bluuebunny/crossref_metadata_2025_split huggingface dataset:
BLOOD PRESSURE CONTROL OF HYPERTENSIVE PATIENTS WITH HIGH HEART RATE (RESULTS FROM NATURE HTN)
Authors: Hammami Rania , Bahloul Amine , Charfeddine Salma , Triki Faten , Ellouze Tarek , Abdessalem Salem Ben , Zakhama Lilia , Added Faouzi , Abid Leila 
Published: April 2021

Objective:
High heart rate (HHR) is related to sympathic hyperactivity and. Betablockers are downgraded in the management of hypertension, however many studies showed that HHR is associated with elevated blood pressure and increased risk for cardiovascular disease. We aimed in this work to analyze the clinical profile of patients with HHR and to assess the implication of this finding on blood pressure control, based on data from the largest Tunisian national registry Nature HTN

Design and method:
Nature HTN is a national multicentric study conducted by the Tunisian society of cardiology and including hypertensive patients who consulted their doctors during one month in 2019. We defined HHR by a HR higher or equal to 80bpm. We compared two groups, group1 = HR lower than 80 bpm and group 2: HR higher than 80 bpm.

Results:
We enrolled 25890 hypertensive patients, with female predominance (SR = 1.2) and mean age 64.4 ± 12.2 yo. The hypertension was newly diagnosed in 2286 patients (8.8%) and known more than six months in 23601 persons. The mean HR was 73.8 ± 11 (extremes: 40–150). HHR was found in 4878 patients (19.2%). Patients of group 2 were more frequently female (56.5% versus 43.5%, p = 0.009). The prevalence of HHR were higher in diabetic (21 versus 18%, p < 0.001), smokers (21.4% versus 18.8%, p < 0.001) and obese (21.3% versus 18.2%, p < 0.001), patients with apnea syndrome (26.5% versus 19%, p < 0.001), patients with atrial fibrillation (29.9% versus 18.3%, p < 0.001). Patients of group 1 practiced physical activity more frequently than group 2 (15.8% versus 11.6%, p < 0.001), and are more compliant to drug and salt intake. BP control was lower in patients with HHR (40.5% versus 52.4%, p < 0.001). HHR was found as a predictor of uncontrolled BP on multivariate analysis (OR = 1.59, 95% CI (1.48–1.71), p < 0.001).

Conclusions:
Our study showed that HR is an integral part of the assessment of the hypertensive patient. Older beta-blockers do not low the central pressure and that s why no effective on cardiovascular events. Newer beta blockers are efficient on central blood pressure and could be largely used in the management of Hypertension.
HEART FAILURE WITH PRESERVED EJECTION FRACTION AMONG SYMPTOMATIC PATIENTS WITH HIGH-RISK HYPERTENSION: DIFFERENCES IN NEW DIAGNOSTIC ALGORITHMS
Authors: Gudieva Khyadi , Safarova Ayten , Kobalava Zhanna 
Published: April 2021

Objective:
We aimed to assess diagnostic scales (H2FPEF, HFA-PEFF) on a frequency of revealing HFpEF in patients with arterial hypertension (AH) and symptoms of heart failure (HF).

Design and method:
Study included 180 high risk hypertensive patients with at least one symptom or sign of HF and left ventricular ejection fraction (LV EF) more or equal 50%, 54,4 % female, 72.3 ± 9.4 years (M ± SD), obesity 54.4 %, diabetes mellitus 38.9 %, atrial fibrillation 61 %, chronic kidney disease 60 %, estimated glomerular filtration rate (eGFR) 57.5 ± 16.33 ml/min/1.73 m2, NT-proBNP level 121 (51.7; 287.7) pg/ml. Patients with significant valvular heart disease, acute coronary syndrome, acute infections, pulmonary embolism, neoplasm, eGFR < 30 ml/min/1.73 m2, body mass index > 40 kg/m2 were not included.
HFpEF was assessed by ESC HFA-PEFF and H2FPEF algorithms. Stress-echo with passive leg raising (PLR) was used to detect impaired LV diastolic function reserve and the increase in LV filling pressure.

