bluuebunny/crossref_metadata_2025_split huggingface dataset:
P652Lower use of statins among patients with peripheral artery disease compared with those with coronary heart disease
Authors: Colantonio L D , Dai Y , Hubbard D , Rosenson R S , Brown T M , Jackson E A , Mues K E , Woodward M , Farkouh M E , Muntner P 
Published: October 2019

Abstract

Background
Adults with atherosclerotic cardiovascular disease are recommended to take a statin to reduce their risk for future cardiovascular events. Prior studies suggest that statins are being taken by most adults with coronary heart disease (CHD). However, there are few data on the use of statins among adults with peripheral artery disease (PAD).

Purpose
To compare the use of statins among US adults with a history of PAD versus those with a history of CHD.

Methods
We conducted a retrospective cohort study among US adults ≥19 years of age with commercial or government health insurance who had a history of CHD or PAD as of December 31, 2014 (n=1,006,451, mean age 63 years, 47% male). We used pharmacy claims between January 1 and December 31, 2014 to identify use of any statin and of a high-intensity statin (i.e., atorvastatin 40–80 mg, rosuvastatin 20–40 mg, simvastatin 80 mg). Patients with a history of CHD without PAD (CHD only), both CHD and PAD, and PAD without CHD (PAD only) were analysed. Prevalence ratios for use of any statin and a high-intensity statin among those taking a statin were calculated after multivariable adjustment for sociodemographics and cardiovascular risk factors.

Results
Overall, 69.1% of patients included in the current analysis had CHD only, 21.4% had both CHD and PAD, and 9.5% had PAD only. Overall, 66.0%, 68.2% and 47.5% of patients with CHD only, CHD and PAD, and PAD only were taking a statin. After multivariable adjustment and compared to patients with CHD only, the prevalence ratio for statin use was 1.02 (95% CI 1.01, 1.02) for those with both CHD and PAD and 0.82 (95% CI 0.82, 0.83) for those with PAD only. Among patients taking a statin, 29.4% of those with CHD only, 28.6% of those with both CHD and PAD, and 17.3% of those with PAD only were taking a high-intensity dosage. Compared to patients with CHD only, the multivariable adjusted prevalence ratio for taking a high-intensity dosage was 1.05 (95% CI 1.04, 1.06) for those with both CHD and PAD and 0.71 (95% CI 0.70, 0.73) for those with PAD only.

Conclusion
Adults with PAD receive less intensive statin therapy compared with their counterparts who have CHD. Interventions aimed to increase statin use among patients with PAD are warranted.

Acknowledgement/Funding
This study was supported through a research grant from Amgen, Inc. (Thousand Oaks, CA, USA).
P670Clincal and echocardiographic characteristics in patients with pathology proven cardiac papillary fibroelastomas
Authors: Kurmann R , El-Am E , Bois M , Scott C , Lee A , Sorour A , Maleszewski J , Klarich K 
Published: October 2019

Abstract

Background
Papillary fibroelastoma (PFE) is a rare benign cardiac tumor with embolic potential. It is most commonly found on cardiac valves but can also be present on non-valvular endocardial surfaces. We sought to better understand the average PFE growth and recurrence rates, and characteristics that might be associated with embolization.

Purpose
To examine growth and recurrence rates and factors associated with embolization in patients with pathology-proven PFE.

Methods
Pathology-proven PFEs from 279 patients were identified at a single center between January 1995 and December 2018,and those with at least two transesophageal echocardiograms (TEE) more than 30 days apart were analyzed (n=62). Medical records were retrospectively reviewed for clinical characteristics and outcomes. In addition, intra-operative TEEs were manually reviewed and compared to previous TEEs at our institution to estimate overall size, location, and average PFE growth rates.

Results
The TEEs from 62 patients with pathology-proven PFE (mean age 65±12 years, female 63%) were reviewed. PFE was discovered incidentally during cardiac surgery in 18% of patients. Most PFEs were located on the aortic valve (AV) (73%) followed by the mitral valve (MV) (16%). The majority of PFEs (71%) presented with a stalk versus a sessile configuration. Average maximal length for PFE (including stalk if present) on the AV was 8.5±3.3 mm, and on the MV 6.8±2.0 mm. The number of PFEs located in other locations was too small to be analyzed for growth. PFE growth varied depending on location and configuration. The PFE growth on the AV was an average increase of 0.47 mm/year, those on the MV was 0.115 mm/year.
Valvular PFE was associated with significant functional valve abnormality in 15% of patients, and the abnormality was attributed to the PFE in 9% of patients. There were 25 patients (40%) who had a documented stroke/transient ischemic attack prior to PFE removal (46% located on AV, 44% on MV, 10% other locations). In addition, some patients had other documented embolic complications, such as myocardial infarction, amaurosis fugax, and peripheral embolization to the spleen and kidney. PFE size and location (up-/ downstream of the valve) were not predictive of cardiovascular thromboembolic events. At a median follow up of 2 years, PFEs recurred in the same location in 7.5% of the patients.

