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Abstract MP64: PREVENT 30-Year CVD Risk During Pregnancy Is Associated With Inflammatory and Vascular Placental Pathology
Introduction: Many adverse pregnancy outcomes (APOs) associated with long-term CVD risk, such as preeclampsia, are mediated by placental function. Notably, the vascular and inflammatory placental pathology underlying APOs are also found in 20-35% of healthy pregnancies. Thus, we aimed to investigate the link between 30-year CVD risk and placental pathology. Hypothesis: We hypothesized that higher 30-year CVD risk, as estimated based on the PREVENT equation calculated in mid-pregnancy, would be associated with greater likelihood of placental pathology, including chronic inflammation (CI), maternal vascular malperfusion (MVM), and fetal vascular malperfusion (FVM). Methods: Data are from the Stress, Pregnancy, and Health (SPAH) study, a prospective pregnancy cohort conducted from 2018-2023 in Evanston, IL. The PREVENT 30-year CVD risk estimate was calculated based on the 2 nd trimester study visit. At the study visit, blood pressure was assessed, and a blood sample was collected and used to measure cholesterol and estimate eGFR from creatinine. Participants self-reported smoking status. Age, pre-gestational diabetes diagnosis, and use of anti-hypertensive or lipid-lowering medications were abstracted from medical records. Following delivery, placentas were collected and reviewed by a perinatal pathologist and patterns of placental injury (CI, MVM, FVM) were identified based on Amsterdam consensus criteria. Logistic models were used to test associations between CVD risk in pregnancy and placental pathology, adjusted for race/ethnicity, socioeconomic position, and gestational age at the study visit. Results: The SPAH study included 605 participants, 505 of whom had placental pathology exams and complete data to estimate 30-year CVD risk during pregnancy. The mean gestational age at the study visit was 23.7 weeks (SD: 1.7) and the mean age of study participants was 33.3 years (SD: 5.6). The mean 30-year CVD risk was 7.6% (SD: 6.7) and 54% had CI, 29% had MVM, and 34% had FVM. In the adjusted model, a 1 SD increase in CVD risk was associated with 24% greater odds of having CI (95% CI: 1.01, 1.52) and 25% greater odds of having MVM (95% CI: 1.04, 1.50; Figure 1) at delivery. CVD risk was not associated with FVM. Conclusions: Results demonstrate that PREVENT 30-year CVD risk estimated in the second trimester is associated with CI and MVM in the placenta at delivery, which may provide insight into the mechanisms linking CVD risk and APOs.
Abstract P2049: Race and Ethnicity and Oral Anticoagulation Adherence in Older Adults with Atrial Fibrillation: A Nationwide Study
Background: Atrial fibrillation (AF) is the most common arrhythmia and is associated with morbidity from ischemic stroke. Oral anticoagulant (OAC) therapy reduces stroke risk. Prior work has shown lower OAC initiation in minoritized racial/ethnic groups. Less is known about how OAC adherence differs by race/ethnicity, which may contribute to higher stroke rates in minoritized groups. Hypothesis: Minoritized racial/ethnic groups will have poorer adherence to OAC therapy than White individuals. Goal/Aim: To examine the association of race/ethnicity and OAC adherence in AF. Methods: Using VA Corporate Data Warehouse data, we identified patients enrolled in VA from 1/1/2014-12/31/2020 with an AF diagnosis. We excluded those who received OAC before their index AF diagnosis, were on multiple OAC drugs within 1 year of treatment or died within 1 year of treatment. The independent variable was race/ethnicity (i.e., non-Hispanic Black, Other, White, and Hispanic). The primary outcome was adherence to OAC therapy (warfarin or direct oral anticoagulant, DOAC) defined as ≥80% proportion of days covered within the first year of index treatment. Multivariable logistic regression was used to estimate racial/ethnic differences in OAC adherence, adjusting for age, OAC type, stroke risk score, area deprivation index, and year of first OAC prescription. Results: We identified 99,461 OAC initiators: 3.4% Hispanic, 8.8% Non-Hispanic Black, 85.7% Non-Hispanic White, 2.1% Non-Hispanic Other, mean age 72.8 years. Overall, 1-year OAC adherence was 70%. Adherence varied by race/ethnicity with DOAC adherence greater than warfarin for all groups except Black patients ( Figure ). In adjusted models, Black (aOR 0.63, 95% CI 0.57-0.62), Hispanic (aOR 0.78, 95% CI 0.65-0.77), and Other patients (aOR 0.79, 95% CI 0.71-0.86) had significantly lower odds of adherence vs. White patients. Cumulatively, 1.4% of patients had a newly diagnosed stroke during their first year of treatment, with stroke rates lower in adherent (1.4%) vs. non-adherent (1.6%) patients. Adherent Black (2.9%) and Hispanic (1.7%) patients had significantly higher rates of strokes than White (1.3%) patients (P<0.001). Conclusion: In a national cohort of VA patients with AF, we found significant racial/ethnic disparities in OAC adherence and incident stroke. Identifying drivers of these disparities is essential to improve outcomes in patients with AF including those managed in the largest, low-drug cost, US health care system.
