bluuebunny/crossref_metadata_2025 huggingface dataset:
RAGE-MEDIATED CELLULAR SIGNALING IS TRIGGERED BY THE ALLOSTERIC ACTIVATION OF THE AT1 RECEPTOR
Authors: Yamamoto Koichi , Yokoyama Serina , Huang Yibin , Kawai Tatsuo , Rakugi Hiromi
Published: April 2021

Objective:

We recently identified the physical interaction of a pattern recognition receptor (PRR), lectin-like oxidized LDL receptor with the GPCR, angiotensin II type 1 receptor (AT1) whereby oxLDL allosterically activates AT1. In this study, we investigated if AT1 physically interacts with another PRR, the receptor for AGE (RAGE), and ligands of RAGE could allosterically activate AT1.

Design and method:

We used normal rat kidney epithelial cells (NRK52E) to investigate the interaction of the endogenous receptors. We also generated five different genetically-engineered CHO cells to individually analyze the G protein and β-arrestin pathways of AT1 activation; CHO cells expressing human RAGE (CHO-RAGE), CHO cells expressing both hRAGE and hAT1 (CHO-RAGE-AT1), CHO cells expressing both hRAGE and mutated hAT1 with impaired ability to activate G protein, and CHO cells expressing both hLOX-1 and mutated hAT1 with impaired ability to activate β-arrestin

Results:

In NRK52E, AGE-BSA provoked the activation of MAP kinase (ERK) that was inhibited by ARB or siRNA of AT1 or RAGE. Activation of NfκB and Epithelial mesanchmal transition induced by AGE-BSA was inhibited by ARBs as well as RAGE inhibitor. In genetically engineered CHO-cells, in situ PLA assay and immunoprecipitation confirmed the physical interaction of AT1 and RAGE on cellular membrane. HMGB1, a RAGE ligand induced Gαi-dependent inhibition of cAMP production only in the presence of both RAGE and AT1 with intact G protein binding. The effect of HMGB1 on cAMP content was abolished by ARB as well as RAGE inhibitor. HMGB1 did not induce the accumulation of IP1, a downstream of Gαq signaling, in CHO cells expressing both AT1 and RAGE. Real-time imaging of cellular membrane revealed that RAGE induced endocytosis of LOX-1 that depends on the intact β-arrestin pathway of AT1, and the phenomenon was not inhibited by ARB.

Conclusions:

RAGE ligands mediates cellular signaling via a physical interaction between RAGE and AT1. The activation of AT1 by RAGE ligands is distinct from that by angiotensin II in terms of selective G protein activation and the effect of ARB on G protein pathway but not on β-arrestin pathway.
ASSOCIATION BETWEEN CARDIAC (PRO)RENIN RECEPTOR EXPRESSION AND MYOCARDIAL HYPERTROPHY IN HUMAN
Authors: Morimoto Satoshi , Morishima Noriko , Watanabe Daisuke , Kato Yoichiro , Sawada Tatsuo , Shibata Noriyuki , Ichihara Atsuhiro
Published: April 2021

Objective:

The (pro)renin receptor [(P)RR] is expressed in vital organs throughout the body, with the highest expression level in the heart, and is thought to regulate the tissue renin-angiotensin system (RAS) through the non-proteolytic activation of prorenin. (P)RR is cleaved by processing enzymes to generate soluble (s)(P)RR, which is secreted into the extracellular space, and blood concentration of s(P)RR is considered to reflect the expression level of tissue RAS. Although it has been suggested that increased expression of (P)RR may be involved in cardiac pathophysiology in experimental studies, the significance of (P)RR expression in human heart remains unclear. Therefore, in the present studies, we investigated association between cardiac (P)RR expression and myocardial hypertrophy in human.

Design and method:

Study (1): We measured serum s(P)RR concentration and assessed the relationships between serum s(P)RR level and background factors including left ventricular mass index (LVMI) in 135 patients (57 males) of our department. Study (2): We performed immunostaining for (P)RR and atrial natriuretic peptide (ANP) and α-skeletal actin (SKA), markers for myocardial hypertrophy, in left ventricle specimens obtained from 13 autopsy cases. The expression level of (P)RR, ANP, or SKA and cardiomyocyte area were analyzed using an image processing software (ImageJ) and expression level of (P)RR was compared with cardiomyocyte area and expression level of ANP or SKA.

Results:

Study (1): The patients’ age was 57 (44–67) y.o., serum s(P)RR concentration was 22.8 (21.1–27.7) ng/ml, eGFR was 74.4 (59.4–91.2) ml/min/1.73 m2, and LVMI was 79 (66–90) g/ m2. Serum s(P)RR level was significantly positively correlated with LVMI (β = 0.238, p < 0.01) independent of other related factors. Study (2): (P)RR immunostaining was observed in cytoplasm of cardiomyocytes. The expression level of (P)RR was significantly positively correlated with cardiomyocyte area (ρ = 0.386, p < 0.001) and expression level of ANP (ρ = 0.782, p < 0.001) or SKA (ρ = 0.373, p < 0.001).

Conclusions:

These data suggested that cardiac (P)RR expression may be associated with myocardial hypertrophy in human. Further studies are needed to determine the underlying mechanism of this association.
BRAIN-PENETRATING AMINOPEPTIDASE A INHIBITORS FOR NEW TREATMENT OF HYPERTENSION AND HEART FAILURE
Authors: Llorens-Cortes Catherine , Hmazzou Reda , Boitard Solene , Marc Yannick , Keck Mathilde , Balavoine Fabrice , Roques Bernard
Published: April 2021

Objective:

Brain renin-angiotensin system (RAS) hyperactivity is involved in the pathophysiology of hypertension and heart failure (HF). Angiotensin III/(AngIII), one of the main effector peptides of the brain RAS, exerts tonic stimulatory control over blood pressure/(BP) in hypertensive rats and plays a pivotal role in sympathetic hyperactivity and left ventricular/(LV) dysfunction in rats post-myocardial infarction/(MI). Thus, aminopeptidase A/(APA), the enzyme generating brain AngIII represents a potential therapeutic target for the treatment of these pathologies. Our aim was to evaluate the mode of action of firibastat, a brain-penetrating prodrug of the APA inhibitor, EC33, to reduce BP in hypertensive rats and prevent LV dysfunction in mice post-MI.

