bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P248: Plasma Proteins Associated With Depressive Symptoms and Perceived Global Stress Among African American Adults in the Jackson Heart Study
Authors: O'Brien Sara , Chen Brian , Cruz Daniel E , Reiner Alex , Sims Mario , Glover LaShaunta M , Raffield Laura M
Published: March 2023

Introduction:
Analyzing plasma proteins is a novel approach to uncover molecular mechanisms by which psychosocial stress may lead to chronic illness, including cardiometabolic disease. Proteomic analyses of cardiometabolic disease have been reported; however, proteomic studies of stress and depressive symptoms are limited.

Hypothesis:
We hypothesized that plasma protein concentrations are both positively and negatively associated with greater depressive symptoms and perceived global stress, respectively, in African American adults from the Jackson Heart Study (JHS).

Methods:
Participants from exam 1 (2000-2004) with SomaScan 1.3k platform proteomics data were utilized (n=2143, mean age=55.3). Depressive symptoms and global stress scores were measured via the 20-item Centers for Epidemiological Studies (CES-D) Scale and an 8-item global perceived stress scale adapted for the JHS, respectively. Multivariable linear models were used to test the association between depressive symptoms and global stress scores and proteins, controlling for age, sex, and proteomics batch. Bonferroni correction was used to adjust the p-value threshold for multiple testing (3.78e-5, for 1,322 tested proteins).

Results:
Six (6) proteins were found to be significantly associated with either depressive symptoms or perceived global stress. Angiopoietin-2 (β=0.014, SE=0.003,
p
=1.33e-5), growth/differentiation factor 15 or MIC-1 (β=0.014, SE=0.003, p=7.08e-8), and kynureninase (β=0.014, SE=0.003,
p
=1.55e-5) were positively associated with depressive symptoms. Contactin-5 (β=-0.017, SE=0.003,
p
=1.40e-7) and neural cell adhesion molecule 1 (120 kDa isoform) (β=-0.016, SE=0.003,
p
=6.74e-7) were negatively associated with depressive symptoms. Leukotriene A-4 hydrolase or LKHA4 (β=0.024, SE=0.005,
p
=2.72e-6) was positively associated with perceived stress. We note that several of these proteins which are associated with higher levels of stress or depression symptoms have also been associated with cardiovascular disease and related phenotypes; for example, LKHA4 was the lead association with left ventricular mass in previous JHS analyses.

Conclusions:
JHS proteomic profiles revealed differences in protein concentrations by psychosocial measures. We will next explore the extent to which identified proteins may mediate relationships between stress and depressive symptoms and cardiovascular endpoints. Future investigations may identify potentially targetable proteomic mechanisms by which psychosocial stressors manifest into disease.
Abstract P253: Neighborhood Socioeconomic Status and Psychosocial Health Among Asian Americans Adults in New York City
Authors: Shyamsunder Suditi , Ramachandran Dyuthy , Kim Chaeyoung , Singh Jaiveer , Dan Shozen , Palaniappan Latha , Srinivasan Malathi , Yang Eugene , Yi Stella , Elfassy Tali
Published: March 2023

Introduction:
Social determinants of health, including one’s neighborhood environment, are a fundamental cause of health inequities. Low neighborhood socioeconomic status (NSES) is associated with adverse psychosocial and physical health profiles, yet limited data exists among Asian Americans. Our study aim was to determine the association between NSES with depressive symptoms and psychological distress among Asian American adults in New York City (NYC).

Methods:
The NYC Community Health Survey (CHS) is a population based annual telephone survey used to track the health of NYC residents. It is conducted in five languages including Mandarin and Cantonese. Data are weighted to be representative of NYC as a whole. Our sample included data from 4,557 Asian American participants of the 2017-2020 CHS cycles who were geolinked to their respective neighborhoods, conceptualized as the community district (CD). From publically available CD profiles, we constructed a NSES factor score from four indicators: proportion of the CD unemployed, in poverty, with a high rent burden, and with less than a high school education. Psychosocial health was measured using the Kessler-6 (K6) for nonspecific psychological distress and the 8-item Patient Health Questionnaire (PHQ8) for depressive symptoms, with higher scores indicating worse psychosocial health. We used hierarchical linear models to determine the association between NSES tertile with outcomes stratified by Asian sub-group or region (Chinese, Indian subcontinent, or other Asian). Models were adjusted for individual level age, sex, income, and education. All analyses accounted for the complex survey design of the CHS.

Results:
Among NYC Asian American residents, 52.1% were women, 45% were age 25-44 years, 25% had less than a high school education, and 56% lived below 200% of the federal poverty level. Among Chinese residents of NYC, living in a neighborhood of low compared with high NSES, was associated with lower PH8 score (beta: -0.65, 95% CI: -1.10, -0.19). Among residents of NYC with heritage from the Indian subcontinent, living in a neighborhood of low compared with high NSES, was associated with a higher K6 score (beta: 1.27, 95% CI: 0.59, 1.95). Associations were not significant among other Asians or for other outcomes.

