bluuebunny/crossref_metadata_2025 huggingface dataset:
INHIBITION OF RAS COMPONENTS ATTENUATES PROGRESSION OF MYOCARDIAL REMODELING IN BOTH NORMOTENSIVE AND HYPERTENSIVE RATS IN EXPERIMENTAL HEART FAILURE
Authors: Sykora Matus , Kratky Vojtech , Tribulova Narcis , Kopkan Libor , Bacova Barbara Szeiffova
Published: June 2022

Objective:

New findings in the pathogenesis of heart failure (HF) with a focus on extracellular matrix (ECM) and communication in the heart are still relevant for more effective treatment. We focused on signaling pathways involved in cardiac structural remodeling in HF due to pressure and volume overload, as well as on investigating the efficacy of substances with possible antifibrotic potential.

Design and method:

We used as experimental model 28-week-old hypertensive (TGR) and normotensive (HSD) rats with created aortocaval fistula (ACF), supplemented with ACE inhibitor (ACEi) (Trandolapril, 15 weeks, 6 mg/L) and AT1 receptor blocker (ARB) (Losartan, 15 weeks, 200 mg/L).

Results:

Echocardiography confirmed an increase in cardiac output and a decrease in ejection fraction in both strains of rats. BW was higher in TGR vs HSD and it was not affected by VO. ACF-induced cardiac volume overload, elevated markers of heart failure and oxidative damage, ANP, BNP-45, and TBARS, were elevated in the blood serum of both strains. ACF induced profibrotic signaling by increasing TGF-, and mRNA collagen I, and collagen I protein expression in the left and right ventricles of HSD rats. In TGR rats ACF decreased TGF- and SMAD2 protein expression in the right ventricle similar to HSD rats, in which ACF also suppressed MMP-2 protein expression. Heart failure affected protein kinase signaling by reducing the protein expression of PKC, PKG, and in part, PKC in both chambers of the heart of both strains. ACF decreased the protein expression of Cx43 and its phosphorylated form, which is significantly proarrhythmic. Hypertension in TGR rats increased mRNA TGF- expression and collagen I, but decreased PKC and PKC protein expression and increased PKC.

Conclusions:

A notable finding was that the signaling pathways involved in cardiac remodeling were more normalized by the ARB, while proteins involved in intercellular communication, ACEi. The results of analyzes of both experiments indicate attenuated responses of the signaling pathways monitored by us in the heart of hypertensive strains reflecting adaptation to primarily induced pathophysiology.

Scientific Grant Agency of the Ministry of Education, Science, Research and Sport of the Slovak Republic VEGA 2/0158/19, 2/0002/20
COST-EFFECTIVENESS OF POLYPILL TREATMENT IN HIGH-RISK HYPERTENSIVE SUBJECTS WITH HYPER-CHOLESTEROLAEMIA
Authors: Mazza Alberto , Bregola Gianni , Cavazzin Enrico , Dell’avvocata Fabio , Giordan Massimo , Rigatelli Gianluca , Rosini Marinella , Bignardi Bruno , Bragiotto Antonio , Crino Tiziano , Chieregato Gabriella , Fante Roberto , Favaron Mauro , Lazzarin Matteo , Petracca Ettore , Roccato Michele , Sartorello Silvia , Scanavacca Giovanni , Zaramella Maria Lucia , Cuppini Stefano
Published: June 2022

Objective:

Hypertension and hyper-cholesterolaemia is a dangerous combination frequently found in clinical practice. Despite a wide range of medications available for these both conditions, a large proportion of treated patients remain uncontrolled. We aimed to evaluate the cost-effectiveness treatment of a polypill in high-risk hypertensive and hyper-cholesterolemic subjects.

Design and method:

46 subjects (mean age 67.4 ± 11.5 years, 69.6% men) treated a with free-combination (FCT) of statins (atorvastatin 63.1%, simvastatin 19.6%, rosuvastatin 8.7%, other 8.6%), renin-angiotensin-system blockers (ramipril 37.1%, perindopril 28.2%, enalapril 11%, zofenopril 4.4%, candesartan 6.5%, valsartan, losartan and telmisartan 4.3%) and calcium-channel blockers (amlodipine 61%, lacidipine and lercanidipine 15.2%, manidipine 6.6%), were switched to once-daily therapy with a polypill containing atorvastatin/perindopril/amlodipine at different doses. The monthly cost for treating patients with FCT and polypill was estimated using pharmacy dispensing records. Blood pressure (BP) and low-density cholesterol (LDL-C) targets values to reach were < 130/80mmHg and < 70 mg/dL, respectively. Categorical variables, were compared using Pearson’s chi-squared test. The change of systolic BP (SBP), diastolic BP (DBP), LDL-C levels and the costs of treatments were compared from baseline to the follow-up (FW, 3.5 ± 1.5 months) by the analysis of variance for repeated measures using the Fisher’s (F) test.

Results:

From baseline to the FW, polypill significantly decrease SBP (141.3 ± 10.1 vs. 133.9 ± 10.5, F = 33.8, p < 0.0001), DBP (81.8 ± 5.3 vs. 77.8 ± 4.1, F = 9.3, p < 0.004) and LDL-C values (99.3 ± 31.5 vs. 70.9 ± 18.5, F = 60.6, p < 0.0001), respectively. The BP and LDL-C targets significantly increased from 24.1 to 56.5% (p < 0.05) and 21.7 to 63.1% (p < 0.05), respectively. The average cost of polypill is lower than the FCT one (13.5 ± 0.7 vs. 23.2 ± 5.3 €, p < 0.0001, difference -9.8 ± 5.2 €). No adverse event was observed during the polypill treatment.

