bluuebunny/crossref_metadata_2025_split huggingface dataset:
P4426Prolonged troponin t elevation in male and female master athletes after long-distance running
Authors: Eliasson S A , Sarajlic P , Wandell P , Wallen H , Back M , Braunschweig F 
Published: October 2019

Abstract

Background
Troponin levels may be elevated after long-distance running, probably due to increased membrane permeability of cardiomyocytes. It is believed that elevated troponin post exercise, in contrast to acute coronary syndromes, normalize within 24 (−48) hours. This phenomenon has been mainly studied in young and elite athletes. However, participation in endurance exercise is increasingly popular among elderly and recreational sportsmen.

Purpose
To assess troponin levels in master athletes before and up to 7 days after long-distance running.

Method
We studied 97 participants (56 males and 41 females, matched for age) in the world's largest cross-country race (30 km, Lidingöloppet). They were ≥45 years (53±5 years). Baseline evaluation included a physical exam, blood pressure, BMI, NT-proBNP and an ECG. Blood tests were taken at baseline, immediately after as well as 1d, 4d and 7d after the race, including high sensitive troponin T (TnT), creatinine and high sensitive CRP. Elevated TnT was defined as ≥15 ng/l.

Results
After the race TnT had increased from 5±3 ng/l at baseline to 46±32 ng/l (range 11–180; p<0.0001). TnT was still significantly elevated at day 1 (16±16ng/l, range 4–106; p<0.0001) and day 4 (8±8 ng/l, range 4–63; p<0.01) with a borderline increase at day 7 (6±3; range 4–22; p=0.062). Both men and women showed a significant TnT increases at day 1 and day 4. Elevated TnT above the diagnostic threshold for myocardial infarction was observed in 96% (post race), 34% (day 1), 9% (day 4) and 3% (day 7). Males had generally higher TnT levels. At day 1, elevated TnT levels were present in 39% of males and 17% of females while all subjects with elevated TnT at day 4 and day 7 were male.

Conclusion
TnT is elevated in the vast majority of male and female master athletes after participation in a 30 km cross country race. To our knowledge, this is the first report showing that TnT levels can be still significantly elevated four days after endurance running. Prolonged TnT values above the diagnostic threshold for myocardial infarction were predominantly seen in males. Our findings are relevant to the clinical management of patients with increased troponin values after endurance exercise.

Acknowledgement/Funding
Hjärt och lungfonden (Swedish heart- and lung fund). Governmental grants.
P4462Atorvastatin and fenofibrate exert opposite effects on the vascularization and characteristics of visceral adipose tissue
Authors: Perez-Mendez O , Luna-Luna M , Mondragon-Garcia A , Aranda-Fraustro A 
Published: October 2019

Abstract

Background
Statins may precipitate the onset of type 2 diabetes (T2D) in high-risk patients. In contrast, only the subset of individuals with insulin resistance (IR) and/or diabetes receives cardiovascular benefits with fibrates. The mechanism responsible of such effects may be related with visceral adipose tissue (VAT). In this context, previous observations have suggested that atorvastatin induced an increase of VAT whereas fenofibrate had the opposite effects in rabbits.

Purpose
To determine the mass, morphology and vascularization of VAT in New Zealand white rabbits that received of atorvastatin or fenofibrate during two months.

Methods
New Zealand white rabbits (n=6 per group) received by oral gavage during 2 months, 0.33 mg/kg of atorvastatin or 2.6 mg/kg fenofibrate. The control group received 0.5 mL of vehicle. Plasma lipids were monitored. The visceral adipose tissue (VAT) was dissected and quantified. The expression of genes related with vascularization, VEGF-A and TGF-β, FGF2 as well as TNF-α were determined by qPCR in VAT. Histological slices were stained by hematoxilin and eosin to determine the size of adipocytes. The marker of angiogenesis, PECAM-1, was determined by immunohistochemistry.

Results
As expected, the cholesterol from atorvastatin was lower after treatment while triglycerides decreased in fenofibrate group. The mass of VAT from fenofibrate group was 46% lower compared with the controls meanwhile atorvastatin was associated with a larger diameter of adipocytes (+65%) than that of the control and fenofibrate groups. FGF2 gene expression was lower in fenofibrate than in control group (−54%). By contrast, VEGF-A gene expression in fenofibrate-treated rabbits was 110% higher than in control group. TGF-β and TNF-α remained comparable among groups. In agreement with the gene expression, the marker of angiogenesis PECAM-1 was slightly but significantly higher (+10%) in rabbits treated with fenofibrate than in controls, as determined by immunohistochemistry.