Results:
Using ESC HFA-PEFF score patients were divided into 3 groups: low probability/absence of HF in 8.6 % of cases (<2 points), 37.9% of patients have confirmed HF (5 points), patients with intermediate risk of HF and required for stress echocardiography – 53.6 % (2–4 points). After the stress-ECHO HFpEF was additionally detected in 13.3% of patients. Low (<2 points), intermediate (2–5 points) and high probability (>5 points) of HFpEF was identified in 7.4, 60 and 32.6 % of patients according to H2FPEF score.

Conclusions:
Thus, the frequency of HFpEF using HFA-PEFF was 60%. Stress - ECHO with PLR increases the verifying of HFpEF in 13.3%. High probability of HFpEF according to H2FPEF score was 32.6%. Considering the differences in HFpEF detection using different algorithms, further research are recommended.
CURRENT PERSPECTIVES FROM THE 2020 VIRTUAL INTERNATIONAL HEART FAILURE SUMMIT FOR THERAPEUTIC HEART RATE REDUCTION WITH CARVEDILOL AND IVABRADINE IN THE FOREFRONT
Authors: Bansal Sandeep , Chaurasia Ajay , Rao Nageshwara , Aravindakumar S. , Dasbiswas Arup , Malhotra Ashish , Khera Ashok , Kumbala Dayanand , Trivedi Ak , Sinha Ajay 
Published: April 2021

Objective:
Disseminate the contemporary global evidences and practices among experts for management of management of (reduced) HFrEF, (mid-range) HFmrEF/ (recovered) HFrecEF and the role of Carvedilol and Ivabradine in the forefront through live webinar

Design and method:
A virtual learning collaborative educational initiative was convened on September 27, 2020 by Prof Michael Bohm live from Germany with high expertise rank within 0.02% of 158,672 published authors worldwide on heart failure in last one decade, with 1853 continuous active participants at forefront of HF management across India. The first module focused on need to target Ejection Fraction (EF) as a measure for improvement in outcomes in HF and second for evidence for the novel combination approach to utilise beta blockers with Ivabradine to improvise the outcomes in HF

Results:
Analysis of ESC HF long term registry represents diverse phenotypes of demography, clinical presentation, aetiology with continuum in HFmrEF and HFrEF. Elevated HR in failing heart is a maladaptation which when lowered to 55 to 65 beats per minute (bpm), with beta blockers, helps improve myocardial oxygen demand and coronary perfusion time with independent effects on heart failure. Therapeutic heart rate reduction is strongly correlated with reduced mortality and HR reduction of 5 bpm using beta blockers provide 14% risk reduction in mortality. Ivabradine mechanistically enables unloading of heart by facilitating the acceptance of higher doses of carvedilol as the drop in HR in tolerated better by conserving energy during systolic phase and improves contractility during diastolic phase. Pharmacokinetic properties of extended release formulation through logical technological innovation enhances the release of Ivabradine which mitigates the levels to fall below the critical levels. Secondary analysis of large trials show that combination works efficiently, and this is substantiated by the 2016 ESC guidelines for acute and chronic HF, which suggests higher level of evidence for the rationale

Conclusions:
Ivabradine improves uptitration of beta blockers in HF. Distinctive pharmacological properties of Carvedilol for unloading the heart makes it an evidence-based choice for the combination with Ivabradine, which antagonises spontaneous depolarisation for effective therapeutic heart rate reduction for managing heart failure.
EARLY AND CONTINUOUS DETECTION OF LEFT ATRIAL PHASIC DYSFUNCTION IN THE PROGRESSION OF HYPERTENSIVE CARDIAC REMODELING
Authors: Liu Yan , Zhao Yixiao , Sun Qiaobing , Lu Yan , Zhang Ying , Song Wei , Cheng Yunpeng , Cong Tao , Jiang Yinong 
Published: April 2021

Objective:
Objective: The left atrium (LA) modulates left ventricular (LV) filling and cardiovascular performance with its reservoir, conduit, and booster pump functions. We used two dimensional speckle tracking echocardiography (2DSTE)-based strain and strain rate to evaluate LA mechanics in hypertensive patients with or without LA/LV structural remodeling.

