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An autoimmunity-associated allele of <i>PTPN22</i> enhances innate antiviral immunity to protect against acute coronavirus infection
Allelic variation can impact viral clearance and disease severity. Still, our understanding of the effect of the autoimmunity-associated allelic variant of Ptpn22 (PEP-R619W) on antiviral immunity remains incomplete, as previous reports have only focused on chronic lymphocytic choriomeningitis virus infection. This research defines how the loss of Ptpn22 (PEP-null) and PEP-R619W changes antiviral immunity during an acute coronavirus infection. We address the hypothesis that CRISPR/Cas9-generated PEP-null and PEP-R619W mice have enhanced antiviral immunity over PEP-wild-type (WT) mice during coronavirus infection. Following mouse hepatitis virus A59 infection, we interrogated pathology, cytokine production, and cellular responses in the blood, spleen, and liver of PEP-WT, PEP-null, and PEP-R619W mice. Key findings show that PEP-R619W mice have reduced viral titer and weight loss, increased survival, and more mature natural killer (NK) cells in the liver and spleen compared to PEP-WT mice. Interestingly, protection against disease in PEP-null mice was inoculation dose dependent, whereas PEP-R619W conferred immunity regardless of infection dose. Further, Rag1 −/− PEP-R619W mice had increased survival and reduced viral titer over Rag1 −/− PEP-WT mice. PEP-R619W mice also had higher concentrations of interferon-gamma (IFNγ) and enhanced IFNγ production by mature NK cells in the liver at 3 d postinfection. Finally, NK cell depletion elevated PEP-R619W viral titer to similar levels as PEP-WT mice. This study investigates the role of Ptpn22 within NK cells and demonstrates that the Ptpn22 allelic variant augments NK cell function and is beneficial during coronavirus infection.
Abstract WE573: Trends in Cardiovascular Disease (CVD) Risk Factors in American Indian Populations: A Phase 7 update from the Strong Heart Family Study (SHFS)
Introduction: CVD is the leading cause of death among American Indians but major CVD risk factors, like hypertension, diabetes, obesity, smoking, and abnormal cholesterol, have not been updated recently. Therefore, we report changes in the prevalence of major CVD risk factors after a median 21.7 (range= 21.0-22.4) years of follow-up. Methods: The SHFS is the longest running, prospective cohort study of CVD in American Indians from Arizona, Oklahoma, and the Dakotas. We included participants from the SHFS, that completed the baseline (2001-2003), first follow-up (2006-2009), and the most recent, Phase 7, examination (2022-2025, n=1,383). We defined hypertension as high blood pressure (systolic ≥140 or diastolic ≥90 mmHg) or taking antihypertensive medication. Diabetes was defined as a measured fasting plasma glucose level ≥126 mg/dL or taking hypoglycemic medication and obesity as a measured body mass index ≥30 kg/m 2 . Current smoking was self-reported through standardized questionnaires. To measure lipids, we drew blood after a 12-hour fast and defined high LDL-C≥100mg/dL and low HDL-C < 40 mg/dL for men, HDL-C < 50 mg/dL for women. We used logistic generalized estimating equations to determine if the prevalence proportion of the CVD risk factors changed overtime, adjusting for age, sex, and center of collection. Results: During Phase 7, the adjusted prevalence proportion of CVD risk factors were hypertension=37%, diabetes=33%, obesity=64%, current smoking=27%, high LDL-C=43%, and low HDL-C=59% (Figure 1). Over a follow-up of 22 years, the prevalence of hypertension increased 6.7%, diabetes increased 16.4%, obesity increased 6.3%, and low HDL-C increased 21.1% (all p<0.01). Current smoking decreased 4.6% (p=0.03) and the prevalence of high LDL did not change. Conclusion: Although these results may only apply to participants who were relatively healthy at baseline, several risk factors appear to be increasing in American Indian populations, at the same time smoking behavior has decreased, and LDL-C has not changed.
Abstract MPTH56: Association of Cognitive Decline with Orthostatic Hypotension among Older Adults: Findings from the Atherosclerosis Risk in Communities Study
Background: Orthostatic hypotension (OH), a blood pressure (BP) dysregulatory condition, is associated with dementia, stroke, and all-cause mortality. OH develops from autonomic impairments, which may involve central control via the brain stem. Cognitive decline may indicate progressive neuropathological changes that could increase risk for developing OH. Hypothesis: We hypothesized that accelerated cognitive decline would be associated with a persistent change in orthostatic BP among older adults. Methods: The Atherosclerosis Risk in Communities (ARIC) Study measured participants’ global cognitive function, using memory, language, and executive function scores based on neuropsychological tests. We derived trajectories and categories of cognitive changes of visit 9 participants using data from visit 5 (2011-13) to visit 9 (2021-22). During visit 10 (2023), three supine and six standing BPs were measured. Supine BPs were measured after 5 minutes of rest at 30-second intervals, and standing BPs were timed at 0, 1, 2, 3, 4, and 5 minutes after standing. OH was determined if a drop in BP of systolic ≥20 or diastolic ≥10 mm Hg occurred after standing from the supine position. Patterns of OH were defined as transient (initial, early) and persistent (late, sustained) (see Table 1 legend for definitions). We determined the associations of cognitive change categories of visit 9 participants with OH patterns via multivariable logistic regression (see Table 2 legend for adjusted factors). We used inverse probability weighting to adjust for participants who attended visit 9 but not visit 10. Results: Of 696 participants (mean age 82.1±3.6 years, 58% female, 18% Black), 42% had initial OH, whereas 16% had sustained OH ( Table 1 ). Half of the participants (50%) had mild decline in global cognition scores, whereas 44% and 6% had stable and accelerated decline, respectively ( Figure 1 ). Similar patterns were observed across domain-specific scores. Participants with accelerated decline in global score had significantly higher odds of late and sustained OH compared to stable ( Table 2 ). Similar but non-significant associations were identified across domain-specific scores. Conclusion: Very old adults with accelerated cognitive decline were more likely to have persistent impairments in orthostatic BP regulation. Future studies should explore the brain regions underlying cognitive decline to better understand how it might contribute to OH.
