tbuckley/cabot-search huggingface dataset:
Abstract 13658: Cholesterol Content of Lipoprotein Particles and Progression of Coronary Artery Calcification From Different Methods in ELSA-Brasil Study - A Metabolomic Approach
Authors: William Tebar, Vandrize Meneghini, Giuliano Generoso, Alexandre Pereira, Marcio Bittencourt, Itamar S Santos, Paulo A Lotufo, Isabela M Bensenor
Journal: Circulation (2023)

Background: Cholesterol content (CC) of lipoprotein particles is heterogeneous according to size and type. Research Question: The association of CC with carotid artery calcium (CAC) progression in different subclasses is not established. Aim: To analyze the association between CC of lipoprotein particles and CAC progression in ELSA-Brasil cohort study. Methods: Data from 883 participants (50.5±7.3 years, 50.7% women) without cardiovascular disease and statin use were analyzed. The CC in mmol/l was assessed by high-throughput proton Nuclear Magnetic Resonance metabolomics platform in 14 subclasses according to type and size at baseline. A 5-year CAC progression was assessed by computed tomography and calculated by log transformed, square root transformed and by methods of Hokanson and of Berry. The association of CC with CAC progression was analyzed by generalized linear models adjusted by sociodemographic (age, sex, race, education, health insurance), lifestyle (physical activity, alcohol consumption, smoking), comorbidities (hypertension, diabetes, obesity and total cholesterol ≥200mg/dL) and further adjusted by particle concentration. Results: A total of 15.6% of sample (n=138) presented a positive follow-up CAC score. The CC of medium VLDL, IDL, and LDL (large, medium and small) was associated with CAC progression by Berry method - Table 1. However, only the CC in medium VLDL (β=3.059 [95%CI: 0.040; 6.078], p=0.047) and large LDL (β=1.007 [95%CI: 0.342; 1.673], p=0.003) remained associated after adjustment for particle concentration. The CC of small HDL was associated with CAC progression by square root method (β=13.427 [95%CI: 0.487; 26.367], p=0.042), but lost significance after adjustment for particle concentration. Conclusions: The CC of medium VLDL and large LDL was associated with CAC progression by Berry method, beyond sociodemographic, lifestyle, comorbidities and particle concentration in a subsample of ELSA-Brasil participants.
Abstract 18186: Four Chambers Strain Analysis in Patients Admitted With Acute Heart Failure: A New Characterization of Heart Involvement?
Authors: Laurie Soulat-Dufour, Ania Bourai, Sylvie Lang, Elodie Capderou, Stephane EDERHY, Saroumadi ADAVANE, Marion Chauvet-Droit, Camille Arnaud, Pauline Issaurat, Stéphanie Jullien, Chloé Cardoso, Manon Gerard, Ghassen Cherif, Karima Addetia, Franck Boccara, Patrick Assyag, Roberto Lang, Ariel Cohen
Journal: Circulation (2023)

Introduction: In heart failure (HF), most of the data available on myocardial strain focused on the left ventricle (LV). Very few data concern the other cavities. Hypothesis: We hypothesized that all cardiac cavities are involved in HF and thus we evaluated all chambers strain profiles in patients admitted with acute HF. Methods: We prospectively evaluated 95 patients hospitalized for HF. Patients were divided into preserved left ventricle ejection fraction (LVEF) (LVEF ≥50%, HFpEF n=24), mildly reduced LVEF ((LVEF 41-49%, HFmrEF n=17), and reduced left ventricular ejection fraction (LVEF) (LVEF ≤40%, HFrEF n=54). In addition to the usual two-dimensional echocardiographic parameters, LV global longitudinal strain, left and right atrial strain (reservoir, conduit, contractile strain), right ventricular free wall strain were determined using speckle tracking transthoracic echocardiography at admission. Results: Patients with HFrEF were younger in comparison with patients with HFmrEF and HFpEF, (respectively 66.3 ± 14.2, 78.3.0 ±8.7, 75.6 ± 10.2 years p&lt;0.001). Table 1 summarizes the main Doppler and echocardiographic comparisons. Myocardial strain analyses demonstrated that patients with HFrEF had significant lower LV global, right ventricular strain, left atrial reservoir strain, left and right atrial conduit strain (Figure 1). Conclusions: Beyond the alteration of LV function, HFrEF involves alteration of right ventricle, left and right atrial functions. Strain analysis is an interesting tool in addition to conventional echocardiographic parameters to assess heart function in heart failure. The prognostic impact of these finding remains to be studied.
Abstract 15468: Factor VII Induced Coronary Thrombosis
Authors: Bala Pushparaji, Supraja Achuthanandan, Nikhil Cordeiro, Nicole S De Leon De La Cruz, Arsalan Hashmi, Michael Friedman
Journal: Circulation (2023)