Conclusion
PFE is highly associated with thromboembolic events and seem to grow slowly, with an average growth rate of 0.47mm/year on AV and 0.115mm/year on MV. Growth rates for PFE have not been previously described. PFE can be safely excised with preservation of the native valve and recurs in 7.5% of patients, suggesting that close follow-up maybe warranted.
P673Moderate anti-tumor effect of the nanoliposomal anti-PCSK9 vaccine in BALB/c mice bearing colorectal cancer
Authors: Momtazi-Borojeni A A , Nik M E , Jaafari M R , Banach M , Sahebkar A 
Published: October 2019

Abstract

Background
The higher levels of low-density lipoproteins (LDL) cholesterol (LDL-C) have been reported to correlate with higher prevalence and risk of colon cancer. Proprotein convertase subtilisin/kexin 9 (PCSK9) function, through reducing protein levels of liver LDL receptor, leads to elevated levels of plasma LDL-C.

Purpose
Here, we evaluated anti-tumor effect of nanoliposomal anti-PCSK9 vaccine in mice bearing colon carcinoma.

Methods
To formulate nanoliposomal anti-PCSK9 vaccine, liposome nanoparticles prepared by lipid-film hydration method were covalently attached to immunogenic PCSK9 peptide. The liposomal vaccine formulation was adsorbed to Alum adjuvant (L-IFPTA+) and injected subcutaneously four times with a bi-weekly interval in BALB/c mice. Two weeks after the last immunization, the vaccinated and unvaccinated mice were subcutaneously inoculated with CT26 colon cancer cells into the right flank. After tumor mass was palpable (approximately 10 mm3), the mice were randomly divided into three groups and involved to different treatments: (1) PBS (untreated control), (2) vaccine group, and (3) Doxil®(positive control) group which involved unvaccinated tumor-bearing mice who received Doxil®. To study therapeutic efficacy, mouse body weight, tumor size, and survival were monitored in a 3-day interval for 50 days.

Results
The nanoliposomal anti-PCSK9vaccine could efficiently induce specific antibodies against PCSK9 in BALB/c mice, and thereby reduce plasma level and function of PCSK9. Tumor size in the vaccinated mice was significantly lower than in Doxil and the control mice. Tumor size analysis revealed that time to reach endpoint (TTE) of the vaccine group was slightly but not significantly higher than that of Doxil and the control groups. The vaccinated mice survived slightly but not significantly longer than Doxil and the control mice. The vaccinated mice's life was prolonged by 24.4% as compared with the control mice, while it was increased by 9.8% in Doxil group (see Figure below).

Conclusions
Our findings declare that the nanoliposomal anti-PCSK9vaccine not only have no harmful effects, but also can mildly reduce tumor growth, and enhance live span and survival in mice bearing colon cancer.
P681Acute Myocardial Infarction in patients with Leukaemia: A national analysis of prevalence, predictors and outcomes in United States hospitalisations (2004 to 2014)
Authors: Mohamed M O , Lopez-Mattei J C , Iliescu C A , Purwani P , Bharadwaj A , Kim P Y , Palaskas N L , Rashid M , Potts J E , Kwok C S , Gulati M , Al Zubaidi A B , Mamas M 
Published: October 2019

Abstract

Background
Patients with leukaemia are at increased risk of cardiovascular events. There is limited outcomes data for patients with a history of leukaemia who present with an acute myocardial infarction (AMI).

Purpose
To examine the prevalence and clinical characteristics of patients with leukaemia presenting with AMI, and evaluate differences in clinical outcomes according to the subtype of leukaemia in comparison to patients without leukaemia.

Methods
We analysed the Nationwide Inpatient Sample (2004–2014) for patients with a primary discharge diagnosis of AMI and concomitant leukaemia, and further stratified according to the subtype of leukaemia into 4 groups; AML; ALL; CML; and CLL. Multiple logistic regression was conducted to identify the association between leukaemia and major acute cardiovascular and cerebrovascular events (MACCE; composite of mortality, stroke and cardiac complications) and bleeding.