Abstract P1005: Associations between circulating reproductive hormones and cardiovascular-kidney-metabolic syndrome in older men
Introduction: The American Heart Association (AHA) recently introduced the cardiovascular-kidney-metabolic (CKM) syndrome as a systemic disorder with connections among heart disease, kidney disease, diabetes, and obesity. The relationship between cardiovascular-kidney-metabolic (CKM) syndrome and reproductive hormones in older men is unclear. Hypothesis: Testosterone and other major reproductive hormones in older men may be important biomarkers for CKM syndrome. Methods: Men ages 70 years and older from the Concord Health and Ageing in Men Project study (n = 1399) were assessed at baseline. Testosterone and dihydrotestosterone (DHT) were measured by liquid chromatography-tandem mass spectrometry, and luteinizing hormone (LH) and follicle-stimulating hormone (FSH) by immunoassay. CKM syndrome was defined based on the Presidential Advisory from the AHA. Logistic regression model (odds ratio, OR) was used for analyses. The model building for all analyses included relevant covariates notably age, marital status, alcohol consumption, smoking, and physical activity. Results: In this cross-sectional observational study of older men aged 76.8 ± 5.5 years, most participants had CKM stage 2 or higher. Approximately 46% in stage 2, 20% in stage 3, and 31% were in stage 4. In the multivariable-adjusted model, participants in the lowest testosterone quartile were more likely to have CKM stage 3 (OR:1.59, 95%CI:1.06-2.39) and stage 4 (OR: 1.59, 95%CI:1.14-2.21) when compared to those in the highest testosterone quartile. Similar observations were shown for DHT. In contrary, participants in the lowest LH quartile were less likely to have CKM stage 3 (OR:0.59, 95%CI:0.40-0.87) and stage 4 (OR:0.65, 95%CI:0.46-0.92) when compared to the highest LH quartile. Similar observations were shown for FSH. No significant associations were observed for the lower CKM stages across all the studied reproductive hormones. Conclusions Low testosterone and DHT, and high LH and FSH are associated with advanced stages of CKM syndrome in older men. Our follow-up longitudinal study will further explore whether observed associations between the reproductive hormones and CKM syndrome represents a causal relationship, or rather biomarkers of risk.
BIN1 reduction ameliorates <i>DNM2</i> -related Charcot–Marie–Tooth neuropathy
Charcot–Marie–Tooth (CMT) disease, the most common inherited neuromuscular disorder, manifests as progressive muscle weakness and peripheral nerve defects. Dominant mutations in DNM2 , encoding the large GTPase dynamin 2, result in CMT without any suggested therapeutic strategy. Different dominant mutations in DNM2 also cause centronuclear myopathy (CNM), and increasing BIN1 (amphiphysin 2), an endogenous modulator of DNM2, rescued CNM in mice. Here, we found that increasing BIN1 level exacerbated the phenotypes of the Dnm2 K562E/+ mouse carrying the most common DNM2 -CMT mutation. Conversely, whole-body reduction of Bin1 expression level, through the generation of Dnm2 K562E/+ mice with heterozygous loss of BIN1, restored motor performance and ameliorated muscle organization and structural defects of peripheral nerves. The rescue of motor defects was maintained at least up to 1 y of age. BIN1 inhibited the GTPase activity of DNM2, and the rescue was driven by an increased activity of the K562E DNM2 -CMT mutant, and a normalization of integrin localization in muscle. Overall, this study highlights BIN1 as a modifier of DNM2 -CMT, and its reduction as a potential therapeutic strategy. It also revealed an opposite pathological mechanism and inverse therapeutic concepts for DNM2 -CMT peripheral neuropathy versus DNM2 -CNM myopathy.
Abstract P1119: Model-based Replacement of Sedentary Time with Light Intensity Physical Activity is Associated with Improved Cardiometabolic Risk Score over 15 Years of Midlife in the CARDIA Study
Introduction: Current physical activity (PA) recommendations support replacing time spent sedentary with PA of any intensity. Replacing sedentary time with light intensity PA (LPA) may be a more accessible behavior change for many individuals compared with increasing moderate/vigorous intensity PA (MVPA). However, the longitudinal associations of replacing sedentary behavior with LPA and cardiometabolic health are not clear. Hypothesis: We hypothesized that replacing time spent sedentary with LPA is associated with improvement in cardiometabolic risk across midlife. Methods: Participants in the CARDIA study with accelerometer and cardiometabolic biomarker data at Year 20 (2005-06) and Year 35 (2020-22) study visits (n=996) were included in this analysis. Waist circumference, mean arterial pressure, fasting glucose, fasting insulin, triglycerides, and HDL cholesterol were standardized and averaged to create a z-score, where higher scores represent worse cardiometabolic health. We used compositional isotemporal substitution models to estimate changes in cardiometabolic risk score resulting from replacement of sedentary time with LPA and whether associations varied by initial sedentary time or MVPA level. Results: Across midlife (mean 45±SD 3.5 [Y20] to mean 60±SD 3.6 [Y35] years old), mean cardiometabolic risk score increased by 0.03 SD. In those with initially low sedentary time, replacing 1 hour of sedentary time with LPA from Y20 to Y35 was associated with a -0.03 SD change in cardiometabolic risk score (95% CI: -0.06, -0.004; Figure) across the same time period. In those with initially high sedentary time, associations were attenuated and not statistically significant (-0.02; 95% CI: -0.04, 0.004). Associations were stronger with more time reallocated (up to 3 hours) and similar in those with low and high MVPA. Conclusions: Model-based replacement of sedentary time with LPA was associated with attenuation of age-related decline in cardiometabolic health across midlife.
