bluuebunny/crossref_metadata_2025_split huggingface dataset:
P6250Mentalplus digital game usefulness in cognitive dysfunction evaluation compared to neuropsychological testing batteries in a hypertensive treated population
Authors: Pereira V , Valentin L 
Published: October 2019

Abstract

Introduction
Cognitive dysfunction has been a time-consuming evaluation when full neuropsychology battery is performed, what is the most used method up to nowadays. The time is a limitation besides the necessity of a specific professional to apply it. Both reasons limit the clinical use and even research widespread of cognitive dysfunction evaluation in a variety of diseases that we suppose that might be linked to cognitive dysfunction in its lifetime evolution.

Purpose
The purpose of this study is to evaluate the correlation between a digital game named Mentalplus and a usual neuropsychology battery to cognitive dysfunction evaluation in a hypertensive medically treated and followed group.

Methods
A 163 hypertensive and followed by cardiologists group was evaluated for cognitive dysfunction by two means: A standard neuropsychology battery that spent around two hours and was performed by neuropsychologists. Then, Mentalplus digital game was applied, for 25 minutes. The Mentalplus digital game was developed to evaluate some cognitive functions like selective and alternate attention, short and long term memory, inhibitory control, language, visuoconstruction, executive function. Spearman test was used to calculate the correlations between specific validated tests with each Mentalplus phase. Staticisticists used IBM-SPSS. The significance level was 5%.

Results
41.7% male, mean age of 51.1±16.2 SD years, mean arterial pressure of 93.1±8.7 SD mmHg in use of up to 3 blood pressure medications. Concerning to cognitive evaluation by both methods, the main findings were strong correlations related to functions below: short term memory, comparing VLT-A-1 and Mentalplus phase developed to evaluate that function: (r=0.563, p<0.005); Long term memory, comparing Rey-figure-long term memory and Mentalplus (r=0.887, p<0.005); Attention and Visuoconstruction, comparing Rey-figure copy and Mentalplus: (r=0.929, p<0.005) and Stroop-C and Mentalplus: (r=0.941, p<0.005); Selective attention, comparing TMT-A and Mentalplus phase: (r=0.889, p<0.005); Alternate attention, comparing STOOP-B and TMT-B and Mentalplus phase is similar (r=0>0.98, p<0.005); Inhibitory control, comparing Rey-Figure immediate memory and Mentalplus phase (r=0.969, p<0.005).
MentalPlus Short Term Memory - Part I

Conclusion
Mentalplus phases present a strong correlation with specific validated neuropsychologic tests usually performed in a normal evaluation battery. It opens a useful way to evaluate the cognitive function in a hypertensive treated group during the lifelong time, to follow cognitive dysfunction during treatment with less time consuming and more convenience for the patients.

Acknowledgement/Funding
FAPESP
P6254Care cascade of hypertension in people living with HIV
Authors: Nascimento Costa A , Bairronuevo M B , Val F , Macedo A R E , Vegas N C , Terro P , Marques M , Ribeiro F , Rabelo A L , Paixao S , Comte De Alencar Filho A , Lacerda M V G 
Published: October 2019

Abstract

Background
Life expectancy of people living with HIV (PLHIV) has been increasing since the advent of antiretroviral therapy. However, prevalence of non-communicable diseases (NCD) and associated deaths has followed the same trend. From these NCDs, those of cardiovascular origin have become the most prevalent among PLHIV.

Purpose
In this study we delineate a cascade of care for hypertension screening, diagnosis, treatment, drug adherence and control in PLHIV.

Methods
Male and female patients diagnosed with HIV above 40 years of age attending to an outpatient clinic of a reference tertiary care centre for infectious diseases were cross-sectionally screened for hypertension through blood pressure (BP) measurement during outpatient consultation.

Results
A total of 298 subject were enrolled. Of these, 107 (35.9%) presented elevated BP consistent with hypertension according to national guidelines. Of these, only 36 (33.6%) were aware of the diagnosis, 19 (17.7%) were on regular cardiological follow-up, 17 (15.8%) were under treatment and 11 (10.2%) responded to be adherent to BP lowering medication.
Care Cascade HIV_HTN

Conclusions
Steep decline was revealed in several steps of the cascade of care, especially regarding the awareness level. Integrative methods for NCD and HIV care are urgently needed. Early screening of hypertension, diagnosis, treatment, adherence and ongoing BP control should be equal targets in HIV care. Finally, there is an urgent need to encourage HIV primary care and infectious disease health professionals to early screen for cardiovascular outcomes.

