tbuckley/cabot-search huggingface dataset:
Abstract P250: Vascular Contributions to Alzheimer's Disease
Authors: Soumilee Chaudhuri, Shiwei Liu, Yen-Ning Huang, Tamina Park, Thea Rosewood, Min Young Cho, Kwangsik Nho, Andrew Saykin
Journal: Circulation (2024)

Introduction: Alzheimer’s disease (AD) is a debilitating neurodegenerative disorder that affects over 50 million people worldwide. The role of vascular risk factors have been described as a contributor to and a major comorbidity of AD pathogenesis; yet there is discordant evidence of this complex relationship between cardiovascular diseases (CVD) and its risk factors (like hypertension, hyperlipidemia, obesity, etc.) with AD pathophysiology and cognitive decline. AD associated Genome-wide association studies (GWAS) and derived polygenic risk scores (AD PRS) have uncovered some significant common genetic variants relating to CVD risk factors; however, we are still yet to unravel the comprehensive impact of these vascular genetic contributions to AD pathogenesis and cognitive decline. Method: In this study, we used 1800 participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort spanning the full spectrum of clinical and pathological diagnoses of the AD spectrum, as our target dataset used for polygenic risk score calculation. Thereafter, we obtained GWAS summary statistics for cumulative cardiovascular risk by searching the Polygenic Score (PGS) GWAS Catalog using CVD as the ‘mapped trait” and then calculated cardiovascular-based PRS using HRS-based imputed GWAS data of the ADNI cohort. We conducted association analysis using a multivariate linear regression model with appropriate covariates (age, sex, APOE, education, etc.) between CVD-related polygenic risk score (CVD-PRS) with the different clinical AD diagnoses groups (Cognitively Normal/CN, Significant Memory Concerns/SMC, Mild Cognitive Impairment/MCI, Alzheimer's Disease/AD). We also performed association analysis of this CVD-PRS with white matter hyperintensity (WMHI) values, a vascular biomarker, at baseline using a linear regression model. Furthermore, we extended our analyses of CVD-related PRS with cognitive performance at baseline using composite scores for memory (MEM) and executive functioning (EF). Results and Conclusion: We found significantly strong correlation of CVD-related PRS with only certain AD Diagnoses groups (Significant Memory Concerns: SMC and Alzheimer's: AD) in the AD continuum. Additionally, we found strong associations (p &lt; 0.05) of this cardiovascular based- polygenic risk score with baseline memory as well as White Matter Hyperintensity (WMH) in our sample, specifically the group with a clinical diagnosis of AD. Furthermore, we are performing longitudinal association analysis of CVD-related PRS with longitudinal cognitive decline using a linear mixed effects model. Our findings will help us understand 1) how a cumulative CVD-related PRS associates with different AD diagnoses subgroups as well as vascular biomarkers for AD and 2) how CVD-related PRS associates with cognitive performance and longitudinal cognitive decline.
Abstract P256: Rationale, Development, and Implementation of a Multidisciplinary Digital Lifestyle Health Education Program for Older Adults With Cardiovascular Disease and Osteoarthritis
Authors: Belinda J Parmenter
Journal: Circulation (2024)