Conclusion:
Our results indicate a heterogeneous association between NSES with psychosocial health among Asian Americans of NYC, persisting beyond individual-level SES. Low NSES was associated with adverse psychosocial health among Asians from the Indian subcontinent but better psychosocial health among Chinese Americans. Further examination into potential sources of resilience such as social cohesion, for Chinese American residents residing in low resourced neighborhoods, is warranted.
Abstract P254: Mental Well-Being of Caregivers With Overweight and Obesity is Associated With Cognitive Stimulation Provided to Children in the Home
Authors: Lew Daphne , Davison Genevieve , Kilanowski Colleen , Eneli Ihuoma U , Cook Stephen R , Quattrin Teresa , Schechtman Kenneth , Epstein Leonard , Wilfley Denise
Published: March 2023

Introduction:
Parents with poor mental health are less likely to engage in cognitively enriching parenting behaviors, such as reading and playing with their children. This, in turn, is associated with increased risk of obesity in the child and poor treatment outcomes for children enrolled in behavioral weight management. Parents and caregivers with obesity also have worse mental health and lower life satisfaction than their non-obese counterparts. Among parents with overweight and obesity who have a child with overweight/obesity, the relationship between parent mental health and cognitive enrichment provided in the home is unknown.

Hypothesis:
We hypothesize that higher depressive symptoms and lower subjective well-being scores among parents will be associated with less cognitive enrichment provided to children. Further, we hypothesize that these relationships will be moderated by the sex of the parent.

Methods:
This study was a secondary analysis of baseline data from 452 parent-child dyads with overweight/obesity enrolled in a family-based behavioral treatment study for obesity. Depression symptoms and subjective well-being were assessed using the Patient Health Questionnaire-9 scale and the MacArthur Scale of Subjective Social Status, respectively. Cognitive stimulation was measured with the Cognitive Stimulation subscale of the Environmental Enrichment scale. Univariable relationships were assessed using Pearson correlations. Multivariable linear regression models were used to control for study site, parent characteristics (age, BMI, sex, race/ethnicity, education), child characteristics (age, and sex), and family characteristics (health insurance status and household income).

Results:
Higher depression symptom score was correlated with lower cognitive stimulation (ρ = -0.165, p < 0.001), whereas higher subjective well-being was associated with higher cognitive stimulation (ρ = 0.377, p < 0.001). These relationships were maintained even after controlling for covariates in the multivariable models, with each one-unit increase in depression symptoms associated with a 0.16 unit decrease in cognitive stimulation (95% CI -0.27 to -0.06, p = 0.003) and each one-unit increase in subjective well-being associated with a 0.04 unit increase in cognitive stimulation (95% CI 0.01, 0.07, p = 0.01). Parent sex did not moderate these effects.

Conclusions:
Mental well-being of parents and caregivers with overweight/obesity is associated with the degree of cognitive enrichment provided to the child in the home, though the effect sizes after controlling for covariates were modest. Thus, interventions targeting parental wellbeing offer a potential avenue to improve their child’s cognitive wellbeing and response to obesity treatment.
Abstract P255: Risk Factors for Incident Depressive Symptoms During the COVID-19 Pandemic Among Multi-Ethnic Older Adults: The Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Sharaf Asma
Published: March 2023

Objectives:
The COVID-19 pandemic has been associated with an increase in the prevalence of depression symptoms among young adults in the US. We examined the impact of the pandemic on the prevalence and incidence of depression symptoms, and related sociodemographic and cardiovascular risk factors, among older adults in a US general population-based sample.

Methods:
The Multi-Ethnic Study of Atherosclerosis (MESA) is a longitudinal cohort study that recruited participants who were 45-84 years old and without cardiovascular disease in 2000-02. Depression symptoms were assessed using the Center for Epidemiologic Studies depression scale (CES-D-10), during the pandemic (2021-2022) and pre- pandemic (2010-2011). We examined depressive symptoms in individuals with scores in both time periods. Incident depressive symptoms were defined as a CES-D-10 score ≥10 among participants with a CES-D-10 score <10 on pre-pandemic assessment. Risk factors for increases in CES-D-10 score and incident depressive symptoms, were examined by linear and logistic regression, respectively, adjusting for socio-demographic factors, health behaviors, and clinical characteristics.

Results:
Pre-pandemic and pandemic era CES-D-10 measures were available in 1602 MESA participants with mean age 75 years including 895 (55 %) women, who self-reported race/ethnicity as Non-Hispanic White (42%), Chinese (15%), Black (22%), or Hispanic (21%). The prevalence of depressive symptoms was 13.6% during the pre-pandemic period and 15.8% during the pandemic, and there were 180 incident cases of depressive symptoms (13%). After adjustment, significant increases in CES-D-10 scores were observed in women (+1.2, P<.001) and participants with lower education (less than high school versus college, +1.1, P=.03). Incident depressive symptoms were associated with female sex (aOR=2.16, p<0.001) and current smoking (aOR=2.04, p=0.03). Incident depressive symptoms were modestly yet not significantly associated with moderate to severe COVID-19 infection (aOR=1.88, p=.06). We did not find hypertension or diabetes to be significantly associated with worsening or incident depression symptoms.

Conclusions:
The prevalence of depressive symptoms increased modestly during the COVID-19 pandemic, compared to assessments one decade earlier, in a sample of multi-ethnic older adults. Greater risk of incident or worsening depressive symptoms was observed in women and current smokers. Additional research is needed on how pandemic-era depressive symptoms could affect future cardiovascular health.
Abstract P304: Association of Epigenetic Age Acceleration With Cognition in the Bogalusa Heart Study
Authors: Huang Zhijie , Bazzano Lydia A , Sun Xiao , Zhang Ruiyuan , Rao Varun , Shi Mengyao , Carmichael Owen , pan Yang , Cao Xi , Liu Yizhuo , Chen Wei , He Jiang , Li Changwei , Kelly Tanika N
Published: March 2023

Background:
Despite known associations of epigenetic age acceleration (EAA), or increased DNA methylation (DNAm)-based age relative to chronological age, with Alzheimer’s disease, few studies have investigated the relation of EAA with midlife cognitive function. We examined cross-sectional associations of EAA with cognition among the 1,252 middle-aged participants of the Bogalusa Heart Study 2013-2016 study visit.