Abstract MPWE38: Effects of the DASH4D diet on biomarkers of glycemia in adults with type 2 diabetes: A secondary analysis of the DASH4D randomized clinical trial
Background: In a recent controlled feeding trial, we showed that a DASH-style diet tailored for individuals with type 2 diabetes (DASH4D diet) improved short-term glycemic control assessed by continuous glucose monitoring. In this secondary analysis of the trial, we examined the effect of the DASH4D diet on biomarkers of glycemia. Methods: In the DASH4D trial, adults with type 2 diabetes were fed four isocaloric diets in a random order: DASH4D diet or comparison diet (representative of a typical American diet), each with higher or lower sodium. Each feeding period lasted 5 weeks and was separated by ≥1 week break. The primary outcome in this analysis was fructosamine, a marker reflecting glycemia over the past 2-3 weeks. Secondary outcomes included fasting glucose (reflecting glycemia at a single moment) and HbA1c (reflecting glycemia over 2-3 months). Outcomes were assessed at the end of each feeding period. Using an intention-to-treat approach, we estimated the effect of the DASH4D (versus comparison) diet on all outcomes with linear mixed effect models. In exploratory analyses, we examined the effect of the DASH4D diet by baseline HbA1c. Results: We included 101 participants (mean age: 67 years; 65% female; 88% Black adults). At baseline, mean HbA1c was 7.0% and 55% of participants were using two or more glucose-lowering medications. Compared to the comparison diet, the DASH4D diet significantly reduced end-of-period fructosamine (adjusted difference: -5.6 umol/L, P<0.002) and fasting glucose (adjusted difference: -4.5 mg/dL; P=0.019) (Figure A1-A2) . The DASH4D diet also had a small effect on HbA1c (adjusted difference: -0.09 %-points; P=0.035) (Figure A3) ; however, the 5-week duration of the feeding periods was suboptimal for estimating the effect of the diets on HbA1c. The effect of the DASH4D diet on fructosamine and fasting glucose was larger for participants with higher baseline HbA1c (Figure B1-B3) . Conclusion: The DASH4D diet significantly lowered fructosamine and fasting glucose in adults with type 2 diabetes. These results support the inclusion of the DASH4D dietary pattern into policy and clinical guidelines to improve glycemic control in type 2 diabetes.
A transcription regulator atlas identifies TOX3 as an Atoh1 coactivator in cerebellar development and tumorigenesis
Organ development and function are orchestrated by intricate transcriptional circuits. Here, we present a comprehensive atlas profiling 1,904 transcription regulators in the brain, cerebellum, heart, kidney, liver, ovary, and testis of fetal, neonatal, and adult mice. Using this dataset, we uncover Thymocyte Selection-Associated High Mobility Group Box Family Member 3 (TOX3) as a potential coactivator of Atoh1 in cerebellar granule neuron progenitors (GNPs). Tox3 -deficient mice display severe ataxia and cerebellar hypoplasia, driven by depletion of GNPs, diminished Atoh1 expression, and impaired primary cilia. Single-nucleus RNA-sequencing analyses reveals compromised maintenance of the progenitor pool. TOX3 is also highly expressed in subsets of medulloblastoma, and its deletion reduces cerebellar neoplasia and prolongs survival in a mouse model. Mechanistically, how lineage-defining factors such as Atoh1 drive robust gene expression despite weak intrinsic transactivation activity remains unclear. We show that Tox3 physically associates with Atoh1 and co-occupies shared regulatory elements, converting an otherwise weak single-copy Atoh1-responsive E-box into a highly active enhancer that drives transcriptional activation by up to 120-fold, including at an ultraconserved E-box downstream of Atoh1 itself. Cross-species single-cell comparisons further show an association between Tox3 expression and cerebellum expansion during vertebrate evolution. Together, this work supports Tox3 as a critical Atoh1 coactivator in cerebellar development, tumorigenesis, and evolution, while providing an atlas and screening strategy as a valuable resource for exploring novel transcriptional regulators in organogenesis and tissue physiology.
