tbuckley/cabot-search huggingface dataset:
Abstract 4141690: Bisphosphonate therapy improves bone deficits but worsens arterial calcification in <i>Mgp</i> -null mice
Authors: Fariborz Soheili, Niloufar Heydarikhorneh, Benjamin Rotstein, Hsiao-huei Chen, Alexandre Stewart
Journal: Circulation (2024)

Background: Arterial calcification often occurs with bone mineral loss in osteoporosis, for which bisphosphonates are a standard therapy. Mice lacking the matrix GLA protein (Mgp) exhibit lethal arterial calcification and cranial bone formation deficits causing dental malocclusion. Mgp not only binds to hydroxyapatite but also inhibits the bone morphogenic protein activation of Runx2 transcription factor, which drives the osteogenic conversion of arterial smooth muscle cells (SMCs). Prior studies showed bisphosphate therapy ameliorates warfarin-induced arterial calcification in rats. This study investigated whether bisphosphonate (Alendronate,ALN) treatment could address bone deficits and arterial calcification in Mgp-null mice. Methods: Mgp-null mice were subjected to various doses of Alendronate therapy starting at weaning or postnatal day 3. Dental malocclusion severity was assessed by incisor trimming frequency. Arterial calcification was quantified by Alizarin red staining and µ-CT. Results: In Mgp-null mice, susceptibility to aortic artery calcification was not uniform but varied by location, with calcification highest at the proximal aorta. Of note, recurring nodes of calcification were found to correspond to branch points of vertebral arteries, with internodal regions showing less calcification. Alendronate therapy started at 3 weeks of age ameliorated dental malocclusion in Mgp-null mice of both sexes and improved but did not normalize body weight gain in males and females. However, no improvement in arterial calcification was observed at 7 weeks. Similarly, Alendronate therapy at lower doses from postnatal day 3 for 5 weeks ameliorated dental malocclusion and improved but did not normalize body weight gain in both sexes, while at higher doses, Alendronate prevented incisor development and caused growth retardation in both wild type and Mgp-null mice. However, Alendronate accelerated the appearance of Runx2 in SMCs of the aorta and worsened internodal arterial calcification in Mgp-null mice in a dose-dependent fashion, but not in Mgp-hemizygous or wild type mice. Conclusion: Our study reveals an important dichotomy in Mgp's function in bone and arteries. The bone deficits in Mgp-null mice, highlighted by incisor malocclusion, could be rescued by bisphosphonate treatment, whereas the arterial calcification could not. Thus, Mgp performs an essential function to prevent arterial calcification that cannot be restored by bisphosphonate therapy.
Abstract 4141680: Reduced Retinal Microvascular Density in Women with Coronary Microvascular Dysfunction: A Pilot Study
Authors: Sakshi Shiromani, Ahmed Al-Badri, Aaron Lindeke-Myers, Arielle Schwartz, Nishant Vatsa, Esha Dave, Fauzia Rashid, Nieraj Jain, Puja Mehta
Journal: Circulation (2024)

Introduction: Patients with myocardial ischemia but no obstructive coronary artery disease (INOCA) often have coronary microvascular dysfunction (CMD), which may be a manifestation of systemic vascular dysfunction. The state of retinal microvasculature is linked to a variety of cardiovascular risk factors, but the relationship between CMD and the retinal microvasculature is unknown. Research Question: Among individuals with INOCA, are retinal microvasculature changes reflective of CMD? Aim: To evaluate the retinal microvasculature in women with INOCA, comparing those with and without CMD. Methods: Women with INOCA (N=18) who had coronary function testing to evaluate for CMD were enrolled at Emory University between 2018-2021. Participants were classified into a CMD group and a non-CMD group, with CMD defined as coronary flow reserve (CFR) &lt;2.5 in response to adenosine. Participants underwent retinal optical coherence tomography angiography to assess the retinal microvasculature. Vessel density, perfusion density, as well as perimeter and circularity of the foveal avascular zone (FAZ) were obtained. Non-parametric statistics were used to compare the two groups. Results: Mean age was 54.7 (SD 12.5) years. The CMD (N=11) and non-CMD (N=7) groups were balanced with respect to age, BMI, and presence of systemic diseases including diabetes, hypertension, and hyperlipidemia. Those with CMD had a lower inner retinal vessel density [22.6(1) vs 21.2(0.5), p=0.006], lower full vessel density [21.2(0.6) vs 19.9(0.8), p = 0.008], lower inner perfusion density [41.1(0.8) vs 38.5(2.1), p=0.006] and lower full perfusion density [38.5(0.6) vs 36.1(1.8), p=0.007]. There were no differences in the FAZ perimeter or circularity between the two groups. Conclusions: In women with INOCA, those with CMD had a lower retinal microvascular density and perfusion density compared to non-CMD group. Direct, non-invasive, and relatively inexpensive imaging of the retinal microvasculature is feasible and may serve as a window to coronary microvascular function in women with INOCA; a larger study, including men, is needed to confirm these findings.
Abstract 4141541: Disparities in Achieving LDL-C Goals After Revascularization in a Diverse Real-World Cohort
Authors: Garred Greenberg, Daniel Lorenzatti, Annalisa Filtz, Vita Jaspan, Christine Park, Bethany Kalich, Niranjan Kathe, Katherine DiPalo, Constance Browne, Evan Lipsitz, Stephen Forest, Andrea Scotti, Azeem Latib, Mario Garcia, Carlos Rodriguez, Martha Gulati, Leandro Slipczuk
Journal: Circulation (2024)