Methods:
Whole-blood DNA methylation data was generated using the Illumina HumanMethylation450 BeadChip. Four EAA measures, including extrinsic EAA (EEAA), intrinsic EAA (IEAA), PhenoAA and GrimAA, were derived from the methylation data. Cognitive function was assessed by a standard battery of eight neurocognitive tests covering five cognition domains, and a global cognition score was calculated. Associations of EAA measures with cognitive function were assessed by 3 multivariable models sequentially adding (i) demographics (age, sex, race, education) and vocabulary; (ii) lifestyle behaviors (smoking, alcohol drinking, and depression), and (iii) clinical measures (blood pressure, lipids, body mass index, glycated hemoglobin, medication, and white blood cell count.

Results:
After Bonferroni correction (α=1.39E-3), PhenoAA and GrimAA were significantly associated with decreased processing speed (lower Digit coding test score) and decreased working memory (higher trail making test A score). GrimAA was also associated with lower global cognition score (
Table
). EEAA was associated with decreased processing speed (lower Digit coding test). After adjusting for lifestyle and clinical measures, such associations were slightly attenuated but remained at least nominally significant. IEAA was not associated with any cognitive test results.

Conclusions:
EAA measured by PhenoAA, GrimAA, and EEAA were significantly associated with decreased processing speed, working memory, and/or global cognition. The associations were independent of known cognitive decline risk factors.
Abstract P307: Elevated Blood Pressure Accelerates White Matter Brain Aging in Late Middle-Aged Women: A Mendelian Randomization Study in UK Biobank
Authors: Feng Li , Ye Zhenyao , Chen Shuo , Ma Tianzhou
Published: March 2023

Background:
Elevated blood pressure (BP) is a modifiable risk factor associated with cognitive impairment and cerebrovascular diseases. However, the causal effect of BP on white matter (WM) brain aging remains unclear. In this study, we hypothesize that increasing BP will accelerate WM brain aging.

Methods:
In our study, we focused on N=219,968 non-pregnant, family-unrelated individuals of European ancestry who had genotype data and two non-null clinical BP measurements available (99,532 male and 120,436 female, age range: 40-69, 16,901 have neuroimaging data available) collected from UK Biobank (UKBB). In the current study, we adopted a chronological age-adjusted brain age metric, Brain Age Gap (BAG), as the outcome variable to measure the brain aging status. As a first step, we applied machine learning method to establish the model to compute BAG based on fractional anisotropy (FA) measurements derived from structural neuroimaging data among a group of subjects without hypertension (N=7,728). The established model will be applied to calculate WM BAG in other subjects with or without hypertension. We then performed association analysis as well as a two-sample Mendelian Randomization (MR) analysis to estimate the causal effect of BP on WM BAG in the whole population and subgroups stratified by gender and age brackets . In the first sample with genotype and BP data but no WM FA data (N=20,3067), we tested the genetic-exposure association and identified relevant genetic variants as instrumental variables. In the second non-overlapping sample with genotype, BP, and WM FA data, we tested the genetic-outcome association (N=8,822). The causal effect of BP on WM BAG is estimated by using a generalized version of the inverse-variance weighted (IVW) approach.

Results:
The non-hypertension group and females had younger brains (WM BAG) across all the year cycles than the hypertension group by 0.3098 year and males by 1.2666 years, respectively, both p <0.0001. The association analysis revealed that both Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) had a stronger significant relationship with WM BAG among females (βSBP=0.0149; βDBP=0.0233), 50-59 aged group (βSBP=0.0163; βDBP=0.0259), and 60-69 aged group (βSBP=0.0086; βDBP=0.0147), all p < 0.0001. The MR analyses showed that DBP had a significant causal effect on WM BAG among females aged 50-59 (β=0.0720, p=0.0243) and females aged 60-69 (β=0.1000, p=0.0085). We only observed SBP had a marginal causal effect (0.05<p<0.1) among males aged 50-59 (β= -0.0458), females aged 40-49 (β= -0.0446) and aged 50-59 (β=0.0326).

Conclusion:
Hypertension and genetic predisposition to higher BP can accelerate WM brain aging specifically targeting at late middle-aged women, providing insights on planning effective control of BP for women in this age group.
Abstract P314: Social Determinants of Cardiovascular Risk Factors Among African Immigrants in New York City
Authors: Madu Ednah N , Ogungbe Oluwabunmi , Osuji Hadiza , OGIEHOR-ENOMA GRACE , Madu Chiamaka A , Bamba Aichata , Commodore-Mensah Yvonne
Published: March 2023

Background:
African immigrants (AIs) constitute a highly diverse and rapidly growing population in the US, particularly in New York City. Yet, their cardiovascular health remains understudied. We examined the prevalence of cardiovascular disease (CVD) risk factors and identified predictors of increased CVD risk among AIs residing in the five New York City (NYC) boroughs.

Objective:
To examine the relationship between social determinants (marital status, education, employment, and health insurance) and CVD risk factors among AIs living in NYC.

Methods:
This cross-sectional study was conducted among AIs ≥30 years residing in NYC. Outcomes of interest were self-reported CVD risk factors assessed individually (hypertension, diabetes, hyperlipidemia, overweight/obesity, and poor sleep). Using logistic regression analyses, we examined the associations between social determinants and individual CVD risk factors, adjusting for age and sex.

