bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract MP23: Cardiovascular Diseases and Risk of Dementia in the General Population: Observational and Genetic Studies
Authors: Luo Jiao , Juul Rasmussen Ida , Nordestgaard Borge G , Tybjaerg-Hansen Anne , Qvist Thomassen Jesper , Frikke-Schmidt Ruth
Published: May 2024

Importance:
Cardiovascular diseases are associated with increased risk of subtypes of dementia. The causal nature is however unclear.

Objective:
To assess observational and genetic associations between a range of cardiovascular disease and risk of all-cause dementia and its major subtypes.

Design, Settings, and Participants:
We performed time-dependent Cox regression analyses in three prospective cohorts, the Copenhagen City Heart Study (N=10,373), the Copenhagen General Population Study (N=101,582), and the UK Biobank (N=377,706); median follow-up times were 15, 9, and 13 years, respectively. Estimates from each cohort were pooled in meta-analyses using fixed-effects models. Subsequently, we investigated genetic susceptibility for cardiovascular diseases and risk of all-cause dementia, Alzheimer’s disease, and vascular dementia, using individual-level data from the UK Biobank and summary statistics from the FinnGen study.

Exposures:
Ischemic heart disease, myocardial infarction, peripheral arterial disease, hypertensive heart disease, stroke, ischemic stroke, atrial fibrillation, heart failure, and the combination of all.

Main Outcomes and Measures:
Outcomes include all-cause dementia, Alzheimer’s disease, and vascular dementia. Measures are hazard ratios (HRs) and 95% confidence intervals (CIs) in observational studies and odds ratios (ORs) and 95% CIs in genetic studies.

Results:
Observationally, cardiovascular diseases were associated with high future risk of incident all-cause dementia, Alzheimer’s disease, and vascular dementia in meta-analyses, with HRs up to 7.49 (95% CI: 6.63, 8.46). Genetically, using individual level data from the UK Biobank, predisposition to ischemic stroke was associated with high risk of all-cause dementia, Alzheimer’s disease, and vascular dementia, with ORs of 1.64 (1.35, 1.98), 1.44 (1.10, 1.89), and 2.06 (1.41, 3.01), respectively, with similar estimates for ischemic stroke; genetic predisposition to ischemic heart disease was associated with high risk of vascular dementia, with an OR of 1.24 (1.03, 1.50). Genetic summary-level data from the FinnGen study confirmed the estimates for stroke and ischemic stroke.

Conclusion and Relevance:
Our study provides novel evidence that the association between stroke and all-cause dementia and its major subtypes may be of a causal nature. Further, we observe that genetic susceptibility for ischemic heart disease is associated with incident vascular dementia. These findings underscore the importance of integrating cardiovascular disease prevention into interventions to reduce dementia risk.
Abstract MP27: Use of Multivitamin Supplements and Risks of Total and Cause-Specific Mortality Among U.S. Adults
Authors: Ding Ming , Chiu Yu-Han , Markon André O , Wang Siwen , Manson JoAnn E , Hu Frank B , Willett Walter C , Giovannucci Edward L , Wolpert Beverly J , Chavarro Jorge E
Published: May 2024

As the most commonly consumed dietary supplement, how multivitamin use associates with risk of mortality remains inconclusive.

Methods:
We used data from three cohort studies to examine the association of time-varying multivitamin use with risk of mortality. We also emulated a target trial to estimate the association by applying the parametric g-formula.

Results:
Of 241,068 eligible participants (mean age at baseline: 50 for NHS, 37 for NHSII, and 53 for HPFS), there were 44,415 deaths over 30-years of follow up. Compared to non-users, the pooled age-adjusted harzard ratio (HR) of mortality was 0.92 (95% CI: 0.89, 0.94) and 0.89 (95% CI: 0.88, 0.91) for users who used <1 and ≥1 pill/day, respectively. These results were attenuated after multivariable adjustment (0.97 [0.95, 1.00] and 0.98 [0.96, 0.99], respectively), and the inverse association was primarily due to lower risk of CVD mortality (
table 1
). In the emulated target trial, the estimated 30-y all-cause mortality under a multivitamin intervention was slightly lower than no intervention (
table 2
).

Conclusions:
Multivitamin use may relate to a small reduction in mortality among middle-aged adults.
Abstract MP31: Incident Type 2 Diabetes Onset Age and Duration, Mortality Risk, and Loss in Life Expectancy
Authors: Zhang Yin , Song Mingyang , Wang Molin , Hertzmark Ellen , Wu Kana , Eliassen A. Heather , Mucci Lorelei , Sun Qi , Stampfer Meir , Willett Walter , Hu Frank , Giovannucci Edward
Published: May 2024

Introduction:
Evidence on the relationship between type 2 diabetes onset age, duration, and mortality risk has been influenced by limited follow-up, inadequate control for confounding, and inability to cover the full range of onset age, duration, and the full spectrum of major causes of death. Moreover, there are scarce data dissecting how type 2 diabetes onset age and duration shape life expectancy.

Hypothesis
We assessed the hypothesis that early onset of type 2 diabetes and longer disease duration may be associated with higher risk of all-cause and cause-specific mortality and greater loss in life expectancy.

Methods:
We prospectively followed 270,075 eligible participants in the Nurses’ Health Study, Nurses’ Health Study II, and Health Professionals Follow-up Study longitudinal cohorts for up to 40 years. The exposures include type 2 diabetes onset age (<40, ≥40 to <50, ≥50 to <60, ≥60 to <70, ≥70 to <80, and ≥80 years) and duration (<10, ≥10 to <20, ≥20 to <30, and ≥30 years). Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for age and a wide spectrum of potential confounders.

