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Abstract P2124: Association between accelerometer-corrected physical activity and the prevalence of hypertension, diabetes, and obesity: Results from Korea National Health and Nutrition Examination Survey, 2014-2017
Background: Self-reported measurements have been used as a monitoring approach because it is difficult to objectively assess physical activity levels at a population level. Our aims were to assess the validity of self-reported physical activity data compared with accelerometer-based measurements in adults and to investigate the association between self-reported physical activity (Study 1) and the prevalence risk of hypertension, diabetes, and obesity, had physical activity been measured by accelerometer instead (Study 2). Methods: We used data from the 2014-2017 Korea National Health and Nutrition Examination Survey, which involved a nationally representative sample of n=20,059 Korean adults aged 20-79 years. Participants in our Global Physical Activity Questionnaire (GPAQ) survey wore an accelerometer (Actigraph GT3X+) for a period of seven days. We used a regression model to calculate validity coefficients and attenuation factors using accelerometer-measured physical activity as the criterion measure. Associations between moderate-to-vigorous physical activity status and the prevalence of hypertension, diabetes, and obesity were determined using multiple logistic regression calibration method. Results: The results from Study 1 showed that participants tended to overreport their physical activity levels when measured through GPAQ, with this tendency being more pronounced among those with lower levels of physical activity. Additionally, women and individuals with higher education or income were more accurate in reporting their physical activity levels than others. Study 2 revealed that the associations between the prevalence of hypertension, diabetes, and obesity and adjusted physical activity were considerably deattenuated, after correcting for measurement error in self-reported physical activity. The prevalence ratio (PR) for hypertension and diabetes for higher levels of self-reported physical activity, using the inverse hyperbolic sine function (IHS) transformation, was 0.79 (95% CI: 0.78, 0.80) and 0.75 (95% CI: 0.74, 0.77), respectively. Conclusions: The associations between physical activity and the prevalence risk of hypertension, and diabetes are significantly attenuated by the overestimation of self-reported physical activity, suggesting that the beneficial effects of physical activity may have been underestimated in the past. Further research will analyze the association between physical activity and mortality.
Abstract 041: A Novel Machine Learning Strategy to Integrate Multi-Omics Data and Detect Genomic Loci and Gene-Environment Interactions for LDL Cholesterol
Introduction: LDL cholesterol (LDLC) is highly heritable, and understanding its mechanism is crucial for cardiovascular disease treatment and prevention. While multi-omics data is widely available, integrating different omics in etiologic research of LDLC is limited due to computational challenge. Machine learning (ML) methods can address the challenge but are primarily used for risk prediction, and their “black box” nature complicates model interpretation. Hypotheses: We hypothesized that top important single nucleotide polymorphisms (SNPs) ranked by an ML-based genomic model contained novel genetic loci for LDLC, and that adding metabolomics data to the genomic model would change SNP importance due to mediation by internal metabolites and interaction with external metabolites. Methods: We developed a random-forest based genomic prediction model for LDLC using genome-wide SNPs among 1239 participants of the Bogalusa Heart Study (BHS), then incorporated 792 known metabolites to develop a multi-omics model. We compared variable importance matrix (VIMs) for SNPs between models. For SNPs losing importance, we tested whether metabolites mediated their associations with LDLC; for those gaining importance, we tested their interactions with all metabolites on LDLC. All analyses controlled for age, sex, race, and the first 10 genetic principal components. Results: VIMs changed significantly between the genomic and multi-omics models. Among the 20 SNPs with the largest drop in VIMs, we found that ( Table 1 ): 1) 256 metabolites, mostly (n=252) in lipid pathways, mediated ( P <0.05) their associations with LDLC. 2) These metabolites were top-ranked inputs in the multi-omics model. 3) Twelve loci have been reported by GWAS of lipid phenotypes, including 5 for LDLC. 4) Five genes, ELOVL6 , VAV2 , CDH10 , ACKR3 , and LMF1 were not reported by lipid GWAS, but were involved in lipid metabolism in animal models. For the 20 SNPs with the largest increase in VIMs, interacting metabolites were of non-lipid pathways or xenobiotics ( Table 2 ). Conclusion: We developed a novel ML strategy to integrates genomics and metabolomics data and provided empirical evidence of using it to discover new loci and gene-environment interactions for LDLC. This strategy can be expanded to other omics.
