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Abstract P2035: All The Common Cardiovascular Diseases Are Aggravated By Climate Hazards: Current Evidence And Mechanisms
Climate change is widely recognized as a significant factor impacting cardiovascular diseases , yet a detailed and comprehensive understanding of this relationship remains underdeveloped. Aim: This study aims to provide a thorough review of the current epidemiological evidence regarding how climate change affects cardiovascular diseases. Method: Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, population-based epidemiological studies focused on climate change and cardiovascular diseases were collected from Google Scholar up to January 2023. A Bibliometric analysis was conducted to describe the basic bibliographic information of the included studies. Due to methodological reasons, a meta-analysis was not performed. Results: A total of 308 relevant studies were identified from 46,200 search records that met the specified criteria, with the USA, China, and Australia being the leading contributors in this field. These studies identified 208 unique pathways through which climate change influences the morbidity and mortality of cardiovascular diseases. Key climate factors such as heatwaves, cold spells, dust storms, air pollution, wildfires, and hurricanes were found to significantly increase the risk of cardiovascular diseases. Among these, temperature change emerged as the most extensively studied topic. Conclusion: Cardiovascular disease can be exacerbated by various climate hazards, underscoring the need for more controlled and high-quality research to further explore these hazardous effects and interventions. Moreover, further measures are needed to mitigate extreme climate changes and reduce their impact on cardiovascular health.
Structural basis of DNA replication fidelity of the Mpox virus
The Mpox virus (MPXV) is an orthopoxvirus that caused a global outbreak in 2022. The poxvirus DNA polymerase complex is responsible for the replication and integrity of the viral genome; however, the molecular mechanisms underlying DNA replication fidelity are still unclear. In this study, we determined the cryoelectron microscopy (cryo-EM) structures of the MPXV F8–A22–E4 polymerase holoenzyme in its editing state, in complex with mismatched primer–template DNA and DNA containing uracil deoxynucleotide. We showed that the MPXV polymerase has a similar replication-to-edit transition mechanism to proofread the mismatched nucleotides like the B-family DNA polymerases of other species. The unique processivity cofactor A22–E4 undergoes conformational changes in different working states and might affect the proofreading process. Moreover, we elucidated the base excision repair (BER) function of E4 as a uracil-DNA glycosylase and the coupling mechanism of genome replication and BER, characteristic of poxviruses. Our findings greatly enhance our molecular understanding of DNA replication fidelity of orthopoxviruses and will stimulate the development of broad-spectrum antiviral drugs.
Abstract 023: Comparison of Office and Ambulatory Blood Pressure in Middle-Aged Adults: Findings from the DASH and DASH-Sodium Study
Background: Ambulatory blood pressure (ABP) captures BP throughout the day during a range of activities, body positions, and environments, while office blood pressure (OBP) is performed in a rested, seated position in clinic. Since ABP on average is lower than OBP, current guidelines recommend setting lower risk thresholds for ABP compared to OBP. Objective: To determine equivalent values of OBP and awake ABP in middle-aged adults with respect to subclinical cardiovascular disease (CVD). Methods: DASH and DASH-Sodium trials were feeding studies that enrolled adults age 22 and older with a systolic BP of 120 to 159 mmHg and diastolic BP of 80 to 95 mmHg without treated hypertension, diabetes, or recent CVD. In both trials, ABP and OBP were concurrently measured at two (DASH) or three (DASH-Sodium) visits. ABP was performed using a Spacelabs device for 24 hours. OBP was performed with a random-zero sphygmomanometer three times per visit over 4-5 visits, following a standardized research protocol. We measured three cardiac biomarkers: N-terminal pro-B-type natriuretic peptide (NT-proBNP), high sensitivity cardiac troponin I (hs-cTnI), and high sensitivity C-reactive protein (hs-CRP) in serum collected concurrent with ABP. We investigated equivalent values of OBP and awake ABP by using the equipercentile equating method. We calculated the risk of elevated biomarkers for OBP and awake ABP using logistic models with generalized estimating equations, and identified BP values that corresponded to the same risk of elevated biomarkers. Results: There were 587 participants (mean age 47.8±10 years, 51.9% female, and 52.9% Black) with 1,238 visits ( Table 1 ). OBP values consistently corresponded with higher values of awake ABP ( Table 2 ). Using the equipercentile equating method, OBP of 130/80 mmHg and 140/90 mmHg corresponded to awake ABP of 136/83 mmHg and 145/95 mmHg, respectively. Based on cardiac biomarkers, an OBP of 130/80 mmHg had the same risk of elevated NT-proBNP, hs-cTnI, and hs-CRP as an awake ABP of 135/83, 135/84, and 138/80 mmHg, respectively. Conclusion: Contrary to current guidelines, ABP thresholds for risk among relatively healthy, middle-aged adults, were higher than OBP. These findings challenge guidelines promoting universal equivalency values for interpreting out-of-office BP measures such as ABP, and imply that risk thresholds may vary by context, population, and the quality of the office measurement.
