Cardiovascular Disease Risk Factors Research Articles

Background: The American Heart Association recognizes the pre-pregnancy period as a window to optimize cardiovascular health and mitigate the risk of adverse pregnancy outcomes, particularly in those with cardiovascular disease (CVD) risk factors (RF). However, disparities in access to and utilization of preventive care are well-established outside of pregnancy. Understanding the social factors associated with lower pre-pregnancy care can inform interventions to improve equity in maternal health. Methods: We used data from the Pregnancy Risk Assessment Monitoring System, a nationally representative survey of women with a recent live birth. We included women age ≥18 years with self-reported data on pre-pregnancy CVD RF (obesity, diabetes, hypertension, or tobacco use) and visit attendance. The primary outcome was attendance at a clinic visit (i.e., “regular checkup”) with an OB/GYN or primary care doctor in the year prior to pregnancy. We calculated age-adjusted odds of attendance in those with 0, 1 or > 2 of the following adverse social factors: poor transportation access, food insecurity, unstable housing, lack of health insurance, difficulty paying bills, history of domestic abuse, and lack of a high school education. Next, we conducted subgroup analyses by presence of 0, 1 or > 2 CVD RF. Analyses were weighted accounting for survey design. Results: Of 233,815 women (weighted N=11,424,885), the mean age was 29.5 years, 32.6% had 1 CVD RF, and 10.2% had > 2 CVD RF. Adverse social factors were more often reported by those with CVD RF: 17.8% of those with no CVD RF, 25.7% with 1 CVD RF, and 28.3% with > 2 CVD RF (p=<0.01). Overall frequency of a pre-pregnancy clinic visit was 55.9% with a lower frequency in those with higher burden of adverse social factors ( TABLE ). For example, odds of a pre-pregnancy clinic visit was lower in those with > 2 compared with no adverse social factors in those with 0 CVD RF (63.8% VS 19.2%; aOR 0.15; 95% CI: 0.13-0.17), 1 CVD RF (60.3% VS 27.9%; aOR: 0.26; 95% CI: 0.23-0.30), and > 2 CVD RF (60.9% VS 33.4%; aOR: 0.35; 95% CI: 0.29-0.42). Conclusion: Adverse social factors are associated with a lower frequency of pre-pregnancy care utilization even among those with CVD RF. Among those with ≥2 adverse social factors, less than one-third of women attended a pre-pregnancy visit. Public health efforts should address upstream drivers of health to improve pre-pregnancy preventive care and optimize cardiovascular health.

Introduction: Over a quarter of US households experience energy insecurity (EI) - the inability to meet household energy needs - and this number is expected to rise due to increasing global temperatures and energy demands. EI has been shown to impact health due to financial tradeoffs with healthcare, but limited evidence exists on how EI may contribute to cardiovascular disease (CVD) risk factors and burden. Methods: Using Behavioral Risk Factor Surveillance – a nationally representative survey – data from 2023, we examined the relationship between EI and CVD risk factors and outcomes among households with incomes at and below 200% of the federal poverty level. EI was defined as experiencing a threat of utility disconnection for electric, gas, oil or water in the past 12 months. CVD risk factors (high cholesterol, hypertension, diabetes and tobacco use) were assessed as a composite risk score (range 0 to 4) by counting the total number of conditions. We performed a complete case analysis and used weighted multinomial regression models to analyze the relationship between EI and CVD risk scores. Demographic and socioeconomic covariates were included in the model. We used logistic regression models to evaluate the relationship with CVD (coronary artery disease (CAD), myocardial infarction (MI) or stroke). CVD risk factors were also included as covariates in these models. Survey weights were used to account for the complex survey design. Results: Within the study population (N= 53,389; 15.72% Black, 44.95% White and 28.38% Hispanic), those who reported EI (N=7,910) were found to be younger (median age: 42 (IQR 33.5) vs. 46 (IQR 31.6) years) and more likely to be female (62.5% vs. 56.7%), unemployed/unable to work (46.2% vs. 35.1%), and have public insurance (67.5% vs. 61.8%). In the adjusted model, EI was associated with significantly higher odds of reporting one or more CVD risk factors (Table) with OR of 2.22 (95% CI 1.48–3.33) for having all four risk factors. EI was also associated with higher odds of CAD or MI [1.42 (95% CI 1.23-1.58)]. There was a non-statistically significant higher odds of stroke [1.29 (95% CI 0.99-1.69)]. Conclusions: EI was associated with higher odds of CVD risk factors and burden among low-income adults. EI may be an important marker of increased risk of CVD, possibly due to financial tradeoffs, impaired healthcare access and management, or stress related physiologic pathways.