Design and method:

Firibastat and MLN4760, an angiotensin-converting enzyme2/(ACE2) inhibitor were administered by central route in hypertensive DOCA-salt rats and mean arterial BP (MABP) was recorded following insertion of a catheter into the femoral artery. Brain APA and ACE2 activities were measured 30 min post-treatment. Two days post-MI induced by the left anterior descending artery ligation, mice were randomized to receive during 4–8 weeks oral treatment with vehicle, firibastat (150 mg/kg) or the ACE inhibitor, enalapril (1 mg/kg). Cardiac function was evaluated by echocardiography

Results:

1-Firibastat, when given centrally in hypertensive rats, is immediately cleaved by brain reductases, generating EC33 which inhibits brain APA activity, blocks brain AngIII formation and decreases BP. At the same time, firibastat treatment increases the activity of brain ACE2, majoring the conversion of AngII to Ang1-7, which by acting on the Mas-receptor, participate to the firibastat-induced BP decrease.

2-Chronic firibastat treatment in mice post-MI normalizes brain APA activity (normalizing brain RAS activity) and prevents sympathetic hyperactivity. It reduced LV end-diastolic pressure, LV end-systolic diameter and volume, and increased LV ejection fraction. It decreased the expression of HF and fibrosis biomarkers. Firibastat treatment prevents cardiac dysfunction and attenuates cardiac hypertrophy and fibrosis.

Conclusions:

Following these data, firibastat was selected for clinical development. Phase IIa/IIb clinical trials provided pharmacological proof-of-principle of firibastat efficacy for decreasing BP in hypertensive patients. The ongoing phase II study/QUORUM will determine if firibastat treatment may constitute a new therapeutic approach for preventing HF post-MI.
THE RELATIONSHIP BETWEEN RESISTANT HYPERTENSION AND RENAL PROGNOSIS IN THE IN PATIENTS WITH CARDIOVASCULAR DISEASES AND CHRONIC KIDNEY DISEASE
Authors: Nakamura Satoko
Published: April 2021

Objective:

In the patients having chronic kidney disease (CKD) and cardiovascular diseases (CVD), the control of the blood pressure (BP) is important to prevent complications and renal function aggravation. Treatment-resistant hypertension (RHT) is hypertension not to fall to suitable BP with the antihypertensive medications more than three. Therefore, in the inpatients, we examined a ratio of RHT and renal prognosis.

Design and method:

417 inpatients (274 men, 143 women, average age 73 ± 11 years old) having CKD and CVD were examined. We investigated BP, blood test, urinalysis and oral medicines at the admission and the discharge.

Results:

The ratio of RHT was 24.5 % at the admission, and 19.9 % at the discharge. We classified the patients into five groups using BP at the admission. A group (normal BP, n = 21): SBP < 130mmHg and DBP < 80mmHg without medications. B group (untreated hypertension, n = 46): SBP more than 130mmHg or DBP more than 80mmHg without medications. C group (controlled hypertension, n = 138): SBP < 130 mmHg and DBP < 80 mmHg with medications (one to three drugs). D group (uncontrolled hypertension, n = 110): SBP more than 130 mmHg or DBP more than 80 mmHg with medications (one or two drugs). RHT group (n = 102): SBP more than 130mmHg or DBP more than 80 mmHg with medications (more than three drugs). The blood pressure at admission was 128 ± 22/76 ± 15, 133 ± 22/84 ± 16, 129 ± 23/71 ± 15, 141 ± 25/77 ± 19 and 146 ± 29/72 ± 16, respectively. The number of the antihypertensive medications was 1.8 ± 1.1 (C group), 1.6 ± 1.1 (D group) and 3.1 ± 1.2 (RHT group). In the RHT group, eGFR and the hemoglobin level were significantly lower, and the complications (diabetes, hyperuricemia, angina, atherosclerosis of lower limbs) were frequent. The factors that participated in RHT at admission were eGFR, diabetes and dyslipidemia. eGFR at the admission have related to the renal function aggravation at the discharge.

Conclusions:

In the inpatients having CKD and CVD, RHT existed frequently. The factors concerning with RHT were the renal function and the aggregation of the lifestyle-relate diseases.
LEFT VENTRICULAR HYPERTROPHY REGRESSION DURING ANTIHYPERTENSIVE TREATMENT IN RESISTANT HYPERTENSION PATIENTS
Authors: Matova Olena , Mishchenko Larysa , Serbeniyk Katerina , Krot Olena
Published: April 2021

Objective:

Objective: to determine the predictors of regression of left ventricular hypertrophy (LVH) in treated resistant hypertensive (RH) patients after 2.1 ± 0.1 years of follow-up.

Design and method:

We studied 51 patients with RH confirmed by the office and ambulatory blood pressure (BP) monitoring despite the use of 3 antihypertensive medications for at least 3 months. During 2 years-period patients had been treated to 12-week rotations of oral daily treatment with spironolactone, nebivolol, torsemide, eplerenone, moxonidine in addition to their baseline triple-combination. Then participants continued to receive the personal most effective fourth-line agent. Patients were divided into 2 groups: 17 patients had LV mass index (LVMI) which was increased or stayed stable after 2 years (1st group), 34 patients with a reduction of LVMI in 2 years (2nd group).