Abstract 064: Fairness Heterogeneity of the PREVENT Equations in US Young Adults
Background: In 2023, the AHA published Predicting Risk of cardiovascular disease EVENTs (PREVENT), a new set of race-agnostic risk prediction equations that estimate 10-year risk of cardiovascular disease (CVD) in US adults ages 30-79 years. Equations include a base model and a model adding social deprivation index (SDI). Aim: To evaluate fairness of the base and SDI-enhanced PREVENT equations across race/ethnicity and sex groups in US young adults. Methods: We included adults aged 20-39 years enrolled between 2008-2009 without a history of CVD from Kaiser Permanente Southern California. From the eligible sample of 266,378, we randomly selected 50,000 young adults for computational efficiency. Primary outcome was incident CVD (defined as myocardial infarction, fatal coronary heart disease, fatal and nonfatal stroke, and heart failure) at 10 years. We estimated 10-year CVD risk using the PREVENT base and SDI-enhanced models. To assess race-sex specific model performance, we used Brier score, Harrell’s C, and mean calibration in each group. Overall algorithmic fairness was evaluated by (1) fair calibration, which measures whether agreement between predicted and observed risk is equally accurate across groups using Hosmer-Lemeshow goodness-of-fit and pairwise Wilcoxon signed-rank tests, and (2) concordance imparity, which measures the largest deviation of discriminative abilities across racial and ethnic groups by taking the difference between maximum and minimum Harrell’s C across groups. Results: We included 50,000 young adults who were mean (SD) age 31.7 (5.4) years, 61.3% female, and 51.1% Hispanic, who had 312 incident CVD events by 10 years. Performance metrics were similar in the base and SDI-enhanced equations. Models were under-calibrated in Black and White females and Asian and Black males, indicating observed risk was higher than predicted risk. Agreement between predicted and observed risk was not equally accurate across racial and ethnic groups in males or females (biased calibrated). Discriminative abilities also varied across groups, with Harrell’s C highest in Black males and lowest in Asian females. Concordance imparity was similar in the base and SDI-enhanced models (0.097 vs. 0.095). Conclusion: The PREVENT equations may not provide consistent risk predictions for young adults across race/ethnicity and sex groups, which could lead to unequal CVD prevention efforts. Addition of SDI to the PREVENT equations did not provide improvement in fairness.
The mechanism of electrical conduction in glassy semiconductors
We argue that the dominant charge carrier in glassy semiconducting alloys is a compound particle in the form of an electron or hole bound to an intimate pair of topological lattice defects; the particle is similar to the polaron solution of the Su–Schrieffer–Heeger Hamiltonian. The spatial component of the density of states for these special polarons is determined by the length scale of spatial modulation of electronegativity caused by a separate set of standalone topological defects. The latter length scale is fixed by the cooperativity size for structural relaxation; the size is largely independent of temperature in the glass but above melting, it decreases with temperature. Thus we predict that the temperature dependence of the electrical conductivity should exhibit a jump in the slope near the glass transition; the size of the jump is predicted to increase with the fragility of the melt. The predicted values of the jump and of the conductivity itself are consistent with experiment.