Abstract TH910: Examining the Associations Between Social Vulnerability and Clinical and Behavioral Risk for Atherosclerotic Cardiovascular Disease among Women with HIV and Women without HIV
Introduction: The Social Vulnerability Index (SVI) is used to assess area-level atherosclerotic cardiovascular disease (ASCVD) risk by identifying communities that are more susceptible to ASCVD due to exposure to adverse social and environmental factors and their associated behavioral and clinical risks. We sought to examine associations of overall SVI score and its thematic elements with clinical (hypertension, diabetes, and dyslipidemia) and behavior (smoking, substance, and heavy alcohol use) risk for ASCVD and estimated 10-year ASCVD risk, as calculated by the ACC/AHA Pooled Cohort Equation. Methods: Women with HIV (WWH) and women without HIV (WWoH) from the MACS/WIHS Combined Cohort Study were included if they were 30–79 years of age, had residential location data available, and attended a study visit between April and September 2019. Addresses were geocoded to 2019 census tract-level SVI. Analyses incorporated both the overall SVI score and its four thematic elements: socioeconomic status, household composition, racial and ethnic minority status, and housing type and transportation. Participants were grouped into tertiles by their SVI, with the third tertile representing those with higher relative vulnerability. Logistic regression models were used to examine the associations between participant tertiles for SVI and clinical and behavior risk factors for ASCVD and 10-year risk scores. Models were adjusted for HIV-status, age, race/ethnicity, employment, income, and insurance, except when modeling 10-year risk, age was removed as a covariate. Results: The analyses included 1699 women (72% WWH). The majority (88%) were virally suppressed. Clinical risk factors for ASCVD were prevalent [(hypertension (73%), diabetes (30%), dyslipidemia (54%)]. Few (<10%) reported substance use or heavy alcohol use and 40% reported smoking. Compared to women in the first SVI tertile, women in third tertile had higher odds of diabetes (OR=1.35, 95% CI: 1.02 – 1.77) and lower odds of substance use (OR=0.73, 95% CI: 0.46 – 1.16) and heavy alcohol use (OR=0.84, 95% CI: 0.55 – 1.27). Women in the third tertile for racial and ethnic minority status had lower odds of hypertension (OR=0.71, 95% CI: 0.53 – 0.94). No other notable associations were present between overall SVI or its thematic elements and behavioral or clinical risk for ASCVD. Conclusion: The SVI may be useful in examining and addressing the impact of area-level social vulnerability on ASCVD risk among WWH and WWoH.
Abstract TU126: Parents are Receptive to Childhood Blood Pressure Screening in Non-Clinical Settings
Introduction: Pediatric hypertension impacts approximately 14% of children in the US and disproportionately impacts low-income families. Regular blood pressure screening in childhood is needed for effective identification and management of this condition. While non-clinic-based blood pressure screening including home and community-based screening have long been used to overcome access issues and support cardiovascular health equity in adult populations they have scarcely been explored for children. Hypothesis: We hypothesized that parents would be receptive to non-clinic-based pediatric blood pressure screening. Methods: We conducted semi-structured interviews with parents of children aged 3-17 years old in Central Massachusetts. Interviews were audio recorded and professionally transcribed. We used rapid qualitative analysis to synthesize themes from the data. All activities were approved by our institutional review board. Results: A total of 32 parents were interviewed, 75% of whom were from a very low or low child opportunity index area. The mean age was 39 years (SD 9.7) for parents and 9 years (SD 4.9) for children. Most parents were female (84%) and had multiple children (87%). Three primary themes emerged. 1) Parents were receptive to the idea of community-based blood pressure screening delivered by public health nurses and viewed it as an additional service to in clinic care. 2) Parents expressed that it is important for any blood pressure screening service to be convenient, quick, and low or no cost. Accordingly, some noted school- or home-based screening would be desirable. Several parents who monitor their blood pressure at home reported their children show interest in the home monitoring. 3) Parents described pediatric primary care providers as important sources of information and key to their acceptance of blood pressure screening in non-clinical settings. Parents reported wanting to learn about non-clinic-based screenings from their child’s primary care provider and wanting to be educated by them on why screening is important. Conclusion: In conclusion, parents are receptive to blood pressure screening for their children in non-clinical settings including community, school, and home settings. This supports the use of such settings to increase access to pediatric blood pressure screening. Such efforts may improve diagnosis of pediatric hypertension and ultimately help reduce cardiovascular health disparities.