Case Description: 69-year-old male with a history of factor VII deficiency and coronary artery disease (CAD) with a stent in the distal left anterior descending (LAD) artery, underwent diagnostic laparoscopy for suspected appendiceal carcinoma. He is a non-smoker, has good exercise tolerance and takes aspirin only three times a week, due to epistaxis. Post-surgery, he complained of 10/10 substernal chest pain. Initial troponin (TnI) was 0.11 ng/dL, peaking at &gt;80 ng/dL in 2 hours. EKG was compatible with an anterior wall STEMI. An emergent coronary angiogram showed a patent distal LAD stent and a 99% occlusive lesion in the mid-LAD, which was treated with a drug-eluting stent. With careful clinical judgment and hematology consultation, dual antiplatelet therapy was continued despite a history of coagulopathy. On probing, it was discovered that the patient received two doses of recombinant factor VII (rVII) prior to the surgery to reduce operative bleeding. Discussion: Recombinant factor VII is known to cause serious arterial and venous thromboembolic events. This risk increases to almost 10% in patients who are elderly with concomitant vascular disease. In our patient with prior history of CAD and in the setting of acute surgical stress, exogenous factor VII unbalanced the coagulation system leading to a STEMI. Surgical teams should be aware of the detrimental consequences of administration of rVII in high cardiovascular risk patients and seek alternative hemostatic strategies. Prothrombotic agents should be used with caution and close monitoring for acute coronary syndromes, especially in patients with a high risk of CAD.
Abstract 13940: Remnant Lipoprotein Particles and Cholesterol Contribute to Proatherogenic Phenotype and Subclinical Inflammation in Youth-Onset Type 2 Diabetes
Authors: Aruba Chowdhury, Faith Davis, Andrea Krenek, Sydney Dixon, Lilian Mabundo, Stephanie T Chung
Journal: Circulation (2023)

Introduction: Youth-onset type 2 diabetes (YT2D) is a rapidly progressive disease characterized by severe insulin resistance (IR), elevated triglyceride concentrations, and low HDL-cholesterol (-C). However, the contribution of triglyceride-rich remnant lipoproteins (TRLp) and remnant-C to overall atherogenic risk in YT2D is unknown, especially in the absence of clinically relevant elevations in LDL-C. Hypothesis: We hypothesized that YT2D would have higher remnant TRLp, remnant-C, and greater subclinical inflammation and IR compared to healthy peers with obesity. Methods: We measured fasting lipoprotein particle size and number, GlycA (a composite marker of inflammation), and lipoprotein IR index (LPIR) using NMR LipoProfile® in 61 YT2D (age 17.2 ±2.9 y, mean±SD, BMI 39.1 ±8.4 kg/m2) and 25 healthy peers (age 17.9 ± 5.1 y, BMI 35.8 ±5.7 kg/m2). Remnant Lp (small TRLp plus very small TRLp) and remnant-C (total-C minus HDL-C minus LDL-C) were calculated and the relationship with GlycA and LPIR determined by spearman correlations. Results: YT2D had higher HemoglobinA1c (7.6 ± 2.0 vs 5.8 ± 0.8%), GlycA (427 [388, 474] vs 376 [332, 406] nmol/L, median[25th,75th]), LPIR (53.7 ± 23.6 vs 29.6 ± 16.5). YT2D had higher remnant TRLp and remnant-C (Figure 1) and a more proatherogenic lipid and lipoprotein profile: LDL-C: 89 ± 23 vs 74 ± 20 mg/dL; total LDLp: 1392 ±368 vs 1075 ±289 nmol/L; small LDLp: 890 ±450 vs 519 ±232 nmol/L, all P&lt;0.01. LPIR was associated with remnant-C (r=0.6, P&lt;0.001) but not with LDL-C (r=0.1, P=0.6). GlycA was associated with remnant-C, remnant TRLp, and small LDLp (all r≥0.3, P&lt;0.01). Conclusion: The proatherogenic profile in YT2D is characterized by higher small LDLp, remnant TRLp, and remnant-C and is related to IR and subclinical inflammation compared to healthy peers with obesity. Future research is needed to determine whether reducing all proatherogenic lipoproteins and inflammation will reduce ASCVD risk.
Abstract 13159: Inverse Relationship Between Genetic Predisposition to Hyper- and Hypo- Cholesterolemia and Incident Type 2 Diabetes
Authors: Akshaya Ravi, Satoshi Koyama, So Mi J Cho, Sara Haidermota, Whitney Hornsby, Patrick T Ellinor, Pradeep Natarajan
Journal: Circulation (2023)