Abstract P2053: Social Vulnerability and Likelihood of Death at Home from Cardiovascular Disease in US Counties, 2016-2020
Introduction: Areas where people disproportionately die at home from cardiovascular disease (CVD) are incompletely described. The United States (US) Centers for Disease Control and Prevention (CDC) developed the Social Vulnerability Index (SVI) using 16 US census measures clustered into four themes of vulnerability. The SVI and its themes may be utilized to score counties based on county-level social determinants of health. We conducted a county-level ecological study on the association of county SVI and its themes with CVD-related deaths occurring at home. Method: We used 2016–2020 CDC Wide-ranging Online Data for Epidemiologic Research data on county-level CVD-related (ischemic heart disease, heart failure, stroke, and hypertension) deaths in persons ≥18 years of age, and location of death (home, etc.), available for 92.4% of 3,226 US counties. The SVI and its themes (socioeconomic status [theme 1], household composition&disability [theme 2], minority status&language [theme 3], and housing type&transportation [theme 4]) are scored from 0 to 1 (low to high vulnerability) based on their national percentile ranking. We grouped county-level SVI from 2018 into quartiles (Q1 [least] to Q4 [most vulnerable]). Due to overdispersion, we used negative binomial regression to estimate the likelihood of CVD-related deaths at home in Q4 vs Q1, offset by the total county CVD-related deaths. We reported rate ratios (RR [95% Confidence Interval], p-value). Results: CVD-related home death rates increased in a stepwise manner from SVI Q1 to Q4 (Fig). For overall SVI, the likelihood of death at home was 15% higher in Q4 vs Q1 (RR 1.15 [1.12–1.18], p<0.0001). The greatest disparity was seen in theme 1, with Q4 vs Q1 having 27% higher likelihood of death at home (RR 1.27 [1.22–1.33], p<0.0001). For theme 2, there was no statistically significant difference in the likelihood of death at home in Q4 vs Q1 (RR 0.98 [0.95–1.01], p=0.36). For theme 3, Q4 vs Q1 had 6% higher likelihood of death at home (RR 1.06 [1.03–1.09], p<0.0001). For theme 4, Q4 vs Q1 had a 6% lower likelihood of death at home (RR 0.94 [0.91–0.97], p<0.001). Conclusion: In US counties, higher social vulnerability was associated with a higher likelihood of CVD-related death at home, with the strength and direction of this association varying between the themes of vulnerability. SVI and its themes may be utilized to target interventions to improve access to hospital or hospice care.
Abstract P3022: Plasma Lipidome is Associated with 10-Year Risk of Incident Diabetes in the Coronary Artery Risk Development in Young Adults (CARDIA) Study
Background: Disordered lipid metabolism is highly prevalent in diabetes. Mechanisms have been identified through which lipids can impact glucose metabolism. Previous cohort studies of lipidomics and diabetes often have been limited to narrow lipidomic coverage or have lacked sample diversity in sociodemographic characteristics. Methods: Data were from CARDIA, a population-based cohort of self-identified Black and White race adults, recruited from 4 U.S. urban centers in 1985-86 (n=5,115). On a sample subset, lipidomics data were generated from fasting plasma collected at the Yr 20 exam, using infusion-mass-spectrometry, yielding n=14 lipid classes and n=756 molecular species. For analysis, molecular species within classes that contained >1 fatty acid were grouped by total carbon length and number of double bonds (n=300 total species). Participants who had prevalent diabetes or were pregnant at Year 20 were excluded from the analysis. Associations between distinct lipid classes/species and 10-year incident diabetes [n (cases) = 1,084 (104)] were quantified with Cox proportional hazards regression, adjusting for sociodemographics, health behaviors, and clinical variables, and accounting for multiple comparisons. Results: Ten of the 14 classes were significantly associated with 10-year incident diabetes (Fig 1). Findings for species within 8 classes were consistent with class-level associations, (direction and significance); other class-species associations displayed discordance (Fig 2). For example, the ceramide class was not, but a ceramide species (22:2) was, associated with incident diabetes. Conclusions: Class- and species-level analysis revealed unique patterns of associations, motivating analysis of both. Lipidomic signatures of diabetes may elucidate metabolic pathways implicated in diabetes risk that are not captured in standard lipid panels. These findings may inform clinical evaluation of diabetes risk in early-middle-age, when preventive measures may be more effective.
Logic-based machine learning predicts how escitalopram attenuates cardiomyocyte hypertrophy
Cardiomyocyte hypertrophy is a key clinical predictor of heart failure. High-throughput and AI-driven screens have the potential to identify drugs and downstream pathways that modulate cardiomyocyte hypertrophy. Here, we developed LogiRx, a logic-based mechanistic machine learning method that predicts drug-induced pathways. We applied LogiRx to discover how drugs discovered in a previous compound screen attenuate cardiomyocyte hypertrophy. We experimentally validated LogiRx predictions in neonatal cardiomyocytes, adult mice, and two patient databases. Using LogiRx, we predicted antihypertrophic pathways for seven drugs currently used to treat noncardiac disease. We experimentally validated that escitalopram (Lexapro) and mifepristone inhibit hypertrophy of cultured cardiomyocytes in two contexts. The LogiRx model predicted that escitalopram prevents hypertrophy through an “off-target” serotonin receptor/PI3Kγ pathway, mechanistically validated using additional investigational drugs. Further, escitalopram reduced cardiomyocyte hypertrophy in a mouse model of hypertrophy and fibrosis. Finally, mining of both FDA and University of Virginia databases showed that patients with depression on escitalopram have a lower incidence of cardiac hypertrophy than those prescribed other serotonin reuptake inhibitors that do not target the serotonin receptor. Mechanistic machine learning by LogiRx discovers drug pathways that perturb cell states, which may enable repurposing of escitalopram and other drugs to limit cardiac remodeling through off-target pathways.
