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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.
Abstract P3112: OBESITY RELATED CARDIOVASUCLAR MORTALITY IN ASIAN AMERICANS
Introduction: The Global Burden of Disease Study suggested 80% of obesity&overweight (OOW) related deaths in US have an underlying cause of either type 2 diabetes, chronic kidney disease, dyslipidaemias&hypertensive heart disease (DKOLH). Studying OOW related cardiovascular deaths (CVD) in Asian Americans (AA), a population known to have heterogeneous risk CVD by nation of origin has not been well studied. Methods: National Vital Statistics System (NVSS) mortality data extracted (2005-2019) for 6 AA subgroups and non-Hispanic Whites between 35-74 years of age (premature). Identified OOW-related CVD with one or more of DKOLH by using ICD.10 coding. Population estimates from American Community Survey (ACS). Age and sex specific mortality rates calculated using negative binomial regression. Weighted average rates calculated for premature deaths in RStudio and Average Annual Percentage Change (AAPC) calculated using Joinpoint Regression Program. Results: For OOW related premature mortality - significant increase in AAPC across all subgroups of AA males (p<0.05), AAPC for Japanese (-3.4%, 95%CI -5.1 to -1.7) females significantly decreased, AAPC for Chinese and Asian Indian females has not shown any significant change over the years, highest AAPC for Koreans and Vietnamese over years for both males (7.01%, CI 4.6-9.5%; 6.88% CI 5.4-8.4%) and females (3.62% CI 1.3-5.9% ; 3.82% CI 1.7-6%). Trends for mortality rates across years remain highest for Filipinos for both genders. The rise in premature OOW related CVD for all AA males is disproportionately higher than the change in their respective all-cause premature mortality over years, for females it is disproportionately higher only for Filipinos (p<0.05). Conclusions: Our study demonstrates a novel way to use NVSS mortality data for estimating premature OOW related CVD rate using reliable population estimates. Decline in Japanese and Chinese female OOW related premature CVD needs to be appreciated and factors leading to the same need to explored, while disproportionate rise in amongst all AA males particularly Koreans and Vietnamese when compared to their respective all-cause mortality is alarming and warrants further direct targeted interventions, while persistently high and rising mortality rates amongst Filipinos demonstrate ineffectiveness of current strategies at various levels of prevention.
Phase transitions in the rolling of irregular cylinders and spheres
When placed on an inclined plane, a perfect 2D disk or 3D sphere simply rolls down in a straight line under gravity. But how is the rolling affected if these shapes are irregular or random? Treating the terminal rolling speed as an order parameter, we show that there are qualitative transitions in the speed as a function of the dimension of the state space and inertia. We calculate the scaling exponents and the macroscopic lag time associated with the presence of first- and second-order transitions and describe the regimes of coexistence of stable states and the accompanying hysteresis. Experiments with rolling cylinders corroborate our theoretical results on the scaling of the lag time. Experiments with spheres reveal closed orbits and their period-doubling in the overdamped and inertial limits, respectively, providing visible manifestations of the hairy ball theorem and the doubly connected nature of S O ( 3 ) , the space of 3D rotations. Going beyond simple curiosity, our study might shed light on a number of natural and artificial systems that involve the rolling of irregular objects, ranging from nanoscale cellular transport to robotics.
Abstract 025: Quantifying the association between gentrification and hypertension risk: The Atherosclerosis Risk in Communities (ARIC) Study
Introduction: Static neighborhood-level factors, such as access to healthcare and the physical environment, are associated with hypertension (HTN) risk. Less is known on how dynamic neighborhood changes (e.g. gentrification) impact HTN risk. We tested the hypothesis that individuals living in gentrified neighborhoods, compared to non-gentrified neighborhoods, have a decreased risk of HTN. Methods: We quantified the association of living in a gentrified neighborhood with HTN status among 6260 participants from Visit 5 (2011-13) of the ARIC Study. A composite z-score was calculated from 2010 Census measures of median household income and gross rent, proportion of adults with a bachelor’s degree, and proportion living above the poverty level. The z-score was used in two frameworks to quantify gentrification: 1) a relative spatial comparison between a geocoded participant address-centric 0.5 mile radius and a surrounding 20-mile radius, and 2) temporal change in the spatial comparison between the 1990 and 2010 Census measures. The outcome was defined as no HTN (systolic blood pressure [SBP] <130 mmHg), controlled HTN (SBP <130 mmHg on medication), unmedicated HTN (SBP ≥130 mmHg), or medicated and uncontrolled HTN (SBP ≥130 mmHg on medication). Adjusted multinomial logistic regression quantified the odds of HTN. Models were further stratified by ARIC study site. Results: Among the 6260 participants (mean age 76 years, 59% female, 22% Black), 843 (13%) had no HTN, 2387 (38%) had controlled HTN, 674 (11%) had unmedicated HTN, and 2356 (38%) had medicated and uncontrolled HTN. Compared to participants with no HTN, a one unit increase in the 2010 spatial gentrification z-score was associated with lower odds of controlled HTN and medicated and uncontrolled HTN, but not unmedicated HTN ( Figure ). There was a strong protective association of gentrification on HTN among White participants living in Forsyth County, NC and Washington County, MD. Among Black participants in Jackson, MS, living in a gentrified neighborhood was associated with increased odds of unmedicated HTN only. The pattern of associations was similar but attenuated for spatial and temporal gentrification z-score from 1990 to 2010. Conclusions: Living in neighborhoods with higher spatial gentrification z-scores is associated with lower odds of HTN. Black and White participants in ARIC may have experienced gentrification differently, potentially alluding to long-term structural factors that impact health.