Introduction: High cholesterol and type 2 diabetes mellitus (T2DM) share metabolic and environmental risk factors. Nevertheless, previous literature suggests an inverse association between monogenic/polygenic hypercholesterolemia and T2DM prevalence. We investigated the extent to which polygenic and monogenic hyper- and hypo-cholesterolemia contributes to incident T2DM in a large prospective cohort. Hypothesis: We hypothesized that genetic predisposition to blood cholesterol would associate with incident T2DM risk. Methods: UK Biobank participants who underwent whole-exome sequencing and genome-wide genotyping were included. Based on the Cox proportional hazards model, the associations of familial hypercholesterolemia (FH), polygenic risk scores (PRS) for low-density lipoprotein cholesterol (LDLC), and APOB and PCSK9 predicted loss of function (pLOF) variants with incident T2DM after adjusting for age, sex, genotyping array, lipid-lowering medication use, and the first ten genetic principal components. Results: Among the 443,428 participants, 2,357 (0.56%) had FH and 1,280 (0.30%) had APOB or PCSK9 pLOF variants; the remaining 425,710 (99.13%) were categorized based on LDLC-PRS percentile. Individuals with FH or higher LDLC-PRS had lower risk of incident T2DM. In contrast, individuals with lower LDLC-PRS and APOB and PCSK9 pLOF had an increased risk of T2DM. Conclusions: Monogenic and polygenic risks for increasing and decreasing LDLC were inversely associated with T2DM risk.
Abstract 18108: Statin Biotransformation and 5-Year Cardiovascular Outcomes in the SAPhIRE Multicentre Observational Trial
Authors: Eugene C goh, Lik Hang Wu, Leroy sivappiragasam Pakkiri, Mei Li Ng, Jielin Yang, Maya George, Folefac Aminkeng, Jianjun Liu, E Shyong Tai, Jack W Tan, Chester L Drum
Journal: Circulation (2023)