Results:
Of 215 participants, the mean age was 54 (SD: 11.7) years, and 70% were female. The majority (93%) had ≥1 of the 6 CVD risk factors. Smoking was least prevalent, and overweight/obesity was most prevalent (76%); with 42%, and 18% having a prior diagnosis of hypertension and diabetes, respectively. Those who were employed had ≥ bachelor's education were less likely to have hyperlipidemia (adjusted Odds Ratio [aOR]: 0.35, 95%CI: 0.15-0.86, or overweight/obesity (aOR: 0.31, 95%CI: 1.11-0.88); and twice (aOR: 2.14, 95%CI: 1.11-4.15), more likely to report poor sleep. However, being married and having health insurance were associated with a 3-fold (aOR: 3.08, 95%CI: 1.12-8.50) and 4-fold (aOR: 4.07, 95%CI: 1.12-14.73) higher likelihood of being overweight/obese.

Conclusions:
The prevalence of CVD risk factors among AIs was particularly high. Culturally-appropriate interventions and policies to reduce CVD risk factors are highly recommended for this population.
Abstract P315: Depressive Symptoms and Cardiovascular Health Among Young Adults in Puerto Rico
Authors: Rosal Milagros C , Lopez-Cepero Andrea , Almodovar Israel , Kiefe Catarina , Tucker Katherine L , Person Sharina , Rodriguez-Orengo Jose , Perez Cynthia
Published: March 2023

Background:
Depressive symptoms are associated with cardiovascular disease (CVD) incidence, morbidity and mortality. Less is known about the association between depressive symptoms and overall cardiovascular health (CVH) of young adults, an age group that commonly experiences depressive symptoms. We examined the association between depressive symptoms and a metric of overall CVH among young Puerto Ricans, a high risk but understudied population.

Measures:
We used data from PR-OUTLOOK, a study of CVH among individuals aged 18-29 residing in Puerto Rico, obtained between September 2020 and September 2022. Depressive symptoms were assessed using the 10-item Center for Epidemiologic Studies Depression Scale (CES-D-10). CVH was assessed using the AHA Life’s Essential 8 metric, which includes modifiable behavioral (nicotine exposure, diet, physical activity, sleep health) and biological (body mass index- BMI, blood lipids, blood pressure, and blood glucose) components. For this analysis, this metric was modified to exclude diet. Higher scores (range 0-100), overall and for each component, indicate better CVH. Covariates included age, sex, marital status, and childhood material deprivation. Multivariable linear regression models were used to assess the relationships of CES-D-10 score with overall CVH score and its individual components. An interaction term for sex and CES-D-10 was added to the models to examine potential differences by sex.

Results:
The sample (n=964; mean age: 22.6 ±3.1) was largely female (64%) and single (89%), and a third (33%) reported having experienced material deprivation in childhood. Over half (58.6%) reported depressive symptoms above the cut-off for likely clinical depression (CES-D-10 >10). The overall mean CVH score was 80.2±12.8, with almost half of the sample (42.8%) having a score < 80. Mean scores for the CVH components were lowest for physical activity (57.2±43.2) and BMI (71.4±33.9). In adjusted models, significant inverse associations were observed between CES-D-10 with overall CVH (-4.21, 95%CI: -5.84,-2.58) and several CVH components: nicotine exposure (-4.28; 95%CI: -8.28,-0.28), physical activity (-9.32; 95%CI: -14.87,-3.78), BMI (-6.54; 95%CI: -10.94,-2.15), and blood pressure (-3.02; 95%CI: -5.81,-0.23). No significant interaction was observed between CES-D-10 and sex.

Conclusion:
Depressive symptoms were inversely associated with CVH and four of the seven assessed CVH components. Longitudinal analyses should elucidate the potential contribution of depressive symptoms to reduction in CVH in young adults. Understanding factors associated with CVH among young Puerto Ricans may help elucidate CVD prevention targets for this vulnerable population.
Abstract P321: Prevalence of Hypertension Among People Diagnosed With Diabetes in Africa, a Systematic Review and Meta-Analysis
Authors: Hinneh Thomas , Akyirem Samuel , Bossman Irene F , Ofori-Aning Patriot , Lambongang Victor , Ogungbe Oluwabunmi V , Commodore-Mensah Yvonne
Published: March 2023

Background:
Hypertension (HTN) and diabetes (DM) share common pathophysiological mechanisms and hence have a high likelihood of co-occurring. The co-existence of HTN and DM increase increases CVD risk and exponentially increases health spending. Little is known about the burden of HTN in people with DM in Africa.

Objective:
To estimate the pooled prevalence of HTN in people with DM in African countries.

Methods:
This review was registered in the International Prospective Register of Systematic Reviews. We searched PubMed, Embase, and Hinari databases to identify peer-reviewed articles which provided data on the prevalence of HTN in people diagnosed with DM in Africa. We included studies that defined DM diagnosis as hemoglobin A1(HbA1c) >7.0 and HTN diagnosis as BP≥140/90mmHg. We quantified the prevalence of HTN using random-effects models. We applied generalized linear mixed models with logit transformation to compute regional and overall pooled prevalence and estimated heterogeneity (I
2
).

Results:
Out of 3810 studies retrieved from the databases, 27 met the inclusion criteria with sample size between (80 - 4122). The mean age was 58 (± 11) years and 56% were women. The pool prevalence of HTN in people diagnosed with DM was 59.8% [95% CI: 52.8% - 66.5%]. By African region, Central Africa recorded the highest 77.6% [95% CI: 53.01% - 91.4%], South Africa 74.5% [95% CI: 67.4% - 80.5%], North Africa 65.5% [95% CI: 54.7% - 75.0%], West Africa 55.7% [95% CI: 44.0% - 66.7%] and East Africa 50.7% [95% CI: 43.7% - 57.3%]. Increasing age, being overweight/obese, being employed, longer duration of DM, urban residence, and male sex were associated with a higher likelihood of HTN diagnosis.