Acknowledgement/Funding
Fundação de Amparo à Pesquisa do Estado do Amazonas – FAPEAM
P6256Revascularisation for acute coronary syndrome: are we offering elderly patients the correct treatment?
Authors: Al-Othman S , Zheng Y , Malik N 
Published: October 2019

Abstract

Purpose
Acute coronary syndrome (ACS) is treated with revascularisation procedures such as percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG). Whilst reasonable clinical exclusion criteria exist, age is not one of them and patients of advanced years have been shown to have better outcomes with both treatments than with medical management. We set out to investigate the management and outcomes of patients age seventy five and over, with ACS.

Methods
A retrospective data analysis of all patients age seventy five and above, prescribed dual antiplatelet therapy (DAPT - aspirin plus clopidogrel or aspirin plus ticagrelor), admitted to our institution over a one year period (April 2015 to April 2016). We analysed electronic records and discharge documents and excluded patients without a diagnosis of ACS.

Results
207 patients over 75 years old were treated for ACS; 83.6% (173) were diagnosed with non ST elevation myocardial infarction (NSTEMI), 9.6% (20) diagnosed with ST elevation myocardial infarction (STEMI) and 6.8% (14) diagnosed with unstable angina. 73.4% (152) of patients were managed medically, 14.5% (30) had an angiogram, 11.1% (23) had PCI and 1.0% (2) had CABG. 74.0% (153) of patients were treated with aspirin plus clopidogrel, 26.0% (54) with aspirin plus ticagrelor. Major bleeds were reported in 21 patients (10.1%), 18 of the medically managed patients (8.7%) and 3 in the intervention group (5.5%) (P value 0.30). There were 17 major bleeds in the aspirin and clopidogrel group (11.1%) and 4 in the aspirin and ticagrelor group (7.4%) (P value 0.60). 93 (61.2%) of the medically treated group were alive at one year compared to 47 (85.5%) of the intervention group (P value 0.0008).

Conclusion
Our data show a clear survival benefit in the intervention group, although comparisons between the groups are challenging given confounding factors, such as co-morbidities and patient preference. However, the high proportion (73.4%) of over 75-years old treated medically warrants further evaluation, given the evidence of benefit for patients in this age group, treated with PCI. We feel there is a need for further research in to the ideas and practice surrounding the management of ACS in the over 75's, and their relation to the available evidence.
P6260ACS-group 75+: real clinical practice
Authors: Kruchinova S , Raff S A 
Published: October 2019

Abstract

Purpose
to evaluate the features of treatment and outcomes in elderly patients with acute coronary syndrome.

Methods
The elderly group comprised 2385 (28.9%) patients ≥75 years of the 8249 patients enrolled in the KRACS registry.

Results
When comparing patients of different ages, it was shown that among the elderly, dyspnoea was the most common manifestation of ACS, 9% vs 4% (p=0.015), they were less often hospitalized in “invasive” hospitals - 36% vs 49% (p=0.003), At admission, they often had the class Killip ≥ II - 36% vs 17% (p<0.001), a high risk for the GRASE-68% vs 30% (p<0.001). In addition, in elderly patients significantly lowered levels of Hb and increased creatinine were detected more often.
Drug treatment of elderly patients was characterized by less frequent use of ticagrelor - 3% vs 21% (p<0.001), LMWH or fondaparinux - 4% vs 12% (p=0.004). Thrombolytic therapy in STEMI in the elderly was more often streptokinase - 30% vs 18% (p=0.04), less often - tissue activator plasminogen - 2% vs 10% (p=0.03).
The frequency of performing any invasive interventions for any type of ACS in elderly patients was significantly lower - 16.7% vs 46.3% (p<0.0001), and the incidence of fatal outcomes during hospitalization for any type of ACS was significantly higher - 16, 0% vs 6.1% (p<0.0001). When assessing the incidence of fatalities in different facilities, it was found that STEMI, patients ≥75 years old hospitalized in “invasive” hospitals died significantly less frequently than when they got into “non-invasive” hospitals - 15.6% vs 50.0% (p=0.013). At the same time, among patients <75 years hospital mortality in “invasive” and “non-invasive” hospitals was not significantly different - 14.7% vs 9.9% (p=0.50).
There was also a clear trend towards a higher incidence of deaths among elderly patients who were left without PCI, compared with those who had been intervened. In patients <75 years, this trend was absent.