Conclusions:

In high-risk hypertensive and hyper-cholesterolemic subjects, the polypill treatment is cost-effective. National and regional epidemiological data show a prevalence of high-risk hypertensives of about 12%. In perspective, in the local public health-unit 5 Polesana, which gathers about 235 thousand inhabitants, using polypill compared to the FCT could result in annual cost savings of about 3.2 million € (Figure). However, for definite conclusions, further studies including a wider number of subjects in this setting are needed.
LOSARTAN, ANGIOTENSIN II TYPE 1 RECEPTOR BLOCKER, REDUCED AORTIC STIFFNESS AND IMPROVED COGNITIVE FUNCTION IN DAHL SALT SENSITIVE RAT MODEL OF AGE-ASSOCIATED VASCULAR DEMENTIA
Authors: Santos Carla Rocha Dos , Grigorova Yulia , Mcdevitt Ross A. , Wei Wen , Zernetkina Valentina , Juhasz Ondrej , Haghkar Mahdi , Lakatta Edward G. , Fedorova Olga V.
Published: June 2022

Objective:

Cardiovascular diseases are the major contributors to the pathogenesis of vascular dementia. The Dahl salt sensitive (Dahl-S) rat model is characterized by the development of central arterial stiffness (CAS), hypertension and cognitive decline with age on a normal salt diet. We hypothesized that treatment with losartan (LOS), angiotensin II type 1 receptor (AT1R) blocker, via reduction of blood pressure (BP) and CAS, will improve cognitive function in aged Dahl-S rats.

Design and method:

Male Dahl-S rats (n = 30) were kept on a normal salt diet (0.5% NaCl) for the duration of the study. Baseline measurements were taken at 3- and/or 6-mo of age following by the treatment with LOS in drinking water (30 mg/kg/day, n = 14) or control treatment (n = 16) for 6-mo. Measurements were taken every 3 months and included systolic and diastolic BP (SBP, DBP), pulse wave velocity (PWV), a measure of CAS, left ventricular posterior wall thickness in diastole (LVPWd), fractional shortening (FS) and LV mass (by echocardiography). At 12-mo of age the rats were tested in operant chambers using a simple reaction task to assess attention and impulsivity, and in elevated plus maze (EPM) to assess anxiety-like behavior. Statistical analyses were performed using 2-way ANOVA and t-test. Data are presented as mean ± SEM.

Results:

Prior to the treatment, LOS and control groups did not display differences in any parameter analyzed. Following the treatment, LOS rats had lower SBP, DBP, PWV, thinner LVPWd, higher FS and smaller LV mass at 9- and 12-mo of age vs. control group (Fig.1A-F). In the reaction task, LOS rats demonstrated more correct responses and fewer premature responses. The LOS rats exhibited lower anxiety level, because they spent more time in the open arm of EPM vs. control rats (Fig.1G,H).

Conclusions:

Beneficial effect of LOS on cognitive function in aged male Dahl-S rats was associated with the improvement of cardiovascular function and remodeling. The CAS stabilizing and BP reduction by LOS treatment was associated with improved attentional performance, lower impulsivity and lower anxiety. The mechanistic basis of these effects of LOS on cognition via cerebrovascular and brain changes will be further investigated.
THE PHARMACOKINETIC PARAMETERS DATA OF THE 20 MOST COMMONLY PRESCRIBED ANTIHYPERTENSIVE MEDICATIONS
Authors: Alghamdi Randah , Muhammad Fahad , Osman Hanad , Salim Farah , Jenkins Sian , Bernieh Dennis , Gill Henry , Lane Dan , Squire Iain , Jones Donald , Gupta Pankaj
Published: June 2022

Objective:

Chemical Adherence Testing (CAT) is now the preferred method for assessing adherence with prescribed medication. Further research is needed to understand the impact of pharmacokinetics(PK) on medication detection and adherence status, but there is no readily available collated literature. This study aims to collate PK data for 20 of the most prescribed antihypertensive medications.

Design and method:

Prescription rates were determined by reviewing CAT data of 3796 unselected hypertension patients whose samples were tested by the Department of Chemical Pathology & Metabolic Diseases, University Hospitals of Leicester NHS Trust.

PK data of medications were obtained from published literature quoted from four sources: Goodman’s & Gilman’s: The Pharmacological Basis of Therapeutics 13th edition, Clarke’s: Analysis of Drugs and Poisons 4th edition, Martindale: The Complete Drug Reference 39th edition and Micromedex: Medication database. All original manuscripts were reviewed and graded by applying robust criteria.

Design and method:

228 articles were screened. A total of 99 articles were deemed suitable and subsequently had data extracted. The results showed the mean range of bioavailability for the 20 medications was 54.33 ± 27.53%, urine excretion 34.95 ± 28.07%, clearance 424.47 ± 745.75 ml/min/kg, the volume of distribution 169.85 ± 281.64L/kg, half-life 8.82 ± 6.53hrs, time to peak concentration 3.07 ± 2.08hrs and peak concentration 639.52 ± 1477.17ng/ml. The range of plasma concentrations was 1.96ng/ml for Moxonidine at the lowest concentration to 6400ng/ml for Valsartan at the highest concentration. Furosemide had the shortest half-life of 0.85hrs and, Amlodipine had the longest half-life of 59.6hrs. Amiloride was the maximum excretion of 87.9% in urine, whereas Spironolactone was the lowest excreted medication at 0.05%. Diltiazem’s distribution volume was the highest at 822L/kg, whereas Furosemide had the lowest at 0.11L/kg. The medication clearance rate from the body ranged from 0.79 ml/min/kg for Valsartan to 2966 ml/min/kg for Diltiazem. Ramipril had the lowest bioavailability at 15%, while Bisoprolol and Indapamide at 90 % had the highest proportion of bioavailability.

Results:

This study is the first one that has collated PK parameters from published literature in a systematic manner for the most commonly prescribed antihypertensive medications. This will be of clinical use in providing interpretative information to clinicians when they review the results of CAT
A STUDY OF SOME GENETIC FACTORS FOR FIBROMUSCULAR DYSPLASIA
Authors: Yaneva-Sirakova Teodora , Dodova Rumiana , Kaneva Radka , Tzveova Reni , Ivanova Raya , Vassilev Dobrin
Published: June 2022

Objective:

Fibromuscular dysplasia (FMD) is relatively rare idiopathic nonatherosclerotic noninfectious disease of the layers of the elastic arteries. Up to the current knowledge, there are not genes/mutations, which can be unequivocally associated with the disease. Eastern Europeans are under-studied and under-represented in the studies in the field. We started to study this group from the database of the Molecular Medicine center Sofia, BG and tested it to rs9349379 in gene PHACTR1, which showed some association in other studies, but is also associated with coronary artery disease (CAD) and arterial hypertension (AH).

