tbuckley/cabot-search huggingface dataset:
Abstract 14353: Deficiency of Protein Kinase Cδ Revamps Atherosclerotic Plaque Complexity by Halting Inflammasome Activation and Intensifying Mitochondrial Function
Authors: Chih-Feng Lien, CHIN LIN, Chin-Sheng Lin
Journal: Circulation (2023)

Introduction: Plaque complexities substantially contribute to acute coronary syndrome. Inflammation and cell death in macrophages play a vital role in the formation of vulnerable plaques. Previous study had shown that protein kinase Cδ (PKCδ) is involved in the initiation and progression of atherosclerosis. However, the role of PKCδ on plaque stability remains unclear. Hypothesis: PKCδ regulates macrophage inflammation and cell death, leading to the formation of vulnerable plaques. Methods: The PKC family gene expressions in human atheroma plaques and nearby macroscopically intact tissues were analyzed from the gene expression omnibus data sets GSE43292. Two main mice models, including Ldlr -/- / PKCδ -/- mice and Ldlr -/- mice lethally irradiated and bone marrow transplanted (BMT) with either PKCδ -/- or wild type (WT), were applied to evaluate the impact of macrophages PKCδ on atherosclerosis. Blood, aorta, and aortic sinus were collected. The effects and underlying molecular mechanisms of PKCδ on inflammasome activation, pyroptosis, and mitochondrial function were explored using bone marrow-derived macrophage (BMDM) from PKCδ -/- and WT mice. Results: The gene expression of PKCδ significantly increases in human atheroma plaques, which is correlated with the expression of NLRP3 inflammasome. The deletion of PKCδ reduces plasma lipid profile and atherosclerosis in Ldlr -/- mice. Moreover, the deletion of PKCδ attenuates necrotic core formation, in both double knockout and BMT models. The RNA-seq analysis revealed that pyroptosis and mitochondrial oxidative phosphorylation (OXPHOS) are the potential mechanisms in PKCδ-regulated atherosclerosis. Additionally, knockout of PKCδ reduces expressions of LPS/IFNγ-induced TNFα, IL-6, and NLRP3 inflammasome in BMDM. Finally, the deficiency of PKCδ increases mitochondrial OXPHOS in BMDM, suggesting a potential role for PKCδ in the regulation of cellular metabolism and inflammation. Conclusions: Our findings indicate a crucial role for PKCδ in the development of complex atherosclerotic plaques, as it promotes inflammation, pyroptosis, and mitochondrial dysfunction. Targeting PKCδ could potentially be a therapeutic strategy for the treatment of atherosclerosis.
Abstract 13220: Independent Effects of Baseline Pulse Wave Velocity versus Advancing Age on Changes in Arterial Stiffness Over Time
Authors: Gayathri Basker, Keerthana Thangaraja, Fei Gao, Ru S Tan, Gina S Lee, Charmaine Cheng, See H Ewe, Loon Yee Teo, Angela S Koh
Journal: Circulation (2023)

Introduction: While arterial stiffness (AS) is a known marker of vascular ageing that prognosticates cardiovascular disease (CVD), prospective analyses of AS evolution alongside chronological age are necessary to understand factors that drive progressive AS. Using pulse wave velocity (PWV) we investigated the impact of baseline factors in predicting PWV changes over a 5-year period. Hypothesis: We hypothesized that certain baseline factors in older Asian adults are predictive of PWV trajectories later in life independent of chronological age. Methods: Participants without CVD from a community-based cohort had their clinical risk factors collected prospectively, and PWV (m/s) measured using a cuff-based oscillometric pulse wave analysis machine at baseline and 5-year timepoint. Results: This analysis included 159 participants (41.5% women, mean age 67.7 ± 10.2 years). ΔPWV (2.19 ± 2.25), the 5-year change in PWV, was associated with baseline PWV (β = -0.687, p &lt; 0.001), age (β = 0.084, p &lt; 0.001), hypertension (β=0.763, p = 0.033), weight (β = -0.042, p = 0.018) and waist circumference (β = -0.045, p = 0.018). Gender, body mass index, dyslipidemia, diabetes mellitus and lifetime smoking status were not significantly associated with ΔPWV. ΔPWV was independently associated with baseline PWV (β = -1.17, 95% CI -1.65 - -0.70, p &lt; 0.001) and age (β = 0.144, 95% CI 0.09 - 0.20, p &lt; 0.001) adjusting for weight, waist circumference and hypertension, with insignificant interaction between baseline PWV and age (p = 0.431). Participants with increases in PWV after 5 years, compared to those without PWV increase, had lower PWV (8.52 ± 1.81 vs 11.10 ± 2.44) at baseline. Conclusions: Baseline PWV was associated with changes in AS over a 5-year period independent of age and clinical risk factors. The inverse relationship between baseline PWV and ΔPWV may suggest plateauing of PWV increases at higher baseline PWV levels. In addition, high baseline PWV may not predict worsening of AS later in life.
Abstract 18392: Sedentary Behavior and Risk of 1-Year Cardiac Events and Mortality After Suspected Acute Coronary Syndrome
Authors: Keith M Diaz, Benjamin Boudreaux, Chang Xu, Gabriel Sanchez, Margaret Murdock, Gaspar Cruz, Ammie Jurado, Alvis Gonzalez, Julia Ellis, Franchesca Diaz, Melinda Chang, Emily Romero, Allie Scott, Alexandra Sullivan, Andrea Duran, Ian M Kronish, Donald Edmondson
Journal: Circulation (2023)