Background: Guidelines and large clinical trials support the cardiovascular benefits of low-density lipoprotein cholesterol (LDL-C) testing and treatment with lipid-lowering therapies (LLT). Research Questions: What characteristics influence attainment of guideline recommended LDL-C goals in patients undergoing coronary (CAD) or peripheral arterial (PAD) revascularization? Goals: We analyzed the rates of LDL-C testing within 6 months and LDL-C goal attainment (&lt;70 mg/dL) in a cohort of patients undergoing CAD or PAD revascularization. Methods: We retrospectively analyzed 8,172 patients from a large health network who underwent percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), or peripheral artery revascularization from 2018-2023. Patients without follow-up LDL-C testing &gt;30 days after revascularization were excluded. The associations between clinical variables and LDL-C goal attainment were assessed with logistic regression analysis. Results: Only about half of the patients (4,319) had LDL-C tests &gt;30 days after their revascularization and were included in the analysis. The median age was 68 years, 2,729 (63%) were male, 1,848 (43%) were Hispanic, 928 (21%) were non-Hispanic Black and 663 (15%) were non-Hispanic White. Overall, 3,373 (78%) patients underwent PCI, 857 (20%) CABG, and 89 (2%) PAD revascularization. Median time to follow-up testing was 11 months (Panel A). Those with earlier follow-up testing, &lt;6 months (35%), had higher utilization of high-intensity statins, ezetimibe, and PCSK9 inhibitors. A follow-up LDL-C &lt;70 mg/dL was achieved in 2,259 (52%) patients with 1,294 (30%) having LDL-C &lt;55 mg/dL (Panel B). Female sex, non-Hispanic Black race/ethnicity, presence of obesity and longer time to LDL-C testing were independently associated with a lower likelihood of achieving LDL-C &lt;70 mg/dL after multivariable adjustment (Panel C) . Conclusions: LDL-C testing and guideline recommended goal attainment were low and female, non-Hispanic Black patients and those with obesity were less likely to reach optimal LDL-C values. Future preventive efforts must focus on efficiently standardizing and implementing an approach to LDL-C testing and lowering after revascularization.
Abstract 4141509: Hypocholesterolemic Effect of Dietary Stearic Acid Modulated by Alterations in Bile Acid and Cholesterol Metabolism in Post-Menopausal Women
Authors: Wen Zhang, Jean Galluccio, Gregory Matuszek, Gregory Dolnikowski, Alice Lichtenstein, Nirupa Matthan
Journal: Circulation (2024)

