bluuebunny/crossref_metadata_2025 huggingface dataset:
ROLE OF H2S AS A PREDICTOR OF CARDIOVASCULAR DISEASE IN METABOLIC SYNDROME
Authors: Birulina Julia , Buyko Evgeniy , Ivanov Vladimir , Voronkova Olga , Efimova Lina
Published: May 2024

Objective:

One of the possible protective factors that can protect target vascular cells (endothelial, smooth muscle cells) from damage during the development of metabolic syndrome (MetS) is hydrogen sulfide (H2S).

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 (HFHC) diet. Biochemical parameters of rat blood were determined. The concentration of H2S in the blood serum and adipose tissue of rats was determined by the photometric method at 670 nm. The expression of the H2S synthesis enzyme CSE was studied in aortic tissue samples using Western blot.

Results:

It was found that HFHC diet led to an increase in body weight, obesity, hyperglycemia, insulin resistance, dyslipidemia, and leptinemia in the experimental group rats. It was found that the concentration of H2S significantly decreased in the blood serum and adipose tissue of rats with MetS. The rate of production of H2S in adipose tissue of rats with MetS also decreased. In the aortic tissue of rats with MetS, there was a decrease in the amount of protein of the CSE.

Conclusions:

Changes in the activity of the H2S/CSE system in MetS may be additional evidence of the development of vascular dysfunction in metabolic disorders.
OSLER MANEUVER FOR BEDSIDE DIAGNOSIS OF PSEUDOHYPERTENSION
Authors: Moccetti Federico , Messerli Franz , Toggweiler Stefan , Schoenenberger-berzins Renate
Published: May 2024

Objective:

Please see results and conclusion. The abstract is a case report.

Design and method:

Please see results and conclusion. The abstract is a case report.

Results:

An 82-year-old man presented with progressive dizziness and orthostatic symptoms. His long-standing hypertension was treated with ramipril, amlodipine and hydrochlorothiazide with increasing, doses over the past months. Cuff blood pressure (BP) was 152/83mmHg. During cuff inflation at suprasystolic pressure levels the pulseless brachial and radial arteries remained distinctly palpable (Panel A), leading to the suspicion of pseudohypertension. Invasive central aortic BP measurement demonstrated a significantly lower BP (116/71 mm Hg) compared to simultaneous brachial cuff BP (152/83 mm Hg), confirming the presence of pseudohypertension. During invasive BP measurement severe calcification of the brachial and radial arteries were also noted (arrows, Panel B) supporting the diagnosis.

Conclusions:

In elderly hypertensive patients, increased arterial stiffness can lead to spuriously elevated cuff BP measurements. Osler maneuver, first described by Messerli et al., can help diagnose pseudohypertension: after cuff inflation to suprasystolic pressure levels, the pulseless brachial and/or radial artery remains palpable due to its stiffness. Confirmatory invasive BP measurement may be considered (although not necessary and/or feasible in many patients). Pseudohypertension should be suspected particularly a) in patients who have persistently elevated cuff BP measurements despite antihypertensive treatment, b) in those without evidence of end-organ damage despite long-standing hypertension and c) especially in patients who report orthostatic symptoms and/or do not tolerate antihypertensive therapy. Once pseudohypertension has been diagnosed BP targets need to be readjusted taking spurious BP elevation and patient's symptoms into consideration.
SUBENDOCARDIAL VIABILITY RATIO PREDICTS MORTALITY IN OLDER NURSING HOME RESIDENTS
Authors: Grillo Andrea , Salvi Paolo , Salvi Lucia , Valbusa Filippo , Tan Isabella , Labat Carlos , Rovina Matteo , Gautier Sylvie , Carretta Renzo , Avolio Alberto P. , Fabris Bruno , Parati Gianfranco , Benetos Athanase
Published: May 2024

Objective:

The subendocardial viability ratio (SEVR), estimate by arterial tonometry, can quantify the degree of myocardial perfusion relative to left-ventricular workload. This study aims to evaluate the ability of SEVR to predict long-term mortality in the older population, in the PARTAGE (Predictive values of blood pressure (BP) and ARTerial stiffness in institutionalized very AGEd population) study. Additionally, we aimed to identify the SEVR cutoff value best predicting mortality.