Introduction: Cardiovascular disease (CVD) is the leading cause of death worldwide. Globally, osteoarthritis (OA) affects 654 million. In 2018, of the 1.2 million Australians who had CVD, half also had arthritis, with the most common form in Australia being OA. Ongoing pain and physical limitations from OA can affect lifestyle choices, contributing to the shared risk factor profile of CVD and OA (physical inactivity, overweight/obesity, poor diet, high medication use). This contributes further to the burden of both diseases including reduced 6-minute walk (6MW) performance, which is directly related to increased CVD mortality. This project outlines the rationale for and development of a multidisciplinary digital lifestyle health education program for the treatment and secondary prevention of CVD and its common comorbidity of OA. Methods: This study is a cross-sectional analysis of older adults in Sydney. Class was classified based on the Australian socioeconomic index for areas. Conditions were defined according to Australian national guidelines. Medical history, body mass index (BMI), waist measurement, muscle strength, and 6MW measurements were assessed. Differences between those with and without OA were determined via one-way analysis of variance. Simple linear regressions assessed potential relationships. Results: In a cohort of 532 adults; n=341 (64.1%) had diagnosed CVD; 48.4% of which had OA (mean age 66±12 years; 73.3% female). Socioeconomic index was deemed high. In the OA cohort mean BMI and waist were above healthy heart recommendations according to the World Health Organisation. There were no significant differences between those with OA and those without for cardiovascular risk factors of body weight, BMI, waist measurement, blood pressure, 6MW, or muscle strength. However, in those with CVD and OA, the relationship between age and 6MW was stronger and age accounted for more of the variance in performance (r=-0.44; r 2 =0.19; p&lt;0.001) than those without OA (r=-0.37; r 2 =0.17; p&lt;0.001), indicating a greater reduction in walking ability in those with OA as they get older. Conclusion: With 6MW performance being related to CVD mortality, interventions are needed to improve health and fitness in this cohort. International guidelines for CVD and OA recommend treatment should prioritise lifestyle changes, including a healthy diet, regular physical activity, and interventions that address all risk factors. Lifestyle LIFEMAP will assess the efficacy of a widely translatable multidisciplinary digital evidence-based 10-module lifestyle, food, exercise, medication, and park prescription education program for adults with the comorbidity of CVD and OA. We expect this program to improve knowledge, and healthy lifestyle choices, thereby improving physical activity and health outcomes in this highly vulnerable population.
Abstract P251: Circulating Immune Cell Phenotypes Are Associated With Inflammatory Biomarkers in the Framingham Heart Study Offspring Cohort
Authors: Jiachen Chen, Margaret Doyle, Ahmed Ragab, Yumeng Cao, Joanne Murabito, Kathryn Lunetta
Journal: Circulation (2024)

Age-related changes in circulating immune cells have been associated with inflammation and immunosenescence, increasing susceptibility to cardiovascular disease. This study investigated the association between circulating immune cell phenotypes and inflammatory biomarkers in the Framingham Heart Study Offspring cohort. Participants (N=865, 52% female, mean age 62) were immunophenotyped using peripheral blood mononuclear cells with 37 immune cell phenotypes and 6 composite ratio measures, including T cells, B cells, NK cells, and monocytes. The inflammatory biomarkers were profiled in plasma samples using the OLINK Proteomics inflammation panel. Pairwise cross-sectional associations between 43 circulating immune cell phenotypes and 68 protein biomarkers were investigated using linear mixed-effect models accommodating familial correlations and adjusting for covariates (sex, age, number of apolipoprotein E ( APOE) ε2 and ε4 alleles, and cytomegalovirus levels), with FDR ≤0.05 to declare significant associations. Age-stratified analyses were performed to explore effect modification. CD8 T naïve cells (CD8Tn) were negatively associated with several proteins ( Figure ). Significant associations were also observed for CD4 T cell subtypes including higher levels of CD4 T helper cells associated with lower Flt3L and TNFRSF9, higher levels of CD4 T central memory (Tcm) and CD4 T effector (Teff) cells associated with lower TNFB, and higher CD4 Teff associated with lower CD40 levels. Among associations identified in the full sample, we observed a large proportion of associations between CD4 T cell subtypes and CD8 Tn in the older age group (&gt;60 years) but not the younger age group. Our results suggest that people tend to have more inflammation-associated immune responses during aging. Future studies are needed to improve understanding of the contribution of these inflammation-immune cell associations to cardiovascular disease.
Abstract P128: Self-Reported Resilience During the COVID-19 Pandemic: The C4R-MESA Study
Authors: Oluwabunmi V Ogungbe, Tianyou Wang, Pallavi Balte, Akshaya Krishnaswamy, Sarah Slone, Diane Meyer, Jana Hirsch, Norrina B Allen, Karen Hinckley Stukovsky, R. Graham Barr, Elizabeth Oelsner, Wendy S Post
Journal: Circulation (2024)

