bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 46: Midlife and Late-Life Population Attributable Fractions of Dementia Risk Factors in the United States: A Cohort Study From the Dementia Risk Pooling Project
Authors: Li Joanne M , Gauen Abigail M , Zmora Rachel , Stephen John , Sedaghat Sanaz , Scholtens Denise , Mansolf Maxwell , Kohli-Lynch Ciaran N , Peterson Elizabeth , Gross Alden , Singh-Manoux Archana , Ikram Mohammad A , Tzourio Christophe , Satizabal Claudia L , Levine Deborah A , Lloyd-Jones Donald M , Briceno Emily M , Sorond Farzaneh , Wolters Frank , Himali Jayandra , Launer Lenore J , Zhao Lihui , Lopez Oscar L , Debette Stephanie , Seshadri Sudha , Judd Suzanne E , Hughes Timothy M , Gudnason Vilmundur , Soumare Aicha , Aiello Allison , Forrester Sarah , Allen Norrina B
Published: May 2024

Introduction:
Dementia cases in the US are projected to nearly double from 5.3 million in 2019 to 10.5 million by 2050. Research has suggested that 41% of US dementia cases may be prevented by eliminating several specific modifiable risk factors. Still, few studies examine risk factor variation between midlife and late-life. Previous studies have also been limited by sample diversity and size. The Dementia Risk Pooling Project (DRPP) is a consortium of longitudinal cohorts including several underrepresented racial/ethnic groups pooled at the individual level.

Methods:
We estimated individual and combined population attributable fractions (PAF) for seven modifiable risk factors in midlife (aged 45-64) and late-life (aged 65+), using data from six US cohorts in DRPP. We also used potential impact fractions (PIF) to estimate dementia cases that could be prevented due to risk factor reduction in midlife and late-life based upon the National Alzheimer’s Advisory Council goal of a 15% reduction in dementia risk factors by 2030.

Results:
In a sample of 41,432 unique participants (ppts), risk factor exposure was measured in midlife for 29,983 ppts (60% female, 77% white) and in late-life for 30,633 ppts (56% female, 70% white). During follow-up, 4,186 midlife ppts and 4,893 late-life ppts developed dementia. We found that eliminating midlife risk factors could prevent a greater proportion of dementia cases [PAF 41.3%, 27.9%-54.6%] compared to late-life risk factors [23.1%, 12.4%-33.7%]. Midlife physical inactivity [18.8%, 15.1%-22.4%] appeared to be the greatest contributor. Late-life hypertension and depression appeared to contribute to 9.8% [5.5%-13.9%] and 4.2% [3.5%-5.0%] of cases, respectively. Given the US prevalence of dementia in 2020, we estimate that a 15% reduction in physical inactivity alone could prevent 148,339 dementia cases.

Conclusion:
The importance of modifiable risk factors for dementia may vary with age. These estimates could inform the timing of public health interventions for dementia prevention.
Abstract 50: Factors Associated With Obesity Pharmacotherapy Prescription Among Ambulatory Patients With Excess Weight
Authors: Haile Meron , Ozkan Bige , Shin Jung-Im , Ogunwole Michelle , Coresh Josef , Gudzune Kimberly A , Ndumele Chiadi E
Published: May 2024

Background:
Semaglutide, liraglutide (GLP1-RA), and tirzepatide (GLP1/GIP-RA) are potent anti-obesity pharmacotherapies resulting in marked weight loss and improved cardiometabolic outcomes. Limited insurance coverage is a well-understood barrier to these new therapies; thus, we sought to characterize additional clinical and sociodemographic factors associated with the prescription of these medications.

Hypothesis:
Likelihood of prescription of novel anti-obesity medications will be lower for individuals within racial and ethnic minority and lower SES subgroups.

Methods:
We identified adults who have obesity (BMI ≥30), existing insurance coverage for anti-obesity medications, and received outpatient care at Johns Hopkins from January 2023 to September 2023. We used multivariable logistic regression to evaluate factors associated with prescription of anti-obesity pharmacotherapies.

Results:
We included 18,164 patients (mean age 51 years, 64% female, 54% White, 35% Black, 5% Asian, mean BMI 36 kg/m
2
). About 3% of eligible adults were prescribed anti-obesity medications. The likelihood of prescription was lower among Black adults (OR: 0.76, 95%CI [0.61-0.96]), males (OR: 0.54 [0.42-0.68]), and adults younger and older than 40-50 years of age; and higher for those with higher BMI (per 1-unit higher BMI, OR: 1.06 [1.05-1.07]). Living in a neighborhood with a higher area deprivation index or lower income was not independently associated with the likelihood of prescription. Clinically, those with diabetes (OR: 3.52 [2.78-4.44]) and hypertension (OR: 1.36 [1.08-1.71]) were more likely to be prescribed novel obesity pharmacotherapies.

Conclusion:
Among those with existing insurance coverage, the likelihood of obesity pharmacotherapy prescription differs by sociodemographic factors and cardiometabolic comorbidities. Understanding the mechanisms of these differences may have key implications for obesity management in diverse populations, and ultimately for cardiometabolic health equity.
Abstract 52: Associations of Ideal Cardiovascular Health and Its Change With Cardiovascular-Kidney Outcomes in Young Adults
Authors: Lee Hokyou , Lee Hyeok-Hee , Jhee Jong Hyun , Kim Eun Jin , Kim Hyeon Chang , Lloyd-Jones Donald M
Published: May 2024

Introduction:
The AHA recently highlighted the linkage of cardiovascular (CVD) and chronic kidney disease (CKD) and the importance of promoting cardiovascular health (CVH) to prevent them. We hypothesized that attaining ideal CVH score or improving it in young adulthood is associated with low risk of cardiovascular-kidney events, but data are scarce.