Abstract P2106: Serum Metabolomic Markers of Dietary Potassium and Incident Chronic Kidney Disease Risk
Introduction: Potassium is found in many foods and has been inversely associated with incident chronic kidney disease (CKD). Untargeted metabolomic profiling is a powerful approach for discovery of novel diet biomarkers and to highlight metabolic pathways that explain associations between dietary potassium and CKD. Methods: Dietary potassium was derived from food items assessed using an interviewer-administered questionnaire administered at visit 1 (1987-89). Incident CKD was a composite outcome using reduced estimated glomerular filtration rate (<60 mL/min/1.73 m 2 and ≥25% eGFR decline), hospitalization and death codes related to CKD stage 3+, or end-stage kidney disease identified via US Renal Data System registry. Participants were followed for CKD until December 31, 2020. Cross-sectional associations between dietary potassium (mg/1000 kcal) and 359 serum metabolites were evaluated with linear regression models. Prospective associations between significant potassium-related metabolites and CKD were studied with Cox regression models. Analyses were adjusted for covariates and accounted for multiple comparisons. Results: In 3,822 U.S. adults, we identified 53 significant associations between dietary potassium and serum metabolites, representing 6 super-pathways (amino acids, n=17; lipids, n=11; cofactors and vitamins, n=9; xenobiotics, n=8; carbohydrate, n=5; peptides, n=3). Over two decades of follow-up, 1,618 (42%) of participants developed incident CKD. Ten of the 53 metabolites from the cross-sectional analysis were prospectively associated with incident CKD. Two metabolites, kynurenine and glycerate, had the a priori expected directions of associations with dietary potassium and CKD ( Table ). There was a significant trend of CKD risk across quartiles of kynurenine and glycerate. Conclusions: Kynurenine and glycerate and their respective pathways may be representative of dietary potassium’s metabolic impact on CKD development.
Respiratory rate and its associations with disease and lifestyle factors in the general population – results from the KORA-FF4 study
Objective The aim of the study was to derive median age- and sex-specific respiratory rates in a population-based sample of adults and to identify disease and lifestyle factors associated with elevated respiratory rates. Methods In the population-based KORA FF4 study conducted in Augsburg, Germany, 5-minute 12-lead resting electrocardiograms (ECGpro-system, AMEDTEC) were recorded in 2,224 participants from 39 to 88 years. Respiratory rate was derived from these electrocardiograms. Sex- and age-specific medians, IQRs, and percentiles were calculated. Associations of sociodemographic, disease, and lifestyle variables with elevated resting respiratory rate were assessed by univariable and multivariable logistic regression analyses. Results Respiratory rate decreased slightly from youngest to middle-aged women and men and increased in old age. Overall, median (IQR) was 15.80 (3.16) breaths per minute (brpm). Five percent of the participants had values lower than 12.06 brpm, and five percent had values above 20.06 brpm (95th percentile). Elevated respiratory rates of ≥ 18.6 brpm were found in 13.8% (n = 308). In an adjusted logistic regression model, age, abdominal obesity, diabetes, COPD, smoking, and low education were significantly associated with elevated respiratory rate. Stratified analyses showed that education appeared to be more relevant in women, while the effect of diabetes was more pronounced in men. Conclusions High respiratory rate may be an indicator of impaired health in the general population, especially regarding pulmonary and metabolic characteristics, and unfavorable lifestyle and living conditions. Individuals with an increased respiratory rate should therefore be examined and followed up more closely to recognize diseases and adverse progressions at an early stage and to possibly prevent them.
Abstract P2149: Obstructive Sleep Apnea Is Associated With Lower In-Hospital Mortality Among Non-ST Segment Myocardial Infarction Patients With Gender Disparities In Cardiac Intervention
Introduction: Obstructive Sleep Apnea (OSA) is a known risk factor for cardiovascular diseases and has been linked to a higher incidence of non-ST segment elevation myocardial infarction (NSTEMI). However, the impact of OSA on in-hospital outcomes remains controversial. This study investigates the association of OSA with in-hospital mortality and clinical outcomes in NSTEMI patients, including gender-based differences. Hypothesis: We hypothesized that OSA would be associated with worse in-hospital outcomes among NSTEMI patients. Methods: This retrospective cohort study used Nationwide Inpatient Sample (NIS) data from 2016 to 2021, identifying 3,935,084 NSTEMI admissions. Multivariable logistic regression and propensity score matching (PSM) adjusted for demographics, comorbidities, and hospital characteristics. Gender-specific outcomes were analyzed using logistic regression. Primary outcomes included in-hospital mortality, with secondary outcomes covering cardiac arrest, cardiogenic shock, arrhythmias, mechanical and ventilatory support, healthcare utilization and cardiac procedures. Results: OSA patients had lower in-hospital mortality (aOR: 0.8; 95% CI: 0.7–0.8; p < 0.001) and reduced odds of sudden cardiac arrest, invasive ventilation, cardiogenic shock, and thrombolysis. However, they were more likely to require non-invasive ventilation (aOR: 2.2; 95% CI: 2.1–2.3; p < 0.001) and had higher odds of atrial fibrillation, atrial flutter, and pacemaker insertion. Female NSTEMI patients with OSA showed lower in-hospital mortality (aOR: 0.9; 95% CI: 0.8–0.9; p < 0.001). However, they underwent fewer procedures, including PCI (aOR: 0.8), CABG (aOR: 0.6), and coronary angiography (aOR: 0.9; p < 0.001 for all). Females also had a higher risk of venous thromboembolism (aOR: 1.12; 95% CI: 1.1–1.2). Hospital costs were $6,460.93 lower for OSA patients, with females incurring $11,104.87 less than males. Length of stay differences were not statistically significant (p = 0.251). Conclusions: OSA is associated with improved in-hospital survival among NSTEMI patients despite the increased need for non-invasive ventilation and arrhythmias. The gender-specific analysis highlights disparities, as female patients had lower mortality but underwent fewer diagnostic and interventional procedures, raising concerns about potential under-treatment. These findings call for further investigation into the role of sex differences in guiding care for NSTEMI patients with OSA.