Abstract P3048: Relationships of Body Roundness Index and Triglyceride–glucose Index with 5-year All-cause Mortality in Patients with Diabetes and Comorbid Hypertension: Evidence from Two Prospective Cohort Studies
Aims: We aimed to characterise the complex relationships of body roundness index (BRI) and triglyceride-glucose index (TyG) with 5-year all-cause mortality in patients with diabetes and comorbid hypertension. Methods: 5,728 patients from the 1999–2014 US National Health and Nutrition Examination Survey (NHANES) cycles and 3,456 from the 2005–2010 China Kailuan cycles were included. BRI was calculated as 364.2−365.5×√(1−(waist circumference in centimeters/2π) 2 ÷(0.5×height in centimeters) 2 ). TyG was calculated as the logarithmic product of the fasting triglyceride and glucose concentrations. The cut-off values of BRI and TyG were based on median values. Results: The prevalence of 5-year all-cause mortality was 8.4% in the NHANES database and 9.2% in the Kailuan cohort. Multivariable Cox regression demonstrated that a BRI of >6.2 (HR: 2.53, 95% CI: 1.71–2.96) and TyG of >9.5 (HR: 1.64, 95% CI: 1.39–2.72) were independent predictors of 5-year all-cause mortality in diabetic patients with hypertension after adjusting forage, gender, marital status, education level, smoking status, history of myocardial infarction, stroke, urinary protein and CKD-EPI eGFR. These results were reconfirmed in the Kailuan cohort for BRI (HR: 2.91, 95% CI: 1.93–3.57) and TyG (HR: 2.13, 95% CI: 1.86–3.02). TyG was found to mediate the association between BRI and all-cause mortality, being responsible for 24.1% (16.8%-28.5%) in the NHANES database and 27.5% (22.7%-30.1%) in the Kailuan cohort. No significant additive interactions were found between BRI and TyG on 5-year all-cause mortality. Significant multiplicative effects were identified between TyG and BRI in the NHANES database alone (Additive: RERI = 0.05, 95% CI – 3.21–1.97; Multiplicative, HR = 1.27, 95% CI 1.13–1.95 in the NHANES database; Additive: RERI = 0.27, 95% CI – 2.17–5.29; Multiplicative, HR = 1.02, 95% CI 0.85–2.21 in the Kailuan cohort). Conclusions: BRI and TyG were independent risk factors for 5-year all-cause mortality in patients with diabetes and comorbid hypertension. TyG was found to mediate a considerable proportion of the effect of BRI on all-cause mortality in cohorts from both the United States and China. Interventions aimed at improving obesity and abnormal fat distribution might reduce the all-cause mortality risk associated with insulin resistance.
Abstract P2158: Neighborhood poverty, John Henryism, and incident cardiovascular disease events in the Jackson Heart Study
Background: John Henryism (JH), or high effort-coping, is common when facing adversity. Little is known about cardiovascular disease (CVD) risk when living in poverty and having to cope with adversity. Objective: Test whether JH moderates the association between neighborhood-level poverty and incident CVD events among African American participants in the Jackson Heart Study (JHS). Hypothesis: High JH will increase the risk of CVD among participants who live in neighborhoods with greater poverty. Methods: JHS participants with complete data and no CVD at baseline (2000-2004) were included (n=2,691, mean age: 52.5 years). We utilized % below poverty as a marker for neighborhood poverty. JH was defined using the 12-item measure for high-effort coping (range: 0 to 36). Three categories were created using a tertile distribution: low JH (<28), moderate JH (29-32) and high JH (>32). Coronary heart disease (CHD) and stroke events were adjudicated from baseline to 2016; heart failure (HF) events were adjudicated from 2005 to 2016. Hazard ratios (HR 95% confidence intervals - CI) estimated the association between neighborhood poverty and CVD, adjusting for demographics, psychosocial factors (i.e., optimism), and risk factors (i.e., diabetes). Moderation by JH was examined via interaction terms and stratification in adjusted models using a p-value <0.05. Results: Median follow-up time was approximately 13 years for CHD and stroke cases and 10 years for HF cases. By 2016, there were 126 CHD, 187 HF, and 93 stroke cases. Greater poverty was associated with a greater risk of CHD [HR 1.37 (95% CI 1.15,1.63)] and HF [HR 1.48 (95% CI 1.29,1.71)]. There was a significant interaction between poverty and JH for CHD (p=<0.0001) and HF (p=<0.001). However, low JH combined with greater poverty was associated with a greater hazard of CHD [HR 1.93 (95% CI 1.34, 2.78)] after full adjustment. Individuals with greater poverty also had a higher risk of HF when reporting low JH [HR 1.58 (95% CI 1.22, 2.03)] and moderate JH [HR 1.53 (95% CI 1.14, 2.06)]. No significant associations were identified for high JH or stroke. Conclusion: Residing in neighborhoods with greater poverty was associated with an increased risk of CHD and HF for individuals who reported low and moderate levels of coping. Low JH may represent lower motivation/ low psychosocial resilience and may increase the risk of heart disease when living in poverty.
