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Abstract P3008: Plasma Proteomic Signatures Of Organ Aging Are Not Responsive To Exercise Training: HERITAGE Family Study
Introduction: A recent study utilized plasma proteins to identify organ-specific aging signatures that were related to health and disease. However, it is unknown whether exercise interventions can change predicted organ aging. Methods: We measured 4979 plasma proteins using the SomaScan assay before and after 20 weeks of endurance exercise training in 673 Black and White adults from the HERITAGE Family Study. Organ age was estimated for 11 major organs using different panels of proteins and age gap was calculated as the difference between predicted age and the LOWESS regression estimate of the population mean. Accelerated aging was defined as an age gap value ±2SD from the mean. Paired t-tests examines changes in predicted organ age with exercise training. Results: We found low-to-modest correlations between predicted organ age and chronological age for 9 of 11 traits ( Table 1 ). These correlations were almost exclusively observed in the oldest (age quartile 4: ages 47.6-65.9) and not younger participants (age quartiles 1-3: age<47.6 yrs) ( Table 1 ). A total of 37% of participants had accelerated aging in at least one organ at baseline, with 15% having 2 or more accelerated organ ages, which was balanced across chronological age quartiles. Exercise training did not significantly alter any of the predicted organ ages in the total sample or by age quartile, with wide interindividual variability in the training responsiveness of predicted organ ages. Moreover, although some participants reduced their number of accelerated organ age traits after training, the prevalence of accelerated organ aging remained 37% at post-training. Conclusions: We found that existing proteomic organ aging signatures only replicated in the oldest (middle aged) HERITAGE participants, which likely reflects the fact the signatures were derived in older populations. Importantly, organ aging signatures were not sensitive to exercise training, which likely limits their potential clinical utility.
Abstract P3144: Association Between Perceived Discrimination and Depression/Anxiety Symptoms
Introduction: Research linking perceived discrimination and depression and anxiety symptoms as well as brain function is limited. Objective: To examine the relationship between perceived discrimination, particularly racial/ethnic discrimination, and depression and anxiety symptoms, as well as brain function related to emotion and cognition, in individuals with depression and/or anxiety. Differences by race and ethnicity were also explored. Methods: We analyzed baseline data on perceived discrimination, depression and anxiety symptoms, and brain activities in an ongoing clinical trial, which investigates a voice-based virtual coach for problem-solving treatment. Perceived discrimination was measured using the PhenX Major Experiences and Everyday Discrimination Scales. Depression and anxiety were assessed using the PHQ-9 and GAD-7, respectively. Activity of a priori neural targets, amygdala for emotional reactivity and dorsolateral prefrontal cortex (dlPFC) for cognitive control, was measured using fMRI. Results: Among 161 participants (mean age 36.6 [SD 11.8] years; 80.8% female; 19.3% Non-Hispanic White, 23.6% Black American, 21.7% AAPI, 31.1% Hispanic), major (r=0.14; p=.01) and everyday (r=0.19; p=.02) discrimination scores were significantly positively correlated with GAD-7 scores. Racial/ethnic discrimination was significantly positively associated with GAD-7 scores (r=.19; p=.01) when reported for everyday discrimination. The association was also positive but not statistically significant when reported for major discrimination (r=.14; p=.07). For differences by race/ethnicity, Black Americans reported the highest levels of both general (p=.002) and racial/ethnic major discrimination (p<.0001). Black Americans, AAPI, and Latinos reported significantly greater racial/ethnic everyday discrimination than non-Hispanic White participants (p<.0001). Neither major or everyday discrimination correlated significantly with PHQ-9 scores or with the neural targets (dlPFC and amygdala). Conclusion: Heightened anxiety but not depressive symptoms or the prespecified neural targets are associated with experiences of discrimination, particularly racial/ethnic discrimination, in adults with depression or anxiety. Research on how to address social determinants of health such as discrimination in mental health interventions is warranted.
Abstract P2097: Association of atrial fibrillation with probable dementia in the SPRINT Trial
Background: Emerging evidence suggests that atrial fibrillation (AF) is associated with cognitive impairment and dementia, though the extent of this relationship in certain populations remains unclear. Methods: We examined the association of baseline AF and incident probable dementia (PD) in patients with hypertension but without diabetes or a history of stroke who were enrolled in the Systolic Blood Pressure Intervention Trial (SPRINT). Incident mild cognitive impairment (MCI) and a composite of PD and MCI were also used as outcomes in additional analyses. Participants with prevalent PD or MCI at baseline were excluded. Baseline AF was detected from electrocardiograms (ECGs) read centrally at an ECG core, and cognitive outcomes were ascertained during follow-up by an adjudication committee. Results: Among the 8,027 participants (mean age 67.9, women 36.5%) included in the analysis, 106 (1.3%) had AF at baseline. During a median follow-up of 5.0 years, 306 (3.8%) incident PD events occurred. Participants with baseline AF had a higher incidence of PD than those without AF (8.5% vs. 3.7%, p-value = 0.01) In a multivariable Cox regression model adjusted for socio-demographics, treatment assignment, cardiovascular risk factors, and potential confounders, participants with baseline AF were at a higher risk of incident PD and the composite of MCI/PD, but not incident MCI. (Table) . Conclusion: In individuals with hypertension but without diabetes or a history of stroke, AF is associated with an increased risk of probable dementia. Further studies are needed to investigate whether AF screening and management might positively impact brain health.