Abstract P3137: Psychological Factors and Coronary Atherosclerosis Progression in the Multi-Ethnic Study of Atherosclerosis
Background: Psychological distress increases the risk of acute cardiac events, but studies are conflicting on whether it causes atherosclerotic progression. In previous longitudinal studies, missing outcome measures across time may have resulted in selection bias. Objective: To estimate the longitudinal association of psychological factors with coronary atherosclerotic burden. Methods: In the Multi-Ethnic Study of Atherosclerosis (MESA), we examined psychological exposures via validated scales (anger trait, anxiety trait, chronic stress, lifetime discrimination, everyday discrimination, and depression) and subclinical atherosclerosis with coronary artery calcium (CAC) at baseline for all participants, who were invited to repeat their CAC scores at four subsequent visits. Linear mixed models tested the association of psychological scales with atherosclerosis progression by the slope of log-transformed CAC score over time, accounting for confounders in the causal model (age, gender, race, income, work status, neighborhood). As a sensitivity analysis to adjust for selection bias, we ran the model after multiple imputations by chain equations of the missing CAC scores at the follow-up visits. Results: The 6,814 MESA participants had a median age of 62 years (IQR53-70), and 47% were males. All participants had a baseline CAC Score measurement: 746 had only the baseline, 2452 participants had two CAC scores, 2831 had three, and 785 had four. The mean time between the baseline and the last CAC score was 6.5 ± 3.5 years. For a standard deviation (SD) increase in each psychological scale, the change in CAC score per visit was estimated to be near zero (Figure 1 shows the 95% confidence intervals of the percent change in CAC Score by SD increment in each scale). The number of missing CAC scores was associated with a more adverse socioeconomic and cardiometabolic risk profile and higher baseline CAC Scores, suggesting selection bias. The analysis performed after imputing missing CAC scores showed consistent associations between higher levels of psychological scales and progression of the CAC scores over time (Figure 1). Conclusion: While no association was found in the analysis of observed outcomes, associations emerged after outcome imputation to account for selection bias due to missing data. Future studies should minimize missing values of the outcome to avoid biased results.
Phased ERK responsiveness and developmental robustness regulate teleost skin morphogenesis
Elongation of the vertebrate embryonic axis necessitates rapid expansion of the epidermis to accommodate the growth of underlying tissues. Here, we generated a toolkit to visualize and quantify signaling in entire cell populations of the periderm, the outermost layer of the epidermis, in live developing zebrafish. We find that oriented cell divisions facilitate growth of the early periderm during axial elongation rather than cell addition from the basal layer. Activity levels of Extracellular signal-regulated kinase (ERK), a downstream effector of the MAPK pathway, gauged by a live biosensor, predict cell cycle entry, and optogenetic ERK activation regulates cell cycling dynamics. As development proceeds, rates of peridermal cell proliferation decrease, and ERK activity becomes more pulsatile and functionally transitions to promote hypertrophic cell growth. Targeted genetic blockade of cell division generates animals with oversized periderm cells, yet, unexpectedly, development to adulthood is not impaired. Our findings reveal stage-dependent differential responsiveness to ERK signaling and marked developmental robustness in growing teleost skin.
