bluuebunny/crossref_metadata_2025_split huggingface dataset:
P3457Oxidative stress and left ventricular remodeling in postmenopausal women
Authors: Lareva N , Govorin A , Luzina E 
Published: October 2019

Abstract

Purpose
To asses the level of oxidative stress in postmenopausal women in dependence of LV structural and functional changes and its filling parameters.

Methods
203 postmenopausal women were included in the investigation: 142 women with surgical menopause (average age 44,3±5,4 years, menopause duration 3,8±2,4 years); and 61 women with natural menopause (average age 46,2±4,7 years, menopause duration 4,3±2,1 years). All patients underwent general clinical examination, menopausal index evaluation, ambulatory blood pressure (BP) monitoring (Cardiotens-01, Meditech, Hungary), echocardiographic examination with systolic and diastolic left ventricular (LV) function assessment. We also measured erythrocyte thiobarbituric acid reactive substances (TBARs), ultimate products of lipid peroxidation (Shiff bases), catalase activity and plasma general antioxidant activity. Control group consisted of 35 healthy menstruating women (mean age 39,2±4,2). Statistical methods such as Cruskell-Walles criteria and χ2 test were used.

Results
Only 39 postmenopausal women (19,2%) had normal LV geometry; 89 pts (43,8%) demonstrated LV concentric hypertrophy, 57 pts (28,1%) – concentric remodeling and 18 women (8,9%) –eccentric hypertrophy. All postmenopausal women showed signs of activation of oxidative stress while reducing the power of antioxidant protection systems, however, these changes were most pronounced in groups of patients with eccentric and especially concentric LV hypertrophy
Nobody of included postmenopausal women had LV systolic function failure. Presence of LV diastolic function disturbance was the same in the patients with surgical and natural menopause (54,1% (33 pts) and 59,1% (84 pts), respectively, p=0,231) and did not depend on BP level: 59,1% (52 pts) in hypertensive and 56,5% (65 pts) in normotensive women, p=0,118. We detected that Shiff bases level in postmenopausal women with diastolic dysfunction was increased in 1,5 times in comparison with healthy menstruating women and in 1,3 times in comparison with those postmenopausal women who had no diastolic function disturbance (p<0,01). The level of erythrocyte TBARs in this group was increased in 1,3 and 1,2 times respectively (p<0,05). Erythrocyte catalase activity and plasma general antioxidant activity were decreased in all postmenopausal women in comparison with healthy ones (p<0,01). The presence of LV diastolic dysfunction correlated positively with erythrocyte Shiff bases level (τ=0,47, p<0,01) and negatively – with erythrocyte catalase activity and plasma general antioxidant activity (τ=−0,35 and τ=−0,35, p<0,01 respectively)

Conclusions
Thus, oxidative stress may play important role in left ventricular remodeling and diastolic dysfunction formation in postmenopausal women.
P3460Structural and functional changes of vascular wall in women of perimenopausal period with long-term menopausal hormone therapy
Authors: Tolstov S N , Salov I A , Rebrov A P 
Published: October 2019

Abstract

Introduction
Features of changes in the vascular wall in women of the menopausal period are not sufficiently illuminated. Most of the studies evaluating the effect of menopausal hormonal therapy (MHT) on the structural and functional state of the vascular wall were limited to the time frame from several months to 1–3 years, which distinguishes them from our study.

Purpose
To evaluate structural and functional changes in the vascular wall in women of early postmenopausal period with prolonged use of low doses of MHT 1 mg of 17β-estradiol (E2) and 2 mg drospirenone (DRSP).