Results:
We documented 73,076 deaths during 8,166,216 person-years of follow-up. In fully-adjusted analyses, incident early-onset type 2 diabetes (diagnosed <40 years of age) was associated with significantly higher mortality from all-causes (HR, 95% CI was 3.16, 2.64-3.79; vs. individuals without type 2 diabetes), cardiovascular disease (6.56, 4.27-10.1), respiratory disease (3.43, 1.38-8.51), neurodegenerative disease (5.13, 2.09-12.6), kidney disease (8.55, 1.98-36.9), and suggestively increased mortality from diabetes-related cancer (1.63, 0.94-2.83) and obesity-related cancer (1.63, 0.92-2.88). The relative risk elevations declined dramatically with each higher decade of age at type 2 diabetes diagnosis for deaths from most of these causes, though the absolute risk difference increased continuously. A substantially higher cumulative incidence of mortality and a greater loss in life expectancy were associated with younger age at type 2 diabetes diagnosis. Comparing individuals with early-onset type 2 diabetes to those without type 2 diabetes, their estimated multivariable-adjusted cumulative incidence of all-cause mortality at age 80 was 0.43 vs. 0.20, and the estimated life expectancy loss at age 40 was 2.5 years. Longer disease duration was associated with generally higher relative and absolute risk of mortality.

Conclusions:
Early onset of type 2 diabetes and longer disease duration are associated with substantially increased risk of all-cause and cause-specific mortality and greater loss in life expectancy. The effect of early-onset type 2 diabetes on mortality risk is stronger than that of later-onset type 2 diabetes.
Abstract MP57: Universal and Targeted Lipid Screening in Youth Living With Overweight or Obesity
Authors: Koebnick Corinna , Li Xia , Sidell Margo A , Kunani Poornima S
Published: May 2024

Background:
Current NHLBI Expert Panel guidelines recommend universal screening once between 9-11 years and, again, between 17-21 years. Targeted screening is recommended for 2 years and older with a) obesity, or b) overweight AND personal or family history of obesity-related co-morbidities. The present study compares compliance with current lipid screening guidelines by race/ethnicity and socioeconomic status (SES).

Methods:
Using electronic health record data for n=300,776 youth between 2 and 17 years of age from Kaiser Permanente Southern California and a BMI-for-age >=85
th
percentile, HR for the ordering of a lipid screening according to the current guidelines were calculated for both, universal screening and targeted screening at any age for children living with obesity with and without comorbid conditions such as diabetes, hypertension, and non-alcoholic fatty liver disease (NAFLD) and adjusted for age, sex, BMI-for-age class (overweight, moderate obesity between 95
th
and 1.2 x 95
th
percentile, obesity >= 1.2 x 95
th
percentile of BMI-for-age), and comorbid conditions (diabetes, hypertension, and NAFLD).

Results:
The average age of the cohort was 8.6 (SD 5.7) years with 49.4% Hispanic, 25.0% White, 7.3% Black, and 9.3% Asian/Pacific Islander youth, 19.8% with state-subsidized insurance. Of these, 13.2 of youth lived with obesity between 95
th
and 1.2 x 95
th
percentile, and 5.2% >= 1.2 x 95
th
percentile of BMI-for-age. For 43.1% of youth, a universal lipid screening was ordered as recommended. The aHR for universal screening was 1.23 (1.21-1.26) for Hispanic, 1.15 (1.11-1.19) for Black, 1.27 (1.23, 1.31) for Asian/PI youth compared to white youth, 1.05 (1.03-1.07) for youth with state-subsidized insurance compared to those without. Among youth living with obesity, targeted screening was ordered as recommended for 38.1% of youth with 23.8%, 68.1%, and 61.6% for 2-8, 9-17, and 15-17 year olds respectively. The aHR for targeted screening was 1.58 (1.58-1.61) for youth living with obesity >= 1.2 x 95
th
percentile of BMI-for-age compared to those between 95
th
and 1.2 x 95
th
percentile, 1.08 (1.06-1.10) for youth with state-subsidized insurance compared to those without, 1.57 (1.49-1.65) for youth with diabetes, and 1.11 (1.04-1.20) for youth with NAFLD compared to those without. The aHR for targeted screening did not vary by race/ethnicity.

Conclusions:
In this integrated health care system, universal and targeted screening missed about 50% of youth living with overweight or obesity. While universal screening rates were higher for minority youth and lower SES, targeted screening rates were driven by obesity severity and comorbid conditions than race or SES.
Abstract P101: The Association Between Residing in a Food Desert and Hypertension in Victims of Sudden Death
Authors: Wiggs Alleigh , Cesmat Andrew , Davy-Mendez Thibaut , Simpson Ross J
Published: May 2024

Introduction:
Sudden deaths, defined as unexpected deaths not attributable to suicide, trauma or cancer account for over 10% of deaths in adults aged 18-64 years. More evidence is needed to understand how socioeconomic factors interplay with physiological processes such as hypertension to contribute to sudden death. We hypothesized that residing in a food desert would be associated with hypertension and poor blood pressure (BP) control in people who died of sudden death.