Characterizing the genetic diversity and population structure of Plasmodium knowlesi in Aceh Province, Indonesia
As in other parts of Southeast Asia, efforts to achieve or sustain malaria elimination in Indonesia have been threatened by the emergence of human infection with the primate species P. knowlesi. To understand the transmission dynamics of this species, investigation of P. knowlesi genetic diversity and population structure is needed. A molecular surveillance study was conducted in two phases between June 2014 and September 2018 at five primary health facilities in Aceh Province, Indonesia, an area nearing malaria elimination. Dried blood spot samples were collected from patients presenting with suspected malaria and testing positive for malaria by microscopy. PCR was performed for molecular confirmation and species identification. Forty-six samples were confirmed to be P. knowlesi, of which 41 were amplified with genotyping targeting ten known P. knowlesi microsatellite markers. For samples within a site, nearly all (9 of 10 loci) or all loci were polymorphic. Across sites, multiple identical haplotypes were observed, though linkage distribution in the population was low (index of association (IAS) = 0.008). The parasite population was indicative of low diversity (expected heterozygosity [HE] = 0.63) and low complexity demonstrated by 92.7% monoclonal infections, a mean multiplicity of infection of 1.06, and a mean within-host infection fixation index (FST) of 0.05. Principal coordinate and neighbour-joining tree analyses indicated that P. knowlesi strains from Aceh were distinct from those reported in Malaysia. In a near-elimination setting in Indonesia, we demonstrate the first evidence that P. knowlesi strains were minimally diverse and were genetically distinct from Malaysian strains, suggesting highly localized transmission and limited connectivity to Malaysia. Ongoing genetic surveillance of P. knowlesi in Indonesia can inform tracking and planning of malaria control and elimination efforts.
Abstract P3075: Diet quality and risk of hypertension in women cancer survivors
Background: Higher diet quality has been associated with reduced hypertension risk in the general population. Although women cancer survivors are at elevated risk of hypertension following cancer treatment, it is unclear if diet quality is also associated with risk of hypertension among women cancer survivors. Methods: We analyzed 1,441 women (aged 35 to 74 years) from the Sister Study (2003-2009) who reported a history of cancer other than non-melanoma skin cancer and had no prevalent hypertension at enrollment. Prevalent hypertension was defined as systolic blood pressure (BP) ≥140 mmHg, diastolic BP ≥90 mmHg, or the use of antihypertensive medication at enrollment. Participants diagnosed with cancer within one year of enrollment were excluded. The median time since diagnosis was 11.4 years. Participants were followed through September 2021 (median follow-up: 11.6 years). Dietary quality was assessed using the validated 110-item Block food frequency questionnaire and categorized into quartiles based on the entire Sister Study population for Dietary Approaches to Stop Hypertension (DASH), Healthy Eating Index (HEI-2015), alternate Mediterranean diet (aMED), and alternative Healthy Eating Index (aHEI-2010). Incident hypertension was self-reported as a new diagnosis or initiation of antihypertensive medication at any time during follow-up. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident hypertension. Results: After adjusting for potential confounders, higher DASH scores were associated with decreased risk of incident hypertension (HR Q4vsQ1 0.63, 95% CI 0.48-0.84, P trend =0.01). Associations were weaker for aMED (HR Q4vsQ1 0.78, 95% CI 0.59-1.03, P trend =0.09) and HEI-2015 (HR Q4vsQ1 0.78, 95% CI 0.60-1.03, P trend =0.12), and no significant association was found for aHEI-2010. A 5-year lag analysis yielded similar results. DASH remained associated with reduced hypertension risk even after adjusting for pre-existing diabetes, dyslipidemia, and cardiovascular disease history. The association between DASH and hypertension risk was not evident in long-term survivors (≥15 years post-diagnosis). A stricter hypertension definition (BP ≥130/80 mmHg) did not materially change the findings. Conclusion: Our findings suggest that higher diet quality, particularly following DASH dietary patterns is associated with reduced risk of hypertension in women cancer survivors.
Abstract P3165: Summary Measure of Social Determinants of Health/Health Equity and Stroke Burden among Mississippi Adults
Background: In 2022, ~97,000 Mississippi adults self-reported receiving a stroke diagnosis. Social determinants of health (SDOH) contribute to stroke burden and associated disparities and mortality. We examined the association between a summary measure of SDOH and stroke burden among Mississippi adults. Methods: Using the SDOH and Health Equity (SDOH/HE) Module data from 3,994 respondents in the 2022 Mississippi Behavioral Risk Factor Surveillance System survey, we conducted multivariable logistic regression models to examine the association between a SDOH/HE summary measure and stroke. Results: Participants who received food stamps or were enrolled in the Supplemental Nutrition Assistance Program (adjusted odds ratio, AOR, 3.10), experienced food insecurity (AOR, 2.49) or mental distress (AOR, 2.20) had significantly higher odds of stroke. Mississippians experiencing three (AOR, 2.79) or more (AOR, 3.27) of SDOH/HE risk factors had higher odds of stroke compared to those experiencing no SDOH/HE risk factors. Conclusions: Mississippi adults with multiple SDOH/HE risk factors had significantly higher odds of stroke than those with no SDOH/HE risk factors. These findings highlight the importance of addressing multiple SDOH/HE factors in stroke burden and the need for targeted interventions among Mississippi adults experiencing multiple SDOH/HE risk factors.
