tbuckley/cabot-search huggingface dataset:
Abstract 37: Urinary Metal Levels and Coronary Artery Calcification: Longitudinal Evidence in the Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Katlyn E McGraw, Kathrin Schilling, Ronald A Glabonjat, Marta Galvez-Fernandez, Arce Domingo-Relloso, Irene Martinez-Morata, Miranda R Jones, Wendy S Post, Joel D Kaufman, Maria Tellez-Plaza, Linda Valeri, Elizabeth R Brown, Richard A Kronmal, Graham R Barr, Steven Shea, Ana Navas-Acien, Tiffany R Sanchez
Journal: Circulation (2024)

Objective: Growing evidence indicates that exposure to metals are risk factors for cardiovascular disease (CVD). We hypothesized that higher urinary levels of metals with prior evidence of an association with CVD, including non-essential (cadmium , tungsten, and uranium) and essential (cobalt, copper, and zinc) metals are associated with baseline and rate of change of coronary artery calcium (CAC) progression, a subclinical marker of atherosclerotic CVD. Methods: We analyzed data from 6,418 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) with spot urinary metal levels at baseline (2000-2002) and 1-4 repeated measures of spatially weighted coronary calcium score (SWCS) over a ten-year period. SWCS is a unitless measure of CAC highly correlated to the Agatston score but with numerical values assigned to individuals with Agatston score=0. We used linear mixed effect models to assess the association of baseline urinary metal levels with baseline SWCS, annual change in SWCS, and SWCS over ten years of follow-up. Urinary metals (adjusted to μg/g creatinine) and SWCS were log transformed. Models were progressively adjusted for baseline sociodemographic factors, estimated glomerular filtration rate, lifestyle factors, and clinical factors. Results: At baseline, the median and interquartile range (25th, 75th) of SWCS was 6.3 (0.7, 58.2). For urinary cadmium, the fully adjusted geometric mean ratio (GMR) (95%Cl) of SWCS comparing the highest to the lowest quartile was 1.51 (1.32, 1.74) at baseline and 1.75 (1.47, 2.07) at ten years of follow-up. For urinary tungsten, uranium, and cobalt the corresponding GMRs at ten years of follow-up were 1.45 (1.23, 1.71), 1.39 (1.17, 1.64), and 1.47 (1.25, 1.74), respectively. For copper and zinc, the association was attenuated with adjustment for clinical risk factors; GMRs at ten years of follow-up before and after adjustment for clinical risk factors were 1.55 (1.30, 1.84) and 1.33 (1.12, 1.58), respectively, for copper and 1.85 (1.56, 2.19) and 1.57 (1.33, 1.85) for zinc. Conclusion: Higher levels of cadmium, tungsten, uranium, cobalt, copper, and zinc, as measured in urine, were associated with subclinical CVD at baseline and at follow-up. These findings support the hypothesis that metals are pro-atherogenic factors.
Abstract 43: Development and Internal Validation of Risk Scores to Predict Survival to Discharge Following Pediatric In-Hospital Cardiac Arrest
Authors: Minaz Mawani, Jessica Knight, Bryan McNally, Ye Shen, Linda Brown, Mark Ebell
Journal: Circulation (2024)

Introduction: In-hospital cardiac arrest (IHCA) in the pediatric population is associated with poor survival and neurological outcomes. We aimed to develop and internally validate a risk score to predict survival to discharge in pediatric IHCA patients. Methods: For model development and validation, we included pediatric IHCA patients captured in the Get With The Guidelines® registry (provided by the American Heart Association) between 2005 and 2021. We used logistic regression (LR), classification and regression trees (CART), and artificial neural networks (ANN) to develop models using 70% of the data and validate them using the remaining 30% of the data. The discrimination of the models was compared based on the area under the receiver operating characteristic curve (AUC), calibration based on the ratio of observed to expected (O: E), and predictive accuracy based on percent survival in each risk group. Results: We included 6141 pediatric patients (mean age 4.82 years, 41.3% infants, 54.7% male). Most patients survived to hospital discharge (60.9%). We developed separate models for infants vs. older children using LR, CART, and ANN. The least absolute shrinkage and selection operator (LASSO) identified age, illness category, acyanotic cardiac malformation, hepatic insufficiency, hypotension/hypoperfusion, metabolic/electrolyte abnormality, metastatic/hematologic malignancy, renal insufficiency, septicemia, and pediatric cerebral performance score on admission as important predictor variables for analysis. Table 1 shows a comparison of model parameters. Logistic regression models were found to be better at classifying survivors into risk categories with higher specificity and discrimination. Conclusion: Pediatric patients experiencing IHCA can be classified into low, moderate, and high-risk categories using a simple risk score and easily identified pre-arrest variables. These risk scores can support clinical decisions, facilitate research, and help monitor the quality of medical services.
Abstract 68: The Association of Pre-Pregnancy Body Mass Index With Gestational Diabetes Across Maternal Race and Ethnicity Subgroups
Authors: Theresa Boyer, Christine Hsueh, Kevin M Sun, Elizabeth Selvin, Allison G Hays, Erin D Michos, Arthur J Vaught, Chiadi E Ndumele, Josef Coresh, Anum Minhas
Journal: Circulation (2024)