Background: Resilience, or the ability to bounce back from adversity, may be associated with health and wellbeing during disaster events such as the COVID-19 pandemic. Objectives: To examine correlates of resilience, as self-reported during the COVID-19 pandemic, in multi-ethnic, US community-dwelling adults. Methods: The Multi-Ethnic Study of Atherosclerosis (MESA) assessed the impact of the pandemic on participants via questionnaires designed by the Collaborative Cohort of Cohorts for COVID-19 Research (C4R) Study. Based on one item from the Brief Resilience Scale, “I tend to bounce back quickly after hard times,” participants who responded with “agree” were defined as resilient and compared to those who responded “neutral” or “disagree” (not resilient). Logistic regression was used to test associations of resilience with age, sex, race and ethnicity, education, BMI, smoking, hypertension, diabetes, COVID infection history, insurance status, and household income. Results: Of 1880 participants (mean age 75.0±7.6 years; 55% female; 75% White, 55% Chinese, 81% Black, 75% Hispanic; 9% uninsured), 73% were identified as resilient. Race and ethnicity were significantly associated with resilience: compared to White, Black participants were more likely to report resilience (aOR:1.51;95%CI:1.10-2.06), and Chinese participants were less likely (aOR:0.47;95%CI:0.34-0.66). There were no differences in self-reported resilience, comparing Hispanic to White participants ( Table ). Conclusion: During the COVID-19 pandemic, three-quarters of community-dwelling US results reported that they were resilient. Variation in self-reported resilience was observed according to race and ethnicity. Further research is needed on resiliency and how it may influence psychosocial well-being and cardiovascular health.
Abstract P247: Rural-Urban Disparities in In-Hospital Stroke Mortality in North Carolina
Authors: Mahesh V Pinapaka, Mehul D Patel, Srihari V Chari, Wayne D Rosamond
Journal: Circulation (2024)

Introduction/Hypothesis: Stroke remains a significant public health concern. North Carolina (NC) has the 11 th highest stroke mortality in the United States and an increasingly diverse population with respect to rurality and race-ethnicity. We assessed the hypothesis that rural stroke patients have higher in-hospital mortality than urban stroke patients in NC. We also explored the interaction between rurality and race-ethnicity on stroke mortality. Methods: We conducted a retrospective study of stroke hospitalizations at 115 NC hospitals from January 2019-September 2020. Data were obtained from an inpatient database of patient demographics, county of residence, insurance, admission date, and discharge disposition and diagnoses. Eligible patients included adults with principal discharge diagnosis codes for stroke (ICD-10-CM I60.xx-I63.xx) and were classified by rurality defined by the NC Office of Rural Health. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) comparing in-hospital mortality in rural versus urban patients, overall and stratified by race-ethnicity subgroups. Results: Among 32,808 patients, 37% resided in rural counties. Patients were mean 69 years old, 50% female, 30% Black, and 3% Hispanic. Unadjusted in-hospital mortality was lower in rural versus urban patients (4.2% and 5.0%, respectively). Adjusted model found a weak, non-significant association between rurality and stroke mortality (OR 1.06, 95% CI 0.95-1.19; Table 1). In race-ethnicity subgroups, rural-urban ORs were not statistically significant although the point estimates suggest modestly greater differences among racial/ethnic minorities compared to White patients. Conclusions: We found minimal, adjusted rural-urban differences in in-hospital stroke mortality in NC statewide and within race-ethnicity subgroups. Further research is needed to investigate potential disparities in long-term stroke mortality and morbidity and their underlying determinants.
Abstract P367: Regularity in Sleep and Eating Timing is Associated With Decreased Carotid Intima-Media Thickness in Healthy Young Adults
Authors: Thomas Keiser, Elissa K Hoopes, Melissa A Witman, Benjamin Brewer, Michele N D'Agata, David G Edwards, Shannon M Robson, Susan Malone, Freda Patterson
Journal: Circulation (2024)

