Characterization of Peripheral Artery Disease and Associations with Traditional Risk Factors, Mobility, and Biomarkers in the Project Baseline Health Study.

BACKGROUND: There is a dearth of research on immunophenotyping in peripheral artery disease (PAD). This study aimed to describe the baseline characteristics, immunophenotypic profile, and quality of life (QoL) of participants with PAD in the Project Baseline Health Study (PBHS). METHODS: The PBHS study is a prospective, multi-center, longitudinal cohort study that collected clinical, molecular, and biometric data from participants recruited between 2017 and 2018. In this analysis, baseline demographic, clinical, mobility, QoL, and flow cytometry data were stratified by the presence of PAD (ankle brachial index [ABI] ≤0.90). RESULTS: Of 2,209 participants, 58 (2.6%) had lower-extremity PAD, and only 2 (3.4%) had pre-existing PAD diagnosed prior to enrollment. Comorbid smoking (29.3% vs. 14%, p<0.001), hypertension (54% vs. 30%, p<0.001), diabetes (25% vs. 14%, p=0.031), and at least moderate coronary calcifications (Agatston score >100: 32% vs. 17%, p=0.01) were significantly higher in participants with PAD than in those with normal ABIs, as were high-sensitivity C-reactive protein levels (5.86 vs. 2.83, p<0.001). After adjusting for demographic and risk factors, participants with PAD had significantly fewer circulating CD56-high natural killer cells, IgM+ memory B cells, and CD10/CD27 double-positive B cells (p<0.05 for all). CONCLUSIONS: This study reinforces existing evidence that a large proportion of PAD without claudication may be underdiagnosed, particularly in female and Black or African American participants. We describe a novel immunophenotypic profile of participants with PAD that could represent a potential future screening or diagnostic tool to facilitate earlier diagnosis of PAD. GOV IDENTIFIER: NCT03154346, https://clinicaltrials.gov/ct2/show/NCT03154346.

Using large language models to assess public perceptions around glucagon-like peptide-1 receptor agonists on social media.

BACKGROUND: The prevalence of obesity has been increasing worldwide, with substantial implications for public health. Obesity is independently associated with cardiovascular morbidity and mortality and is estimated to cost the health system over $200 billion dollars annually. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as a practice-changing therapy for weight loss and cardiovascular risk reduction independent of diabetes. METHODS: We used large language models to augment our previously reported artificial intelligence-enabled topic modeling pipeline to analyze over 390,000 unique GLP-1 RA-related Reddit discussions. RESULTS: We find high interest around GLP-1 RAs, with a total of 168 topics and 33 groups focused on the GLP-1 RA experience with weight loss, comparison of side effects between differing GLP-1 RAs and alternate therapies, issues with GLP-1 RA access and supply, and the positive psychological benefits of GLP-1 RAs and associated weight loss. Notably, public sentiment in these discussions was mostly neutral-to-positive. CONCLUSIONS: These findings have important implications for monitoring new side effects not captured in randomized control trials and understanding the public health challenge of drug shortages.

Obesity is a global public health burden that increases heart disease risk. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a class of medications originally developed for diabetes but are now used to improve lifespans in those with heart disease and increase weight loss. To better understand how the public views this type of drug, over 390,000 discussions from the social media platform Reddit were analyzed using computer software. Topics of discussion included experiences with weight loss, side effects of different GLP-1 RAs, and concerns about drug access and supply. The results showed a mainly neutral-to-positive view of these medications. The findings may help identify new side effects not previously seen in clinical trials and highlight future directions for research and public health efforts.

Digital Footprints of Obesity Treatment: GLP-1 Receptor Agonists and the Health Equity Divide.

Our research investigates the societal implications of access to glucagon-like peptide-1 (GLP-1) agonists, particularly in light of recent clinical trials demonstrating the efficacy of semaglutide in reducing cardiovascular mortality. A decade-long analysis of Google Trends indicates a significant increase in searches for GLP-1 agonists, primarily in North America. This trend contrasts with the global prevalence of obesity. Given the high cost of GLP-1 agonists, a critical question arises: Will this disparity in medication accessibility exacerbate the global health equity gap in obesity treatment? This viewpoint explores strategies to address the health equity gap exacerbated by this emerging medication. Because GLP-1 agonists hold the potential to become a cornerstone in obesity treatment, ensuring equitable access is a pressing public health concern.

The turnover of ABI5 by scaffold proteins to attenuate ABA signaling.