Methods:
We screened Emergency Medical Services (EMS) records from 2013 to 2015 in Wake County, NC, which includes the capital city of Raleigh and >1 million residents, and adjudicated 399 sudden death victims using a standardized protocol. We collected medical history and BP measures from health records and linked geocoded patient addresses to census-tract data from the USDA’s Food Access Research Atlas. Of these, 350 victims had address data available, and of these 196 had blood pressures available. Residing in a food desert was defined as living in a low income and low access area, which is defined as no access to grocery stores within 1 mile in urban areas and 10 miles in rural areas. The ten most recent systolic BP measures prior to death were used to calculate average BP. We calculated unadjusted differences in mean BP by residence in a food desert. We also calculated unadjusted odds ratios (ORs) comparing the probability of having a hypertension diagnosis and of having controlled BP (systolic BP <130 mmHg) by residence in a food desert.

Results:
We examined 350 sudden decedents who were 33% Black (116 of 350), 64% White (224 of 350), 31% women (109 of 350), and a median age of 55. Of these, seventy-nine (23%) resided in a food desert, and these were more likely to have diabetes mellitus (38.0% vs. 26.6%), (30 of 79 and 72 of 271 respectively). Sudden decedents who resided in a food desert had higher systolic BP with a mean of 140 mmHg compared with 134 mmHg for those who did not reside in a food desert (mean difference 6.15, CI 6.012-6.298). Of those residing in a food desert, 60.8% (48 of 79) had a medical diagnosis of hypertension, and 33.3% (14 of 48) had controlled BP. There was no association between residing in a food desert and a diagnosis of hypertension (OR 1.04, 95% CI 0.62-1.74) or controlled BP (OR 1.73, 95% CI 0.85-3.54).

Conclusion:
Almost a quarter of sudden decedents resided in a food desert at the time of death. In this case group, residing in a food desert was associated with a small BP increase but not with diagnosed hypertension or controlled BP. Large population studies are necessary to investigate the risk of sudden death and poor blood pressure control associated with residing in a food desert.
Abstract P132: Paso a Paso, Designing a Culturally Relevant Diabetes Prevention Intervention for Hispanic/Latino (H/L) People That Adheres to Evidence Based, Diabetes Prevention Program (DPP) Intervention Principles in the Hispanic/Latino (H/L) Community of Salt Lake County
Authors: Cedillo Maribel , Miller Megan N , Conroy Molly B , Estabrooks Paul , Molina Isabel T , Portugal-Bouza Gabriela , Cortes Patricia
Published: May 2024

One of five Salt Lake County residents identify as Hispanic/Latino(H/L) and are at higher risk for type 2 diabetes(T2D) compared to non-Hispanic whites. Evidence-based interventions to reduce T2D have not been as effective for H/Ls as for non-H/L whites. This study uses a shared-leadership, community-engaged approach to develop a model for H/L T2D prevention based on DPP with members of the H/L community, community-based organization partners (Utah Mexican Consulate; University Neighborhood Partners), and an interdisciplinary University of Utah team. Two groups of 10-15 people each (one for community members (CM) eligible to participate in a diabetes prevention program; one for community organization members(CBO) potential DPP-like program implementers). As part of a comprehensive participatory planning and evaluation(CPPE) process, each group met to (1)review existing Spanish DPP program components, learning objectives, and materials, (2)identify barriers to successful T2D prevention, and (3)suggest facilitators and areas for adaptation specific to H/L audiences. Participants in each group rated the DPP program structure and content related to healthy eating, increasing physical activity (PA), self-monitoring and meal planning using validated measures of acceptability, appropriateness, and feasibility. In addition, qualitative data was gathered and reduced to provide directions for potential adaptations. Quantitative data (Figure 1) indicates CM and CBO agree on importance of DPP program structure and content, however CBO members rated the acceptability, appropriateness, and feasibility more neutrally than CM participants. Qualitative data indicated a stronger focus on collective support, culturally aligned healthful eating options, and PA promotion that addressed safe activities for laborers. Conclusions CM and CBO participants found DPP to be an important resource for the H/L community, but also identified adaptations that could improve program reach, retention, and effectiveness.
Abstract P134: Bidirectional Association of Diabetes and Heart Failure
Authors: Echouffo Justin B , Zhang Sui , Matsushita Kuni , NAMBI VIJAY , Ballantyne Christie M , Shah Amil M , Coresh Joe , Selvin Elizabeth , Ndumele Chiadi E
Published: May 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.
Abstract P160: Prevalence of Genetic Dilated Cardiomyopathy: A Systematic Literature Review
Authors: Fazeli Mir Sohail , Myers Michael , Zhong Yue , Maruyama Sonomi , Bueno Cindy , Bastien Arnaud , Breznen Boris , Golchin Negar
Published: May 2024

Background:
Dilated cardiomyopathy (DCM) is a leading cause of heart failure and cardiac transplantation worldwide. Many cases of DCM are due to genetic or idiopathic etiology. Two prominent contributors to genetic DCM (gDCM) are the
TTN
and
MYH7
genes, which encode proteins associated with DCM etiology.

Purpose:
This study aimed to synthesize the published literature on the global prevalence of adult and pediatric gDCM within the clinical DCM population and the general population.

Methods:
A systematic review was conducted by searching MEDLINE® and Embase from database inception to 09/19/2022. We included observational studies reporting the prevalence of gDCM within any population; prevalence of
TTN
and
MYH7
mutations were also extracted. Excluded were studies using family history as a proxy for gDCM. Median with interquartile range (IQR) or mean with standard deviation (SD) weighted by sample size (in cases of calculations with <10 studies) were used to summarize the data.