Design and method:

Eleven patients with angiographically proven FMD, 108 patients with AH, 89 patients with angiographically proven CAD and 112 healthy population controls were included. We used TaqManTM technology (Applied Biosystems) for the real time PCR sequencing of the rs9349379 in gene PHACTR1. SPSS 19, p = 0.05, CI 95% was used for the statistics.

Results:

The allelic and genotypic frequencies of rs9349379 in Bulgarians (Eastern European) do not differ from the European. The frequency of the A allele was higher (without reaching statistical significance) in FMD patients. This is in accordance with the results from literature. There was also a tendency (without reaching statistical significance) for association of G allele with CAD.

Conclusions:

We were not able to prove a significant association between rs9349379 in gene PHACTR1 and FMD. However, the group of FMD patients is very small. Maybe FMD is not the perfect “candidate’’ disease for genetic studies for the very few familial cases, multiple genes overlapping in common diseases, varieties in the clinical presentation. Nonetheless, this can be the basis for further research and attempts to study the disease should continue.

The study is conducted with Contract D-132/24.06.2020 from the proposal Grant 2020 of Medical University - Sofia
ENDOTHELIAL NITRIC OXIDE SYNTHASE GENE POLYMORPHISM (894G>T, 786T>C) CONTRIBUTE TO HYPERTENSION RISK AND LIPIDS PROFILE DISORDERS
Authors: Dzhuryak Valentyna , Sydorchuk Andrii , Sydorchuk Larysa , Sydorchuk Ruslan , Sydorchuk Iryna , Iftoda Oksana
Published: June 2022

Objective:

Endothelial nitric oxide synthase (eNOS) gene meet the criteria for candidate genes of cardiovascular disease, including essential arterial hypertension (EAH). The aim of the study was to evaluate the association of eNOS gene polymorphism (894G>T, 786T>C) with EAH risk, lipids profile and some concomitant diseases.

Design and method:

100 EAH patients with target-organ damage, moderate, high/very high cardiovascular risk were involved in the case-control study. 79.0% females and 21.0% males, mean age 59.87 ± 8.02; disease duration 6–25 years. Control included 48 practically healthy persons of relevant age. eNOS gene polymorphisms (894G>T, 786T>C) was examined by Real-Time PCR. Lipids’ profile was studied by total cholesterol (TC), high-, low density cholesterol (HDL-C, LDL-C), triglycerides (TG) and atherogenic index (AI).

Results:

eNOS gene mutants’ T-allele of 894G>T and C-allele of 786T>C were observed in 34.2% and 32.2% patients, that was almost 2 times less, than G-allele carriers (p = 0.006) and T-allele patients (p = 0.004) respectively. eNOS gene T-allele (894G>T) and C-allele (786T>C) were associated with increased relative risk of EAH 1.8 times [OR = 2.43; 95%CI:1.20–4.95] and 2.15 times [OR = 3.48; 95%CI:1.58–7.68], also with higher risk of concomitant Diabetes Mellitus type 2, cerebrovascular disease and acute myocardial infarction in anamnesis 1.53–1.72 times (p < 0.05). eNOS gene haplotype analysis proved the contribution of -894G/786C and -894T/786C haplotypes to EAH risk increase 2.05 times [OR95%CI:1.18–4.04] and 3.18 times [OR95%CI:1.27–7.29], elevation of TG level and atherogenic index by 10.5–18.7% (p < 0.05) and 12.65–14.19% (p < 0.05) accordingly. The HDL-C level was significantly lower in -894G/786C and -894T/786C carriers by 18.16% (p < 0.01) and 22.07% (p < 0.001). -894G/786T genotypes combination played a protective role against EAH [OR = 0.55; 95%CI:0.39–0.76; P < 0.001].

Conclusions:

eNOS gene -894G/786C and -894T/786C increased the EAH risk and lipids profile metabolism disorders.
LINKAGE BETWEEN NOS3 (RS2070744) AND GNB3 (RS5443) GENES’ POLYMORPHISM, CAROTID ARTERIES STRUCTURAL CHANGES AND ENDOTHELIAL DYSFUNCTION IN ESSENTIAL HYPERTENSION
Authors: Sydorchuk Andrii , Voroniuk Ksenia , Sydorchuk Larysa , Semianiv Marianna , Sydorchuk Ruslan , Repchuk Yulia
Published: June 2022

Objective:

This study aims to verify the risk of endothelial dysfunction (ED) and carotid intima media thickness (IMT) changes depending on GNB3 (rs5443) and NOS3 (rs2070744) genes’ polymorphism in essential arterial hypertensives (EAH).

Design and method:

One-hundred EAH patients (moderate-very high cardiovascular risks, aged 45–65 years) and 48 practically healthy (control) participated in the case-control study. Soluble Vascular Cell Adhesion Molecule (sVCAM-1), total NO metabolites, transcriptional activity of NOS3 gene, Endothelium-Dependent Flow-Mediated Dilation of the Brachial Artery (FMD BA) and carotid IMT were studied. GNB3 (rs5443) and NOS3 (rs2070744) genotyping performed by TaqMan probes (CFx96ÔReal-Time PCR).

Results:

C-allele of NOS3 gene elevates the risk of atherosclerotic plaques on the carotid arteries over 3.5 times [OR95%CI:1.24–11.20; p = 0.019 and OR95%CI:1.22–10.18; p = 0.018], ED – by total NO metabolites decrease (<25 mol/l) and sVCAM-1 value raise (>1050 ng/ml) – 12 and 4 times [OR95%CI:1.23–112.7; p = 0.023 and OR95%CI:1.24–11.20; p = 0.019], respectively. Moreover, C-allele of NOS3 gene heighten the low NOS3 gene expression probability 69 times [OR95%CI:17,72–520,0; p < 0,001].