Importance: Individual variation in statin biotransformation may explain differences in clinical outcomes but remains poorly understood. Objectives: To quantify statin biotransformation phenotypes in cardiology patients and validate predictors of 5-year clinical outcomes in two independent cohorts. Design: SAPhIRE is a multicentre, prospective, observational trial of 1363 general cardiology patients taking atorvastatin or simvastatin. The study was initiated in 2014. Sample collection was completed in 2016, and outcomes of participants were followed-up to June 2020 via the Singapore National Registry of Diseases Office (NRDO). Setting: Participants were enrolled across the National University Hospital of Singapore (NUH) and Singapore General Hospital (SGH). Pharmacologic, genotypic, and mechanistic predictors of 5-year clinical outcomes were determined using clinical data, quantitative mass spectrometry and GWAS. Main Outcome(s): Major Adverse Cardiovascular Events (MACE) via linkage with NRDO. Risk analysis (multivariable Cox hazards modelling, univariable Kaplan Meier) was used to assess association of metabolism, genomics, and co-prescriptions on 5-year outcomes. Results: In both independent cohorts, increased statin lactone production of the upper tertile (ATVLAC≥3.9ng/ml) predicted MACE (HR=2.45, CI=1.60-3.44, P&lt;0.001) and all-cause mortality (HR=3.18, CI=1.96-5.16, P&lt;0.001), independently of LDL and drug dose. UGT1A, a lactone-producing gene, associated with ATVLAC at genome-wide significance. In a candidate gene analysis of UGT1A, UGT1A1*80-associated GOF mutations (rs887829, rs11891311, rs6742078, rs4148324, rs4148325 and rs10929302) predicted 1.34-fold higher ATVLAC compared to major allele homozygotes, and after controlling for clinical variables, exhibited higher rates of MACE (average HR=1.40, p&lt;0.05). Among 51 co-prescriptions, omeprazole was the strongest predictor of increased ATVLAC (1.41-fold, P&lt;10-8) and MACE (HR=1.46, CI=1.06-2.00, P=0.020). Conclusion: A phenotype of low statin lactone production predicts preferential cardiac outcomes in two-thirds of statin takers and is influenced by both UGT1A variation and omeprazole co-prescription.
Abstract 16581: Impact of Drug Eluting Stent Deployment and Calcification on Worsening Target Lesion Failure in Femoropopliteal Lesions
Authors: Yuta Azumi, Tatsuya Nakama
Journal: Circulation (2023)

Introduction: Endovascular therapy (EVT) with drug coated balloon (DCB) has been proven superior to balloon angioplasty only in the patency rate. EVT with drug eluting stent (DES) also has shown to be superior to balloon angioplasty only or implantation of bare metal stents. Primary patency of EVT in femoropopliteal lesions (FP-EVT) for DES and DCB is around 80%-90% at 12 months respectively. Therefore, the use of drug technology for FP-EVT is reasonable and generally accepted. However, in daily clinical practice, some target lesion failure (TLF) cases show worse clinical and/or angiographic conditions than the original before the intervention, and many of those cases have bad outcomes. There are no reports on predictors of the worse condition. Methods: A total of 292 consecutive FP lesions of 194 patients who visited our hospital from April 2017 to March 2021 and underwent FP-EVT with drug technologies (DES: 104, DCB: 188) were retrospectively reviewed. "Worsening target lesion failure (WTLF)" was defined as TLF with acute limb ischemia symptom or occlusion of the lesion which had been stenosis at the initial treatment. We investigated the predictor of WTLF. Results: The mean age of all study patients was 72.5±9.3 years and 68% were male. During the follow-up period (median: 568 days), 13 WTLFs were observed. 9 (8.7%) cases were treated with DES and 4 (2.1%) were with DCB at the initial treatment (p=0.01). Cases with WTLF had severer and longer calcification (bilateral calcification: 84.6% vs. 47.7%, p=0.007; calcium length: 162±74mm vs. 85±11mm, p=0.005). Multivariate Cox regression analysis indicated that DES use (Hazard ratio (HR)=4.66, 95% confidence interval [1.28-16.92], p=0.046) and bilateral calcification (HR=7.21, [1.04-50.14], p=0.020) were independently associated with the occurrence of the WTLF. The prevalence of composite outcome, major amputations and all cause deaths, was 54% in the group with WTLF, which was higher than the group without WTLF (p=0.02). Conclusions: Patients with WTLF had bad outcomes. Bilateral calcification and DES deployment were associated with an increased risk for WTLF. For stenotic lesions with bilateral calcification, it may be better to avoid DES deployment.
Abstract 14760: Elevated Heart Rate at Diagnosis is Associated With Adverse Outcomes in Peripartum Cardiomyopathy
Authors: Julia Berkowitz, Emilija Sagaityte, Zoltan Arany, Natalie A Bello, Gaurav Choudhary, Luc Djousse, Katharine French, Jacob Joseph, Mahnoor Khalid, Diana Lopez, Donya Mohebali, Athena Poppas, Marwa Sabe, Wen-Chih "Hank" Wu, Tasnim F Imran
Journal: Circulation (2023)