Conclusion
thus, the results obtained indicate that elderly patients, with a higher risk and worse outcomes, receive treatment that is less consistent with the requirements of modern guidelines for the treatment of ACS. Important factors associated with better outcomes in elderly patients is their hospitalization in “invasive” hospitals and the implementation of PCI.
P6261Aortic stiffness and carotid intima thickness in hypercholesterolemic males with erectile dysfunction: relation to smoking status and statin therapy
Authors: Ioakeimidis N , Vlachopoulos C , Terentes-Printzios D , Koutagiar I , Pantou S , Abdelrasoul M , Sigala E , Angelis A , Skoumas I , Rokkas K , Tousoulis D 
Published: October 2019

Abstract

Purpose
Aim of the study was to examine possible differentiation of aortic stiffness and carotid atherosclerosis among hypercholesterolemic patients with erectile dysfunction (ED) according to smoking status and statin therapy.

Methods
We measured carotid intima-media thickness (cIMT) and carotid-femoral pulse wave velocity (cfPWV) in three age-matched groups of ED patients with a moderate cardiovascular risk (SCORE) and low-density lipoprotein cholesterol (LDL-C) level greater than or equal to 100 mg/dL: Smokers not receiving statin therapy (n=106), Smokers actively under statin treatment for at least three months with no dose adjustment for a minimum of six weeks (n=59) and Non-smokers not receiving statin therapy (n=97). The severity of ED was evaluated with measurements of penile peak velocity (PSV) 20 min after the intracavernous injection of prostaglandin E1 (20 μg).

Results
The groups of untreated smokers and non-smokers had similar mean LDL-C level. The mean LDL-C of patients under statin therapy was lower, however the differences with the level of the untreated patients was not statistically significant. Overall 33 (56%) of the patients under statin therapy reached their LDL-C goal. Body mass index and the prevalence of hypertension were not different between the three groups. The PSV was significantly lower in smokers with or without therapy compared to that of non-smokers, denoting significant influence of smoking status on the smaller in size penile arteries and consequently, a unfavorable effect on erectile function. Figure illustrates the differences in cfPWV (left plot) and cIMT (right plot) mean (±SE) values between the three groups. Smokers not receiving statin therapy had significantly higher cfPWV compared to the other groups while smokers under statin therapy had no different cfPWV than that of non-smokers not receiving therapy. The cIMT values were not different between the three groups.
Smoking, statins and vascular changes

Conclusions
Smokers ED patients receiving statin therapy exhibited similar atherosclerotic burden compared to untreated hypercholesterolemic individuals, however, the cfPWV was significantly lower, possibly because of the known pleiotropic effects of these drugs on the aortic elastic properties. Although the cross-sectional design precludes drawing conclusions of causal relationships, the findings of this study have important clinical implications given the harmful effect of both hypercholesterolemia and smoking in men suffering from ED and the higher risk for future cardiovascular events that ED confers.
P6267Novel direct effects of SGLT2 inhibitor, Canagliflozin, on myocardial redox state in humans
Authors: Kondo H , Akoumianakis I , Akawi N , Cristina M , Herdman L , Badi I , Kotanidis C , Akbar N , Antonopoulos A , Oikonomou E , Chuaiphichai S , Channon K , Antoniades C 
Published: October 2019

Abstract

Background
Sodium glucose cotransporter 2 (SGLT2) inhibitors are antidiabetic drugs that control plasma glucose levels by inhibiting reabsorption of glucose in kidney. Recent clinical trials have suggested a class effect of SGLT2 inhibitors in preventing hospitalization due to heart failure. However, the underlying mechanism has not been fully elucidated.

Purpose
We investigated the direct effect of the SGLT2 inhibitor, Canagliflozin (Cana), on myocardial redox state in humans.

Methods
The study included 48 patients undergoing cardiac surgery. Fresh myocardial tissues were incubated ex vivo with or without Cana and then used for superoxide quantification and Western immunoblotting. NADPH-oxidases activity was evaluated with NADPH 100μM stimulation, while nitric oxide synthase (NOS) coupling was assessed by using N(ω)-nitro-L-arginine methyl ester (L-NAME, a NOS inhibitor). A human cardiomyocyte (HCM) cell line was also used for in vitro validation of the effects of Cana on myocardium.

Results
Ex vivo incubation of myocardium with Cana significantly reduced baseline (A) and NADPH-oxidase-derived O2·− (B) and improved NOS coupling reflected by positive L-NAME delta O2·− values (C). Regulation of NADPH-oxidases activity by Cana was found to result from reduced GTP-activation (D) and consequent membrane translocation (E) of Rac1, a key subunit of NADPH-oxidases. Cana also reduced tetrahydrobiopterin (BH4) oxidation, increasing its bioavailability (F), which is a key mechanism to improve NOS coupling. Incubation with Cana enhanced phosphorylation of AMPK, and the downstream signalling, ACC (not shown). Additional Compound C, which is inhibitor of AMPK, significantly reversed these effects of Cana (A, B, C, D, E, F). These findings were replicated in HCM (not shown). In line with these, Cana increased the ADP/ATP ratio of cytoplasm in HCM, which could provide an upstream mechanism for AMPK activation.