Results
Out of 6,750,927 AMI admissions, a total of 21,694 patients had a leukaemia diagnosis. The leukaemia group experienced higher rates of MACCE (11.8% vs. 7.8%), mortality (10.3% vs. 5.8%) and bleeding (5.6% vs. 5.3%). Following adjustments, leukaemia was independently associated with increased odds of MACCE (OR 1.26 [1.20,1.31]) and mortality (OR 1.43 [1.37,1.50]) without an increased risk of bleeding (OR 0.86 [0.81,0.92]). Acute myeloid leukaemia (AML) was associated with approximately three-fold risk of MACCE (RR 2.81 [2.51, 3.13]) and a four-fold risk of mortality (RR 3.75 [3.34, 4.22]) (Figure 1). Patients with leukaemia were less likely to undergo coronary angiography (CA) (48.5% vs. 64.5%) and percutaneous coronary intervention (PCI) (28.2% vs. 42.9%) compared to those without leukaemia.
Figure 1.Relative risk of adverse events

Conclusion
Patients with leukaemia, especially those with AML, are associated with poor clinical outcomes after AMI, and are less likely to receive CA and PCI compared to those without leukaemia. A multi-disciplinary approach between cardiologists and haematology oncologists may improve the outcomes of patients with leukaemia after AMI.
P693Cardiac biomarkers for the detection of anthracycline cardiotoxicity in childhood cancer - a meta-analysis
Authors: Michel L , Mincu R I , Mrotzek S M , Neudorf U , Rassaf T , Totzeck M 
Published: October 2019

Abstract

Introduction
Heart failure is the most concerning cardiovascular side effect of anthracycline chemotherapy. Pediatric cancer patients and survivors of childhood cancer are particularly vulnerable to cancer therapy-related cardiotoxicity. Cardiac biomarkers may be beneficial for screening and diagnosis of anthracycline-related heart failure in pediatric cancer patients and survivors of childhood cancer but systematic data is not yet available.

Purpose
To evaluate (N-terminal pro) brain natriuretic peptide (BNP/NT-proBNP) and cardiac troponin for screening and prediction of cancer therapy-related cardiotoxicity in pediatric cancer patients and survivors of childhood cancer.

Methods
Cochrane, PubMed, Web of Science, and Wiley Library were screened for studies investigating cardiac troponin or BNP/NT-proBNP in pediatric cancer patients receiving anthracycline therapy or survivors of childhood cancer. The primary endpoint was left ventricular (LV) dysfunction as defined by decreased ejection fraction (EF) or fractional shortening (FS). The study was registered at the International prospective register of systematic reviews (PROSPERO) (CRD42018106616).

Results
A total of 1643 subjects from 27 studies were included. BNP/NT-proBNP levels were higher in patients post-treatment compared to control subjects or pre-treatment values (standardized mean difference = 1.0; 95% CI: 0.6–1.4; n=239). The risk for left ventricular (LV) dysfunction was increased in patients with elevated BNP/NT-proBNP (OR=5.5; 95% CI: 2.0–15.2; n=357). This was demonstrated for acute cardiotoxicity (OR=22.3; 95% CI: 3.3–151.1; n=88) and in survivors of childhood cancer (OR=3.2; 95% CI: 1.0–10.0; n=269). Sensitivity for the prediction of acute or subacute LV dysfunction was 28.9% and specificity was at 91.7%. The frequency of troponin elevations was increased after anthracycline therapy (OR=3.6; 95% CI: 2.0–6.5; n=305) but troponin was not associated with LV dysfunction (OR=0.2; 95% CI: −0.2 to 0.5; n=273).

Conclusion
BNP/NT-proBNP is elevated in pediatric patients receiving anthracycline chemotherapy and serves as a marker for the prediction of cardiotoxicity and screening for late cardiotoxicity in survivors of childhood cancer. So far, there is no systematic evidence on a benefit of cardiac troponin for the detection of anthracycline cardiotoxicity in children. Standardized recommendations on the role of cardiac biomarkers are needed for the optimal detection of anthracycline cardiotoxicity in childhood cancer patients.