Results:

Initially there were no significant differences in sex, duration of hypertension, body mass index, office and average 24-h ambulatory BP between the 2 groups. Compared with the 1st group patients from the 2nd group had a higher prevalence of non-dippers (24.3 vs 65 %, P < 0.001, respectively) and larger baseline LVMI (127.3 ± 4.1 vs 147.8 ± 6.5 g/m2, P < 0.01, respectively). Patients with persistent LVH included more subjects with coronary artery disease, chronic kidney disease and had less baseline active renin concentration (all P < 0.05). After 2 years in both groups office and average 24-h BP levels have been reduced, but goal rates were achieved at 28.6 % patients of the 1st group and 44.1 % patients of the 2nd group (P < 0.05). Reduction in nighttime BP was greater in the 2nd group. Initial higher LVMI (β = 0.655; P < 0.0001), baseline 24-h urinary albumin excretion (β = - 0.475; P < 0.0001), active renin concentration (β = 0.442; P = 0.005) were predictors of δ LVMI in multivariate modeling.

Conclusions:

Regression of LVH is possible in patients with RH in case of BP control, especially at night. Baseline higher LVMI, an increase of active renin concentration, decline of urinary albumin excretion are factors that determine reversibility LVH.
HYPERTENSIVE URGENCY, EMERGENCY AND KIDNEY FUNCTION
Authors: Jug Juraj , Prkacin Ingrid , Eder Gregor , Prkacin Ingrid
Published: April 2021

Objective:

The aim of this study was to determine risk factors for hypertensive crisis development just as an impact of the kidney function on it.

Design and method:

From January to October 2019, 237 patients (109 males, 128 females) with hypertensive crisis were analyzed at the Emergency department in Clinical Hospital Merkur, Zagreb. We defined the hypertensive crisis as a rapid increase in blood pressure above 180/120mmHg (SBP range 182–260mmHg). Hypertensive crises were divided into two subgroups due to the evidence of end-organ damage. Elementary lab results and pulse wave velocity were checked in all patients.

Results:

Hypertensive urgency was found in 184 patients (77.64%), emergency in 53 (22.36%). Comparison of these two subgroups showed that patients with an emergency were significantly older (70.51 vs. 64.44 years, p < 0.01), had significantly elevated serum glucose levels (10.04 vs. 6.94mmol/L, p < 0.0001), decreased glomerular filtration rate (CKD-EPI formula 75.96 vs. 59.15 mL/min/1.73m2, p < 0.0001) and high heart rate (mean 96.32 vs. 77.17bpm, p < 0.0001) which showed as the most significant risk factor. Body mass index didn’t show any relevance in the hypertensive crisis development (31.26 vs. 30.58 kg/m2, p = 0.18). Hypertensive emergency incidence increased with a decline in kidney function. Such events developed in 16.94% patients with CKD stage 1, 14.42% in stage 2, 34.61% in stage 3a, 50.00% in stage 3b, 60.00% in stage 4 and 50.00% in stage 5. Within main groups, patients were divided into two groups whether they used antihypertensive medication. A group of 53 patients was without medication (22.36%) of which 13 met criteria for a hypertensive emergency. Pulse wave velocity was much higher in patients with CKD-EPI < 45 ml/min/1.73m2 (13.01 vs. 10.74m/s, p = 0.01). Even though female patients were significantly older (69.02 vs. 62.02years, p < 0.0001), no other differences between genders were found.

Conclusions:

Age, elevated plasma glucose and a decline in glomerular filtration rate combined with high heart rate values, but gender and body mass index independently are the main factors which are linked to the development of hypertensive emergency.
DIFFERENCE IN THE EFFECT OF RENAL DENERVATION ON HEART RATE VARIABILITY IN RESISTANT HYPERTENSION WITH AND WITHOUT DISTURBANCE OF GLUCOSE METABOLISM AFTER 12 MONTH FOLLOW-UP
Authors: Manukyan Musheg , Shelemekhov Aleksey , Falkovskaya Alla , Mordovin Victor , Pekarskiy Stanislav , Zyubanova Irina , Lichikaki Valeriya , Kurlov Igor , Baev Andrey
Published: April 2021

Objective:

To investigate the effects of renal denervation (RDN) on heart rate variability (HRV) in resistant hypertension (RHTN) with and without disturbance of glucose metabolism.

Design and method:

In a single-arm prospective interventional study with renal denervation (NCT02667912 and NCT01499810 on ClinicalTrial.gov) were included 87 patients with RHTN: 39 patients without disturbance of glucose metabolism (RHTN group) (mean age 51.2 ± 8.5years, 20 (51%) men, 24-hour (24 h) blood pressure (BP) (systolic/diastolic) 162.3 ± 19.4/99.6 ± 13.5 mmHg); 34 patients with type 2 diabetes mellitus (RHTN + DM group) (mean age 59.2 ± 7.8 years, 11 (32%) men, 24 h BP 157.8 ± 17.4/80.1 ± 12.4 mmHg, mean HbA1c 6.9 ± 1.4%) and 14 patients with impaired glucose tolerance (RHTN + IGT group) (mean age 54.0 ± 10.0 years, 3 (27%) men, 24 h BP 156.6 ± 14.3/89.5 ± 15.6 mmHg). All patients were underwent ABPM and 24-h Holter monitoring with analysis of time and frequency domain-based HRV. Follow-up after 12 months was completed by 38 patients of RHTN group, 22 patients of RHTN + DM group and 9 patients of RHTN + IGT group.