Conclusion
Fenofibrate enhanced the VEGF-A gene expression, PCAM-1 in VAT whereas decreased its total mass. In contrast, atorvastatin increased the adipocyte size without any effect on vascularization markers. These results suggest that fenofibrate is associated with a favorable remodeling of VAT, in contrast with atorvastatin, which induced a non-favorable remodeling of VAT. These results may be related with the cardiovascular benefits of fenofibrate and the increased risk of T2D in high-risk subjects induced by atorvastatin.
P4481NI956/QGC006, a potent orally active, brain-penetrating aminopeptidase A inhibitor prodrug for treating hypertension
Authors: Keck M , De Almeida H , Compere D , Inguimbert N , Flahault A , Balavoine F , Roques B P , Llorens-Cortes C 
Published: October 2019

Abstract

Background
Brain renin-angiotensin system hyperactivity has been implicated in the development and maintenance of hypertension. We previously showed that aminopeptidase A (APA) generates in the brain, angiotensin III, which exerts a tonic stimulatory control over blood pressure in hypertensive rats. Thus, the central injection of the specific and selective APA inhibitor, EC33 ((3S)-3-amino-4-sulfanyl-butane-1-sulfonic acid), by blocking the formation of brain angiotensin III, normalizes blood pressure in experimental models of hypertension. Therefore, brain APA appears as a potential new therapeutic target for the treatment of hypertension. We then developed RB150/firibastat, a prodrug of EC33, able of inhibiting brain APA activity and decreasing blood pressure in hypertensive rats after oral administration.

Purpose
However, considering the high dose of orally active RB150/firibastat required to decrease BP in spontaneously hypertensive rats (SHR) (150 mg/kg) and deoxycorticosterone acetate-salt (DOCA-salt) (50 mg/kg) rats, the aim of our work was to develop new more potent APA inhibitor prodrugs with greater bioavailability for inhibiting brain APA activity.

Methods
We used a salt- and volume-dependent model of hypertension, the DOCA-salt rat. For in vivo assessments of brain APA activity, brains were collected 4 hours after the oral administration. A catheter was inserted into the right femoral artery to monitor mean arterial blood pressure in alert rats. We evaluated plasma arginine-vasopressin (AVP) levels by radioimmunoassay. Rats were individually housed in metabolic cages for urine and electrolyte output measurements.

Results
We report here the development of a new APA inhibitor prodrug, NI956/QGC006, obtained by the disulfide bridge-mediated dimerization of NI929 ((3S,4S)-3-amino-4-mercapto-6-phenyl-hexane-1-sulfonic acid). NI929 is 10 more efficient than EC33 at inhibiting recombinant mouse APA activity in vitro. Following oral administration at a dose of 4 mg/kg in conscious DOCA-salt rats, NI956/QGC006 normalized brain APA activity and induced a marked decrease in blood pressure of −44±13 mmHg four hours after treatment (p<0.001), sustained over ten hours (−21±12 mmHg, p<0.05). Moreover, NI956/QGC006 decreased plasma AVP levels, and increased diuresis and natriuresis, that may decrease blood pressure by reducing the size of the fluid compartment. Finally, NI956/QGC006 did not affect plasma sodium and potassium concentrations.

Conclusions
This study shows that NI956/QGC006 is a “best-in-class” central-acting APA inhibitor prodrug, belonging to the same drug class as RB150/firibastat, supporting the strategy of brain APA inhibition for hypertension treatment.

Acknowledgement/Funding
ANR (Agence Nationale de la Recherche) grant to Catherine Llorens-Cortes (LabCom CARDIOBAPAI) and Quantum Genomics financial support.
P4482Antihypertensive drugs in experimental NAFLD as the first step to the establishment of criteria for choosing appropriate treatment of hypertension in NAFLD carriers
Authors: Soares Sturzeneker M C , Noronha L , Olandoski M , Wendling L U , Precoma D B 
Published: October 2019

Abstract

Background/Introduction
Hypertension is highly prevalent in NAFLD patients (39%). NAFLD has been independently associated with an increased risk of arterial hypertension in observational studies and emerge as the most frequent cause of chronic hepatic disease in adults. Therefore, we can deduce that treating hypertension in NAFLD carriers will be often necessary. However, there are no established criteria for choosing the most appropriate drug therapy for hypertension in patients with NAFLD, and the basic research may be the first step to the development of these criteria.