Conclusion:
The high prevalence of HTN among people with DM in Africa, supports an integrated differentiated service delivery to improve primary healthcare-level cardiovascular disease response mechanisms. The data generated from this review may inform the delivery of interventions to avert premature cardiovascular disease mortality among Africans.
Abstract P323: Three Year Changes in Adipokine Levels and Metabolic Risk Status: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Aryee Ebenezer K , Zhang Sui , Ozkan Bige , Michos Erin D , Echouffo Tcheugui Justin B , Gerstenblith Gary , Blumenthal Roger S , Coresh Josef , Selvin Elizabeth , Ndumele Chiadi E
Published: March 2023

Introduction:
Adipokine levels are strongly linked to diabetes and metabolic syndrome, with higher adiponectin having protective associations and higher leptin having harmful associations. Little is known about how past changes in adipokine levels relate to current metabolic risk.

Methods:
Among ARIC Visit 3 (1993-1995) participants, we examined the association of past changes in adiponectin and leptin levels over the 3-year period from ARIC Visit 2 (1990-1992) to Visit 3 with prevalent diabetes and metabolic syndrome at Visit 3. Adipokines were measured using aptamer technology (correlated 0.9x with immunoassay) and analyzed categorically as >50% increase, >50% decrease and <50% change (stable). Multivariable logistic regression was performed to assess associations with stratification by obesity (BMI ≥ 30 kg/m
2
) status.

Results:
Among 9,287 Visit 3 participants, the mean age was 61 years with 56% female and 19% Black adults. Relative to stable levels, a >50% increase in adiponectin over the past 3 years was associated with higher odds of prevalent diabetes (OR 1.62; 95% CI: 1.29-2.03) and metabolic syndrome (OR 1.45; 95% CI: 1.22-1.72). Past increases in leptin were associated with lower odds of diabetes (OR 0.64; 95% CI: 0.53-0.77) and metabolic syndrome (OR 0.70; 95% CI: 0.62-0.77) (Table). Compared to stable levels, >50% decrease in adiponectin over time was associated with lower likelihood of diabetes and metabolic syndrome. Decreasing leptin had nonsignificant associations. Patterns were largely consistent in obesity stratified analyses, with the principal difference being that adiponectin increase was only associated with increased metabolic risk in those without obesity.

Conclusion:
Recent changes in adipokine levels are linked to current metabolic status. A past increase in adiponectin has direct associations, while increasing leptin has inverse associations. The underlying mechanisms and implications for metabolic risk in older age should be further studied.
Abstract P330: Effect of Randomized Omega-3 Treatment on Downstream Bioactive Lipids and Their Association With Incident Cardiovascular Disease Events: Metabolomic Studies of the Vital and Jupiter Trials
Authors: Demler Olga , Liu Yanyan , Alotaibi Mona , Hoshi Rosangela , Giulianini Franco , Gibson Heike , Watrous Jeramie , Cook Nancy R , Costenbader Karen , Okereke Olivia , Glynn Robert , Ridker Paul M , Manson Joann E , Cheng Susan , Chasman Daniel , Jain Mohit , Mora Samia
Published: March 2023

Background:
The effect of omega-3 (n-3) treatment on cardiovascular disease (CVD) outcomes in randomized controlled trials remains inconsistent. We hypothesize that the downstream products of n-3 metabolism, including bioactive lipids (BALs), have a heterogeneous relationship with CVD, which may provide insight into response heterogeneity.

Methods:
Using state of the art LC-MS, we assayed the plasma bioactive lipidome (>10K BALs) across 3,512 individuals at baseline and Y1 or -2, in the VITAL substudies (CVD case control N=1540; CTSC subcohort N=1054; 45% women, median age 70, 20% non-white) and JUPITER CVD case control (N=918) (NCT01169259, NCT00239681). Linear regression revealed BALs that change consistently with n-3 treatment (n3BALs) (discovery in VITAL controls, validation in an independent VITAL CTSC substudy, cumulative FDR .05). n3BALs that are also associated with CVD in VITAL CVD were identified using adjusted conditional logistic regression (p<.05). A BAL score was established using a multivariable adjusted model and validated externally in JUPITER CVD. Y1 or -2 change in BAL score in response to randomized n-3 and nonrandomized fish intake were tested using 2-sample t-test (p<.05).

Results:
354 BALs changed in response to randomized n-3 vs placebo. Baseline levels of 8 of these BALs were significantly associated with incident CVD (Figure, panels A, B). When combined into the multivariable BAL score, 5 were inversely and 3 positively associated with the CVD risk. The BAL score was significantly associated with CVD with fully adjusted HR/SD of 1.32, 95%CI [1.12 - 1.55] in external study, Figure panel C. N-3 therapy, statin therapy and baseline fish intake were associated with weak Y1 or -2 reduction in BAL score.

Conclusions:
Downstream BALs are altered in response to n-3 treatment and associate with both decreased as well as increased risk of CVD. BAL response to n-3 treatment may explain clinical heterogeneity associated with fish oil supplementation and may be utilized for selection of more specific treatment.
Abstract P338: Circulating microRNA-19 and Cardiovascular Risk Reduction in Response to Weight-Loss Diets: The Preventing Overweight Using Novel Dietary Strategies (Pounds Lost) Trial
Authors: Xue Qiaochu , Heianza Yoriko , Li Xiang , Wang Xuan , Ma Hao , Kou Minghao , Rood Jennifer , Bray George , Sacks Frank M , Qi Lu
Published: March 2023

Introduction:
MicroRNA-19 (MiR-19) plays a critical role in cardiac development and cardiovascular disease (CVD).