Results:

There was a significant decrease in 24 h BP in all groups at 12 months after RDN (p < 0,001). In the RHTN group, there were no significant changes in both high frequency (HF) and low frequency (LF) (for HF from 14.8 (8.6; 24) to 29.5 (19.0; 40), p > 0.05, and for LF (from 23.1 (15, 0; 61) to 61.0 (40.5; 70), p > 0.05). There were also no significant changes in both LF and HF in the RHTN + IGT group (for LF from 52 (38; 61) to 50 (42; 61), p > 0.05, for HF from 37 (30; 50) to 44 (29; 47), p > 0.05). On the contrary, in the RHTN + DM group, there was a significant decrease in LF (from 55 (39; 63) to 50 (42; 61), p = 0.004), which occurred independently from BP effects, and a non-significant increase in HF. Other measured HRV parameters (mean NN, SDNN, SDNN-I, SDANN-I, r-MSSD, pNN50) were unchanged in all groups (p > 0.05).

Conclusions:

RDN was associated with a reduction of LF, HRV parameters that mainly reflect sympathetic overactivity, only in patients with resistant hypertension and diabetes mellitus.
RENAL SODIUM HANDLING ABNORMALITY IN OBSTRUCTIVE SLEEP APNEA-RELATED HYPERTENSION
Authors: Shiina Kazuki , Tomiyama Hirofumi , Fujii Masatsune , Nakano Hiroki , Chikamori Taishiro
Published: April 2021

Objective:

Obstructive sleep apnea (OSA) has been much focused as one of underlying factors of resistant hypertension. A substantial number of mechanisms (sympathetic nerve activation, oxidative stress, renin-angiotensin-aldosterone system, systemic inflammation and fluid retention) contributed to OSA-related hypertension, and these factors can lead to resistant hypertension. However, renal sodium handling abnormality in OSA patients with hypertension has not been fully clarified.

Design and method:

We evaluated the urine sodium excretion before and after continuous positive airway pressure (CPAP) therapy in OSA. 24-h urinary sodium excretion was estimated at baseline and after 6 months of CPAP using the Kawasaki formula, and fractional urinary sodium excretion (FENa) was also calculated in 23 OSA patients with hypertension.

Results:

In patients with severe OSA, 24 h Na excretion had no significant correlation with AHI, abdominal circumference and plasma aldosterone. After CPAP therapy, systolic blood pressure significantly decreased (P < 0.05), and estimated sodium excretion significantly increased compared to baseline (P < 0.05). The increase in Na excretion was significantly associated with BP reduction by CPAP therapy.

Conclusions:

These results suggested that urine sodium excretion abnormality contribute to the blood pressure elevation in patients with OSA.

Therefore, urine sodium excretion may be a key mechanism in managing OSA-related hypertension.
THE ASSOCIATION BETWEEN BLOOD PRESSURE AND PHYSICAL ACTIVITY DURING CLIMBING MT. FUJI -THE COMPARISON STUDY WITH DAILY LIVING-
Authors: Komori Takahiro , Hoshide Satoshi , Kario Kazuomi
Published: April 2021

Objective:

Hiking and mountaineering are one of the aerobic exercises, and blood pressure (BP) changes greatly. In high altitude, cardiovascular response is differed from daily living. However, BP change during mountaineering in high altitude was not clear at high altitude. The hypothesis of this study is to investigate BP change and physiological response during mountaineering at high altitude.

Design and method:

We enrolled cumulative 14 healthy people. Multi-sensor ambulatory blood pressure monitoring which has barometer, thermometer, and accelerometer was performed during climbing Mt. Fuji. Climbing was started from 5th station of Mt. Fuji, and study participants stayed overnight at summit of Mt. Fuji research station. Pulseoxymetry was performed during sleep. Ambulatory blood pressure monitoring during daily living was performed in another day.

Results:

Blood pressure parameters were significantly higher during climbing than daily living (24-hr SBP: 119 ± 6 mmHg vs. 113 ± 5, p < 0.01, Awake SBP: 125 ± 9 mmHg vs. 118 ± 6 mmHg, p = 0.01, Sleep SBP: 106 ± 8 mmHg vs. 100 ± 5 mmHg, p < 0.01). Atmosphere, temperature, and activity were significantly associated with BP parameters during mountaineering. Compared to daily living, BPs during mountaineering was strongly correlated with activity. (figure)

Conclusions:

BP change during mountaineering was significantly associated with activity. BP response to the activity was different between high altitude and daily living.
RECLASSIFICATION OF CARDIOVASCULAR RISK IN PATIENTS WITH UNCOMPLICATED ARTERIAL HYPERTENSION WHO SAW PRIMARY CARE PHYSICIANS FOR THE FIRST TIME
Authors: Nebieridze David , Kamyshova Tatiana , Safarian Anush , Sarycheva Anna , Sargsyan Vardui
Published: April 2021

Objective:

Assessment of changes in the structure of cardiovascular risk (CVR) determined by the SCORE scale (Systematic Coronary Risk Evaluation) in patients with arterial hypertension, who first contacted with primary care setting, taking into account the target organ damages (TOD) identified during additional examination.

Design and method:

300 men and women (aged 40–65) with newly diagnosed uncomplicated hypertension were included in the study. All patients underwent medical examination, history taking to identify risk factors, blood pressure measurement, biochemical blood, blood lipids assessment. Based on the specified parameters, the risk was determined by SCORE scale. After that additional examination was done aimed at revealing TOD: echocardiography, duplex ultrasonography of the brachiocephalic arteries and determination of microalbuminuria. Based on the results obtained, the CVR was reclassified taking into account the presence of TOD

Results:

The study showed frequent prevalence of TOD in patients with different CVR assessed by the SCORE scale. In the high and very high risk groups the prevalence of TOD was 96.5% and 98.1%, respectively. Attention was drawn to the high prevalence of TOD in the moderate risk group – 73.1%. The obtained data significantly changed the structure of CVR. The main changes affected patients with moderate and high CVR: the number of moderate risk patients decreased by 31.7%, while the number of patients with high risk increased by 36.7%. As a result, if initially high CVR had 28,7% pts (86 pts) assessed by SCORE scale after taking into account the presence of TOD 62.3% pts (186pts) were classified as high risk ones (p < 0,001). So there was an impressive changes in the structure of CVR towards to increase of high-risk patients.