Design and method:
Design and Method: We enrolled 30 healthy controls (Group I) and 302 HT patients, and we divided HT patients according to LV and LA structural remodeling. Group II (n = 101), HT without LVH and LA volume index (LAVI) < 28 mL/m2; Group III (n = 82), HT without LVH and LAVI > 28 mL/m2; Group IV (n = 98), HT with LVH and E/e‘ < 13; Group V (n = 21), HT with LVH and E/e‘ > 13. The strain and strain rate images were studied, and the following parameters were measured: LA reservoir strain and strain rate (LAS-S, LASR-S), LA conduit strain and strain rate (LAS-E and LASR-E), LA booster strain and strain rate (LAS-A and LASR-A). LA stiffness index (LASI) was defined as the ratio of E/e‘ to LAS-S.

Results:
Results: LASI was significantly higher in Group II than Group I (p < 0.05), and further increased in Group III and IV. LASI is the highest in Group V (p < 0.001 vs Group I and II, p < 0.05 vs Group III and IV). Generally, All strain and strain rate parameters, including LAS-S, LASR-S, LAS-E, LASR-E, LAS-A and LASR-A, gradually and significantly decreased from Group I to Group V. We also explored the correlation between LASI and cardiovascular risk factors as well as the other markers of TOD in HT. LASI was correlated with age, diabetes, hemoglobin A1c, systolic blood pressure, BMI, LVMI, Ma/Cre, carotid IMT, PWV, Triglycerides and eGFR. Multivariate regression analysis revealed that age, BMI, PWV and Ma/Cre were independent factors related to LASI.

Conclusions:
Conclusions: The abnormality of LA mechanics precedes LA enlargement and LVH in HT, and strain-derived LA phasic function declined further along with LA and LV remodeling and diastolic dysfunction. LASI can be identified as a detective biomarker of left cardiac remodeling and diastolic dysfunction in HT.
DOES ALDOSTERONE VIA MINERALOCORTICOID RECEPTORS AND ENAC PROMOTE INTERLEUKIN-17 PRODUCTION IN LYMPHOCYTES?
Authors: Thangaraj Sai Sindhu , Oxlund Christina , Mortensen Line Aas , Thiesson Helle , Abildgaard Ib , Jensen Boye 
Published: April 2021

Objective:
Despite availability of antihypertensive therapeutic strategies, 20% of hypertensive patients remain resistant towards conventional treatment. Studies have shown that interleukin 17 (IL-17) from Th17 lymphocytes may be an important factor in the pathophysiology of hypertension. IL-17 plasma concentration is increased in hypertensive type 2 diabetes (T2D) patients compared to non-hypertensive diabetes patients. In vitro studies have shown the epithelial sodium channel ENaC to be expressed in lymphocytes. Activation of the mineralocorticoid receptor (MR) promotes pro-inflammatory Th17 lymphocyte differentiation in a spironolactone-sensitive way. We therefore hypothesized that aldosterone and ENaC may promote IL-17 production in lymphocytes ex vivo and from T2D hypertensive and kidney transplant patients in vivo.

Design and method:
Treatment resistant hypertensive T2D patients were included in a randomized double blinded study where patients were allocated to receive either spironolactone or placebo for 16 weeks (n = 116). After a two-week wash-out period the patients were included in an open label non-controlled follow-up study receiving amiloride for 8 weeks (n = 60). In a third randomized double blinded study, kidney transplant patients were allocated to receive either placebo or spironolactone for 1 year (n = 80). Plasma samples were available from all trials before and after intervention.
Key cytokines involved in Th17 differentiation (IL-17, IL-6, IL-1β, IL-10, IFN-γ, TNF-α) were measured in plasma samples from the three interventional studies using ELISAs from Mesoscale.