Background: Patients hospitalized with acute coronary syndrome (ACS) remain at high risk for recurrent cardiac events in the first year after discharge, necessitating a need to identify modifiable targets to improve outcomes. While moderate-vigorous physical activity (MVPA) is a hallmark of secondary prevention in this population, sedentary behavior (SB) has emerged as a potentially unique aspect of the physical activity profile that may also have prognostic relevance. Yet little is known regarding whether SB confers risk independent from MVPA and what types of activity should be substituted for SB to impart health benefit among ACS patients in the first year after discharge. Aim: Examine the association between SB and risk of 1-year cardiac events and mortality among patients evaluated for ACS. Methods: Patients (n=609, 52% male, 62 ± 13 y) evaluated in the emergency room for ACS were fitted with a GENEActiv wrist accelerometer in-hospital and wore the device for 30 days post discharge to measure SB, light intensity physical activity (LIPA), MVPA, and sleep. Major adverse cardiovascular events 1-year post discharge were defined as the composite of unstable angina, myocardial infarction, or death. Results: Over follow up, 50 patients (8%) had a major adverse cardiovascular event. SB was associated with an increased risk of 1-year major adverse cardiovascular events after adjusting for demographic and disease severity indicators (HR per 1 h/d increase: 1.33, 95% CI: 1.12, 1.58). The association remained significant after adjusting for MVPA (HR per 1 h/d increase: 1.30, 95% CI: 1.06, 1.59). In isotemporal substitution analyses there were beneficial associations for replacing SB with sleep (per 30 min HR: 0.89, 95% CI: 0.81, 0.97), LIPA (per 30 min HR: 0.51, 95% CI: 0.34, 0.76), and MVPA (per 30 min HR: 0.32, 95% CI: 0.12, 0.85) on 1-year major adverse cardiovascular event risk. Conclusion: SB was associated with increased risk of 1-year cardiac events and mortality among patients evaluated for ACS, independent of MVPA. Replacing SB with sleep, LIPA, or MVPA was associated with lower risk. These findings suggest reducing SB may improve outcomes in ACS survivors and support the public health message that ACS patients should sit less and move or sleep more to mitigate risk.
Abstract 16267: Burden of Cardiovascular Disease in Sub-Saharan Africa
Authors: Laith Alhuneafat, Omar Al Taani, Adee Elhamdani, Tala Altarawneh, Abdallah Naser, Fares Ghanem, Rand Al-Adayleh, Majd Al Ahmad, Mohannad Al Akeel, ahmad jabri
Journal: Circulation (2023)