Conclusions:

The results of the study indicate that TOD determination should be an inseparable part of the screening of hypertensive pts who see primary care physicians first time. It would provide correct estimation of the CVR and the development of adequate strategy of patient treatment aimed at effective decrease of cardiovascular mortality.
EFFECTIVENESS AND SAFETY OF NUTRACEUTICAL COMPOUNDS ADDED TO EZETIMIBE TREATMENT IN HYPERTENSIVE AND HYPER–CHOLESTEROLEMIC SUBJECTS WITH STATIN–INTOLERANCE
Authors: Mazza Alberto , Nicoletti Mariaceleste , Lenti Salvatore , Torin Gioia , Rigatelli Gianluca , Fratter Andrea , Pellizzato Marzia
Published: April 2021

Objective:

The effectiveness of statins in the primary and secondary prevention of cardiovascular (CV) diseases has been widely proven. However, the onset of adverse events associated with their use, prevents to achieve the therapeutic targets recommended by the guidelines (GL) for the management of dyslipidaemia. In the event of statin intolerance, is recommend to use bile acid sequestrants, fibrates and ezetimibe in monotherapy, but their benefits in improving lipid pattern are quite modest. This study aims at evaluating the effectiveness and safety of a nutraceutical compound (NC) associated with ezetimibe (E) on the lipid profile in statin-intolerant patients with moderate-to-high CV risk

Design and method:

Ninety-six statin-intolerant hypertensive and hyper-cholesterolemic subjects treated with E 10 mg daily, were randomised in open label (n = 48) to take for 3 months a NC containing Monacolin K (MK) 5 mg, Berberine Hydrochloride, t-Resveratrol, Quercetin, and Chromium, in the form of a gastro-resistant tablet that improves enteric bio-accessibility and bio-availability of these substances. The control group (n = 48), took only E in monotherapy at the same dosage; both groups followed a standardised lipid-lowering diet. The total serum cholesterol (TC), low density lipoprotein cholesterol (LDLC), high density lipoprotein cholesterol (HDLC), triglycerides (TG), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and creatinine phosphokinase (CPK) levels were compared at the follow-up in both groups using Student's t-test.

Results:

TC and LDL levels reduced in both groups, but there lower in the group treated with E+ NC vs E alone (-25.9 vs -15%, p < 0.05 and -38.7 vs. -21.0%, p < 0.05, respectively). No changes were observed in either group regarding to a decrease in TG (-9.4 vs. -11.7%, NS) and an increase in HDLC (+ 4.2 vs. +1.1%, NS). The AST, ALT and CPK levels increased in the E + NC compared to the control group, but were still within the acceptable range. There was no difference for the lipid-lowering treatment between gender, and no patient withdrawn the study.

Conclusions:

In hypertensive and hyper-cholesterolemic subjects with statin-intolerance, the E + NC combination therapy is well-tolerated and effective in the short term in improving TC and LDLC levels.
EFFECTS OF EXERCISE TRAINING ON ARTERIAL STIFFNESS IN PATIENTS WITH HYPERTENSION: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Lopes Susana , Afreixo Vera , Teixeira Manuel , Garcia Catarina , Leitão Cátia , Gouveia Marisol , Alves Alberto J. , Oliveira José , Mesquita-Bastos José , Ribeiro Fernando
Published: April 2021

Objective:

This review aims to determine the effects of exercise training on arterial stiffness, namely Pulse Wave Velocity (PWV), in patients with hypertension. The identification of possible moderator variables of the effect of exercise on PWV was defined as a secondary objective.

Design and Methods:

For this systematic review and meta-analysis (PROSPERO CRD42019138658), MEDLINE, Scopus, Cochrane and Web of Science were searched up until July 2019. Randomized controlled trials assessing the effect of exercise interventions lasting 4 or more weeks on PWV in (pre)hypertensive subjects were included. The standardized mean difference between the pre-post of the intervention group versus the control group was calculated for PWV using the Cohen's d index as the effect size statistic. The type of exercise, PWV assessment site, use of medication, baseline PWV and study quality assessment score were used to perform subgroup analysis.

Design and method:

Fourteen trials, involving 15 exercise groups (5 aerobic, 2 dynamic resistance, 6 combined, and 2 isometric resistance groups), totaling 694 subjects with pre- and hypertension (374 exercise). Exercise program duration ranged from 4 to 26 weeks, with a mean duration of 13.1 ± 6.1 weeks. The overall effect size showed statistically significant differences in PWV [(d (95% CI) = 1.35 (0.72, 1.98)] in favor of the exercise group. Aerobic exercise [d (95% CI) = 1.93 (0.31, 3.55)], combined exercise [d (95% CI) = 0.79 (0.09, 1.49)] and isometric resistance exercise [d (95% CI) = 2.23 (1.66, 2.81)] reduced PWV for the exercise group when compared to the control group. There was no significant reduction in PWV in subjects undertaking dynamic resistance training [d (95% CI) = 0.69 (-2.32, 3.69)]. Subgroup analysis demonstrated that the positive effects of exercise training on PWV are independent of medication use, PWV assessment site, study quality assessment score and baseline PWV, although higher baseline PWV values presented a more significant reduction with exercise.