Results:
Spironolactone intervention in T2D hypertensive patients lead to a decrease in plasma IFN-γ and IL-6. Amiloride intervention in the same patient group showed with a decrease in plasma IL-6 and TNF-α and an increase in IL-10 levels

Conclusions:
Spironolactone and amiloride treatment of hypertensive and kidney transplant patients had no effect on IL-17 concentrations in plasma. Spironolactone suppressed the cytokines IFN-γ and IL-6, whereas amiloride decreased the levels of IL-6 and TNF-α and cause an increase in the anti-inflammatory cytokine IL-10. Since these are key cytokines of macrophage activation, MR and ENaC may be relevant for monocyte-macrophage activation. Future ex vivo experiments will be performed to elucidate the effect of amiloride and spironolactone on cytokine release from Th17 cells and macrophages.
IL-6 AND IL-10 ACTIVITY IN HYPERTENSIVE MEN WITH MODERATE OR HIGH CARDIOVASCULAR RISK
Authors: Orlova Natalya , Goryaynova Svetlana , Khachirova Asiyat , Spiryakina Yana , Posokhov Igor 
Published: April 2021

Objective:
To assess IL-6, IL-10 activity in hypertensive men with moderate or high cardiovascular risk (CVR).

Design and method:
60 hypertensive men with moderate and high CVR were included. Two groups were formed: 1st - 30 hypertensive men with moderate CVR; 2nd - 30 men with high CVR. Control group - 15 men, 45–62 years old, without chronic diseases and hypertension. Anamnesis collection, CVR study, general examination, biochemical blood test, ECG, ECHO were held. IL-6, IL-10 were determined by the enzyme-linked immunosorbent assay method. The Mann-Whitney nonparametric test was used for groups comparison. The statistical significance of different values was determined by using the Pearson's Chi-square test. Correlation analysis was carried out on the basis of Spearman's nonparametric rank correlation.

Results:
IL-10 activity: moderate risk group - 5.18 [3.74; 7.03] pg/ml, high-risk group - 4.92 [2.96; 6.36] pg/ml, control group - 6.63 [5.90; 9.07] pg/ml. There was a statistically significant IL-10 decrease in the high-risk group in comparison with the control group (p = 0.0175). IL-6 activity: moderate risk group - 1.55 [0.75; 2.68] pg/ml, high-risk group - 1.16 [0.48; 2.41] pg/ml, control group - 1.02 [0.00; 9.83] pg/ml, there were no statistically significant differences in the groups. Correlation analysis revealed a multidirectional relationship between IL-10 and the hypertension duration in two groups: with a high risk a negative correlation was revealed (R = - 0.5, p < 0.01), with a moderate risk a positive correlation was revealed (R = 0.46, p < 0.05). IL-6 positively correlated with the thickness of the carotid artery intima-media complex (R = 0.41, p < 0.05) in men with moderate CVR.

Conclusions:
IL-10 decrease was revealed in hypertensive men with high CVR as compared to the healthy people. It can be used as an additional criterion for high CVR. The negative IL-10 correlation with the hypertension duration reflects the unfavorable development of hypertension in hypertensive men with high CVR. The detection of high IL-6 values in hypertensive men indicates the risk of endothelial dysfunction.
LONG-TERM CALORIC RESTRICTION IMPROVES MYOCARDIAL SIRT1/AMPK/PGC-1A PATHWAY IN C57BL/6J MICE
Authors: Ma Lina , Wang Rong 
Published: April 2021

Objective:
Caloric restriction (CR) is capable of improving heart function, there is as yet no consensus on the mechanism of effect of CR. Silent mating-type information regulation 1 (SIRT1), adenosine monophosphate-activated protein kinase (AMPK), and mTOR are key players in metabolic stress management. We aimed to explore the effect of CR on myocardial SIRT1/AMPK/mTOR pathway in mice.

Design and method:
Thirty 6-week-old male C57BL/6J mice were randomly divided into three groups: normal control group (NC group, n = 12), high-energy group (HE group, n = 12) and CR group (n = 12) according to different diet. After 11 months, western blot was used to examine proteins such as p-AMPK, peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1a), SIRT1, and p-mTOR, whereas real-time PCR was used to examine the expression of AMPK, PGC-1a, and SIRT1 transcripts.