Methods:
We studied 3,836,283 participants of the Korean national health screening in 2009-2010 (baseline age 20-39 y) without prior CVD or CKD. Participants were categorized by the number of ideal CVH components met (range 0-6; diet data unavailable). A subgroup of 2,768,705 participants who underwent follow-up health exam in 2011-2014 (median 4.2 y from baseline) were stratified by combination of baseline and follow-up CVH scores. The primary outcome was a composite of CVD events, incident CKD, and death from kidney disease or CVD, until 31 Dec 2021 (Fig, footnote).

Results:
At baseline, participants had median age 31 y, and 38.2% were female. During a median follow-up of 12.1 y, 172,217 cardiovascular-kidney events occurred. The multivariable-adjusted risk of cardiovascular-kidney event decreased gradually (HR 0.81 per 1 p higher CVH score) with higher CVH scores (Fig, A). A CVH score of 6 was associated with a 65% lower risk of cardiovascular-kidney event than a CVH score of 0. An increase in CVH score from the baseline to follow-up exam was associated with a lower risk of cardiovascular-kidney event (HR 0.87 per +1 p CVH score change). The risk was lowest in participants with high CVH at both baseline and follow-up; having high CVH at baseline, and improving from low to high CVH, were also associated with lower risk than those who maintained low CVH (Fig, B). Findings were similar for CKD and other individual endpoints.

Conclusions:
Achieving, maintaining, or improving ideal CVH during young adulthood was associated with lower risk of cardiovascular-kidney events, highlighting the importance of promoting early-life CVH for combined prevention of cardiovascular and kidney disease.
Abstract 54: Circulating Biomarkers and Anticoagulation Breakthrough Stroke Risk in Atrial Fibrillation: The REGARDS Study
Authors: Short Samuel , Wilkinson Katherine , Hald Erin , Howard George , Howard Virginia J , Judd Suzanne E , Soliman Elasayed , Kissela Brett , Robinson David , Stanton Robert J , Cushman Mary
Published: May 2024

Introduction:
Anticoagulation reduces ischemic stroke risk in atrial fibrillation (AF), but “breakthrough” stroke occurs. Blood biomarkers might help identify patients at risk for anticoagulation breakthrough stroke, but existing studies are limited by examining few biomarkers in select populations.

Hypotheses:
Established biomarkers of ischemic stroke risk will also be associated with ischemic stroke risk in people with AF on anticoagulation sampled from the general population.

Methods:
REGARDS is a prospective cohort of 30,239 Black or White adults aged ≥45 on enrollment in 2003-7 monitored for stroke. Nine established blood biomarkers of ischemic stroke risk were measured at baseline in participants with AF and with no prior stroke who were taking oral anticoagulation at baseline. Hazard ratios of ischemic stroke were estimated by Cox models adjusted for demographics and stroke risk factors.

Results:
Among 713 participants with AF on anticoagulation (median age 76, 36% female, 17% Black, all taking vitamin K antagonists), 67 (9%) developed a first-time ischemic stroke over 12 years. In models adjusted for demographics, there were positive associations of all biomarkers with stroke risk except for galectin-3, lipoprotein(a), and cystatin C which had inverse or null associations (Figure). Adjustment for risk factors minimally impacted interpretation of results. The greatest associations were with higher N-terminal pro-B type natriuretic peptide, factor VIII, D-dimer, and growth differentiation factor 15; associations for D-dimer and growth differentiation factor 15 were not statistically significant. Hazards for galectin-3, gamma glutamyl transferase, interleukin 6, and lipoprotein (a) were modest and not statistically significant.

Conclusion:
Biomarkers of cardiac strain (specifically atriopathy), coagulation, and inflammation were associated with higher ischemic stroke risk in people with AF on anticoagulation at baseline. Findings highlight new avenues for reducing stroke risk in AF.
Abstract 57: Gut Microbiota, Blood Metabolites and Left Ventricular Diastolic Dysfunction in US Hispanics/Latinos
Authors: Luo Kai , Taryn Alkis , Moon Eun Hye , Peters-Samuelson Brandilyn , Solomon Scott , Daviglus Martha L , Kansal Mayank M , Thyagarajan Bharat , Gellman Marc , Cai Jianwen , Burk Robert , Knight Rob , Kaplan Robert , Cheng Susan , Rodriguez Carlos J. , Qi Qibin , Yu Bing
Published: May 2024

Background:
Left ventricular diastolic dysfunction (LVDD) is a precursor of heart failure (HF), but its relationship with gut dysbiosis and microbial-related metabolites remains unclear.

Hypothesis:
Alerted gut microbiota composition is associated with LVDD and blood metabolites, which can be used as indicators of gut dysbiosis.

Methods:
This study included up to 1996 adults (mean age: 59.4 years; 67.1% female; 45.9% with prevalent LVDD) from the Hispanic Community Health Study / Study of Latinos with echocardiography assessments, gut microbiota (512 bacteria species), and blood metabolome (669 metabolites) data. Cross-sectional associations of gut bacteria with prevalent LVDD and metabolites, and prospective associations of microbial-associated metabolites with incident LVDD were assessed.