The minor T-allele of GNB3 gene increases the risk of carotid arteries structural changes: by IMT (>0,9 mm) – 3 times [OR95%CI:1.09–7.74; p = 0.027], atherosclerotic plaques – 10 and 5 times [OR95%CI:2.55–38.0; p < 0.001 and OR95%CI:1.61–13.27; p = 0.003]. Besides, the T-allele of GNB3 gene enhances the high sVCAM-1 levels probability over 3 times [OR95%CI:1.06–9.59; p = 0.032].

Moderate and severe ED grades increase the risk of severe EAH 3 and 5.5 times [OR95%CI:1.13–9.34; p = 0.025 and OR95%CI:1.96–14.45; p < 0.001]. The severe EAH course risk is associated more with the structural changes of the carotid arteries (IMT > 0,9 mm increases the likelihood 3.5 times (p = 0.012), atherosclerotic plaques – 4 and 3.5 times (p < 0,05) and decreased NOS3 gene expression – 3 times (p = 0.042), but not depend on separate ED markers (FMD BA, total NO metabolites or sVCAM-1).

Conclusions:

ED enhance the risk of severe EAH course 3–5.5 times. c-allele of NOS3 gene elevates the risk of both structural changes of the carotid arteries 3.5 times and particularly ED – 4–69 times. T-allele of GNB3 gene increases the risk of the carotid arteries structural changes more than ED – 3.5–4 vs 3 times as well.
25(OH)D AS A RISK FACTOR OF ESSENTIAL ARTERIAL HYPERTENSION CONSIDERING THE GENES POLYMORPHISM AGTR1 (RS5186) AND VDR (RS2228570)
Authors: Semianiv Marianna
Published: June 2022

Objective:

Essential arterial hypertension (EAH) remains the most common global non-communicable disease. More than 50% of patients with hypertension have additional cardiovascular risk factors. The aim of this study is to establish the role of 25-hydroxyvitamin D as an additional risk factor of EAH depending on 1166A>C polymorphism of AGTR1 gene (rs5186) and A/G polymorphism of VDR gene (rs2228570).

Design and method:

100 subjects with EAH and target-organ damaging (2nd stage), moderate, high, very high cardiovascular risk were involved in the case-control study. Among them, 70.84% females, 29.16% males, mean age 57.86 ± 7.81 yo. The control group consisted of 60 healthy individuals of relevant gender and age. All recruited subjects were tested for serum levels 25-hydroxyvitamin D (immune luminescent test “MAGLUMI’’, “SNIB’’, China). To detect gene polymorphism the qualitative real-time polymerase chain reaction was done. AGTR1 gene genotyping was performed for 72 patients and 48 healthy individuals and VDR gene – for 100 patients and 60 healthy subjects.

Results:

EAH associates with the decreased 25-hydroxyvitamin D (<30 ng/ml) regardless the genotypes AGTR1 (rs5186) and VDR (rs2228570) genes. Reduced serum level of 25-hydroxyvitamin D escalate the risk of EAH almost threefold (OR – 2.90; 95%CI OR:1.0–8.59; p = 0.048).

Conclusions:

Low level of 25-hydroxyvitamin D increases the EAH risk regardless the AGTR1 (rs5186) and VDR (rs2228570) genes’ alleles in the examined population.
OBESITY AND VITAMIN D RECEPTOR (VDR, RS2228570) GENE POLYMORPHISM ASSOCIATION IN PATIENTS WITH ESSENTIAL ARTERIAL HYPERTENSION
Authors: Repchuk Yuliya
Published: June 2022

Objective:

The study purpose was to analyze the association of vitamin D receptor (VDR, rs2228570) gene polymorphism with obesity in patients with essential arterial hypertension (EAH).

Design and method:

The study involved 100 patients suffering from EAH with target-organ damaging, moderate, high or very high cardiovascular risk. Among them, 79.0% (79) women and 21.0% (21) men, average age 59,86 ± 6,22 y o. The control group involved 60 practically healthy persons, matched by age and sex distribution. All enrolled/screened patients signed the Informed Consent to participate in the research. To examine polymorphism of VDR (rs2228570) gene a qualitative real-time polymerase chain reaction was made. Obesity was defined as a body mass index (BMI) of > 30 kg/m2.

Results:

The genotypes distribution of the VDR (rs2228570) gene in patients vs control group did not differ reliably and was as follows: AA-, AG-, GG-genotypes – 23.0% vs 30.0%, 50.0% vs 46.67%, 27.0% vs 23.33% (p> 0.05) accordingly. Distribution of the genes polymorphic variants corresponded to the Hardy-Weinberg Equilibrium (p > 0.05).

There were no statistically significant differences in the distribution of BMI between patients with EAH and almost healthy GG-genotype carriers of the VDR gene. AG- and AA-genotype carriers in control group were relatively more likely to register persons with normal BMI (18.5 - 24.9 kg/m2) than among patients - by 14.0 % (x2 = 6.06; p = 0.014) and 15,67 % (p < 0.001). While among A-allele carriers with EAH were more patients with obesity - by 17.67 % (x2 = 9.51; p = 0.002) and 8.67 % (x2 = 3.53, p = 0.05), respectively.

Conclusions:

Regarding polymorphic variants of the VDR gene, in A-allele carriers with EAH (AA-, and especially AG-genotypes) the risk of obesity increases almost 4 and 8 times [OR = 3.95; p = 0.05 and OR = 7.71; p = 0.001] with the lowest probability of having a normal BMI. In this case, the GG-genotype of the VDR gene is not a risk factor for obesity in the population we examined.
TELOMERE LENGTH IS NEGATIVELY ASSOCIATED WITH BMI, R WAVE IN AVL AND IL-6 LEVEL IN PATIENTS WITH NEW CASES OF HYPERTENSION
Authors: Podpalova Olga , Kaliadka Marina , Babenka Andrei , Mrochek Aleksandr
Published: June 2022

Objective:

The aim of the study was to investigate the association between lymphocyte telomere length and cardiovascular risk factors in patients with new cases of hypertension according to 10-years prospective study in urban randomised population.