Introduction: Understanding predictors of adverse outcomes in patients with peripartum cardiomyopathy (PPCM) is essential to inform clinical practice and improve outcomes. Aim: The aim of this study is to examine the relationship between heart rate (HR) at diagnosis and adverse outcomes in PPCM. Methods: We conducted a multi-center cohort study to identify patients with PPCM (1993-2017) who met the inclusion criteria: left ventricular ejection fraction (LVEF) &lt;40%, development of heart failure within the last month of pregnancy or 5 months of delivery, and no other identifiable cause of heart failure with reduced ejection fraction. The primary composite outcome of major adverse events included heart failure hospitalization, need for extra-corporeal membrane oxygenation, left ventricular assist device, orthotopic heart transplant, or all-cause death. Using Cox proportional hazards models, we examined the relationship between categories of HR at diagnosis and adverse outcomes. Results: A total of 177 women met criteria (81 with HR &lt;100bpm, 54 with HR 100-119bpm, 42 with HR ≥120bpm) with a mean age of 33 ± 7 years and median follow up 3.4 years (IQR 1.0-8.8); 48 (27%) experienced the composite outcome. In a multivariable model adjusting for age, race, preeclampsia or hypertension, women with HR ≥ 120 bpm were four times more likely to experience major adverse events compared to women with HR &lt; 100 bpm (HR 4.1, 95% CI 1.6- 10.4). HR was significantly associated with LVEF in age adjusted linear regression (F= 39.1, p &lt;0.001). Patients with HR &lt;100 bpm were significantly more likely to have survival free from adverse events in survival analysis (logrank p= 0.03, Fig 1). Conclusions: Tachycardia may be an early prognostic indicator of adverse outcomes in PPCM and could identify high risk patients who may benefit from close follow-up and early intervention.
Abstract 11402: Impact of the Severe Familial Hypercholesterolemia Status on Atherosclerotic Risks
Authors: Hayato Tada, Kenji Sakata, Soichiro Usui, Masa-aki Kawashiri, Masayuki Takamura
Journal: Circulation (2023)

Background and aims: Risk of atherosclerotic events substantially vary even among patients with familial hypercholesterolemia (FH) with extremely high risk based on life-long exposure to elevated LDL cholesterol. We aimed to examine impact of the severe FH status defined by the International Atherosclerosis Society (IAS). Methods: The data of patients with FH (N = 1,050, male = 490) who were admitted to Kanazawa University Hospital between 2000 and 2020 and who were followed-up were retrospectively reviewed. The number of MACEs, including mortality associated with cardiovascular disease, acute coronary syndrome, and ischemic heart disease requiring coronary revascularization per 1,000 person-years, was calculated. In addition, hazard ratio was calculated using Cox proportional model. Results: Overall, we identified 545 patients (51.9 %) with severe FH in this population. The median follow-up duration was 12.6 years. In total, 171 MACEs were recorded during the follow-up period. We found that severe FH was significantly associated with MACE (hazard ratio = 6.48, 95% confidence interval = 2.56 - 10.40, P = 1.2 х 10 -5 ). The event rates per 1,000 person-years for in the primary prevention group (non-severe FH and severe FH) were 0.0 and 15.6, respectively. The event rates per 1,000 person-years in the secondary prevention group (non-severe FH and severe FH) were 2.0 and 32.3, respectively. Conclusion: Patients with severe FH exhibited significant higher risks in primary as well as secondary prevention settings. This simple criterion provides us useful information to identify patients with even higher risk who may need further managements.
Abstract 16437: An Infectious Rise in Fats - Severe Hypertriglyceridemia Secondary to SARS-CoV-2 Infection
Authors: Vasili Katsadouros, Erik C Hoffman
Journal: Circulation (2023)