Abstract MP69: Nursing facility use and frailty index as indicators of reserve and resilience in adults with hospitalization for a cardiovascular event: The REasons for Geographic And Racial Differences in Stroke (REGARDS) study
Introduction: Reserve and resilience refer to the degree of robustness prior to, and the subsequent ability to recover from a health stressor. Frailty and nursing facility use (NFU) may characterize varying levels of physical reserve and resilience among individuals hospitalized for a cardiovascular event. Objective: To characterize older US adults who had a CVD hospitalization using novel indicators of reserve and resilience: nursing facility use and a frailty index. Methods: We analyzed data from 1,605 Black and White REasons for Geographic And Racial Differences in Stroke (REGARDS) study participants with Medicare fee-for-service coverage who were age ≥65.5 years and had no NFU before an adjudicated myocardial infarction, heart failure, or stroke hospitalization in 2004-2019. Participants were grouped into mutually exclusive categories based on Medicare claims for NFU and vital status (i.e., alive without NFU, alive with NFU, and death) within 182 days and 183-365 days following discharge. We calculated a claims-based frailty index (index ranges from 0 to 1, with higher values indicating greater deficit accumulation) within 182 days before admission, and within 182 days and 183-365 days following discharge. Results: The mean age at admission was 77.4 years, 43.6% were female, and 30.4% were Black. Most participants were alive without NFU for 365 days post-discharge (64.9%), followed by those who died within 182 days following discharge (11.6%), and those who were alive with NFU within 182 days and alive without NFU in the 183-365 days following discharge (10.3%). Participants who were alive without NFU for 365 days post-discharge had the lowest frailty index in each assessment period (Figure) and were younger (mean age 76.5 years) versus the other groups (range 77.3-80.4 years). There were no substantial differences in subgroups defined by NFU and vital status post-discharge in analyses stratified by sex or race. Conclusion: NFU and frailty index identify older adults with varying levels of apparent reserve and resilience before and after a cardiovascular hospitalization.
Abstract P2165: Association of neighborhood environment chracteristics and suboptimal cardiovascular health based on Life’s Essential 8 among young adults in Puerto Rico
Background: Cardiovascular health (CVH) among young adults in Puerto Rico (PR) is below optimal levels, underscoring the vulnerability of this understudied population. Understanding the influence of neighborhood environment on CVH is crucial for designing public health interventions that promote and sustain CVH. We assessed the association between neighborhood environment characteristics and CVH among young adults living in PR. Methods: This study analyzed data from 2,179 adults aged 18–29 years (mean age: 22.6 y; 60.8% women) participating in the PR-OUTLOOK study. CVH was measured using the AHA's Life’s Essential 8 metric score (range 0-100), with suboptimal CVH defined as a score below 80. The neighborhood environment was evaluated using the Mujahid Neighborhood Health Questionnaire, which assesses neighborhood violence, safety, aesthetic quality, walkability, access to healthy foods, social cohesion, and interaction with neighbors. Responses were recorded on a 5-point Likert scale (1=strongly disagree to 5=strongly agree), except for the violence and neighbor interaction scales, which ranged from 1=often to 4=never. Separate logistic regression models examined the association between each neighborhood environment characteristic and suboptimal CVH, adjusting for age, sex at birth, education, and subjective social status. Results: Mean scores (±SD) for neighborhood environment characteristics were as follows: violence (3.7±0.5), safety (3.4±1.1), aesthetic quality (2.8±0.5), walkability (3.1±0.8), availability of healthy foods (2.4±1.0), social cohesion (3.3±0.7), and activities with neighbors (1.3±0.8). Approximately 72.5% of participants had suboptimal CVH. In adjusted models, young adults who perceived their neighborhoods as having higher aesthetic quality (OR = 0.70, 95% CI: 0.57–0.85), greater walkability (OR = 0.84, 95% CI: 0.75–0.94), and better availability of healthy foods (OR = 0.89, 95% CI: 0.81–0.98) had lower odds of suboptimal CVH compared to their counterparts. Conclusions: Young adults in PR residing in neighborhoods with better aesthetics, walkability, and access to healthy foods have lower odds of suboptimal CVH. Further research is necessary to explore the long-term effects of these neighborhood characteristics on CVH, which could inform the design of targeted interventions to improve cardiovascular outcomes in this population.