Evolution of Critical Care Cardiology: An Update on Structure, Care Delivery, Training, and Research Paradigms: A Scientific Statement From the American Heart Association
Critical care cardiology refers to the practice focus of and subspecialty training for the comprehensive management of life-threatening cardiovascular diseases and comorbid conditions that require advanced critical care in an intensive care unit. The development of coronary care units is often credited for a dramatic decline in mortality rates after acute myocardial infarction throughout the 1960s. As the underlying patient population became progressively sicker, changes in organizational structure, staffing, care delivery, and training paradigms lagged. The coronary care unit gradually evolved from a focus on rapid resuscitation from ventricular arrhythmias in acute myocardial infarction into a comprehensive cardiac intensive care unit designed to care for the sickest patients with cardiovascular disease. Over the past decade, the cardiac intensive care unit has continued to transform with an aging population, increased clinical acuity, burgeoning cardiac and noncardiac comorbidities, technologic advances in cardiovascular interventions, and increased use of temporary mechanical circulatory support devices. Herein, we provide an update and contemporary expert perspective on the organizational structure, staffing, and care delivery in the cardiac intensive care unit; examine the challenges and opportunities present in the education and training of the next generation of physicians for critical care cardiology; and explore quality improvement initiatives and scientific investigation, including multicenter registry initiatives and randomized clinical trials, that may change clinical practice, care delivery, and the research landscape in this rapidly evolving discipline.
Abstract P3018: Spanish Language Preference is not associated with Prediabetes Risk among Hispanic Adolescents with Overweight or Obesity in an Integrated Healthcare System
Introduction: Nationally, up to 1 in 5 Hispanic adolescents have prediabetes. While obesity and other metabolic risk factors contribute to their disproportionate metabolic risk, fewer studies have examined the role of sociodemographic factors such as language proficiency. In this study, we examined whether primary language preference is associated with differences in prediabetes prevalence among Hispanic youth with overweight or obesity. Methods: This retrospective study was conducted using data from Kaiser Permanente Northern California. The cohort included 37,578 Hispanic youth aged 10-17y with body mass index (BMI)≥85 th percentile at exam visits in 2013-2019 and hemoglobin A1c measured within 1 year of the visit. Youth with diabetes or A1c ≥6.5% were excluded. Prediabetes (outcome) was defined by A1c ≥5.7%-6.4%. We also examined A1c ≥6% (secondary outcome). Family/self-reported English vs Spanish language preference was obtained from health records. BMI was classified as overweight (85th to <95th percentile) and obesity (≥95th percentile). A neighborhood deprivation index (NDI) was calculated using area of residence and US Census data. Modified Poisson regression was used to examine the association of language preference with prediabetes, reporting relative risks (RR) and 95% confidence intervals [CI]. Results: The cohort included 37,578 Hispanic youth (mean age 13.1±2.3y), of whom 26,910 (71.6%) reported English and 10,668 (28.4%) reported Spanish as their preferred language. Prediabetes prevalence was 19.3% for both English and Spanish language groups and was similar among those with overweight (13.3% vs 14.3%) and obesity (21.4% vs 21.0%). Adjusting for age, sex, NDI quartile, and BMI (percent of 95 th percentile), the risk of prediabetes for those with Spanish language preference remained similar to those with English language preference (RR 0.99 [0.95-1.04]. There were no differences within overweight or obesity subgroups, when A1c ≥6.0% was used as the outcome, and when analyses were restricted to older or younger age subsets. Conclusion: Prediabetes prevalence was similar among Hispanic youth with elevated BMI who had Spanish compared to English language preference. While differences in dietary and lifestyle factors were not examined, these findings point to similar metabolic risk profiles among Hispanic youth regardless of language preference, when examined in a healthcare system focused on preventive health and uniform access to language services.
Coupled CFD-DEM simulation of progressive failure of tunnel face in sand
Many studies have investigated tunnel face failure using the discrete element method (DEM). However, DEM simulations that incorporate water-soil interactions in tunnel face failure are still limited. In this study, the coupled CFD-DEM method is employed to simulate the progressive failure of the shield tunnel face in both saturated and dry sand. The dynamic mesh method is applied in the CFD component to accurately simulate the changes in the CFD domain due to the movement of the tunnel face. The excavation face is moved forward or backward at a uniform rate to simulate passive and active failure, respectively. The analysis focuses on progressive failure, ground surface displacement, tunnel face support forces, force chain distribution, and vertical stress distribution. Our results at both macro- and micro-scales reveal significant effects of soil-water interactions.