This article comments on: Li Z, Zhang D, Liang X, Liang J. 2024. Receptor for Activated C Kinase 1 counteracts ABSCISIC ACID INSENSITIVE5-mediated inhibition of seed germination and post-germinative growth in Arabidopsis. Journal of Experimental Botany 75, 3932-3945.

Lipoprotein(a) Levels in Disaggregated Racial and Ethnic Subgroups Across Atherosclerotic Cardiovascular Disease Risk Levels.

Background: Lipoprotein(a) [Lp(a)] is a causal risk factor for atherosclerotic cardiovascular disease (ASCVD). Objectives: The authors assessed differences in Lp(a) testing and levels by disaggregated race, ethnicity, and ASCVD risk. Methods: This was a retrospective cohort study of patients from a large California health care system from 2010 to 2021. Eligible individuals were ≥18 years old, with ≥2 primary care visits, and complete race and ethnicity data who underwent Lp(a) testing. Race and ethnicity were self-reported and categorized as follows: non-Hispanic (NH) White, NH-Black, Hispanic (Mexican, Puerto Rican, other), NH-Asian (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese, other). Logistic regression models tested associations between elevated Lp(a) (≥50 mg/dL) and race, ethnicity, and ASCVD risk. Results: 13,689 (0.9%) individuals underwent Lp(a) testing with a mean age of 54.6 ± 13.8 years, 49% female, 28.8% NH Asian. Over one-third of those tested had Lp(a) levels ≥50 mg/dL, ranging from 30.7% of Mexican patients to 62.6% of NH-Black patients. The ASCVD risk of those tested varied by race: 73.6% of Asian Indian individuals had <5% 10-year risk, whereas 27.2% of NH-Black had established ASCVD. Lp(a) prevalence ≥50 mg/dL increased across the ASCVD risk spectrum. After adjustment, Hispanic (OR: 0.76 [95% CI: 0.66-0.88]) and Asian (OR: 0.88 [95% CI: 0.81-0.96]) had lower odds of Lp(a) ≥50 mg/dL, whereas Black individuals had higher odds (OR: 2.46 [95% CI: 1.97-3.07]). Conclusions: Lp(a) testing is performed infrequently. Of those tested, Lp(a) levels were frequently elevated and differed significantly across disaggregated race and ethnicity groups. The prevalence of elevated Lp(a) increased with increasing ASCVD risk, with significant variation by race and ethnicity.

Inequities in atherosclerotic cardiovascular disease prevention.

Atherosclerotic cardiovascular (CV) disease (ASCVD) prevention encompasses interventions across the lifecourse: from primordial to primary and secondary prevention. Primordial prevention begins in childhood and involves the promotion of ideal CV health (CVH) via optimizing physical activity, body mass index, blood glucose levels, total cholesterol levels, blood pressure, and sleep while minimizing tobacco use. Primary and secondary prevention of ASCVD thereafter centers around mitigating ASCVD risk factors via medical therapy and lifestyle interventions. Disparities in optimal preventive efforts exist among historically marginalized groups in each of these three prongs of ASCVD prevention. Children and adults with a high burden of social determinants of health also face inequity in preventive measures. Inadequate screening, risk factor management and prescription of preventive therapeutics permeate the care of certain groups, especially women, Black, and Hispanic individuals in the United States. Beyond this, individuals belonging to historically marginalized groups also are much more likely to experience other ASCVD risk-enhancing factors, placing them at higher risk for ASCVD over their lifetime. These disparities translate to worse outcomes, with higher rates of ASCVD and CV mortality among these groups. Possible solutions to promoting equity involve community-based youth lifestyle interventions, improved risk-factor screening, and increasing accessibility to healthcare resources and novel preventive diagnostics and therapeutics.

Artificial Intelligence in Cardiovascular Disease Prevention: Is it Ready for Prime Time?

PURPOSE OF REVIEW: This review evaluates how Artificial Intelligence (AI) enhances atherosclerotic cardiovascular disease (ASCVD) risk assessment, allows for opportunistic screening, and improves adherence to guidelines through the analysis of unstructured clinical data and patient-generated data. Additionally, it discusses strategies for integrating AI into clinical practice in preventive cardiology. RECENT FINDINGS: AI models have shown superior performance in personalized ASCVD risk evaluations compared to traditional risk scores. These models now support automated detection of ASCVD risk markers, including coronary artery calcium (CAC), across various imaging modalities such as dedicated ECG-gated CT scans, chest X-rays, mammograms, coronary angiography, and non-gated chest CT scans. Moreover, large language model (LLM) pipelines are effective in identifying and addressing gaps and disparities in ASCVD preventive care, and can also enhance patient education. AI applications are proving invaluable in preventing and managing ASCVD and are primed for clinical use, provided they are implemented within well-regulated, iterative clinical pathways.