Results:
Of 2,720 identified abstracts, 57 studies were included in the review. Among the adult or mixed (adults and children) DCM population in any country, median prevalence was 21.0% for overall DCM-related genetic mutations, 11.4% for
TTN
mutations, and 3.2% for
MYH7
mutations (
Table
). The prevalence of pediatric gDCM within the DCM population was similar (weighted mean: 21.3%). Data on prevalence of gDCM within the general population were scarce.

Conclusion:
This study highlights the variable prevalence of gDCM reported across different populations and settings. The current evidence may underestimate the genetic causes due to technical limitations in genetic testing and limited screening. Accurately determining the prevalence of gDCM is critical for identifying high-risk populations, developing targeted prevention strategies for disease complications, and improving outcomes; epidemiological studies using long-read sequencing techniques and large cohort datasets with genotype-phenotype correlation analyses are needed.
Abstract P167: Association Between Obesity and New-Onset Heart Failure Among People With Hypertension in Thailand
Authors: Sakboonyarat Boonsub , Poovieng Jaturon , Rangsin Ram
Published: May 2024

Obesity establishes cardiovascular risk factors, including high blood pressure, hyperlipidemia, and high blood glucose, and also results in cardiovascular events. In Thailand, the epidemiological data on the relationship between obesity and heart failure (HF) among high-risk populations was limited. We assessed the hypothesis that increased body mass index (BMI) was associated with the new-onset HF among people with hypertension (HTN); we also assessed the effect modifier of uncontrolled HTN on this association. We conducted a retrospective cohort study in 2018. Thai people with HTN aged 20 years and older receiving continuous care at out patient clinic in the hospitals nationwide were included. While those with a history of HF before 12 months from the data collection date were excluded. The new-onset HF was defined regarding the ICD-10 as I50 in the medical records within 12 months. The information on the characteristics and BMI of participants was extracted from the medical records by well-trained registered nurses. Obesity was defined as BMI ≥25 kg/m
2
. We performed multivariable log-binomial regression analysis to determine the association between BMI and new-onset HF and presented as the adjusted risk ratio (aRR) and 95%CI. A total of 35,756 participants were included in the analysis. The mean age of participants was 64.5±0.1 years. In all, 61.4% were women, and 50.0% had controlled HTN (SBP<140 mmHg and DBP <90 mmHg) two visits consecutively. The mean BMI was 25.1±0.02 kg/m
2
. New-onset HF occurred in 75 participants (0.21%). Adjusting for age, sex, health schemes, geographic regions, hospital types, type 2 diabetes, dyslipidemia, renal insufficiency, history of ischemic heart disease, smoking status, alcohol use, uncontrolled HTN, and ACEI/ARB use, increased BMI per 1 kg/m
2
was significantly associated with new-onset HF (aRR 1.09 [95%CI: 1.05-1.14]). In comparison with participants with BMI of 18.5-22.9 kg/m
2
, the aRR for new-onset HF was 1.57 (95% CI:0.80-3.08), 3.69 (95%CI: 1.73-7.87), and 5.18 (95% CI: 1.81-14.81) in those with BMI 25.0-29.9, 30.0-34.9, and ≥35.0 kg/m
2
, respectively. For participants with obesity, aRR for new-onset HF was 2.05 (95% CI: 1.24-3.39) compared to non-obese participants. The effect modification of uncontrolled HTN on the association between obesity and new-onset HF was not observed (
p
-value = 0.641). In conclusion, an increased BMI had a higher risk for new-onset HF among Thai people with HTN. Obesity was independently associated with new-onset HF among people with HT, regardless of uncontrolled HTN.
Abstract P221: Association of Posttraumatic Stress Disorder With Physical Activity Among Vietnam-Era Male Twin Veterans
Authors: Suvada Kara , Vaccarino Viola , Johnson Dayna A , Ko Yi-An , Smith Nicholas , Bremner James Douglas , Huang Minxuan , Haddad George , Ahmed Hashir , Shah Amit J
Published: May 2024

Introduction:
Post-traumatic stress disorder (PTSD) can develop after a traumatic event and is associated with cardiovascular diseases (CVDs), but the mechanisms are not clear. Behavioral factors like physical activity (PA) may play a role if associated with PTSD, but few studies have examined whether PTSD may be associated with lower PA. By studying twins, we can examine this relationship and adjust for demographic and shared familial characteristics.

Methods:
We studied the relationship between current PTSD diagnosis and PA in 146 male twins (73 pairs) from the Emory Twin Study within the Vietnam Twin Registry. Twin pairs were discordant for PTSD symptoms. PA was continuously measured over 7 days using wrist actigraphy and used validated algorithms to calculate daily hours of sedentary time and moderate-to-vigorous PA (MVPA). We also examined self-reported leisure PA score with the Baecke questionnaire. We controlled for familial effect using generalized linear regression within PTSD discordant twin pairs. We dichotomized MVPA based on established cutpoints for normal values and estimated the prevalence ratio (PR) of the likelihood of achieving the minimum recommended average daily MVPA using Poisson regression. Multiple imputation was used to reduce the impact of missing data.

Results:
Veterans (mean (SD) age: 68.2 (2.1); 97% (142/146) White) had a low prevalence of achieving daily MVPA goals —35% among those with PTSD and 25% among those without and spent over 9 average sedentary hours per day. We did not find any significant relationship between current PTSD diagnosis and any of the PA outcomes in fully adjusted models.