Abstract WE446: Global Macroeconomic Impact of Cardiovascular Disease: A Value of Lost Welfare Analysis, 1990–2023
Background: Cardiovascular disease (CVD) remains the leading cause of global mortality and disability. Traditional economic assessments underestimate its true impact by excluding welfare losses associated with health and productivity decline. This study applies a welfare-based economic framework to estimate the global macroeconomic burden of CVD from 1990 to 2023. Methods: Disability-Adjusted Life Years (DALYs) for CVD and its major subtypes—ischemic heart disease, stroke, hypertensive heart disease, and cardiomyopathy were utilized from the Global Burden of Disease 2023 tool. Gross domestic product (GDP) and GDP per capita (PPP-adjusted, constant 2017 USD) were used to derive country-specific Values of Statistical Life (VSL), anchored to the U.S. baseline of $10.5 million (2017 PPP). The Value of Lost Welfare (VLW) was calculated as the product of age-adjusted VSLY and DALYs. Sensitivity analyses were conducted using income elasticities (IE) of 0.55, 1.0, and 1.5 across seven GBD super-regions. Results: In 2023, the global VLW attributable to CVD totaled $3.8 trillion (3.6% of world GDP) at IE = 1.0. Lower elasticity (IE = 0.55) yielded $2.1 trillion (2.0%), while higher elasticity (IE = 1.5) increased losses to $5.6 trillion (5.2%). Ischemic heart disease accounted for 45% of the total burden, stroke for 27%, and hypertensive heart disease for 11%. The highest VLW/GDP ratios were seen in Eastern Europe (8.4%), Central Asia (7.9%), and Sub-Saharan Africa (6.3%). From 1990–2023, total global VLW more than doubled, despite a 26% decline in age-standardized DALY rates. Conclusions: Despite epidemiological progress, CVD continues to exact an enormous macroeconomic toll equivalent to 3–5% of global GDP annually. Integrating welfare-based economic measures into national health planning underscores that investing in CVD prevention yields both health and economic dividends.
Myeloarchitecture, intra- and interhemispheric and thalamocortical connections of area 3b representing the teeth and tongue in galagos
The representations of the face and oral cavity occupy a large but understudied portion of primary somatosensory cortex (S1 or area 3b) in primates. These studies are clearly important in processing food, taste, and vocalizations. Little is known about the neuronal representations of the teeth and tongue, their relationship with myeloarchitecture, and their cortical and thalamic connections in area 3b of strepsirrhine galagos. In owl and squirrel monkeys, and likely in macaque monkeys, the most lateral portion of S1 represents the face, teeth, and tongue in a series of myelin-dense ovals, including ovals for the contralateral teeth and tongue and ipsilateral teeth and tongue. As this complex representation of the teeth and tongue may differ among mammals and even primates, we sought to evaluate these representations in the galagos, representing an early branch of primates. Using a combination of neuronal responses to touch, neuroanatomical tracer injections, and tissue processing to reveal anatomical area borders, we found that lateral S1 in galagos resembles those of studied monkeys by having a series of ovals that double the representation of the tongue and teeth, along with similar intracortical, callosal, and thalamic connections, suggesting that these features of S1 emerged in the first primates.
Abstract WE453: Global Development Assistance for Cardiovascular Disease in Low- and Middle-Income Countries, 2007–2023
Background: Cardiovascular disease (CVD) is the leading cause of premature mortality in low- and middle-income countries (LMICs). However, the scale, distribution and trajectory of international development assistance for CVD have not been systematically characterized. Understanding these patterns is essential for informing targeted policy interventions and optimizing resource allocation. Hypothesis: Development assistance for CVD is limited, concentrated among a few donors and recipients, and marked by temporal volatility. Methods: We examined development assistance projects reported to the Organisation for Economic Co-operation and Development (OECD) Creditor Reporting System between 2007 and 2023. We identified CVD-related projects using a keyword-based search strategy, translated across 21 languages. We analyzed funding trends across 34 donors and 65 recipients, including countries and regions. Joinpoint regression was applied to identify statistically significant changes in disbursements over time. Results: Of the 4,507,692 projects analyzed, 815 were identified as CVD-related. These received US$434.98 million in disbursements, representing 0.008% of all international development assistance funding. The three largest donors, including the United Kingdom (US$71.62 million), the Wellcome Trust (US$70.17 million), and the United States (US$48.16 million), accounted for 43.7% of total CVD-related aid. The three largest recipient countries were Uganda (US$50.71 million), Uzbekistan (US$41.77 million), and Kenya (US$30.85 million). Funding declined significantly during the COVID-19 pandemic to US$9.99 million in 2019 and US$9.36 million in 2020, then rebounded to US$63.99 million in 2023. Joinpoint analysis identified four significant transition points (2011, 2014, 2017, 2020), with an average annual percent change of US$37.03 million (95% CI: US$15.45-67.15 million; p < 0.001). Conclusions: Between 2007 and 2023, CVD-related development assistance to LMICs remained exceedingly low, fragmented, and donor-dominated. These findings highlight the urgent need for global health donors to elevate CVD within funding priorities, expand support to LMICs, and commit to equitable financing strategies.