Introduction: Team-based care and shared decision-making (SDM) have been recommended to improve the management of cardiovascular disease (CVD) risk factors. However, decision aids to support team-based SDM for health behavior change and medication management in adults with multiple CVD risk factors are lacking. Objectives: To design and develop a web-based decision aid in health behavior change and medication management to improve multiple CVD risk factor management. Methods: A mixed method study was conducted to develop a web-based decision aid in health behavior change and medication management to improve CVD risk factor management using human-centered design principles and the International Patient Decision Aid Standards. The development process included three phases: (1) SDM workflow and needs assessment: we conducted a modified two-round Delphi study with 18 expert panelists including cardiologist, nurse, community health worker, pharmacist, physician assistant to develop the SDM workflow in multiple CVD risk factor management, (2) Needs assessment: we interviewed 6 clinicians and conducted 3 focus groups with 13 adult patients living with multiple CVD risk factors to understand clinician and patient perceived barriers and facilitators to SDM for CVD risk factor management; and (3) Prototype design and development: we conducted a co-design workshop to design and develop the Preferred-Heart prototype with 15 key stakeholders including software developer, patients with CVD risk factors, primary care providers, pharmacists, and community health workers. Results: The Delphi process resulted in a SDM workflow to improve health behavior change and medication management with 75 items and 8 SDM steps (Figure 1). The qualitative study identified multi-level barriers and facilitators to SDM in CVD risk factor management (Figure 2). Figure 3 shows the developed prototype of the web-based decision aid for multiple CVD risk factor management (“Preferred-Heart”). Conclusion: Key stakeholder input informed development of a web-based decision aid prototype to support health behavior change and medication management to improve multiple CVD risk factor management. Future studies are needed to test the usability, acceptability, and effectiveness of the developed decision aid in improving SDM and health outcomes.

Background: Social determinants of health (SDOH) impact the burden of cardiovascular disease (CVD) among Black adults, but limited information is available on how various SDOH dimensions are linked to CVD risk factors for Black ethnic subgroups and White adults. The study aimed to examine differences in the association between SDOH dimensions and CVD risk factors among Black ethnic subgroups including Black Americans (BAs), Afro-Caribbeans (ACs), African immigrants (AIs), and White adults. We hypothesized differences in the SDOH indices and CVD risk factors with stronger associations for the U.S born adults. Methodology: Using the National Health Interview Surveys 2013-2018, we categorized 143,459 participants based on race and birthplace. A principal component analysis was used to reduce fourteen variables to four indices. Multivariable-adjusted logistic regression models were utilized to assess the associations between these SDOH indices and self-reported CVD risk factors, including hypertension, high cholesterol, and diabetes. Results: The sample included 24, 830 Black (90% BAs, 5% ACs, 5% AIs) and 118, 979 White adults. Significant differences were observed in several social determinant factors among Black subgroups and White adults (Table 1). For AIs, there was no association between SDOH indices and CVD risk factors, except for diabetes and poor neighborhood cohesion (Table 2). Among ACs, only socioeconomic disadvantage was associated with lower odds of hypertension (OR= 0.74, 95% CI: 0.59-0.94), and all SDOH indices were associated with diabetes except for poor neighborhood cohesion. Among BAs and White adults, all SDOH indices were associated with diabetes and hypertension, except for socioeconomic disadvantage. Socioeconomic disadvantage and low healthcare access were significantly associated with high cholesterol (OR= 0.93, 95% CI: 0.89-0.98) and (OR= 1.12, 95% CI:1.04-1,19) in BAs. Among White adults, all SDOH indices were associated with high cholesterol apart from poor neighborhood cohesion (OR= 0.98, 95% CI: 0.97-1.00). Conclusions: The relationship between CVD risk factors and SDOH indices varied across Black ethnic subgroups and White adults with more significant associations among BAs and White adults. These findings suggest that nativity may play a role in the association between SDOH and CVD risk factors.

Social determinants of health are known to influence cardiovascular disease (CVD) risk. Communities experiencing greater social vulnerability often face structural disadvantages that contribute to higher morbidity and mortality from chronic diseases, including CVD. However, their relationship to sudden death (SD) has not been thoroughly researched yet. The present study aims to explore the relationship between CVD risk factors, CVD outcomes, and social vulnerability in victims of sudden death. As part of the SUDDEN Project at the University of North Carolina, we screened and adjudicated 399 sudden death victims from Wake County, NC. Each victim’s address was geocoded and linked to census tract level data, including the CDC PLACES: Local Data for Better Health, and the CDC Social Vulnerability Index (SVI) datasets. We compared our sample of SD victims against census tract data in terms of CVD, other comorbidities (e.g., DM2), and healthcare utilization. We assessed the distribution of CVD risk factors (e.g., smoking), and healthcare utilization in our sample across SVI quartiles. Chi-square tests were used to evaluate differences in demographics, risk factors, and outcomes. Overall, the 399 sudden death victims were uniformly distributed across all four SVI quartiles. However, African Americans who died suddenly were more likely to reside in high-SVI areas compared to Whites (p < 0.001). Contrary to established population-level patterns from prior studies, CVD risk factors were also uniformly distributed across SVI quartiles in our sample of SD victims. No significant differences in comorbidities were found across the SVI categories except for chronic kidney disease, which was more common in higher SVI areas, p < 0.05). However, living in an area with a higher SVI was associated with lower healthcare utilization prior to death. While overall CVD risk factors and comorbidities were largely similar across the different levels of social vulnerability, certain disparities could be found (e.g., regarding healthcare utilization). The findings suggest that structural and access-related factors may influence healthcare engagement prior to sudden death, even when traditional CVD risk profiles appear similar. Further research is needed to clarify the relationship between social vulnerability, healthcare access, and sudden death to determine how tailored interventions can reduce these disparities.