Discussion:
Our findings reveal low PA and high levels of sedentary behavior among Veterans, with PTSD showing no significant impact on average PA. This suggests that PA is unlikely to explain excess CVD risks that have otherwise been observed in PTSD. Nonetheless, in this cohort of Vietnam era veterans, interventions to increase PA are warranted regardless of PTSD status.
Abstract P227: Association Between Depressive Symptoms and Insulin Resistance in Midlife Women: The Study of Women’s Health Across the Nation (SWAN)
Authors: Chen Yuqing , Colvin Alicia B , Brooks Maria M , El Khoudary Samar R , Thurston Rebecca C
Published: May 2024

Introduction:
Recent meta-analyses and cross-sectional studies propose that insulin resistance (IR) is a transient and not a lasting feature of depression. However, longitudinal evidence is lacking, particularly in midlife women across the menopause and ethnically diverse cohorts. The goals of this study were to 1) assess the longitudinal association between IR and concurrent and prior depressive symptoms among midlife women and 2) determine if these associations vary by menopausal status and ethnicity.

Methods:
We included 2694 women (48.4% White, 27.3% Black, 6.5% Hispanic, 8.1% Chinese, and 9.7% Japanese) from The Study of Women’s Health Across the Nation (SWAN) followed for approximately 20 years. The Center for Epidemiologic Studies Depression Scale (CES-D) score was used to assess depressive symptoms (CES-D ≥16 indicating high depressive symptoms) and IR was obtained from the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) and log-transformed for analysis. Multivariable linear mixed regression was used to estimate IR as a function of concurrent and prior depressive symptoms adjusting for baseline and time-varying covariates. We tested interactions between depressive symptoms and 1) time-varying menopausal status and 2) race/ethnicity in relation to IR.

Results:
At baseline women (mean age 45.86 ± 2.70 years, 48.4% white) were premenopausal (54.7%) or early perimenopausal (45.3%). In separate adjusted models, neither concurrent high depressive symptoms nor high depressive symptoms from the prior visit were statistically associated with log-HOMA-IR. When both concurrent and prior visit depressive symptoms were included in the model, the estimated effect of concurrent high depressive symptoms was comparable and statistically significant. High depressive symptoms were associated with a 0.03 increase in log-HOMA-IR (95% CI: 0.01, 0.06), equivalent to a 3% change in HOMA-IR compared to women with low depressive symptoms. Interaction effects were detected between high depressive symptoms and race/ethnicity (P=0.005) but not with menopausal status in relation to HOMA. The relationship between concurrent high depressive symptoms and IR was driven by the association observed among Hispanic women [β=0.18, 95% CI: 0.18 (0.08, 0.27), a 20% change in HOMA-IR].

Conclusion:
Current reporting of high depressive symptoms, but not prior reporting, was associated with elevated future IR over time among midlife women. This study provides longitudinal evidence in support of IR as a transient and not a lasting feature of depression. Moreover, the results suggest that Hispanic women with high depressive symptoms may be particularly susceptible to IR.

Supported by NIH/DHHS {Grants U01NR004061; U01AG012505, U01AG012535, U01AG012531, U01AG012539, U01AG012546, U01AG012553, U01AG012554, U01AG012495, and U19AG063720}
Abstract P230: Association Between Gratitude and Lifestyle Related Diseases: The JAGES Cross-Sectional Study
Authors: Eguchi Eri , Shirai Kokoro , Hayazhi Fumikazu , Hamaguchi Yuhi , Kondo Katsunori , Ohira Tetsuya
Published: May 2024

Purpose:
Positive psychological factors have been reported to be effective in preventing lifestyle-related diseases. People with high frequency of gratitude are considered to have positive psychological factors and to be in a state of social participation. Serum levels of IL-6, an inflammatory marker, have also been reported to decrease in grateful individuals. However, the association between frequency of gratitude and lifestyle-related diseases has not been reported.

Methods:
Participants of the study was 25,036 (11,656 men and 13,346 women) who responded to the question about gratitude among those who answered the JAGES2019 questionnaire. To the question, "In your daily life, how often do you say "thank you" to those around you?", possible answers were "1. several times a day or more," "2. about once a day," "3. several times a week," "4. several times a month," or "5. almost never. Multivariate odds ratios and 95% confidence interval of hypertension, diabetes, hyperlipidemia, depression, stroke, heart disease, cancer, and dementia were calculated using logistic regression analysis for those who were less grateful compared to those who were grateful "several times a day or more" and the same analyses were conducted for men and women. Covariates were smoking habits, drinking habits, whether they lived alone, exercise time, and body mass index.

Results:
The prevalence of hypertension, diabetes, depression, and dementia was higher among those who were less frequently grateful compared to those who were more frequently grateful. Multivariate odds ratios (95% confidence interval) were 1.08 (1.00-1.16) for hypertension, 1.12 (1.02-1.24) for diabetes, 1.82 (1.25-2.64) for depression, and 1.81 (1.16-2.8) for dementia, respectively. In men, the association was more pronounced for dementia for 2.37 (1.16-4.87), and similar trends for hypertension, diabetes, and depression. For women, the association was more pronounced for depression for 1.86 (1.17-2.95) and similar trends for hypertension, diabetes, and depression. The prevalence of cancer was lower with lower frequency of gratitude.