Design and method:

In 2007/2008 10-years prospective study of 3500 persons living in a district of Vitebsk (Belarus) and selected by the random number method started (coverage of the survey was 97.9%). According to the results of first examination 2170 persons had normal blood pressure. 1862 of them were examined on the second stage of the study in 2012/2013 (coverage of the survey was 85,8%). 286 new cases of hypertension were revealed and they had significant positive relationship with the IV quartile of uric acid level (> = 339 mol/l), determined on the first stage of the study. A 10-years prospective analysis was provided in 2017/2018 and included 145 randomized subjects with hypertension diagnosed on the second stage of the study.

Results:

We examined 2170 persons with normal blood pressure in 2007/2008. On the second stage of the study 286 new cases of hypertension were diagnosed in these subjects (14,4% of men and 12,2% of women). According to multifactorial regression analysis of 145 randomized subjects of 286 new cases of hypertension, adjusted for age and sex, the IV quartile of uric acid level (339–527 mol/l), determined on the first stage of the study, was associated with the I quartile of telomere length in 10 years (df = 1; 2Wald = 4,5; p < 0,05). Cross-sectional analysis of these subjects showed that the level of telomere length had a significant negative association with BMI (=-0,19; p < 0,05), R wave in aVL (=-0,18; p < 0,05), IL-6 level (=-0,20; p < 0,05) in 2017/2018.

Conclusions:

Regardless of age and sex, telomere length has negative association with BMI, R wave in aVL and IL-6 level in patients with new cases of hypertension.
ANGIOTENSIN CONVERTING ENZYME GENE POLYMORPHISMS AND PULSE PRESSURE INDEX
Authors: Ozturk Onder , Ozturk Cansu
Published: June 2022

Objective:

Elevated pulse pressure (PP) may lead to an increased risk of cardiovascular morbidity and mortality. To get over the failure of PP, there is a new parameter, “pulse pressure/systolic pressure’’ called “pulse pressure index (PPI)’’ for assessment of cardiovascular prognosis. The present study aimed to determine the effects of polymorphism of the Angiotensin Converting Enzyme (ACE) gene polymorphisms on the PPI after a first anterior acute myocardial infarction (AMI).

Design and method:

Overall 140 patients with a first anterior AMI were included in this cross-sectional study. Based on the polymorphism of the ACE gene, they were classified into 2 groups: Deletion/Deletion (DD) genotype (Group 1, n = 57), Insertion/Deletion (ID), Insertion/Insertion (II) genotypes (Group 2, n = 83) (Figure 1). PPI was calculated “ pulse pressure / systolic pressure’’. Echocardiographic examinations were performed to the recommendations of the American Echocardiography Committee.

Results:

There were no significant differences among clinical parameters of patients (Table 1). PPI was significantly higher in patients who have ACE DD genotypes than in patients who have ACE II / ID genotype (0.467 ± 0.0483 and 0.391 ± 0.0415, P 0.028).

Conclusions:

In this study we found that ACE Gene I / D polymorphism D allele affects PPI in patients with a first anterior AMI.
IDENTIFICATION OF A GROSS DELETION MUTATION OF GLA GENE IN A FABRY DISEASE FAMILY CHARACTERIZED BY ATRIAL FIBRILLATION AND MYOCARDIAL HYPERTROPHY
Authors: Lu Yiting , Fan Peng , Zhou Xianliang
Published: June 2022

Objective:

Fabry disease is a rare X-linked lysosomal storage disease caused by GLA gene mutations, which results in the deficient activity of -galactosidase A. The decreased enzymatic activity consequently leads to abnormal accumulation of the substrate glycosphingolipids in multi-organ. Herein, we reported a Chinese family with Fabry disease predominantly characterized by atrial fibrillation and myocardial hypertrophy.

Design and method:

We collected venous blood samples from all participants and genomic DNA was exacted for genetic testing. Conventional GLA cDNA analysis and multiplex ligation-dependent probe amplification (MLPA) analysis was performed in a Chinese family highly suspected of Fabry disease.

Results:

Genetic analysis identified a gross deletion (IVS1_IVS2del) in GLA gene in the proband and other 3 family members. There was a large deletion on both sides of the 5’ breakpoint of the first Alu repeat in intron 1 and the 3’ breakpoint of the seventh Alu repeat in intron 2, which may be caused by the recombination of AluAlu repeat. The proband mainly presented with cardiac symptoms, including atrial fibrillation and myocardial hypertrophy. Family history of heart disease was positive, including index’ maternal uncle and grandmother who died of sudden cardiac death, index’ mother and aunt with atrial fibrillation and myocardial hypertrophy. All affected patients had insufficient -galactosidase A activity.

Conclusions:

The phenotype of Fabry disease is complex and variable. Patients with Fabry disease are often complicated with cardiac involvement, which may be neglected easily. Enzyme activity test and genetic analysis are effective methods for the precise diagnosis of Fabry’s disease.
EFFICACY AND SAFETY OF NIFEDIPINE GASTROINTESTINAL THERAPEUTIC SYSTEM VERSUS RAMIPRIL IN CHINESE AND EUROPEAN PATIENTS WITH HYPERTENSION
Authors: Zhang Wei , Liu Chang-Yuan , Bilo Grzegorz , Soranna Davide , Zambon Antonella , Kyriakoulis Konstantinos , Kollias Anastasios , Ceravolo Isabella , Cassago Silvia , Pengo Martino , Stergiou George S. , Wang Ji-Guang , Parati Gianfranco
Published: June 2022

Objective:

In a post-hoc analysis of a multinational, randomized trial, we investigated whether the efficacy and safety of ramipril and nifedipine gastrointestinal therapeutic system (GITS) differed between the Chinese and European patients with hypertension.