Intro There are many complications because of COVID-19 infections. These have ranged from organ dysfunctions to severe disease states. The global nature of SARS-CoV-2 pandemic has allowed clinicians to discover new pathophysiology associated with infections. We present a case of a patient with severe hypertriglyceridemia (HTG) after a SARS COVID-19 infection and propose a correlation between his infection and elevated triglyceride (TG) levels. Case A 64 y/o man living with a history of HFpEF, COPD, and HLD presented to our clinic after being diagnosed with SARS-CoV-2 infection two days prior. He had upper respiratory symptoms of a productive cough, fevers, decreased appetite, and mild dyspnea with exertion not requiring supplemental oxygen. He was prescribed paxlovid and discharged home. On follow up his symptoms had improved. He was due for a repeat lipid level and this was drawn during his visit. His last lipid panel results were normal. His repeat TG was 2,186 mg/dL. It was thought his levels were elevated because of his SARS-CoV-2 infection. His fasting TG levels were repeated and found to have normalized with a low-fat diet alone and had no further interventions. Discussion There have been few reports demonstrating a rise in TG levels after SARS-CoV-2 infections. Hepatic injury secondary to the infection or medications prescribed for treatment may lead to elevated TGs levels. When these are excluded, it is unknown what leads to HTG. Studies have evaluated lipoprotein lipase (LPL) activity levels and how they were decreased after SARS-CoV-2 infections. LPL assists in the metabolism of TG’s and activity is decreased in many disease states. It is thought that the COVID-19 infection causes HTG secondary to acquired LPL deficiency. These patients require close monitoring to decrease complications. Conclusion HTG is known to cause increased incidence of pancreatitis and ASCVD events. While treating these, one must assess the underlying etiology that led to the disease state. In patients found to have elevated TG levels it is important to include questions pertaining to recent infectious processes. Further research is needed to deduce how infectious processes can lead to elevated TG levels. Treatment consists of initiating a low-fat diet and may include fibrates.
Abstract 17921: Diastolic Dysfunction Might Predict Outcomes in Acute Coronary Syndrome Patients Undergoing Primary Percutaneous Coronary Intervention
Authors: Prakash Upreti, Muhammad Saad, Neelanjana Pandey, Nassim R Krim, Timothy Vittorio
Journal: Circulation (2023)

Introduction: Acute coronary syndrome (ACS) leads to diastolic dysfunction which might cause unfavorable long-term clinical outcomes. We aim to evaluate the association between diastolic parameters in patients with an ACS and event rates including 30-day mortality and 6-month readmission rates. Methodology: We studied 1579 patients with ACS who underwent primary percutaneous coronary intervention (PCI) from January 1, 2010 through December 31, 2020. Clinical, laboratory, transthoracic echocardiographic (TTE) and coronary angiographic parameters were retrospectively reviewed. Diastolic parameters (E/A ratio, TR velocity, LVEF and LAVI) in patients with left anterior descending artery (LAD) PCI (n=879) were compared with those who underwent PCI to non-LAD artery (n=700). Percentage of 6-month all-cause readmission, cardiogenic shock as well as mortality rates were calculated in both cohorts. Results: The mean age of 1579 ACS patients was 65 + 12 years, BMI 29 + 5 kg/m 2 , peak high sensitivity troponin 624 ng/L, E/A ratio 1.065, TR velocity 3.2 m/s, LAVI 34.26 mL/m 2 and LVEF 50.1%. The percentage of hospital readmission within 6 months was higher in patients with diastolic dysfunction and LAD PCI compared to those with non-LAD PCI (19% versus 16%, p - value=0.004). Although patients with diastolic dysfunction and LAD PCI had higher percentage of cardiogenic shock compared to non-LAD PCI group (6.0% versus 3.7%, p -value&lt;0.001), 1-year mortality did not differ between the 2 groups ( p -value=0.84). Conclusion: Diastolic dysfunction is associated with worse clinical outcomes in patients undergoing LAD PCI which warrants a larger prospective clinical study.