Results:
Compared with NC group, the CR group displayed increased expression of myocardial p-AMPK, SIRT1 protein and mRNA, and PGC-1a mRNA. However, no difference was observed in the expression of p-mTOR protein and mTOR mRNA in the myocardium among the three groups.

Conclusions:
CR improves SIRT1/AMPK/PGC-1a pathway in mice myocardium with no effect on the mTOR pathway.
HYPERTENSIVE PATIENTS AS CANDIDATES FOR RENAL SYMPATHETIC DENERVATION: CONSENSUS OPINION OF HYPERTENSION EXPERTS IN GREECE
Authors: Doumas Michael , Andreadis Emmanouil , Davlouros Periklis , Dimitriadis Kyriakos , Gkaliagkousi Eugene , Grassos Harris , Hatzitolios Apostolos , Imprialos Konstantinos , Kalaitzidis Rigas , Kallistratos Emmanouil , Konstantinidis Dimitrios , Kotsis Vasilios , Makris Thomas , Manolis Athanasios , Marketou Maria , Papadakis Ioannis , Papadopoulos Dimitrios , Poulimenos Leonidas , Sanidas Ilias , Savopoulos Christos , Stavropoulos Konstantinos , Stergiou George , Thomopoulos Konstantinos , Triantafyllidi Helen , Triantafyllou Areti , Vlachakos Dimitrios , Zebekakis Pantelis , Ziakas Antonios , Tsioufis Costas 
Published: April 2021

Objective:
Several studies have evaluated the efficacy and safety of renal sympathetic denervation (RSD) in patients with hypertension and other conditions characterized by sympathetic overactivity. However, to date there is no consensus in the literature about which patients are the most appropriate candidates for RSD. This analysis presents the opinions of hypertension experts in Greece regarding potential candidates for RSD.

Design and method:
Chairpersons of ESH Hypertension Excellence Centers in Greece and their senior clinical research fellows, were invited to participate in a meeting aiming to discuss the current evidence on the clinical utility of RSD. Individual responses were recorded and qualitatively analyzed, in order to reach consensus about potential RSD candidates.

Results:
Twenty-five experts participated in the meeting (cardiologists 52%, internists 40%, nephrologists 8%). (i) 84% of the experts agreed that patients with resistant or uncontrolled hypertension are the most eligible candidates for RSD. (ii) Patients who are either non-adherent to treatment (72%) or discontinued antihypertensive drugs due to adverse events (64%) were suggested as potential candidates. (iii) Patients with severe left ventricular hypertrophy or other TOD were also proposed as potential candidates (24%). (iv) Individuals with diseases associated with sympathetic overactivity (72%), such as obstructive sleep-apnea syndrome, chronic kidney disease, heart failure, arrhythmias, and polycystic ovary syndrome. (v) Patients at the initial stages of hypertension (12%), women of child-bearing potential (4%), drug naïve patients (16%), and patients of young age without TOD were also considered (12%). (vi) Hypertensive patients with increased sympathetic activity, such as patients with excessive white-coat hypertension or sodium sensitivity, were also proposed as potential candidates (8%). (vii) Patients preferring RSD over life-long drug treatment might also be eligible (24%).

Conclusions:
Seven patient groups were identified as potential candidates for RSD. Experts agreed on the eligibility of patients with resistant hypertension, yet other groups of patients were also proposed. More data are needed to properly identify those patients who will benefit the most from RSD, aiming towards personalized therapy in this field.
A 3-YEAR DURABILITY OF POWERFUL BLOOD PRESSURE LOWERING EFFECT OF DISTAL RENAL DENERVATION
Authors: Pekarskiy Stanislav , Baev Andrei , Falkovskaya Alla , Sitkova Ekaterina , Zubanova Irina , Lichikaki Valeria , Mordovin Viktor 
Published: April 2021

Objective:
To evaluate efficacy and safety of anatomically optimized distal renal denervation (RDN) in segmental branches of renal artery.