Shorter Door-to-ECG Time Is Associated with Improved Mortality in STEMI Patients.

Background: Delayed intervention for ST-segment elevation myocardial infarction (STEMI) is associated with higher mortality. The association of door-to-ECG (D2E) with clinical outcomes has not been directly explored in a contemporary US-based population. Methods: This was a three-year, 10-center, retrospective cohort study of ED-diagnosed patients with STEMI comparing mortality between those who received timely (<10 min) vs. untimely (>10 min) diagnostic ECG. Among survivors, we explored left ventricular ejection fraction (LVEF) dysfunction during the STEMI encounter and recovery upon post-discharge follow-up. Results: Mortality was lower among those who received a timely ECG where one-week mortality was 5% (21/420) vs. 10.2% (26/256) among those with untimely ECGs (p = 0.016), and in-hospital mortality was 6.0% (25/420) vs. 10.9% (28/256) (p = 0.028). Data to compare change in LVEF metrics were available in only 24% of patients during the STEMI encounter and 46.5% on discharge follow-up. Conclusions: D2E within 10 min may be associated with a 50% reduction in mortality among ED STEMI patients. LVEF dysfunction is the primary resultant morbidity among STEMI survivors but was infrequently assessed despite low LVEF being an indication for survival-improving therapy. It will be difficult to assess the impact of STEMI care interventions without more consistent LVEF assessment.

An "Inclisiran First" Strategy vs Usual Care in Patients With Atherosclerotic Cardiovascular Disease.

BACKGROUND: Most patients with atherosclerotic cardiovascular disease fail to achieve guideline-directed low-density lipoprotein cholesterol (LDL-C) goals. Twice-yearly inclisiran lowers LDL-C by ∼50% when added to statins. OBJECTIVES: This study evaluated the effectiveness of an "inclisiran first" implementation strategy (adding inclisiran immediately upon failure to reach LDL-C <70 mg/dL despite receiving maximally tolerated statins) vs representative usual care in U.S. patients with atherosclerotic cardiovascular disease. METHODS: VICTORION-INITIATE, a prospective, pragmatically designed trial, randomized patients 1:1 to inclisiran (284 mg at days 0, 90, and 270) plus usual care (lipid management at treating physician's discretion) vs usual care alone. Primary endpoints were percentage change in LDL-C from baseline and statin discontinuation rates. RESULTS: We randomized 450 patients (30.9% women, 12.4% Black, 15.3% Hispanic); mean baseline LDL-C was 97.4 mg/dL. The "inclisiran first" strategy led to significantly greater reductions in LDL-C from baseline to day 330 vs usual care (60.0% vs 7.0%; P < 0.001). Statin discontinuation rates with "inclisiran first" (6.0%) were noninferior vs usual care (16.7%). More "inclisiran first" patients achieved LDL-C goals vs usual care (<70 mg/dL: 81.8% vs 22.2%; <55 mg/dL: 71.6% vs 8.9%; P < 0.001). Treatment-emergent adverse event (TEAE) and serious TEAE rates compared similarly between treatment strategies (62.8% vs 53.7% and 11.5% vs 13.4%, respectively). Injection-site TEAEs and TEAEs causing treatment withdrawal occurred more commonly with "inclisiran first" than usual care (10.3% vs 0.0% and 2.6% vs 0.0%, respectively). CONCLUSIONS: An "inclisiran first" implementation strategy led to greater LDL-C lowering compared with usual care without discouraging statin use or raising new safety concerns. (A Randomized, Multicenter, Open-label Trial Comparing the Effectiveness of an "Inclisiran First" Implementation Strategy to Usual Care on LDL Cholesterol [LDL-C] in Patients With Atherosclerotic Cardiovascular Disease and Elevated LDL-C [≥70 mg/dL] Despite Receiving Maximally Tolerated Statin Therapy [VICTORION-INITIATE]; NCT04929249).

Atherosclerosis evaluation and cardiovascular risk estimation using coronary computed tomography angiography.