Background: Cardiovascular disease (CVD) is the number one cause of mortality in the United States and those experiencing homelessness are at a higher risk for developing CVD. The American Heart Association’s Life’s Essential 8 (LE8) risk factors for CVD (diet, physical activity, sleep, tobacco use, weight, cholesterol, blood sugar, and blood pressure) are effective predictors of CVD and related mortality in the general population but are under-studied in patients experiencing homelessness. Methods: We utilized the Health Center Patient Survey (HCPS 2022) to compare client's risk factors for cardiovascular disease for those accessing Health Care for the Homeless (HCH) clinics to those visiting a Community Health Center (CHC) clinic to identify potential opportunities for intervention or care recommendations. The data was analyzed using survey-weighted, bivariate, and multivariate logistic regressions. Results: HCH clinic patients were less likely to report sleeping between 7-9 hours (optimal), and more likely to report being overweight and engaging in moderate/vigorous physical activity 7 days per week compared with CHC patients. Those utilizing HCH clinics still had 2.07 (95% CI: 1.24, 3.46) greater odds of smoking at least 100 cigarettes in their lifetime and 2.29 (95% CI: 1.19, 4.40) greater odds of being diagnosed as pre-diabetic compared to CHC clinic patients, after adjusting for demographics and socioeconomic measures. There were no differences between clinic type in the frequency and management of diabetes, cholesterol, and hypertension. Conclusion: People experiencing homelessness experience a higher burden of CVD than the general population. Despite comparable chronic disease management, those using HCH clinics were at higher adjusted odds of smoking history and having pre-diabetes when compared to those who used CHC clinics. They also demonstrated greater unadjusted odds of being overweight, all of which can increase risk of CVD. Further research should identify and evaluate potential HCH clinic interventions for high-risk homeless populations to help reduce CVD mortality. Learning Objectives: 1) Compare Life’s Essential 8 cardiovascular risk factors between Health Care for Homeless clinic patients and Community Health Centers as the reference population. 2) Assess the odds of having life’s essential 8 factors between clinic types accounting for age, sex, and race, language preference, marital status, and employment status.

Background: Breast arterial calcification (BAC) assessment on screening mammogram is a promising tool to improve cardiovascular disease (CVD) risk evaluation. Purpose: To evaluate the association between BAC and incident CVD in patients with and without CVD risk factors (RFs). Methods: This single-center retrospective study included women aged 40–90 years who underwent screening mammograms from 2006 to 2016. BAC was quantified using an automated platform (cmAngio, CureMetrix). Primary outcome was all-cause death. Secondary outcomes were acute myocardial infarction (MI), heart failure (HF), stroke, and time to CVD composite event (MI, HF, stroke, or CVD-death). Patients were stratified by presence/absence of BAC (BAC+, BAC-) and CVD RFs [hypertension (HTN), hyperlipidemia (HLD), diabetes, chronic kidney disease, smoking history, antiplatelet use, or anti-HLD or anti-HTN therapy] at time of mammogram. Results: Of 22,314 index mammograms included, mean age of participants was 55 ± 13 years. There were 780 CVD events (4.6%) in BAC- women and 765 (14.2%) in BAC+ women (p<0.001) over a median follow-up of 4.1 years [IQR 1.7, 6.5]. There were 486 deaths (2.9%) in BAC- women and 535 (9.9%) in BAC+ women (p<0.001) over a median follow-up of 5.8 years [IQR 3.3, 8.3]. Highest frequency of composite events and death occurred in the BAC+/RF+ group (18% and 12%, respectively). In multivariable analyses, BAC+/RF- women were not at increased risk of CVD event or death compared to BAC-/RF- women. However, among RF+ women, BAC+ was linked with higher CVD risk (aHR 1.50, p<0.001) and mortality (aHR 1.44, p<0.001) than BAC-. Among RF+ women on anti-HLD therapy, BAC+ was linked with higher CVD risk (aHR 1.42, p<0.001) and mortality (aHR 1.28, p<0.001) than BAC- counterparts. Among BAC+/RF+ women, no anti-HLD therapy was linked with higher CVD risk (aHR 1.44, p<0.001) and death (aHR 1.46, p<0.001) than use of anti-HLD therapy. Among RF+ women on anti-HTN therapy, BAC+ was linked with higher CVD risk (aHR 1.55, p<0.001) and death (aHR 1.42, p<0.001) than BAC- counterparts. Among BAC+/RF+ women, no anti-HTN therapy was linked with higher CVD risk (aHR 1.28, p<0.001) and death (aHR 1.28, p<0.001) than use of anti-HTN therapy. Conclusions: BAC is independently associated with increased death and CVD outcomes in women with CVD RFs, especially those not receiving anti-HTN or anti-HLD therapy. These findings suggest opportunities for using BAC to help guide clinical management of CVD risk.