Adeno-associated viruses for efficient gene expression in the axolotl nervous system
Axolotls are amphibian models for studying nervous system evolution, development, and regeneration. Tools to visualize and manipulate cells of the axolotl nervous system with high-efficiency, spatial and temporal precision are therefore greatly required. Recombinant adeno-associated viruses (AAVs) are frequently used for in vivo gene transfer of the nervous system but virus-mediated gene delivery to the axolotl nervous system has not yet been described. Here, we demonstrate the use of AAVs for efficient gene transfer within the axolotl brain, the spinal cord, and the retina. We show that serotypes AAV8, AAV9, and AAVPHP.eB are suitable viral vectors to infect both excitatory and inhibitory neuronal populations of the axolotl brain. We further use AAV9 to trace retrograde and anterograde projections between the retina and the brain and identify a cell population projecting from the brain to the retina. Together, our work establishes AAVs as a powerful tool to interrogate neuronal organization in the axolotl.
Abstract 005: Plasma Senescence-Associated Secretory Phenotype (SASP) Proteins are Associated with the Development of Cognitive Impairment in Late Life: the ARIC study
Introduction: The senescence-associated secretory phenotype (SASP) consists of paracrine signaling molecules with deleterious effects secreted by senescent cells. However, little human data exist linking circulating SASP proteins to cognitive decline. Hypothesis: Plasma levels of SASP proteins will be associated with the development of mild cognitive impairment (MCI) or dementia and with subclinical neurodegenerative disease. Methods: Among participants in the Atherosclerosis Risk in Communities (ARIC) cohort study 5 th visit (2011-2013), we measured 26 SASP plasma proteins using an aptamer-based platform (SomaScan). Participants underwent protocol cognitive evaluations at Visit 5, Visit 6 (2016-2017) and Visit 7 (2018-2019), and a subset underwent brain magnetic resonance imaging at Visit 5. Among MCI/dementia-free individuals at Visit 5, we assessed associations of SASP proteins with incident MCI or dementia at Visit 6 (median interval 4.9 years) or Visit 7 (median interval 6.6 years) using multivariable logistic regression. We further assessed the associations of cognitive decline-related SASP proteins with total brain volume, temporal lobe meta-ROI volume, and volume of white matter hyperintensities using multivariable linear regression. All models were adjusted for age, sex, race and visit center. Two-sample cis-Mendelian randomization (MR) was performed to evaluate potential causal effects of proteins on overall dementia and specific dementia etiologies. Results: Among 2,024 participants included, mean age was 74±5 years, 59% were female, and 18% reported Black race. Between study Visit 5 and Visits 6 or 7, 639 (32%) participants developed MCI or dementia. Of the 26 SASP proteins, higher levels of 5 (GDF15, IGFBP7, CTSD, CST3 and HSPA8) were associated with higher risk of incident MCI or dementia (FDR-corrected p<0.05; Figure 1). Among these proteins, GFD15, CST3 and HSPA8 were associated with lower total brain volume and lower temporal lobe meta-ROI volume, and GDF 15, CST3, IGFBP7, and CTSD were associated with greater volume of white matter hyperintensities (Figure 2). Two-sample MR identified a potential causal effect of GDF15 on Alzheimer’s Disease (p<0.001). Conclusions: Higher plasma levels of a subset of the SASP proteins are associated with higher risk of developing MCI or dementia, and with greater subclinical alterations on neuroimaging. These findings support the potential role of cellular senescence in cognitive impairment.
Abstract MP13: Insomnia with Objective Short Sleep Duration is Associated with Hypertension in Adolescents
Introduction: Several studies have examined the association between insomnia and short sleep duration with elevated blood pressure (eBP) and stage 2 hypertension (HTN) in middle-aged adults. However, no study to date has examined the joint effect of self-reported insomnia and objective short sleep on eBP and HTN in adolescents. Methods: 421 adolescents (16.5±2.3 years old, 53.9% male, 21.9% racial/ethnic minority) from the Penn State Child Cohort, a randomly-selected population-based sample, underwent 9-hour polysomnography (PSG) and physical examinations. Insomnia was defined by a self-report of difficulties falling and/or staying asleep, while objective short sleep duration was defined based on the median PSG-measured total sleep time (i.e., < 7.7 hours of sleep). BP levels were measured 3 consecutive times in the seated position and the average of the last 2 was used to ascertain the presence of eBP (i.e., systolic ≥120 and diastolic <80 mmHg) and HTN (i.e., systolic ≥140 or diastolic ≥90 mmHg). Logistic regression models assessed the association of each group based on insomnia and objective sleep duration with eBP and HTN, while adjusting for age, sex, race/ethnicity, body mass index, apnea/hypopnea index, periodic limb movement index, socioeconomic status, and working status. Results: Compared to the reference group (n=126), adolescents who reported insomnia and slept objectively short (n=77) had 5-fold odds (95%CI=1.1-23.0, p-value=0.041) of having HTN. Adolescents who did not report insomnia but slept objectively short (n=136) had 2.7-fold odds (95%CI=1.5-4.8, p-value=0.001) of having eBP. Adolescents who reported insomnia and slept objectively normal (n=82) did not show any significant associations with either eBP or HTN. Conclusions: Insomnia with objective short sleep duration in adolescents is associated with stage 2 HTN, while short sleep alone is associated with incipient eBP. These findings further support that insomnia with short sleep duration is a more biologically severe phenotype of the disorder requiring different therapeutic approaches to improve sleep and reduce cardiovascular risk.