Hypothesis:
We assessed the hypothesis that change in circulating miR-19 would be associated with changes in 10-year atherosclerotic CVD (ASCVD) risk and individual cardiovascular risk factors in a dietary weight-loss intervention.

Methods:
This study included 509 participants with overweight or obesity from the 2-year weight-loss diet intervention study (the POUNDS LOST trial) and with available data on circulating miR-19a/b-3p at baseline and 6 months. The primary outcome was the 6-month change in the ASCVD risk score, which estimates the 10-year probability of hard ASCVD events. Secondary outcomes were the change in each ASCVD component including blood pressure, lipid profiles, insulin resistance, glucose metabolism, and adiposity measures. Change in habitual physical activity and sleep disturbance were assessed from baseline to 6 months.

Results:
Circulating miR-19a/b-3p levels significantly decreased during the initial 6-month dietary intervention period (P=0.008, 0.0004, respectively). We found that greater decreases in log-transformed miR-19a/b-3p were related to a greater reduction in ASCVD risk (β[SE]=0.35 [0.13], P=0.01 for miR-19a-3p; β[SE]=0.33 [0.13], P=0.01 for miR-19b-3p) over 6 months. Similar positive associations were observed for changes in diastolic blood pressure with miR-19a/b-3p. Moreover, we found that sleep disturbance was significantly associated with reductions in miR-19a/b-3p from baseline to 6 months (P
trend
<0.05). There were significant interactions between changes in miR-19a/b-3p and sleep disturbance for changes in ASCVD risk (P interaction<0.005). Participants with greater decreases in miR-19a/b-3p with no/slight amount of sleep disturbance had a greater reduction of ASCVD risk from baseline to 6 months than those with moderate/great amount of sleep disturbance. In addition, changes in physical activity modified the associations between changes in miR-19a-3p and ASCVD risk. A greater decrease in miR-19a-3p was significantly associated with a greater reduction in ASCVD among participants with an increase in physical activity from baseline to 6 months. These positive associations were reversed and not significant among participants with no change/decrease in physical activity and moderate/great amount of sleep disturbance.

Conclusions:
In conclusion, decreased circulating miR-19 levels induced by dietary weight-loss interventions were related to a significant reduction in ASCVD risk, and such associations were more evident in people with no/slight amount of sleep disturbance and an increase in physical activity.
Abstract P350: Modifiable Features of a Group Weight Loss Program: The Patient Perspective
Authors: Pressman Alice , Huang Qiwen , Szwerinski Nina , Romanelli Robert , Nasrallah Catherine , Sudat Sylvia , Azar Kristen M
Published: March 2023

Introduction:
The Group Lifestyle Balance™ (GLB) program is an adaptation of the landmark Diabetes Prevention Program (DPP) group lifestyle intervention that is approved by the Centers for Disease Control and Prevention as a model curriculum for diabetes (T2D) prevention. While participation in the program has been associated with clinically significant weight loss and decreases in other risk factors for T2D and cardiovascular disease in community settings, participant retention and sustained engagement throughout the 12-month program have been major challenges. Little is known about participant preference for key customizable structural aspects of program delivery that are known to influence program acceptability.

Hypothesis:
We hypothesized that there are features of GLB that can be customized by the delivery system to enhance recruitment and retention.

Methods:
We conducted a discrete choice experiment at Sutter Health, a large integrated healthcare system in northern California. We invited 122,744 patients who met DPP eligibility criteria and had elevated BMI (>25), to complete an online survey. The questions were constructed to address four aspects of the structure of the program: delivery mode (in-person vs online); timing of sessions (day and time of day); facilitator (lifestyle coach vs. lifestyle coach with extra formal training); session format (group vs group plus 1:1). Three cohorts answered four different questions - each with 2 choices to determine optimal design of the program. We also asked participants to rate qualities of the facilitator and the group according to importance.

Results:
Surveys were completed by 6,923 (5.6%) of those invited. Two-thirds of respondents reported they would rather meet online with live video than in-person (64.2%, 1556 of 2425) and preferred the program be set in the health system (68.6%, 1664 of 2425). Most preferred the addition of private sessions (72.8%, 3273 of 4498), and a lifestyle coach with formal clinical training (80.9%, 1962 of 2425). A plurality of respondents rated facilitator personal experience with weight management as important/very important (45.2%, 3132 of 6923) and the majority also reported importance of teaching experience, and professional training (50.0%, 3456; 71.2%, 4932; both of 6923, respectively). One-quarter reported that it was important/very important for the other participants to be of similar age and sensitive to cultural differences (25.4%, 1759; 23.7%, 1639; both of 6923, respectively).

Conclusions:
This study identified patient preferences for several modifiable features of GLB (delivery mode, timing, session format) and several group factors. Understanding and optimizing these factors to meet the needs of participant subpopulations may be an important mechanism for improving intervention uptake and retention. Multivariable analysis is forthcoming to determine preferences for subgroups.
Abstract P357: Gender Disparities in Utilization of Statins in Patients With Cancer and Atherosclerotic Cardiovascular Disease: Results From Houston Methodist Learning Health System Outpatient Registry
Authors: Shahid Izza , Mandania Roshni , Gullapelli Rakesh , Avenatti Eleonora , Farooq Nihan , Carrasco Avila Jorge , Shah Aayush , Nagueh Sherif F , Malahfji Maan , Chang Jenny , Nasir Khurram
Published: March 2023

Background:
Gender disparities in utilization of statins have been reported across patients with cardiovascular disease, however these patterns remain unknown amongst cancer patients. We sought to evaluate gender differences in statin use amongst cancer patients with atherosclerotic cardiovascular disease (ASCVD) using data from a large US healthcare system.