Methods
The study included 162 women in the early postmenopausal period with climacteric syndrome were divided into 2 groups: the main group of 84 women assigned MHT 1 mg E2 /2 mg DRSP, control group of 78 women who did not receive MHT. Duration of follow-up 5,2 (4,8; 5,7) years. Explored pulse wave velocity (PWV). Bbrachial blood pressure was measured non-invasively over the 24 h with an electronic, oscillometric, automated device (BPLab) with the assessment of 24-h central arterial pressure (CAP), aortic augmentation index (AIx), arterial stiffness index (ASI); ambulatory arterial stiffness index (AASI). Endothelium-dependent vasodilation (EDV) of the brachial artery was evaluated.

Results
In women of the main group PWV made up 7.19±1.7 m/s initial and 7.53±1.3 m/s to the end of the study (p>0.05); in the control group - 7,21±1.8 m/s and 7.95±1.9 m/s (p<0.001). In the women of the main group by the end of the study a decrease in the CAP was noted from 38.4±6.2 to 35.3±4.1 mm Hg. (p<0.001), in the women of the control group there were no changes of 41.4±9.6 and 40.9±9.8 mm Hg. (p<0.001 between women of both groups at the end of the study). In women of the control group, a significant increase in AIx was found from 31.0 (20.0; 35.0)% initially to 33.0 (29.0; 37.0)% by the end of the study (p<0.05) and no changes in women of the main group – 27.0 (20.0; 35.0)% and 28.0 (20.0; 33.0)%. Multidirectional changes ASI were revealed: a decrease in women of the main group from 132.0 (121.0; 142.0) to 127.0 (115.5; 137.0) cu and an increase from 133.0 (111.0; 155.0) to 148.0 (134.2; 171.0) cu in women of the control group (p<0.01 between women of both groups at the end of the study).
By the end of the study, there was a decrease in AASI in women of the main group from 0.379 (0.320; 0.463) to 0.264 (0.203; 0.329) cu (p<0.001) and the absence of changes AASI value in women of the control group – 0.360 (0.283; 0.471) and 0.370 (0.310; 0.476) cu. In women of the main group, an increase in the brachial artery EDV was found from 8.6±7.4% initially to 11.1±6.8% by the end of the study (p<0.05) and no change in women in the control group −7.3±5.6% and 6.2±5.0%.

Conclusion
In women in early postmenopause with prolonged MHT of 1 mg E2/2 mg DRSP positive changes in the structural and functional state of the vascular wall were established.
P3471Anti-inflammatory effects of direct oral anticoagulants in patients with non-valvular atrial fibrillation: insights from 2216 patients in the DIRECT registry
Authors: Hamanaka Y , Sotomi Y , Hirata A , Hirayama A , Higuchi Y 
Published: October 2019

Abstract

Background
Several previous studies reported anti-inflammatory effect of direct oral anticoagulant (DOAC). However, it was limited to basic pathological data with small sample size. Real-world large clinical data is still scarce.

Methods
We conducted a single-center prospective observational registry of NVAF patients treated with DOACs: the DIRECT registry (UMINehz745.034333283). All patients with nonvalvular atrial fibrillation (NVAF) (N=2216) who were users of dabigatran (N=648), rivaroxaban (N=538), apixaban (N=599), or edoxaban (N=431) from June 2011 to November 2017 were enrolled (71.6±10.8 years, 36.4% female, follow-up duration: 407.2±388.3 days). High sensitive C-reactive protein (hsCRP) test was performed before (within 3 months from the start) and after the start of DOAC prescription (6±3 months after the start). Patients with a hsCRP value >1.00 mg/dL were excluded from the analysis due to possibility of other systemic inflammatory conditions. The present post-hoc study of the DIRECT registry assessed anti-inflammatory effect of DOAC. Pre-hsCRP and post-hsCRP were compared by Wilcoxon Signed Ranks test.