On the shape of air bubbles trapped in ice
Water usually contains dissolved gases, and because freezing is a purifying process these gases must be expelled for ice to form. Bubbles appear at the freezing front and are then trapped in ice, making pores. These pores come in a range of sizes from microns to millimeters and their shapes are peculiar; never spherical but elongated, and usually fore-aft asymmetric. We show that these remarkable shapes result of a delicate balance between freezing, capillarity, and mass diffusion. A nonlinear ordinary differential equation suffices to describe the bubbles, which features two nondimensional numbers representing the supersaturation and the freezing rate, and two additional parameters representing simultaneous freezing and nucleation treated as the initial condition. Our experiments provide us with a large variety of pictures of bubble shapes. We show that all of these bubbles have their rounded tip well described by an asymptotic regime of the differential equation and that most bubbles can have their full shape quantitatively matched by a full solution. This method enables the measurement of the freezing conditions of ice samples, and the design of freeze-cast porous materials. Furthermore, the equation exhibits a bifurcation that explains why some bubbles grow indefinitely and make long cylindrical “ice worms,” well known to glaciologists.
Abstract 050: Diet quality, pathway-specific polygenic risk scores, and risk of type 2 diabetes among US men and women
Background: Healthy diets are associated with lower risk of type 2 diabetes (T2D) risk, but it is unclear if individuals with different genetic risks benefit from specific dietary strategies. Hypothesis: The associations between healthy dietary patterns and lower T2D risk may be modified by global and pathway-specific polygenic risk scores (PRS). Methods: We conducted prospective analyses in 40,609 participants from the Nurses’ Health Studies and Health Professionals Follow-Up Study, who were free of baseline diabetes, cardiovascular disease, and cancer, with up to 36 years of follow-up. Diet was assessed every 4 years via a food frequency questionnaire. We examined 6 recommendation-based and 2 mechanistic-based dietary patterns. A global PRS and 12 pathway-specific PRS denoting distinct T2D mechanisms were calculated. Cox regression was used to examine diet, PRS, and their interactions with T2D risk. Results: We identified a total of 4,760 T2D cases during the follow-up. Higher global PRS and 11 pathway-specific PRS, except the one related to bilirubin metabolism, significantly predicted higher T2D risk. In multivariable-adjusted analyses, all dietary indices indicating a lower dietary quality were associated with higher T2D risk (hazard ratios comparing extreme quintiles 1.06-2.21, P-trend <0.05/8). We found additive interactions between the Global PRS and the alternate Healthy Eating Index, healthy plant-based diet index, and proinflammatory and hyper-insulinemic diets, in relation to T2D risk (relative excess risk due to interaction 0.09 to 0.32, P-interaction ≤0.004; Figure ). PRS for beta-cell dysfunction and fat deposition-mediated insulin resistance also showed interactions with proinflammatory and hyper-insulinemic diets ( P-interaction ≤0.004; Figure ). Conclusions Healthy dietary patterns are associated with lower T2D risk across a wide genetic risk spectrum. Diets targeting inflammation and insulinemia may be particularly beneficial for those genetically predisposed to beta-cell dysfunction and fat deposition-mediated insulin resistance.
Abstract P3029: Phenotypic and Genetic Correlations of Imaging Traits in the Abdomen-Heart-Brain Axis: Insights into Multimorbidity of Cardiometabolic Diseases and Depression
Objective: The development of multimorbidity of cardiometabolic diseases (CMDs) and depression likely involves pathophysiological processes across multiple organs. This study aimed to investigate imaging traits in the abdomen-heart-brain axis linked to the CMDs-depression multimorbidity and assess their phenotypic and genetic connections using magnetic resonance imaging (MRI) data. Methods: This study analyzed multi-organ MRI data including 7 abdominal, 82 cardiac, and 676 brain traits from 31,839 UK Biobank participants. CMDs included coronary artery disease, stroke, heart failure, type 2 diabetes, hypertension and hyperlipidemia. First, multivariable logistic regressions estimated associations of imaging traits with the CMDs-depression multimorbidity. Second, multivariable linear regressions quantified pairwise correlations among significant cross-organ traits. Third, transcriptome-wide association study (TWAS) identified shared genes of traits significantly correlated with each other across all 3 regions (i.e., triads). Fourth, LASSO regressions constructed genomics scores using single nucleotide polymorphisms from the shared genes. Fifth, the prediction performance of imaging traits and genomics scores for the CMDs-depression multimorbidity was evaluated by AUCs. FDR correction was used to adjust for multiple testing. Results: Seven abdominal, 27 cardiac, and 340 brain traits were significantly associated with the CMDs-depression multimorbidity. Among 11,749 pairs of significant cross-organ imaging traits, 6385 abdomen-heart-brain triads were identified, with liver volume as the most connected node. The directions of associations among imaging traits in these cross-organ triads aligned with directions of their biological functions, suggesting multiple organs acting as a coordinated system. TWAS revealed TNFSF12 from whole blood as the shared gene underlying the significant liver-heart-brain connection associated with the CMDs-depression multimorbidity. The integration of imaging traits with genomics score (AUC = 0.84) improved prediction performance for the CMDs-depression multimorbidity, outperforming demographic and lifestyle models (AUC = 0.78) (P = 0.014). Conclusions: This study identified highly correlated cross-organ imaging traits that were associated with the CMDs-depression multimorbidity. A shared gene was found for a liver-heart-brain triad. Imaging traits and genomic score significantly enhanced prediction performance on top of traditional factors.