Design and method:

Previously treated and untreated (2 weeks washout) male and females patients aged 35–75 years with a clinic systolic/diastolic blood pressure (BP) over 140/90 mmHg and a daytime ambulatory systolic/diastolic BP over 135/85 mmHg were randomly assigned to ramipril 10 mg or nifedipine GITS 30 mg for 10 weeks in monotherapy (main study) and for an extension to 12 months with the possible up-titration of the monotherapy and combination with a diuretic or an alpha-blocker (extension study). BP lowering efficacy was evaluated for clinic, ambulatory and home BP at 10 weeks and 12 months follow-up.

Results:

The 67 Chinese and 101 European patients significantly (P < 0.01) differed in several major characteristics such as age (50.9 vs. 54.6 years), body-mass index (24.5 vs. 27.0 kg/m2), heart rate (75.0 vs. 70.8 beats/minute) and clinic (87.9 vs. 92.5 mmHg) and nighttime diastolic BP (79.3 vs. 75.9 mmHg), but did not differ in any characteristic between the ramipril and nifedipine GITS groups within each ethnicity (P> 0.05). BP was similarly reduced in the two treatment groups in both Chinese and European patients, except for a significantly greater daytime systolic/diastolic BP reduction in the ramipril than nifedipine-GITS group in the Chinese patients (+7.4/ + 4.1 mmHg, P = 0.02). The Chinese, compared with European patients, had a higher incidence rate of all adverse events (13 [38.2%] vs. 14 [28.6%], P = 0.48) and dry cough in the ramipril group (11 [32.4%] vs. 3 [6.1%], P = 0.003) but lower incidence rate of all adverse events in the nifedipine GITS group (4 [12.1%] vs. 18 [34.6%], P = 0.02).

Conclusions:

In the Chinese and European patients with hypertension, ramipril and nifedipine GITS had similar BP lowering efficacy, but different incidence rate of adverse events.
PREVALENCE AND INCIDENCE OF ARTERIAL HYPERTENSION OVER 36 MONTHS IN AMBULATORY HIV INFECTED PATIENTS ON ANTIRETROVIRAL THERAPY IN LILONGWE, MALAWI
Authors: Steffen Hans-Michael , Nhlema Angellina , Phiri Sam , Kasper Philipp , Chaweza Tom , Forest Andrew De , Heller Tom , Tweya Hannock , Mahanani Melani Ratih , Winkler Volker , Neuhann Florian
Published: June 2022

Objective:

According to a meta-analysis hypertension (HT) prevalence is higher in HIV infected patients (PLHIV) on antiretroviral therapy (ART) compared to ART-naïve patients. As part of the prospective LighTen Cohort Study (ClinicalTrials.gov NCT02381275) we examined blood pressure (BP) changes in ambulatory PLHIV who had initiated tenofovir-containing ART.

Design and method:

Anthropometric measurements of study participants (age > = 18 years) were documented at baseline and during study visits after 1, 3, 6 and every 6 months thereafter. Systolic and mean office BP values (OBP, oscillometric measurements) for PLHIV, who were still active study participants at month 36 were analyzed. Age, gender, and anthropometric measurements were included in univariate and multivariate multilevel analysis to test for their effects on changes in BP (R statistical software, version 4.1.2).

Results:

BP measurements on at least two occasions were available for 1,288 PLHIV and HT was confirmed at baseline and during follow-up in 173 (13.4%) and 50 cases (4.7%), respectively. For the whole cohort systolic and mean BP increased from month 12 onwards with a significant (p < 0.001) impact of weight gain and age while female sex was protective. 36-month data from 799 (474 females, 325 males, mean age 37.1 ± 9.2 years) could be analyzed. Although the number of patients on antihypertensive drug treatment (HT Tx) nearly tripled (23 vs. 61), BP was uncontrolled in 125/799 PLHIV (15.6%) compared to 115/799 (14.4%) at baseline (Chi2-test p < 0.001).

Conclusions:

The proportion of patients with hypertensive BP values increased after initiating ART despite higher HT Tx rates. Counselling of PLHIV on measures regarding control of body weight and improved HT Tx compliance should be embedded into patient education programs at HIV centers.
TOTUM-854 REDUCTION OF BLOOD PRESSURE IS ASSOCIATED WITH AN ANTI-OXIDATIVE EFFECT IN SHR RATS
Authors: Ripoche Doriane , Michaux Arnaud , Pialoux Vincent , Vallier Marie , Langhi Cedric , Chavanelle Vivien , Otero Yolanda F. , Peltier Sebastien , Sirvent Pascal
Published: June 2022

Objective:

Arterial Hypertension (AHT) is a major cause of premature death worldwide. We have developed Totum-854 (T-854), a polyphenol-rich botanical composition to reduce the risk of developing AHT. We assessed the acute and chronic effects on blood pressure in spontaneous hypertensive rats (SHR).

Design and method:

Acute protocol: 12-week-old SHR rats received a dose of vehicle or T-854 (1250 mg/kg) per os with a 48h-wash-out interval between two gavages, in random order.

Chronic study: 18-week-old SHR rats received vehicle or T-854 (1000 mg/kg) per os once a day for 8 weeks.

Arterial pressure was recorded during 24 h post-gavage (acute protocol) and for 2 hours once a week (chronic protocol) with a radio-telemetry device (HD-S10, DSI) directly implanted into the abdominal aorta.

Results:

Acute supplementation with T-854 induced a reduction in SBP and DBP during the 24 h recording after gavage in comparison to vehicle, with 24h-AUC decreased by 93.6mmHg.h ± 67.8mmHg.h and 70.8mmHg.h ± 54.6mmHg.h respectively.

When T-854 was administered chronically, SBP and DBP were decreased from the 4th week after the start of supplementation in comparison to vehicle group. This reduction was maintained in the last weeks, with blood pressure values around baseline in T-854 SHR rats. Tissue analysis showed a plasma SOD activity increase and a decrease of aorta media thickness after 8-weeks T-854 supplementation, suggesting a potential protector role of T-854 on oxidative stress and vascular function.