Clinical risk scores based on traditional risk factors of atherosclerosis correlate imprecisely to an individual's complex pathophysiological predisposition to atherosclerosis and provide limited accuracy for predicting major adverse cardiovascular events (MACE). Over the past two decades, computed tomography scanners and techniques for coronary computed tomography angiography (CCTA) analysis have substantially improved, enabling more precise atherosclerotic plaque quantification and characterization. The accuracy of CCTA for quantifying stenosis and atherosclerosis has been validated in numerous multicentre studies and has shown consistent incremental prognostic value for MACE over the clinical risk spectrum in different populations. Serial CCTA studies have advanced our understanding of vascular biology and atherosclerotic disease progression. The direct disease visualization of CCTA has the potential to be used synergistically with indirect markers of risk to significantly improve prevention of MACE, pending large-scale randomized evaluation.

Patient-Centered Adult Cardiovascular Care: A Scientific Statement From the American Heart Association.

Patient-centered care is gaining widespread acceptance by the medical and lay communities and is increasingly recognized as a goal of high-quality health care delivery. Patient-centered care is based on ethical principles and aims at establishing a partnership between the health care team and patient, family member, or both in the care planning and decision-making process. Patient-centered care involves providing respectful care by tailoring management decisions to patients' beliefs, preferences, and values. A collaborative care approach can enhance patient engagement, foster shared decision-making that aligns with patient values and goals, promote more personalized and effective cardiovascular care, and potentially improve patient outcomes. The objective of this scientific statement is to inform health care professionals and stakeholders about the role and impact of patient-centered care in adult cardiovascular medicine. This scientific statement describes the background and rationale for patient-centered care in cardiovascular medicine, provides insight into patient-oriented medication management and patient-reported outcome measures, highlights opportunities and strategies to overcome challenges in patient-centered care, and outlines knowledge gaps and future directions.

Cardiovascular Disease in Hispanic Women: JACC Review Topic of the Week.

Cardiovascular disease affects 37% of Hispanic women and is the leading cause of death among Hispanic women in the United States. Hispanic women have a higher burden of cardiovascular risk factors, are disproportionally affected by social determinants of health, and face additional barriers related to immigration, such as discrimination, language proficiency, and acculturation. Despite this, Hispanic women show lower rates of cardiovascular disease and mortality compared with non-Hispanic White women. However, this "Hispanic paradox" is challenged by recent studies that account for the diversity in culture, race, genetic background, country of origin, and social determinants of health within Hispanic subpopulations. This review provides a comprehensive overview of the cardiovascular risk factors in Hispanic women, emphasizing the role of social determinants, and proposes a multipronged approach for equitable care.

Statin utilization and cardiovascular outcomes in a real-world primary prevention cohort of older adults.

Background: Statins are a cost-effective therapy for prevention of atherosclerotic cardiovascular disease (ASCVD). Guidelines on statins for primary prevention are unclear for older adults (>75 years). Objective: Investigate statin utility in older adults without ASCVD events, by risk stratifying in a large healthcare network. Methods: We included 8,114 older adults, without CAD, PVD or ischemic stroke. Statin utilization based on ACC/AHA 10-year ASCVD risk calculation, was evaluated in intermediate (7.5%-19.9%) and high-risk patients (≥ 20%); and categorized using low and 'moderate or high' intensity statins with a follow up period of ∼7 years. Cox regression models were used to calculate hazard ratios for incident ASCVD and mortality across risk categories stratified by statin utilization. Data was adjusted for competing risk using Elixhauser Comorbidity Index. Results: Compared with those on moderate or high intensity statins, high-risk older patients not on any statin had a significantly increased risk of MI [HR 1.51 (1.17-1.95); p<0.01], stroke [HR 1.47 (1.14-1.90); p<0.01] and all-cause mortality [HR 1.37 (1.19-1.58); p<0.001] in models adjusted for Elixhauser Comorbidity Index. When comparing the no statin group versus the moderate or high intensity statin group in the intermediate risk cohort, although a trend for increased risk was seen, it did not meet statistical significance thresholds for MI, stroke or all-cause mortality. Conclusion: Lack of statin use was associated with increased cardiovascular events and mortality in high-risk older adults. Given the benefits appreciated, statin use may need to be strongly considered for primary ASCVD prevention among high-risk older adults. Future studies will assess the risk-benefit ratio of statin intervention in older adults.

Volcanic soil gas 4He/CO2 ratio: a useful geochemical tool for real-time eruption forecasting.