Effects of binding partners on thermal reversion rates of photoswitchable molecules
The binding of photoswitchable molecules to partners forms the basis of many naturally occurring light-dependent signaling pathways and various photopharmacological and optogenetic tools. A critical parameter affecting the function of these molecules is the thermal half-life of the light state. Reports in the literature indicate that, in some cases, a binding partner can significantly influence the thermal half-life, while in other cases it has no effect. Here, we present a unifying framework for quantitatively analyzing the effects of binding partners on thermal reversion rates. We focus on photoswitchable protein/binder interactions involving LOV domains, photoactive yellow protein, and CBCR GAF domains with partners that bind either the light or the dark state of the photoswitchable domain. We show that the effect of a binding partner depends on the extent to which the transition state for reversion resembles the dark state or the light state. We quantify this resemblance with a ϕ switching value, where ϕ switching = 1 if the conformation of the part of the photoswitchable molecule that interacts with the binding partner closely resembles its dark state conformation and ϕ switching = 0 if it resembles its light state. In addition to providing information on the transition state for switching, this analysis can guide the design of photoswitchable systems that retain useful thermal half-lives in practice. The analysis also provides a basis for the use of simple kinetic measurements to determine effective changes in affinity even in complex milieu.
Abstract MP30: Estimated Health Benefits, Costs, and Cost-Effectiveness of Eliminating Dietary Industrial Trans-fatty Acids in China
Objectives: To estimate the potential health benefits, costs, and cost-effectiveness of mandating a limit on industrial trans-fatty acids (iTFA) in all foods, fats, and oils in China. Methods: A multiple cohort proportional multistate life table model was used to project the impact of eliminating dietary iTFA on ischemic heart disease (IHD) burden and costs over different time horizons (5 years, 10 years, and population lifetime). Nationally representative data on iTFA intake were derived from the 2015-2018 China Total Diet Study and China National Health and Nutrition Survey 2011. The health benefits were modelled as averted IHD deaths, events, and health-adjusted life years (HALYs) gained. Net costs were estimated by combining healthcare costs and policy implementation costs, which included government monitoring and industry reformulation costs. Cost-effectiveness was assessed through incremental cost-effectiveness ratios, with both costs and HALYs discounted at 3%. Results: Over 10 years, the mandatory iTFA limit was estimated to prevent approximately 111K IHD deaths (95% uncertainty interval [UI]: 101K-120K), 744K IHD events (95% UI: 678K-807K), 330K HALYs (95% UI: 301K-357K), resulting in a healthcare cost saving of around 2.8 billion USD (95% UI: 2.5-3.0). Over the population lifetime, the intervention was projected to avert 1.9 million (95% UI: 1.7-2.0) IHD deaths, 3.4 million (95% UI: 3.0-3.7) IHD events, and 5.9 million (95% UI: 5.4-6.4) HALYs, saving approximately 5.1 billion USD (95% UI: 4.6-5.7) Policy implementation costs were estimated at 165 million USD (95% UI: 132-198) over the first 10 years and 295 million USD (95% UI: 261-329) over the population lifetime ( Figures 1-2 ). The intervention was estimated to be cost-saving regardless of the time horizon, with robust findings across sensitivity analyses. Conclusions These findings suggest that legislating a mandatory limit on iTFAs could be a cost-saving strategy to prevent a substantial number of IHD events and deaths in China.