Results:
Seven bacterial species were associated with LVDD (FDR-q <0.1), with inverse associations found for
Intestinimonas_massiliensis
,
Clostridium_phoceensis,
and
Bacteroide_coprocola
, and positive associations for
Gardnerella_vaginali
,
Acidaminococcus_fermentans, Pseudomonas_aeruginosa
and
Necropsobacter_massiliensis
. A total of 220 metabolites were found to be associated with identified bacteria (FDR-q <0.1), with 46 associated with prevalent LVDD (FDR-q <0.1). Of note, 21 metabolites were associated with incident LVDD over a median 4.3 years of follow-up, including many known microbial metabolites (e.g., indolepropionate, 3b-hydroxy-5-cholenoic acid and glycohyocholate). The use of these metabolites significantly improved the prediction of incident LVDD, outperforming models only with traditional risk factors (AUC=0.73 vs. 0.70, p=0.001). Metabolite-based proxy association analyses revealed potential prospective associations between 3 gut bacteria species (e.g.,
I.massilliensis
and
C.phoceensis
) and incident LVDD.

Conclusion:
Our study found gut bacteria and bacteria-associated metabolites linked to LVDD, suggesting their potential roles in this preclinical HF entity.
Abstract 68: The Association of Pre-Pregnancy Body Mass Index With Gestational Diabetes Across Maternal Race and Ethnicity Subgroups
Authors: Boyer Theresa , Hsueh Christine , Sun Kevin M , Selvin Elizabeth , Hays Allison G , Michos Erin D , Vaught Arthur J , Ndumele Chiadi E , Coresh Josef , Minhas Anum
Published: May 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 69: Trajectory of Cardiovascular Health Across Childhood and Adolescence in Project Viva
Authors: Aris Izzuddin , Rifas-Shiman Sheryl , Perng Wei , de Ferranti Sarah , Hivert Marie-France , Oken Emily
Published: May 2024

Introduction:
The American Heart Association recently put forth the Life’s Essential 8 (LE8) algorithm to assess cardiovascular health (CVH) status based on 8 health and behavioral factors. Few studies, however, have characterized the natural history of CVH status across development or identified sociodemographic determinants of CVH trajectories in children. We sought to address this research gap using data from Project Viva, a pre-birth cohort in eastern Massachusetts.

Methods:
We applied the LE8 algorithm to derive CVH score (range 0-100 points) in early childhood (median age 3.2y), mid-childhood (7.7y), early adolescence (13y), and late adolescence (17.5y). We used segmented mixed-effect models to characterize sex-specific CVH trajectories across these life stages and estimate three subject-specific trajectory parameters: timing of inflection point when CVH score declines; slope before and after the inflection point. We used linear regression models to assess the association of child race and ethnicity, mother’s education level, and annual household income with each trajectory parameter.

Results:
Among 1,523 children included, 48.7% were female, 3.5% Asian, 15.2% Black, 4.8% Hispanic, 11.5% Other, and 65.0% White. The mean (SD) CVH score was 82.6 (8.6) points in early childhood, 84.1 (8.3) points in mid-childhood, 82.0 (9.8) points in early adolescence, and 73.8 (11.5) points in late adolescence. Females (vs. males) exhibited slower rate of CVH score gain before the inflection point (0.3 vs. 1.0 points/y), later timing of inflection point when CVH score started declining (10.1 vs. 9.6y), and slower rate of CVH score decline after the inflection point (-1.3 vs. -1.5 points/y). Children of Black (β 0.48y; 95% CI 0.28, 0.68) or Other (β 0.28y; 95% CI 0.08, 0.49) race had a later timing of inflection point compared with White children. Children whose mothers were college-educated (vs. non-college educated) had higher CVH score throughout childhood, and exhibited faster rate of CVH score gain before the inflection point (β 0.19 points/y; 95% CI 0.03, 0.34), earlier timing of inflection point (β -0.37y; 95% CI -0.53, -0.22), and faster rate of CVH score decline after the inflection point (β -0.24 points/y; 95% CI -0.38, -0.10). No associations were observed for household income.

Conclusions:
This cohort study identified a key timepoint between mid-childhood and early adolescence where CVH trajectory declines over time, as well as sociodemographic differences in CVH trajectory parameters. Future studies are warranted to assess other determinants and consequences of these trajectory parameters.
Abstract MP02: Sociodemographic and Behavioral Factors Associated With Diet Quality Among Low-Income Community Health Center Patients With Hypertension
Authors: Cheng Jessica , Faulkner Katherine , Malone Ashlie , Gu Kristine , Thorndike Anne N
Published: May 2024

Objective:
Identify sociodemographic and behavioral factors related to the diet of low-income adults with hypertension to inform the development of a community health worker (CHW) nutrition security intervention to improve blood pressure.

Design:
In this cross-sectional analysis, dietary recalls were used to assess Healthy Eating Index-2020 (HEI-2020) total (range: 0 to 100 [best diet quality]) and component scores and sodium intake. Self-reported sociodemographic and behavioral data were entered into a Least Absolute Shrinkage and Selection Operator (LASSO) regression model to determine the relative importance of factors related to diet quality.

Setting:
Five community health centers in Boston, Massachusetts.

Participants:
Adults (>20 years old) with a hypertension diagnosis.