Abstract P2135: Nicorandil improves health status outcomes in patients with angina pectoris: a prospective, multicenter, cohort study (GREAT)
Background: Coronary artery disease (CAD) is a major contributor to cardiovascular mortality, with angina pectoris affecting nearly half of CAD patients. The GREAT study aims to establish a large cohort of Chinese patients with angina pectoris, evaluating the effectiveness of anti-anginal treatments through the Seattle Angina Questionnaire (SAQ). Methods: This multicenter, prospective cohort study included 1556 adult CAD patients with angina pectoris receiving or eligible for oral anti-anginal therapy. Patients were observed over 12 months. All participants were registered on an ePRO system via a WeChat Mini program, allowing them to submit questionnaires and clinic visit data. The primary outcome was the 12-month change in the SAQ summary score (SAQ-SS) from baseline. Secondary outcomes included changes in SAQ-SS at 3, 6, and 9 months. Patients were categorized into two groups: those treated with nicorandil (nicorandil group) and those not receiving it (non-nicorandil group). Propensity score matching (PSM) was used to reduce bias and control for confounding factors. Results: A total of 1528 patients were analyzed (FAS), of which 529 (34.6%) were in the nicorandil group and 999 (65.4%) in the non-nicorandil group. Following PSM, 450 matched pairs were identified. Baseline characteristics were well-balanced. The median age was 60 years in the nicorandil group and 61 years in the non-nicorandil group, and most patients were male (74.2% and 73.3%, respectively). β-blockers were widely used (68.7% and 70.2%, respectively). Both groups showed improvements in mean SAQ-SS across all follow-up points, but the nicorandil group had significantly greater improvements (P<0.05). At 12 months, the nicorandil group had a mean SAQ-SS improvement of 17.6 points, compared to 15.1 points in the non-nicorandil group (P=0.003). Furthermore, nicorandil users had significantly greater improvements in the SAQ quality-of-life (18.9 vs 16.3; P=0.042) and physical limitation (11.7 vs 8.4; P=0.001) domains (Table 1). In terms of clinical benefit, a higher proportion of patients in the nicorandil group experienced large or very large improvements in SAQ-SS at 12 months (24.0% vs 20.7% for 20–29 points; 18.2% vs 12.0% for ≥30 points; P=0.005) (Table 2). Conclusion: This real-world evidence demonstrates that nicorandil-based regimens lead to superior health status improvements in patients with angina pectoris compared to non-nicorandil treatments.
Endozoochory by the cooperation between beetles and ants in the holoparasitic plant Cynomorium songaricum in the deserts of Northwest China
Cynomorium songaricum Rupr. first described by Carl Johann (Ivanovič) Ruprecht in 1840 is a desert parasitic plant that mainly parasitizes the roots of Nitraria L. (especially of Nitraria tangutorum Bobrov., Nitraria sibirica Pall.). During seed maturation, C. songaricum releases a distinct smell, and its seeds are round and dust-like. Previous studies indicated that most parasitic plants produce small seeds, which are primarily dispersed by the wind. Recent studies reveal the significant role of animals in the seed dispersal of parasitic plants. In this study, we combined (1) the direct observation of the seed dispersal of C. songaricum, and (2) the indoor breeding of beetles and ants to assess the viability of seeds, clarify the seed dispersal system, and explore the mechanisms by which the seeds attract dispersal agents. By a population study, we identified beetles (Mantichorula semenowi Reitter, 1888) and ants (Messor desertora He & Song, 2009) as the primary seed dispersal agents for the C. songaricum. These plants rely on the visits from these agents to transfer their seeds near the roots of the host plant, Nitraria L.. The release of a distinct volatile compound from C. songaricum seeds attracts M. semenowi and M. desertora to consume and/or transport the seeds. This study provides the first evidence of a multi-medium and inter-species seed dispersal system in the C. songaricum. This study elucidates the role of invertebrates in the seed dispersal of desert parasitic plants. We propose that the two seed dispersal agents play distinct roles in the sequential seed dispersal of C. songaricum, representing two key stages in the overall seed dispersal mechanism.