Methods:
Houston Methodist Learning Health System Outpatient Registry was utilized to obtain data of adult population between 2016 to 2022. All patients with a cancer and ASCVD diagnosis listed on their problems list using the ICD-10 CM codes were included. Statin use and dose were identified in the database using ATC codes, and this information was recorded based on medication reconciliation reviews with patients at each clinical encounter. Multivariate logistic regression analysis and chi-square test were utilized to compare statin use between the two genders.

Results:
A total of 16,926 patients with cancer and ASCVD were included (41.6% women). Women with cancer and ASCVD reported lower statin use (63.9% vs 73.7%; p<0.01) and lower high-intensity statin use (27.5% vs 37.2%; p<0.01) compared with men. Women with cancer and ASCVD were also less likely to have LDL-C<70mg/dL (25.8% vs 35.2%; p<0.01) compared with men. Consistent results were observed even after adjusting for demographic and cardiovascular risk factors (any statin OR 0.68 [0.63, 0.72]; high-intensity statin OR 0.66 [0.61, 0.70]). These disparities persisted across age (<65, ≥65 years) and racial/ethnic (NHW, Hispanics, NHB, Asian/Other) strata.

Conclusion:
Although statins can potentially ameliorate risk of adverse cardiovascular events in patients with cancer, significant gender disparities exist in utilization of statins among US patients with cancer and established ASCVD, with women less likely to have guideline defined goal of LDL<70 mg/dL and receive any and high-intensity statin therapy across age and racial/ethnic subgroups.
Abstract P363: Knowledge of COVID-19-Related Risk Factors and Conditions Among Asian American, Native Hawaiian, and Pacific Islander Adults, February-April 2022
Authors: Doan Lan N , Wyatt Laura , Park Jin , Kwon Simona C , Yi Stella S
Published: March 2023

Introduction:
Communities of color, including Asian Americans (AAs), Native Hawaiians and Pacific Islanders (NH/PIs), experienced higher rates of COVID-19 infection, hospitalization and death compared to white populations during the early pandemic. Further, there are known disparities in cardiovascular disease (CVD) risk factors among AA and NH/PI groups that existed pre-pandemic (e.g., greater prevalence of diabetes among Filipino and Asian Indian compared to white adults). These outsized risks are combined with the increased experience of anti-Asian racism in this period along with historical distrust of health institutions, and legacies of structural racism that have made communities of color vulnerable to the pandemic. The purpose of this study was to understand knowledge of COVID-19-related conditions among AA and NH/PI ethnic groups, in order to anticipate and mitigate further COVID-19 and CVD disparities.

Hypothesis:
We hypothesize that knowledge of post-COVID-19 conditions and variants would vary by disaggregated AA and NH/PI ethnic group.

Methods:
The National COVID-19 Rapid Needs Assessment was conducted among AA and NH/PI adults from February to April 2022 with the help of ten community partners (n = 1,358; 1,197 AAs and 153 NH/PIs). The survey was primarily administered online in English and 11 Asian languages. We examined the following COVID-19 knowledge outcomes: vaccine breakthrough infections, COVID-19 variants, and long COVID. Responses included: ‘I know a lot about it,’ ‘I know a moderate amount about it,’ ‘I have heard of it, but don’t know much about it,’ and ‘I haven’t heard of it.’ Outcomes were disaggregated by seven AA (Chinese, Taiwanese, Filipino, Japanese, Korean, Vietnamese, South Asian) and two NH/PI (Polynesian, Micronesian) subgroups. Additional analyses will examine differences in knowledge based on misinformation and disinformation in the absence of timely, language concordant COVID-19 information.

Results:
Among AAs overall, 14.0% had not heard of vaccine breakthrough infections; 7.4% had not heard of COVID-19 variants; and 11.7% had not heard of long COVID. South Asian adults reported the lowest knowledge of COVID-19, while Filipinos reported the highest knowledge. Among NH/PI adults, 27.2% had not heard of vaccine breakthrough infections; 6.6% had not heard of COVID-19 variants; and 28.4% had not heard of long COVID. Both NH/PI subgroups reported very low knowledge of breakthrough infections and long COVID.

Conclusion:
Findings indicate COVID-19-related knowledge disparities across AA and NH/PI ethnic subgroups which may be more pronounced among South Asian and NH/PI communities. The COVID-19 pandemic will exacerbate known CVD health disparities if the pandemic mitigation strategies (e.g., disaggregated racial/ethnic data collection) are not inclusive of communities of color, immigrants and limited English fluent populations.
Abstract P366: Enrollment in Medicare Managed Care Plan is Associated With Higher Adherence to Anti-Hypertensive Drugs
Authors: Zhang Donglan , Xu Jianing , Hall Daniel , Chen Xianyan , Divers Jasmin , Wei Jingkai , Rajbhandari-Thapa Janani , Young Henry
Published: March 2023

Introduction:
Adherence to anti-hypertensive drugs, which is sub-optimal despite public health and policy efforts, is essential in controlling high blood pressure. Medicare Advantage plans are gaining popularity, partly due to their managed care designs that held promise to improve chronic disease management.