Purpose
We aimed to evaluate the effects of the renin-angiotensin system blockade with angiotensin-converting enzyme inhibitor ramipril and angiotensin 2 type 1 receptor antagonist olmesartan, used preventively, in NAFLD induced in rabbits fed hypercholesterolemic diet. Antihypertensive drugs in experimental NAFLD as the first step to the establishment of criteria for choosing appropriate treatment of hypertension in NAFLD carriers.

Methods
Olmesartan study: Thirty-four rabbits were divided into three groups (control, untreated and olmesartan). The untreated and olmesartan group were fed a hypercholesterolemic diet. Animals from olmesartan group were treated with olmesartan 1mg/kg/day.
Ramipril study: Twenty-nine rabbits were divided into three groups (normal, placebo, and ramipril). The placebo and ramipril groups were fed a hypercholesterolemic diet. The groups were orally administered 0.35 mg/kg/day of ramipril, and an equivalent volume of vehicle was administered to the placebo group. In both studies, at the end of the 8th week, all rabbits underwent segmental hepatic resection and were euthanised. Blood samples were collected to determine glucose, creatinine, total cholesterol, triglycerides, high-density lipoprotein cholesterol, and aminotransferase levels at baseline and euthanasia. Haematoxylin and eosin and Gomori trichrome stained slides were analysed based on the histological scoring system for NAFLD.

Results
The comparison between two groups (olmesartan with untreated group and ramipril with placebo) showed that ramipril and olmesartan significantly diminished the development of steatosis (p<0.013, p=0.032), lobular inflammation (p<0.001, p=0.006), and fibrosis (p=0.015, p=0.02). Based on NAFLD activity score, olmesartan and ramipril significantly reduced the development of nonalcoholic steatohepatitis (p<0.001, p=0.003).

Conclusion(s)
The preventive use of olmesartan and ramipril attenuates the development of hepatic steatosis, lobular inflammation and fibrosis in hypercholesterolemic rabbits. These results can serve as the basis to the establishment of criteria for choosing the most appropriate drug therapy for hypertension in NAFLD carriers.
P4496Copeptin and coronary artery calcium score in elderly adults without a cardiovascular history. A report from the ICELAND MI cohort
Authors: Smaradottir M I , Andersen K , Eiriksdottir G , Gudnason V , Nasman P , Ryden L , Mellbin L G 
Published: October 2019

Abstract

Background
Copeptin, a marker for vasopressin, is related to advanced cardiovascular disease such as myocardial infarction.

Purpose
The aim of the present investigation was to assess whether copeptin is associated with the different atherosclerotic plaque stages expressed by coronary artery calcium scores (CAC score).

Methods
Copeptin and CAC score were studied in 677 participants in the ICELANDIC MI cohort without a history of a myocardial infarction at baseline. The Agatston method was used to measure coronary artery calcification visualized by means of computed tomographic scans. The CAC score was categorized into four classes: 0, 1–99, 100–399, and ≥400. Correlations between the CAC score and copeptin were assessed using Spearman's Rank Correlation while the predictive value of copeptin and CAC score were evaluated with Cox proportional Hazard regression analysis (unadjusted and adjusted for age groups, serum creatinine, gender, hypertension and type 2 diabetes mellitus). The primary outcome was cardiovascular events (CVE) while total mortality served as secondary outcome.

Results
The median copeptin level was 6.4 pmol/L and the median CAC score 227.0 (IQR: 48.3–692.4) for the total cohort. The highest copeptin level was seen in people with a CAC score ≥400. Copeptin predicted total mortality in the unadjusted analysis and the CAC score predicted both outcomes. Only the CAC score that predicted outcome following adjustments (CVE: HR 1.35, 95% CI 1.23–1.48; p<0.001; and total mortality: HR 1.29, 95% CI 1.16–1.43; p<0.001). The cardiovascular prognosis was similar in those with CAC score less than 400 and above 400 regardless of the copeptin level (Figure).
Figure 1