Abstract P3002: Hypoalbuminemia genetic variants are associated with higher cholesterol levels but not atherosclerotic heart disease
Introduction: Secondary hypoalbuminemia is associated with many clinical conditions including hypercholesterolemia, liver disease, kidney disease, and diabetes. These clinical conditions are often associated with atherosclerotic cardiovascular disease (ASCVD). It is unknown if primary hypoalbuminemia from genetic causes (rare monogenic variants or polygenic score [PGS]) is associated with hypercholesterolemia and ASCVD risk similar to secondary hypoalbuminemia. Here, we tested the hypothesis that primary hypoalbuminemia has the same association with cholesterol and incident ASCVD as secondary hypoalbuminemia. Methods: Geisinger’s MyCode cohort is a US-based healthcare cohort with linked genomic and electronic health record data for all participants. Among 146,030 MyCode participants with serum albumin measurements, a rare loss-of-function ALB variant was identified in 30 subjects. An albumin level PGS was calculated for each participant. Regression coefficients were calculated using linear models and hazard ratios (HR) were calculated using Cox proportional hazard models controlling for age at first serum albumin measurement, sex, diabetes, and principal components of ancestry. Results: With regard to LDL-C level, across the entire cohort, each standard deviation (SD) reduction in serum albumin was associated with a 3.4mg/dL (95% confidence interval [CI], 3.2-3.6) decrease in LDL-C. The relationship between the albumin PGS and LDL-C followed the same pattern. Each SD reduction in albumin PGS was associated with a 0.7mg/dL decrease in LDL-C (95% CI, 0.5-0.9). In contrast, ALB variant carriers had 0.69g/dL (95% CI, 0.57-0.81) lower albumin, but 37.7mg/dL (95% CI, 23.3-52.1) higher LDL relative to non-carriers. Contradictory results were observed with regard to ASCVD. Across the entire cohort, a reduction in serum albumin was associated with increased incident ASCVD (HR, 1.13 per SD reduction in albumin; 95% CI, 1.12-1.14; p=3.1x10 -90 ). However, neither the albumin PGS (HR, 0.99 per SD reduction in albumin PGS; 95% CI, 0.98-1.00; p=0.19) nor ALB variants (HR, 0.6; 95% CI, 0.19-1.85; p=0.37) were associated with incident ASCVD. Conclusions: The association of hypoalbuminemia with ASCVD is likely related to secondary causes as no association of albumin with incident ASCVD was seen with genetic causes. ALB variants are novel in that they are associated with higher LDL-C but are unrelated to incident ASCVD. Further investigation of the ALB gene is warranted.
Abstract P1134: Sedentary and Lighter-Intensity Activity Patterns across Trimesters of Pregnancy: the Pregnancy 24/7 Cohort
Background: At least 150 minutes/week of moderate intensity physical activity is recommended during pregnancy, yet pregnancy presents barriers to achieving these guidelines. Some data suggest that activities such as standing, daily steps, and breaking up sedentary behavior may also improve pregnancy health. We aimed to describe and compare typical patterns of these lighter intensity behaviors across pregnancy in a large cohort of pregnant women using gold standard, device-based measures. Methods: Pregnancy 24/7 is an ongoing multi-site cohort study in 500 pregnant participants conducted at the University of Iowa, University of Pittsburgh, and West Virginia University. The study’s primary objective is to identify optimal 24-h behavior compositions associated with the lowest risk of hypertensive disorders of pregnancy and other adverse pregnancy outcomes. Herein, we describe patterns of lower-intensity behaviors across trimesters. Participants aged 18-45 years, not on medications for blood pressure or diabetes, and without physical or medical conditions that severely impact 24-h behaviors, were recruited in the first trimester. They were instructed to wear a thigh-worn activPAL3 micro for 24-h x 7 full days and complete a concurrent wear diary during each trimester of pregnancy. Accelerometer data were processed by PALTechnologies software and a customized R program that quantified average daily standing (h/day), steps, sit-stand transitions, and prolonged sedentary behavior accumulated in 30-min or 60-min bouts (h/day) each trimester. Linear mixed models compared accelerometer outcomes across trimesters of pregnancy. Results: Participants (n=474) with valid accelerometer data for least one visit (to date) had an average age of 30.8 years and 84% reported Non-Hispanic White race/ethnicity. Sedentary behavior and lighter-intensity activities all differed across trimesters (p≤0.002, see Table ), with optimal patterns in the second trimester. Pregnant women were least likely to engage in standing and break up prolonged sedentary behavior (lower sit-stand transitions and higher sedentary behavior in bouts) in the first trimester, while steps were lower by ~500 steps per day in the third trimester. Conclusions: Sedentary behaviors, standing, and daily steps vary differentially across pregnancy. These patterns, along with how these behaviors associate adverse pregnancy outcomes, will guide the design of comprehensive activity interventions to promote pregnancy health.