Abstract P3074: Metabolomic Insights into Meat Consumption and Blood Pressure: The INTERLIPID Study
Introduction: The westernization and modernization of diet have gradually increased among the Japanese people, resulting in greater consumption of meat. Metabolic profiling can be considered a useful tool to ensure more accurate assessment of meat consumption and to clarify its underlying mechanisms associated with cardiovascular health outcomes. Hypothesis: We hypothesized that greater meat consumption could potentially lead to an elevation in blood pressure (BP), which was elucidated through meat-related candidate serum metabolites. Methods: A total of 1,007 Japanese participants aged 40-59 years residing in Japan were selected from the INTERLIPID study. Data on systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), dietary intakes, urinary, serum metabolites and lifestyle factors were collected. Serum metabolites were measured by nuclear magnetic resonance (NMR) spectroscopy and liquid-chromatography mass spectrometry (LC-MS). Associations between BP and serum metabolites were identified through partial Spearman correlation, and the effect of candidate serum metabolites of meat consumption on BP was explored by stepwise multiple linear regression considering age and sex. Results: The median of self-reported total meat intake was 28.98 g/1000kcal in men and 24.50 g/1000kcal in women. The multivariable linear regression results indicated that total meat and poultry intakes were significantly and positively related to BP. A total of 7 metabolites among 25 NMR and 29 metabolites among 51 LC-MS serum metabolites significantly correlated with meat consumption. Stepwise multiple linear regression indicated that the commonly related metabolites (p-value <0.05) for SBP, DBP and MAP were palmitoylcarnitine, carnitine and octanoylcarnitine. Additionally, the other associated metabolites included isovalerylcarnitine for SBP (β 1.24, CI 0.32-2.15), while for DBP, hexanoylcarnitine (β 1.61, CI 0.78-2.44), and niacinamide (β 0.73, CI 0.16-1.30). Conclusions: Higher meat consumption was significantly associated with elevated BP in Japanese. Some metabolites including palmitoylcarnitine, carnitine and octanoylcarnitine were suggested as important contributors to this association, offering novel insights into the metabolic mechanisms linking diet and BP.
Abstract P2085: Variation in Incident Atherosclerotic Cardiovascular Disease Across Asian American, Native Hawaiian and other Pacific Islander Subgroups: The PANACHE Study
Introduction: Atherosclerotic cardiovascular disease (ASCVD) risk varies substantially across racial and ethnic groups, yet few data exist among disaggregated Asian American, Native Hawaiian, and Pacific Islander (AANHPI) subgroups. Methods: We identified 2,653,007 members of Kaiser Permanente Northern California and Kaiser Permanente Hawaii integrated healthcare delivery systems from 2012-2022 who were aged ≥30 years with no evidence of prior cardiovascular disease. ASCVD events (acute myocardial infarction and stroke) were identified through December 2023 using validated discharge codes and death certificates. We calculated age- and sex-adjusted rates of incident ASCVD by racial/ethnic subgroup. We then examined the multivariable association between AANHPI subgroup with incident ASCVD compared to non-Hispanic White, after adjustment for age, sex, diabetes, hypertension, dyslipidemia, chronic kidney disease, body mass index, and tobacco use. Results: Between 2012-2022, we identified 182,776 Chinese, 193,327 Filipino, 64,488 Native Hawaiian/other Pacific Islander, 45,502 Japanese, 21,989 Korean, 92,738 South Asian, 50,141 Vietnamese, 26,602 other Southeast Asian, and 1,975,444 non-Hispanic White eligible adults. Mean (SD) age was 49 (15) years overall, ranging from 41 (12) years in South Asian to 55 (16) years in Japanese, with 53% women and higher proportions of women in AANHPI subgroups compared to non-Hispanic Whites. Age- and sex-adjusted rates (per 1000 person-years) of incident ASCVD vs. non-Hispanic Whites (3.61) from highest to lowest in AANHPI subgroups were: Native Hawaiian/other Pacific Islander (6.97), other Southeast Asian (5.37), South Asian (4.85), Filipino (4.23), Vietnamese (3.28), Japanese (3.20), and Chinese (2.50). After adjustment for traditional mediators of cardiovascular risk, compared to non-Hispanic Whites, incident ASCVD was higher for Native Hawaiian/other Pacific Islanders, South Asians, and other Southeast Asians; lower for Chinese, Japanese and Korean; and not significantly different for Filipino and Vietnamese ( Figure ). Conclusions: In a large, contemporary population in California and Hawaii, notable variation existed in the risk of incident ASCVD across AANHPI subgroups that was only partially explained by differences in demographic characteristics and clinical ASCVD risk factors. Delineating AANHPI-specific factors will help to reduce disparities in ASCVD in these growing populations within the U.S.