Abstract P2051: Community-academic partnership to optimize retention in a hypertension prevention trial in Black Men
Background: Black adults, particularly Black men are underrepresented in cardiovascular research studies, limiting interpretation and generalization of findings, adversely impacting health equity. Analyses of enrollment strategies often focus on recruitment. Retention strategies to optimize study participation among Black adults, specifically Black men are underexplored. Objectives: To describe retention strategies for Black male participants of a community-engaged hypertension prevention trial. Methods: Community-to-Clinic Linkage Implementation Program (CLIP) is a cluster-randomized barbershop-based implementation study of hypertension prevention for Black men. Eligible participants (age 18-85 years, blood pressure (BP) <130/80 mmHg), were recruited from 22 Black-owned barbershops in Staten Island, New York City. Recruitment was managed by Community Health Workers (CHWs) from a local service organization. Enrolled participants receive navigation to medical care, social services, and lifestyle coaching. Data collection includes questionnaire completion and BP measurement at time of enrollment, 6, 12, and 18 months. BP change at 12 months is the primary outcome. Results: We enrolled 425 participants. All 425 participants have reached the 6-month mark since enrollment and baseline data collection. 293 participants completed a 6-month follow-up visit. 12 and 18-month follow-up periods are ongoing with 206 participants completing the 12-month follow-up, and 71 participants completing the 18-month follow-up to date. After experiencing challenges with re-engaging participants for follow-up visits, new retention strategies were informed by input from CHWs, and the community advisory council (CAC) comprised of local leaders and collaborative community partners. Novel strategies included co-management of retention by CHWs and research staff, hiring a retention specialist, outreach to barbershops, evening and weekend appointments, and availability of mobile vans to meet participants at their choice of location. Conclusions: Retention is a vital component of community-engaged trials and requires creative thinking, flexibility, and cooperation between community and academic partners to optimize outcomes. We offer our experience as an example of real-world strategies for improving retention in a community-engaged trial.
HCV NS3/4A protease relocalizes CCTα to viral replication sites, enhancing phosphatidylcholine synthesis and viral replication
Positive-sense single-stranded RNA [(+)RNA] viruses constitute more than one-third of all virus genera, including numerous pathogens of clinical significance. All (+)RNA viruses reorganize cellular membranes from organelles to establish replication compartments (RCs). These RCs are thought to form a platform for membrane-associated replicases, in addition to protecting the viral RNAs from cytosolic innate immune signaling and RNA-degradation machinery. Previous work demonstrated that three families of (+)RNA viruses, namely Bromoviridae , Picornaviridae , and Flaviviridae , commonly induce the accumulation of phosphatidylcholine (PC) at their RCs. This phenomenon suggests a potential avenue for a broad-spectrum antiviral strategy targeting PC metabolism. Our study elucidates three key observations: i) hepatitis C virus (HCV) infection prompts the relocalization of CCTα, the rate-limiting enzyme in PC synthesis, to the RCs; ii) the enhancement of PC synthesis is contingent upon the protease activity of the NS3/4A protein; and iii) utilizing click chemistry, we demonstrate that HCV infection stimulates de novo PC synthesis at the viral replication site through the Kennedy pathway. These findings provide significant insights into the manipulation of lipid metabolism by HCV during RC formation, a mechanism likely conserved across various (+)RNA virus families.
