bluuebunny/crossref_metadata_2025_split huggingface dataset:
P5331Aspirin use for prevention of cardiovascular events in patients with high lipoprotein(a): a population-based study
Authors: Karrthik A , Gad M , Bazarbashi N , Ahuja K , Sammour Y , Kaur M , Ahmed H , Kapadia S 
Published: October 2019

Abstract

Background
High lipoprotein(a) [Lp(a)] levels have been shown to increase Myocardial Infarction (MI) and all-cause mortality. However, studies evaluating the optimal preventive measures for that subset of cardiac patients are scarce. This study aims to study the outcomes of aspirin use versus no aspirin for the prevention of all-cause mortality and myocardial infarction in patients with high Lp(a) levels.

Purpose
We sought to determine the effect of Aspirin in reducing the rate of MI and all-cause mortality among patients with high lipoprotein(a) [Lp(a) ≥50mg/dL]

Methods
Patients who attended the preventive cardiology clinic from 2005 to 2016 and included in the Preventive Cardiology Database were included in the current single-center, retrospective, observational cohort study that was conducted according to the guidelines of the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology Statement) checklist. The primary outcome was the incidence of myocardial infarction and the secondary outcome was all-cause mortality. Patients were excluded in cases of I) Lp(a)a <50mg/dL, II) history of malignancy, or III) being on anticoagulation/ dual antiplatelet therapy. The median duration of follow-up was 92 months from time of Lp(a) measurement to the last follow-up. Continuous variables were expressed as means ± standard deviation or median (IQR), and categorical variables were expressed as percentages (%). All statistical tests were two-sided. A propensity score-matched analysis was performed with 1:1 nearest match for Age, Gender, Race, Smoking status, BMI, Diabetes, Peripheral artery disease, Carotid artery disease, coronary artery disease, chronic kidney disease, Heart failure, Hypertension, Dyslipidemia, Stroke, family history of coronary artery disease, Lp (a), LDL, HDL, Triglycerides, glucose and total cholesterol.

Results
1,805 patients fulfilled the inclusion and exclusion criteria out of 7,410 patients initially identified with recorded Lp(a) levels in the Preventive Cardiology Database. Of these, 376 patients were taking aspirin, and 1429 patients were not receiving aspirin. After propensity score matching for different baseline characteristics and comorbidities as mentioned above, 316 patients were matched in each group. Patients who were on Aspirin had a significantly lower rate of MI events compared to patients who were not on aspirin (6.96% vs 12.02%, P=0.03) and a lower rate, however statistically non-significant, of all-cause mortality (2.84% vs 4.11%, P=0.385).

Conclusion
The use of aspirin in patients with elevated Lp(a) levels significantly lowers the rate of myocardial infarction events. Larger randomized clinical trials are warranted to evaluate the use of aspirin for primary and secondary prevention of major adverse cardiovascular events in patients with high Lp(a) levels.
P5336Waist:Hip ratio (WHR): a better predictor of cardiovascular risk (CVR) than BMI in people living with HIV
Authors: Manmathan G P R , Little C , Kotecha T , Ngwu N , Hunter A , Kinloch S , Burns F , Johson M A , Rakhit R D 
Published: October 2019

Abstract

Introduction
Antiretroviral therapy (ART) has dramatically reduced morbidity and mortality among people living with HIV (PLWH), including wasting syndrome. Metabolic and cardiovascular diseases are leading causes of death for PLWH in high-income countries.
Obesity is increasing in the HIV population but a lack of data exists in PLWH, and the association with cardiovascular risk. The aim to determine if central obesity (measured using waist to hip ratio) is a better predictor of CV risk than Body Mass Index (BMI) which is the current standard to define obesity in PLWH.

Methods
Single centre, prospective study performed in a large metropolitan HIV unit. 129 PLWH had weight, height, waist and hip circumference, and blood pressure (BP) recorded. Data on sex, age, ethnicity, past medical history including CV risk factors and kidney disease, smoking status and postcode was used to calculate waist to hip ratio (W/H), BMI and Q-Risk2.