Results:
Participants (N=291) were mostly female (65.0%), on Medicaid (82.8%), food insecure (59.5%), and Hispanic (52.2%). The mean (95% CI) HEI-2020 score was 63.0 (62.3, 65.7) Component scores were low for sodium and whole grains; mean (SE) sodium intake was 2676.9 (45.5) mg/day. The most important factors associated with lower HEI-2020 scores were: not having own housing, male gender, tobacco use, marijuana use, and skipping meals; the most important factors associated with higher HEI-2020 scores were Hispanic ethnicity and receipt of community food resources (5-fold cross-validated R
2
=0.17).

Conclusions:
In this population of low-income adults with hypertension, diet quality would be improved by reducing sodium and increasing whole grain intake. In the future, a CHW intervention could help provide tailored dietary guidance while addressing social (e.g., community food resources) and behavioral (e.g., meal skipping) factors associated with poor diet in patients with hypertension.
Abstract MP21: Differences in Cardiovascular Risk Factors Across Age Strata in Five Race and Ethnic Groups: The Mediators of Atherosclerosis in South Asians Living in America (MASALA) and Multi-Ethnic Study of Atherosclerosis (MESA) Studies
Authors: Pedamallu Havisha , Aghabazaz Zeynab , Lancki Nicola , Rodriguez Luis A , Siddique Juned , Moorthy Meena , Shah Nilay S , Allen Norrina B , Kanaya Alka M , Kandula Namratha
Published: May 2024

Introduction:
Few studies have comprehensively examined if South Asian Americans develop atherosclerotic cardiovascular disease (ASCVD) risk factors at younger ages than other race/ethnicity groups. We compared ASCVD risk factors across age strata by race/ethnic group from two US community cohorts.

Methods:
We included 1164 South Asians from the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study and 2262 non-Hispanic White, 1892 Black, 1496 Hispanic, and 804 Chinese adults from the Multi-Ethnic Study of Atherosclerosis (MESA) study. Participants were 40-85 years (mean = 61.4, SD = 10.3) at initial exam. Mixed-effects linear or logistic regression models were used to predict the prevalence of risk factors by race/ethnic group at ages 45, 55, 65, and 75 years. We tested whether prevalence at age 45 and trends over time were different for South Asians compared to other groups. All models controlled for education, insurance status, and baseline smoking status.

Results:
At age 45, South Asians had a higher prevalence of hypertension than White, Chinese, and Hispanic/Latino adults, the highest prevalence of prediabetes or diabetes, and more dyslipidemia than Black and Chinese individuals. At age 45, South Asians reported higher diet quality and more exercise than other race/ethnic groups, and they also had significantly lower alcohol use than White, Black, and Hispanic groups. In addition, the change in these risk factors over time in South Asians differed from the trends in the other race/ethnic groups, (Table).

Conclusions:
South Asians have a high level of clinical risk factors and lower level of behavioral risk factors at age 45 compared to other race/ethnic groups. There are also different trends in risk factors with increasing age by race/ethnic group. Understanding trends and disparities in risk and protective factors across the lifecourse can help equitably improve prevention and treatment strategies for US populations.
Abstract MP24: Contemporary Trends in Incident Ischemic Stroke, Intracranial Hemorrhage, and Mortality in Individuals With Atrial Fibrillation
Authors: Noubiap Jean Jacques , Tang Janet J , Dewland Thomas A , Marcus Gregory M
Published: May 2024

Background:
The prognosis for atrial fibrillation (AF) patients is based on data that is decades old. Given evolving standards of clinical practice that may now include lifestyle factor modification, catheter ablation, and DOACs, we evaluated temporal trends in clinically important outcomes among patients with AF.

Methods:
California’s Department of Health Care Access and Information databases were used to identify adults aged ≥18 years with AF receiving hospital-based care in California. We compared 3 time-periods in this population-based cohort corresponding to 2005-2009, 2010-2014, and 2015-2019. The outcomes were incident ischemic stroke, intracranial hemorrhage, and mortality.

Results:
We included 1,859,901 patients with AF (52.7% males, 71.0% Whites, and mean age of 74.8 years), divided in 3 cohorts: 2005-2009 (n=680,872), 2010-2014 (n=558,365), and 2015-2019 (n=620,664). Each of these outcomes became substantially less common with time: compared to 2005-2009 (
Figure 1A
), AF patients diagnosed in 2015-2019 experienced a 42% (adjusted hazard ratio [HR] 0.58, 95% CI 0.57-0.60), 17% (HR 0.83, 95% CI 0.80-0.88), and 28% (HR 0.72, 95% CI 0.71-0.73) reduction in risk of incident ischemic stroke, intracranial hemorrhage, and mortality, respectively. Between 2005-2009 and 2015-2019, the decline in the incidence rate of adverse outcomes was greater in patients aged ≥65 years (p<.001), females (p=.02), and Whites (p<.001) for ischemic stroke; more pronounced in patients aged ≥65 years (p=.008), females (p=.02), and Whites and Asians (p=.005) for intracranial hemorrhage; and greater in patients aged ≥65 years (p<.001), in males (p=.04), and in Whites (p<.001) for mortality (
Figure 1B
).