Results:

Aerobic, combined and isometric resistance exercise significantly decreased PWV in (pre)hypertensive patients. Despite the small number of studies, data from the isometric resistance exercise has the potential for the largest reductions in PWV.
THERAPEUTIC EFFECTS OF MINERAL CORTICOID RECEPTOR BLOCKER IN THE COMBINATION ANTIHYPERTENSIVE DRUG THERAPY IN HYPERTENSIVE PATIENTS
Authors: Murayama Yoshiki , Yokoyama Shohei , Abe Makoto , Nagase Akihiko , Ohira Takehiro , Iwashima Yoshio , Tojo Akihiro , Ishimitsu Toshihiko
Published: April 2021

Objective:

Among the components of renin-angiotensin-aldosterone system, aldosterone is supposed to facilitate the progression of cardiovascular organ injuries not only by promoting renal tubular Na reabsorption but also by causing oxidative stress, inflammation and cardiovascular tissue hypertrophy and fibrosis. Therefore, mineral corticoid receptor blockers (MRB) are expected to exhibit protective effects against cardiovascular organ injuries in hypertensive patients. In the present study, the therapeutic effects of MRB in the combination antihypertensive treatment were examined in hypertensive patients.

Design and method:

Fifty mg eplerenone (EPL) was added to 24 hypertensive patients under antihypertensive drug therapy who were not achieved the target blood pressure levels. The combination was continued for 3 to 4 months and the effects on blood pressure (BP) and laboratory data including renal function and cardiovascular endocrine system were evaluated.

Results:

After 3–4 months, office BP was lowered from 148/91 to 135/86 mmHg (p < 0.001/p = 0.002) as well as the home BP (morning 150/86 to 134/81, p = 0.001/p = 0.033; evening 139/80 to 127/74, p = 0.005/p = 0.030). Serum K (4.2 to 4.3mEq/L, p = 0.014) and creatinine (0.82 to 0.87 mg/dL, P < 0.001) were slightly but significantly increased. Serum uric acid was significantly also increased from 5.8 to 6.4 mg/dL (p = 0.015). However, the indices of glucose metabolism and serum lipids were not affected. In addition to the natural increases in plasma renin and aldosterone, plasma B-type natriuretic peptide (BNP: 23 to 17 pg/mL, p = 0.028) and urinary albumin excretion (111 to 70 mg/gCr, p = 0.009) were significantly decreased.

Conclusions:

In the combination antihypertensive drug therapy, MRB is expected to cardiac and renal injuries and the influences on glucose and lipid metabolisms seem negligible, however, care should be taken for the development of hyperuricemia and renal dysfunction in addition to hyperkalemia.
ADHERENCE DECREASES WITH HIGHER NUMBER OF MEDICATIONS IN CONTROLLED HYPERTENSIVE PATIENTS, CONTROLLED RESISTANT PATIENTS HAVE LOWER ADHERENCE THAN CONTROLLED NON-RESISTANT PATIENTS
Authors: Siddiqui Mohammed , Gupta Pankaj , Tomazewski Maceij , Patel Prashanth , Oparil Suzanne , Calhoun David
Published: April 2021

Objective:

Controlled hypertension in treated hypertensive patients is defined as controlled blood pressure (BP) in clinic (automated office BP [AOBP] < 130/80 mmHg) and out-of-clinic by 24-hr ambulatory blood pressure monitoring (ABPM < 125/75 mmHg). Uncontrolled resistant hypertension (RHTN) is defined as uncontrolled blood pressure (BP) on 3 or more medications, including a diuretic; BP controlled on 4 or more medications is defined as controlled RHTN. Controlled non-RHTN is BP controlled on 3 or less medications. Antihypertensive medication adherence is known to decrease with increase in number of antihypertensive medications, as well as medication adherence is lower in patients with uncontrolled RHTN. Unknown is the relative medication adherence in patients with controlled hypertension with number of antihypertensive medications and medication adherence in controlled RHTN versus controlled non-RHTN.

Design and method:

In this prospective evaluation patients were recruited from the Hypertension Clinic after having controlled BP readings at 3 or more clinic visits. All the patients were evaluated by in-clinic AOBP with use of the BpTRU device, out-of-clinic 24-hr ABPM monitoring and 24-hr urine collection to determine antihypertensive medication adherence by high-performance liquid chromatography-tandem mass spectrometry. After excluding patients with masked uncontrolled hypertension, 82 patients were controlled by AOBP and 24-hr ABPM. Of these, 40 patients had controlled RHTN and 42 patients had controlled non-RHTN.

Results:

Higher number of prescribed antihypertensive medications was associated with lower levels of medication adherence in patients with controlled hypertension. In addition, patients with controlled RHTN (72.7%) had significantly lower medication adherence than controlled non-RHTN (90.9%).

Conclusions:

Similar to uncontrolled hypertension, patients with controlled hypertension have less medication adherence with use of higher numbers of antihypertensive medications. In addition, similar to uncontrolled RHTN, patients with controlled RHTN have lower medication adherence than patients with controlled non-RHTN.
A PRACTICAL APPROACH TO SWITCH FROM A MULTIPLE PILL THERAPEUTIC STRATEGY TO A POLYPILL-BASED STRATEGY FOR SECONDARY PREVENTION IN PATIENTS WITH HYPERTENSION
Authors: Coca Antonio , Kreutz Reinhold , Manolis Athanasios , Mancia Giuseppe
Published: April 2021

Objective:

The recommendation in hypertension is to initiate treatment with a combination of two blood pressure-lowering drugs in a single pill regardless of the cardiovascular (CV) risk, to add a statin in patients with established CV disease (CVD) or at moderate or high risk, and to add as well an antiplatelet agent only among those with established CVD.

Some clinical guidelines nowadays endorse the polypill approach to increase the efficiency of the pharmacological treatment and decrease CV morbidity and mortality. The CNIC polypill is the only CV polypill marketed in Europe and the only approved by the EMEA for the secondary prevention of CVD. This polypill contains aspirin, ramipril, and atorvastatin. We aimed at helping clinicians to start treatment with the CNIC polypill switching from any other statin to atorvastatin, and from any angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) to ramipril.

Design and method:

We looked for available data and recommendations to build tables of equivalent effective daily doses of two of the polypill components (ramipril and atorvastatin), and we developed a treatment algorithm based on expert opinion.