Acknowledgement/Funding
IFORES research grant of the Medical Faculty, University Duisburg-Essen, Essen, Germany
P729The functional relevance of bile acids in the improvement of HDL-mediated endothelial protection after bariatric surgery
Authors: Jomard A , Chavez-Talavera O , Tailleux A , Bueter M , Taheri A , Wolfrum C , Lutz T A , Von Eckardstein A , Ruschitzka F , Staels B , Osto E 
Published: October 2019

Abstract

Introduction
Roux-en-Y gastric bypass (RYGB) reduces cardiovascular mortality. We showed that high density lipoproteins (HDL)-mediated vasoprotection is improved early after RYGB. Circulating BAs increase upon RYGB and contribute to the weight-loss independent metabolic improvements after surgery. Bile acids (BA) are signaling molecules increasingly recognized as regulators of cardiometabolic homeostasis. BAs circulate in the blood either free or bound to albumin and HDL. The signaling role of HDL-bound BAs (HDL-BAs) is unknown. Indeed, HDL may facilitate BA delivery directly to endothelial cells where BA may synergize with HDL to promote vasoprotection.

Purpose
We studied whether RYGB changes the composition of HDL-BA and whether HDL functional properties may be modulated by specific BA bound to HDL.

Methods
HDL were isolated by ultracentrifugation from 29 morbidly obese patients before and 1 year after RYGB. The HDL-BA composition was determined by liquid chromatography-mass spectrometry (LC/MS-MS) and HDL vasoprotective properties were evaluated ex-vivo in human aortic endothelial cells (HAEC). The size and abundance of HDL particles were determined by NMR spectroscopy in plasma.

Results
The increase in total BA concentrations observed in plasma 1 year after RYGB also translated into higher concentrations (up to 25%) of BA bound to HDL. Moreover, obesity-induced HDL dysfunction was reversed after surgery, as shown by improved HDL-mediated endothelial NO production, anti-apoptotic effects and cholesterol efflux capacity. The size function analyses showed a post-operative shift towards larger HDL. After RYGB there was a remodeling of BA bound to HDL, which are either agonists of the endothelial nuclear farnesoid X receptor (FXR), e.g. chenodeoxy-CA (CDCA), cholic acid (CA) or for the membrane TGR5 receptor, e.g. deoxy-CA (DCA). The composition-function analysis revealed that among all BA subclasses, the specific enrichment in CA and in CDCA bound to HDL correlated with an improved endothelial anti-apoptotic capacity of HDL (R −0.52, p=0.006 for CA-HDL and R −0.35, p=0.07 for CDCA-HDL). Further, the exogenous loading of CA onto healthy native HDL isolated from human serum significantly enhanced their endothelial anti-apoptotic function. In the case of obese, dysfunctional, pro-apoptotic HDL, exogenous CA loading was able to restore HDL anti-apoptotic function.

Conclusion
Exogenous loading of CA restored HDL anti-apoptotic function of HDL from obese patients mimicking the beneficial remodeling of BA bound to HDL observed after RYGB. These results suggest a crucial interaction between endothelial cells and BA in the improvement of HDL's vasoprotective properties.

Acknowledgement/Funding
Swiss national Science Foundation Ambizione and PRIMA grant to EO
P765One-year mortality risk after intensification of outpatient diuretics
Authors: Madelaire C , Gustafsson F , Kristensen S L , Stevenson L W , Koeber L , Torp-Pedersen C , D'Souza M , Andersen J , Gislason G , Biering-Sorensen T , Andersson C , Schou M 
Published: October 2019

Abstract

Background
Mortality is increased following a hospitalization for heart failure (HF). It is not clear whether outpatient intensification of diuretic confers the same increased risk in the general population with heart failure

Purpose
This study sought to assess 1-year mortality risk after worsening HF, defined either as hospitalization due to HF or as intensified diuretic therapy in an outpatient setting, in a complete nationwide cohort of patients with HF on angiotensin converting enzyme inhibitors/ angiotensin receptor blocker and beta blockers.

Methods
From nationwide administrative registers, we identified all patients in Denmark diagnosed with HF in 2001–2016 and prescribed angiotensin converting enzyme inhibitor/ angiotensin receptor blocker and beta blocker within 120 days. During follow-up we defined worsening HF by the following events: Inpatient worsening (HF readmission) and outpatient worsening (intensified diuretic therapy, defined as the first event of new addition or doubled dosage of loop diuretic therapy or new onset addition of thiazide to loop diuretic therapy). Patients with a worsening event were risk set matched to two HF controls each at time of the event – based on age, sex and calendar year. One-year mortality risk was estimated with Kaplan-Meier and multivariable Cox regression models.