Abstract 021: The Effectiveness of a Community Health Worker-Led Intensive Blood Pressure Intervention on Coronary Heart Disease and Heart Failure
Background: Coronary heart disease (CHD) and heart failure are increasing in China and represent significant public health and economic challenges. Although community health worker (CHW)-led interventions have shown effectiveness in blood pressure (BP) control within low-resource environments, their impact on CHD and heart failure is yet to be fully documented. Objectives: This study estimated the effectiveness of a CHW-led intensive BP intervention on risk of myocardial infarction and heart failure. Methods: The China Rural Hypertension Control Project (CRHCP) included 33,995 hypertensive patients from 326 villages in rural China. We randomly assigned 163 villages to a non-physician community healthcare provider-led intervention and 163 villages to usual care. In the intervention group, trained non-physician community healthcare providers (NPCHPs) initiated and titrated antihypertensive medications according to a simple stepped-care protocol to achieve a systolic BP (SBP) goal of <130 mmHg and a diastolic BP (DBP) goal of <80 mmHg, with supervision from primary care physicians. The primary outcomes were myocardial infarction and heart failure, with secondary analyses exploring fatal and nonfatal myocardial infarction. Results: Over 48 months, the net reduction in SBP was 22.0 mmHg (95% CI: 20.6-23.4) and in DBP was 9.3 mmHg (8.7-10.0) in the intervention group compared to usual care. During follow-up, we observed 174 myocardial infarction events (0.26% yearly rate) in intervention compared to 204 (0.32% yearly rate) in usual care participants. The NPCHP-led intervention demonstrated a 19% reduction in myocardial infarction (HR=0.81; 95% CI: 0.67-0.99). Notably, nonfatal myocardial infarction was reduced by 23% (HR=0.77; 0.62-0.96), although no significant reduction was observed for fatal events (HR=0.88; 0.63-1.53). For heart failure, we observed 107 events (0.16% yearly rate) in the intervention group compared to 147 (0.23% yearly rate) in usual care group, corresponding to a 32% reduction in heart failure (HR=0.68; 0.54-0.85). Conclusion: This study provides compelling evidence that intensive BP control, led by NPCHPs, is effective at reducing CHD and heart failure among rural residents in China. This NPCHP-led intervention is both cost-effective and feasible for implementation in low-resource settings. These findings support the scale-up of the CRHCP intervention across low- and middle-income countries to reduce the global burden of CHD and heart failure.
Abstract P2098: The Interaction of Vascular Risk Factors in Midlife and Late-life on Incident Dementia: The Atherosclerosis Risk in Communities Neurocognitive Study
Introduction: Vascular risk factors of hypertension, diabetes, and smoking in midlife (45-64 years) and possibly early late-life (65-74 years) are associated with increased risk of dementia. Current estimates of population attributable risk for dementia assume vascular factors are independent and do not interact to increase risk of dementia, which may underestimate the combined impact of vascular risk reduction on dementia incidence. In this study, we evaluated the joint association and interaction of vascular risk factors on risk of dementia. Methods: We performed a prospective cohort analysis using the Atherosclerosis Risk in Communities Neurocognitive Study using up to 33 years of follow-up (1987-2020). We used age as baseline (45-54 years, n=7,731; 55-64 years, n=12,273; and 65-74 years, n=6,660). We defined hypertension as systolic blood pressure ≥130 mm Hg, diastolic blood pressure ≥80 mm Hg, or anti-hypertension medication use. We defined diabetes as fasting glucose level ≥126 mg/dL, non-fasting glucose ≥200 mg/dL, self-reported physician diagnosis, or use of any diabetes medication. Current smoking was self-reported. We investigated additive and multiplicative interactions for combinations of vascular risk factors on incident (adjudicated) dementia by age 80 using joint effect variables in Cox regression models stratified by age of risk factor measurement (45-54 years, 55-64 years, or 65-74 years). For interaction analyses, parameter values >1 indicate positive interaction (synergy) and values <1 indicate negative interaction (antagonism). Results: In participants with risk factors measured in these baseline age strata, there were 801 (10%), 995 (8%), and 422 (6%) cases of incident dementia by age 80, respectively. Hypertension and diabetes exhibited positive interactions on the additive and multiplicative scales in midlife (Figure 1). Diabetes and smoking in midlife had positive additive interaction (value >1, Figure 2). All vascular risk factor combinations in late-life had negative interactions on the multiplicative scale (values <1, Figures 1-3). Conclusions: Hypertension with diabetes and diabetes with smoking, all measured in midlife, interact to increase risk of dementia by age 80. The overall impact of reducing midlife vascular risk factors on incident dementia could be sizeable. These findings highlight the importance of multifactor interventions addressing combinations of vascular risk factors for dementia prevention strategies.
Abstract MP18: Association of Sleep Duration with Cardiac Structure and Function in African Caribbeans: a preliminary report from the Tobago Heart Study
Emerging evidence suggests a potential relationship between sleep and cardiac abnormalities, even in the absence of apnea. Therefore, we aimed to test the association of sleep duration and cardiac structure and function as assessed by echocardiography in African Caribbeans aged 50-80 years from the Tobago Heart Study (THS). Between 2021-2024, participants without history of heart failure underwent clinical examinations, 4 to 7-day actigraphy-based sleep assessment, and transthoracic echocardiography (preliminary analysis of 401 participants with all measures). Echocardiograms were analyzed by a central core lab with measures including left ventricular ejection fraction (EF), diastolic function, and left ventricular hypertrophy (LVH), among other indices. Statistical analyses tested the association of 24-hour sleep duration or nighttime sleep (between 8PM-8AM) with echocardiographic parameters adjusted for age, sex, BMI, systolic blood pressure, diabetes, smoking, snoring frequency, and heart rate using linear or logistic regression, as appropriate. The cohort was middle-aged (mean 60 years), predominantly female (89%), hypertensive (73%), and obese (median BMI 31 kg/m 2 ). Mean 24-hr sleep duration was 5.8 hours (range=2-9 hours, median=5.5 hours), with a mean nighttime sleep duration of 5.5 hours. In adjusted models, longer nighttime sleep duration was not associated with echocardiography indices. However, when limited to just individuals who slept at least 5 hours at night, a 1-hour greater nighttime sleep duration was associated with ~5% lower left atrial volume index and ~5% lower pulmonary vascular resistance (P=0.01 for both). In contrast, nighttime sleep duration was not associated with left ventricular EF (b = -0.03 (-0.73 to 0.67), P=0.93). Results were similar when testing 24-hour sleep duration. Overall, among African Caribbean adults who sleep more than 5 hours per night, greater sleep duration may be associated with less risk of atrial fibrillation or pulmonary hypertension. This may be particularly relevant given that the African Caribbean population is at high risk for both hypertensive-related cardiac abnormalities and short sleep duration.