Conclusions
We demonstrate for the first time in humans, that Cana suppresses myocardial NADPH-oxidases activity and improves NOS coupling through an AMPK-mediated pathway. This could be an underlying mechanism for the cardioprotective effects of SGLT2 inhibitors.
P6275Role of autophagy in imatinib-induced cardiotoxicity
Authors: Kobara M , Naseratun N , Watanabe Y , Toba H , Nakata T 
Published: October 2019

Abstract

Background
Cardiotoxicity is one of the severe adverse effects of chemotherapeutic agents. Imatinib, a therapeutic agent for chronic myelogenous leukemia, has been reported to induce cardiotoxicity. Autophagy is an intracellular bulk protein and organelle degradation process, but it is unclear whether autophagy functions as pro-death or pro-survival program during disease conditions. We examined whether imatinib induces myocyte autophagy and the role of autophagy in imatinib-induced cardiotoxicity in in vitro and in vivo experiments.

Methods
In in vitro experiments, neonatal rat cardiac myocytes were treated with imatinib (1, 5, 10 μM; 1–6 hrs). Inhibition of autophagy was performed using 3-methyl-adenine (3MA), an autophagic inhibitor, and transfection with Atg5-targeted siRNA. Myocyte apoptosis was detected by morphological change in nuclei and caspase 3 activity. Mitochondria-derived reactive oxygen species production was detected using MitoSOX and mitochondrial membrane potential was assessed by TMRM staining. Expressions of cytochrome c in mitochondria and cytosole were examined by Werstern blotting. Myocyte autophagy was assessed by monodansylcadaverine staining and microtubule-associated protein light chain (LC) 3-II expression. In in vivo experiments, C57BL6 mice were treated with imatinib (50 and 200 mg/kg/day) for 5 weeks in the presence or absence of 3MA. Cardiac function was examined by echocardiography. In cardiac tissue, apoptotic myocytes were examined by TUNEL assay and autophagy was examined by LC3-II expression.

Results
In in vitro experiments, imatinib increased apoptotic nuclei and caspase 3 activity, in a dose-dependent manner. Consequently, imatinib augmented production of mitochondria-derived reactive oxygen species, loss of mitochondrial membrane potential, and the release of cytochrome c from mitochondria to cytosole, suggesting that imatinib induced mitochondrial-apoptotic pathway. On the other hand, imatinib significantly increased monodansylcadaverine stained dots and LC3-II expression, suggesting that imatinib increased autophagy. 3MA and Atg5 siRNA augmented imatinib-induced apoptosis by 60% and 30%, respectively. In in vivo experiments, imatinib (200 mg) exhibited the dilatation of left ventricle by 15% and the depression of left ventricular fractional shortening by 23%. Ratio of apoptotic myocytes was significantly increased and LC3-II expression in cardiac tissue was enhanced by imatinib in a dose-dependent fashion. Co-treatment with 3MA and imatinib further impaired imatinib-induced myocyte apoptosis by 3 fold and LV dysfunction by 20%.

Conclusion
These results indicate that imatinib induced myocyte apoptosis, leading to cardiac dysfunction. Imatinib enhanced myocyte autophagy as a consequence of apoptosis and autophagy was a beneficial phenomenon in this condition.
P6282Myocardial redox state predicts 3-year mortality in patients undergoing cardiac surgery: the ox-HVF study
Authors: Kotanidis C , Antonopoulos A , Psarros C , Akoumianakis I , Herdman L , Oikonomou E K , Badi I , Krasopoulos G , Sayeed R , Petrou M , Srivastava V , Farid S , Channon K , Antoniades C 
Published: October 2019

Abstract

Background
NADPH oxidase activity is a major source of superoxide anions (O2·−) in the human myocardium, linked with adverse short-term clinical outcomes after cardiac surgery, but its prognostic value for the long-term clinical outcome of these patients is unknown.

Purpose
To explore the association between NADPH oxidase activity in the human myocardium and the clinical outcome of patients undergoing cardiac surgery.