Introduction: This study aims to explore the burden of cardiovascular disease (CVD) and associated risk factors in Sub-Saharan Africa (SSA) using data from the Global Burden of Disease (GBD). Hypothesis: That the burden of CVD has increased in SSA over time, and there are associated risk factors contributing to this burden. Methods: We analyzed CVD prevalence, mortality, and incidence in 46 SSA countries using Bayesian regression, demographic methodologies, and mortality-to-incidence ratios. Disability-adjusted life years (DALYs) were calculated, and risk factors were assessed through the comparative risk assessment framework of the GBD. Results: Between 1990 and 2019, CVD prevalence in SSA increased by 131.7%, with a modest rise of 2.1% in age-standardized prevalence rates. Ischemic heart disease, stroke (CVA), and rheumatic heart disease were the most prevalent conditions. CVD deaths increased from 564,140 to 1,003,893, with a 14.4% decrease in death rates. Non-rheumatic valvular disease showed a significant increase. DALYs increased by 68.4%, but some CVDs saw decreases in DALY rates. Conclusions: Despite rising CVD prevalence in SSA, age-standardized rates only modestly increased. However, the persistently high burden, increasing non-rheumatic valvular disease, and rising DALYs highlight challenges in prevention and management. These findings highlight the persistent challenge of CVD in SSA and emphasize the need for continued efforts in prevention and management strategies to address the growing burden of CVD in this region.
Abstract 18555: Global Burden of Congenital Heart Disease and Its Trend From 1990-2019 in 38 OECD Countries: A Benchmarking Analysis for the Global Burden of Disease Study
Authors: Hardik Y Patel, RANI RATHEESH, . Anum, Anjani Kumar Thota, Shasank V Rachapudi, Jobby John, Viswaja Koppana, Khawaja Muthammir Hassan, HARDIK D DESAI
Journal: Circulation (2023)

Introduction: Congenital heart disease (CHD) is the 1st leading cause of deaths among all deaths associated with congenital birth defects in (Organization for Economic Cooperation and Development) OECD countries, constituting a significant health concern that imposes a substantial burden on healthcare systems and society. Methods: Using the Global Burden of Disease methodology, this study assesses the prevalence, incidence, mortality, and disability-adjusted life years (DALYs) associated with CHD in 38 OECD countries by sex, year, and location, covering the period from 1990 to 2019. The results are presented in both all age counts and age standardized rates (ASR) per 100,000 person-years. Results: From 1990 to 2019, the total number of prevalent cases of CHD increased from 1,469,128 (95%UI: 1,292,909-1,671,743) to 1,590,654 (1,387,114-1,815,338). In contrast, CHD-related deaths decreased from 37,291 (31,629-47,869) in 1990 to 13,886 (10,668-16,919) in 2019. The annual percentage of change (APC) in age-standardized mortality (ASMR) decreased by 60%, while the ASIR showed almost no change but decreased by 3%. Notably, the highest APC in ASIR was observed in Czechia (27%), Sweden (21%), Hungary (18%), and the United States (11%), while Turkey (28%) and Canada (21%) had the lowest APC increases. The highest APC increase in ASIR among females was observed in France (29%) Conclusions: Despite a decrease in the burden of CHD over the last three decades, it remains a significant concern in OECD countries. The impact of CHD is felt by individuals, families, healthcare systems, and the economy, emphasizing the ongoing need for comprehensive strategies to address this burden.
Abstract 14767: Obesity is Associated With Greater Intensity of Guideline Recommended Therapy in Patients With Heart Failure With Reduced Ejection Fraction in the CHAMP-HF Registry
Authors: Mirza S Khan, Timothy J Fendler, Javed Butler, Adam D Devore, Gregg C Fonarow, John A Spertus
Journal: Circulation (2023)

Introduction: Despite the importance of guideline-directed medical therapy (GDMT) in heart failure with reduced ejection fraction (HFrEF), treatment disparities by sex, race and age have been described. We hypothesized obesity might also be associated with less aggressive GDMT, due to both the difficulty of assessing volume status in obese patients and the challenge of separating the symptoms of obesity from those of HFrEF. We recently developed an intuitive measure for quantifying GDMT, the Kansas City Medical Optimization (KCMO) score, which is the average of total daily to target dose percentages for eligible GDMT drug classes, reflecting the percent of optimal GDMT prescribed (range 0-100%). Aim: To examine the association between BMI and KCMO score, accounting for other factors influencing GDMT use. Methods: Using the CHAMP-HF registry, we applied the KCMO score as the dependent variable and BMI as the primary predictor in a hierarchical linear regression model with site-level random effects to account for clustering by site, and adjusting for age, sex, SBP, CKD, and KCCQ-12 scores. We also fit a separate model using WHO BMI classes in place of BMI. Non-linear associations were tested with restricted cubic splines. Results: Among 4,163 patients across 150 sites in the CHAMP-HF registry, we found a significant and positive association between BMI and KCMO score (β BMI = 0.40, SE = 0.06; p &lt; 0.001). Compared to those with normal BMI, those with Class I-III obesity had higher KCMO scores by 3.95 ± 1.16, 6.11 ± 1.44, and 8.68 ± 1.53, respectively ( p &lt; 0.001 for each). Conclusions: Patients with HFrEF and higher BMIs received more intense GDMT. It remains to be seen whether this may contribute to the known “obesity paradox” in HFrEF, where higher BMI is associated with lower mortality. Further study is also needed to examine whether obese patients with HFrEF receive similar intensity and extent of treatment in regard to decongestive strategies.
Abstract 15365: The Effect of Mobile Phone Messaging in the Reduction of Ambulatory Blood Pressure in Adults: A Systematic Review
Authors: Michael Brouner, Jared Ridgeway, Rex Farris, Charlie Sang, Ross Hansen, James Hammock, Mohammed Siddiqui, Elizabeth A Jackson
Journal: Circulation (2023)