Abstract P3025: Evaluating the Correlation Between Urinary Microalbumin (ACR), Serum C-Reactive Protein (CRP), and Cardiovascular Risk Markers in Type 2 Diabetes Mellitus
Introduction: Diabetes mellitus (DM) is a common endocrine disorder characterized by hyperglycemia due to insulin deficiency. Over the past 35 years, the incidence of DM has nearly quadrupled, contributing to around 1 million deaths in 2019, with cardiovascular complications as a leading cause. Current management strategies in type 2 DM patients focus on early detection of cardiovascular risk markers, such as urinary microalbumin and serum C-reactive protein (CRP), both of which are cost-effective and minimally invasive. Objectives: To determine the correlation between urinary microalbumin, serum CRP, and albumin-to-creatinine ratio (ACR) with traditional cardiovascular risk markers in patients with type 2 diabetes mellitus. Methods: The study included 87 clinically diagnosed type 2 diabetes mellitus patients on oral antidiabetic medication, aged 35 to 60 years, and with normal serum creatinine levels. After obtaining informed consent, blood and urine samples were collected to assess blood glucose, serum CRP, renal profile, lipid profile, liver function tests, and urinary microalbumin. Albumin creatinine ratio (ACR) and atherogenic index of plasma (AIP) were calculated. Results: Comparison of profiles in the study revealed a significant decrease in serum HDL levels, a higher TG: HDL ratio, elevated glycated hemoglobin (HbA1c), and a raised atherogenic index of plasma (AIP) in cases with CRP ≥ 0.3 mg/dL compared to those with CRP < 0.3 mg/dL. Conversely, serum albumin (p<0.01), ALT, and A:G ratio were decreased in cases with CRP ≥ 0.3 mg/dL. MAU and blood urea nitrogen (BUN) were elevated in cases with ACR ≥ 30 mg/g (p<0.01) compared to those with ACR < 30 mg/g. Pearson’s correlation with CRP showed a negative correlation with total protein, albumin (p=0.01), A:G ratio, and hemoglobin, while BUN and serum ALP showed a positive correlation with CRP. ACR correlated positively with MAU (p=0.01) and negatively with albumin (p=0.05), with both correlations being statistically significant. These results demonstrate an association between urinary microalbumin (ACR), serum CRP, atherogenic index of plasma, and cardiovascular risk markers in type 2 DM. Conclusion: The study suggests that spot microalbuminuria and serum CRP are correlate well with traditional cardiovascular risk markers and can be used as screening tools for cardiovascular disease in DM patients. These markers are inexpensive, minimally invasive and can warrant for timely intervention's.
Characterization of microRNA candidates at the primary site of infectious bronchitis virus infection: A comparative study of in vitro and in vivo avian models
Infectious bronchitis virus (IBV) is an important avian pathogen with a positive-sense single-stranded RNA genome. IBV is the causative agent of infectious bronchitis (IB), a primarily respiratory disease affecting chickens, with the ability to disseminate to other organ systems, such as the gastrointestinal, renal, lymphoid, and reproductive systems. Tracheal epithelial cells are the primary target of IBV, and these cells play a vital role in the effective induction of the antiviral response and eventual clearance of IBV. The host immune system is regulated by a number of different molecular players, including micro-ribonucleic acids (microRNAs), which are small, conserved, non-coding RNA molecules that regulate gene expression of complementary messenger RNA (mRNA) sequences, resulting in gene silencing through translational repression or target degradation. The goal of this study was to characterize and compare the microRNA expression profiles in chicken tracheal epithelial cells (cTECs) in vitro and the trachea in vivo upon IBV Delmarva/1639 (DMV/1639) or IBV Massachusetts 41 (Mass41) infections. We hypothesized that IBV infection influences the expression of the host microRNA expression profiles. cTECs and young specific pathogen-free (SPF) chickens were infected with IBV DMV/1639 or IBV Mass41 and the microRNA expression at 3 and 18 hours post-infection (hpi) in the cTECs and at 4 and 11 days post-infection (dpi) in the trachea were determined using small RNA-sequencing (RNA-seq). We found that the profile of differentially expressed (DE) microRNAs is largely dependent on the IBV strain and time point of sample collection. Furthermore, we predicted the interaction between host microRNA and IBV viral RNA using microRNA-RNA interaction prediction platforms. We identified several candidate microRNAs suitable for future functional studies, such as gga-miR-155, gga-miR-1388a, gga-miR-7/7b and gga-miR-21-5p. Characterizing the interaction between IBV and the host cells at the level of microRNA regulation provides further insight into the regulatory mechanisms involved in viral infection and host defense in chickens following IBV infection.
Genetic ablation of the TET family in retinal progenitor cells impairs photoreceptor development and leads to blindness
The retina is responsible for converting light into electrical signals that, when transmitted to the brain, create the sensation of vision. The mammalian retina is epigenetically unique since the differentiation of retinal progenitor cells (RPCs) into retinal cells is accompanied by a decrease in DNA methylation in the promoters of many genes important for retinal development and function. However, the pathway responsible for DNA demethylation and its role in retinal development and function were unknown. We hypothesized that the Ten-Eleven Translocation (TET) family of dioxygenases plays a key role in this pathway. To this end, we knocked out the TET family in RPCs and characterized the TET-deficient and control retinas using various approaches including electron microscopy, electroretinogram tests, TUNEL, RNA-seq, WGBS, and 5hmC-Seal. We found that while the TET-dependent DNA demethylation pathway contributes to the development of many retinal cell types, it is the most significant contributor to rod and cone photoreceptor development and function. We found that genetic ablation of TET enzymes in RPCs prevents demethylation and the activity of genes essential for rod specification and for rod and cone maturation. Reduced activity of genes responsible for rod specification results in the TET-deficient retina being depleted of these neurons. Meanwhile, reduced activity of genes responsible for rod and cone maturation leads to the underdevelopment or complete absence of outer segments and synaptic termini in the TET-deficient photoreceptors, which results in loss of their function and leads to blindness. These function-deprived, underdeveloped photoreceptors die over time, leading to retinal dystrophy.