Design and method:

Patients were enrolled from the PARTAGE, a multicenter, longitudinal study aimed at determining the predictive value of blood pressure and arterial mechanical parameters in a large population of individuals aged 80 years and over living in nursing homes. Data from central blood pressure derived from arterial tonometry (PulsePen, DiaTecne, Milan) were used to elaborate the SEVR. The mortality over a 10 years follow-up was analyzed according to SEVR, using Kaplan–Meier curves and Cox regression multivariate models.

Results:

A total of 828 people were enrolled (mean age: 87.7±4.7 years, 78% female). 735 patients died within 10 years and 24 were lost to follow-up. SEVR was inversely associated with mortality at univariate Cox-regression model (risk ratio, 0.683 per unit increase in SEVR; 95% confidence interval (CI) [0.502–0.930], p = 0.015) and in a model including age, sex, body mass index, Activity of Daily Living index and Mini-Mental State Examination score (risk ratio, 0.647; 95% CI [0.472–0.930]). The lowest tertile of SEVR was associated with higher 10-years total mortality than the middle (p < 0.001) and the highest (p < 0.004) tertile. A SEVR cutoff value of 83% was identified as the best predictor of total mortality.

Conclusions:

SEVR is significantly and independently associated with mortality among nursing home residents aged 80 years and over, with a proposed cutoff value of 83%. An accurate non-invasive estimation of SEVR could be a useful and independent parameter to assess survival probability in very old adults.
EFFECTS OF ALAMANDINE ON SYMPATHETIC OUTFLOW AND ANGIOTENSIN II-INDUCED HYPERTENSION IN RAT
Authors: Wei Shunguang , Chen Qing , Irfan Nafis Md , Yu Yang
Published: May 2024

Objective:

Alamandine, a recently identified component of the renin-angiotensin system (RAS), is an endogenous heptapeptide derived from angiotensin-(1-7) or angiotensin A. Synthesized primarily through the enzymatic actions of angiotensin-converting enzyme 2 and aspartate decarboxylase, alamandine exerts its effects by binding to the Mas-related G protein-coupled receptor (MrgD). In contrast to the well-studied angiotensin II (ANG II), alamandine exhibits vasodilatory, anti-inflammatory, and anti-fibrotic properties, thereby representing a novel player in the cardioprotective axis of RAS, countering the detrimental effects associated with classical RAS activation. However, the role of alamandine in regulating sympathetic outflow remains unclear.

Design and method:

The present study sought to examine the effects of systemic alamandine on hemodynamic and sympathetic responses in rats and determine whether alamandine counteracts ANG II-caused hypertension. Blood pressure (BP, mmHg), heart rate (HR, beats/min), and renal sympathetic nerve activity (RSNA, % change) were recorded in urethane-anesthetized male Sprague Dawley rats.

Results:

While intravenous (IV) vehicle (n=6) did not induce a significant change, IV injection of alamandine (n=6) elicited a substantial (p<0.05) reduction in BP (from 91.5 ± 3.4 to 77.6 ± 3.1∗), HR (from 313 ± 7 to 274 ± 6∗), and RSNA (25.1 ± 2.4% change∗), beginning within 10-15 mins after IV injection. The responses peaked at 45-60 min and returned to baseline within 120 min. Additionally, while a two-week subcutaneous infusion of ANG II significantly elevated BP, concurrent treatment with alamandine obviously attenuated ANG II-induced pressor response (from 115.9 ± 4.7 to 90.1 ± 3.2∗).

Conclusions:

These results indicate that systemic alamandine has inhibitory effects on sympathetic drive and ANG II-induced hypertension. The diminished impact of alamandine on sympathetic outflow may play a role in the attenuation of pressor responses. Further study to elucidate its molecular mechanisms and physiological implications holds significant potential for advancing our understanding of RAS regulation and identifying novel therapeutic targets in the treatment of cardiovascular disorders such as hypertension and heart failure.
HYPERTENSION URGENCY IN A HOSPITAL EMERGENCY SERVICE
Authors: Paz Grethzel Prado , García Fernando Martínez
Published: May 2024

Objective:

The aim of this study is to know the percentage of patients who are discharged with Blood Pressure levels in safe ranges after a hypertensive urgency and what is the most frequent range of SBP in these patients.