Monitoring chalcogenide ions–guided in situ transform active sites of tailored bismuth electrocatalysts for CO <sub>2</sub> reduction to formate
Although bismuth catalysts enable accelerated electrochemical CO 2 -to-formate conversion, the intrinsic active sites and forming mechanisms under operating conditions remain elusive. Herein, we prepared Bi 2 O 2 NCN, Bi 2 O 3 , and Bi 2 O 2 S as precatalysts. Among them, Bi 2 O 2 NCN-derived catalyst possesses optimum performance of electrochemical CO 2 -to-formate, exhibiting an upsurge of Faradaic efficiency to 98.3% at –0.6 V vs. reversible hydrogen electrodes. In-situ infrared and electrochemical impedance spectra trace and interpret the superior performance. Multimodal structural analyses utilizing quasi-in-situ X-ray diffraction, in-situ X-ray absorption near edge structure and in-situ Raman spectra provide powerful support to monitoring the catalysts’ in-situ transforms to metallic Bi, identifying the formation of the active sites influenced by the chalcogenide ions-guided: Carbodiimide promotes to form of the dominant Bi(003) facet exposure, which distinguishes from sulfide- and oxide-preferred dominant Bi(012) facets exposure. Concurrently, theoretical insights garnered from multiscale/multilevel computational analyses harmoniously corroborate the experimental findings. These findings show the pivotal role of chalcogenide in tailoring bismuth electrocatalysts for selective CO 2 reduction to formate, illuminating the significance of controlling structural chemistry in designing catalysts toward high-efficiency renewable energy conversion.
Abstract MP03: Metabolite Signature of Ultra-processed Foods Intake and Cardiovascular Morbidity and Mortality Among Low-income Black and White Americans
Background: High ultra-processed foods (UPF) intake may increase risks of CVD morbidity and mortality, but the mechanisms are unclear, and there is no biomarker for UPF intake. We aimed to identify UPF-related circulating metabolite signature (UPFsig) and evaluate its associations with incident coronary heart disease (CHD) and CVD mortality in a cohort of mostly low-income Black and White Americans. Methods: Untargeted profiling of baseline plasma metabolites was conducted in two nested case-control studies of incident CHD (n=1023) and incident prostate cancer (n=665). An 89-item food frequency questionnaire was administered at baseline (2002-2009). UPF intake (classified by Nova) was calculated as % of weight per day. The associations of UPF intake with 1,100 metabolites were evaluated by linear regression, adjusting for fasting status, batch, age, sex, race, education, income, smoking, alcohol drinking, physical activity, sitting hours, daily calories, BMI, and history of diabetes, hypertension, and hypercholesterolemia. Metabolites with P <0.05 were selected by elastic net with repeated 10-fold cross-validation to construct the UPFsig. Conditional logistic and Cox regression were used to examine the associations of UPFsig with incident CHD and CVD mortality, respectively. Results: Of 1,688 participants, 70% were men, 61% were Black, and the mean baseline age was 56.5 (SD:12.0) years. The mean intake of UPF was 41.1% (SD:15.3). A total of 126 metabolites were selected to construct UPFsig (correlation r=0.51, P <0.0001). The UPFsig was associated with incident CHD (adjusted OR [95%CI] per SD increase =1.43 [1.20-1.69]), particularly among Black (1.73 [1.35-2.22]) compared to White participants (1.17 [0.93-1.47], P interaction =0.01). Additionally, during a mean 13.4-year follow-up, 285 CVD deaths were noted. The UPFsig was associated with CVD mortality (adjusted HR [95%CI] per SD increase =1.22 [1.07-1.39]), even after adjusting for UPF score (1.17 [1.01-1.36]). The adverse associations were largely consistent across participants of varied sociodemographics, lifestyles, and metabolic disease status. Conclusions: We identified a metabolite signature of UPF and demonstrated its significant associations with CVD morbidity and mortality. The UPFsig may serve as a biomarker and provide insight into mechanisms of UPF intake on CVD. The racial difference in the association of UPFsig with incident CHD warrants further research.