Abstract P3021: Inflammatory Metabolomic Profiles are Associated with Increased Cardiovascular Disease Risk in Women
Background: Cardiovascular disease (CVD) is the leading cause of death worldwide; ischemic stroke (IS) and coronary heart disease (CHD) are the two leading causes of CVD. The burden of CVD is particularly pronounced in women, who have a 20% higher lifetime risk of stroke than men and have worse outcomes for CHD and IS. Inflammation is a risk factor for CVD, yet the mechanisms through which chronic inflammation increases this risk remain uncertain. Methods: Metabolomic data from 11 case-control studies in the Nurses’ Health Study (NHS) focusing on chronic inflammatory disease outcomes were used. In this cohort, 1,734 women also had data on inflammatory biomarkers (i.e., hs-CRP, IL6, TNFaR2, adiponectin). A composite inflammatory score was created based on these four biomarkers, and elastic net regression was used to identify metabolites associated with the inflammatory score. A metabolomic signature index of inflammation (i-MSI) was subsequently calculated as the sum of retained metabolites with weights equal to their regression coefficients. In an independent NHS IS case-control study ( n = 405 cases and 405 controls), conditional logistic regression was used to determine the odds ratios (OR) for the i-MSI and IS risk, controlling for standard CVD risk factors. Additionally, the association between the i-MSI and CHD risk was assessed in a case-control dataset from the Women’s Health Initiative (WHI; n = 793 cases and 795 controls). Results: The i-MSI comprised 92 metabolites in the NHS and 87 overlapping metabolites in the WHI, showing enrichment in branched-chain amino acid biosynthesis and degradation pathways. Moreover, weighted coexpression network analysis revealed distinct pro- and anti-inflammatory metabolite clusters, identifying diacylglycerides in the pro-inflammatory cluster and cholesteryl esters in the anti-inflammatory cluster. Every standard deviation (SD) increase in the i-MSI was associated with an OR for IS of 1.31 (95% CI: 1.06 – 1.62), and women in the highest i-MSI quartile had an OR of 1.96 (95% CI: 1.12 – 3.42). These findings were consistent in the CHD case-control cohort from the WHI, where the OR for CHD was 1.27 (95% CI: 1.07 – 1.51) per SD of the i-MSI. Conclusions: These data identify an association between metabolites linked with inflammation and CVD risk. These findings may aid in identifying novel metabolic targets that can be utilized to develop therapies for mitigating IS and CHD risk in women.
Introducing carbon quantum dot-Capivasertib drug carrier complex for enhanced treatment of breast cancer
Capivasertib (AZD5363) is a 2023 FDA-approved pyrrolopyrimidine-derived compound that treats hormone receptor positive, HER2 negative metastatic breast cancer in adult patients. It is a novel pan-AKT kinase catalytic inhibitor in ER + breast cancer cell lines, including MCF7. The dominant influence of carbon quantum dots (CQDs) in combination with multiple chemotherapy drugs is also demonstrated as a drug delivery system that significantly enhances the effectiveness of cancerous tumour treatments by providing reduced side-effects, through targeted delivery of the drug, controlled release, enhanced solubility, permeability and retention. In this study, the impact of the conjugation of AZD5363 drug to N-doped, S-doped, and N/S-doped CQDs was investigated on inducing apoptosis by inhibiting the AKT signalling pathway in the MCF7 cell line. Initially, hydrothermal and pyrolysis methods were used to construct CQDs. Then, the synthesized quantum dots were conjugated with AZD5363 at three different concentrations, i.e., 0.03, 0.3, and 3nM. The MTT test results, on MCF7 cells, showed that although all the studied CQDs were biocompatible, the complex of N/S-doped CQD-AZD5363 at a concentration of 0.03nM was the most effective. After obtaining immunocytochemistry results, flow cytometry and cell invasion tests were employed to demonstrate the high potential of the introduced drug carrier complex in reducing AKT protein expression, induction of apoptosis and prevention of cell metastasis and invasion. According to these results, the binding of N/S-doped CQD to AZD5363 increases the effectiveness of this drug, with reducing the IC50 concentration, and more specificity to cancerous cells, introducing it as a suitable candidate for the treatment of breast cancer.