Results
The study population included 30 (23%) women and 98 (77%) men; 76 (59%) Caucasian, 38 (30%) black African/Caribbean and 14 (11%) were other ethnicity. In total, 43 (34%) were overweight and 31 (24%) obese using BMI measurement, this changed to 25 (20%) and 39 (30%) when using WHR.
Q-Risk2 demonstrated that 82 PLWH (64%) had mild risk, 25 (20%) moderate, and 21 (16%) were high cardiovascular risk (excluding HIV as a risk factor).
There was significant correlation between WHR and Q-Risk2 (r=0.44, p<0.01,graph A) but not between BMI and Q-Risk2 (r=0.13, p=0.15, graph B). ROC analysis demonstrates that WHR is able to predict Q-Risk2 (AUC 0.74, 95% CI 0.66–0.82, p<0.01) with a cut-off of 0.98 having 67% sensitivity and 81% for predicting Q-Risk2 >20 (high risk). WHR performed significantly better than BMI (AUC 0.58, 95% CI 0.49–0.67, p=0.24) at predicting Q-Risk2 (p=0.02 for difference, graph C).
W/H ratio and BMI against Q-Risk 2

Conclusion
Temporal change in waist circumference can indicate change in abdominal fat, with increased abdominal fat being associated with increased CV risk. WHR is superior to BMI at predicting high risk (Q-Risk >20%). It should be included as part of routine clinical assessment and lifestyle intervention implemented to reduce CV risk in PLWH.
P5339Association between high-sensitive troponin I and subclinical coronary atherosclerosis in well-controlled HIV-infected adults
Authors: Vassara M , Siwamogsatham S , Buddhari W , Tumkosit M , Ketloy C , Apornpong T , Boonyaratavej S , Avihingsanon A , Chattranukulchai P 
Published: October 2019

Abstract

Background and objectives
Patients with human immunodeficiency virus (HIV) infection live longer and the prevalence of coronary heart disease is increasing among them. High-sensitive troponin I (hs-TnI) is associated with coronary artery calcification as determined by non-contrast cardiac computed tomography (CT) in general population without established cardiovascular disease (CVD). Nevertheless, the relationship in well-controlled HIV-infected patients has not been validated.

Design and methods
A cross-sectional study among HIV-infected adults aged >50 years free from known CVDs. All subjects underwent non-contrast cardiac CT and blood test for serum hs-TnI was concomitantly performed. Relationship between Agatston score, a parameter used to quantify coronary artery calcification and serum hs-TnI level was analysed using spearman correlation and logistic regression models.

Results
A total of 338 HIV-infected adults (median age 54 years, 62% men) were included. All of them were in antiretroviral therapy with a median 18 years of exposure. The median CD4 cell count was 614 cell/mm3, 98% were virologically suppressed. Hs-TnI was correlated with coronary artery calcification with the correlation coefficient of 0.287 (p<0.0001). Multivariated logistic regression analysis demonstrated that serum hs-TnI concentration was associated with an increased odd of coronary artery calcification (Agatston score>0) (OR 1.64; 95% CI, 1.05–2.56, p=0.029). To detect coronary artery calcification, using the hs-TnI in addition to Thai CV risk score slightly increased the ROCAUC from 0.6827 to 0.692 (p=0.45).
Distribution of CAC score over hs-TnI

Conclusion
Among well-controlled HIV-infected patients without established CVDs, hs-TnI concentration was associated with coronary artery calcification. This could be a potential biomarker for an early risk stratification of subclinical coronary atherosclerosis in this population. The association with long-term adverse cardiovascular outcome needs to be validated in the future study.
P5348Aspirin versus clopidogrel treatment for refractory migraine with patent foramen oval
Authors: Toomsoo T 
Published: October 2019

Abstract

Background
The association between migraine with aura (MA+) and persistent foramen ovale (PFO), as well as other right-to-left shunts, is described. Observational studies suggested that when a PFO is closed patients who have MA+ are usually improved. Many observational studies have shown that when PFOs are closed in patients who have had a stroke the patients have a high prevalence of migraine before the procedure and ∼80% report that their migraine symptoms were improved after the closure procedure. Migraine with aura is also improved by medical treatment (aspirin, clopidogrel).