Abstract WE528: Wearable Devices and Meeting Physical Activity Guidelines in Adults with Hypertension
Introduction: Physical activity provides multiple benefits for managing hypertension. Wearable devices are popular tools aimed to promote physical activity among its users. Currently, there are limited literature examining the effectiveness of wearable devices in promoting physical activity among people with hypertension. The purpose of the current study is to examine the association between wearable device usage and meeting of aerobic physical activity guidelines among people with hypertension. Hypothesis: Wearable device users with hypertension are more likely to meet the aerobic physical activity guidelines than nonusers with hypertension. Methods: Adults with hypertension from the 2017 Behavioral Risk Factor Surveillance System were included in the analysis. Participants self-reported their utilization of wearable devices along with their physical activity levels. Participants were determined to meet the aerobic physical activity guidelines if they engaged in at least 150 minutes of moderate intensity physical activity per week. Adjusted binary logistic regression with survey analysis techniques was used to examine the association between wearable device usage and meeting of aerobic physical activity guidelines among participants with hypertension accounting for demographic factors. Results: Among the 1602 participants with hypertension, only 18.09% (95% CI [14.14, 22.53]) reported using wearable devices. A higher proportion of wearable device users met the aerobic physical activity guidelines than nonusers (79.27%, 95% CI [69.92, 88.61] vs 70.33%, 95% CI [64.66, 75.99]). Participants using wearable devices were 2.25 (95% CI [1.17, 4.33]) times the odds of nonusers in meeting the aerobic physical activity guidelines accounting for demographic factors. Conclusion: Adults with hypertension who used wearable devices were more likely to achieve recommended levels of aerobic physical activity, suggesting that these devices may be a promising tool to support physical activity promotion in this population.
Abstract WE531: Association of hypertension, hyperlipidemia, and physical activity levels among individuals with Type 2 Diabetes
Introduction: Physical activity (PA) is an established protective factor for managing conditions such as hypertension (HT) and hyperlipidemia (HL). Existing research highlights the importance of lifestyle modifications, particularly for high-risk populations such as people with Type 2 Diabetes (T2D). People with T2D have an elevated risk of HT and HL, yet few studies have examined their associations with PA. Therefore, the purpose of this study was to explore the associations between HT, HL, and PA among people with T2D. Hypothesis: Adults with T2D from the 2022–2024 National Health Interview Survey (NHIS) were included. Participants self-reported diagnoses of HT and HL, as well as PA levels (moderate-to-vigorous physical activity [MVPA]) and frequency of resistance training (RT). Participants were classified as meeting PA guidelines if they reported ≥150 minutes of MVPA per week and meeting RT guidelines if they reported RT ≥2 times per week. Binary logistic regression models accounting for survey weights were conducted separately for HT and HL with each of the different PA variables. Results: Among 4,600 participants with T2D, the mean age was 63.7 years, mean diabetes duration was 14.1 years, and 27.2% reported insulin use. Overall, 74.0% had HT and 66.5% had HL. Average MVPA was 173.0 minutes per week, and average RT frequency was 0.7 times per week; 28.7% met the PA guideline and 15.7% met the RT guideline. No significant associations were observed between PA and HT (p > .05). However, meeting the PA guideline (OR = 0.83, 95% CI [0.70, 0.98]) and the RT guideline (OR = 0.80, 95% CI [0.65, 0.98]) were associated with lower odds of HL. Additionally, greater RT frequency was associated with lower odds of HL (OR = 0.95, 95% CI [0.91, 0.99]). Conclusion: While no associations were found between PA and HT, engaging in PA, particularly RT, was associated with lower odds of HL among people with T2D. Since HT and HL are closely related, reducing cholesterol through PA can help lower blood pressure reducing lipid build up in the arteries. Encouraging PA participation, including RT, may be beneficial for managing HL in this population. Further research is needed to examine the impact of PA and RT on HT in people with T2D.
Monkeypox virus protein OPG188 antagonizes cGAS–STING antiviral signaling pathway to mediate immune evasion
Innate immune evasion is critical for productive viral replication. Activation of the cGAS–STING antiviral signaling pathway and its downstream effector genes plays a pivotal role in restricting viral replication during early DNA virus infection. Through a comprehensive genomic screen of monkeypox virus (MPXV), we identified three viral genes, OPG147, OPG188, and OPG200, whose expression potently suppresses cGAS–STING pathway activation. Notably, the N-terminal domain of the Poxin protein encoded by OPG188 exhibits nuclease activity and cleaves the cyclic dinucleotide second messenger 2′3′-cGAMP. Using site-directed mutagenesis, we further delineated nine conserved regions and four key amino acid residues—H15, K140, R182, and I79—within Poxin that are essential for antagonism of cGAS–STING signaling. Moreover, via molecular docking and high-throughput screening of 7,155 small molecules targeting the catalytic pocket of Poxin, we identified two compounds that competitively bind to Poxin, inhibiting its cGAMP—degrading activity and consequently restoring cGAS–STING-mediated antiviral signaling upon MPXV infection. Collectively, these findings underscore the pivotal role of OPG188 in modulating antiviral immune responses and highlight NAD + and Theaflavin-3’-gallate as promising candidates for the development of anti-MPXV therapeutics.