At many dormant volcanoes, magmatic gases are not channeled through preferential degassing routes as fumaroles and only percolate through the flanks of the volcano in a diffuse way. This type of volcanic gas emission provides valuable information, even though the soil matrix contains an important atmospheric component. This study aimed to demonstrate that chemical ratios such as He/CO2 in soil gases provide excellent information on the evolution of volcanic unrest episodes and help forecast the volcanic eruption onset. Before and during the occurrence of the October 2011-March 2012 submarine of El Hierro, Canary Islands, more than 8500 soil He analyses and diffuse CO2 emission measurements were performed. The results show that the soil He/CO2 emission ratio began increasing drastically one month before eruption onset, reaching the maximum value 10 days before. During the eruptive period, this ratio also showed a maximum value several days before the period with the highest magma emission rate. The He/CO2 ratio was also helpful in forecasting the eruption onset. We demonstrate that this tool can be applied in real-time during volcanic emergencies. Our results also encourage a reevaluation of the global He emission from the subaerial volcanism.

Patterns and gaps in guideline-directed statin use for atherosclerotic cardiovascular disease by race and ethnicity.

Objective: There remain disparities by race and ethnicity in atherosclerotic cardiovascular disease (ASCVD). Statins reduce low-density lipoprotein cholesterol (LDL-c) and improve ASCVD outcomes. ASCVD treatment patterns across disaggregated race and ethnicity groups are incompletely understood. We aimed to evaluate statin use and LDL-c control for ASCVD by race and ethnicity. Methods: From an electronic health record (EHR)-based cohort from a multisite Northern California health system, we included adults with an ASCVD diagnosis from 2010 to 2021 and at least 2 primary care visits, stratified by race and ethnicity (Non-Hispanic White [NHW], Non-Hispanic Black [Black], Hispanic, and Asian). Hispanic (Mexican, Puerto Rican, Other) and Asian (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese, Other) groups were disaggregated. Primary outcomes were 1-year post-ASCVD statin use (prescription) and LDL-c control (at least one value <70 mg/dL). Adjusted odds ratios (ORs) were estimated using logistic regression. Results: Of 133,158 patients, there were 89,944 NHW, 6,294 Black, 12,478 (9.4 %) Hispanic and 13,179 (9.9 %) Asian patients. At 1 year after incident ASCVD, there was suboptimal statin use (any statins <60 %, high-intensity <25 %) and LDL-c control (<30 %) across groups, with lowest proportions in Black patients for statin use (46.7 %, any statin) and LDL-c control (10.7 %, OR 0.89 (0.81-0.97), referent NHW). Disaggregation of Asian and Hispanic groups unmasked within-group heterogeneity. Conclusions: In patients with incident ASCVD, we describe suboptimal and heterogenous 1-year post-ASCVD guideline-directed statin use and 1-year post-ASCVD LDL-c control across disaggregated race and ethnicity groups. Findings may improve understanding of ASCVD treatment disparities and guide implementation.

Contemporary attitudes and beliefs on coronary artery calcium from social media using artificial intelligence.

Coronary artery calcium (CAC) is a powerful tool to refine atherosclerotic cardiovascular disease (ASCVD) risk assessment. Despite its growing interest, contemporary public attitudes around CAC are not well-described in literature and have important implications for shared decision-making around cardiovascular prevention. We used an artificial intelligence (AI) pipeline consisting of a semi-supervised natural language processing model and unsupervised machine learning techniques to analyze 5,606 CAC-related discussions on Reddit. A total of 91 discussion topics were identified and were classified into 14 overarching thematic groups. These included the strong impact of CAC on therapeutic decision-making, ongoing non-evidence-based use of CAC testing, and the patient perceived downsides of CAC testing (e.g., radiation risk). Sentiment analysis also revealed that most discussions had a neutral (49.5%) or negative (48.4%) sentiment. The results of this study demonstrate the potential of an AI-based approach to analyze large, publicly available social media data to generate insights into public perceptions about CAC, which may help guide strategies to improve shared decision-making around ASCVD management and public health interventions.

Racial and Ethnic Disparities in the Management of Chronic Coronary Disease.

Chronic coronary disease (CCD) comprises a continuum of conditions that include obstructive and non-obstructive coronary artery disease with or without prior acute coronary syndrome. Racial and ethnic representation disparities are pervasive in CCD guideline-informing clinical trials and evidence-based management. These disparities manifest across the entire spectrum of CCD management, spanning from non-pharmacological lifestyle changes to guideline-directed medical therapy, and cardiac rehabilitation to invasive procedures. Recognizing and addressing the historical factors underlying these disparities is crucial for enhancing the quality and equity of CCD management within an increasingly diverse population.