Background: Type 1 diabetes (T1D) is an autoimmune disorder resulting from destruction of beta cells in the pancreas by autoreactive CD8 T cells. AI4 is a highly pathogenic CD8 T cell clone, which was previously isolated from the islets of a young diabetes-prone non-obese diabetic (NOD) mouse. The AI4 T cell receptor (TCR) recognizes multiple natural and synthetic peptide ligands presented by the class I MHC molecule H2-D b . The highly diabetogenic nature of AI4 is likely linked to this promiscuity, or cross-reactivity, which can trigger autoimmunity. However, the underlying mechanisms by which this autoreactive AI4 TCR accommodates diverse ligands remain to be determined. Hypothesis: Defining the chemical and structural determinants of H2-D b /peptide interactions and autoreactive AI4 TCR cross-reactivity will aid in understanding the recognition mechanism in T1D. Methods: H2-D b /peptide complexes recognized by AI4 were refolded from inclusion bodies and purified by size exclusion chromatography. The complexes were crystallized and structures determined by X-ray crystallography. Results: Three crystal structures of H2-D b with AI4 ligands (YQLENYCAL, derived from insulin; FQDENYLYL, derived from dystrophia myotonica kinase; and YFIENYLEL, a synthetic mimotope peptide) were determined. The structures of these ligand complexes highlight a common network of interactions. The side chain of Asn5 of the peptide is a key anchoring residue, fitting inside the C-pocket and participating in polar interactions with the side chains of Gln94 and Gln121 of the H2-D b heavy chain. In all three complexes, Glu4 and Tyr6 side chains are solvent-exposed to serve as potential TCR contact points. In the complexes of FQDENYLYL and YFIENYLEL, Tyr8 and Glu8, respectively, are also solvent-exposed and may serve as additional TCR contact points. Because of its shorter side chain, Ala8 in YQLENYCAL does not seem to be solvent-exposed. Conclusion: Conserved Glu4 and Tyr6 of the peptides are solvent-exposed and available for contact with the TCR in the three complexes, suggesting they play important roles in the recognition by the AI4 TCR. This hypothesis will be verified by obtaining the structures of the AI4 TCR bound to these H2-D b complexes. The promiscuous and pathogenic nature of the autoreactive AI4 TCR can be understood by elucidating its recognition mechanism. This information could be used to block promiscuous TCRs to prevent T1D, a major risk factor for cardiovascular disease.

Background: Hypertension (HTN) is a major modifiable risk factor for cardiovascular disease and heart failure, contributing to about three-quarters of acute cardiovascular events. The American Heart Association (AHA) launched an initiative to improve blood pressure control across 14 health care organizations and 14 community-based organizations (CBOs) in Buffalo, Columbus, and Houston. Community-based blood pressure stations offer regular monitoring opportunities outside clinical settings, empowering individuals and raising awareness of hypertension risks. Integrated with clinical care, these stations connect individuals to medical care, follow-up, and chronic disease management, improving health outcomes through referrals and education. This approach is scalable, equitable, and sustainable for preventing and managing hypertension. Methods: CBOs began reporting monthly hypertension screening data in June 2024 via an online portal. Data included the number of individuals screened, those with elevated blood pressure (per AHA Guidelines), and referrals provided. Interviews with the 14 CBOs in early 2025 gathered detailed information on station locations, setup, training, referral processes, and success stories. Results: By March 2025, 14 CBOs reported 10,248 hypertension screenings at AHA-sponsored stations. There were 554 individuals with elevated readings and 269 referrals to care. Referrals were made to primary physicians, local clinics, walk-in and emergency care clinics, and hospital emergency departments. Reasons for not making referrals included individuals already under a physician’s care or taking hypertension medication, and lack of CBO staff to monitor stations. Interviews revealed trends such as increased recognition of hypertension symptoms and management, and the importance of AHA educational materials. Barriers to referrals included lack of insurance, cultural barriers, and resource availability like transportation and affordability of other services. Conclusions: The AHA initiative effectively partnered with CBOs to launch community-based blood pressure screening stations in three markets. CBO partners reported high satisfaction and positive feedback from individuals using the stations, though there are opportunities for improvement in implementation.

Background: Obesity is a major risk factor for cardiovascular disease (CVD), but individuals can differ in their metabolic health status, leading to varying CVD risks. Metabolic health is not static and can change over time; however, the impact of these changes on CVD remains poorly understood, particularly in aging populations. This study examines how transitions in metabolic obesity phenotypes are associated with CVD risk using data from two large national cohort studies. Methods: We conducted parallel analyses using data from the China Health and Retirement Longitudinal Study (CHARLS) and the English Longitudinal Study of Ageing (ELSA). At baseline, participants were classified into four metabolic obesity phenotypes: metabolically healthy normal weight (MHNW), metabolically unhealthy normal weight (MUNW), metabolically healthy overweight/obesity (MHOO), and metabolically unhealthy overweight/obesity (MUOO). These phenotypes were reassessed approximately four years later. Transitions between phenotypes were tracked, focusing on changes in metabolic health and BMI status. Associations with incident CVD were analyzed using multivariable-adjusted Cox proportional hazards models. Results: Among 10,675 participants, 2,436 (23.19%) developed CVD during follow-up. In multivariable-adjusted models, baseline MUOO, MHOO, and MUNW were each linked to higher CVD risk versus MHNW (HRs: 1.75, 1.46, and 1.38; all p < 0.001). Among 6,272 participants, 1,361 CVD events occurred. Compared with stable MHNW, individuals transitioning from MHOO to MUOO had the highest risk increase (HR: 1.858; p < 0.001), followed by those remaining MHOO (HR: 1.436; p = 0.002). Transition from MHOO to MUNW nearly doubled CVD risk (HR: 2.236; p = 0.007). Among individuals initially classified as MUNW or MUOO, transitions toward metabolically unhealthy phenotypes further elevated risk (HRs: 1.940–2.360; p < 0.01). Stable MUOO individuals had the most events and over two-fold higher risk (HR: 2.039; p < 0.001). Conclusions: Metabolic transitions from healthy to unhealthy states are linked to elevated CVD risk, even in normal-weight individuals. Preserving metabolic health despite obesity is associated with lower risk, highlighting its importance beyond BMI. These findings support dynamic monitoring and early intervention to reduce CVD risk in aging populations, especially among those with obesity.