Discussion:
The prevalence of hypertension, diabetes, depression, and dementia was higher among those who were less frequently grateful, and the associations were particularly pronounced for hypertension, diabetes, and depression, especially among women, and for dementia, especially among men. The frequency of gratitude was thought to be influenced by the frequency of social participation, and there is a possibility of a causal reversal in depression, dementia, and cancer. We will examine the association more in detail longitudinally.
Abstract P243: Association Between a Brain Care Score and Risk of Cerebrovascular Events in American Women
Authors: Gutierrez-Martinez Leidys , Rist Pamela M , Buring Julie E , Vandenburgh Martin , Kourkoulis Christina , Rosand Jonathan , Anderson Christopher , Yechoor Nirupama
Published: May 2024

Background:
The McCance Brain Care Score (MBCS) is a novel tool derived through a modified Delphi process to motivate lifestyle changes to reduce the risk of cerebrovascular events (CVE) based on prior studies and expert knowledge. However, few studies to date have determined the association between the MBCS and incident CVE. Studying this potential association is particularly important given the higher risk of stroke among women and the potential for unique risk profiles given physiologic and pharmacologic hormonal changes across the lifespan.

Methods:
The study population was participants in the Women’s Health study (WHS) who had available risk factor information needed to calculate the modified MBCS 5 years after enrollment and no prior history of CVE. The WHS-adaptation of the MBCS is illustrated in Figure 1; higher scores suggest better brain health. Participants were followed from MBCS assessment until first CVE (Stroke or Transient Ischemic Attack), end of study, loss to follow-up, or death, whichever occurred first. CVE were confirmed by medical record review. Cox proportional hazards models were used to examine the association between the MBCS, modeled as a continuous variable, and incident CVE adjusted for potential confounders.

Results:
In total, 22,965 women were eligible with a median age of 58.0 (Interquartile Range 54.0-63.9) and median MBCS of 15 (14-17). There were 1,364 (5.9%) incident CVE events during a median follow-up of 22.5 (16.8-23.6) years. A one-point higher baseline MBCS was associated with 11% decreased risk of incident CVE after adjusting for age, postmenopausal status, and use of hormonal replacement therapy (HR=0.89; 95%CI=0.87-0.91). This association remained significant after adjusting for comorbidities, race, educational attainment, and income (HR=0.90; 95%CI=0.88-0.93).

Conclusion:
Higher baseline MBCS was associated with a decreased risk of incident CVE among women. Future studies are needed to understand how longitudinal changes in the MBCS impact risk of CVE.
Abstract P270: Higher Long-Term Fasting Glucose Variability From Childhood is Associated With Poorer Cognitive Function in Midlife: The Bogalusa Heart Study
Authors: Kang Soo Jung , De Anda-Duran Ileana , Fernandez Alonso Camilo , JIN XUANYI , Carmichael Owen , Bazzano Lydia A
Published: May 2024

Background:
Elevated fasting blood glucose(FBG) levels have been associated with poorer cognitive function. High FBG variability has also been associated with accelerated cognitive decline in late life. However, the impact of long term FBG variability from childhood on midlife cognitive function (CF) remains understudied.

Hypothesis:
We hypothesized that there would be an association of higher long-term FBG variability from childhood with poorer midlife CF measures.

Aim:
We aimed to identify the influence of higher long term FBG variability on midlife CF.

Methods:
We studied 1,005 midlife Bogalusa Heart Study participants (age at baseline: mean 9.4 years +/- SD 3.5 years; age at neuropsychological(NP) exam: mean 47.9 years+/- SD 5.2 years; 60.4% women(607 of 1005); 33.5 % Black(337 of 1005)) with ≥3 FBG measurements across follow up. Participants having type 2 diabetes mellitus(T2DM) were excluded. T2DM was defined as FBG ≥126 mg/dL or taking diabetes medication. Long-term visit-to visit FBG variability was measured as deviation from age predicted values (DEV) and residual SD (RSD). Using ≥3 FBG measurements, DEV and RSD were obtained from individual growth curves created by fitting random-effects models stratified by race and sex. Participants’ midlife CF was first measured with 10 NP tests, then were classified into 3 distinct NP profiles (optimal, average, and mixed-low) using cluster analysis. Multinomial logistic regression models were used to analyze the associations between long-term FBG variability parameters and NP profiles, adjusting for education status and mean of FBG measures from childhood to midlife . DEV and RSD were standardized to z-scores by race and sex before regression analysis. Tests for interaction according to race and sex were conducted.

Results:
After adjusting for the mean FBG level and education status, for a 1 SD increase in DEV, the odds of having a mixed-low CF increased by 57.3% (95% CI 1.244, 1.990) and the odds of an average CF increased by 36.9% (95% CI 1.144, 1.640) respectively, compared to optimal CF. After adjusting for the mean FBG level and education status, for a 1 SD increase in RSD, the odds of having a mixed-low CF increased by 56% (95% CI 1.232, 1.974) and the odds of an average CF increased by 37.7% (95% CI 1.147, 1.653), respectively, compared to optimal CF. No significant interactions between long-term FBG variability parameters and race and sex were found.