Purpose
To investigate the MA+ reduction effect with the aspirin or clopidogrel in 90 with MA+ with PFO.

Methods
MA+ patients were screened for PFO by transcranial sonography and echocardiography. Participants with documented right to left shunt (RLS) and ≥12 monthly MA+ days received aspirin or clopidogrel therapy for 60 days. Those with ≥50% reduction in monthly MA+ days were deemed responders and completed 10 additional treatment months.

Results
The 90 participants had a mean age of 33.2 years and mean MA+ frequency of 16.4 d/mo. A total of 57/80 were female. A total of 66/80 met criteria for episodic MA+, 14/80 for chronic MA+, 59/80 had a moderate–large RLS. 38 of 80 participants (47%) were responders. MA+ reduction continued through 10 treatment months in all responders. MA+ responder rates were not statistically different in participants with episodic or chronic MA+ or with small/larger RLS shunt magnitude, treatment with aspirin or with clopidogrel. All three (8%) patients had aspirin side effects, without serious adverse events.

Conclusion
Both medications reduced MA +symptoms and participants seemed to have less MA+ and only small amount had side effects with aspirin.

Acknowledgement/Funding
None
P5359Pulmonary artery pressure is elevated three month after delivery in patients with preeclampsia and antiphospholipid syndrome
Authors: Buffle E , Neagoe A , Raio L , Rimoldi S F , Messerli F H , Scherrer U , Rexhaj E 
Published: October 2019

Abstract

Introduction
Preeclampsia (PE) is a multisystem disease affecting 2–8% of all pregnancies. Recently we found that the prevalence of antiphospholipid syndrome (APS) in PE patients at 13.9%. APS can be the cause of thromboembolic pulmonary hypertension. However, data on heart function and pulmonary pressure in PE and in PE with APS are sparse.

Purpose
We sought to investigate cardiac hemodynamics in this population.

Method
Between July 2016 and December 2018, we performed echocardiography in patients who had suffered from PE alone (n=102, age=32.6±4.8 y) or PE with APS (n=21, age=32.1±4.2 y) 3 months after delivery. APS was diagnosed according to the Sapporo criteria.

Results
The overall prevalence of APS was 17%. Right ventricular to right atrial pressure (RV/RA) gradient was significantly higher in PE + APS patients than in patients who had PE only (21.1±3.8 vs. 17.9±4.6mmHg, p=0.04, PE+APS vs. PE). The indexed volume of the left atrium (LA: 20.3±4.4 vs 23.5±5.5ml/m2, p=0.01, PE+APS vs. PE) and the birthweight of the newborn (1379.8±759.1 vs 1848.1±879.6.1g, p=0.02, PE+APS vs. PE) were lower in APS patients.

Conclusion
In patients with preeclampsia and APS, three month after delivery, pulmonary artery pressure was higher and the left atrium size smaller than in patients who had PE only. Conceivably this may reflects multiple subclinical clots in the pulmonary vessels in APS patients and may put these patients at an elevated risk of pulmonary hypertension later in life.
P5366Eicosapentaenoic acid therapy is associated with decreased coronary plaque instability assessed using optical frequency domain imaging
Authors: Konishi T 
Published: October 2019

Abstract

Background
The relationship between eicosapentaenoic acid (EPA) therapy and coronary plaque stability assessed by optical frequency domain imaging (OFDI) has not been thoroughly described.