Results
We included 74,990 patients, median age 71 years (interquartile range: 62–79), 36% women. During five years of follow up, 8,727 patients had an inpatient worsening event, and 12,290 had an outpatient worsening event as first event. Absolute risk of 1-year mortality was 22.6% (95%-confidence interval (95%-CI): 21.7%-23.5%) after inpatient worsening, 18.0% (95%-CI: 17.3%-18.7%) after outpatient worsening compared to 9.8% (95%-CI: 9.5%-10.1%) for the matched controls. In a multivariable Cox model adjusted ischemic heart disease, atrial fibrillation, chronic obstructive pulmonary disease and diabetes, the hazard ratio for mortality among patients experiencing inpatient worsening was 2.46 (95%-CI: 2.33–2.60) and for outpatient worsening was 1.87 (95%-CI: 1.77–1.97), compared with the matched HF controls as reference (figure 1). Among patients who had an outpatient worsening as first event, 1,245 (10.1%) had a subsequent HF readmission within one year.

Conclusion
In a nationwide cohort of patients with HF, outpatient worsening defined by a diuretic intensification was associated with almost 2-fold risk of mortality during the next year. Although HF hospitalization is associated with a higher risk, the need to intensify diuretics in the outpatient setting is a signal to review and intensify efforts to improve HF outcomes.

Acknowledgement/Funding
The Danish Heart Foundation, (grant number 17-R116-A7610-22048)
P771Metoprolol succinate efficacy in patients with chronic heart failure on the background of obesity: genetic aspects of individual sensitivity and tolerability
Authors: Gasanov I , Medentseva O , Rudyk I , Galchinskaya V 
Published: October 2019

Abstract

Background
The cornerstone of modern cardiology is the problem of comorbidity, the combination of chronic heart failure (CHF) with obesity as well. Efficacy of treatment with beta-blockers in different patients varies significantly, partly depending on genotypically determined features of its metabolization with enzymes.

Purpose
To improve the CHF treatment with metoprolol succinate efficacy in patients with obesity by detection of genetic aspects of individual sensitivity and tolerability.

Methods
A prospective randomized dynamic (1 year) study was conducted involving 127 patients with CHF II–III stages at the age of 32–87 years; they were distributed into main group with combination of CHF and obesity (73 patients) and control group with only CHF (54 patients). The examination included an assessment of CYP2D6 gene 1846G/A polymorphism, clinical symptoms, quality of life (by Minnesota questionnaire), 6-minute walk test data, doppler echocardiography, heart rate variability, serum insulin, N-terminal prohormone of brain natriuretic peptide (NT-proBNP). Metoprolol succinate was administered according to a standard regimen with dose titration every 2 weeks from 12.5 to 100–200 mg. The critical p-level was 0.05.

Results
An association of “unfavorable” allele A with an increase in body weight was found (p=0.05). As a result of treatment, better indicators of the clinical status were found in control group (6 [5; 7] versus 7 [6; 8] points in obese patients, p=0.05) and quality of life in patients with genotype GG than the GA genotype (p<0,05).
The use of metoprolol succinate in patients with GG genotype is associated with more pronounced positive dynamics of treatment efficacy. In contrast to the carriers of the GA genotype, in patients with the GG genotype there were an increase in left ventricle ejection fraction (by 21.5% versus 9.3%, p<0.01) and the reduction of the left ventricle end-diastolic size (p=0.02). The GG genotype carriers significantly increased the amount of exercise tolerance (p<0.05), and showed a more pronounced improvement in quality of life (p<0.03) and the clinical state (p=0.05), as well as the normalization of the vegetative balance (LF/HF index). The level of serum NT-proBNP in the GG genotype was lower than in patients with GA genotype (p=0.05). At the same time, patients with a GA genotype showed a more pronounced decrease in heart rate compared to those with a GG genotype (p<0.05).
In carriers of the GA genotype, a tendency to a greater incidence of side effects compared with the GG genotype (bradycardia 42.0% vs. 28.0%, p<0,05; cold extremities 44.0% vs. 32.0%, p<0.05, fatigue 39.0% vs. 31.0%, p<0.05, headache 32.0% vs. 24.0%, p<0,10, drowsiness 38,0% vs. 27,0%, p<0,05).

Conclusions
It is useful to take into account the CYP2D6 gene 1846G/A polymorphism in order to improve the CHF treatment with metoprolol succinate in patients with obesity.