Background: Lipoprotein(a) [Lp(a)] and metabolic syndrome (MetS) are well-established risk factors for cardiovascular disease. Recent evidence suggests that high Lp(a) levels may increase the risk of coronary heart disease (CHD) in patients with diabetes, raising the question of whether similar interactions exist between Lp(a) and metabolic syndrome. We aimed to evaluate the joint association of Lp(a) and MetS with incident CHD risk in a large, multi-ethnic, prospective cohort. Methods: We analyzed 6,664 participants from the MESA (Multiethnic Study of Atherosclerosis) cohort (median follow-up 14.0 years) without baseline CHD. MetS was defined as ≥3 of the following criteria: waist circumference ≥102 cm (men), or ≥88 cm (women), triglycerides ≥150 mg/dL or use of a fibrate medication, HDL-C <40 (men) or <50 (women) or use of a fibrate medication, SBP ≥130 mm Hg and/or DBP ≥85 mm Hg or use of antihypertensive medication, fasting glucose ≥100 mg/dL or use of antidiabetic medication (4). Elevated Lp(a) was defined as a level ≥50 mg/dL. CHD was defined as myocardial infarction, resuscitated cardiac arrest, or CHD death. Participants were divided into four groups: group 1: Normal Lp(a) without MetS, group 2: elevated Lp(a) without MetS, group 3: normal Lp(a) with MetS, group 4: elevated Lp(a) with MetS. Survival analysis using Kaplan-Meier and multivariable Cox proportional hazard models were performed to assess the relationship between Lp(a), MetS, and time to CHD. Results: In an adjusted model, log [Lp(a)] and MetS were both independently associated with CHD (HR: 1.14; 95% CI: 1.03, 1.25) and (HR: 1.75; 95% CI: 1.35, 2.27). Compared to the reference group (normal Lp(a) without MetS), those with elevated Lp(a) without MetS (group 2) did not have increased risk of CHD (HR: 1.30; 95% CI: 0.94, 1.80). However, those with normal Lp(a) with MetS (group 3) had greater risk of CHD (HR: 1.56; 95% CI: 1.18, 2.05). The highest risk for CHD were in those with elevated Lp(a) with MetS (group 4) (HR: 2.37; 95% CI: 1.66, 3.37). Conclusions: In this analysis. elevated Lp(a) and MetS independently increase CHD risk. MetS alone significantly increases risk, whereas elevated Lp(a) without MetS does not demonstrate a significant effect. However, their combination confers the highest risk, suggesting a synergistic interaction. These results emphasize the value of assessing Lp(a) in individuals with MetS to improve cardiovascular risk stratification and guide targeted prevention.

Background: Blood lipid levels are among the leading causal risk factors for cardiovascular disease. While genome-wide association studies (GWAS) have identified numerous loci associated with mean lipid levels, genetic contributions to blood lipid variability remain underexplored. To address this, we conducted a multi-population genome-wide variance quantitative trait loci (vQTL) analysis to identify single nucleotide polymorphisms (SNPs) influencing the variability of blood lipid traits. Methods: vQTL analyses were performed on five circulating lipid measures: high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglycerides (TG), and lipoprotein(a) (Lp(a)) in the Penn Medicine Biobank (PMBB). Analyses were implemented using QUAIL, which transforms the phenotype into a quantile integrated rank score and employs quantile regression to assess genetic effects on trait variance. Analyses were performed for each population, adjusting for age, sex, and genetic principal components. Genome-wide significance was set at p < 5e-8. Results: vQTL analysis identified 306 genome-wide significant loci associated with lipid variability. Nearby genes identified included CETP, CELSR2, APOA5, LPL, LPA, and PPM1H. Several loci overlapped with known GWAS loci for lipid levels, while others were novel, suggesting unexplored genetic mechanisms regulating variance. Conclusions: These findings provide new insights into the genetic regulation of lipid variability, which may improve risk stratification for cardiovascular disease and inform precision medicine approaches. Future analyses will replicate this work in the other cohorts (MVP, AoU, and UKB) to validate findings and further elucidate the genetic architecture of lipid variability.

Introduction: Chronic psychosocial stress (CPSS) is a well-known risk factor for depression and anxiety disorders and a significant risk factor for cardiovascular disease. CPSS has been linked to the development of atrial fibrillation, coronary heart disease, and sudden cardiac death. However, the mechanisms of CPSS on cardiac dysfunction and arrhythmias remain less understood. Hypothesis: We hypothesize that CPSS triggers secretion of stress hormones resulting in an autonomic imbalance that impacts cardiac excitability. We aim to test the structural and functional remodeling of the brain by CPSS, and determine the mechanisms underpinning brain-heart interactions and cardiac autonomic control. Methods: We used a multi-hit CPSS mouse model by chronically exposing mice to noise, overcrowding, and sleep-deprivation for 8 hours/day over 3 months. c-Fos staining and whole-brain 3-D mapping were used to identify the neuronal activity, and serum corticosterone was measured. ECG telemetry and heart rate variability (HRV) analysis were performed to assess cardiac excitability and autonomic control. Results: To study brain-heart interactions, we established a carotid artery perfusion technique to fix brain in situ, allowing for the concurrent harvest of unfixed heart from the same experimental animal. We identified increased neuronal activities in brain regions associated with CPSS including cortical amygdala, paraventricular hypothalamic nucleus, cerebral cortex, and auditory cortex. Serum corticosterone levels were elevated by CPSS exposure indicating the activation of hypothalamic–pituitary–adrenocortical axis. ECG telemetry recordings and HRV analysis demonstrated exposure time-dependent alterations in heart rates and HRV parameters, suggesting the remodeling of sinoatrial node and autonomic imbalance. Moreover, the effects of CPSS showed significant differences between male and female mice, with greater increase in serum corticosterone levels in female mice. Conclusion: CPSS altered brain-heart interactions through activation of amygdala and hypothalamus resulting in stress hormone release. The shift in autonomic balance caused significant changes in cardiac rhythm and HRV parameters with significant sex differences, consistent with the increased vulnerability to CPSS in females compared to males. Additionally, carotid artery perfusion technique provided a useful tool for concurrent collection of fixed brain and other unfixed organs from preclinical animals.