Hypothesis:
We assessed the hypothesis that hypertensive patients with a managed care plan have higher adherence to antihypertensive drugs than those with a non-managed care plan.

Methods:
We analyzed medication adherence – measured using proportion of days covered (PDC) over 12 months for antihypertensive drugs – among 174,172 patients with a hypertension diagnosis from the medical and pharmacy claims and benefits data in the 2017-2019 IBM MarketScan Research Database. We fitted separate generalized linear regression models among monotherapy (use of one class of antihypertensive drugs) and polytherapy (combined use of at least two classes of antihypertensive drugs) users and computed postestimation margins with the best-fitted model to compare medication adherence by plan type: 1) Managed Care exclusive provider organization and health management organization (EPO/HMO) plan, 2) Managed Care point-of-service plan, 3) Managed Care preferred provider organization plan, 4) non-Managed Care comprehensive plan, 5) non-Managed Care consumer driven health plan / high deductible health plan. Other patient characteristics included in the analyses were age, age-squared, sex, comorbidities, census region, and their interaction terms.

Results:
The average PDC among Medicare patients on monotherapy was 0.53 and among those on polytherapy was 0.74. Patients with a managed-care EPO/HMO plan had the highest PDC (0.53, 95% confidence interval [CI]: 0.52, 0.54 among monotherapy users and 0.73, 95% CI: 0.72, 0.74 among polytherapy users, respectively) and those with a non-managed care comprehensive plan had the lowest PDC (0.42, 95% CI: 0.41, 0.43 among monotherapy users and 0.62, 95% CI: 0.61, 0.63 among polytherapy users, respectively). By census region, patients living in the North Central region with a managed care EPO/HMO plan had the highest average PDC (0.71, 95% CI: 0.70, 0.72 among monotherapy users and 0.85, 95% CI: 0.84, 0.86 among polytherapy users, respectively). Other factors such as age, sex, and number of chronic conditions were significantly associated with PDC.

Conclusions:
In conclusion, with an increase in the proportion of older adults enrolled in Medicare Advantage insurance, managed care models may play a more important role in influencing adherence to essential drugs such as anti-hypertensive drugs among Medicare beneficiaries. Future research should investigate factors that promote adherence to medications across different managed care plan designs.
Abstract P389: Sex-Specific Genetic Interrogation of Cardiovascular Disease Drug Targets
Authors: Dib Marie-Joe , Meena Devendra , Zagkos Loukas , Dipender Gill , Elliott Paul , Dehghan Abbas , Tzoulaki Ioanna
Published: March 2023

Investigating sex-specific effects of genetically-proxied drug target inhibition on cardiovascular disease (CVD) liability may improve the understanding of CVD pathophysiology and therapeutic intervention, to enhance the formulation of sex-specific treatment in clinical practice. We aimed to investigate sex-specific associations between genetic variation at CVD drug targets and CVD risk factors in the UK Biobank for anti-hypertensive, lipid-lowering and anti-inflammatory drug targets. Firstly, we conducted genome-wide association studies (GWAS) for systolic blood pressure (SBP), C-reactive protein (CRP), low density lipoprotein (LDL)-cholesterol for 488,226 women and men in the UK Biobank. We then performed genetic colocalization analyses to identify shared or differential genetic loci for CVD risk factors in males and females. Our findings highlight that females and males share potentially causal variants for SBP at the
ADRB1, CACNA1D, CACNB2, CACNB3
and
SLC12A3
drug targets, for LDL-cholesterol at
PCSK9, HMGCR,
and for CRP at
IL6R
. Notably, we highlight heterogeneous effects of SBP in men and women at
ACE, CACNA1S, CACNA1C
. This is the first comprehensive genetic interrogation of sex-specific effects on drug targets, suggesting physiological differences in hypertension-mediated CVD between men and women and potential differential response to anti-hypertensive medication. Whether this has viable clinical implications is yet to be formally tested in further sex-specific analyses in genetic association studies and clinical trials.
Abstract P391: Genetic Analysis of Blood Pressure Traits in African Populations
Authors: Onyenobi Ebuka I , Chen Guanjie , Doumatey Ayo , Famooto Ayotunde , Zhou Jie , Adeyemo Adebowale , Rotimi Charles , Adebamowo Clement , Adebamowo Sally
Published: March 2023

High blood pressure is a heritable risk factor for cardiovascular disease, stroke and other chronic conditions. There is an increasing prevalence of high blood pressure in sub-Saharan Africa. We aimed to identify genetic variants underlying blood pressure traits in Sub-Saharan Africa. We conducted a GWAS, meta-analyses and gene-set analyses of blood pressure traits (systolic, diastolic, pulse pressure), in African populations. We used the African Collaborative Center for Microbiome and Genomics Research data (ACCME, n=~15,000) for GWAS discovery and the Africa America Diabetes Mellitus study data (AADM, n=~5,200), for GWAS replication. Multiple SNPs were identified reaching genome-wide significance. The lead SNP from the elevated blood pressure group was on chromosome 16 (rs148403740, minor allelic frequency (MAF)=0.0176, p= 9.28x10
-9
, odds ratio(OR)= 2.58) nearest to the MGRN1 gene. The lead SNP from the hypertension stage 1 group was on chromosome 7 (rs4236415, MAF= 0.4912, p= 1.33x10
-8
, OR= 1.2). The index SNP within the pulse pressure group was on chromosome 10 (rs61836106, MAF= 0.1828, p= 7.4x10
-9
, OR= 5.7). The findings provide promising candidate SNPs for developing risk stratification models in African populations.