Introduction: Ample evidence supports a lower risk for cardiovascular disease (CVD) with controlled blood pressure (BP), yet hypertension (HTN) remains a leading cause of CVD. Mobile health such as text messaging is commonly included in BP management programs; however, the association of texting with BP interventions is less well known. We sought to examine the effectiveness of mobile messaging on BP in adults in the ambulatory setting. Methods: In this systematic review, we searched 4 databases from date of inception through February 2023 using search terms (texting, messaging, mobile phone, BP, HTN). After removing duplicate citations, two reviewers independently reviewed the references for eligibility (randomized control trial [RCT], participants &gt; 18 years of age, participants either with elevated BP, and/or a diagnosis of HTN). Results: A total of 1,786 RCTs were identified of which 48 met eligibility criteria, for a combined total of 19,720 participants from 21 countries, including 13 US studies. Twenty-seven studies reported significant reductions in BP (systolic, diastolic or both). All three RCTs using texting and pharmacist counseling (n=3) demonstrated significant changes in BP, while 13 of 16 RCTs with texting and provider involvement observed significant improvement in BP. For the studies reporting between group changes in systolic BP from baseline, 7 studies noted significant improvements in BP (Figure 1). Conclusions: Despite heterogeneity in study components, we found text messaging when used with other intervention components was associated with BP reductions among adults with HTN. Larger studies using novel designs such as SMART (sequential multiple assignment randomized trials) are warranted to understand efficacy of texting with other intervention components.
Abstract 17773: Novel Partition Scores Identify Pathways Implicated in Clonal Hematopoiesis of Indeterminate Potential (CHIP) Mediated Heart Failure
Authors: Nathan Chen, Miles Shen, Veena Rao, Juan Ivey Miranda, Zhen Tan, Wei Wei, Jeffrey M Testani, Stephanie Halene, Jianlei Gu, Hongyu Zhao, John Hwa, Alokkumar Jha, Jennifer M Kwan
Journal: Circulation (2023)

Background: Peripheral blood somatic genetic variants such as those in clonal hematopoiesis of indeterminate potential (CHIP) increase the risk of both ischemic and non-ischemic cardiomyopathy but mechanisms beyond inflammation are unclear. Research question/Objectives: We sought to understand the prevalence and impact of CHIP and extended somatic variants (ExSV) using a new deep learning algorithm in heart failure patients on the outcome of all-cause mortality and leverage novel partition scores to identify pathways involved. Methods: CHIP and ExSV were evaluated using a novel proprietary deep learning algorithm in a heart failure cohort at Yale using whole exome sequencing and somatic variants identified were validated using UKB and TOPMED cohorts. Cox regression including somatic variants on the outcome of death was performed. Partition score analysis integrating patient demographics, co-morbidities, genomic and transcriptomic data was performed to identify traits and biological pathways implicated in heart failure Results: CHIP was highly prevalent in the 189 patient Yale heart failure cohort at 42% with mean age of 66. Fifty percent had diabetes and 46% had CAD. Using UKB and TOPMED cohorts, novel “CHIP-like” somatic variants were identified that conferred increased or decreased risk of heart failure. Some ExSV were associated with increased risk of death. Partition score assessment identified top traits associated with increased risk of heart failure, including LDL, triglycerides, diabetes, BMI and CAD and pathway analysis identified that metabolic pathways including cholesterol metabolism, glucose signaling and AMPK were implicated in the heart failure phenotype mediated by somatic variants (Table). Conclusions: CHIP and ExSV are prevalent in heart failure patients, impact the outcome of death and metabolic pathways are implicated in mediating the effects of somatic variants/CHIP in heart failure
Abstract 18083: Surgical vs. Endovascular Revascularization for Chronic Limb Threatening Ischemia: A Meta-Analysis of Randomized Controlled Trials
Authors: Syed H Mufarrih, Mohammad Saud Khan, Nada Q Qureshi, Muhammad Akbar, Mohammed Kazimuddin, Herbert D Aronow
Journal: Circulation (2023)