Conclusion:
The risk of stroke, intracranial hemorrhage, and mortality have significantly declined among AF patients, although significant disparities in the magnitude of improvement of these outcomes by demographic groups were observed. Estimates of the prognosis for AF patients should be updated to reflect contemporary care.
Abstract MP25: Effect of Marine Omega-3 Fatty Acids on Risk of Incident Cardiovascular Disease Among Individuals With Non-Alcoholic Fatty Liver Disease: Secondary Analysis of a Randomized Clinical Trial
Authors: Qian Frank , Ajala Remi N , Li Chunying , Luttmann-Gibson Heike , Demler Olga , Cook Nancy R , Lee I-Min , Buring Julie , Zhang Xuehong , Danik Jacqueline , Manson JoAnn , Mora Samia
Published: May 2024

Background:
Individuals with non-alcoholic fatty liver disease (NAFLD) are at increased risk for developing cardiovascular disease (CVD), often attributed to adverse metabolic derangements such as insulin resistance and elevated triglycerides. Marine omega-3 (n-3) fatty acids may partially ameliorate these metabolic consequences. Whether supplementation with n-3 fatty acids can reduce the risk of CVD in NAFLD remains unknown.

Aims:
To investigate the association between a NAFLD phenotype and incident CVD as well as assess whether randomization to n-3 fatty acids can modify this risk.

Methods:
Among 16,824 participants from the Vitamin D and Omega-3 Trial (VITAL; NCT01169259; a 2x2 factorial randomized trial of 1 g/d of EPA+DHA or 2000 IU/d of vitamin D
3
) who provided baseline blood samples, we measured liver function tests. NAFLD was defined as baseline alanine aminotransferase (ALT)>40 U/L and/or aspartate aminotransferase (AST)>35 U/L, per guidance from the American Association for the Study of Liver Diseases. Incident CVD was a composite of myocardial infarction (MI), stroke, and CVD death. Multivariable-adjusted Cox models (adjusted for demographics, cardiovascular risk factors, and treatment assignment) were used to estimate hazard ratios (aHRs) and 95% confidence intervals (CI) for NAFLD with incident CVD. Effect of randomization to n-3 fatty acids was assessed among individuals with and without NAFLD.

Results:
We identified 2,495 participants with NAFLD at baseline, who tended to be younger, male, and non-White compared to individuals without NAFLD. After a median follow-up of 5.3 years, 522 CVD events were ascertained, with 101 occurring among those with NAFLD. Compared to individuals without NAFLD, those with NAFLD were at higher risk of developing CVD, aHR (95%CI): 1.48 (1.19, 1.84),
P
=0.0004. This association was predominantly driven by a higher incidence of total stroke, 1.53 (1.08, 2.17),
P
=0.02, compared with MI, 1.15 (0.81, 1.64),
P
=0.43. Randomization to n-3 fatty acids did not significantly reduce CVD incidence among individuals with, 1.13 (0.77, 1.68) or without NAFLD, 1.02 (0.85,1.24),

P
interaction

=0.70.

Conclusion:
In a large primary prevention trial of older individuals, NAFLD was associated with a higher risk of CVD, particularly stroke. Randomization to n-3 fatty acids did not significantly reduce CVD outcomes in this high-risk population.
Abstract MP35: Long-Term Trajectories of Self-Rated Health Are Similar Following Incident Diabetic Foot Disease and Acute Myocardial Infarction Among Adults With Diabetes in the Atherosclerosis Risk in Communities (ARIC) Study
Authors: McDermott Katherine M , Wang Dan , Fang Michael , Lutsey Pamela L , Windham B Gwen , Selvin Elizabeth , Hicks Caitlin W
Published: May 2024

Introduction:
Incident diabetic foot disease is associated with significant morbidity and mortality. However, data are lacking on long-term patient-reported outcomes. We aimed to evaluate trajectories of self-rated health among adults with diabetes before and after incident foot disease compared to incident acute myocardial infarction (MI), another major diabetes complication.

Methods:
We conducted a longitudinal analysis of participants in the ARIC Study with diabetes and incident diabetic foot disease (N=749 hospitalizations, N=73 outpatient encounters) or incident MI (N=703). Diagnosis and procedure codes from active hospitalization surveillance and Medicare claims were used to identify events; only MI events were adjudicated. Self-rated health was collected during annual telephone calls and rated from 1 (poor) to 4 (excellent); a score of 0 was assigned to deaths. We used linear regression to examine changes in self-rated health from 1 year pre-event (baseline). Relative effects of index event type over time were estimated by repeated-measures ANOVA.

Results:
Self-rated health was similar between groups at baseline (
Figure
). Participants with MI had sharper declines from baseline at 1 year post-event than those with diabetic foot disease (-0.93 vs -0.50 points, P<0.01), largely due to higher mortality (29.4% after MI vs 15.9% after diabetic foot disease). Self-rated health stabilized in the outpatient diabetic foot group after 2 years post-event, whereas it continued to decline over 10 years following both MI and inpatient diabetic foot disease (
Figure
).

Conclusions:
Our findings suggest outpatient diabetic foot disease is primarily associated with a short-term drop in self-rated health, but inpatient diabetic foot disease is associated with long-term declines in self-rated health similar to those experienced after MI. These results reinforce the importance of early diagnosis and treatment of foot disease and of including patient-reported outcomes to measure sequelae of diabetes complications.
Abstract MP55: The Cardioprotective Feature of High-Density Lipoprotein Function Diminishes as Women Transition Through Menopause: The Swan HDL Study
Authors: El Khoudary Samar R , Matuk James , Billheimer Jeffrey , Brooks Maria M , Orchard Trevor , Janssen Imke , McConnell Dan , Crawford Sybil , Matthews Karen A , Rader Dan
Published: May 2024

Objective:
HDL cholesterol efflux capacity (CEC) is a key metric of the cardioprotective HDL functionality. CEC generally rises as women traverse the menopause but it is unclear whether this rise reduces future CVD risk. We tested whether the association between CEC and subclinical CVD burden, measured using a composite subclinical CVD score based on carotid-intima media thickness (c-IMT), carotid-femoral pulse wave velocity (cf-PWV) and presence of coronary artery calcium (CAC score ≥10), varies by time relative to the final menstrual period (FMP).