Results
A total of 1,855 patients were analyzed in the present study (71.0±10.7 years, 677/1,855 (36%) females). In the overall cohort, hsCRP significantly decreased after the start of DOAC prescription (pre median 0.08 interquartile range [0.04–0.17] mg/dL vs. post 0.06 [0.03–0.12] mg/dL, p<0.001). The significant reduction of hsCRP was consistent across all DOACs (p=0.301) [dabigatran (N=562), pre 0.08 [0.04–0.1625] mg/dL vs. post 0.06 [0.03–0.12] mg/dL, p<0.001: rivaroxaban (N=457), pre 0.07 [0.04–0.16] mg/dL vs. post 0.07 [0.03–0.125] mg/dL, p<0.001: apixaban (N=494), pre 0.09 [0.04–0.19] mg/dL vs. post 0.06 [0.03–0.13] mg/dL, p<0.001: edoxaban (N=342), pre 0.08 [0.04–0.19] mg/dL vs. post 0.06 [0.03–0.13] mg/dL, p<0.001].

Conclusions
The present study of DIRECT registry suggested anti-inflammatory effect of DOAC presented as a significant reduction of hsCRP. Although further investigation would be warranted to evaluate the clinical significance of the suppressed systemic inflammation, the recent favorable clinical data of DOACs might be attributed to the present finding.
P3472Modifications of renal function in atrial fibrillation patients treated with different oral anticoagulants: a multicentre cohort study
Authors: Pastori D , Lip G Y H , Sciacqua A , Perticone F , Melillo F , Godino C , Marcucci R , Berteotti M , Violi F , Pignatelli P 
Published: October 2019

Abstract

Background
A decline of estimated glomerular filtration rate (eGFR) has been described in atrial fibrillation (AF) patients on Vitamin K antagonists (VKAs). Few real-world data on the modifications of eGFR in AF patients treated with non-vitamin K antagonist oral anticoagulants (NOACs) do exist.

Purpose
To evaluate changes of renal function in AF patients treated with VKAs or NOACs.

Methods
Multicentre prospective cohort study including 1,667 patients with non-valvular AF from 5 clinical centres of Internal Medicine and Cardiology in Italy.
Renal endpoints were: 1) median annual decline of eGFR; 2) transition to eGFR <50 ml/min/1.73 m2; 3) eGFR class worsening according to KDIGO 2012 classification. The eGFR was assessed by the CKD-EPI formula at baseline and during follow-up.

Results
Median age was 73.7±9.1 years and 43.3% were women. 743 patients were on VKAs and 924 on NOACs (Dabigatran, Rivaroxaban e Apixaban). Median annual eGFR decline was −2,11 (Interquartile Range [IQR] −5,68/−0,62] in patients on VKAs, −0,27 [IQR −9,00/4,54] with Dabigatran (p<0.001 vs. VKAs), −1,21 [IQR −9,98/4,02] with Rivaroxaban (p=0.004 vs. VKAs) and −1,32 [IQR −8,7/3,99] with Apixaban (p=0.003, vs. VKAs). Use of Dabigatran and Apixaban was associated to a lower transition to eGFR <50 mL/min/1.73 m2, compared to VKAs: adjusted Odds Ratio (aOR) 0.492, 95% Confidence Interval (CI) 0.298–0.813, p=0.006 for Dabigatran; aOR 0.449, 95% CI 0.276–0.728, p=0.001 for Apixaban). Regarding the eGFR class worsening, Dabigatran (aOR 0.70, 95% CI 0.503–0.975, p=0.035), Rivaroxaban (aOR 0.591, 95% CI 0.423–0.825, p=0.002), and Apixaban (aOR 0.591, 95% CI 0.429–0.815, p=0.001) were all associated to a lower rate of eGFR class worsening compared to VKAs.
Forest plot

Conclusions
In this prospective multicentre cohort study, NOACs use was associated with a lower decline of renal function compared to VKAs. Patients on Dabigatran showed the lowest annual rate of eGFR decline and those on Apixaban and Rivaroxaban a lower eGFR class worsening.