Abstract WE526: Association Of Social Network Size With Physical Activity Patterns Among Middle-Aged Korean Adults
Background: Adhering to guideline-recommended leisure-time physical activity (LTPA) is a key component for chronic disease prevention and recent studies suggest social relationships influence LTPA. However, the influence of social networks on activity patterns in Asian populations remains unclear. Methods: This cross-sectional study included 125,457 adults aged 40-69 years from the Health Examinees study-G (HEXA-G) cohort. They were recruited from 38 health centers and hospitals in Korea from 2004 to 2013. The primary exposure was social network size by type (total, family, and non-family), each categorized into quartiles (Q1-Q4). Physical activity patterns, the primary outcome, were defined as inactive (<150 minutes moderate-to-vigorous physical activity (MVPA)/week), weekend warrior (≥150 minutes MVPA/week in ≤2 days), and regularly active (≥150 minutes MVPA/week in ≥3 days). Multinomial logistic regression analysis was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for age, BMI, waist circumference, education, income, marital status, smoking, alcohol intake, total caloric intake, chronic diseases and cancer diagnosis. Results: Among participants (53±8 years of age; 66% women), 8.7% of men and 3.4% of women were weekend warriors, and 33.1% of men and 33.0% of women were regularly active. Regarding LTPA types, mountain climbing was most common among weekend warriors (41.2% in men and 39.7% in women), whereas aerobics/gym activities predominated among those regularly active (10.6% in men and 17.0% in women). Larger total networks were associated with greater physical activity. Associations were stronger for non-family networks, whereas family networks showed no consistent trends. Using inactive participants as reference, both men and women in Q4 of non-family networks had higher odds of being a weekend warrior than regularly active, compared to those in Q1: ORs (95% CIs) were 1.44 (1.29-1.61) and 1.22 (1.14-1.30) in men and 1.33 (1.18-1.50) and 1.25 (1.19-1.31) in women. Conclusions: Larger social networks, particularly non-familial ties, were significantly associated with higher likelihood of being a weekend warrior or regularly active. Strengthening non-family social connections may be an effective approach to promote active lifestyles and reduce inactivity among middle-aged adults.
Abstract TH915: Binge Eating Symptoms are Prospectively Associated with Cardiovascular Disease Risk Factors in Early Adolescence: the Adolescent Brain Cognitive Development (ABCD) Study
Introduction: Binge eating symptoms, defined as consuming an atypically large amount of food with associated loss of control, are common in adolescents and may represent an early psychosocial risk factor for adverse cardiovascular and metabolic outcomes. Binge eating has been associated with cardiovascular disease (CVD) risk factors such as diabetes, hypertension, obesity, and dyslipidemia, but the long-term cardiovascular effects among adolescents remain unclear. In the present study, we examined the prospective associations between binge eating symptoms and CVD risk factors in early adolescents. Hypothesis: We hypothesized that binge eating symptoms would be prospectively associated with greater CVD risk factors among adolescents. Methods: This prospective cohort study included data from 7,577 adolescents from the Adolescent Brain Cognitive Development (ABCD) Study collected at Year 2 (2018-2020, ages 11-12) and Year 4 (2020-2022, ages 13-14) across 21 diverse sites in the US. Adjusted multivariable linear regression models estimated the prospective associations between Year 2 binge eating symptoms and Year 4 cardiovascular health outcomes (body mass index [BMI] percentile, waist circumference percentile, systolic blood pressure percentile, diastolic blood pressure percentile, hemoglobin A1c [HbA1c], total cholesterol, high-density lipoprotein [HDL] cholesterol, and non-HDL cholesterol). Presence of binge eating symptoms was assessed via parent report using the Kiddie Schedule for Affective Disorders and Schizophrenia (KSADS-5). Results: In our sample, 6.03% of adolescents experienced binge eating symptoms. After covariate adjustment, binge eating symptoms were prospectively associated with higher BMI percentile (adjusted coefficient [B] 2.61; 95% confidence interval [CI] 0.96, 4.26; p=0.002), higher waist circumference percentile (B 4.87; 95% CI 2.61, 7.13; p<0.001), higher diastolic blood pressure percentile (B 1.41; 95% CI 0.48, 2.35; p=0.003), higher HbA1c (B 0.12; 95% CI 0.04, 0.20; p=0.005), and lower HDL cholesterol (B -3.86; 95% CI -6.70, -1.01; p=0.008) two years later. Conclusion: Binge eating symptoms were associated with greater CVD risk factors, highlighting the importance of early identification and intervention. Clinicians caring for early adolescents should consider screening for binge eating symptoms and initiate conversations and interventions to promote cardiovascular health.