Design and method:

It is a observational, retrospective study where all clinical histories of patients over 18 years old attended during a period of 8 months in a Hospital Emergency Service, with the diagnostic of Hypertensive crisis, were reviewed.

Patients with history of Major Cardiovascular Events (Ischemic or hemorrhagic stroke, acute myocardial infarction, acute pulmonary edema and aortic dissection), hypertensive pseudocrisis, patients with decreases in blood pressure levels who had been treated in primary care or at home and who did not need further hypotensive treatment, were excluded.

The data obteined were: Sex, age, Sysolic and Diastolic levels at the begining and at the discharge.

The proportion of patients with a decrease in Systolic Blood Pressure less than 160 mmHg or woth a decrease of more than 20% of their initial levels, were calculated. Although, the mos frequent levels of Systolic Blood Pressure.

Results:

Of 457 Clinic histories reviewed, 351 were included. Participants median age was 68 (±13,8) years old, 62% were female. The 50% of patients arrived to the hospital with SBP between 180-200mmHg. The 62% of patients were discharged with a decrease of SBP equal or more than 20% of their initial SBP. Only the 20% decreased their SBP between 20-25% that some guides recommend, 42% decreased more than 25%. When datas were analized repect to the measure of SBP less than 160mmHg the result was 60%

Conclusions:

There is a 40% of patients who are not discharged with safe ranges of Systolic Blood Pressure. Therefore, there is a long way to go to improve these results.
SUSTAINABLE HYPERTENSION CARE - HOW CAN IT BE ACHIEVED? - A SYSTEMATIC REVIEW
Authors: Nilsson Peter , Gottsäter Anders , Midlöv Patrik
Published: May 2024

Objective:

Hypertension represents a major public health problem, but the enormous amount of people (patients) in need of treatment to blood pressure (BP) target and regular controls entails a difficult logistic problem, especially for primary health care, including the costs of care. The aim was to search the literature for experiences of possible cost-effective and practical solutions to this problem - aiming for a sustainable care of patients with hypertension, in line with the WHO Sustainable Development Goals 2030 (SDG2030).

Design and method:

A PubMed search was conducted until January 2024 for search terms: sustainable AND primary care AND hypertension AND cost-effective. The abstracts of full papers or editorials were read and categorised.

Results:

Only five papers were found, two from low- or middle-income countries (LMIC) and two with a focus on screening and prevention of chronic kidney disease (CKD). One Editorial from 2023 addressed the problem and possible solutions to sustainable hypertension care, also in high-income countries.

Conclusions:

There is a discrepancy between the full burden of hypertension on the health care system in general and possible solutions based on sustainable and cost-effective strategies for hypertension care with very few papers published. This challenge will increase further following even more strict thresholds for a diagnosis of elevated BP, as well as BP treatment targets, in contemporary guidelines. New strategies including the promotion of e-Health, PolyPill, home-BP measurements, and involvement of non-physician staff members should be developed for a sustainable hypertension care.
EFFECTS OF GRAPE SEED PROANTHOCYANIDINS ON SERUM LIPID METABOLISM AND ITS MECHANISM IN INDUSTRIAL TRANS FATTY ACIDS INDUCED OBESITY RATS
Authors: Ma Weiping , Zhu Huarui , Zhang Ling
Published: May 2024

Objective:

To study the effects of GSPE on the serum lipids induced by industrial trans fatty acids (ITFAs) in obese rats and its possible mechanism.

Design and method:

Forty-five newly weaned male SD rats were randomly divided into 3 groups with 15 rats in each group. The control group were fed with basal diet, ITFAs group was fed with ITFAs diet, ITFAs +GSPE group were fed with ITFAs diet, and GSPE 100 mg /kg/day1 ml were gavaged daily, and the other two groups were given corresponding volume of normal saline. Weights were monitored weekly. After 10 weeks of intervention, blood were collected from the inferior vena cava, fat coefficient were calculated, serum lipid, mRNA and protein expression levels of adipose triglyceride lipase (ATGL), hormone-sensitive triglyceride lipase (HSL) and lipoprotein lipase (LPL) in adipose tissue were detected.