Background: Dietary stearic acid (18:0), a saturated fatty acid (SFA) commonly present in Western diets, has an LDL-C lowering effect compared to shorter chain SFAs such as palmitic acid (16:0), and a similar effect compared to oleic acid (18:1). However, the underlying mechanisms remain unclear. Hypothesis: We tested the hypothesis that the hypocholesterolemic effect of dietary 18:0 and 18:1 relative to 16:0 is modulated by alterations in cholesterol and bile acid (BA) metabolism. Methods: This secondary analysis used archived plasma and fecal samples from a randomized crossover feeding study (N=20 mildly hypercholesteremic postmenopausal women, 64±7 years, BMI 26.4±3.4kg/m 2 ). Participants consumed each of 3 isocaloric diets enriched in either 18:0, 16:0 or 18:1 for five weeks with a 2-week washout. Primary (P) and secondary (S) BAs, and their conjugates were measured in fecal, fasting and non-fasting (NF) plasma samples using the Biocrates MxP Quant 500 kit and Quadrupole Time-of-Flight mass spectrometry. Fasting and NF plasma cholesterol synthesis (lathosterol) and absorption (-sitosterol) markerswere quantified using gas chromatography. Mixed-effect and generalized linear mixed models were used to test the difference in outcome measures among diets, with Tukey-Kramer post hoc comparison. Spearman correlation coefficients with FDR adjustment was calculated between BA, cholesterol synthesis/absorption markers, and CVD risk factors. Results: Compared to the 16:0 diet, consumption of the 18:0 diet resulted in significantly lower fasting and NF plasma lathosterol (-22%); higher -sitosterol (19%); higher fecal PBAs (31%) and lower fecal SBAs (-17%) concentrations. Plasma PBAs were significantly lower in the fasted state (-34%), but higher in the NF state (21%; 18:0 vs. 16:0). Interestingly, conjugated PBA and SBA concentrations in the NF state were significantly higher after participants consumed the 18:0 compared to the 18:1 diet (all p &lt; 0.05). Plasma NF PBAs were positively associated with -sitosterol (r=0.56, p &lt; 0.05), while plasma fasting PBAs were negatively associated with lathosterol (r=-0.58, p &lt; 0.05). Conjugated PBA and SBA concentrations were negatively associated with LDL-C, hsCRP, E-selectin and insulin concentrations in the fasted but not NF state. Conclusion: The favorable effects of 18:0 on CVD risk factors may be modulated, in part, by changes in BA and cholesterol metabolism, with distinct effects in the fasted and NF states.
Abstract 4140907: Trends and Disparities of Ischemic Stroke–Related Mortality Among the Young Adults in the United States from 1999-2020
Authors: Jia Ee Chia, Song Peng Ang, Debabrata Mukherjee
Journal: Circulation (2024)

Background: Stroke remains a leading cause of mortality and morbidity globally, with a notably increasing incidence among young adults. Despite this trend, detailed insights into mortality trends specifically for young adults suffering from ischemic stroke (IS) are sparse. Methods: Leveraging data from the CDC's Wide-ranging Online Data for Epidemiologic Research database, we identified individuals aged 15 to 44 with IS-related mortality. We calculated age-adjusted mortality rates (AAMR) per million persons and analyzed annual percent changes. Subgroup analysis was conducted to examine differences by age, gender, race, and geographic region. Results: From 1999 to 2020, there were 9,906 ischemic stroke-related deaths among young adults. The overall AAMR for ischemic stroke-related mortality increased from 4.19 in 1999 to 5.20 in 2020 (p-trend&lt;0.001). Notably, men exhibited a higher AAMR (3.91 [95% CI, 3.81-4.01]) compared to women (3.19 [95% CI, 3.10-3.29]). Mortality rates peaked in the 35-44 year age group. Among racial groups, Black or African American individuals had the highest AAMR at 5.92 ([95% CI, 5.68-6.15]), significantly higher than White individuals (AAMR 3.25 [95% CI, 3.17-3.33]). Geographically, the Southern region of the U.S. recorded the highest AAMR (4.10 [95% CI, 3.98-4.23]). Conclusion: Our analysis reveals a concerning increase in ischemic stroke–related mortality among young adults in the United States. The data highlight significant disparities, with notably higher mortality rates among men and Black or African American individuals. Furthermore, pronounced geographical variations in mortality rates emphasize the necessity for targeted, region-specific public health interventions to address these disparities effectively.
Abstract 4140823: Differences Exist in Cardiovascular Death among Asian Heritage Groups Based on Nativity Status in the US: Analysis of 1999-2018 National Health Interview Survey
Authors: Arshia Ramesh, Chitchanok Benjasirisan, Arum Lim, Suratsawadee Kruahong, Yuling Chen, Bunmi Ogungbe, Ruth-Alma Turkson-Ocran, Yvonne Commodore-Mensah, Binu Koirala
Journal: Circulation (2024)