Hypothesis
EPA therapy is associated with decreased plaque instability in patients undergoing percutaneous coronary intervention (PCI) using OFDI.

Methods
Data on coronary artery plaques from 121 patients presenting with acute coronary syndrome or stable angina who consecutively underwent PCI between October 2015 and July 2018 were retrospectively analyzed. Of these patients, 109 were untreated (no-EPA group), whereas 12 were treated with EPA (EPA group). Each plaque's morphological characteristics were analyzed using OFDI.

Results
We used 1:4 propensity score matching for patients who received or did not receive EPA therapy before PCI. Baseline characteristics were balanced between both groups (age, sex, body mass index, diabetes mellitus, hypertension, dyslipidemia, chronic kidney disease, smoking, previous PCI or coronary artery bypass grafting, previous myocardial infarction, prior statin use, acute coronary syndrome, hemoglobin A1c level, low-density lipoprotein cholesterol concentration, triglyceride concentration, and high-density lipoprotein cholesterol concentration). The EPA group had significantly lower mean lipid index (818±806 vs. 1,574±891) and macrophage grade (13.5±5.9 vs. 19.3±7.4) but higher mean minimum fibrous cap thickness (109.2±55.7 vs. 81.6±36.4 μm) than the no-EPA group (P=0.010, 0.019, and 0.040, respectively). Multiple logistic regression analyses showed that prior EPA use was independently associated with lower lipid index and macrophage grade (P=0.043 and 0.024, respectively).

Conclusion
This OFDI analysis suggests that EPA therapy is associated with decreased plaque instability in patients undergoing PCI.

Acknowledgement/Funding
None
P5370Pulmonary pressure overload stimulates cardiac stem or progenitor cell-derived cardiac regeneration in the right ventricular area
Authors: Kanda M , Nagai T , Kondou N , Tateno K , Hirose M , Akazawa H , Komuro I , Kobayashi Y 
Published: October 2019

Abstract

Introduction and purpose
The number of patients with right heart failure due to pulmonary hypertension has been increasing. Although several drugs have reportedly improved pulmonary hypertension, no treatments have been established for decompensated right heart failure. The heart has an innate ability to regenerate, and cardiac stem or progenitor cells (e.g., side population [SP] cells) have been reported to contribute to the regeneration process. However, their contribution to right ventricular pressure overload has not been clarified. Here, this regeneration process was evaluated using a genetic fate-mapping model.

Methods and results
We used Cre-LacZ mice, in which more than 99.9% of the cardiomyocytes in the left ventricular field were positive for 5-bromo-4-chloro-3-indolyl-β-D-galactoside (X-gal) staining immediately after tamoxifen injection. Then, we performed either a pulmonary binding (PAB) or sham operation on the main pulmonary tract. In the PAB-treated mice, the right ventricular cavity was significantly enlarged (right-to-left ventricular [RV/LV] ratio, 0.24±0.04 in the sham group and 0.68±0.04 in the PAB group). Increased peak flow velocity in the PAB group (1021±80 vs 1351±62 mm/sec) was confirmed by echocardiography. One month after the PAB, the PAB-treated mice had more X-gal-negative (newly generated) cells than the sham mice (94.8±34.2 cells/mm2 vs 23.1±10.5 cells/mm2; p<0.01). The regeneration was biased in the RV free wall (RV free wall, 225.5±198.7 cells/mm2; septal area, 88.9±56.5/mm2; LV lateral area, 46.8±22.0/mm2; p<0.05). To examine the direct effects of PAB on the cardiac progenitor cells, bromodeoxyuridine was administered to the mice daily until 1 week after the PAB operation. Then, the hearts were isolated and SP cells were harvested. The SP cell population increased from 0.65±0.23% in the sham mice to 1.87% ± 1.18% in the PAB-treated mice. Immunostaining analysis revealed a significant increase in the number of BrdU-positive SP cells, from 11.6±2.0% to 44.0±18%, therefore showing SP cell proliferation.