Background: Lp(a) has gained increased attention as a significant risk factor for cardiovascular disease (CVD), and its plasma levels are up to 3-fold higher in African Americans (AAs) likely contributing to the heightened CVD risk. While it is widely acknowledged that Lp(a) levels are largely determined by genetics, the potential impact of epigenetic alterations and a connection to adverse social determinants of health (SDoH) is unknown. Adverse SDoH are known to accelerate CVD risk, partially through epigenetic changes of the genome. In this pilot study, we aim to investigate a potential connection between socioeconomic status (SES) measures of SDoH, methylation levels within the Lp(a) gene, and circulating plasma Lp(a) levels in AAs. Methods: Sixty AAs (93.3% female, mean age: 61 years, mean BMI 33.7kg/m^2) at moderate CVD risk and living in under-resourced neighborhoods within the Washington DC area, were recruited to the NIH. Baseline sociodemographics were collected, including individual-level SES and census tract-based neighborhood socioeconomic deprivation (NSD). Methylating patterns determined by DNA methylation analysis on the Lp(a) gene ( LPA ) were detected utilizing the Illumina technique. Lp(a) plasma levels were measured using ELISA. We conducted a multivariable regression analysis with adjustment for ASCVD 10-year risk score and BMI to explore associations between NSD, methylation levels on LPA , and Lp(a) plasma levels. Results: We examined 20 LPA methylation sites. Four sites were significantly associated with circulating Lp(a) levels. None of these four methylation sites was significantly associated with SES. However, two methylation sites associated negatively with NSD (cg17028067 b= -0.27, p=0.04; cg22888279 b= -0.38, p=0.003). Neither SES nor NSD were directly associated with Lp(a) plasma levels. In a final step, we determined if either cg17028067 or cg22888279 would associate with 18 FDG-PET/CT-measured amygdala activity, a pathophysiological measure of chronic stress. Amygdala activity was negatively associated with LPA -cg22888279 (b= -0.28, p = 0.03) (Figure). Conclusion: Our data highlight the importance of chronic stress-related epigenetic modification of the LPA gene, especially in the cg22888279 locus, to increasing plasma Lp(a) levels, potentially further accelerating CVD development and progression in AAs.

Background: Suboptimal dietary patterns constitute a leading modifiable risk factor for cardiovascular disease (CVD) in women, yet the global and temporal dynamics of diet related CVD burden remain incompletely characterized. Understanding how specific dietary components have influenced CVD outcomes in women from 1990-2021 can inform targeted prevention strategies across diverse settings. Method: Using Global Burden of Disease 2021 framework, we quantified age-standardized DALYs and deaths due to CVD attributable to dietary risks in women across 204 countries from 1990–2021. Dietary exposure estimates came from population surveys and were linked to CVD outcomes via meta-analytic relative risks. We calculated absolute counts and percentage changes over time, with stratification by age, year and location. Results: From 1990-2021, DALYs for CVD in women attributable to high consumption of sugar-sweetened beverages increased by 75%, followed by deficits in omega-6 polyunsaturated fatty acids 48%, insufficient whole grain intake 33%, excessive sodium intake 24%, inadequate fruit consumption 23%, low seafood omega-3 fatty acids 18%, insufficient vegetable intake 15%, inadequate legumes 14%, low nuts and seeds 14%, and inadequate dietary fiber 2%. In contrast, DALYs related to high red meat consumption declined by 1%, while burdens linked to trans fatty acids and processed meats rose by 28% and 34%, respectively. Regionally, South Asia (SA) experienced the largest rise in CVD DALYs due to dietary risks, climbing from 6.76 million to 14.14 million (an increase of 7.78 million), whereas High-SDI regions saw a decline from 7.29 million to 5.17 million (a decrease of 2.12 million). Mortality attributable to dietary risks increased most markedly in SA 136%, followed by Low-Middle SDI 90%, Low SDI 83%, and Sub-Saharan Africa 78% between 1990 and 2021. Age-specific trends revealed that women aged 55 years and older experienced a 38% rise in deaths and a 31% rise in DALYs, whereas those aged 20–54 years saw a 17% increase in both deaths and DALYs over the same period. Conclusion: Over three decades, high sugar-sweetened beverage intake and insufficient whole grains, omega-6 fats, and fruits have driven rising CVD burden in women—most pronounced in SA and lower-SDI regions—while High-SDI areas saw declines. Tailored policies to reduce sugar-sweetened beverages and boost consumption of whole grains, fruits, and polyunsaturated fats are urgently needed to reverse these trends.