Abstract TH909: Psychosocial Adversity Associates with Lipid Profiles Among African American Women in Resource-Limited Neighborhoods: Findings from the Step It Up Community-Engaged, Digital Health Physical Activity Intervention
Introduction: Adverse psychosocial factors worsen cardiovascular risk through chronic inflammation and dysregulation of the sympathetic nervous system and hypothalamic-pituitary-adrenal axis. Social determinants of health are closely related to psychosocial risk in underserved populations within the United States, though few studies have examined relationships between psychosocial factors and lipoproteins in communities with elevated social risks. We hypothesized that higher psychosocial risk would be associated with less favorable lipid profiles among African American women living in resource-limited Washington, DC neighborhoods. Methods: African American women with overweight or obesity aged 21-75 years residing in Wards 5, 7, and 8 of Washington, D.C. and Prince George’s County in Maryland were recruited for the Step It Up study. Principal component analysis of baseline psychosocial survey data was performed and identified high loadings for depression, social isolation, and loneliness. Participants were assigned psychosocial risk based on sums of these survey scores, with higher scores indicating greater psychosocial adversity. Fasting lipid profiles were measured using Nuclear Magnetic Resonance spectroscopy, quantifying lipoprotein particle concentrations, numbers, and sizes as well as apolipoprotein (Apo) A/B levels. Associations between psychosocial risk and lipid profiles were assessed using linear regression models, adjusting for demographic, socioeconomic, and comorbidity covariates. Results: Participants with psychosocial survey data were included in analyses (n=165, age 57.4±12.6 years, BMI 36.2±6.7). Women in the high psychosocial risk tertile had higher BMI and systolic blood pressure and greater proportions of lipid-lowering therapy compared to those in the low risk tertile. High-risk individuals also had lower Healthy Eating Index scores and lower socioeconomic status. Increased psychosocial risk was associated with low density lipoprotein (LDL) concentration (β= 4.75, p=0.01), LDL particle numbers (β= 68.61, p=0.01) and ApoB concentrations (β= 3.50, p=0.01) (Table). Psychosocial factor scores were not associated with lipid size. Conclusions: Psychosocial adversity was associated with more atherogenic lipid profiles, including higher LDL concentration and particle numbers and ApoB concentrations. These findings suggest that psychosocial risk factors among at-risk populations may contribute to cardiovascular risk through lipid dysregulation.
Orthogonal disentanglement of single-cell multi-omics reveals private and shared drivers of tissue development and pathogenesis
Characterizing gene expression and regulatory dynamics underlying both normal tissue function and disease progression requires an integrative analysis of single-cell multi-omics data. However, the asynchrony of gene regulation and the snapshot of single-cell multi-omics data give rise to private signals unique to each omics layer and shared signals reflecting cross-modality coordination. Here, we present Omics Separation Modeling using Domain Adaptation (OmiDos), a flexible annotation-free deep learning framework that disentangles omic-specific and interomic shared latent variables in multi-omics data with private-shared component analysis. Its modular architecture enables seamless extension to incorporate adversarial learning for unpaired data misalignment and to restructure its components to leverage the maximum mean discrepancy regularization, thereby minimizing interference with biological variability. Through this disentanglement, OmiDos enables the estimation of gene expression and regulatory dynamics at finer biological granularity and empowers various downstream analyses. We demonstrated the superior performance of OmiDos in terms of clustering accuracy, batch-effect correction, and misalignment resolution across datasets spanning diverse platforms and tissue types. In mouse secondary palate development, OmiDos precisely identified a cell type–specific unlinked distal enhancer, elucidating its essential role in the regulation of epithelial cell differentiation and migration. The application of OmiDos to medulloblastoma revealed a potential role deficiency in driving partial closure of the distal enhancer region of Neurod1 may contribute to the progression of medulloblastoma from normal to tumor states.
Abstract 72: Association of Diet Quality and Physical Activity through Young Adulthood With Mid-Life Cardiovascular Health Trajectories: The Coronary Artery Risk Development in Young Adults (CARDIA) Study
Background: Poor diet quality and inadequate higher intensity physical activity (PA) are associated with cardiovascular morbidity and mortality. However, no studies have assessed dietary quality and PA, or specifically the joint association of the two, through young adulthood and their associations with midlife cardiovascular health (CVH). Methods: CARDIA participants (enrolled in 1985-86) provided dietary data at exam years (Y) 0, 7 and 20, and PA information at Y0, 2, 5, 7, 10, 15, and 20. DASH diet and PA scores (in exercise units) were calculated from Y0 to Y20 (mean ages 25 to 45 yrs), and participants were stratified into groups using multiple latent class analysis based on similar patterns of joint DASH and PA score evolution from Y0 to Y20. CVH from Y20 onward (mean age 45 to 60 yrs) was quantified using the American Heart Association’s Life’s Essential 8 (LE8) score. LE8 trajectory groups from Y20 to Y35 (mean ages 45 to 60 yrs) were identified using trajectory modeling (SAS PROC TRAJ). Results: Data are from 2,806 participants (57% women, 43% Black).[RI1] We identified four groups of joint DASH-PA patterns through young adulthood ( Figure 1A ): Group 1, low DASH/very low PA (10.9%); Group 2, low DASH/moderate-declining PA (25.6%); Group 3, moderate DASH/high-declining PA (41.5%); Group 4, high DASH/high-declining PA (22.0%). There were three distinct mid-life LE8 trajectories identified (low, moderate, and high CVH). Individually, diet and PA had significant associations with midlife CVH. Considering patterns of diet and PA jointly, participants in Groups 2, 3, and 4 had 4.8-, 8.6-, and 21.7-fold higher odds, respectively, of having high CVH compared to low CVH in midlife ( Figure 1B) . Participants in Groups 2, 3, and 4 had 1.4-, 1.6-, and 2.2-fold higher odds, respectively, of having moderate CVH compared to low CVH in midlife. Results were similar after additional adjustment for the Y0 LE8 score and with or without considering diet and PA in the midlife overall LE8 score trajectories. Conclusions: Our findings show the substantial importance of diet and PA, and particularly maintaining a combination of high-quality diet and greater PA, through young adulthood for mid-life CVH. These findings underscore the importance of initiating lifestyle prevention strategies early to achieve and sustain high mid-life cardiovascular health.