Design and method:
We performed a double blind, randomized control study of the efficacy and safety of distal RDN versus conventional main trunk treatment in patients with true resistant hypertension (NCT02667912) with 3 year follow-up period. The efficacy of the RDN was evaluated by changes in ambulatory and office BP at 6, 12 and 36 month. The safety was assessed by a number of procedure-related adverse events, changes in the 24-h protein excretion, serum creatinine and eGFR during the same time periods.

Results:
Of 55 randomized patients who undergone RDN (28 - distal denervation vs 27 - main trunk treatment) 51 completed 6 month (27 vs 24), 47 - 12 month (23 vs 24), and 39 - 36 month follow-up (21 vs 18).
There was a powerful significant decrease in 24-h mean ambulatory systolic BP at 6 month after distal RDN that was, also, maintained throughout the follow-up, and remained statistically significant at the end of the study, -21.1 (95% CI -28.9;-13.3), -18 (95% CI -27.6;-8.5), -16.9 (95% CI -27.3;-6.5), mmHg, at 6, 12, and 36 month, respectively. In group of conventional main trunk treatment the same BP decreased substantially less at all study periods, and lost significance at 36 month. -10.3 (95% CI -17.8;-2.8), -12.1 (95% CI -19.2;-5.0), -8.7 (95% CI -19.7;2.2). Other ambulatory BP indices changed accordingly.
eGFR decreased in group of distal RDN at 1 year post-procedure -8.9 (95% CI -14.8;-3.1), mL/min/sq.m, however, slightly increased during next 2 years with finally non-significant change at the end of the study, -6.5 7 (95% CI -13.2;0.3). In contrast, in group of main trunk treatment eGFR remained unchanged during 1st year, -1.3 (95% CI -6.6;4.0) but progressed to statistically significant decrease at 3-year post-procedure, -5.0 (95% CI -9.6;-0.3).

Conclusions:
Anatomical optimization of renal denervation by redistributing treatments to segmental branches of renal artery produces a durable increase in the efficacy of the intervention without additional risk to the kidney.
EFFECT OF CHILD-TO ADULT RESTING HEART RATE TRAJECTORY ON SUBCLINICAL RENAL DAMAGE IN MIDLIFE
Authors: Yuan Yue , Mu Jian-Jun , Chu Chao , Zheng Wen-Ling , Ma Qiong , Hu Jia-Wen , Wang Yang , Yan Yu , Liao Yue-Yuan , Chen Chen 
Published: April 2021

Objective:
It has been well established that an elevated resting heart rate (RHR) is associated with the development of chronic kidney damage (CKD), but the relationship between the developmental patterns of RHR and CKD has not been studied before.

Design and method:
A total of 2339 participants enrolled in the large-scale Hanzhong Adolescent Hypertension cohort study, which was established in 1987 and was followed up over 30 years, were included in the final analysis. Latent mixture modelling was used to explore the child-to-adult trajectories of the RHR.

Results:
We identified four RHR trajectories from childhood to adulthood: a low-stable group (class 1, n = 1104), a moderate-stable group (class 2, n = 1098), an increasing-decreasing group (class 3, n = 78), and a decreasing-increasing group (class 4, n = 59). Individuals in class 4 had the highest risk ratio (RR) of incident subclinical renal damage (SRD) after they were fully adjusted compared with those in class 1 [RRs = 4.12 (1.65–10.33), P < 0.01], and individuals in class 3 had nearly 1.43 times the risk of prevalent SRD compared with those in class 1. Significant differences existed in body mass index (BMI) by RHR trajectory groups in prepuberty, puberty and middle-aged adulthood (all P < 0.05). In subjects who were overweight, those in class 2 and class 4 had significantly higher risk of prevalent SRD when compared with those in class 1 [RRs = 1.65 (1.09–2.50), RRs = 5.39 (1.45–20.11), respectively].

Conclusions:
RHR lacks stability in middle-aged segments of the population. Elevated RHR and increasing RHR in midlife are independently associated with the development of SRD, particularly in overweight participants.