Design:
We included 279 women (at baseline: age 51±2.8 years; 68.5% White; 31.5% Black; 60.6% Pre-/perimenopausal) who had HDL metrics and subclinical CVD outcome measures measured once (N=115 [41.2%]) or twice (N=164 [58.8%]). The composite subclinical CVD score was computed using a factor analysis for mixed data approach (FactoMineR R package), which combines principal component analysis for continuous (c-IMT, cf-PWV) and multiple correspondence analysis for categorical data (CAC≥10). A linear mixed effects model was used to model the composite score of subclinical CVD and estimates were back transformed to the individual observed components. We tested the interaction between CEC and time relative to FMP in this model.

Results:
Higher CEC was associated with a lower composite subclinical CVD score at FMP in unadjusted analyses (Illustration). This association was negligible after adjustment for confounders. In all models, association of CEC varied by time relative to FMP such that the pre-FMP protective association of CEC diminishes after the FMP. This pattern was consistent across all components of the composite score (Illustration).

Conclusions:
In women, higher CEC is associated with a lower risk of subclinical CVD burden before but not after menopause. High CEC is not a consistent indicator of CVD protection in women traversing menopause.
Abstract MP62: Adherence to Guideline-Recommended Physical Activity Nullifies Mortality Risks of Extended Sitting in Adults With Diabetes
Authors: Dai Wen , Albrecht Sandra S
Published: May 2024

Introduction:
Sedentary lifestyles have been associated with increased mortality for people with diabetes. While most governments and health organizations advocate for adults with diabetes to engage in at least 150 min/week of moderate-to-vigorous physical activity (MVPA), it is unclear whether meeting these guidelines can mitigate the heightened mortality risks associated with prolonged sedentary time in this population.

Hypothesis:
We hypothesized that adhering to the guideline-recommended 150 min/week of MVPA could mitigate the mortality risk from prolonged sedentary time in U.S. adults with diabetes.

Methods:
This study included 3,533 nonpregnant adults aged 20 years diagnosed with diabetes from the U.S. National Health and Nutrition Examination Survey (2007-2018). Sitting time and MVPA were assessed using the Global Physical Activity Questionnaire. We analyzed sitting time as both a continuous variable (h/d) and as a categorical variable (<4, 4-<6, 6-8, >8 h/d). The mortality status of the participants were ascertained via linkage to the National Death Index by December 31, 2019. Hazard ratios (HRs) and 95% CIs for associations between sitting time and mortality were estimated using Cox models, adjusted for sociodemographic characteristics, lifestyle factors, and Carlson comorbidity index, stratified by MVPA (inactive [<10 min/week], insufficiently active [10-<150 min/week], active [150 min/week]). The presence of multiplicative effect measure modification was evaluated by contrasting the model incorporating continuous sitting time, categorical MVPA, and their interaction term, and the model excluding the interaction. We accounted for the NHANES complex survey design (sampling weights, clustering, and stratification) in all analyses.

Results:
Among 3,533 adults diagnosed with diabetes (mean [SE] age: 60.3 [0.3] years; 48.7% females; 60.6% non-Hispanic White), 695 deaths were documented over a median (interquartile range) follow-up of 5.6 (3.1-8.7) years. In the fully adjusted models, sitting time was positively associated with mortality risk among adults with diabetes who were physically inactive or insufficiently active but not among active adults (
P
for interaction=0.04). Specifically, the HRs (95% CIs) of mortality for 1h/d increment in sitting time across MVPA levels were 1.08 (1.04, 1.12) in inactive adults, 1.09 (1.01, 1.18) in insufficiently active adults, and 1.01 (0.96, 1.06) in active adults. Results remained unaltered when comparing the most sedentary (>8 h/d) to the least sedentary (<4 h/d) categories: across MVPA levels (from low to high), the HRs (95% CIs) of mortality were 1.83 (1.23, 2.72), 1.84 (0.81, 4.17), and 1.11 (0.73, 1.69), respectively.

Conclusions:
Our findings show that achieving 150 min/week of MVPA can substantially mitigate the elevated mortality risks associated with extended sitting time among U.S. adults with diabetes.
Abstract MP66: Accelerometer Measured Diurnal Movement Patterns Associated With Frailty in Older Adults: UK Biobank
Authors: Kong Lingsong , Lee Chi Hyun , Sturgeon Susan R , Spracklen Cassandra N , Paluch Amanda E
Published: May 2024

Introduction:
Frailty is a significant health challenge for the aging population. Older adults with cardiovascular diseases (CVD) tend to be physically inactive and have a high risk of frailty. Little is known about the relationship between diurnal movement patterns and frailty and whether this association differs in older adults with and without CVD.

Hypothesis:
Less morning, afternoon, and evening movements but more night movements are associated with frailty, especially among those with CVD.

Methods:
This cross-sectional study included 10,082 participants ≥ 65 years (66.8±1.5 years; 49% female) from UK Biobank. CVD status was identified using ICD-9&10 diagnosis and self-reported CVD. Participants wore Axivity AX3 on the dominant wrist for 7 days, 24 hours/day. Mean accelerations during night (12-6 am), morning (6 am-12 pm), afternoon (12-6 pm) and evening (6 pm-12 am) were calculated. Frailty was determined using Modified Fried Frailty Phenotype. Multivariate logistic regression models were used to examine associations between total movement and diurnal movement patterns with frailty, stratified by CVD status.