Conclusions:

T-854 24h-post-gavage acute effect on blood pressure in hypertensive SHR rats suggests a rapid effect, with a decrease in blood pressure few hours after oral administration, and maintained during the time of the experiment. Moreover, T-854 prevents the development of AHT in SHR supplemented during eight weeks. In conclusion, T-854 appears as an efficient strategy to prevent AHT.
BLOOD PRESSURE REDUCTION AND OUTCOMES IN PATIENTS WITH DIFFERENT BASELINE CARDIOVASCULAR RISK: SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED TRIALS
Authors: Manta Eleni , Thomopoulos Costas , Konstantinidis Dimitris , Tatakis Fotis , Polyzos Dimitris , Drogkaris Sotiris , Tsioufis Konstantinos
Published: June 2022

Objective:

Blood pressure (BP) lowering is accompanied by reducing cardiovascular (CV) outcomes and death in hypertensive patients. No data are available for the effect of BP lowering in trials stratified according to baseline CV risk that was assessed according to SCORE-2.

Design and method:

A systematic review was conducted to identify randomized trials in electronic databases (Pubmed and CENTRAL, years: 1966 to 9/2021) for the effect of BP-lowering treatment against placebo or less aggressive BP reduction on 6 fatal or non-fatal CV outcomes and all-cause death. Selected studies reported outcomes in patients without a history of previous CV disease. In each study, we calculated baseline cardiovascular risk using SCORE-2. Risk ratios (RR) were calculated together with their 95% confidence interval (CI) under the random-effects model.

Results:

We included 54 studies (i.e., 12 trials with low-to-moderate CV risk, n = 21,192 patients; 13 trials with high risk, n = 66,886; and 29 trials with very high risk, n = 79,061). For a standard SBP/DBP reduction of 10/5 mmHg, the relative risk of the combined outcome of major CV events (i.e., myocardial infarction, stroke, and heart failure) was decreased by 27% (95% CI, 22–35%) in the category of very high-risk patients, and this reduction was significantly greater (P = 0.02) compared to high-risk trials (0.90 [95% CI, 0.77–1.04]). Moreover, CV death showed a significant reduction in the high-risk group compared to the low-moderate risk group (p = 0.005), as well as in the very high-risk group compared to the low-moderate risk group (p = 0.001). The same pattern was observed for all-cause death in the very high-risk group compared to the high-risk group (p = 0.045).

Conclusions:

The greatest outcome benefit from BP lowering in primary prevention is observed in patients at higher baseline cardiovascular risk as calculated by the SCORE-2.
ESTIMATES ON MEDICATION COST OF DRUG DOSE SPECIFIC TREATMENT PROTOCOL FOR HYPERTENSION MANAGEMENT IN PUBLIC AND PRIVATE HEALTHCARE SECTORS IN INDIA
Authors: Sahoo Swagata Kumar , Pathni Anupam Khungar , Krishna Ashish , Sharma Bhawna , Cazabon Danielle , Moran Andrew E. , Hering Dagmara
Published: June 2022

Objective:

Hypertension is a major public health challenge in most low- and middle-income countries and calls for prioritization of large-scale hypertension control programs. Adoption of drug and dose specific treatment protocols as recommended by the WHO-HEARTS is crucial for scaling up effective hypertension treatment in resource-limited settings. This study estimated the annual cost of medication per patient using three such protocols in India.

Design and method:

The medication requirement was simulated with a range of hypertension control assumptions for the selected protocols based on preliminary observations from sentinel sites of a large-scale hypertension control program in the public sector. Two five-step single molecule and a single pill combination (SPC) based antihypertensive treatment protocols were selected for this study and the approximate medication costs was calculated based on Indian prices in the public and private sectors.

Result:

The approximate annual cost of antihypertensive medication per patient ranged from $33.88–58.44 in the private sector when using a single molecule drug protocol and from $51.57–68.83 when using a SPC drugs protocol. The cost of medication was lower in the generic stores ranging between $5.78–9.57 for single molecule protocols and $7.35–9.89 for protocol with SPC. The cost of medication for patients covered by the public sector was the lowest at $2.05–3.89 for single molecule protocols and $2.94–3.98 for SPC.

Conclusion:

At less than $4 per patient per annum, scaling up hypertension control program with drug and dose specific treatment protocols is a potentially cost-effective public health intervention to save lives and reduce expenses associated with cardiovascular complications in India. Generic drug prescription enforcement and the development of low-cost generic retail networks would increase affordability in the private sector. The cost of treatment with SPCs is comparable to the single molecule protocol, and therefore SPC based treatment protocol can be adopted in a public health program considering the advantage of simplified logistics, reduced pill burden, improved treatment adherence and blood pressure control.
RIGHT HEART PULMONARY CIRCULATION UNIT RESPONSE TO EXERCISE IN PATIENTS WITH SYSTEMIC ARTERIAL HYPERTENSION. INSIGHTS FROM THE RIGHT-NET STUDY
Authors: Vriz Olga , Rudski Lawrence , Frumento Paolo , Limongelli Giuseppe , D’Andrea Antonello , Cittadini Antonio , Ekkehard Grunig , Guazzi Marco , Bossone Eduardo , Palatini Paolo
Published: June 2022

Objective:

Systemic arterial hypertension is the main risk factor for the development of heart failure with preserved ejection fraction (HFpEF). The aim of this study was to assess the right heart-pulmonary circulation unit response to exercise doppler echocardiography (EDE) in patients with hypertension in order to evaluate the capacity of EDE to unmask a pre-HFpEF state.

Design and method:

EDE was performed in 155 hypertensive patients and in 145 healthy normotensive subjects on a semi-recumbent cycle ergometer with load increments of 25 watts every 2 minutes. Left ventricular (LV) and right ventricular (RV) dimensions, function and hemodynamics were evaluated. Linear mixed models were used to test the interaction between hypertension and age group on the echocardiographic parameters at peak exercise, adjusting for baseline values.