Results:

We provide the approximate equivalent effective daily doses of other ACEIs and ARBs with ramipril and of other statins according to atorvastatin's potency. Moreover, to guide clinicians in the management of patients for secondary prevention of CVD, we provide a treatment algorithm and detail the indications and different available preparations to start treatment with the CV polypill in patients with high BP and prior CVD, and how to associate other BP-lowering drugs or lipid-lowering drugs if need be. Finally, we give advice on how to switch and adapt the treatment of patients already on fixed-dose combinations of antihypertensive medications to initiate the CV polypill regimen.

Conclusions:

The multiple doses of the individual components of the CNIC polypill versions allow for increased flexibility in prescribing and use it to start treatment in patients with high BP and prior CVD, and probably also in the particular scenario of hypertensive patients at high CVD risk without previous CV event and no significant risk of major bleeding.
CLINICAL FACTORS AND HYPERTENSION ASSOCIATED WITH HOSPITAL READMISSION IN HEART FAILURE PATIENTS
Authors: Tun Han Naung , Raza Syed Haseeb
Published: April 2021

Objective:

To systematically investigate the patients’ perspectives about the reasons for their hospital readmission related to hypertension after discharged of stabalized HF patients and to study how to improve our heart failure care system to reduce the number of readmission in cost effective way.

Design and method:

Patients were recruited for this study was admitted to national institute of cardiovascular diseases, through emergency department. Patients discharged with a primary discharge diagnosis for HF who were then readmitted for any cause in the subsequent 6 month were eligible for the study. We recruited patients over the period of 3 month form June 2019 till August 2019. Eligible patients were approached, consented, and interviewed within the next 24 hours while they were still in hospital.

Results:

For the readmission, median length of stay was 6 days. Total 500 patient included, out of which 375 (75%) were male and most important cause of heart failure is ischaemic cardiomyopathy 400 (80%). No death recorded. Common reasons for readmission are lack of counselling 200(40%), under dose 75(15%), non-compliance 60(12%), volume over load 50(10%), hypertension 50(10%), secondary infection 35(7%). Only 50 out of 500 patients which is 10 % of the study participants were associated with hypertension in hospital readmission. Out of 500 patients, 80% had ischemic cardiomyopathy which is directly proportional to HF.

Conclusions:

We concluded that hypertension is not largely associated with heart failure hospitalization in our single center study. But patient compliance of medication, appropriate fluid intake, self-care and life style modification are the important elements in hospital readmission of heart failure.
OUTCOMES OF A QUALITY ASSESMENT PROGRAM FOR HYPERTENSION MANAGEMENT IN A UNIVERSITY HOSPITAL
Authors: Lemo Tatiana , Kotliar Carol , Princz Magdalena , Obregon Sebastian
Published: April 2021

Objective:

We developed an institutional Clinical Practice Guidelines for hypertension (HT) management in a large university hospital, and after one year of its approval and communication we follow up its rate of implementation by physicians.

Aims:

Four outcomes (metrics) were defined and established as objectives; 1) rate of office BP measurement registered in electronic clinical record first 6 months of the year, 2) rate of reaching BP goals in hypertensives (office BP < 140/90 mm Hg), 3) rate of ambulatory (out of office) BP measurement in (ABPM/HBPM) outpatients diagnosed with HT in the last year, and 4) rate of evaluation of hypertension-mediated organ damage through transthoracic echocardiogram (TTE) in outpatients with diagnosis of HT, in the last year.

Design and method:

A random sample of 500 cases (Excel™ randomization function, incremental order) was analyzed, from a total population of 72393 clinical visits from January to July 2019 attending to General Medicine, Cardiology, Hypertension Unit, Diabetes and Nephrology. All subjects were 18 years or older, both genders.

Each visit was evaluated, and only those corresponding to clinical evaluations were included, excluding those visits related to evaluation of medical studies results or administrative. This sample was randomly follow-up until 50 subjects diagnosed with HT were identified.

Results:

A final random selected sample of 206 consultations was included, and after exclusion of not valid data (n:72), we analyzed 134 valid cases. Diagnosis of HT was reported in 50 (37.3%) and rate of BP properly registered in clinical record from the whole population was 63.43% (123 / 74.7 mm Hg). Among those with HT, BP registration rate was 72% (128.83 / 76.5 mm Hg), and 61.1% at therapeutic goals. The utilization rate of ABPM/HBPM was 22.2%., and 64% for TTE in the last year.

Conclusions:

BP registration and use of ABPM/HBPM were suboptimal, but BP control in HT subjects was largely better than reported in epidemiological studies in Argentina. A significative HMOG evaluation was observed. Monitoring clinical performing lead to improvement in management of HT.
VERIFY AND EVALUATE FOUR SPOT URINARY METHODS FOR ESTIMATING 24-HOUR URINARY SODIUM EXCRETION RATE IN TIBETAN POPULATION
Authors: Zhang Xin , Chen Xiaoping
Published: April 2021

Objective:

To verify and evaluate four spot urinary methods for estimating 24-hour urinary sodium excretion rate in Tibetan population (Kawasaki method, Tanaka method, INTERSALT method and SH2 method).

Design and method:

323 subjects were selected from the Ganzi Tibetan Autonomous Prefecture of Sichuan Province, China. The morning second urine samples and 24 hours urine samples were collected. The concentrations of creatinine, sodium and potassium in the morning second urine samples and 24 hours urine samples were measured. To compare the mean deviation, correlation, and consistency between the measured values and estimated 24-hour urinary sodium excretion by Kawasaki method, Tanaka method, INTERSALT method and SH2 method.