Methods
A total of 216 patients from the Oxford Heart Vessels and Fat (OxHVF) cohort were enrolled. Myocardial tissue samples were collected during cardiac surgery and used for RNA isolation and myocardial O2·− quantification using lucigenin-enhanced chemiluminescence (5μmol/L). The specific contribution of NADPH oxidase activity to myocardial O2·− production was quantified as the Vas287021 (40 μmol/L)-inhibitable signal following NADPH (100μmol/L) stimulation (Vas2870 is a NADPH oxidases inhibitor). Malonyldialdehyde and hsCRP levels were measured in plasma isolated from peripheral blood collected pre-operatively. Patients were followed-up for a mean of 2.9±1.4 years for the primary endpoint of cardiovascular mortality.

Results
Myocardial NADPH oxidase activity was not correlated with systemic oxidative stress (evidenced by malonyldialdehyde, panel A) or systemic inflammation (reflected by hsCRP levels, panel B). NADPH oxidase activity was significantly higher in the cardiovascular death group (panel C) and was associated with cardiovascular (HR [95% CI]: 1.53 [1.10–2.13], p=0.01 per SD increase) but not all-cause mortality (HR [95% CI]: 1.32 [0.96–1.80], p=0.08 per SD increase). This association remained significant after adjustment for EuroscoreII (HR [95% CI]: 1.80 [1.14–2.82], p=0.01 per SD increase). For an optimal cut-off value of 7,920 RLU/sec/mg tissue, patient survival was significantly poorer in the high vs. low NADPH oxidase activity subgroup (panel D). Adding NADPH oxidase activity to the baseline clinical model significantly improved model's performance (panel E). Interestingly, myocardial NOX gene expression levels didn't show any significance in mortality prediction, highlighting the fact that NADPH oxidase activity, rather than enzyme levels, is the key outcomes regulator.

Conclusion
Increased NADPH oxidase activity in the human myocardium independently predicts high cardiovascular mortality in patients with advanced coronary atherosclerosis. Targeting NADPH oxidase in the human heart may be a rational therapeutic approach.

Acknowledgement/Funding
BHF, EPSRC
P6294NLRP3 inflammasome is activated in the atrium of an ovine model of sustained obesity
Authors: Saljic A , Hohl M , Li N , Agbaedeng T , Twomey D , Lau D H , Mahajan R , Linz D , Jespersen T , Sanders P 
Published: October 2019

Abstract

Introduction
Obesity and enhanced inflammatory response are two independent risk factors involved in the pathogenesis of atrial fibrillation (AF). Components of the NLRP3 inflammasome have been found to be expressed in cardiomyocytes and cardiac fibroblasts and that increased inflammasome activation contributes to the pathogenesis of AF. The NLRP3 inflammasome is a multi-protein signaling complex that is activated in two steps: 1st) a priming event that includes a NFκB-activating stimuli which increases the expression of pro-inflammatory cytokines, and 2nd) a triggering event that includes the assembly of the inflammasome complex and activation of caspase-1 which promotes the production of pro-inflammatory cytokines like interleukin 1 beta (IL-1b).

Purpose
We used a sheep model of sustained obesity to characterize the association between atrial myocardial fat infiltration, atrial activation of the NLRP3 inflammasome and the development of an atrial arrhythmogenic substrate for AF.

Methods
Eight sheep were fed ad libitum calorie-dense diet over 40 weeks to gain weight and were maintained in this state of sustained obesity for another 40 weeks. Eight lean, weight-controlled and aged-matched sheep served as control. Atrial fat infiltration was determined by oil-red staining and NLRP3 inflammasome activation was assessed by immunoblot in atrial whole-tissue lysate. Atrial effective refractory periods (aERPs) were evaluated (twice diastolic threshold, cycle length (CL) of 400 ms, S1S2 -protocol).

Results
Sustained obesity was associated with increased atrial fat infiltration (lean: 0.8±0.3% vs. obese: 2.3±1.2%, p=0.1) and shorter aERP (lean: 169±22ms vs. obese: 138±26ms, p=0.03). Protein levels of caspase-1 and mature IL-1β were significantly enhanced (p=0.04 and p=0.01, respectively). Further shortening of aERP correlated with increasing atrial protein levels of caspase-1 (r=0.59, p=0.02). In contrast, levels of TNFα and NFκB were not significantly changed in atria of sheep with sustained obesity.

Conclusions
Sustained obesity is associated with increased expression of NLRP3 inflammasome-related proteins and the development of an arrhythmogenic substrate for AF. Our study suggest that the increased activity is due to increased triggering, rather than increased gene transcription. Whether NLRP3 inflammasome activation represents a modifiable target to prevent AF in obesity warrants further study.