Abstract MP44: Plasma Proteomic Signature Of BMI Reveals Heterogeneous Cardiometabolic Risk Profiles Within And Across Standard BMI Classifications
Background: The proteome is altered in obesity and proteomic signatures of BMI have been identified. However, few studies have examined differences in clinical profiles between actual and protein-predicted BMI. Hypothesis: Plasma protein-based BMI classification will better capture cardiometabolic risk compared to actual BMI classification. Methods: Data on cardiometabolic phenotypes and plasma proteins (4979 proteins via SomaScan) were available in 645 adults (56% Female, 35% Black, 17-65 yrs) from the HERITAGE Family Study. LASSO regression models with 10-fold-cross-validation were used to create a BMI proteomic signature. Protein-predicted BMI was classified into weight classes and compared to actual BMI classification to create 7 groups (underpredicted, matched, or overpredicted) ( Fig 1A ). General linear models adjusted for age, sex, race, and measured BMI were used to examine differences in cardiometabolic traits across groups. Results: The LASSO model (R 2 =0.82, RMSE=2.2) included 208 proteins. Protein-predicted BMI correlated with actual BMI at r=0.95 (p<0.0001), with a 16% misclassification rate ( Fig 1A ). Participants whose proteins underpredicted BMI class generally had more favorable cardiometabolic profiles than matched groups of the same class, while overpredicted BMI class groups showed worse cardiometabolic profiles than matched groups of the same class ( Fig 1B ). Conclusions: We identified individuals matched for BMI but with opposing proteomic signatures that differed in cardiometabolic risk profiles. Proteomic profiling may identify clinically meaningful heterogeneity in cardiometabolic health not fully captured by BMI that could potentially be used as biomarkers and/or targets of therapeutic responsiveness.
Abstract P2101: Association of circulating senescence-associated secretory phenotype (SASP) proteins with the development of frailty in late-life: the Atherosclerosis Risk in Communities (ARIC) Study
Introduction: Emerging evidence suggests a role for cellular senescence in the pathogenesis of adverse late-life outcomes including frailty. Senescence-associated secretory phenotype (SASP) is a hallmark of senescent cells, but the extent to which circulating SASP protein levels associate with the development of frailty is not known. Hypothesis: Circulating markers of cellular senescence, reflected in the SASP, will associate with greater risk of developing frailty in late life. Methods: We studied 2,359 older adults in the community-based Atherosclerosis Risk in Communities (ARIC) cohort study who were free of HF and frailty at study Visit 5 (2011-13), had large-scale aptamer proteomics (SomaScan) measured at Visit 5, and had frailty assessed at study Visit 6 (2016-17). Protocol assessments of frailty were performed at each study visit using the Fried criteria. We assessed the association of 29 aptamers representing 26 unique SASP proteins at Visit 5 with incident frailty and frailty components at Visit 6 using multivariable logistic models adjusted for age, sex, race, and visit center. Two-sample cis-Mendelian randomization (cis-MR) was performed to evaluate potential causal effects of proteins on frailty. Results: Mean age at Visit 5 was 74±5 years, 57% were women, and 16% reported black race. Over the 5 years between Visits 5 and 6, 152 participants developed frailty. Seven of 26 SASP proteins were associated with the development of frailty at FDR significance (FDR-adjusted p < 0.05 ; Figure ): five with higher risk of frailty (CST3, GDF15, CTSZ, CTSD, HSPA1A) and two with lower risk (GSN, SERPING1). These proteins demonstrated the most consistent associations with low energy, while GDF15, CST3, and CTSZ were significantly associated with all five frailty components (FDR-adjusted p < 0.05). In cis-MR analysis, GDF15 and SERPING1 showed potential causal effects on frailty. Conclusion: Higher circulating levels of a subset of senescence-associated proteins are associated with greater risk of developing frailty in late life, two of which may have causal effects on frailty. These findings support a potential role for cellular senescence in the pathogenesis of the frailty syndrome.
Abstract P3036: Predicting Risk of Obesity-Related Outcomes in People with Obesity or Overweight: the Role of Social Risk Factors
Introduction: Social risk factors have been shown to be related to overweight/obesity and developing related poor health outcomes. Prediction models for obesity-related outcomes in people with obesity or overweight developed within clinical care settings can be used in decision making to identify individual patient risk for poor outcomes. There have been calls to link person-level or census tract level social risk factors to Electronic Health Record (EHR) data for use in clinical decision-making. However, such methods have not been fully developed and more information is needed regarding which social risk factors are relevant for predicting risk. Objective: To examine whether adding primary payer type and publicly available zip code level composite (Area Deprivation Index; National Walk Index; Rural-urban Commuting Area) or non-composite (poverty rate, low-income tract, median family income, population density) risk factors improve risk prediction model fit and accuracy. Methods: EHR data for 837,373 eligible patients (18-80 years, BMI 25-80 kg/m 2 , with 5-digit zip code to link to census data) were utilized to determine the value of adding social risk factors to validated prediction models developed for use in clinical care settings. Outcomes were times to event for type 2 diabetes (T2DM), atherosclerotic cardiovascular disease, heart failure, sleep apnea, and obesity-related cancer. Models were fit using a multi-level Cox regression with a competing risk of death. Adaptive LASSO was applied to add social risk factors to existing models. Full models with all significant social risk variables and reduced models in which highly correlated social risk variables were removed, were examined. Assessments of model fit were done utilizing the AIC/BIC and Harrel’s C-index was calculated to assess predictive ability. Results: Several models retained some social risk factors. The model for T2DM was the only one in which social risk factors did not improve the EHR-only models, though increases in Harrel’s C-index values were small (<0.01) for the other models with social risk factors added. Conclusions: Individual and composite zip code level social risk factors were statistically significantly associated with all outcomes and improved the models, except for T2DM, but did not meaningfully improve predictive ability. Additional studies are warranted examining effects of social risk closer to, or at, the individual level, such as census block or neighborhood.