Conclusion
In this cohort of elderly individuals without a previous MI a high CAC score was as a significant predictor of future cardiovascular events. People with high a CAC score had elevated copeptin levels but copeptin did not serve as a prognostic indicator. This suggests that copeptin elevation in people with CAD is an expression for the general state of disease rather than an indicator of a pathophysiological role of vasopressin in this context.
P4504Pulmonary circulatory-right ventricular uncoupling in acute decompensated heart failure: a key mediator of congestion
Authors: Losito M , Barki M , Labate V , Giammarresi A , Caracciolo M , Bandera F , Rovida M , Alfonzetti E , Guazzi M 
Published: October 2019

Abstract

Background
The degree of congestion in patients hospitalized for acute decompensated heart failure (ADHF) is estimated using traditional non-invasive markers such as echo-derived inferior vena cava diameter (IVCD) and NT-proBNP levels. The deterioration of right ventricular (RV) function and its uncoupling to pulmonary circulation (Pc) represents a turning point in terms of prognosis and clinical outcome in patients affected by heart failure. However, how RV-to-Pc uncoupling correlates with markers of decompensation and congestion in ADHF patients has never been explored.

Purpose
To investigate, in a cohort of ADHF patients, the association between the degree of RV-to-Pc uncoupling, assessed by the ratio between tricuspid annular plane systolic excursion (TAPSE) to pulmonary artery systolic pressure (PASP), IVCD and right atrial pressure (RAP) estimated at echocardiography.

Methods
Fourty-six ADHF patients both with reduced and preserved EF (mean age 73.15±10.85 years, 60.8% males) admitted to the Cardiology Department were prospectively enrolled within 24–48 hours from admission. In the acute phase all patients underwent transthoracic echocardiography and laboratory blood tests. Patients were then stratified in tertiles according to TAPSE/PASP ratio (group I: <0.4 mm/mmHg; group II: 0.4 to 0.6 mm/mmHg and group III: >0.6 mm/mmHg) correlating the degree of RV-to-Pc with non-invasive markers of congestion such as NT-proBNP, IVC maximum diameter and RAP. Other echocardiographic parameters including left ventricular (LV) systolic function and LV filling pressures were considered.

Results
An exponential inverse relationship was found between NT-pro-BNP levels at admission with levels decreasing progressively with the increment of the ratio (Group I: 12828±10600 ng/l; Group II 5549±5383 ng/l; Group III 3695±3870 ng/l; p=0.004) (Figure 1a). An analogous correlation was observed when considering the IVC maximum diameter (Group I: 20.87±5.37 mm; Group II 18.08±4.35 mm; Group III 10.9±3.36 mm; p<0.001) (Figure 1b) and the RAP estimated at echocardiography (Group I: 12.875±5.25 mmHg; Group II 9.157±4.82 mmHg; Group III 4±1.61 mmHg; p<0.001) (Figure 1c).
In addition, progressively increasing values of LVEF (Group I: 28±11.3%; Group II 42±17.3%; Group III 49±11.8%; p=0.001) were detected from the lowest to the highest TAPSE/PASP tertiles. No correlation was observed in the three groups for E/E' values at admission (Group I: 17.17±6.7; Group II 19.42±8.36; Group III 15.92±5.7; p=0.5).
Figure 1

Conclusions
In ADHF, the association between RV to Pc uncoupling, echo-derived measures of congestion and natriuretic peptide levels is here described for the first time. The extent of RV dysfunction in ADHF deserves attention and seems to represent a critical and quite underestimated key mechanism between congestion resolution and in-hospital worsening HF.
P4529Atrioventricular optimization in cardiac resynchronization therapy with quadripolarleads, improves energy handling and quality of life in heart failure patients: HUMVEE Trial
Authors: Antoniou C K , Konstantinou K , Chrysohoou C , Dilaveris P , Magkas N , Skiadas J , Antonakos V , Kakioris K , Gatzoulis K , Tousoulis D 
Published: October 2019

Abstract

Background
Cardiac resynchronization therapy (CRT) is a well-established technique for symptomatic heart failure (HF) patients, producing significant clinical benefits. Recent studies have revealed the potential role of multipoint pacing (MPP) in improving response and clinical outcomes. The aim of Heart failUre study of Multisite pacing effects on VEntriculoartErial coupling (HUMVEE) trial was to evaluate the association between MPP of the left ventricle vs those of standard biventricular pacing (BVP) on: a) ventriculoarterial coupling (VAC) and energy efficiency of the failing heart, b) diastolic function, c) quality of life, and d) NT-proBNP levels.