Results:
The diurnal movement patterns showed lower movements during night, increasing during morning, peaking at noon, and decreasing in afternoon and evening, with frail CVD adults having the lowest accelerations during all daytime hours (6 am-midnight). In both CVD and non-CVD older adults, each 5 mg higher overall mean acceleration was associated with 11-18% lower odds of frailty (
Table
). Each 5 mg higher mean acceleration during morning, afternoon and evening was associated with 5-10% lower odds of frailty (
Table
). Every 5 mg higher mean acceleration during night was associated with 14% higher odds of frailty only in non-CVD older adults (
Table
).

Conclusions:
More activity during any daytime period was associated with lower odds of frailty among older adults in both with and without CVD. Greater night activity was associated with higher odds of frailty, primarily observed in older adults without CVD.
Abstract P108: Stroke Incidence and High Sensitivity C-reactive Protein Among African Americans: The Jackson Heart Study
Authors: Hayes Cellas , Thorpe Roland J , Dhamoon Mandip S , Heitman Elizabeth , Norris Keith , Beech Bettina , Bruce Marino , Walker Benjamin , Reneker Jennifer C
Published: May 2024

In the United States, strokes are a leading cause of death and disabilities, especially for older adults; however, effective biological markers to predict stroke remain elusive. The objective of this study was to investigate the association between inflammation, as measured by high-sensitivity c-reactive protein (hs-CRP) and stroke incidence among African Americans (AA) enrolled in a community-based longitudinal observational study, the Jackson Heart Study.Baseline hs-CRP levels were categorized in quintiles: Quintile 1 (0.0084 mg/L); Quintile 2 (0.0085 - 0.0189 mg/L); Quintile 3 (0.0190 - 0.036 mg/L); Quintile 4 (0.037 - 0.0675 mg/L); Quintile 5 (≥ 0.0676 mg/L). Stroke risk factors/covariates were compared across hs-CRP tertiles. Continuous variables were compared using a one-way ANOVA, and a Chi-Square test was used for categorical variables. To determine whether baseline hs-CRP levels were associated with stroke incidence, Cox regression analyses were conducted to estimate hazard ratios (HRs) and 95% confidence intervals (CI).Results from the unadjusted model of the Cox regression indicates hs-CRP levels in quintile 2 (HR 1.48; 95% CI 0.96-2.29), quintile 3 (HR 1.44; 95% CI 0.93-2.24), and quintile 4 (HR 1.09; 95% CI 0.68-1.74) were not associated with stroke incidence when compared to quintile 1 (reference). Participants with the highest hs-CRP levels, quintile 5, were at an increased risk for stroke (HR 1.78; 95% CI 1.17-2.72) compared to the reference quintile. In a fully adjusted model including risk factors and mediators for stroke/hs-CRP (demographics, anthropometrics, health condition covariates, health behavioral risk factors, and cardiovascular disease history), the increased stroke risk incidence remained present for quintile 5 (HR 1.87; 95% CI 1.17-2.98) compared to reference quintile 1.Overall, these results corroborate previous studies’ findings in Black Americans that hs-CRP is associated with stroke incidence only at most severe levels. Although several studies have demonstrated higher hs-CRP in AAs, there have been a lesser association of hs-CRP and cardiovascular disease; hence, these findings provide new insights that hs-CRP l may not be a reliable predictor for stroke incidence among AAs.
Abstract P111: Pre-Diagnostic Free Testosterone and Estradiol Influence Heart Failure Risk in Both Women and Men: A Prospective Cohort Study in the UK Biobank
Authors: Lim Jungeun , Hashemian Maryam , Blechter Batel , Roger Veronique L , Wong Jason Y
Published: May 2024

Introduction:
Heart failure (HF) is a highly fatal manifestation of many cardiovascular diseases (CVDs). Free testosterone and 17β-estradiol have been linked to future risk of CVD. However, their roles in the pathogenesis of HF in both men and women are unclear.

Hypothesis:
We investigated the associations between free testosterone and 17β-estradiol (unbound to sex hormone binding globulin), and future risk of HF in the UK Biobank.

Methods:
Multivariable Cox regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) of incident HF (first hospitalization) in relation to quartiles (Q) of free testosterone and 17β-estradiol, and potential confounders, while stratifying by sex and in women by menopausal status. Non-linear relationships were tested using cubic splines.

Results:
There were 180,712 men (5585 cases with free testosterone and 571 cases with 17β-estradiol), and 177,324 women (2858 cases with free testosterone and 314 with 17β-estradiol). Increased free testosterone was associated with decreased HF risk in both men (HR
Q4 vs. Q1
=0.86, 95%CI: 0.79-0.94, p-trend
continuous
<0.0001) and post-menopausal women (HR
Q4 vs. Q1
=0.83, 95%CI: 0.73-0.95), with non-linear relationships. Additionally, 17β-estradiol was significantly associated with decreased HF risk among men (HR
Q4 vs. Q1
=0.76, 95%CI: 0.59-0.98), but positively associated among pre-menopausal women (HR
Q4 vs. Q1
=2.16, 95%CI: 1.11-4.18).