Conclusions:
Higher long-term FBG variability was associated with poorer midlife CF. Further studies are needed to identify the role of long-term FBG variability in the association of cardiometabolic risk factors and midlife CF.
Abstract P278: 1-year Outcomes of A1c Reduction, Weight Loss, and Lowered QRISK3 Scores in Type 2 Diabetes Remission: Insights From an RCCT Leveraging Whole-Body Digital Twin Technology
Authors: Joshi Shashank , Dharmalingam Mala , Vadavi Arun , Thajudeen Mohamed , Keshavamurthy Ashok , Bhonsley Suchitra , Shamanna Paramesh
Published: May 2024

Background and Aims:
The effects of digital twin (DT) technology for remission of T2D on cardiovascular risk reduction is unknown. We evaluated the effectiveness of the DT to improve A1c and body weight and QRISK3 (QResearch Cardiovascular Disease Risk Algorithm 3), which is a prediction algorithm to estimate the 10-year risk for developing cardiovascular disease (CVD), in patients enrolled to achieve remission of T2DM. DT platform uses AI and Internet of Things, to integrate multi-dimensional data to give precision nutrition and health recommendations via the mobile app and by coaches.

Materials and Methods:
We evaluated the data from prospective cohort of 204 participants who had been on DT for 1 year. Remission was defined as A1C levels less than 6.5% without medication for over 3 months. Outcomes included the change in HbA1c, body weight and change in QRISK3 scores. The DT uses a machine learning algorithm to integrate clinical and sensor data to predict personal glucose response. Patients were connected to continuous glucose monitoring (CGM) throughout the study and self-recorded dietary intake using the mobile app.

Results:
The study participants had a mean diabetes duration of 3.7±2.6 years and a mean age of 44±8.2 years. Based on the ADA criteria, at 1 year, 73% (n=149/204) continued to be under remission. The mean QRISK3 at baseline was 12.6 (±10.7, 95% CI 11.2 to 14) which significantly reduced to 9.5 (±7.9, 95% CI 8.5 to 10.6) at 360 days, p=0.0009. A1c (%) at baseline was 8.9 (±1.8, 95% CI 8.6 to 9.1, minimum 5.5, maximum 16.2) which reduced to 6 (±0.6, 95% CI 5.9 to 6, minimum 4.7, maximum 9.2), p<0.0001. Body weight (kg) at baseline was 78.3 (±14.2, 95% CI 76.4 to 80.2) which reduced to 70.7 (±12.8, 95% CI 69 to 72.4), <0.0001. There was a significant correlation between the reduction in body weight and QRISK3 (Pearson r 0.24 95% CI 0.1 to 0.3, p=0.0004). However, the correlation between the reduction in A1c and QRISK3 (Pearson r 0.04, 95% CI -0.09 to 0.18, p=0.53 ns) was comparable. At baseline, there were 53% of participants who had low risk score (<10), 28% as intermediate risk (10-20), 19% as high risk (>20%) that at 1 year shifted to 67% as low risk, 23% as intermediate risk and 10% as high-risk scores.

Conclusion:
Incorporating the Digital Twin (DT) technology, which blends AI and IoT for tailored health guidance, our RCCT indicated significant 1-year advancements in A1c, weight, and QRISK3 scores among T2DM patients aiming for remission. The transformative potential of DT is evident, particularly in shifting a majority of participants towards lower cardiovascular risk categories.
Abstract P290: Telephone Lifestyle Coaching - Sex Differences in Referrals and Enrollment During National Implementation
Authors: Farmer Melissa , Claire Kimberly , Chanfreau Catherine , Hurley Sophia , Pear Eric , Goldstein Michael , Kim Jane , Raffa Susan , Hamilton Alison , Bean-Mayberry Bevanne
Published: May 2024

Objectives:
Telephone Lifestyle Coaching (TLC) is an evidence-based program providing individualized telephone coaching and self-management support to Veterans working on personalized, healthy living SMART goals. Given the flexibility of telephone support, we explored sex differences in TLC referrals and enrollment. We focus on sex to identify potential opportunities with virtual/telephone prevention programs in VA.

Methods:
Since March 2019, 44 VA sites have implemented TLC nationwide. Under VA’s QUERI rapid response evaluation program, we examined sex differences in referrals and enrollment with logistic regression controlling for demographics, mental and physical health, prior participation in a VA Whole Health Program and VA’s MOVE! Weight Management Program, and site-level clustering. The sample included all Veterans with at least one primary care visit one year prior to starting TLC.

Results:
As of 12/31/22, a total of 11,719 Veterans had at least one TLC referral, with 9,514 enrolled (82%), totaling 122,233 encounters. For both referrals and enrollment, mean age was 54, with 33% female, 29% Black, 7% Hispanic, and 34% with rural residence. In adjusted models, female Veterans had increased odds of being referred (OR=2.40, CI:1.89-3.05) and enrolling (OR=1.27, CI:1.13-1.42) compared to male Veterans. Odds of referral were higher for younger Veterans (OR=0.98, CI:0.97-0.98), those with depression (OR=1.62, CI:1.46-1.81), PTSD (OR=1.45, CI:1.21-1.73), overweight/obesity (OR=2.38, CI:1.58-3.57), at least one cardiovascular (CV) risk (OR=1.94, CI:1.63-2.30), and prior participation in Whole Health (OR=2.46, CI:1.74-3.51) or MOVE! (OR=6.40; CI:4.02-10.19). Similar associations with enrollment were observed, except Veterans with depression had decreased odds of enrollment (OR=0.84, CI:0.750.93), and effects for PTSD and CV risks were not significant.

Conclusions:
TLC demonstrated success in reach and engagement of female Veterans at rates above their national proportions in VA care. Referrals targeted weight and CV risk consistent with Veteran clinical needs. Our findings suggest that prior participation with MOVE! and Whole Health may facilitate engagement. Mental health diagnoses were not a barrier to referral, but depression status may reduce patient participation.