Background: Asians are the fastest-growing population in the United States (US). Cardiovascular disease (CVD) remains the leading cause of disability and death among persons of Asian heritage in the US. Certain groups of Asian heritage may be at disproportionately high risk of CVD and all-cause death. Hypothesis: We hypothesize that there is heterogeneity in CVD and all-cause death among disaggregated Asian heritage groups (Chinese, Filipino, and Asian Indian, and others) based on nativity status (US- vs Foreign-born). Methods: The study analyzed pooled data from the 1999-2018 National Health Interview Survey linked with the National Death Index. The outcomes were CVD death (disease of heart and cerebrovascular disease deaths, based on ICD-10) and all-cause death, in years, derived from the time of interview to the year of death or December 31, 2019 (last date of follow-up). Survey-weighted Cox regression models were used to explore differences in CVD and all-cause death among Asian heritage groups, controlling for covariates (age, sex, marital status, poverty-income ratio, and education). Results: The study included 37,104 Asian adults (21.8% Chinese, 33.5% Filipino, and 44.6% Asian Indians and others). Over a median follow-up of 11 years (Interquartile range: 7-15), there were 1.7 CVD deaths and 5.6 all-cause deaths per 1,000 person-years. The fully adjusted model revealed a 33% lower CVD death hazard among foreign-born Filipino adults (Hazard Ratio [HR]: 0.67; 95% Confidence Interval [CI]: 0.49–0.91) compared to their US-born counterparts. Similarly, for all-cause death, foreign-born Asian Indians exhibited a 40% lower hazard (HR: 0.60; 95% CI: 0.48-0.74), and Filipinos showed a 33% lower hazard (HR: 0.67; 95% CI: 0.51-0.88) when compared to their US-born counterparts. Conclusion: There was heterogeneity in CVD and all-cause death among Asian heritage groups. Overall, CVD and all-cause death were lower among foreign- than US-born adults specifically among Filipino and Asian Indian and others. These findings warrant the targeted implementation of evidence-based approaches to CVD prevention and promotion.
Abstract 4141290: The Role of Automated External Defibrillator Use in the Out-of-Hospital Cardiac Arrest Survival Rate and Outcome: A Systematic Review
Authors: Mohamed Elhussain, Fatima Ahmed, Nafisa Mustafa, Doaa Mohammed, Ibrahim Berkiah, Namariq Alnaeim, Ragda Ali, Noura Mohyeldeen, Hassan Ahamed, Fatima Elataya, Nadir Abdelrahman
Journal: Circulation (2024)

Background: Out-of-hospital cardiac arrest (OHCA) is a leading cause of mortality worldwide, with prompt defibrillation being crucial for improving survival rates. Public access defibrillators (PADs) offer a means for rapid intervention outside hospital settings. This systematic review evaluates the effectiveness of PADs in OHCA scenarios. Method: A systematic review was conducted following PRISMA guidelines. Global studies from 2000 onwards assessing bystander and emergency medical service (EMS) interventions during OHCA, particularly focusing on AED usage, were included. Data synthesis and quality assessment were performed using established frameworks, including Covidence for screening and the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) framework for risk of bias assessment. Results: Thirty studies met inclusion criteria. PAD deployment significantly improved survival outcomes, with better results observed in public settings compared to private residences. Bystander-initiated defibrillation correlated with higher survival rates and improved neurological outcomes. School and airport settings demonstrated particularly favorable outcomes due to AED accessibility and trained personnel. The combination of CPR and AED use by bystanders markedly increased survival chances compared to EMS intervention. The difference in survival rates between bystander-initiated defibrillation and EMS intervention ranged from 5% to 42%. Regarding neurological outcomes, the difference between bystander-initiated defibrillation and EMS intervention ranged from 16.4% to 34%. Discussion: The review underscores the critical role of immediate bystander response and PAD accessibility in OHCA survival. Strategic AED placement in high-risk areas and widespread CPR training are essential for enhancing outcomes. Challenges include variable data collection methods and limited benefits in certain OHCA scenarios. Conclusion: Bystander interventions, including CPR and AED usage, significantly increase OHCA survival rates. Promoting widespread CPR training, strategic AED placement, and continuous outcome monitoring are vital for improving OHCA outcomes. Further research is warranted to address challenges and optimize intervention strategies.
Abstract 4141272: Trends in Cancer Versus Cancer with Heart Failure Related Mortality in the United States from 1999-2020. A CDC WONDER Database Analysis
Authors: Faizan Ahmed, TEHMASP MIRZA, Brijesh Patel, Muhammad Abdullah Naveed, Salman Abdul Basit, Farman Ali, Syed Ishaq, Usman Akbar, Mobeen Haider, yasar sattar, Faisal Khosa
Journal: Circulation (2024)

