bluuebunny/crossref_metadata_2025_split huggingface dataset:
LONG-TERM EFFECT OF DIFFERENT TRIPLE COMBINATION ANTIHYPER-TENSIVE MEDICATIONS: DATA FROM THE BRISIGHELLA HEART STUDY
Authors: Cicero Arrigo F.G. , Fogacci Federica , Rizzoli Elisabetta , D’Addato Sergio , Borghi Claudio 
Published: June 2022

Objective:
The aim of this study was to comparatively evaluate clinical, laboratory and hemodynamic effects on the long term of different triple combination antihypertensive medications in a well-characterized population cohort.

Design and method:
We considered data of a subset of Brisighella Heart Study (BHS) participants who were consecutively evaluated in three epidemiological surveys between 2012 and 2020. For the current analysis, we excluded normotensive subjects, patients treated with < 3 or 3 or more high blood pressure (BP) medications without taking angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), calcium-channel blockers (CCB) and/or thiazide/thiazide-like diuretics. The remaining participants were divided into three groups depending on whether they were treated with ACE-inhibitors/CCBs/Thiazide, ARBs/CCBs/Thiazide or Perindo-pril/Amlodipine/Indapamide, either with separate drugs or fixed pill combinations. A further group of age- and sex-matched volunteers was selected as control and included patients receiving other antihypertensive medications. The long term effects of the different antihypertensive medications were compared among the pre-defined groups.

Results:
On the long-term, combination treatment with renin-angiotensin system (RAS) modulators, CCBs and thiazide/thiazide-like diuretics was associated with better control of diastolic BP and lipid pattern than other triple combination antihypertensive medication. Patients treated with Perindopril/Amlodipine/Indapamide did not experience any age-related increase in serum levels of total cholesterol. Moreover, during the follow-up they neither developed type 2 diabetes nor had a need for a greater number of antihypertensive drugs to improve BP control.

Conclusions:
Based on our observations, combination treatment with RAS modulators, amlodipine and thiazides/thiazide-like diuretics is more effective than other combination antihypertensive medications for lowering the diastolic BP and has a better impact on serum lipids. Perindopril/amlodipine/indapamide is associated with better lipids’ profile than any other considered combination antihypertensive medication.
PREVALENCE, TREATMENT AND CONTROL OF ASYMPTOMATIC HYPERURICAEMIA IN THE GENERAL CROATIAN POPULATION (EH UH 2 STUDY)
Authors: Bukal Nikolina , Domislovic Marija , Gellineo Lana , Fucek Mirjana , Begic Zvonimir , Frkanec Stjepan , Jelakovic Ana , Radunovic Danilo , Prelevic Vladimir , Dika Zivka , Karanovic Sandra , Stevanovic Ranko , Jelakovic Bojan 
Published: June 2022

Objective:
Hyperuricemia is acknowledged cardiovascular risk factor and determination of uric acid is a routine laboratory test in arterial hypertension. Debate is going on whether asymptomatic hyperuricemia should be treated or not, and what should be the targets. Our aim was to analyze prevalence of asymptomatic hyperuricemia, treatment and control in general Croatian population.

Design and method:
EHUH -2 study is nation-wide survey (Croatian Science Foundation) on hypertension and numerous cardiovascular risk factors in Croatia. In 2018–2021 a random sample of 1321 subjects were enrolled. Extended questionnaire was applied and subjects were clinically examined. Office blood pressure (BP) and heart rate were measured in sitting position using Omron 3 device three times and average BP values were calculated. Fasting blood sample was drawn after measurements and all lab data including uric acid were determined in a central laboratory. Hyperuricemia was defined as uric acid > 428 umol/l for men and > 357 umol/l for women

Results:
Prevalence of asymptomatic hyperuricemia was 12.6% without difference between men and women. Only 14.2 % of patients with asymptomatic hyperuricemia was treated with xanthine oxidase inhibitors. Normal values of uric acid were achieved in 71.5%. However, it means that in the entire group of patients with asymptomatic hyperuricemia only 10.1 % were under control.

Conclusions:
Prevalence of asymptomatic hyperuricemia is in line with reports from some countries (Italy 9–12%, Spain 5.11% and Sweden 10.16%), but lower than in North America, Russia, Japan and China. Small number of patients is treated and majority were not controlled. This therapeutic inertia should be improved by increasing awareness among physicians.
MORPHOFUNCTIONAL ABNORMALITIES WITHIN THE AORTA AS A PREDICTOR OF ARTERIAL HYPERTENSION IN METABOLIC SYNDROME
Authors: Birulina Yuliya , Buyko Evgeniy , Ivanov Vladimir , Dzyuman Anna , Grigoreva Anna 
Published: June 2022

Objective:
Arterial hypertension is an important component of the metabolic syndrome, the development of which is caused by the occurrence of endothelial dysfunction and impaired contractile activity of vascular smooth muscle cells. In the presented work, the morphological basis of an increase in blood pressure under the influence of a high-fat high-carbohydrate diet in rats was investigated.

Design and method:
A study was carried out in male Wistar rats weighing 250–320 g, 140 days old at the end of research. The rats from the control group were fed standard rat chow. The rats from the experimental group had a high-fat high-carbohydrate diet (proteins 16%, fats 21%, carbohydrates 46%, including 17% fructose, 0.125% cholesterol, 90 days). Body weight, blood pressure were assessed. It was determined the morphological changes in the aortic wall. Mechanical tension of isolated aortic rings was measured by Myobath Tissue Bath System II. Sections of aorta were stained with hematoxylin and eosin, sudan III.