Background: Hypertension (HTN) is the leading risk factor for cardiovascular disease. Medical discrimination (i.e., discrimination in healthcare settings) is linked to poor disease management and delayed care. However, the influence of medical discrimination on HTN awareness, treatment, and control remains understudied. We sought to examine the associations of medical discrimination with HTN outcomes. Hypotheses: We hypothesized that: (1) medical discrimination would be associated with higher odds of elevated office blood pressure (BP) in the full sample, and (2) that among those with elevated office BP, medical discrimination would be associated with lower odds of being aware of having elevated BP, current antihypertensive medication use, and having controlled BP. Methods: We analyzed cross-sectional data from the All of Us Research Program. Medical discrimination was assessed with the 7-item Discrimination in Medical Settings Survey (a = 0.85) with higher scores indicating greater medical discrimination. We first assessed the presence of elevated office BP (i.e., systolic BP ≥130 and/or diastolic BP ≥80 mm Hg). Among participants with elevated office BP, we assessed whether they were aware of having elevated BP, were currently taking antihypertensive medication, and if they had controlled BP (all dichotomous). We ran separate logistic regression models to examine the associations of medical discrimination with each outcome. Models were adjusted for demographics, insurance, healthcare utilization, and history of heart attack or stroke. Results: The sample included 29,811 adults (mean age 58.6±15.9 years), of whom 64% were women and 83% were White. Approximately 69% reported experiencing any medical discrimination and 35% met criteria for elevated office BP. Medical discrimination was associated with higher odds of elevated office BP (AOR 1.13, 95% CI = 1.03-1.24; p = 0.01) and lower odds of being aware of having elevated BP (AOR 0.85, 95% CI = 0.75-0.96 ; p = 0.01). Medical discrimination was not associated with current antihypertensive medication use or BP control. Conclusion: Medical discrimination was associated with greater odds of elevated office BP and lower odds of being aware of having elevated BP. Findings underscore the need for efforts aimed at reducing medical discrimination to improve awareness of elevated office BP. Researchers should examine mechanisms by which medical discrimination influences these HTN outcomes in diverse patient samples.

Introduction: Hypertension is a major risk factor for cardiovascular disease, and the Dietary Approaches to Stop Hypertension (DASH) diet is the most effective diet for lowering blood pressure in adults with hypertension. However, little is known about how adherence to the DASH diet has changed in recent years. Research Questions: We evaluated changes in adherence to the DASH diet among US adults with hypertension overall and by age (20-44 years, 45-64 years, ≥65 years), sex (male, female), and race and ethnicity (Asian, Black, Hispanic, White) between 2013 and 2023. Methods: We identified adults aged ≥20 years with hypertension who completed a 24-hour dietary recall in the National Health and Nutrition Examination Survey (NHANES) between 2013 and 2023. NHANES survey weights were used to generate nationally-representative estimates. We calculated a validated DASH adherence score ranging from 0 to 9 by assessing adherence to 9 nutrient intake targets in the DASH diet. DASH adherence was defined as a DASH adherence score ≥4.5. We assessed trends in DASH adherence using survey-weighted linear regression models. Age- and sex-adjusted outcomes were determined with direct standardization to the 2020 US Census. To provide a contemporary assessment of DASH adherence, we pooled the most recent NHANES cycles (2017-2020 and 2021-2023) and fit multivariable logistic regression models to compare DASH adherence scores by sex (after adjustment for age and race and ethnicity) and by race and ethnicity (after adjustment for age and sex). Results: The unweighted study population included 8,556 adults with hypertension. The proportion of adults with hypertension who were adherent to the DASH diet decreased from 8.7% (95% CI, 7.2%-10.1%) in 2013-2014 to 6.5% (95% CI, 4.7%-8.1%) in 2021-2023 (P=0.04), including significant decreases among adults ≥65 years, women, and Black adults. In recent years, mean DASH adherence scores were lower among men compared with women (1.8 vs. 1.9, P=0.004). Compared with White adults, mean DASH adherence scores were lower among Black adults (1.6 vs. 1.8, P<0.001) and higher among Asian (2.5 vs. 1.8, P<0.001) and Hispanic adults (2.2 vs. 1.8, P=0.005). Conclusion: From 2013 to 2023, adherence to the DASH diet decreased among US adults with hypertension, and by the end of the study period, fewer than 7 in 100 were adherent to the DASH diet. Adherence was lower among men and Black adults than among women and other racial and ethnic groups, respectively.

Background: Obesity is a well-established risk factor for cardiovascular diseases, including atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF). Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may reduce AF burden and adverse cardiac outcomes through weight loss and metabolic improvements. Objective: To assess whether GLP-1 RA use is associated with reduced incidence of atrial fibrillation and other adverse outcomes among obese patients (BMI ≥35 kg/m2). Methods: A retrospective cohort study was conducted using the TriNetX global federated health research network, encompassing 103 healthcare organizations. Adults with BMI ≥35 kg/m2 between October 1, 2022 and December 31, 2022 were identified. Patients prescribed GLP-1 RAs (n = 74,539) were compared to propensity score-matched controls not using GLP-1 RAs (n = 74,539). Outcomes included atrial fibrillation (ICD-10 I48), all-cause mortality, major adverse cardiovascular events (MACE), and changes in BMI. Analyses included risk ratios, risk differences, odds ratios, and Kaplan-Meier survival statistics. Results: GLP-1 RA use was associated with lower incidence of AF (8.4% vs 8.9%; risk difference -0.4%, 95% CI [-0.7%, -0.1%]; risk ratio 0.95, 95% CI [0.92–0.98]; p=0.003) and reduced all-cause mortality (1.7% vs 2.6%; risk difference -0.9%, 95% CI [-1.0%, -0.7%]; risk ratio 0.67, 95% CI [0.62–0.72]; p<0.001). MACE risk was also lower in the GLP-1 RA group (6.8% vs 7.8%; risk difference -1.1%, 95% CI [-1.3%, -0.8%]; risk ratio 0.87, 95% CI [0.84–0.90]; p<0.001). Mean BMI at follow-up was slightly higher in the GLP-1 RA group (40.16 vs 39.87 kg/m2; p<0.001). Kaplan-Meier analysis confirmed significant reductions in AF and mortality risk (log-rank p<0.001 for both). Conclusions: Among obese patients, GLP-1 RA use was associated with a modest reduction in atrial fibrillation incidence, lower rates of major adverse cardiovascular events, and reduced all-cause mortality compared to matched controls. These findings support the potential cardioprotective effects of GLP-1 RAs in high-risk obese populations.