Abstract P3004: Plasma and Serum Water T <sub>2</sub> are Strong Predictors of Cardiometabolic Health: Implications for Point-Of-Care Screening
Introduction: Plasma and serum water T 2 are global biosensors of metabolism. They detect changes in the average rotational diffusion time of water induced by shifts in metabolic balance (Fig. 1). Water T 2 can be measured using a miniaturized magnetic resonance device (Fig. 2). However, the performance of T 2 parameters in combination with other readily available measures of cardiometabolic health is unknown. Hypothesis: The accuracy of water T 2 for predicting cardiometabolic health can be enhanced by including age, body mass index, and pulse rate. Specific Aim: Quantify the predictive accuracy of plasma or serum water T 2 with and without other measures. Methods: This is a secondary analysis of FWT2, an observational cross-sectional study of 72 disease-free adults. Other study exclusions were pregnancy and fasting <10 h. Hydrogen T 2 relaxation decay curves were recorded for plasma or serum at 37°C using a Bruker mq20 magnetic resonance relaxometer. Water T 2 was resolved using a discrete component analysis (XPFit, Alango Ltd.). Statistical analyses utilized JMP Pro v17.2 (SAS Institute): factor analysis, machine-learning predictor screening, and multi-variable linear regression. Goodness-of-fit and predictive accuracy were measured using adjusted R-squared (R 2 adj), root mean square error, corrected Akaike’s information criterion (AICc), Bayesian information criterion (BIC), and k-fold cross-validation R 2 (R 2 k-fold). Results: Table 1 shows the parameters for each regression model. Cardiometabolic health, the outcome or Y variable, was one of two latent variables generated by factor analysis: CMH1 for Phase 1&2 and CMH2 for Phase 2 only (Table 1). By itself, plasma water T 2 was a good predictor of cardiometabolic health (models 1A and 3A). The addition of age, BMI, and pulse rate improved the R 2 adj from 0.631 (3A) to 0.796 (3B). Improvements (decreases) were observed for RMS error, AICc, and BIC, with an improvement (increase) in R 2 k-fold. Models with serum water T 2 showed similar trends. Conclusions: Plasma and serum water T 2 are strong predictors of cardiometabolic health, especially when combined with age, BMI, and pulse rate. Water T 2, along with other predictors, explained up to 84% of the variance in cardiometabolic health. The predictive value of T 2 is independent of adiposity. Buoyed by predictive accuracy, measurement simplicity, and device portability, plasma and serum water T 2 show promise for metabolic health screening at the point of care.
Environmental justice beyond race: Skin tone and exposure to air pollution
Recent research, focused mostly on the United States and Western Europe, shows that marginalized communities often face greater environmental degradation. However, the ethnoracial categories used in these studies may not fully capture environmental inequality in the Global South. Moving beyond conventional ethnoracial variables, this study presents findings exploring the link between skin tone and fine particulate matter (PM 2.5 ) exposure in Colombia. By matching household geolocations from a large-scale longitudinal survey with satellite-based PM 2.5 estimates, we find that skin tone predicts both initial pollution exposure levels and their changes over time. Although average exposure levels remained stable during our study period, the environmental justice (EJ) landscape in Colombia contemporaneously underwent a complete transformation. In 2010, lighter-skinned individuals faced higher PM 2.5 exposure, but darker-skinned individuals experienced steeper increases in the following years. By 2016, the EJ gap had reversed, with people with the darkest skin tones exposed to PM 2.5 levels nearly one SD higher than those faced by people with the lightest skin tones. These patterns remain robust when controlling for a comprehensive set of theoretically relevant covariates, including ethnoracial self-identification and income. Disproportionate exposure to pollution from fires partially explains the observed disparities. Decomposition analysis shows that this variable, local collective action, and economic marginalization account for a sizeable share of the EJ gap. However, one-third of the gap remains unexplained by observable characteristics. With climate change intensifying fire incidence, the disproportionate disease burdens that vulnerable groups face might deepen unless policy measures are taken to reverse this trend.
Abstract P1104: The Association Between Subjective Social Status and Dietary Quality Within Occupational Groups of African Americans: The Jackson Heart Study
What people eat is a major contributor to health outcomes, including development of metabolic, cardiovascular, and other chronic diseases. Dietary quality varies widely is influenced by factors including sex, race, geographic location, socioeconomic status, self-perception of community standing, and occupation. These factors potentially interact, making an understanding of dietary quality difficult to fully disaggregate and therefore challenging to modify from a population health perspective. This study sought to analyze the interaction between subjective social status (SSS) and occupation on dietary quality among African Americans in the Deep South, as well as assess their marginal effects. Hypotheses Dietary quality will vary by occupational groups and levels of SSS. There will be an interaction between occupational groups and (SSS) on dietary quality. Methods: A cross-sectional analysis of data from participants of the Jackson Heart Study was completed. Participants ( n = 4,727) who had complete data for occupation, the alternative healthy eating index (AHEI, a measure of diet quality) score, and SSS (as measured by the Community MacArthur Scale) at exam 1 were included in the analysis. A general linear model with main and interaction effects for SSS and occupation group was fit to AHEI. Results: Type III F -tests from ANOVA showed no significant interaction between SSS and occupational groups with respect to mean AHEI scores ( p = 0.7635). Significant main effects were found for both the occupational groups and SSS level ( p < 0.0001). Pairwise comparisons of occupational groups revealed significantly different mean AHEI scores among several groups. Most notably, those in the management/professional occupation appeared to have higher mean AHEI compared to all the other groups. Mean AHEI was estimated to increase by 0.3723 units (SE = 0.0781) for every one-unit increase in SSS. Residual diagnostics and goodness-of-fit methods verified model adequacy. Conclusions In conclusion, occupation and SSS each contribute significantly to dietary quality as measured by AHEI; some occupational groups show significant differences in dietary quality; and there is no evidence of an interaction between occupation groups and SSS, indicating that the positive association between subjective social status and dietary quality is the same for each occupational group.