Conclusions
Pulmonary pressure overload stimulated cardiac stem or progenitor cell-derived regeneration with a RV bias, and SP cell proliferation may partially contribute to this process.

Acknowledgement/Funding
JSPS KAKENHI Grant Number JP 17K17636, GSK Japan Research Grant 2016
P5396CRISPR/Cas9 mediated miR-29b editing restores muscle atrophy and exercise capacity in mice
Authors: Li J , Wang L J , Wang F , Tang H F , Chen R , Yang T T , Das S , Xiao J J 
Published: October 2019

Abstract

Background
Muscle atrophy is the loss of skeletal muscle mass and strength in response to diversity catabolic stimuli, such as heart failure. At present, no effective treatment except exercise is validated on reducing multiple muscle atrophy clinically. We have recently reported that microRNA-29b (miR-29b) promotes multiple types of muscle atrophy.

Purpose
The goal of this study was to assess whether genome editing using a clustered regularly interspaced short palindromic repeat/Cas9 (CRISPR/Cas9) system can efficiently introduce loss-of-function mutations into the endogenous miR-29b in vivo and as a potential therapy by treating muscle atrophy.

Methods
We used lentivirus to express CRISPR-associated 9 and a CRISPR guide RNA targeting miR-29b. Mutagenesis rate of miR-29b and off-target mutagenesis were detected by T7 Endonuclease I (T7EI) Assay. The expression level of miR-29b were measured in vitro and vivo after administration of the virus by using qRT-PCR. After intramuscular administration of the virus, the angiotensin II (AngII), immobilization and denervation-induced muscle atrophy were performed. Then muscle function was assessed in exercise capacity, the appearance and weight of muscle, the size of the muscle fibers, molecular and cellular detection.

Results
Here, we report that CRISPR/Cas9 mediated genome editing through intramuscular administration efficiently targeting the biogenesis processing sites in pre-miR-29b. No off-target mutagenesis was detected in 10 selected sites. This CRISPR-based treatment resulted in decreased miR-29b levels specifically. In vivo, this CRISPR-based treatment could ameliorate the muscle atrophy induced by angiotensin II (AngII), immobilization and denervation via activation of PI3K-AKT-mTOR signaling pathway and protect against AngII-induced apoptosis in mice. Moreover, the exercise capacity is also significantly enhanced.

Conclusion
Our work establishes CRISPR/Cas9 based gene targeting on miRNA as a potential durable therapy for treatment of muscle atrophy and expands the strategies available interrogating miRNA function in vivo.

Acknowledgement/Funding
The grants from National Natural Science Foundation of China (81722008, 91639101 and 81570362 to JJ Xiao)
P5403Platelet lncRNA and mRNA: unravelling the role of epigenetic modulation in acute coronary syndrome
Authors: Grimaldi M C , Fabiani I , Aretini P , Mazzanti C M , Mandolini C , Larosa G , Liuzzo G , Volpe M , Crea F , Biasucci L M 
Published: October 2019

Abstract

Background
Platelets (PLT) play a pivotal role in thrombosis that represents the key event of acute coronary syndrome (ACS). Long noncoding RNA (lncRNA) are transcripts of more than 200 nucleotides not encoding for proteins and they are a challenging class of epigenetic regulators. As PLT are anucleated cellular fragments, they represent an ideal scenario to unlock ncRNAs undiscovered functions. In diabetic metabolic setting, PLT switch to a hyper-reactive phenotype, enhancing thrombotic risk of these subjects. As diabetes leads to macro and microvascular complications, lncRNA profile may unlock mechanism leading to pro-thrombotic milieu.

Purpose
Although PLT transcriptome and proteome have been widely investigated, only little is known about PLT lncRNA asset. Our pilot study aimed to assess how diabetes influences PLT coding and noncoding RNA in ACS.