Impact:
TLC and virtual modalities of lifestyle coaching may have broader application for reaching and engaging female Veterans, as well as Veterans with mental health and CV risks who can benefit from health behavior change to optimize care.
Abstract P303: Investigating the Relationship Between Cardiovascular Diseases and Major Depressive Disorder Among Asians and Pacific Islanders
Authors: Gibbs Sophia , Bacong Adrian , Amaturo Lily , Frankland Timothy , Rosales Ana , Li Jiang , Daida Yihe , Fortmann Stephen P , Palaniappan Latha
Published: May 2024

Background:
Poorer mental health is associated with greater cardiovascular disease (CVD) morbidity, recovery, and mortality. Experiencing CVD is also associated with poorer mental health after a CVD event. What has been less examined, is how these associations differ among disaggregated Asian and Pacific Islander (API) groups who have a lower burden of both CVD and poor mental health relative to other racial groups.

Objective:
To examine the association between CVD diagnosis and experiencing major depressive disorder (MDD) among API people and how it differs between racial groups.

Methods:
We used survey data (n=5,229) from a study of API patients in Hawai’i and California with a linked electronic health record (EHR) data. Race, sex, body mass index (BMI) and CHD, Stroke, and PVD diagnosis were obtained from EHR while MI and CAD diagnoses were from the survey. Data on health behaviors and social determinants were obtained from the survey. Multivariate logistic regression models were used to determine the association between CVD and MDD.

Results:
Overall prevalence of MDD was 9.2%. Non-Hispanic White people (6.1%) had the lowest prevalence while “Pacific Islander and White” people had the highest prevalence (12.8%). In the fully adjusted models (Table), people who had a stroke (OR = 1.34, p < .001), CHD (OR = 1.32, p = .01), CAD (OR = 1.35, p = .016) or PVD (OR = 1.49, p < .001) had increased odds of MDD. There was a significant interaction between CAD and increased MDD that differed for Filipino, Asian Indian, “Pacific Islander and Asian”, “Asian and White”, and “Pacific Islander and White” groups compared to Non-Hispanic White people.

Conclusion:
Diagnosis of certain CVDs could increase the risk of experiencing MDD with potential race group differences for CAD. Further efforts should be made to protect the mental health of patients that have experienced a diagnosis of CVD as MDD can further harm their health outcomes. Moreover, research and treatment should consider potential racial differences in the experience of depression and CVD.
Abstract P311: Metabolomic Associations With Blood Pressure and Hypertension in Multi-Ethnic Populations
Authors: Alkis Taryn , Bartz Traci , Borges Carolina , Faquih Tariq , Gao Yan , Hu Jie , Moon Jee-Young , Rong Jian , Rossing Peter , YAO Jie , Ahluwalia Tarunveer S , Allred Nicholette D , Arnett Donna K , Balasubramanian Raji , Boerwinkle Eric , Bowler Russell P , Brody Jennifer , Clish Clary , Gerszten Robert E , Goulding Neil , Guo Claire , Guo Xiuqing , Hutton Scott , Kaplan Robert , Kelly Tanika N , Larson Martin , Lawlor Debbie , Lemaitre Rozenn N , Levy Daniel , Mook-Kanamori Dennis O , North Kari E , Psaty Bruce M , Raffield Laura M , Vasan Ramachandran , Rexrode Kathryn M , Rich Stephen S , Rotter Jerome I , Simino Jeannette M , Taylor Kent D , De Vries Paul , Williams Dylan , Wong Kari E , Morrison Alanna C , Yu Bing
Published: May 2024

Introduction:
Hypertension (HTN) is a leading cause of cardiovascular disease and premature death. A few circulating metabolites have been associated with blood pressure or HTN; however, findings from multi-ethnic populations are limited.

Methods:
Discovery analysis included eight population-based cohorts from the Trans-Omics for Precision Medicine (TOPMed) consortium, including adults of White, Black and Hispanic/Latino ancestries. Replication analyses were performed in six independent studies from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) and TOPMed. Fixed-effect inverse variance weighted meta-analysis was applied, on study- and ethnic-specific linear and logistic regression results, to estimate circulating metabolites association with systolic (SBP), diastolic blood pressure (DBP), and HTN cross-sectionally, adjusting for age, sex, body mass index, smoking status, lipids, kidney function, and diabetes prevalence. Global metabolomic analysis and pathway enrichment were performed to identify potentially altered metabolic pathways, and two-sample Mendelian randomization (MR) was performed to test for causal relationships between replicated metabolites and SBP, DBP, and HTN.

Results:
Out of 1,055 meta-analyzed metabolites, 336 were significantly associated (FDR<0.05) with all three BP traits among 17,767 participants (7,097 White, 5,406 Black, and 5,264 Hispanic/Latino). Xanthopterin had the strongest positive association (SBP: β=3.16, DBP: β=1.78, HTN: OR=1.34), and NH4_C18:2 CE had the strongest inverse association (SBP: β=-2.31, DBP: β=-1.49, HTN: OR=0.75), per SD increase of the metabolite level. The directions of associations were generally consistent across sex and racial/ethnic groups. Pathway enrichment analysis identified two enriched pathways (FDR<0.05): alanine, aspartate and glutamate metabolism and citrate cycle. Of 222 metabolites available for replication, 114 metabolites associated with all three traits (FDR<0.05) among 20,567 participants. MR analysis identified 18 potentially causal associations between metabolites and BP traits, including palmitoylcarnitine - a carnitine derivative that showed consistent positive causal associations across SBP, DBP and HTN (FDR<0.05).