Objective: Gestational diabetes mellitus (GDM) complicates 5-11% of pregnancies within the US and maternal obesity is a strong risk factor. Asian individuals are known to have a higher risk of GDM at a lower body mass index (BMI) compared to European populations. However, Asian Americans represent a heterogenous group, and no studies have captured the variation between BMI and GDM across racial groups at a national level. Our objective was to characterize differences in the association between BMI and GDM by maternal race/ethnicity with a specific focus on Asian subgroups. Methods: We used data from the National Vital Statistics System natality files from 2016 to 2019, capturing all live births in the US, to ascertain incidence of GDM. We used logistic regression with BMI modeled as a cubic b-spline to model the association with risk (predicted probability) of GDM. All analyses were stratified by maternal race/ethnic group. Results: Of the eligible 13.3M pregnancies resulting in live births, 6.5% were affected by GDM, ranging from 5.2% among non-Hispanic Black individuals to 12.3% among Asian individuals. The incidence of GDM was highest among women with obesity with rates of 20.3% in Asian individuals, and 16.0% in American Indian and Alaska Native individuals with obesity (Figure 1A). At a BMI of 23 kg/m2 the predicted probability of GDM was 6.5% for Asian individuals compared to 2.3% for non-Hispanic Black individuals (Figure 1B). There was substantial heterogeneity across Asian ancestry subgroups between pre-pregnancy obesity and GDM incidence (Figure 1C), with Vietnamese and Korean individuals having the largest increase in risk with higher pre-pregnancy BMI (Figure 1D). Conclusion: The risk of GDM increased with higher pre-pregnancy BMI across all maternal race/ethnicity groups, but risk was higher for Asian Americans at a lower BMI. There was substantial variation in BMI-related risk of GDM across Asian ancestry subgroups, suggesting need for more tailored screening and intervention strategies for GDM.
Abstract 56: Associations Between the Plasma Proteome and a Polygenic Risk Score for Venous Thromboembolism: The Atherosclerosis Risk in Communities Study (ARIC)
Authors: Aixin Li, Weihua Guan, Jim S Pankow, Nathan Pankratz, Pamela L Lutsey, Ethan Moser, Mary Cushman, Aaron R Folsom, Weihong Tang
Journal: Circulation (2024)

Introduction: Venous thromboembolism (VTE) is a leading cause of cardiovascular morbidity and mortality. While coagulation system variation causes VTE, other novel biological pathways remain underexplored. This study aims to provide a comprehensive understanding of the plasma proteomics signature associated with genetic susceptibility for VTE, as captured by a polygenic risk score (PRS). Methods: We constructed a race-specific PRS for VTE for participants in the ARIC, an ongoing community-based prospective cohort, based on the two newest large genome-wide association studies (GWAS) reports: one reported 93 risk loci in individuals of European ancestry (PMCID: 36658437); another identified 135 risk loci from a cross-ancestry GWAS (36154123). We selected one SNP for each gene locus from each study, retaining a single SNP when the same gene was identified by both studies. These SNPs were then clumped within a 250kb window with an r 2 threshold of 0.1. We included 139 SNPs in the PRS calculation in ARIC European American (EA) and African American (AA) participants using SNP dosage and race-specific estimates when possible. A total of 4,955 plasma proteins were measured by SOMAscan v4 from samples collected at ARIC visit 2 in 1990-92. We then employed race-specific linear regression to associate the VTE PRS with levels of all 4,955 proteins, controlling for potential confounders. We treated the analysis in EAs (n=7,402) as discovery and that in AAs (n=1,933) as replication, applying Bonferroni correction to account for multiple testing. We then conducted pathway analysis using the Ingenuity Pathway (IPA) to identify enriched biological signaling pathways for the top PRS-protein associations based on FDR&lt;0.01. Results: In the EA participants, 90 proteins were statistically significantly associated with the VTE PRS (p&lt;5x10 -5 ). Among these, 15 were replicated in the AA participants (p&lt;0.00056) with the consistent direction of associations and 7 of these 15 proteins at p&lt;5x10 -5 . Beyond the well-documented proteins for VTE, such as VWF and coagulation factors VIII, and XI, novel proteins were also identified, such as sulfhydryl oxidase 2, interleukin-3 receptor subunit alpha, ephrin type-A receptor 4, and insulin receptor. The IPA analysis indicated enrichment of the coagulation system, IL-15 pathways, and heparan sulfate biosynthesis pathways. Conclusion: This comprehensive proteomic analysis offers valuable insights into the circulating proteomics signature and biological pathways underlying the genetic predisposition for VTE, potentially enhancing our understanding of VTE etiology and prevention.
Abstract 11: Biological Age as a Predictor of Arterial Stiffness in Midlife Women
Authors: Telisa Spikes, Roland J Thorpe, Alvaro Alonso, Jordan Pelkmans, Sandra B Dunbar, Puja Mehta, Priscilla Pemu, Herman A Taylor, Arshed A Quyyumi
Journal: Circulation (2024)