Abstract MPWE40: Food-is-Medicine Intervention Effects on Lipid Profiles and PREVENT Cardiovascular Risk Scores in Black and Hispanic Adults with Hypertension: The THRIVE Pilot Trial
Background: Hypertension and dyslipidemia disproportionately affect Black and Hispanic adults, contributing to cardiovascular disparities. Food-is-Medicine interventions combining produce prescriptions with nutrition education may prevent cardiovascular risk by improving lipid profiles. The THRIVE pilot examined whether a culturally tailored intervention could improve lipid profiles and PREVENT risk scores in Black and Hispanic adults with hypertension. Method: THRIVE is a 6-month pilot randomized controlled trial enrolled 80 Black and Hispanic adults with hypertension. Participants received THRIVE intervention (produce prescriptions, dietitian coaching with motivational interviewing, and culturally tailored nutrition messaging) or enhanced usual care (standard produce bags without coaching). Laboratory measurements including comprehensive metabolic panel, lipid panel, hemoglobin A1C, and spot urine sodium and potassium were collected at baseline, 12, and 24 weeks. The AHA PREVENT equations were used to calculate 10-year risk for atherosclerotic cardiovascular disease (ASCVD), total cardiovascular disease (CVD), heart failure, coronary heart disease (CHD), and stroke. Outcomes were changes in lipid parameters and PREVENT risk scores. Between-group intervention effects were estimated using difference-in-differences (DiD) analysis via linear mixed-effects regression models. Results: Among 80 participants (mean age 54.5±11.4 years, 56.8% female, 62.2% Black), THRIVE group showed decreased total cholesterol at 24 weeks (-10.4 mg/dL, p=0.041; Table 1), increased HDL at 12 weeks (5.7 mg/dL, p=0.046), and reduced LDL at 24 weeks (-12.6 mg/dL, p=0.004). Controls showed no significant lipid changes. Urinary sodium increased at 12 weeks (23.6 mEq/L, p=0.032) and potassium at 24 weeks (15.0 mEq/L, p=0.043) in THRIVE group, potentially reflecting improved dietary quality. PREVENT risk scores showed numerical reductions across most cardiovascular domains at 24 weeks in both groups, with trends toward greater reductions in controls, though no changes reached statistical significance (Figure 1). Conclusion: The THRIVE pilot showed favorable within-group lipid profile improvements that may contribute to cardiovascular disease prevention in Black and Hispanic adults with hypertension. Larger definitive trials with extended follow-up are needed to determine whether these lipid improvements translate to meaningful reductions in cardiovascular risk and clinical events.
Abstract TU147: Association Of Perfluorooctanoic Acid With Cardiovascular Disease In The United States
Background: Per- and polyfluoroalkyl substances (PFAS) are widespread environmental contaminants linked to cardiometabolic risk factors, but evidence for associations with clinical cardiovascular disease remains limited, particularly in populations with low exposure. We aimed to evaluate the association of serum linear perfluorooctanoic acid (n-PFOA), a major type of PFAS, with cardiovascular diseases in a recent, nationally representative U.S. sample. Methods: We performed a cross-sectional analysis of 3,516 adults (≥20 years) from the National Health and Nutrition Examination Survey (NHANES) 2015-2018. Survey-weighted logistic regression models were used to assess the association between log-transformed serum n-PFOA and hypertension, coronary heart disease (CHD), myocardial infarction, and congestive heart failure (CHF). Models were adjusted for key sociodemographic, lifestyle, and clinical confounders including age, sex, race/ethnicity, BMI, smoking, diabetes, physical activity, and education. Results: The median survey-weighted serum n-PFOA concentration was 1.4 ng/mL. In fully adjusted models, n-PFOA was not significantly associated with hypertension (OR 1.02 95% CI 0.88-1.18; p = 0.75), CHD (OR 0.75, 95% CI 0.52-1.07; p=0.1), or myocardial infarction (OR 0.8, 95% CI 0.65-1.00; p=0.054). In contrast, higher n-PFOA levels were unexpectedly associated with lower odds of CHF (OR 0.68 95% CI: 0.59- 0.95; p=0.02). Conclusions: In a recent representative sample of the U.S. population, serum n-PFOA concentrations were not associated with hypertension, CHD, or myocardial infarction. The observed inverse association with CHF warrants cautious interpretation and may be attributable to residual confounding from factors like diet or other complex biological mechanisms. These findings highlight the need for longitudinal studies to clarify the evolving role of PFAS in cardiovascular health as environmental exposures decline.