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BACKGROUND: The ISCHEMIA trial (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) demonstrated greater health status benefits with an initial invasive strategy, as compared with a conservative one, for patients with chronic coronary disease and moderate or severe ischemia. Whether these benefits vary globally is important to understand to support global adoption of the results. METHODS: We analyzed participants' disease-specific health status using the validated 7-item Seattle Angina Questionnaire (SAQ: >5-point differences are clinically important) at baseline and over 1-year follow-up across 37 countries in 6 international regions. The average effect of initial invasive versus conservative strategies on 1-year SAQ scores was estimated using Bayesian proportional odds regression and compared across regions. RESULTS: Considerable regional variation in baseline health status was observed among 4617 participants (mean age=64.4±9.5 years, 24% women), with the mean SAQ summary scores of 67.4±19.5 in Eastern Europe participants (17% of the total), 71.4±15.4 in Asia-Pacific (18%), 74.9±16.7 in Central and South America (10%), 75.5±19.5 in Western Europe (26%), and 78.6±19.2 in North America (28%). One-year improvements in SAQ scores were greater in regions with lower baseline scores with initial invasive management (17.7±20.9 in Eastern Europe and 11.4±19.3 in North America), but similar in the conservative arm. Adjusting for baseline SAQ scores, similar health status benefits of an initial invasive strategy on 1-year SAQ scores were observed (ranging from 2.38 points [95% CI, 0.04-4.50] in North America to 4.66 points [95% CI, 2.46-6.94] in Eastern Europe), with an 88.3% probability that the difference in benefit across regions was <5 points. CONCLUSIONS: In patients with chronic coronary disease and moderate or severe ischemia, initial invasive management was associated with a consistent health status benefit across regions, with modest regional variability, supporting the international generalizability of health status benefits from invasive management of chronic coronary disease. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01471522.

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Introduction: Lower statin utilization is reported among women compared to men, however large-scale studies evaluating gender disparities in LDL-C management in individuals with ASCVD and its subtypes remain limited, particularly across age and racial/ethnic subgroups. In this study, we address this knowledge gap using data from a large US healthcare system. Methods: All adult patients with established ASCVD in the Houston Methodist Learning Health System Registry during 2016-2022 were included. Statin use and dose were extracted from the database. The association between gender and statin utilization was evaluated using multivariate logistic regression analyses in patients with ASCVD overall, across ASCVD subtypes, and by age, racial/ethnic subgroups, and socioeconomic risk factors. Results: A total of 97,819 patients with prevalent ASCVD were included. Women with ASCVD had lower utilization of any statin (64.3% vs 72.6 %; p < 0.001) and high-intensity statin (29.8% vs 42.5 % p < 0.001) compared with men. In fully adjusted models, women had 40 % lower odds of any (adjusted odds ratio [aOR]:0.58, 95 % CI 0.57-0.60) and high-intensity statin use (aOR:0.59, 0.57-0.61) relative to men. Women were also less likely to have guideline-recommended LDL-C < 70 mg/dL (30.2% vs 42.7 %; p < 0.01). These differences persisted across age, racial/ethnic and socioeconomic subgroups. Conclusion: Significant gender disparities exist in contemporary lipid management among patients with ASCVD, with women being less likely to receive any and high-intensity statin and achieving guideline defined LDL-C goal compared with men across age and racial/ethnic subgroups. These disparities underscore the need to further understand potential socioeconomic drivers of the observed lower statin uptake in women.

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Objective: Apolipoprotein B (ApoB) and lipoprotein (a) (Lp[a]) are predictors of cardiovascular disease (CVD) risk; therefore, current recommendations for CVD risk assessment and management advocate that patients receive testing for ApoB and Lp(a) in addition to the standard lipid panel. However, US guidelines around ApoB and Lp(a) testing have evolved over time and vary slightly by expert committee. The objective of this analysis was to estimate the number of insured individuals in the USA who received any component of a lipid test, or ApoB and/or Lp(a) testing, during 2019. Methods: We conducted a cross-sectional analysis to estimate the prevalence of any component of a lipid test, ApoB, and/or Lp(a) in the USA using four different claim data sources (including Medicaid, Medicare, and commercially insured enrollees). Prevalence estimates were age-, sex-, payor-, and region-standardized to the 2019 US Annual Social and Economic Supplement of the Current Population Survey. We also described the clinical profile of patients who received lipid testing between 2019 and 2021 (cohort analysis) in Optum claims database. Enrollees were grouped into four non-mutually exclusive cohorts based on their completion of any component of the lipid panel, ApoB, Lp(a), or ApoB and Lp(a). Results: In the prevalence cohort, over a third (38 %) of insured adults in the USA underwent testing for any component of a lipid panel in 2019. This proportion was higher for individuals aged ≥65 years compared to younger adults (62% vs 31 %). The proportion of ApoB and Lp(a) testing represented only <1 % of testing for any component of a lipid panel. In the cohort analysis, we found that lipid testing increased with age and comorbidities. Conclusion: These data should be considered by guideline-issuing agencies and organizations to develop education campaigns encouraging more frequent use of tests beyond the standard lipid panel.