Introduction: Black women develop hypertension (HTN) earlier in life and experience higher cardiovascular disease (CVD) morbidity and mortality rates at younger ages compared to White women. Growing evidence suggests this may be due to Black women experiencing premature physiological deterioration and accelerated biological aging, true global state of an aging organism. Yet, the relationship between biological aging and arterial stiffness, a precursory marker of subclinical CVD, in Black women has not been studied. We investigated the association between biological age (BA) and arterial stiffness in Black and White women. Hypothesis: BA will be associated with arterial stiffness and this association will be modified by race. Methods: In 219 women (n=140 White, n=79 Black) enrolled in the Morehouse-Emory Center for Health Equity and Predictive Health Institute cohorts (age range 25-49), arterial stiffness was assessed using carotid-femoral pulse wave velocity (CFPWV), measured by applanation tonometry (SphygmoCor®). BA was estimated using the Klemera-Doubal method from 10-select clinical biomarkers (BUN, Creatinine, Total Cholesterol, Alkaline Phosphatase, MCV, RDW, Albumin, Lymphocytes, WBC, CRP) and chronological age. Overall and race-specific associations between BA and arterial stiffness adjusting for demographics (race, education, income, marital status), lifestyle (alcohol, smoking), clinical (body mass index, HTN, diabetes history, SBP), and mental health factors (depressive symptoms) were estimated using multiple linear regression. Results: Mean chronological and BA age was 40 (SD=6.1) and 43 (SD=7.2) years, respectively. Black women had a BA that was 3.4 (SD=5.7) years older than their chronological age, while the difference was 1.3 (SD=4.8) years older for White women. Thus, Black women’s BA was 2.1 (95%CI: -3.5, -0.6) years older than White women. Mean (SD) CFPWV was 7.3 (1.1) in Black women and 6.3 (0.8) in White women. Overall, BA was associated with higher (worse) CFPWV in the minimal (β=0.06 m/s per year, 95%CI: 0.03, 0.08) and fully adjusted models (β=0.04 m/s, 95%CI: 0.01, 0.08). There was no significant interaction between race and BA in the association with arterial stiffness. Conclusions: Black women had older BA and worse CFPWV than White women. BA may partially account for the higher arterial stiffness in Black women.
Abstract 03: Cardiovascular Disease Risk Factor Control Following Release From Carceral Facilities
Authors: Jenerius A Aminawung, Lisa Puglisi, Brita Roy, Nadine Horton, Johanna Elumn, Hsiuju Lin, Kirsten Bibbins-Domingo, Harlan M Krumholz, Emily Wang
Journal: Circulation (2024)