Acknowledgement/Funding
None
P3474Relationship between international normalized ratio variability, quality of anticoagulation control and outcomes in patients with atrial fibrillation: an AFFIRM post-hoc analysis
Authors: Proietti M , Romiti G F , Olshansky B , Lip G Y H 
Published: October 2019

Abstract

Introduction
Quality of anticoagulation control is essential to ensure better clinical outcomes in patients with atrial fibrillation (AF). Time in therapeutic range (TTR) is recommended as a measure of the quality of anticoagulation control. The International normalized ratio (INR) variability has been suggested as an alternative index, even though large independent validations for this index are still lacking.

Purpose
To provide validation of clinical usefulness of INR variability as a measure of the quality of anticoagulation control in a large cohort of AF patients.

Methods
Data from the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial were analysed. INR variability was defined as the standard deviation (SD) of mean INR values [INR-SD] recorded throughout the follow-up observation for each patient. All patients with available INR values were included in the analysis. Stroke, major bleeding, cardiovascular (CV) death and all-cause death were study outcomes.

Results
Among the original 4060 patients, a total of 3185 (78.4%) were available for analysis. Mean (SD) INR-SD was 0.58 (0.25). According to INR-SD patients were categorized into four quartiles. Mean (SD) CHA2DS2-VASc score was increased (p=0.040), with no difference in proportions of CHA2DS2-VASc ≥2 (p=0.582) between the subgroups. A significant inverse correlation was found between INR-SD and TTR (Spearman's Rho: −0.536, p<0.001). Continuous INR-SD, after multiple adjustments, was inversely associated with TTR (standardized beta: −0.451, p<0.001) and directly associated with SAMe-TT2R2score (standardized beta: 0.084, p<0.001). A fully adjusted Cox multivariate regression analysis found that INR-SD was directly associated with increased risk of stroke, major bleeding and all-cause death (Table). An INR-SD ≥0.85 was directly associated with all the study outcomes, on multivariate analysis (Table).
Cox Regression Analysis INR-SD INR-SD ≥0.85 HR (95% CI) HR (95%) Stroke 2.52 (1.34–4.67) 1.62 (1.00–2.63) Major Bleeding 2.43 (1.49–3.96) 1.61 (1.10–2.36) CV Death 1.50 (0.87–2.59) 1.54 (1.07–2.24) All-Cause Death 1.79 (1.21–2.66) 1.55 (1.17–2.05) CI = Confidence Interval; CV = Cardiovascular; HR = Hazard Ratio; INR-SD = International Normalized Ratio Standard Deviation.

Conclusions
INR variability, expressed as INR-SD, was significantly correlated and associated with TTR. Both continuous INR-SD and INR-SD ≥0.85 were significantly associated with a higher risk of all study adverse outcomes.

Acknowledgement/Funding
None
P3478Glucose-dependent insulinotropic peptide is essential for maintenance of cardiac lipid metabolism via FGF21-dependent pathway
Authors: Remina Y , Kureishi Bando Y , Ozaki R , Kamihara T , Nishimura K , Murohara T 
Published: October 2019

Abstract

Background/Introduction
Incretin hormones, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are secreted from the small intestine and emerged as important participants in glucose homeostasis that involves in the pathogenesis of type 2 diabetes (T2D). stimulate glucose-dependent insulin biosynthesis. Emerging data suggest important extrapancreatic functions for GLP-1 on cardiovascular system. However, limited evidence has been emerged whether GIP may play any pathophysiological role in heart. GIP promotes insulin secretion leading to augment insulin-induced lipogenesis. Recent research has highlighted the relevance of the GIP/GIPR axis in principal insulin-sensitive organs such as adipose tissue. Heart is another insulin-sensitive organ in which insulin promotes hypertrophy of myocardium presumably via activation of Akt pathway. In T2DM, ectopic accumulation of lipid and fat to myocardium that is known as “cardiac steatosis”; however, it remains uncertain whether the GIP/insulin axis may modulate cardiac steatosis observed in T2DM.

Purpose
To elucidate that physiological GIP may play a regulatory role in cardiac pathophysiology.