Introduction: Greater regularity in daily sleep and eating timing are independently and separately associated with lower carotid intima-media thickness (CIMT), a marker of subclinical atherosclerotic development in early adulthood. Not known is the extent to which achieving regularity in both sleep and eating would be associated with a lower CIMT as compared to achieving regularity in either behavior alone, or neither. Such information could help identify behavioral target priorities for cardioprotective interventions. Hypothesis: We tested the hypothesis that individuals achieving both sleep and eating regularity would have a lower CIMT than individuals with either sleep or eating regularity, or neither. Methods: Healthy adults aged 18-45 years (N=65, 29.7±7.2 years, 63% female) completed 14 days of sleep and dietary assessments via wrist accelerometry and photo-assisted diet records, respectively. Mean time for sleep midpoint (midpoint time between sleep onset and offset) and caloric midpoint (time at which 50% of total daily calories are consumed), sleep regularity (i.e., a mean sleep midpoint standard deviation (SD) of &lt;60 minutes), and eating regularity (i.e., caloric midpoint SD &lt; median of 154 minutes) values were generated. A 4-level ‘sleep and eating regularity’ variable was generated that distinguished between participants achieving regularity in: (1) both sleep and eating, (2) only eating, (3) only sleep, or (4) neither. A linear regression model evaluating the association between sleep and eating regularity with CIMT adjusting for age, sex, systolic blood pressure, sleep duration, and total energy intake was estimated. Results: Participants who achieved regularity in both sleep and eating (n=23) had the lowest M CIMT =0.523mm (SD=0.043), those who achieved only sleep regularity (n=10) had a M CIMT =0.549mm (SD=0.078), only eating regularity (n=16) had a M CIMT =0.568mm (SD=0.065), and those achieving neither sleep or eating regularity (n=16) had the highest M CIMT =0.575mm (SD=0.074). In a controlled model, the 4-level sleep and eating regularity variable was significantly associated with CIMT (F=2.95, p=.04, model R 2 =.33), with regularity in both demonstrating pairwise significance as compared to neither (p = 0.02) and eating regularity only (p = 0.02). Given that a 1-SD increase in CIMT (~0.06-0.07mm) has been shown to confer a 40% increased risk for first-time CVD events in adults &lt;45 years old, the ~0.05mm difference in CIMT between regular vs. irregular groups has clinical meaning. Conclusions: Regularity in sleep and eating may be associated with lower subclinical atherosclerosis as early as young adulthood. Future studies evaluating the cardioprotective effects of promoting regularity of modifiable behaviors (eating and sleep) in adults at elevated CVD risk are warranted.
Abstract P248: Women With Migraine Had Higher Progression of 10-year Stroke Risk Than Those Without Migraine: Findings From a Nested Case-Control Study
Authors: Longben Tian, Yao Jie Xie, Yunyang Deng, Harry Haoxiang Wang, Justina Liu
Journal: Circulation (2024)

Introduction: There was limited understanding of the association between migraine status and longitudinal changes in stroke risk. Hypothesis: We hypothesized that migraine patients would have higher growth in 10-year stroke risk than those without migraine during a 1-year follow-up period in Hong Kong Chinese women. Methods: A nested case-control study was conducted using data from the Migraine Exposures and Cardiovascular Health in Hong Kong Chinese Women (MECH-HK). The MECH-HK initially enrolled 4,221 Hong Kong Chinese women aged 30-74 years between 2019 and 2021 and followed up with 3,435 participants in the second-round survey until September 2023. Diagnosis of migraine was confirmed according to the ICHD-3 criteria. Stroke risk was calculated using the 10-year China-PAR (Prediction for Atherosclerotic Cardiovascular Disease Risk in China) stroke risk model. The change in China-PAR stroke risk between the baseline and second-round survey was then computed. Cases were identified as individuals with the top 20% high growth in China-PAR stroke risk. The age-matched controls (±2 years) were randomly selected from the cohort at a 1:1 ratio. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariable conditional logistic regression models. Subgroup analyses were performed based on participants' baseline age (&lt;65 years or ≥65 years) and the presence of migraine aura (migraine with or without aura). Results: A total of 589 cases (aged 60.70 ± 4.31 years) and 589 controls (aged 60.57±6.05 years) were identified (p &gt;0.05). The baseline 10-year China-PAR stroke risk was 2.80%±1.73% and 2.97%±2.01% in the cases and controls, respectively (p &gt;0.05). A total of 48 (8.1%) and 15 (2.5%) women with migraine in the cases group and controls group were identified (p&lt;0.01). During the 1.13-year follow-up period (Interquartile range: 1.07-1.22), migraine was associated with a 3.39-fold increase in the odds of being high growth in China-PAR stroke risk after adjustment for age, education level, drinking, and previous use of oral contraceptive (95% CI: 1.91-6.38, p&lt;0.01). In subgroup analyses, the association was only found in women aged 65 years and older (adjusted OR: 4.12, 95% CI: 2.02-9.34, p&lt;0.01). In addition, a stronger association was observed in women with migraine with aura (adjusted OR: 6.97, 95% CI: 2.33-30.01, p&lt;0.01, migraine with aura vs. non-migraine) than those without aura (adjusted OR: 2.52, 95% CI: 1.29-5.21, p&lt;0.01, migraine without aura vs. non-migraine). Conclusion: Migraine was associated with higher growth of 10-year stroke risk in a sample of Hong Kong Chinese women, typically in older women and the women with migraine with aura.
Abstract P131: Individualized Risk Prediction for Type 2 Diabetes: A Secondary Analysis of the Diabetes Prevention Program
Authors: Byron C Jaeger, Ramon Casanova, Brian Wells, Yitbarek Demesie, Jeanette Stafford, Michael Bancks
Journal: Circulation (2024)