Abstract 014: Healthy sleep score, plasma metabolome, and subclinical cardiovascular risk factors: the Bogalusa Heart Study
Introduction: A healthy sleep pattern (HSP) has been related to lower risks of cardiovascular diseases. However, sleep behaviors are usually self-reported, which introduces bias. While metabolomics provides an objective method and complements traditional biomarkers, the underlying metabolomic mechanisms linking a comprehensive sleep pattern and subclinical cardiovascular risk factors are not well known. Hypothesis: We hypothesize that an HSP is associated with metabolites, which may subsequently influence subclinical cardiovascular risk factors. Methods: A total of 1032 participants from the Bogalusa Heart Study who underwent untargeted metabolomics profiling and had existing sleep data were included in the current analysis. HSP was estimated using information on sleep duration, chronotype, insomnia, snoring, and daytime sleepiness. Elastic net regularized regression was applied to generate an HSP-related metabolomic signature. Subclinical cardiovascular risk factors were measured by echocardiography and ultrasonography, including left ventricular mass index (LVMI), relative wall thickness (RWT), left ventricular geometry, pulse wave velocity (PWV), and carotid intima-media thickness (cIMT). Results: The HSP was inversely associated with subclinical cardiovascular risk factors [LVMI (β: -0.88, SE: 0.29; p=0.002), RWT (β: -0.004, SE: 0.002; p=0.03), IMT (β: -0.02, SE: 0.01; p=0.018), and concentric LV hypertrophy (OR: 0.72, 95% CI: 0.59 – 0.88; p=0.001)]. Using elastic net regularized regression, we identified a metabolomic signature ( Figure ), comprised of 44 metabolites, robustly associated with the HSP (r=0.22; p<0.001). In multivariable regression models, the metabolomic signature showed significant inverse associations with LVMI (β: -2.5, SE: 0.77; p=0.001), RWT (β: -0.016, SE: 0.006; p=0.004), IMT (β: -0.09, SE: 0.02; p<0.001), and lower odds of concentric remodeling (OR: 0.52, 95% CI: 0.33 – 0.82; p=0.005), eccentric LV hypertrophy (OR: 0.26, 95% CI: 0.09 – 0.69; p=0.007), and concentric LV hypertrophy (OR: 0.38, 95% CI: 0.19 – 0.76; p=0.007) ( Figure, Model 2 ). The associations persisted after further adjustment for the HSP ( Figure, Model 3 ). Conclusion: We identified a metabolomic signature that robustly reflected the HSP, and was associated with lower subclinical cardiovascular risk factors, independent of traditional risk factors and phenotypic sleep measurements.
Abstract P3156: Cardiovascular Kidney Metabolic Syndrome Stage Prevalence varies by Asian Subgroup
Introduction: Cardiovascular Kidney Metabolic (CKM) Syndrome characterizes the interplay of cardiovascular, renal, and metabolic disorders with five progressive stages. Prior data have shown that CKM syndrome is lower among aggregated Asian people when compared to Non-Hispanic White (NHW) people. However, when disaggregated, some Asian groups have a greater burden of CKM-related conditions (e.g., diabetes) compared to NHW people. We examined CKM prevalence among Asians compared to NHW people using the National Health Interview Survey (NHIS). Hypothesis: We hypothesize that CKM syndrome prevalence will be higher in Asian subgroups compared to NHWs. Methods: Using 2015-2018 NHIS data, we estimated the prevalence of CKM Stages among Asian Indians, Chinese, and Filipinos compared to NHW people. Variables included obesity, using Asian-specific Body Mass Index (BMI) values, diabetes status, hypertension, cholesterol, and the presence of cardiovascular symptoms to distinguish CKM stages. Kidney function was unavailable in NHIS. Stages were defined as: 0 (BMI <23), 1 (BMI ≥23 or prediabetes), 2/3 (BMI ≥23, prediabetes, hypertension, diabetes, or high cholesterol), or 4 (established cardiovascular disease). Associations between level of physical activity, access to care, socioeconomic status, and CKM stages were tested using bivariate (ANOVA, Pearson’s chi-squared) and regression analysis. Results: We examined 86,762 adults aged 20-80 (mean = 45.8). Prevalence of stages varied by race, with CKM being highest in Chinese (45.7%) for Stage 0, Asian Indians (53.8%) for Stage 1, and Filipinos (29.6%) for Stage 2/3 (Figure 1). The prevalence of CKM in the aforementioned groups was significantly higher compared to NHW, with Stage 0 prevalence being 15.2% higher in Chinese, Stage 1 prevalence being 19.0% among Asian Indians, and Stage 2/3 prevalence being 3.7% higher among Filipinos (Figure 1). Conclusions: When disaggregated, Asian Americans experience a different burden of CKM syndrome when compared to NHW people. Factors such as the prevalence of prediabetes, diabetes, high cholesterol, and higher BMI values undoubtedly contribute to the disparities that are noted. The different burden of CKM stage by race highlights the need for culturally appropriate interventions to reduce racial disparities in CKM syndrome. Further research is warranted on the impact of demographic, socioeconomic, and behavioral factors on CKM in Asian Americans.
Nanoscale distribution of bioactive ligands on biomaterials regulates cell mechanosensing through translocation of actin into the nucleus
Cells respond to adhesive ligands such as arginine-glycine-aspartate (RGD) through integrins, which regulates cellular activities via influencing cytoskeleton assembly. Herein, we report that the nanoscale distribution of active ligands on biomaterials regulates cells through not only cytoplasmic tension but also nuclear tension. This is particularly related to translocation of actin into nucleus and highlighted in our interpretation of an “abnormal” phenomenon that large RGD nanospacing (>70 nm) disassembles integrin clusters, inhibits cell adhesion, but promotes osteogenic differentiation of mesenchymal stem cells. Our studies reveal that the unstable adhesion at the 150 nm RGD distance increases actin dynamics, resulting in the nuclear translocation of globular (G) actin. The compartment polymerization of more G-actins to filamentous actins in nucleus increases nuclear tension, facilitating transcription activity and releasing calcium ions from the endoplasmic reticulum. This noncanonical mechanotransduction process sheds insight into mechanotransduction pertinent to cell–material interactions.