Methods
Microarray analysis was performed on PLT RNA from three groups of patients (pts): 3 non-diabetic pts with not ST elevation (NSTE) ACS (ND-NSTE); 3 diabetic pts with NSTE (T2DM-NSTE) and 3 healthy controls (CTRL). We considered as significant RNA transcripts, those with a threshold of fold change >2 and p<0.05.

Results
Global transcriptomic analyses detected 20.642 lncRNAs and 18.949 mRNAs. We found significant dysregulation between T2DM-NSTE and ND-NSTE vs CTRL according to mRNA and lncRNA transcripts. Among the top ranked coding transcripts, mitochondrial-derived mRNAs, (ALAS, AHSP), were differentially expressed compared to CTRL. In addition, mRNAs linked to oxygen transport (HBG, HBA), PLT activation (SLC4A1), microparticles machinery (CORO6), calcium-homeostasis (CISD2), immune-thrombosis, apoptosis (APOPT1, EIF2AK2, IFI-6), cellular commitment (NOTCH3) related pathways were differently modulated. We identified a huge number of lncRNAs in PLT. Among them Linc ENSTehz746.03620452053 is a long intergenic noncoding RNA that could be involved in modulation of PI3K/AKT pathway, a central node for PLT activities
Different expressed mRNA Volcano Plot

Conclusion
Our platelet-derived RNA template pilot study confirms the central role of PLT in ACS and shows a potential role of lncRNAs, as master of the epigenetic control. As we found the main difference of expression between ND-NSTE vs T2DM-NSTE groups, our data show the critical role of diabetes in the transcriptional setting of ACS.
P5409Plasma volume status provides the additional prognostic information to the Get With the Guidelines-Heart Failure risk score in acute decompensated heart failure patients
Authors: Yamada T , Morita T , Furukawa Y , Tamaki S , Kawasaki M , Kikuchi A , Kawai T , Seo M , Nakamura J , Abe M , Yamamoto K , Kayama K , Kawahira M , Tanabe K , Fukunami M 
Published: October 2019

Abstract

Background
The Get with The Guidelines (GWTG) heart failure (HF) risk score was developed in the GWTG inpatient HF registry to predict in-hospital mortality and also reported to be associated with post-discharge long-term outcomes. Plasma volume (PV) expansion plays an essential role in HF. Recently, it has been reported that PV is estimated by a simple formula based on hematocrit and body weight, not using radioisotope assays, and PV status provides prognostic information in patients (pts) with acute decompensated heart failure (ADHF). However, there is no information available on the long-term prognostic value of the combination of PV status and GWTG-HF risk score in pts admitted for ADHF.

Methods and results
We studied 301 ADHF pts discharged with survival. Variables required for the GWTG-HF risk score were race, age, systolic blood pressure, heart rate, serum levels of blood urea nitrogen and sodium, and the presence of chronic obstructive pulmonary disease. PV status was calculated as the following: Actual PV = (1 − hematocrit) x [a + (b x body weight)] (a=1530 in males and a=864 in females, b=41 in males and b=47.9 in females), Ideal PV = c x body weight (c=39 in males and c=40 in females), and PV status = [(actual PV − ideal PV)/ideal PV] x 100(%). During a follow-up period of 4.3±3.2 yrs, 95 pts had all-cause death (ACD). At multivariate Cox analysis, GWTG-HF risk score and PV status were significantly associated with the total mortality, independently of eGFR and the prior history of heart failure hospitalization, after the adjustment with serum albumin level and anemia. Pts with both high GWTG-HF risk score (≥39 by ROC analysis; AUC 0.655 [0.586–0.724]) and greater PV status (≥8.1% by ROC analysis; AUC 0.624 [0.566–0.692]) had a significantly higher risk of ACD than those with either or none of them (58% vs 30% vs 21%, p<0.0001, respectively).

Conclusion
PV status would provide the additional long-term prognostic information to GWTG-HF risk score in ADHF pts.