Abstract P1128: Trajectories of Physical Activity Before and After Cardiovascular Disease Events in a Diverse Cohort
Background: Physical activity plays a critical role in cardiovascular health throughout the life course. However, data on its trajectories before and after cardiovascular disease (CVD) are limited. We analyzed a bi-racial U.S. cohort with 35 years of repeated assessments of moderate-to-vigorous-intensity physical activity (MVPA) to examine trends and potential variations by race. Methods: CARDIA participants (n=5,115) underwent up to 10 MVPA assessments from 1985-6 to 2020-2. MVPA was assessed via a Physical Activity History Questionnaire and scored in exercise units (EU), with 300 EU approximating 150 minutes/week. During follow-up, 332 participants experienced an incident non-fatal CVD event, and 236 (71%) had subsequent MVPA data, forming the case group. Nested controls were matched 1:1 to cases by age, sex, and race using risk set sampling. LOESS regression explored non-linear MVPA trends, while linear mixed-effects models assessed differences in MVPA slopes between groups. Generalized estimating equation (GEE) models evaluated the odds ratio (OR) of low MVPA (<300 EU) post-CVD. Results: The mean baseline age of the matched sample (n=472) was 26 years; 64% were Black, and 60% were men. The mean age at incident CVD was 49 years. The median (IQR) number of MVPA assessments in cases was 6 (5-8) before and 2 (1-3) after CVD. MVPA levels were consistently higher in controls than in cases, with the gap widening after CVD (Figure), supported by a significant time-by-CVD status interaction ( P = .002). The OR for low MVPA post-CVD in cases vs. controls was 2.45 (95% CI: 1.76-3.41) and was stronger in Black (OR = 3.67, 95% CI: 2.36-5.70) than in White (OR = 1.49, 95% CI: 0.90-2.48) participants ( P interaction = .017). No heterogeneity was detected across CVD types (CHD, stroke, heart failure; P = .90). Conclusions: MVPA levels were consistently lower in cases than controls, with a more pronounced decrease after CVD, perhaps due to physical limitations. The odds of lower-than-recommended MVPA post-CVD were notably higher among Black participants.
Abstract P2095: Demographics, Vascular Risk Factors, and History of Cardiovascular Disease in Relation to Prevalent Epilepsy in Older Adults: A Pooled Analysis of ARIC, CHS, MESA, NOMAS, and WHICAP Cohorts
Introduction: Epilepsy is the third most common neurological disorder in older adults after dementia and stroke. Previous research suggests that vascular risk factors (VRFs) and cardiovascular disease (CVD) are more common in people with epilepsy. Pooling multiple cohorts with detailed characterization of vascular risk factors, CVD, and harmonized epilepsy case ascertainment increases diversity of the sample to be more representative of the US population and increases the numbers of epilepsy cases for greater statistical power. Methods: We pooled individual participant data from five cohorts, including ARIC, CHS, MESA, NOMAS, and WHICAP. For this analysis, we included participants who were 65 years of age or above. In ARIC, CHS, MESA, and WHICAP, which were linked to Medicare Claims, we included participants who had a minimum 2-year continuous Medicare enrollment and ascertained prevalent epilepsy using an algorithm based on ICD codes and antiepileptic medication. In NOMAS, which was not Medicare-linked, prevalent epilepsy cases were ascertained by telephone interview, medical record review, and ICD codes in New York Statewide Planning and Research Cooperative System (SPARCS) data. Risk factors were assessed by self report, blood measures, ECG, physical exams, and medications at cohort baseline. We calculated unadjusted prevalence of epilepsy in each risk factor category and prevalence differences and prevalence ratios adjusted for age, sex, race/ethnicity, and cohort. Results: Among 26,476 participants, 264 had prevalent epilepsy (9.9 cases per 1,000). Unadjusted prevalence of epilepsy was higher in older age groups, women, non-Hispanic Black and Hispanic groups, those with less education, never or current smokers, heavier alcohol drinkers, those with hypertension, diabetes, high cholesterol, underweight, obesity, history of stroke or heart disease, or 2 APOE e4 alleles (Table). Adjusted prevalence of epilepsy was higher among participants in the non-Hispanic Black group (5.3 additional cases per 1,000 [95% CI: 2.1, 8.5]) and among participants who had a history of stroke (12.9 additional cases per 1,000 [95% CI: 3.5, 22.3]). Conclusions: In this pooled cohort analysis, adjusted for age, sex, race/ethnicity, and cohort, prevalence of epilepsy in those over the age of 65 was higher among non-Hispanic Black individuals and among those with a history of stroke.