Results:

At the 10th week after intervention, the body weight of rats in ITFAs group was significantly higher than that in control group. The body weight and visceral fat coefficient of rats in ITFAs group were higher than that in ITFAs+GSPE group, and there were different degrees of dyslipidemia. The mRNA expression levels of ATGL and HSL in Adipose tissue of ITFAs group and ITFAs+GSPE group were significantly decreased, while the mRNA expression levels of LPL were significantly increased. HSL protein expression level was significantly decreased and LPL protein expression level was significantly increased in ITFAs group. The mRNA expression levels of ATGL and HSL in ITFAs+G group were higher than those in ITFAs group, while the mRNA expression level of LPL was lower than that in ITFAs group. All the differences were statistically significant (P<0.05).

Conclusions:

ITFAs can induce obesity and changes in serum lipid levels in rats by acting on the expression of key enzymes in fat metabolism, and grape seed proanthocyanidins have a certain protective effect on serum lipid metabolism disorders in obese rats induced by ITFAs.
NETRIN-1 MAY BE ATHEROPROTECTIVE THROUGH INHIBITION OF MONOCYTE RECRUITMENT TO THE VESSEL WALL
Authors: Claro Vasco , Ferro Albert
Published: May 2024

Objective:

To investigate the effect of netrin-1 on monocyte / macrophage migration, both in vitro and in an in vivo model of inflammation.

Design and method:

THP-1 cells-derived macrophages were used to study migration in a xCELLigence Real-Time Cell Analysis DP system (Agilent Technologies, USA). 80,000 cells were transferred into the top chamber of a CIM-plate and MCP-1 (100 ng/mL) and/or netrin-1 (300 ng/mL) were included in the cell medium in the bottom chamber.

Monocyte interaction with the endothelium was tracked using intravital microscopy, in mice whose monocytes / macrophages express enhanced green fluorescent protein. Inflammation was induced in the cremaster muscle of treated or non-treated (with netrin-1 – 500 ng) mice, using LPS.

Statistical analysis was by one-way ANOVA, with P < 0.05 denoting statistical significance.

Results:

When compared with chemokine-free media, media containing MCP-1 exhibited a chemoattractant effect on macrophages, as expected. However, when combined with netrin-1, the MCP-1 chemoattractant effect was abolished (A).

Mice treated with netrin-1 exhibited a significant reduction in number of cells in the tissue after inflammatory stimulation (B). Netrin-1 did not significantly affect number of cells adherent to the endothelium (C), whilst on the other hand it increased number of cells rolling on the endothelium (D) in response to LPS.

Conclusions:

Netrin-1 abolished the chemoattractant effect of MCP-1 in THP-1 cells in vitro, and reduced the number of monocytes infiltrating the vasculature in response to an inflammatory stimulus in vivo. The latter appeared to be mediated not by prevention of endothelial adhesion but by increasing rolling without subsequent vascular infiltration. Netrin-1 may present a novel therapeutic opportunity for inhibiting atherosclerosis through preventing monocytic vascular infiltration.
DIVERSE EFFECTS OF CAFFINE AND ITS METABOLITES AFTER FASTING ON SYSTOLIC AND DIASTOLIC BLOOD PRESSURE IN NORMO- AND HYPERTENSION
Authors: Casper Janis , Kuhnt Alexander , Schmidt-ott Kai , Schmidt Bernhard
Published: May 2024

Objective:

Caffeine consumption, a ubiquitous habit in modern society, has been extensively examined for its effects on the human body. However, there is an ongoing debate about its positive and negative impacts, with an immediate rise in blood pressure and diverse results on an increased risk of cardiovascular disease and potential beneficial effects. In this cross-sectional study, we aim to investigate the effects of caffeine and its main metabolites on blood pressure in hypertensive and normotensive patients over an intermediate term.