Convergent validity of 12-item World Health Organization Disability Assessment Schedule (WHODAS 2.0) among people with neck pain
Objective To explore the convergent validity of 12-item World Health Organization Disability Assessment Schedule (WHODAS 2.0) comparing it to Neck Disability Index (NDI). Design Cross-sectional cohort study. Subjects/Patients 962 patients visiting a university outpatient Physical and Rehabilitation Medicine Clinic due to musculoskeletal complaints. Methods Spearman´s rank correlation between WHODAS 2.0 and NDI. Results The average age was 49.2 (SD 14.5) years, 67% were women. Of all the possible 143 correlations between WHODAS 2.0 and NDI, 99 (69%) were positive, significant and strong or, at least, moderate. The correlation between the composite scores of two scales was strong. The weakest correlations were seen for the NDI items ‘pain intensity and ‘headaches’. Conclusion Most of the items and the composite scores of the WHODAS and the NDI demonstrated significant positive correlations. Pain intensity, as defined by the NDI, did not correlate with disability severity measured by the WHODAS 2.0. Also, the NDI items ‘headaches’ and ‘sleeping’ were associated with the WHODAS 2.0 only loosely. It seems that one of these two scales may not directly be substituted by another. When used simultaneously, The WHODAS and the NDI may complement each other covering comprehensively the different dimensions of functioning among people with neck pain.
Abstract MP78: Device-Based Assessment of 24-Hour Activity Across Three Trimesters of Pregnancy: The Pregnancy 24/7 Cohort Study
Introduction: The 24-hour activity cycle, including moderate-to-vigorous intensity physical activity (MVPA), light-intensity physical activity (LPA), sedentary behavior (SED), and sleep, is increasingly recognized as critical for health. However, little is known about 24-hour activity during pregnancy. This is an important research gap given that these behaviors are modifiable and individually related to maternal and child cardiovascular health outcomes. The purpose of this study was to characterize 24-hour activity across pregnancy using gold standard, device-based measures and examine differences by trimester. Hypothesis: We hypothesized there would be varying patterns of 24-hour activity across pregnancy trimesters. Methods: The ongoing Pregnancy 24/7 multi-site cohort study was conducted to examine associations of 24-hour activity across pregnancy trimesters with hypertensive disorders of pregnancy and other adverse pregnancy outcomes. Participants were instructed to wear the activPAL3 micro (MVPA, LPA, and SED) and the Actiwatch Spectrum Plus (sleep) concurrently for 24 hours x 7 full days in each trimester of pregnancy and to complete a log denoting non-wear and sleep times. Data sources were integrated using PAL Technologies software and a customized R program and descriptive statistics were calculated for each component of 24-hour activity, including the percentage of participants meeting guidelines (when applicable). Differences across trimesters were examined using nested linear or generalized mixed models. Results: A total of n=474 participants to date (mean age 30.8 years ± 4.3, 15.6% Underrepresented Minority) wore both devices in at least one trimester. Time spent in each behavior significantly differed across trimesters (see Table ). MVPA and sleep were highest in the first trimester, while LPA was highest and SED lowest in the second trimester. The percentage of women meeting MVPA guidelines decreased from 54.8% to 44.2%, while the percentage meeting sleep guidelines (time attempting to sleep) increased from 63.2% to 76.1% across trimesters. Meeting a SED threshold of <10 hours/day did not differ across pregnancy trimesters. Conclusions: Declining levels of MVPA during pregnancy suggest a need for tailored health promotion interventions. It may be more feasible to target other components of 24-hour activity during pregnancy, such as decreasing SED by increasing LPA.