Background: Incarceration is a social determinant of cardiovascular disease (CVD) but is rarely addressed in clinical settings or cardiovascular prevention efforts. People who have been incarcerated are more likely to develop CVD at younger ages and have worse cardiovascular outcomes compared with the general population, even after controlling for traditional risk factors. The objective of this study is to identify incarceration-specific factors that are associated with uncontrolled CVD risk factors and identify potential targets for prevention specific to this population. Methods: Using data from Justice-Involved Individuals Cardiovascular Disease Epidemiology (JUSTICE), a prospective cohort study of individuals released from incarceration with CVD risk factors, we examine the association between incarceration-specific and psychosocial factors and CVD risk factor control, including systolic blood pressure (SBP≥140 mmHg, diastolic blood pressure (DBP)≥90, body mass index (BMI)≥40, glycosylated hemoglobin (HbA1c) ≥8%, and low-density lipoprotein cholesterol (LDL-c) ≥160). Incarceration-specific factors include the conditions of confinement (jail vs. prison, time spent in solitary confinement), the carceral health care delivery system (co-payment, medication self-management, discharge planning), and collateral sanctions following release (barriers to housing, food, employment due to criminal record). Psychosocial factors included perceived discrimination and stress, self-efficacy, and lifetime adversity. Results: The mean age of participants (N=417) was 45.2 ±SD 10.7 years and disproportionately men (92%), racially minoritized groups (80%), and poor (66% without an income). Over half (53%) had at least one uncontrolled CVD risk factor. Having been incarcerated in a jail, as compared with prison, was associated with an increased odds of having an uncontrolled CVD risk factor, even after adjusting for age, race and ethnicity, gender, perceived stress, depression symptoms, and life adversity score (AOR 1.79, 95% CI 1.08-2.94). People held in jail, as compared with prison, had higher rates of smoking, uncontrolled hypertension, fewer opportunities to manage one’s own medications while incarcerated, or receive medications prior to release. Discussion: Release from jail is associated with worse CVD risk factor control and requires tailored intervention focused on smoking cessation, hypertension control, and improved discharge planning. These data are especially informative as states design and implement the Centers of Medicare &amp; Medicaid Services new Medicaid Reentry Section 1115 Demonstration Opportunity, which allow Medicaid programs for the first time in history to cover services prior to release from correctional facilities that address chronic health conditions like cardiovascular disease and its risk factors.
Abstract 35: Association of SGLT2 Inhibitors and Other Second Line Therapies With Incident Chronic Kidney Disease in Patients With Type 2 Diabetes
Authors: Wendy Wang, Paul Drawz, Lisa Chow, Lin Y Chen, Rob F Walker, Faye L Norby, Pamela L Lutsey
Journal: Circulation (2024)

Introduction: Type 2 diabetes (T2D) is a strong risk factor for chronic kidney disease (CKD). Clinical trials have shown that intensive glycemic control prevents the development of kidney failure and decreases in eGFR in patients with T2D and CKD. Furthermore, sodium-glucose cotransporter-2 inhibitors (SGLT2i) slow the progression of CKD compared to other glucose lowering medications. However, it’s unknown whether SGLT2 inhibitors reduce the risk of incident CKD. Using data from the US MarketScan administrative databases (2014-21), we assessed the association between use of SGLT2i vs. other 2 nd line therapies and risk of incident CKD among patients with T2D on metformin. Methods: We included 428,814 matched patients with T2D on metformin and a 2 nd line therapy. SGLT2i users were matched with up to 5 other 2 nd line therapy users by age, sex, date of enrollment, and date of 2 nd line therapy initiation. Other 2 nd line therapies included dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, sulfonylureas, thiazolidinediones, and insulin. Incident CKD was defined using ICD codes. Those with prevalent CKD were excluded. Cox proportional hazards models were used. Results: Participants were on average age 53±10 years at baseline and 46% were female. Over a median follow-up of 2.0 years, 6,024 patients were diagnosed with CKD. After multivariable adjustments, SGLT2i users had a lower risk of incident CKD than those taking other 2 nd line therapies (Table; HR [95% CI]: 0.43 [0.39-0.47]). When compared to users of each 2 nd line therapy individually, SGLT2i users consistently had a lower risk of CKD. Conclusion: In this analysis using real-world data, among patients with T2D on metformin, SGLT2i use was associated with a lower risk of incident CKD than other 2 nd line diabetes therapies (when assessed as a group and individually). Results from this study may inform clinical guidelines regarding treatment options for those with diabetes at high-risk for CKD.
Abstract 51: Association Between Cumulative “Life’s Essential 8” Scores Through Young Adulthood and Cardiovascular Disease Risk: The Coronary Artery Risk Development in Young Adults (CARDIA) Study
Authors: James Walker, Daniel Won, James W Guo, Jamal S Rana, Norrina B Allen, Hongyan Ning, Donald M Lloyd-Jones
Journal: Circulation (2024)