Abstract P3045: Symptoms of Hypoglycemia in Older Adults With and Without Diabetes
Background: The ability of the body to maintain glucose homeostasis decreases with age, and symptoms of non-life-threatening hypoglycemia are non-specific (e.g. hunger, lack of concentration), which may put older adults at risk of hypoglycemia. The prevalence and correlates of symptoms of hypoglycemia in persons without diabetes are poorly understood. Objective: To examine the prevalence and correlates of symptoms of hypoglycemia among older adults with and without diabetes. Methods: Participants in the Atherosclerosis Risk in Communities (ARIC) Study (2021-22) with or without diabetes who were administered the 17-item Hypoglycemia Symptom Rating Questionnaire (HypSRQ) to assess symptoms of hypoglycemia experienced over the past 2 weeks. We quantified the burden of self-reported symptoms of hypoglycemia according to diabetes and high-risk diabetes medication status and evaluated the associations of symptoms with comorbidities including poor physical functioning (short physical performance summary battery score<7) and depression (CES-Depression scale score9). Results: Among 1,085 participants (mean age 83, 60% female), 20.6% had diabetes (not on insulin/sulfonylurea (SU)) and 9% had diabetes (on insulin/SU). Overall, the number of symptoms reported were similar among those without diabetes (1.18 1.9 SD) and those with diabetes not taking insulin/SU (1.18 2.2) and higher among those with diabetes taking insulin/SU (1.41 2.0). Persons with diabetes (on insulin/SU) were more likely to report at least one symptom of hypoglycemia compared to persons with diabetes (not on insulin/SU) or without diabetes. Persons not on insulin/SU most commonly reported feelings of fatigue while persons on insulin/SU reported headaches, sudden temperature changes, feeling unsteady and faint ( Figure ). Irrespective of diabetes status, among those with 1 symptom (vs. none), 18% (vs. 14%) had poor physical functioning, 31% (vs. 23%) had obesity, and 6.5% (vs. 2.5%) had depression. Conclusion: The burden of symptoms of hypoglycemia among very old adults is highest among those with type 2 diabetes and on high-risk diabetes medication. The most prevalent symptom reported differed by high-risk diabetes medication status. Hypoglycemic symptoms are non-specific in older adults who are often experiencing a high burden of comorbidities; therefore, it may be useful to screen for hypoglycemia in older, high-risk patients.
Core dimensions of human material perception
Visually categorizing and comparing materials is crucial for everyday behavior, but what organizational principles underlie our mental representation of materials? Here, we used a large-scale data-driven approach to uncover core latent dimensions of material representations from behavior. First, we created an image dataset of 200 systematically sampled materials and 600 photographs (STUFF dataset, https://osf.io/myutc/ ). Using these images, we next collected 1.87 million triplet similarity judgments and used a computational model to derive a set of sparse, positive dimensions underlying these judgments. The resulting multidimensional embedding space predicted independent material similarity judgments and the similarity matrix of all images close to the human intersubject consistency. We found that representations of individual images were captured by a combination of 36 material dimensions that were highly reproducible and interpretable, comprising perceptual (e.g., grainy, blue) as well as conceptual (e.g., mineral, viscous) dimensions. These results provide the foundation for a comprehensive understanding of how humans make sense of materials.
Abstract P1024: Associations between DASH Diet Adherence and Cardiovascular-Kidney Metabolic (CKM) Syndrome Stages: 2011-2020 National Health and Nutrition Examination Survey
Background: Cardiovascular-kidney metabolic (CKM) syndrome substantially contributes to rising healthcare costs and reduced life expectancy, particularly in underserved communities. The relationship between dietary approaches such as Dietary Approaches to Stop Hypertension (DASH) in managing CKM syndrome is unclear. Objective: To assess the relationship between DASH adherence and CKM syndrome stages among US adults. Methods: Cross-sectional data from the 2011-2020 National Health and Nutrition Examination Survey (NHANES) were analyzed. DASH scores (range: 17-37) were divided into quintiles: Q1 (<24.5, lowest), Q2 (>24.5-27), Q3 (>27-29), Q4 (>29-32), and Q5 (>32, highest). CKM syndrome stages were defined as stage 0: no CKM (reference); stage 1: excess adiposity, prediabetes; stage 2: metabolic risk factors, high-risk kidney disease; stage 3: very high-risk kidney disease; and stage 4: clinical CVD with CKM risk factors. Separate multivariable logistic regression models were fitted, modeling the odds of each CKD stage 1-4 vs. 0, adjusting for covariates. Results: Our sample included 22,746 adults, mean age: 49 ±17 years, 52% female, median DASH score of 26.5. Compared to Q5 (highest adherence), those in the lowest DASH adherence quintile (Q1) consistently showed higher odds of being in more advanced CKM syndrome stages ( Figure ). For CKM stage 1 vs. stage 0, participants in Q1 had 1.46 times the odds (95% CI: 1.08, 1.97) of being classified in stage 1. For CKM stage 2 vs. stage 0, individuals in Q1 were 1.87 times more likely (95% CI: 1.48, 2.37) to be in stage 2. The association was even stronger for advanced stages: for CKM stage 3 vs. stage 0, those in Q1 had 4.76 times the odds (95% CI: 1.92, 14.48) of being classified in stage 3. Similarly, for CKM stage 4 vs. stage 0, participants in Q1 were 3.46 times as likely (95% CI: 2.02, 6.11) to reach stage 4, compared to those demonstrating the highest level of DASH adherence. Conclusion: Our findings suggest that lower DASH adherence is associated with higher odds of advanced CKM syndrome stages, highlighting its potential role in CKM syndrome prevention beyond hypertension management.