Abstract P3078: Long-Term Sustainability of a Hypertension Control Initiative
Sustainability, the continuation of a new program, is an ongoing challenge and a barrier to “sustaining” success. The American Heart Association (AHA) has completed the National Hypertension Control Initiative (NHCI), a 3-year demonstration project jointly funded by the United States Department of Health and Human Services’ Office of Minority Health and the Health Resources Services Administration (HRSA) to improve blood pressure (BP) control in 350 low-performing HRSA-funded community health centers (CHCs) with about 1.5 million persons with hypertension (HTN). Implementation strategies to improve BP control included accurate BP measurement, team-based care, standardized treatment protocols, culturally and linguistically appropriate services, and use of self-measured BP (SMBP) monitoring. Sustainability strategies for NHCI include the standardization and protocolization of care processes; adoption of data-informed performance improvement; and continuation and reinforcement of BP control efforts through Target: BP™, a BP control initiative jointly developed and delivered by AHA and the American Medical Association, serving about 9 million persons with HTN. Eligibility for NHCI included BP control < 60%. In 2023, year 3, 55.5% of NHCI CHCs reported BP control ≥60%. They experienced a 9.6% improvement (18.8% relative change) in BP control from 2020-2023, compared to a 7.7% improvement (13.2% relative change) for all HRSA CHCs. In 2023, 89% of NHCI CHCs reported using a BP measurement protocol, 93% reported an SMBP protocol, and 77% reported a BP treatment algorithm. Implementation of protocols and BP improvement will be sustained by pursuing participation in Target: BP. In the 1st and 2nd years of NHCI, 33% and 35%, respectively, of 346 NHCI CHCs concurrently participated in Target: BP. Of those submitting data in 2023, 25% reported control rates ≥70% and 67% reported adoption of evidence-based practices. In 2024, 55% of all CHCs participated in Target: BP. AHA’s NHCI work can be sustained by 1) enrollment of all NHCI CHCs in Target: BP through efforts of AHA staff that supported NHCI activities, 2) leveraging Target: BP tools, resources, and quality improvement support, and 3) seeking extramural funding to support AHA BP control efforts. Sustainability of NHCI through Target: BP could be extended from 346 NHCI CHCs to all 1487 CHCs with over 31 million patients. AHA can ensure sustainability of NHCI efforts beyond the 3-year NHCI period through Target: BP.
Atomic ionization: sd energy imbalance and Perdew–Zunger self-interaction correction energy penalty in 3d atoms
To accurately describe the energetics of transition metal systems, density functional approximations (DFAs) must provide a balanced description of s- and d- electrons. One measure of this is the sd transfer error, which has previously been defined as E ( 3 d n − 1 4 s 1 ) − E ( 3 d n − 2 4 s 2 ) . Theoretical concerns have been raised about this definition due to its evaluation of excited-state energies using ground-state DFAs. A more serious concern appears to be strong correlation in the 4s 2 configuration. Here, we define a ground-state measure of the sd energy imbalance, based on the errors of s- and d-electron second ionization energies of the 3d atoms, that effectively circumvents the aforementioned problems. We find an improved performance as we move from the local spin density approximation (LSDA) to the Perdew-Burke-Ernzerhof (PBE) generalized gradient approximation (GGA) to the regularized and restored Strongly Constrained and Appropriately Normed (r 2 SCAN) meta-GGA for first-row transition metal atoms. However, we find large (∼2 eV) ground-state sd energy imbalances when applying a Perdew–Zunger 1981 self-interaction correction. This is attributed to an “energy penalty” associated with the noded 3d orbitals. A local scaling of the self-interaction correction to LSDA results in a balance of s- and d-errors.
Abstract P1100: Risk of Incident Heart Failure by Gender Identity among US Veterans
Background: Disparities in heart failure (HF) are driven in part by social and structural determinants of health. Rates of HF among transgender and gender diverse (TGD) individuals relative to cisgender (cis) peers are not well described. Methods: We used EHR data from the Veterans Healthcare Administration (VHA) to identify veterans with >2 outpatient encounters from 2010-2019. Gender identity was ascertained using natural language processing in combination with gender-affirming hormone therapy (GAHT) and a validated algorithm utilizing ICD codes and VHA data. Among 1,103,923 veterans, 42,157 were classified as TGD. We examined sample characteristics by gender identity and used Cox regression to assess the association of gender identity with incident HF. Results: TGD veterans’ mean age was 46 years (cis females=40; cis males=53). Median follow-up was 9.41 years. There were 107,766 incident HF events (3,078 among TGD veterans). The HF rate among TGD veterans was 8.19 [95% CI: 7.90-8.48] per 1,000 person-years compared to 13.05 [12.97-13.13] and 3.87 [3.76-3.98] among cis male and cis female veterans, respectively. Adjusting for age, race, Hispanic ethnicity, and sexual minority identity, TGD veterans had 1.51 [1.44-1.58] and 0.89 [0.86-0.92] times the risk of HF compared to cis females and cis males, respectively. Results remained statistically significant with adjustment for additional social, clinical, and structural factors ( Table ). When stratified by gender identity, trans feminine veterans (HR [95% CI]: 1.19 [1.07-1.33]) were at higher HF risk than cis females; trans masculine (HR [95% CI]: 0.79 [0.72-0.86]) and trans feminine veterans (HR [95% CI]: 0.80 [0.72-0.89]) were at lower HF risk than cis males. Conclusion: Trans feminine veterans experienced greater HF risk than cis females, while trans feminine and trans masculine veterans’ HF risk was less than cis males. Future studies should consider the underlying mechanisms of these associations, HF subtypes (HFrEF and HFpEF), and the role of GAHT on HF risk.