Methods
We employed mouse model of GIPR deficiency (GIPR-KO) that was generated by lacking the GIPR gene (GIPR), by replacing exons 4 and 5 of GIPR with the PGK-neo cassette. Cardiac evaluation of GIPR-KO was performed at the age of 6 week-old (w/o), 10 w/o, 23 w/o, and 53 w/o.

Results
GIPR deficient mice (GIPR-KO) exhibited normoglycemia, but their circulating free acid level and ketone level were elevated. Interestingly, GIPR-KO at younger age (6-week-old and 10-week old) exhibited normal left-ventricular (LV) function, however, older mice aged older than 20-week-old exhibited significant systolic left-ventricular dysfunction (FS (%) 55.2±1.9 for Wild-type, 32.1±2.6 for 23-w/o-GIPR-KO, 28.5±2.6 for 56-w/o-GIPR-KO, P<0.01). Histological analysis revealed that cardiomyocyte size was decreased and capillary density was increased in GIPR-KO. Interestingly, TUNEL staining revealed that there was no increase in cardiac apoptosis in GIPR-KO. In contrast, GIPR-KO exhibited increase in cardiac fibrosis (Picro-sirius staining) and oxidative stress (DHE staining). Myocardial triglyceride accumulation was decreased in GIPR-KO heart. QPCR analysis revealed GIPR-KO heart exhibited increase in BNP level and decline in fibroblast growth factor 21 (FGF-21), an hormonal activator for energy expenditure in adipocyte. GIP augmented FGF-21 expression in cardiomyocytes via PPARalfa.

Conclusion
Loss of GIP signaling caused impaired fatty acid metabolism in heart via impairment of FGF21 pathway and oxidative stress, leading to an age-dependent progression of cardiac dysfunction.
P3529Prognostic impact of cohabitation status in hospitalized patients with acute heart failure
Authors: Kenichiro Y , Oguri M , Takahara K , Takahashi H , Ishii H , Murohara T 
Published: October 2019

Abstract

Background
The prevalence of heart failure (HF) in the elderly is steadily increasing, therefore, the prudent care and treatment according to individual's characteristics, comorbidities, or prognosis, should be prerequisite. Although cohabitations status in each elderly patient is different, an association of this condition with long-term prognosis remains to be identified definitively in Japan.

Purpose
The purpose of the present study was to examine the prognostic impact of cohabitation status on 3-year mortality among hospitalized acute HF patients.

Methods
The study population comprised a total of 817 individuals who were hospitalized for acute HF between November 2009 and December 2015, and was followed up for 3 years. We classified patients into three groups (cohabitation with spouse, cohabitation with another generation, and living alone). We evaluated relative predictive values between these three groups for 3-year mortality by Cox regression model.

Results
The median age was 79 (interquartile range 70–85) years, and 55.7% of the subjects were male. Median length of hospital stay was 16 (interquartile range 11–23) days. The distribution of three groups was cohabitation with spouse (50.9%), cohabitation with another generation (28.5%), and living alone (20.6%). The overall rate of 3-year mortality was 32.2% (n=263), 31.5% (n=131) in cohabitation with spouse, 38.2% (n=89) in cohabitation with another generation, and 25.6% (n=43) in living alone. Cohabitation with another generation was significantly related to the occurrence of 3-year mortality by univariate analysis (P<0.001). Age (84 years vs. 77 years), the frequency of female (69.1% vs. 33.4%), left ventricular ejection fraction (52.7% vs. 47.5%) were significantly greater, whereas body mass index (21.2 vs. 22.6), smoking status (27.0% vs. 53.4%), ischemic etiology (27.5% vs. 35.6%), and the prevalence of type 2 diabetes mellitus (32.2% vs. 41.4%) and atrial fibrillation (20.6% vs. 29.8%) were significantly (P<0.05) smaller in cohabitation with another generation than others. The ratio of home return and optimal medical therapy were similar between the 2 groups. Cohabitation with another generation was associated with higher relative risk of 3-year mortality than living alone [Hazard Ratio (HR) 1.65; 95% Confidence Interval (CI) 1.15–2.38, P=0.007], or cohabitation with spouse (HR 1.46; 95% CI 1.12–1.92, P=0.006). Multivariable Cox regression model, with adjustment for age, albumin, brain natriuretic peptide, and prior HF hospitalization, revealed that cohabitation with another generation was no longer significant.

