were then used to calculate the coefficient of variation (CV) for each protein. Proteins measured across platforms were matched based on Entrez gene name, and cross-platform Spearman correlations were calculated. Results: Mean age was 60±11 years, 51% were female, 53% reported Black race, 22% reported Asian race, and 7% reported Hispanic ethnicity. The total number of proteins assayed and the number detectable in >50% of samples for each platform were: Olink 5,420 and 2,348 respectively; SomaLogic 7,138 and 7,172 respectively; and SEER 7,796 and 6,831 respectively ( Figure 1A ). Cross-platform correlations were modest, with a median [25 th -75 th percentile range] of 0.49 [0.20-0.70] for SomaLogic vs Olink; 0.32 [0.15-0.51] for SomaLogic vs SEER; and 0.35 [0.17-0.49] for SEER vs Olink. Inter-assay CV was lowest for SomaLogic, and for both SEER and Olink, technical variability tended to decrease as the protein detectability increased ( Figure 1B ). Proteins values below the limit of detection in Olink significantly inflated the CV. Conclusions: These three large-scale proteomics platforms exhibit moderate overlap in proteome coverage, and modest agreement in protein quantification for shared proteins assayed. Discovery of novel biomarkers may benefit from verification in multiple proteomics platforms to assess validity of significant hits.
Powers of magnetic graph matrix: Fourier spectrum, walk compression, and applications
Magnetic graphs, originally developed to model quantum systems under magnetic fields, have recently emerged as a powerful framework for analyzing complex directed networks. Existing research has primarily used the spectral properties of the magnetic graph matrix to study global and stationary network features. However, their capacity to model local, nonequilibrium behaviors, often described by matrix powers, remains largely unexplored. We present a combinatorial interpretation of the magnetic graph matrix powers through directed walk profiles—counts of graph walks indexed by the number of edge reversals. Crucially, we establish that walk profiles correspond to a Fourier transform of magnetic matrix powers. The connection allows exact reconstruction of walk profiles from magnetic matrix powers at multiple discrete potentials, and more importantly, an even smaller number of potentials often suffices for accurate approximate reconstruction in real networks. This shows the empirical compressibility of the information captured by the magnetic matrix. This fresh perspective suggests further applications; for example, we illustrate how powers of the magnetic matrix can identify frustrated directed cycles (e.g., feedforward loops) and can be effectively employed for link prediction by encoding local structural details in directed graphs.
Abstract TH866: Associations of Plasma Very Long-Chain Saturated Fatty Acids with Cardiovascular Disease Risk are Influenced by Lipid Interactions
Introduction: Very long-chain saturated fatty acids (VLCSFA: C20:0, C22:0, C24:0) may influence cardiometabolic health differently from other, often detrimental, saturated fatty acids (SFA). Evidence remains inconclusive, partly because VLCSFA are metabolically derived from SFA, making it difficult to disentangle their individual effects due to potential confounding. Prior studies rarely accounted for correlations with other lipids or do not consider VLCSFA-specific lipid classes. Hypothesis and Objectives: VLCSFA have distinct cardiovascular health effects compared to other SFA with which they are correlated, and this might mask the associations of VLCSFA with disease risk. We investigated prospective associations of circulating VLCSFA across multiple plasma lipid classes with the incidence of cardiovascular disease (CVD), accounting for confounding by correlated lipids. Methods: We constructed a nested case-cohort study within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort with 1,704 participants (547 cases of CVD). Plasma concentrations of VLCSFA were measured in 12 lipid classes. A data-driven network including VLCSFA, precursors, and downstream metabolites was used to identify correlations and adjust for them in multivariable-adjusted Cox regression models between individual lipids and disease risk. Results: C20:0 was distributed across more lipid classes than C22:0 and C24:0. Associations for C20:0 and C24:0 with CVD varied by class; however, these relationships were only observed adjusting for correlated lipids identified in the network. Free fatty acid C20:0 (hazard ratio [HR] per SD: 0.68, 95% CI: 0.50-0.91), diglyceride C20:0 (0.69, 0.57-0.84), dihydroceramide C24:0 (0.62, 0.39-0.98), and lactosylceramide C24:0 (0.62, 0.46-0.83) were inversely associated with CVD only after adjusting for direct lipid neighbors. However, dihydroceramide C20:0 (1.34, 1.05-1.70) showed a positive association. Monoglycerides and cholesteryl esters containing VLCSFA were associated to higher risk of CVD. Conclusions: VLCSFA show different metabolic roles in CVD and highlight the importance of adjusting for confounding by correlated lipids to isolate their relationships. These findings challenge the traditional view that SFA exert uniform negative effects and suggest class-specific VLCSFA profiles may improve risk prediction of cardiometabolic diseases, guiding more precise prevention strategies.