Abstract P2104: Prevalence of Hypertrophic Cardiomyopathy Core Gene Variants in Hispanics/Latinos: A Study from The Hispanic Community Health Study / Study of Latinos (HCHS-SOL)
Introduction: Hypertrophic cardiomyopathy (HCM) is an inherited disease associated with genetic variants in sarcomeric genes, mostly studied in White populations. There is a paucity of literature, especially Hispanics/Latinos (H/L) populations where HCM sarcomeric variant prevalence is unknown. Methods: We analyzed whole-genome sequencing data from the Hispanic Community Health Study to assess sarcomeric variants in a diverse H/L sample. We identified HCM variant carriers based on eight sarcomeric genes (MYBPC3, MYH7, TNNT2, TNNI3, MYL2, MYL3, TPM1, ACTC1). Carriers were defined according to predictions from the HumDiv model of PolyPhen-2, by having at least one nonsynonymous deleterious (category D) variant. The prevalence of HCM genetic carrier was estimated accounting for complex survey design. Sociodemographic and clinical variables were analyzed across HCM variant carrier/non-carrier carrier status, with sampling weights used to calculate weighted means, frequencies, and population estimates. Results: Among 7,724 individuals self-identified as H/L, the overall prevalence of HCM variant carrier was 6.08%. The most commonly detected variants were on MYBPC3 and MYH7 while ACTC1 was not observed. (Figure 1. A) HCM variant carriers had a mean age of 41.20 ± 1.00 years, 50.32% were female, and the mean BMI was 30.13 ± 0.36 kg/m^2. There was no difference in burden of comorbidities among carriers and non-carriers. HCM variant carrier status was more likely among the H/L of Dominican descent than any other H/L background group (p<0.001). (Figure 1. B) Conclusions: The prevalence of HCM sarcomeric variants among H/L individuals was higher than previously reported in non-Hispanic populations. Among H/L, MYH7 and MYBPC3 were the most common, consistent with previous reports in non-Hispanic populations. HCM variant carrier prevalence varied across Hispanic background groups, likely due to different makeup of genetic ancestries. Our results identify the H/L population at possible elevated risk for developing clinical HCM, underscoring the need for inclusion of H/L in ongoing studies of HCM evaluation and management strategies. Authors: Jorge Silva Enciso and Reniell Iñiguez are co-first authors.
Abstract P3056: A Metabolomic Study of Cardiac Dysfunction in Hyperglycemia
Objective: Hyperglycemia (pre-diabetes and diabetes, DM) is associated with heart failure (HF). We aimed to identify distinct metabolites for subclinical cardiac dysfunction (CD), a precursor of HF, in hyperglycemic vs. euglycemic groups. Method: We used data from the ARIC study (Atherosclerosis Risk in Communities). In HF-free 2492 participants at baseline (2011-2013), 1297 were hyperglycemic (HbA1c>5.7%, fasting glucose>100 mg/dL, DM medication, or a DM diagnosis) and 1195 were euglycemic. We performed logistic regression for the association of 790 metabolites and CD, defined by echocardiographic abnormalities (LV hypertrophy, systolic or diastolic dysfunction) or elevated biomarkers (NTproBNP>125 pg/mL or HS troponin T>14 ng/L in women, >22 ng/L in men) at baseline in two glycemic groups separately. We used Cox regression to evaluate the association between CD-related metabolites (i.e., significant metabolites in the cross-sectional analyses) with HF risk. Analyses were adjusted for clinical risk factors and multiple comparisons (FDR< 5%) and replicated in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Results: 34 out of 790 and 16 out of 790 metabolites were associated with CD in the hyperglycemic (15% Black, 33% men) and euglycemic (22% Black, 47% men) groups, respectively. Metabolites previously identified as microvascular disease-related markers (e.g., pseudouridine, N6-carbamoylthreonyladenosine, N6-acetyllysine, N2, N5-diacetylornithine) were associated with CD in the hyperglycemic group (Fig1). Carbohydrate and cofactor-derived metabolites (e.g., gulonate, erythrocyte) were associated with CD in the euglycemic group (Fig1). 10 and 12 distinct CD-related metabolites in hyperglycemic and euglycemic groups, respectively, were also prospectively associated with HF risk (Hazard Ratios 1.2-1.9)(Fig2). 24 out of 34 and 11 out of 16 CD-related metabolites in the hyperglycemic and euglycemic groups, respectively, were available for validation in HCHS/SOL (n 1202, 34% men). The results were consistent with ARIC, where 10 and 12 distinct CD-related metabolites showed nominal significant association with incident HF in two glycemic groups, respectively. Conclusion: Metabolites known for microvascular complications (retinopathy, kidney disease) were associated with CD among hyperglycemic participants, supporting the premise that microvascular dysfunction contributes to HF pathogenesis in people with hyperglycemia.