Background: Timely revascularization is essential for limb salvage and to reduce mortality in patients with chronic limb threatening ischemia (CLTI). The optimal revascularization strategy, in patients who are candidates for surgical bypass and endovascular therapy, remains uncertain, despite recent publication of 2 randomized controlled trials (RCTs). Research Question: Do outcomes differ following surgical and endovascular revascularization for CLTI? Methods: PubMed, Web of Science and the Cochrane Library were searched to identify RCTs comparing outcomes of endovascular versus surgical revascularization for CLTI. Data were pooled for major outcomes including mortality, re-intervention, major amputation, and major adverse cardiovascular events (MACE). Aggregate risk ratios with 95% confidence intervals were calculated using a random-effects model. Results: Three RCTs with 2,627 patients (1,312 endovascular; 1,315 surgical) were included in the meta-analysis. Of these, 1,864 (70.9%) of patients were male and 347 (13.2%) were older than 80 years of age. When comparing endovascular and surgical revascularization, there was no significant difference in 30-day mortality (RR: 0.74 [0.38,1.48], p=0.40), long- term mortality (RR: 1.02 [0.87, 1.19], p=0.82), re-intervention (RR: 1.24 [0.74, 2.07], p=0.41), major amputation, (RR: 1.16 [0.87, 1.54], p=0.31), therapeutic cross-over (RR: 0.92 [0.37, 2.26], p=0.85), or MACE (RR: 1.07 [0.92, 1.26], p=0.37). Conclusion: Current data suggest there is no difference in outcome following endovascular and surgical revascularization for CLTI. A planned patient-level meta-analysis may provide further insight.
Abstract 18509: NT-proBNP Trajectories and Heart Failure Risk Associations in Middle to Older Ages in Adulthood: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Bige Ozkan, Noelle Pavlovic, Vijay Nambi, Justin B Echouffo, Xiaoming Jia, Christie M Ballantyne, Amil M Shah, Roger S Blumenthal, Kuni Matsushita, Elizabeth Selvin, Josef Coresh, Chiadi E Ndumele
Journal: Circulation (2023)

Background: NT-proBNP is a powerful marker of heart failure (HF) risk. NT-proBNP levels increase with age; however, the impact of distinct longitudinal trajectories of NT-proBNP on future HF risk with aging is largely unexplored. Hypothesis: Middle-aged adults with higher baseline concentrations and steeper increases of NT-proBNP through older ages have greater HF risk. Methods: We performed a prospective analysis of 12,124 ARIC participants with 2 or more serial NT-proBNP measurements from Visits 2 through 6, without HF at baseline or HF events between the NT-proBNP assessments. We constructed linear mixed models to evaluate NT-proBNP trajectories for males and females. We defined 4 trajectories, using sex-specific medians to define high versus low: low baseline/low slope, low baseline/high slope, high baseline/low slope, high baseline/high slope. We used Kaplan Meier survival curves and multivariable Cox regression to evaluate the HF risk associations of different NT-proBNP trajectories. Results: The mean age was 57 years with 56% women and 23% Black adults, BMI 27. The median baseline NT-proBNP concentrations were 62 and 36 pg/mL and the average NT-proBNP slopes were 4.6% and 7.2% increase/year for women and men, respectively. Black individuals were more likely to have lower baseline levels, whereas those with diabetes, obesity, or prevalent coronary heart disease had higher slopes. Over a median 22-year follow-up, 2,772 HF events occurred. There was a stepwise increase in HF risk with higher baseline levels and slopes of NT-proBNP, with individuals with the high baseline/high slope NT-proBNP trajectory having a HR for HF of 3.70 (95% CI 3.26-4.20) compared to those with low baseline-low slope ( Figure ). Conclusions: Higher baseline concentrations and steeper increases of NT-proBNP with aging are associated with greater HF risk. Identifying and addressing modifiable determinants of NT-proBNP trajectories with aging may have implications for HF prevention.