Design and method:

Utilizing data from the National Health and Nutrition Examination Survey from 2011 to 2014 (non-institutionalized US participants), including demographic variables, questionnaires, systolic and diastolic blood pressure (SBP, DBP) measurements, blood and urine laboratory results, linear regression analyses were performed, and corrections for established risk factors of hypertension were applied.

Results:

In the total cohort comprising normo- and hypertensive participants, higher caffeine intake (b=- 0.00485; P<0.0001), higher metabolite levels (theophylline: b=-0.05 5; p=0.010 and paraxanthine levels b=- 0.01 9; p=0.0296) correlated with lower SBP. Caffeine intake (b=0.003640; p<0.0001) and paraxanthine levels (b=0.03940; p<0.0001) were positively correlated with higher DBP.

Among hypertensive participants, caffeine intake showed a significant correlation with lower SBP (b=- 0.00648; p=0.0013). Paraxanthine levels in urine the day after caffeine consumption correlated with higher DBP (b=0.0335; p=0.0332).

In normotensive participants, higher caffeine intake correlated with lower SBP (b=-0.00265; P=0.001) but higher DBP (b=0.0031; P<0.0001). Paraxanthine levels correlated positively with higher DBP (b=0.01622; p=0.0329). There was a trend towards lower SBP in normotensive participants with higher theophylline levels (b=-0.03 48; p=0.050).

Conclusions:

Conclusion: In this cross-sectional study, we focused on non-acute effects of caffeine and the effects of its active metabolites and show that caffeine intake on the day before the measurement and paraxanthine and theophylline effects independent of caffeine levels are associated with lowered systolic blood pressure but higher diastolic blood pressure. This association appears irrespective of hypertension status. Our findings underline the importance of carefully considering caffeine intake when diagnosing and treating hypertension, addressing systolic and diastolic blood pressure.
RAPID ENDOGENOUS PRODUCTION OF ENDOTHELIN-1 REVEALED BY AN ENDOTHELIN NEUTRALIZING ANTIBODY IN A SERIES OF EXPERIMENTAL AND MODELING STUDIES
Authors: Wang Xiaojun , Lee Stacey , Schroeder Richard , Lin Joanne , Witek Marta A , Budge Kevin , Abraham Trent , Irelan Courtney , Porter Gina , Bellinger Melissa , Zhang Hong , Berna Michael , Ni Wei , Kowala Mark , Hansen Ryan , Verdino Petra Petra
Published: May 2024

Objective:

The endothelin pathway is implicated in driving pathophysiological changes leading to pulmonary and systemic hypertension, chronic kidney disease and heart failure. Small molecule antagonists that selectively blocked endothelin A receptors (ETA) as well as non-selective ETA and endothelin B receptor (ETB) antagonists were successfully developed for the treatment of these vascular diseases. However, the treatment-related adverse events, such as fluid retention and edema, significantly limit the utility of this class of therapeutics, especially in the heart failure patients.

Design and method:

A monoclonal antibody that selectively neutralizes endothelin-1 (ET-1) may offer an attractive alternative therapeutic approach that remedies ETA-mediated vasoconstriction without impacting desirable ET-3/ETB mediated fluid regulation. A selective ET-1/2 neutralizing antibody, S69glC21 was discovered and optimized through protein engineering to 80 pM and 30 pM binding affinities to ET-1 and ET-2, respectively.

Results:

When administered into rats exogenously infused with ET-1, S69glC21 prevented blood pressure increase. In a hypoxia-induced pulmonary hypertension rat model, S69glC21 reduced pulmonary pressure. Compared to atrasentan, a selective small molecule ETA antagonist, S69glC21 had a distinct pharmacodynamic (PD) effect characterized by initial complete inhibition followed by a delayed rise of pulmonary pressure as the hypoxia condition persisted. To further dissect these findings, S69glC21 pharmacokinetics (PK) and circulating ET-1 target engagement (TE) analysis were performed. In the S69glC21 treated rats, antibody bound ET-1 was shown to accumulate relative to baseline plasma levels at all dose levels. In the 30 mpk group, the antibody bound ET-1 accumulated nearly 40,000-fold above the baseline plasma level of 2.25 ± 0.87 pg/mL indicating a rapid production rate of ET-1.