Abstract P3017: <i>Helicobacter pylori</i> Seroprevalence and its Association with Blood Pressure and Hemoglobin A1c in the National Longitudinal Study of Adolescent to Adult Health (Add Health)
Introduction: Chronic Helicobacter pylori ( H. pylori ) infection, a ubiquitous enteric bacterium, may lead to systemic inflammation, possibly increasing the risk of hypertension (HTN) and type 2 diabetes mellitus (T2D). Studies linking H. pylori infection with HTN and T2D have produced mixed results. Objective: To determine if H. pylori seropositivity is associated with elevated blood pressure (BP), hemoglobin A1c (HbA1c), and annual change in SBP, DBP, and HbA1c over a median of 10 years using Add Health. Methods: Wave IV (2008-2009) Add Health participants were tested for immunoglobulin antibodies to H. pylori with a binary cutoff for seropositivity of 13.217 U/mL. Systolic BP (SBP), diastolic BP (DBP), and HbA1c were measured at Waves IV and V (2016-2018). Annual rates of change in SBP, DBP, and HbA1c were calculated by dividing the difference in value between Waves IV and V by the number of years elapsed for each participant. Prevalence differences (PD), differences in point estimates, and 95% confidence intervals (CI) were determined using multivariable linear regression models accounting for Add Health's complex sampling design and adjusting for age, sex, race/ethnicity, education, income, childhood socioeconomic status, body mass index, smoking, alcohol use, and medication use. Results: The median ages in Wave IV and V were 28 and 37 years, respectively, with 54% being female. In the final analytic sample (N=4,600), 958 (21%) participants were seropositive for H. pylori . Seropositive participants were more likely to be non-Hispanic Black (24% vs 9.3%) and less likely to be college graduates (12% vs 19%) than seronegative individuals. In adjusted models, there were no differences in SBP (PD -0.79 mmHg (CI -2.79, 1.22)), DBP (PD -0.65 mmHg (CI -2.79, 1.22)), and HbA1c (PD -0.01% (CI -0.08, 0.05)) by H. pylori seroprevalence. The adjusted annual mean (standard deviation) change in SBP (-0.12 (0.81) vs 0.03 (0.85)), DBP (0.23 (0.60) vs 0.22 (0.59)), and HbA1c (-0.02 (0.05) vs -0.02 (0.04)) from Wave IV to V was not different between seropositive and seronegative participants. Conclusions: In a cohort of younger adults, H. pylori seropositivity was not associated with higher BP or HbA1c or differences in annual rate of change in SBP, DBP, and HbA1c over a median of 10 years. Further research is needed to understand the relationship between H. pylori infection and cardiometabolic disorders over a longer period of time as individuals age into mid to late life.
Decoding planetary surfaces by counting cracks
Planets are often covered with thin cracked shells. From mud films to lithospheres of rock or ice, fracture networks form two-dimensional (2D) tessellations of convex polygons whose geometry encodes their genesis. Here, we chart the geometry of 2D fracture mosaics across the solar system, and decode their formative conditions using a new dynamical crack model. We show that mosaics can be projected onto a Symbolic Ternary Diagram, where the relative proportions of “T,” “X,” and “Y” junctions are uniquely related to contributions from distinct modes of fracture. Most planetary mosaics cluster in a region associated with hierarchical fracture networks, where sequential cracking favors formation of T junctions. Exceptions to this rule may betray the presence of water. Europa’s fracture networks stand apart due to the predominance of X junctions; this is a special feature of ice, where healing of cracks by refreezing of water allows new fractures to overprint older ones. Several fracture networks on Mars appear as outliers due to the high proportion of Y junctions. These patterns—previously interpreted as ancient mudcracks and frozen polar terrain, based on geological evidence—are consistent with the twisting of crack junctions by cyclic volume change. Our findings suggest that counting cracks could aid in the identification of other water-influenced planetary environments.