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Carpal tunnel syndrome (CTS) is the most frequent entrapment neuropathy. Patients commonly experience neuropathic pain, leading them to seek medical advice. However, other symptoms experienced in patients with CTS, such as paresthesia, dysesthesia and allodynia, classed as positive sensory symptoms (PSS), are often under-reported. In the present study, patients with surgically-managed CTS were observed pre- and post-surgery to evaluate PSS, using the symptoms scale component of the Boston Carpal Tunnel Questionnaire (BCTQ) and the Sensory Frequency of Symptoms Scale. In total, 19 patients were included in the present study, with 79% female patients, and a mean age of 54±10.59 years. In addition, the mean follow-up was 63±29.91 months. The results of the present study revealed a pre-surgery BCTQ score of 3.52±0.63 and a post-surgery BCTQ score of 1.58±0.61. Notably, improvements in pain were observed, at 7.7±2.26 pre-surgery compared with 1.65±2.88 post-surgery. Compared with pre-surgery, post-surgery paresthesia scores were reduced from 2.94±0.82 to 0.47±0.45, dysesthesia scores were reduced from 2.52±0.84 to 0.47±0.39 and allodynia scores were reduced from 0.63±0.75 to 0.26±0.47. In conclusion, the results of the present study demonstrated that median nerve decompression ameliorated CTS symptoms, such as paresthesia and dysesthesia. However, further investigations are required to verify the benefits of surgery in relieving allodynia.

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BACKGROUND: Disparities in guideline-based quality measures likely contribute to differences in heart failure (HF) outcomes. We evaluated between- and within-hospital differences in the quality of care across sex, race, ethnicity, and insurance for patients hospitalized for HF. METHODS: This retrospective analysis included patients hospitalized for HF across 596 hospitals in the Get With the Guidelines-HF registry between 2016 and 2021. We evaluated performance across 7 measures stratified by patient sex, race, ethnicity, and insurance. We evaluated differences in performance with and without adjustment for the treating hospital. We also measured variation in hospital-specific disparities. RESULTS: Among 685 227 patients, the median patient age was 72 (interquartile range, 61-82) and 47.2% were women. Measure performance was significantly lower (worse) for women compared with men for all 7 measures before adjustment. For 4 of 7 measures, there were no significant sex-related differences after patient-level adjustment. For 20 of 25 other comparisons, racial and ethnic minorities and Medicaid/uninsured patients had similar or higher (better) adjusted measure performance compared with White and Medicare/privately insured patients, respectively. Angiotensin receptor neprilysin inhibitor measure performance was significantly lower for Asian, Hispanic, and Medicaid/uninsured patients, and cardiac resynchronization therapy implant/prescription was lower among women and Black patients after hospital adjustment, indicating within-hospital differences. There was hospital-level variation in these differences. For cardiac resynchronization therapy implantation/prescription, 278 hospitals (46.6%) had ≥2% lower implant/prescription for Black versus White patients compared with 109 hospitals (18.3%) with the same or higher cardiac resynchronization therapy implantation/prescription for Black patients. CONCLUSIONS: HF quality measure performance was equitable for most measures. There were within-hospital differences in angiotensin receptor neprilysin inhibitor and cardiac resynchronization therapy implant/prescription for historically marginalized groups. The magnitude of hospital-specific disparities varied across hospitals.

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Background: Patients are increasingly using online reviews to evaluate cardiologists. Online reviews can provide insights into factors driving patient satisfaction. Little is known about the effects of age and sex on the patient experience with cardiologists. Objectives: The purpose of this study was to apply natural language processing techniques on online reviews to determine the factors underlying positive and negative patient experiences and the effects of age and sex on the patient experience with cardiologists. Methods: Mixed effects logistic regression and sentiment analysis were applied to online cardiologist reviews from Healthgrades between 1998 and 2023. The results were then analyzed by sex and age to show trends with respect to rating statistics, sentiment analysis, and frequency of 2-word phrases. Results: There were 100,334 online reviews of 9,461 cardiologists. Female cardiologists received lower average ratings compared to male cardiologists and were 34.5% less likely to receive a positive review (OR: 0.655; 95% CI: 0.481-0.893; P = 0.015). Older cardiologists received lower average ratings compared to younger cardiologists (4.145 ± 0.908 vs 4.348 ± 0.795; P < 0.01). Positive reviews were associated with time spent with patients (OR: 1.383; 95% CI: 1.251-1.528; P < 0.01), answering questions (OR: 2.622; 95% CI: 2.324-2.959; P < 0.01), and patients feeling they could trust their providers' decisions (OR: 2.285; 95% CI: 2.053-2.543; P < 0.01). Conclusions: Positive reviews were associated with cardiologists being comprehensive and patients feeling a sense of trust in the relationship. There was a difference in ratings based on age and sex with female and older cardiologists receiving lower ratings.

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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, multicenter, 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 < .001), hypertension (54% vs 30%, P < .001), diabetes (25% vs 14%, P = .031), and at least moderate coronary calcifications (Agatston score >100: 32% vs 17%, P = .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 < .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 < .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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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).

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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.

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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.

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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.

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