Introduction: Type 2 diabetes (T2D) risk prediction models that predict risk with individualized preventive intervention effects can help targeted prevention. Hypothesis: An individualized T2D risk prediction model developed in the Diabetes Prevention Program (DPP) randomized trial that incorporates differential treatment effects based on an individual’s fasting glucose (FG) level and body mass index (BMI) will provide more accurate predictions than a model without individualized treatment effects. Methods: We included 2640 DPP participants randomized to the placebo, metformin, or lifestyle arms. Using 50% of the DPP sample, we developed a non-individualized Cox model predicting T2D risk over 3 years with adjustment for sex, hemoglobin A1c, triglycerides, FG, BMI, and treatment, and an individualized model with adjustment for these variables plus interactions between treatment and age, FG, and BMI. In the remaining 50%, we evaluated the prediction accuracy of both models using the concordance (C)-statistic. We repeated this process 100 times with different random splits. We externally validated models among Multi-Ethnic Study of Atherosclerosis (MESA) adults with prediabetes (n=1067) where model predictions were computed for each intervention scenario and averaged for all participants. Results: Mean (standard deviation) age of participants was 51 (11) years in the DPP and 64 (10) in MESA, with 67% and 54% women, respectively. Mean C-statistics for our individualized and non-individualized prediction models (100 splits) in DPP were 0.71 and 0.70, respectively (table). The individualized model predicted higher benefit of lifestyle intervention at lower BMI levels and higher benefit of both metformin and lifestyle at higher FG. The C-statistic of the individualized model was 0.78 in the MESA validation. Conclusion: Creating individualized estimates of intervention effects can improve accuracy of T2D risk prediction models, allowing patients to make more informed decisions about prevention strategies.
Abstract P134: Bidirectional Association of Diabetes and Heart Failure
Authors: Justin B Echouffo, Sui Zhang, Kuni Matsushita, VIJAY NAMBI, Christie M Ballantyne, Amil M Shah, Joe Coresh, Elizabeth Selvin, Chiadi E Ndumele
Journal: Circulation (2024)

Background: Diabetes and heart failure (HF) frequently coexist. Diabetes is a major risk factor for HF, but physiological studies have also shown that HF promotes insulin resistance, and thus may predispose to diabetes. However, the bidirectional association between diabetes and HF has seldom been examined in community-based studies. Methods: We conducted a prospective analysis of 10982 individuals (mean age 63.3 years, 56% women, ~22% Black adults, 1822 [16.6%] with prevalent diabetes and 606 [5.5%] with prevalent HF) who attended Visit 4 (1996-1998) of the Atherosclerosis Risk in Communities (ARIC) Study. We used Cox regression to examine the association of prevalent HF at Visit 4 or incident HF after Visit 4 with the incidence of diabetes, as well as the association of prevalent diabetes at Visit 4 or incident diabetes after Visit 4 with the incidence of HF. We also assessed individual and joint associations of diabetes and HF at Visit 4 with mortality. Results: Of the 606 individuals with prevalent HF by Visit 4, more than half (52.3%) had or developed diabetes. Among 1822 individuals with prevalent diabetes at Visit 4, 44% had a history of HF. Prevalent HF (hazard ratio [HR]: 1.34, 95%CI: 1.09, 1.64; no HF as referent) and incident HF (HR: 1.32, 95%CI: 1.08, 1.61) were each associated with incident diabetes. Prevalent diabetes (HR, 1.83; 95% CI, 1.64, 2.03; no diabetes as referent) and incident diabetes (HR: 1.37, 95%CI: 1.21, 1.56) were each associated with incident HF. The presence of both prevalent HF and diabetes conferred greater overall mortality (HR: 2.59, 95% CI: 2.22, 3.02) and cardiovascular mortality (HR: 3.82, 95% CI: 3.06, 4.78) risks compared with the absence of both conditions or either condition alone. Conclusions: Diabetes precedes and follows HF, with each condition being a risk factor for the other. The coexistence of both diabetes and HF is associated with a markedly elevated risk of mortality.