Background: Associations of cardiovascular health (CVH) with incident cardiovascular disease (CVD) largely come from studies with single measures of CVH in mid-life. We used the American Heart Association’s “Life’s Essential 8” (LE8) score to examine the association of cumulative CVH through young adulthood, and time course of CVH exposure, with risk of incident CVD in mid-life. Methods: We estimated subject-specific LE8 score trajectories of 3932 CARDIA young adults aged 18-45 years (56.2% female, 48.1% Black) using a spline-based mixed effect model. Using multivariable Cox proportional models, we assessed associations of 1) cumulative LE8 score (cumLE8) from 18-45 by quartile, 2) cumLE8 continuous score from 18-45 and LE8 score at age 45, and 3) cumLE8 continuous score and slope of LE8 score from ages 18-45, with incident fatal or non-fatal CVD after age 45, adjusting for age, sex, race, and maximal education. Area under the LE8 curve from ages 18-45 was used to calculate cumLE8 for each subject. Results: There were 3932 CARDIA participants (56.2% female, 48.1% Black). The mean cumLE8 exposure from 18-45 was 2075.2 points*years, and mean LE8 score at age 45 was 69.9 points (out of 100; higher is better). After adjustment, the lowest 2 quartiles (Q1 and Q2) of cumLE8 score (poorest CVH) from 18-45 had significantly higher hazards for CVD after age 45 compared to the highest (best CVH, Q4) ( Figure 1, Model 1 ). When cumLE8 score from 18-45 and LE8 score at age 45 were in the model together ( Model 2 ), both were significantly associated with lower risk for CVD. Likewise, both cumLE8 score and positive slope of (improving) LE8 score from ages 18-45 were significantly associated with lower hazards for incident CVD after age 45 ( Model 3 ). Conclusion: Greater cumulative CVH and improvement in CVH during young adulthood, as well as better CVH in middle age, were all independently associated with lower risk for incident CVD in mid-life. These results emphasize the importance of maintaining and improving CVH throughout young adulthood.
Abstract 63: Change in Cardiovascular Health and Risk of Multimorbidity in Two Community-Based Studies
Authors: Christof Prugger, Marie-Cecile Perier, Severine Sabia, Aurore Fayosse, Thomas Van Sloten, Xavier Jouven, Jaana Pentti, Mika Kivimäki, Jean-Philippe Empana
Journal: Circulation (2024)

Introduction: Better cardiovascular health is associated with lower risk of various chronic diseases, but its association with multimorbidity is poorly understood. We aimed to examine whether cardiovascular health and its change are associated with multimorbidity risk. Methods: The primary analysis was conducted in the Whitehall II study (UK), a prospective cohort study established in 1985-1988, with clinical examinations in 1991-1993 and 1997-1999, and morbidity follow-up until 2019. The validation analysis was conducted in a cohort of Finnish public employees (Finnish Public Sector study, Finland). Exposures were the level of and change in cardiovascular health, assessed by the American Heart Association Life’s Simple 7 (LS7, ideal levels of smoking, physical activity, healthy diet, body mass index, blood pressure, fasting blood glucose, and total cholesterol) and Life’s Essential 8 (LE8, additionally considering sleep duration) at baseline and re-assessment. Primary outcome was incident multimorbidity defined as the presence of two or more of 12 chronic diseases during follow-up (coronary heart disease, stroke, heart failure, chronic obstructive pulmonary disease, chronic kidney disease, liver disease, depression, dementia, other mental disorders, Parkinson’s disease, arthritis/rheumatoid arthritis, and cancer). We estimated hazard ratios and 95% confidence intervals (CI) using Cox’s proportional hazard models with age as time scale, adjusting for sex, education, occupation, marital status, and ethnicity. Results: In the primary analysis among 9715 participants, mean age was 44.8 (standard deviation 6.0) years and 67.6% participants were men at baseline. During the median follow-up of 31.4 (interquartile range 26.8-32.3) years, 2751 participants developed multimorbidity. The hazard of multimorbidity decreased by 21% (adjusted hazard ratio (adj HR) 0.79, 95% CI 0.76-0.82) per one ideal LS 7 metric increment and by 23% per 10 points higher LS8 score (adj HR 0.77, 95% CI 0.74-0.79) at baseline, respectively. The hazard of multimorbidity decreased by 8% (adj HR 0.92, 95% CI 0.88-0.96) per ideal LS7 metric increment over 5 years (from baseline to 1991-1993) and by 14% (adj HR 0.86, 95% CI 0.80-0.93) per ten points increase in LE8 score over 10 years (from baseline to 1997-1999) respectively. These findings were replicated in the validation analysis among 75377 participants, both in terms of the baseline level and 4-year change in cardiovascular health. Conclusions: Better cardiovascular health and its improvement were associated with lower multimorbidity risk in two community-based cohorts.