Results:

Impaired echo-Doppler LV and RV function was observed both at rest and peak exercise in hypertensives compared to healthy subjects. Pulmonary artery systolic pressure (PASP) and pulmonary vascular resistance were higher in the former. The entire population was then divided into tertiles of age: at rest no significant differences were recorded for each age group between hypertensives and normotensives except for E/E’ that was higher in the hypertensives of the middle age tertile. At peak exercise, hypertensives had higher pulmonary artery systolic pressure (PASP) and E/E’ but lower tricuspid annular plane systolic excursion (TAPSE) as age increased, compared to normotensives. Differences in E/E’ and TAPSE between the 2 groups at peak exercise were explained by the interaction between hypertension and age even after adjustment for baseline values (p < 0.001 for E/E’, p = 0.011 for TAPSE). At peak exercise, the oldest group of hypertensive patients had a mean E/E’ of 13.0, suggesting a significant increase in LV diastolic pressure combined with increased PASP.

Conclusions:

Age and hypertension have a synergistic effect on E/E’ and TAPSE at peak exercise indicating that the detrimental effect of aging on cardiac function is amplified in hypertension. EDE appears a useful tool for unmasking a pre-HFpEF state in hypertension even in patients with controlled resting blood pressure.
RIGHT VENTRICULAR LONGITUDINAL SYSTOLIC STRAIN AS A PREDICTION MARKER OF NEW ONSET HEART FAILURE WITH PRESERVED EJECTION FRACTION IN ESSENTIAL HYPERTENSION
Authors: Zervakis Stylianos , Marketou Maria , Danelatos Christos , Maragkoudakis Spyros , Pateromichelakis Themistoklis , Plevritaki Anthoula , Savva Eirini , Fragkiadakis Kostas , Kladou Eleni , Kampanieris Emmanouil , Kassotakis Spyros , Kalomoirakis Petros , Peponaki Eirini , Kochiadakis George
Published: June 2022

Objective:

Accurate assessment of right ventricular (RV) systolic function is important, as it is an established prognostic marker in cardiac diseases. Speckle-tracking echocardiography is a sensitive tool for detection of subclinical left ventricular impairment in essential hypertension. We associated RV function using longitudinal peak systolic strain (GLS) in patients with essential hypertension with the risk of future development of heart failure with preserved ejection fraction (HFpEF).

Design and method:

We performed a retrospective observational study that included 458 patients with essential hypertension (266 males, aged 63 ± 18 years) and 179 normotensives (100 males, aged 66 ± 15 years). Standard echocardiography was performed at the initial visit. 2D speckle tracking echocardiography with evaluation of longitudinal strain in each segment of the RV (basal: RVLS-B; mid: RVLS-M, apical: RVLS-A) and global RV free-wall strain (RVLS-G) were also performed. We studied the cases of new onset HFpEF in hypertensive patients.

Results:

The median follow up was 85 months (22–122). RVLS-G, RVLS-B and RVLS-M were significantly impaired in hypertensives compared to controls (RVLS-G: -16.1 ± 9.7 vs -20.0 ± 5.1, RVLS-B: -11.7 ± 3.7 vs -20.6 ± 3.3, RVLS-M:-16.3 ± 5.4 vs -20.7 ± 4.9, p < 0.05 for all). No significant difference was detected for the RVLS-A (-20.1 ± 3.8 for hypertensives vs -21.31 ± 6.5 for controls, p = NS). Thirty two hypertensive patients developed HFpEF (7 %). A cut-off RVLS-G worse than -17 % was significantly associated with new onset HFpEF (p < 0.001) in those patients. A multivariate Cox regression analysis showed that RVLS-G had independent significant prognostic value for the risk of HFpEF (HR: 10.5, 95% confidence interval (CI): 7.3–25.4).

Conclusions:

Essential hypertension leads to a decrease of RVLS which is strong predictor of a new onset HFpEF. Future studies are needed to assess the significance of these findings and the effects of treatment.
INTRAVASCULAR ULTRASOUND SUBTYPES OF UNIFOCAL RENAL ARTERY FIBROMUSCULAR DYSPLASIA
Authors: Xu Jianzhong , Wu Qihong , Kang Yuanyuan , Hong Mona , Gao Pingjin , Wang Jiguang
Published: June 2022

Objective:

A binary angiographic classification of renal artery FMD lesions into multifocal or unifocal is well established. The multifocal type, with the ‘string-of-beads’ appearance, is related to medial FMD. While the unifocal type (focal or tubular type), is not clearly related to specific histological lesions. IVUS is a useful tool, in addition to the angiography for evaluation of the anatomical changes of structures of the vessel wall.

The purpose of this study was to reveal the different subtypes of unifocal renal artery fibromuscular dysplasia (FMD) based on intravascular ultrasound (IVUS) and assess the clinical characteristics.

Design and method:

Thirty-six hypertensive patients (mean age 24 ± 7 years, 13–39 years) with computer tomography angiography (CTA) scan suggestive of unifocal renal artery FMD underwent renal angiography, IVUS and angioplasty, with both immediate and long-term blood pressure (BP) response assessment.

Results:

Of the total 36 patients, renal angiography revealed focal type in 22 (66.1%) and tubular stenoses in 14 (38.9%) patients. On IVUS, two subtypes of unifocal renal artery FMD were identified include intima-media thickening (IMT, n = 21, 58.3%) and negative remodeling of the whole vessel (NR, n = 15, 41.7%). In the 22 patients with focal type on angiography, 18 (81.8%) showed IMT and 4 (18.2%) showed NR on IVUS. 14 patients with tubular type on angiography, IVUS showed IMT in 3 (21.4%) and NR in 11 (78.6%) patients. No difference in age of onset, gender, BMI, initial BP levels were found between two IVUS subtypes. However, the proportion of BP returning to normal in the immediate term (48 hours after angioplasty procedure) (76.2% vs 26.7%, p = 0.004) and the long-term (1–5years) cure rate of hypertension (90.5% vs 20.0%, p < 0.001) were much higher in the IMT subtype than those in the NR subtype.

Conclusions:

In this study, we describe a new classification into IMT or NR of unifocal renal artery FMD based on IVUS. Patients with IMT renal FMD were more likely to achieve cure of hypertension.