Methods
HUMVEE is a single-center, prospective (13 months) trial (clinicaltrials.gov identifier NCT03189368), of 54 NYHA III patients (69±9 years; 79% men; 50% dilated cardiomyopathy), under optimal tolerated medical therapy, with standard BVP indication, having being implanted with a CRT system able to deliver both modes of pacing. Creatinine and NT-proBNP levels and echocardiographic measurements (VAC calculation, strain rate, diastolic function assessment), as well as 6-min-walking-test and quality of life (MLHF questionnaire) were measured at baseline, 6 months post BVP optimization (right before MPP activation) and at the end of follow-up (6 months post MPP optimization). Cardiac power (CP) was calculated according the equation: CP=Cardiac Output x Mean Aortic Pressure/451.

Results
Both CRT and MPP improved 6-min-walk (differences at baseline/6 mo/end of FU: 277±27 vs. 345±27 vs 363±27 m, p=0.07); left ventricular ejection fraction (24,2% vs 30,6%vs, 32%, p=0.05); end -diastolic diameters of left ventricle (65±1,4 vs. 63±1.7 vs. 61±1.1, p=0.03); end-systolic volume (150±15 vs. 140±10 vs. 131±13, p=0.08); stroke volume (41.6±9 vs. 53.6±14 vs. 62±9, p=0.0001 for MPP); left atrial volume (76±5 vs. 74±10 vs 61±6, p=0.001 for MPP), E/Emv (14±5 vs. 12±4 vs. 11±3, p=0.05 for MPP); NtproBNP (2782±1000 vs. 2080±2500 vs. 2000±1000, p=0.05 for MPP). VAC was reduced from 1.14±0.27 to 1.1±0.17 (p=0.1) while CP increased from 564.2±142 to 768±103 (p=0.009). Quality of life score (the lower the better) improved from 23.75±17 at baseline to 17.25±10 at end of FU (p=0.05).

Conclusions
MPP is a new, promising pacing modality with the potential to improve HF patients' outcome, offering additive effects on myocardial energy balance, cardiac power, systolic and diastolic ventricular function and aortoventricular coupling, especially in ischemic patients. HUMVEE trial illustrates those clinical, imaging and biochemical divergences of MPP from standard BVP that reflect significant improvement in quality of life in patients with advanced HF and cardiac dysychronization.
P4557Factors associated with treatment and control of hypertension in a healthy elderly population free of cardiovascular disease: a cross-sectional study
Authors: Chowdhury E , Nelson M R , Ernst M E , Margolis K L , Beilin L J , Johnston C I , Murray A M , Woods R L , Wolfe R , Tonkin A M , Williamson J D , Stocks N P , McNeil J , Reid C 
Published: October 2019

Abstract

Introduction
Despite readily available treatments, control of high blood pressure (BP) in the ageing population remains suboptimal. Gaps in understanding the management of high BP amongst the elderly exist, as most studies have been in predominantly middle-aged populations.

Purpose
We explored pharmacological BP lowering treatment and control among elderly hypertensive participants free from overt cardiovascular disease (CVD), and identified factors related to both “untreated” and “treated but uncontrolled” high BP.

Methods
We analyzed baseline data from 19,114 individuals aged ≥65 years enrolled from Australia and the US in the ASPirin in Reducing Events in the Elderly (ASPREE) study. Hypertension was defined as an average systolic/diastolic BP ≥140/90 mmHg and/or use of any BP-lowering medication. `Controlled hypertensives” were those receiving BP-lowering medication and with BP <140/90 mmHg. Descriptive analyses were used to summarize hypertension control rates; logistic regression was used to investigate relationships with treatment and BP control.

Results
Overall, 74% (14,213/19,114) of participants were hypertensive, and of these 29% (4,151/14,213) were untreated. Among those treated, 47% (4,732/10,062) had BP <140/90 mmHg. Participants who were untreated were more likely to be men, have higher educational status, and be in good physical health, and less likely to have significant comorbidities. The factors related to “treated but uncontrolled” hypertension included older age, being men, Black race (versus White), using BP lowering monotherapy and residing in Australia (versus US) (Figure 1).

Conclusion(s)
There were high levels of “untreated” and “treated but uncontrolled” BP, in an otherwise healthy elderly population, suggesting that opportunities for better BP control exist through targeting intervention to high-risk individuals.

Acknowledgement/Funding
National Institute on Aging and the National Cancer Institute at NIH; NHMRC Australia, Monash University, Victorian Cancer Agency (Australia)