Results:

The average differences between the estimated values and measured values by Kawasaki method, Tanaka method, INTERSALT method and SH2 method were 124.86 mg/days, -937.58 mg/days, -1314.15 mg/days and -1747.436 mg/days, respectively. The correlation coefficient with the measured values was 0.434, 0.38, 0.273 and 0.348, respectively. The intraclass correlation coefficient was higher for Kawasaki method (0.473) than for Tanaka method (0.397), INTERSALT method (0.269) and SH2 method (0.348). The Bland Altman analysis showed 3.4%, 6.2%, 5.9% and 5.6% of the subjects’ estimated values exceeded the consistent boundary of ± 1.96 for Kawasaki method, Tanaka method, INTERSALT method and SH2 method. When four spot urinary sodium methods used for evaluating the individual salt intake, the misclassification rate was more than 45%. Compared with the other three methods, the misclassification probability of Kawasaki method was 48.2%, while the misclassification probability of Tanaka, INTERSALT and SH2 methods was 72.1%, 75.5% and 74.6%, respectively. However, when individual's salt intake was higher than 12.8 g/days, the probability of misclassification of Kawasaki method, Tanaka method, INTERSALT method and SH2 method was 20%, 90%, 97.5% and 97.5%, respectively.

Conclusions:

When the Kawasaki method is used to evaluate the salt intake of Tibetan population, the deviation, consistency and reproducibility were better than Tanaka method, INTERSALT method and SH2 method. It was especially suitable for the evaluation of 24-hour urinary sodium excretion rate of people with high salt intake. It can be used to investigate the salt intake of Tibetan population in a large-scale epidemiological study.
ADHERENCE AND ASSOCIATED FACTORS OF ANTIHYPERTENSIVE DRUGS AMONG ADULT HYPERTENSIVE PATIENTS AT CHRONIC FOLLOW UP CLINICS OF WEST GOJJAM ZONE, NORTH-WEST ETHIOPIA 2020
Authors: Yirga Zelalem , Elfu Birhanu , Mehari Zelalem , Abiye Melkam
Published: April 2021

Objective:

To assess the adherence and associated factors of anti hypertensive medications among adult hypertensive patients at chronic follow up clinics of West Gojjam, North West Ethiopia.

Design and method:

Institutional based cross-sectional study was conducted in chronic follow up clinics of randomly selected hospitals from June 1/2020-June15/2020. Systematic Random sampling technique used to select participants and pretested structured questioner with observation of medical charts, and the MMAS-8 tool was used to assess the adherence status. Data entered to Epi-Info version-7.3 and analyzed by SPSS version-25. Variables with P-value < 0.25 in bi-variate logistic regression analysis entered to multivariate logistic regression. P-value < 0.05 used to determine the statistical association.

Results:

Among five hundred forty one participated hypertensive patients, 60.6% participants were male and the mean age of the participants was 54.39 and SD of ± 11.4. The adherence level of the participants was 61.4%(95%CI = 0.573–0.655). Factors like, abused by alcohol (AOR = 0.213,95%CI = 0.072–0.632), rural residency (AOR = 0.423, 95% CI = (0.224–0.798), forgetful of taking the medication (AOR = 0.116–95%CI = 0.063–0.213), poor knowledge about treatment and control of hypertension (AOR = 0.191, 95%CI = 0.085–0.43), and thinking AHD as non-useful (AOR = 0.537, 95%CI = 0.309–0.936) were inversely associated with adherence.

Conclusions:

Only 61.4% of the participants found adherent, which is below the WHO standards. Adherence to anti hypertensive medications affected by the residency, knowledge status, forgetfulness, attitude towards the medications, and alcohol abuse. Adherence counseling and patient education about hypertension and its treatment is important to improve adherence status of patients.
SHIFT WORK IN NURSES AND 7-DAY/24H AMBULATORY BLOOD PRESSURE MONITORING
Authors: Siegelova Jarmila , Havelkova Alena , Krabkova Marie , Dusek Jiri , Dunklerova Leona , Pohanka Michal , Dobsak Petr , Cornelissen Germaine
Published: April 2021

Objective:

The aim of the study is to evaluate seven day/24 h ambulatory blood pressure monitoring (ABPM) during shift work in nurses and compared then with 170 healthy subjects from our database of 7 day/24 h ABPM.

Design and method:

297 healthy subjects and ten shift workers in hospital were monitored during shift work. The seven day working process was composed from the day with day work shift, night work shift systolic and diastolic blood pressure and weekly mean blood pressure values from the seven-day/24-h ambulatory blood pressure monitoring T 2431 (A and D, Japan).

Results:

In healthy subjects with aerobic training, seven days of systolic blood pressure was 115 ± 1.1 mmHg, diastolic 69 ± 1.4 mmHg, in days with exercise (0–24 h) systolic blood pressure was 115 ± 2.8 mmHg, diastolic 69 ± 1, 7 mmHg, in days without exercise (25–48 h) systolic blood pressure was 116 ± 3.4 mmHg, diastolic 69 ± 2.2 mmHg.

In healthy subjects with combined training seven days of systolic blood pressure blood pressure was 113 ± 1.8 mmHg, diastolic 68 ± 1.4 mmHg, days with exercise (0–24 h) systolic blood pressure were 112 ± 1.9 mmHg, diastolic 69 ± 1, 5 mmHg, in days without exercise (25–48 h) systolic blood pressure was 113 ± 1.8 mmHg, diastolic 68 ± 1.4 mmHg.

In patients with myocardial infarction, seventy-day mean systolic blood pressure was 122 ± 4 mmHg, diastolic 74 ± 3 mmHg, in days with exercise (0–24 h) systolic blood pressure was 121 ± 3 mmHg, diastolic 74 ± 2 mmHg, in days without exercise systolic blood pressure 121 ± 3 mmHg, diastolic 73 ± 3 mmHg.

Conclusions:

Our results showed that 1 hour of aerobic training, combined training did not change the 24-hour mean blood systolic and diastolic blood pressure profile assessed from a seven-day ambulatory blood pressure monitoring (7 days / 24 hours) in healthy subject and in patients, if the timing of exercise is during the day hours (6:00–22:00).