Background: Clonal hematopoiesis of indeterminate potential (CHIP), the age-related clonal expansion of hematopoietic stem cells with preleukemic driver mutations, is a novel risk factor for cardiovascular diseases (CVD). While associations between CHIP and plasma proteins are emerging, the causal nature of these relationships remains undetermined. Hypothesis: We aimed to identify specific CHIP driver mutations that causally alter plasma protein levels using human genetics and validate key findings in experimental models. Approach: We analyzed 61,833 participants from the NHLBI TOPMed Program (SomaScan for proteomics measurement) and UK Biobank (Olink for proteomics measurement) with paired DNA sequencing and proteomics. Associations between CHIP variables (composite or drivers DNMT3A , TET2 , ASXL1 ) and proteins were analyzed separately by platform. Bi-directional Mendelian Randomization (MR) was performed to assess causal relations between CHIP, DNMT3A , or TET2 and protein levels. Proteins implicated by MR for TET2 (LCN2, MPO, FLT3LG) were selected for validation via ELISA in 8-9 week-old hematopoietic Tet2 -/- vs wild-type (WT) mice. Results: MR analyses identified multiple instances where CHIP likely causes proteomic changes, with less evidence for reverse causality. In TOPMed (SomaScan), we identified 9 causal pairs (FDR<0.05) among 35 (24 examined) significant CHIP-protein pairs, with TET2 causally increasing MPO levels being the strongest (beta [SE]:0.022[0.008]; P=3.6x10 -3 ). In UK Biobank (Olink), among 473 (318 examined) significant CHIP-protein pairs, 121 were causal, with TET2 showing the strongest effects on increased LCN2 (beta[SE]:0.056[0.008]; P=4.3x10 -11 ) and decreased FLT3LG (beta[SE]:-0.089[0.015]; P=1.1x10 -9 ). The causal effect of TET2 on LCN2 was consistent across platforms. Murine experiments corroborated these findings: hematopoietic Tet2 -/- mice exhibited significantly increased plasma MPO and LCN2 levels compared to WT controls. Plasma FLT3LG levels were not significantly different, though a decrease in Tet2 -/- mice was directionally consistent with human MR. Conclusions: This study provides robust human genetic and experimental evidence for causal effects of CHIP, particularly TET2 mutations, on the plasma proteome. This validation of MR-identified proteomic changes strengthens the causal link and offers potential mechanistic insights into how CHIP may influence downstream outcomes, including CVD.

Background: Hypertension remains the most prevalent modifiable risk factor for cardiovascular disease. Although national access to care has improved, disparities in antihypertensive treatment by insurance type remain poorly defined in recent population-level data. Methods: We conducted a pooled cross-sectional analysis of U.S. adults aged ≥18 years using National Health and Nutrition Examination Survey (NHANES) data from 2013–2022. Adults who self-reported a physician diagnosis of hypertension were included. The primary outcome was current use of prescription antihypertensive medication. Insurance type was classified as Medicare (reference), Medicaid, Private, or Uninsured. Treatment prevalence was estimated using survey-weighted proportions. We then performed logistic regression accounting for NHANES survey design. To adjust for confounding, we applied inverse probability of treatment weighting (IPTW) based on a multinomial propensity score model including age, sex, race/ethnicity, education, and income. Results: Among 4,333 adults with diagnosed hypertension, treatment rates were highest in Medicare (91.5%) and lowest among the Uninsured (61.5%). In survey-weighted models, the odds of receiving treatment were significantly lower for Medicaid (OR 0.23; 95% CI 0.15–0.38), Private (OR 0.27; 95% CI 0.20–0.35), and Uninsured (OR 0.15; 95% CI 0.11–0.24) groups compared to Medicare. IPTW-adjusted models yielded consistent findings: Medicaid (OR 3.50; p=0.024) and Private (OR 4.25; p=0.0018) groups had significantly higher odds of being untreated. The Uninsured group showed a trend toward undertreatment (OR 1.58), but this was not statistically significant (p=0.33). Conclusion: Despite national improvements in insurance coverage, significant disparities in hypertension treatment persist. Adults with Medicaid and private insurance are at substantially higher risk of being untreated compared to Medicare recipients, even after adjustment for sociodemographic factors. The Uninsured group demonstrated a consistent but non-significant trend toward undertreatment. These findings highlight the urgent need for targeted, insurance-sensitive interventions to promote equitable hypertension care.