Abstract 060: Associations of Neighborhood Walkability with Baseline Physical Activity and Sedentary Time among US South Asian Adults from the SAHELI Randomized Clinical Trial
Introduction: High neighborhood walkability, defined as presence of crosswalks, sidewalks, and parks, is associated with higher physical activity (PA) and lower sedentary time (ST) among United States (US) adults. The associations between neighborhood walkability, PA, and ST have not been studied among US South Asians adults, a group which experiences significantly higher cardiovascular disease (CVD) mortality compared to other race-ethnic groups. Methods: The SAHELI clinical trial randomized South Asian adults from the Chicago, IL metro area (18-65 years with CVD risk factors) to a 16-week lifestyle intervention versus a control group between 2018-2023. Baseline PA and ST were measured by an Actigraph worn by participants for 7 consecutive days. Moderate-to-vigorous physical activity (MVPA), light physical activity (LPA), and ST were defined by Troiano cut points. Neighborhood was defined by a 500-meter radius around participants’ home address. Neighborhood walkability measures included: the National Walkability Index (measured at the US Census block level), total number of crosswalks, total number of sidewalks, and percentage of neighborhood which contained a park, all measured by Google Street View. In separate models, multivariate linear regression evaluated the association between each neighborhood walkability measure and baseline MVPA, LPA, and ST, adjusting for age, sex, country-of-origin, years in US, and Actigraph wear time. Results: Participants from SAHELI with valid Actigraph data (defined as at least 600 min/day of wear time for >3 days) and geocoded neighborhood walkability data were included (N=432; 59% female, 98% immigrant, 79% Indian origin). Mean±SD MVPA was 24±19 min/day, LPA was 299±95 min/day, and ST was 564±136 min/day. Distribution of neighborhood walkability variables are shown in Figure . Neighborhood walkability exposures were not associated with MVPA. The National Walkability Index, total number of crosswalks, and total number of sidewalks were significantly associated with higher LPA and lower ST in maximally-adjusted models ( Figure ). The percentage of neighborhood containing a park was not associated with LPA or ST. Conclusion: National Walkability Index, number of neighborhood crosswalks and sidewalks were significantly associated with higher LPA and lower ST, but not with MVPA. Neighborhood walkability may be important to consider when designing CVD prevention interventions that promote PA and minimize ST among US South Asians.
Abstract P3071: Trends in blood pressure among Veterans who initiated antihypertensive medication from 2014 to 2020
Introduction: The prevalence of blood pressure (BP) control of <140/90 mmHg in the Veterans Health Administration (VHA) in the early 2000s was high (>75%). However, the 2017 American College of Cardiology (ACC)/American Heart Association (AHA) BP guideline and COVID-19 pandemic may have affected pre-and-post treatment BP. Research Question: Were there changes in pre-and-post treatment systolic BP (SBP, mmHg) and control prevalence relative to the 2017 BP guidelines and COVID-19 pandemic? Methods: Our retrospective study included Veterans initiating antihypertensive medication in VHA outpatient settings from 11/13/2014-11/12/2020. Using the first antihypertensive prescription fill date, Veterans were placed into one of 4 cohorts (Panel A): 1) pre-ACC/AHA 2017 guideline; 2) first year post-guideline; 3) second year post-guideline (included first confirmed US COVID case); and 4) during-COVID. Linear and logisitc regression estimated age- and dropout-adjusted mean SBP levels and likelihood of BP control at 1 year. Results: Among 94,551 Veterans included (mean age 65 years, 94% male, 69% non-Hispanic White), 68.5% had pre-treatment SBP ≥130. In this group, over time, the mean pre-treatment SBP decreased and post-treatment SBP increased (Panel B). Overall, the respective proportion in each cohort with 1-year BP control of <130/80 was 31.3%, 33.1%, 32.5%, and 31.5% (p-trend=0.16) (Panel C). Assessment of 1-year BP control of <140/90 was 72.7%, 74,4%, 74.0%, and 71.8% (p-trend=0.91). The prevalence of 1-year BP control pre- and during-COVID was 31.8% vs 31.5% (p=0.44). Conclusions: Mean post-treatment SBP levels and 1-year BP control prevalence were stable after the release of the 2017 guideline and during the COVID-19 pandemic.
Examining safety of cardiac surgery in patients with preoperative cardiac arrest
Background Although postoperative cardiac arrest is a well-studied complication of cardiac surgery, few guidelines exist regarding timing of surgery in preoperative cardiac arrest (pCA). We examined the association between delayed timing of operation and postoperative outcomes following cardiac surgery in a large cohort of pCA. Methods Adults with a diagnosis of pCA undergoing a cardiac operation were identified in the 2016-2020 National Inpatient Sample. Those requiring surgery within 24 hours fo cardiac arrest were excluded. Patients who underwent a cardiac procedure after 5 days of cardiopulmonary resuscitation were classified as Delayed (others: Early). Multivariable regression models were constructed to evaluate associations between delayed timing of surgery with in-hospital mortality, postoperative complications, hospitalization duration, and costs. Results Of an estimated 9,240 patients meeting study criteria, 4,860 (52.6%) received delayed cardiac surgery. Following entropy balancing, delayed surgery was significantly associated with decreased odds of in-hospital mortality (Adjusted Odds Ratio [AOR] 0.75, 95% Confidence Interval [CI] 0.58 – 0.97). However, delayed operation demonstrated greater odds of postoperative thromboembolic (AOR 1.44, 95% CI 1.02 – 2.04), and infectious (AOR 1.65, 95% CI 1.31 – 2.08) complications. Notably, delay did not alter odds of neurologic complication, and was linked to a decrement in per-day costs (β -$2,100, 95% CI -2,600 – −1,700). Conclusions While preoperative cardiac arrest remains challenging, the present study demonstrates the safety profile of delaying cardiac operation among patients tolerating at least 24 hours of a delay to surgery. Future studies are needed to elucidate the factors associated with favorable outcomes in this population.