Conclusion
Our present results suggest that cohabitation status affected on long-term prognosis in patients with HF, especially cohabitation with another generation posed as worst predictor. We should pay more attention to social factors including cohabitation status in the clinical practice.
P3548Noninvasive estimation of left ventricular diastolic function in patients with hypertension and normal ejection fraction using 3-dimensional speckle tracking echocardiography
Authors: Minatoguchi S , Tanaka R , Yoshizane T , Deguchi T , Sato H , Ono K , Nagaya M , Miwa H , Iwama M , Noda T , Watanabe S , Kawasaki M , Okura H 
Published: October 2019

Abstract

Background
Left ventricular (LV) relaxation (eTau) and pulmonary capillary wedge pressure (ePCWP) were reported to be estimated by speckle tracking echocardiography (STE). LV camber stiffness (e-c stiffness) may be estimated with the use of 2 diastolic pressure-volume coordinates. The minimum diastolic pressure (mP) is reported to have a strong correlation with Tau.

Purpose
We sought to examine the impact of hypertension on LV diastolic function and LA properties and to elucidate the feature of hypertensive heart failure with preserved EF (HFpEF).

Methods
The e', E/e', Tau, PCWP, LVEDP, LV stiffness, LAV, LA emptying function (LAEF) and LA strain were examined in 53 controls (age 66±11), 136 hypertensive patients (HTN) with normal EF (69±11) and 39 HFpEF (77±14). ePCWP and estimated EDP (eEDP) was calculated as previously reported. Tau was calculated as isovolumic relaxation time/(ln 0.9 x systolic blood pressure − ln PCWP). Myocardial stiffness (e-m stiffness) was estimated as LVED stress/LV strain. LV c-stiffness was calculated as LV pressure change (from mP to EDP) obtained by catheterization divided by LV volume change. Estimated LV c-stiffness (e-c-stiffness) was noninvasively obtained using e-mP and e-EDP. The eTau, eEDP and e-mP by STE were validated by catheterization (n=126).

Results
The mP had a good correlation with Tau (r=0.70, p<0.01). The eTau, eEDP and e-mP by STE had a good correlation with those by catheterization (r=0.75, 0.63 and 0.70, p<0.01). Multivariate analysis revealed that ePCWP and LA strain were independent predictors of HFpEF.
LV diastoric function Variables Control HTN HFpEF LVEF, % 68±6 68±8 63±9*+ LV longitudinal strain x (s–1) 19.1±3.0 16.8±4.3* 14.5±5.1*+ E/e' 9.2±2.6 11.6±4.5* 15.9±7.9*+ eTau, ms 35±12 48±17* 59±17*+ ePCWP, mmHg 7.3±2.7 8.3±4.3 15.0±4.4*+ eLVEDP, mmHg 9.4±2.2 10.4±3.5 15.9±3.7*+ LV e-myocardial stiffness, kdynes/cm 0.56±0.25 0.69±0.56 1.27±0.71*+ LV e-chamber stiffness, mmHg/ml 0.19±0.06 0.20±0.08 0.36±0.19*+ Maximum LAVI, ml/m2 42±15 50±21* 68±17*+ Total LAEF, % 55±7 51±11 36±12*+ LA peak strain 41±15 40±17 19±8*+ *p<0.05 vs Control, +p<0.05 vs HTN.

Conclusion
We demonstrated that LV diastolic function in HTN may be accurately and noninvasively evaluated by STE.