Results:
It was found that blood pressure increases in animals kept on a high-carbohydrate high-fat diet. The high-carbohydrate high-fat diet causes endothelial vascular dysfunction, impaired contractile activity of vascular smooth muscles. In the rats the experimental group a changes in the activity of calcium and potassium channels, Na +, K +, 2Cl - cotransporter and chlorine conductivity was found. In the aortic wall of the animals of the experimental group, there are signs of elastolysis (initial remodeling of the media), accumulation of lipids in the interstitial cells of the media, hyperplasia of fat cells in the adventitia.

Conclusions:
Functional and morphological abnormalities in the vascular wall in metabolic syndrome can be the basis for an increase in blood pressure and arterial hypertension.
THE INTERRELATION OF HYPERTENSION AND HYPERURICEMIA THE PRISM OF SCORE2
Authors: Ruf Ruslan , Grinshtein Yuri , Shabalin Vladimir 
Published: June 2022

Objective:
Hyperuricemia increases the risk of hypertension. At the same time, hypertension is a part of the SCORE2 model, which assesses the total cardiovascular risk. In the present study, we analyzed the interrelation between the prevalence of hyperuricemia and the cardiovascular risk calculated with the SCORE2 model.

Design and method:
A total of 1603 Krasnoyarsk Krai inhabitants were recruited in the ESSE-RF study. The study protocol provided a standard questionnaire, anthropometry, office blood pressure measurement, and biochemical blood analyses to find the prevalence of known cardiovascular diseases and their risk factors. These data allowed us to calculate an individual cardiovascular risk with the SCORE2 model for each study participant. After that, we compared the prevalence of hyperuricemia (uric acid levels higher than 360 micromole/l in females and 400 micromole/l in males) in the low, medium, and high cardiovascular risk subgroups.

Results:
We found 30.7% (95% CI = 28.4%-33.0%) of the study participants having hyperuricemia. In persons aged 40 and older, 10.8% had a low risk, 37.0% had a medium risk, and 52.2% had a high cardiovascular risk, according to the SCORE2.
In the low-risk subgroup, the prevalence of hyperuricemia was at 11.3% (95% CI = 5.3%-17.4%). At a medium risk, 27.0% (95% CI = 22.4%-31.6%) of people had hyperuricemia. Finally, in the subgroup of high risk, hyperuricemia was found in 37.0% (95% CI = 32.8%-41.2%) of people. Chi-square was for trend at p < 0.001.

Conclusions:
Due to the interrelations between hypertension and hyperuricemia, the higher is the SCORE2-calculated cardiovascular risk of a patient, the higher is the probability that this patient also has hyperuricemia.
RESTING ELECTROCARDIOGRAM ABNORMALITIES IN PATIENTS WITH ARTERIAL HYPERTENSION AND THEIR ASSOCIATION WITH CARDIOVASCULAR RISK FACTORS
Authors: Bendoudouch Houssam , Dahmani Ikram , Mahdi Zaynab , Benali Mehdi , Ouadfel Oussama , Dhimene Safae , Mhani Hafida , Najib Anas , Berhil Taha , Lahnin Fadoua , Soussan Ilias , Hara Loubna , Boussaad Pr Badr , Najdi Pr Adil , Raisso Pr Zainab 
Published: June 2022

Objective:
Study the socio-epidemiological aspects of hypertensive patients in the North of Morocco, analyze the prevalence of electrocardiogram abnormalities, and find an association between the presence of the abnormalities and both the age of hypertension and other cardiovascular risk factors.
Methods: This work is based on a study of 300 out of 1108 patients who consulted the Cardiology Department of the Tangier. The study also includes 50 Control subjects. Data consisted of anamnesis, clinical examination & an electrocardiogram. All data was collected through a survey.

Design and method:
The mean age was 60,23 [40;93]. The sex ratio was 0.38 (72,3% F, 27,8%M). The patients with obesity (BMI> 30 kg/m2) were at 24%. The mean duration of the arterial hypertension was 5,77 years [1;32]. They take the same medication for hypertension for 4,14 years [1;17]. The mean heart rate of our study group is 77,13 b/min [49;112]. 13,7% have left heart axis. 19 patients have a PR interval superior to 200ms. Conduction abnormalities were observed in 10,3%.17% have Left Ventricular Hypertrophy. The voltage Cornell index was the most positive in patients with LVH (60,78%). Rhythm abnormalities were found in 18 subjects (6%). Repolarization disorders were observed in a total of 37 (12,3%) patients. 64,7% take only one HTN-specific medication, while 33,7 % take 2. 49,3% of our study group are treated with Calcium Channel blockers, represented by Amlodipine. The second most frequent medication is ACE inhibitors (30%) (Ramipril (55,7%)), followed by Angiotensin Receptor blockers at 26,7% (Losartan (80%). 35 % of our patients presented ECG abnormalities. LVH was the most prevalent anomaly (34%), Hypertensive patients present significantly more ECG abnormalities than controls (p < 0,018) (OR: 2,45). Patients with ECG abnormalities have a higher mean of years of HTN (6,59) than those with a normal resting ECG (5,32) (p < 0,021). Patients with LVH (7,29) have a higher mean of years of HTN than patients who do not have LVH (5.45) p < 0.027. The presence of more cardiovascular risk factors (other than HTN) increases the risk of ECG anomalies by 2,21. There is no significant association between the presence of other CVRF and the existence of electrical LVH (p = 0,275).
Conclusion: To our knowledge, this is the first characterization of hypertensive patients in Morocco since 2000. Arterial hypertension is associated with more frequent electrocardiogram abnormalities, especially with Left ventricular hypertrophy. It also increases the frequency of these anomalies in comparison to non-hypertensive patients. ECG findings are correlated to the age of HTN. Other cardiovascular risk factors increase the ECG abnormalities, thus influence the prognosis of the hypertension.
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