Conclusions:
In this large cohort free of CVD at baseline, we detected a significant protective association between free testosterone and new HF diagnosis among men. In women however, the association differed by menopausal status as increased free testosterone was associated with elevated risk of HF before menopause but not after menopause. Further, 17β-estradiol was associated to elevated HF risk among pre-menopausal women but not post-menopausal women and men. Our findings suggest that sex hormones influence the pathogenesis HF and may offer potential pathways for interventions.
Abstract P116: Exploring The Cardioprotective Potential Of Roflumilast (pde-4 Inhibitor) Against Experimental Epirubicin-induced Cardiotoxicity.
Authors: Singh Akashdeep , Singh Gurfateh , Sharma Ramica
Published: May 2024

Introduction:
Cardiotoxicity is an important side effect of the treatment of a malignant tumour with Anthracyclines. The anthracycline family drug epirubicin (EPI) is one of the most potent chemotherapeutic agents for treating a range of solid and hematologic malignant tumours. However, its anti-tumor efficacy is dose-dependent, and the development of cardiac-toxicities limits its clinical use. In various Pharmacological Studies Roflumilast (ROF), a PDE-4 Inhibitor has been shown a Neuroprotective and Cardioprotective response but its role in EPI-induced cardiotoxicity and the underlying mechanisms has never been Evaluated.

Hypothesis:
The Study hypothesized that Roflumilast exerts cardioprotection against EPI-induced cardiotoxicity through attenuating cardiac mitochondrial dysfunction and inflammatory markers.

Methods:
Wistar rats of either sex were employed into 4 groups 3 groups comprised 7 animals while the control group had 5 animals, EPI-treated rats were intraperitoneally injected with 10 mg/kg for 1 day, while control rats were on normal diet. EPI+ROF (Low Dose) treated rats were intraperitoneally injected with 10 mg/kg of EPI for 1 day and 1mg/kg of ROF via oral gavage for 7 days. While in the higher dose of EPI+ROF treated rats were intraperitoneally injected with 10 mg/kg of EPI for 1 day and 2mg/kg of ROF via oral gavage for 7 days. The rat hearts were rapidly removed to determine cardiac mitochondrial functions and various cardiac biomarkers.

Results:
EPI induced significantly excessive mitochondrial Oxidative Stress, increased tissue TBARS and decreased levels of SOD and GSH. Conversely, a 7-day treatment with ROF (1mg/kg/day
, p.o
.) and ROF (2mg/kg/day,
p.o
.) significantly reduced TBARS levels while increasing SOD and GSH concentrations. The levels of TNF-α, CK-MB AST, ALT, and LDH were noted to be markedly increased in EPI-induced rats. While treatment with ROF (1mg/kg/day,
p.o.,
7 days
)
and ROF (2mg/kg/day,
p.o.,
7 days) showed significantly decreased levels of TNF-α, CK-MB AST, ALT, LDH.

Conclusion:
In the current investigation, it can be concluded that administration of EPI leads to Oxidative Stress, Inflammation and Cardiotoxicity. Treatment with the ROF 2mg/kg showed cardioprotective potential by significantly decreasing inflammatory markers, oxidative stress parameters and cardiotoxic parameters. Our findings suggest that ROF protects the heart from EPI-induced cardiotoxicity, and it may serve as a guide for future cardioprotective research strategies.
Abstract P122: A Semi-Automated Tool Can Increase Stroke Clinical Trial Recruitment
Authors: Sari Murat ,   UPMC Enterprise Productivity and Collaboration Services, Rocha Marcelo
Published: May 2024

Introduction:
Stroke is a major public health problem, and stroke-related research is crucial. However, enrollment in randomized controlled stroke trials of acute therapies is challenging, leading to missed patients during the screening phase. The current screening process is person-dependent and can be highly variable across stroke team members, time of the day, and hospitals. High-volume stroke centers participate in more than 15 simultaneous NIH and industry-sponsored stroke trials. We hypothesize that a HIPAA-compliant screening tool can optimize screening and increase trial enrollment.

Methods:
This tool is a HIPAA-compliant application, developed by the Power Team at the University of Pittsburgh Medical Center, using Microsoft Power Apps. It has three purposes: screening, maintaining the database, and reporting. The screening process begins with patient demographics, and basic stroke-related data, followed by acute ischemic, subacute ischemic, and hemorrhagic stroke trial groups. Users can select their preferred subgroup of studies and continue filling in the rest of the form by answering pertinent questions. Upon form submission, the tool calculates the patient’s eligibility status for each trial in that group. The database is immediately available on the opening page or on the cloud. After submission, this can be edited, e.g., refusal for enrollment, or change in the patient’s condition. Reporting can be automated by using Power tools or it can be done manually. For manual reporting, the database gives filtering options based on time frames, patients, trials, and more.

Results:
The tool is in the testing phase, and we expect to have enrollment data by the time of the meeting.

Conclusions:
This tool has several advantages over manual screening. First, it reduces the orientation time for new research team members. Second, it mitigates the risk of overlooking potentially eligible patients in time-sensitive scenarios. Third, it is highly customizable by editing the codebook and can be adjusted per research site. This can be particularly helpful for smaller hospitals surrounded by underserved areas and can decrease health disparities by extending the chance of clinical trial participation. Fourth, it automatically maintains an up-to-date data log, which can be extracted at various intervals, such as monthly or per study. This not only streamlines the data recording but also simplifies reporting to study sponsors. Lastly, it expedites trial completion by accelerating the enrollment process. In conclusion, this tool can have significant benefits for research teams and for the broader public.