Aims: This study aimed to analyze two decades of consecutive mortality data to investigate the association between cancer and cancer with heart failure across the United States (US), discerning patterns and disparities in mortality rates. Methods: Data were obtained from the multiple cause of death files using CDC WONDER spanning 1999 to 2020; ICD-10 codes were used to identify cancer and cancer with heart failure related deaths in adults aged ≥25. Demographic and regional distributions of mortality were analyzed. Joinpoint regression analysis was used to determine trends in age-adjusted mortality rates (AAMR) to estimate annual percentage changes (APC). Results: Between 1999 and 2020, 14,309,991 cancer-related deaths occurred in the US out of which 612,346 were associated with cancer and heart failure. The overall AAMR per 100,000 for cancer-related deaths decreased from 353.9 in 1999 to 260.9 in 2020 characterized by an annual percentage change (APC) of -1.60 spanning from 1999 to 2018, and an APC of 0.58 thereafter till 2020. AAMR per 100,000 for heart failure and cancer-related deaths decreased from 16.1 to 14.0, with varied APCs, declining from 1999 to 2013, reaching a minimum AAMR of 11 followed by a rise from 2013 to 2020. For cancer related only, men accounted for 52.7% of deaths, compared to 47.3% for women. Similarly, cancer with heart failure had mortality higher in males. Non-Hispanic (NH) White and Hispanic populations had the highest AAMRs for cancer related mortality while NH White and NH American Indian or Alaskan Native had the highest mortality in cancer with heart failure. Regional differences were observed, with the most cancer-related deaths observed in the South while the most cancer with heart failure related deaths occurred in the Midwest. State-wise stratification further supported the difference. Conclusions: Cancer-related mortality is decreasing while cancer with heart failure related mortality is increasing following initial decline. The highest AAMRs were observed for cancer related mortality among NH White population, men, people living in the South; and non-metropolitan US while cancer with heart failure had highest mortality in NH White population, men, people living in Midwest; and non-metropolitan areas. The findings underscore the need for focused interventions aimed at reducing mortality related to cancer and cancer with heart failure, particularly among vulnerable populations.
Abstract 4140929: The Usefulness of the Quick Forrester Classification with Respiratory Rate and Serum Lactate Levels for Predicting Decreased Left Ventricular Function in Patients with ST-elevation Myocardial Infarction
Authors: Yosuke Matsumoto, Shoji Kawakami, Hidenobu Koga, Tetsuhisa Yamada, Jun-ichiro Nishi
Journal: Circulation (2024)

Background: Although respiratory rate (RR) is one of the vital signs, few studies have evaluated the association between respiratory rate at hospital arrival and clinical outcomes in patients with ST-elevation myocardial infarction (STEMI). Serum lactate levels, which can be rapidly measured in the emergency department, have been reported to be associated with prognosis in STEMI patients with or without cardiogenic shock. We hypothesized that profiling by RR, which reflects hypoxia or metabolic acidosis, and serum lactate level, which reflects tissue perfusion, at hospital arrival named the Quick Forrester Classification (QFC), would be associated with clinical outcomes in STEMI patients. Methods: This is a retrospective analysis of STEMI patients between 2018 and 2023. Patients were divided into 4 classifications: RR &lt;22/min and lactate &lt;2.0mmol/L (Class-1), RR ≧22/min and lactate &lt;2.0mmol/L (Class-2), RR &lt;22/min and lactate ≧2.0mmol/L (Class-3), RR ≧22/min and lactate ≧2.0mmol/L (Class-4) as the QFC. The primary outcome was decreased cardiac function (left ventricular ejection fraction [LVEF] less than 45% measured during hospitalization). Results: Of 592 STEMI patients (age, 71±13 years; male, 72%), 569 patients were classified by QFC (Class-1, n=156; Class-2, n=52; Class-3, n=213; Class-4, n=148). The proportion of patients with decreased cardiac function increased from 15% in Class-1, 13% in Class-2, 16% in Class-3 to 30% in Class-4 (P=0.003 for trend). Multivariable analysis revealed that a patient in QFC Class-4 was a significantly predictor of decreased LVEF when compared with a patient in QFC Class-1(Odds ratio [OR] 2.29, 95% confidence interval [CI] 1.15-4.55, p=0.018) as were age (OR 1.03, 95%CI 1.01-1.06, p=0.003), heart rate at hospital arrival (OR 1.03, 95%CI 1.02-1.05, p&lt;0.001), and anterior wall infarction (OR 2.21, 95%CI 1.31-3.73, p=0.003). Conclusion: In STEMI patients, the QFC with RR and serum lactate level at hospital arrival was significantly associated with decreased LVEF.