Conclusions:

Thus, PK/PD modeling reveals significant druggability challenges for the development of a highly effective, commercially viable ET-1 selective neutralizing antibody for the treatment of cardiovascular, pulmonary, and/or renal diseases.
ACUTE RENAL FAILURE DUE TO SPRUE-LIKE SYNDROME INDUCED BY OLMESARTAN
Authors: Spagnuolo Vitaliano , Rosa Giuseppe La , Maletta Maria , Napolitano Brunella , Pietrantoni Antonella , Ruffolo Andrea Domenico , Ruffolo Carlo , Scarpelli Mirko , Balsano Mario
Published: May 2024

Objective:

Olmesartan is an antihypertensive, blocking angiotensin II receptor. It has an excellent tolerability profile but, more than other angiotensin II receptor inhibitors, it can cause severe sprue-like enteropathy (OAS). Although the first description of this syndrome dates back to 2012, still today, the diagnosis can be difficult; delay in the diagnosis can lead to the appearance of a severe clinical complicance.

Design and method:

We describe the case of acute renal failure in a patient on treatment with olmesartan. 79-year-old hypertensive female. From eight weeks presence of diarrhoea and a reduction of six kilograms. For this reason she had undergone a gastroenterological evaluation which had excluded thyroid, parasitological and celiac causes and had recommended coloscopy. For the subsequent finding of hypokalaemia (2.7 mM/L) and renal insufficiency (clearance of 11.8 ml/min 1.73 m2), patient was referred from the ED to our Unit. Patient underwent to clinical, biochemical, virological and instrumental tests, including coloscopy that excluded specific causes. Withdrawal of olmesartan resulted in diarrhea disappearing within a few hours. Patient was discharged in good condition, with normalization of kidney function. She received an ACE-I as antihypertensive therapy. At the 10-week outpatient follow-up, patient continues to have no diarrhea and has regained the lost weight.

Results:

Olmesartan can rarely cause severe enteropathy. Symptoms may appear months or years after starting treatment; this may contribute to the diagnostic delay. Diagnosis is substantially one of exclusion and, given the seriousness of the enteric symptoms, rechallenge is often not possible. Withdrawal of olmesartan usually results in termination of the syndrome within a few hours. In the case presented, the severity of the OAS led to the onset of severe renal insufficiency which hospitalization. Discontinuation of the drug led to the disappearance of the sprue-like symptoms already on the second day

Conclusions:

Although olmesartan is generally well tolerated, rarely, it can induce OAS and severe renal impairment as reported in our case report. In subjects treated with olmesartan it is necessary to consider the possibility of incurring OAS and to interrupt the therapy as soon as this clinical evidence is suspected.
SINGLE-PILL COMBINATION OF THIRD-DOSE TRIPLE ANTIHYPERTENSIVE THERAPY VERSUS STANDARD-DOSE MONOTHERAPY IN PATIENTS WITH MILD TO MODERATE HYPERTENSION
Authors: Rhee Moo -YONG , Sung Ki -CHUL , Hone Soon Jun , Jeong Myung -HO , Kim Dae -HEE , Lim Sang -WOOK , Park Kyungil , Lee Jin Bae , Kim Seok -YEON , Cho Jin -MAN
Published: May 2024

Objective:

The study compared the single-pill combination of third-dose triple antihypertensive therapy (amlodipine 1.67 mg, losartan potassium 16.67 mg, chlorthalidone 4.17 mg) with standard-dose monotherapy (amlodipine 5mg) in reducing systolic blood pressure (SBP) among patients with mild to moderate hypertension.

Design and method:

This was a multicenter, randomized, double-blind, active-controlled, parallel-group phase III noninferiority trial. Eligible participants aged >=19 years with SBP >=140 to <180 mmHg and diastolic blood pressure (DBP) <110 mmHg after 4 weeks placebo run-in period were randomized to either 8 weeks of combination therapy (ALC) or monotherapy (A5). The primary efficacy endpoint, noninferiority in SBP reduction, was assessed using the upper limit of the one-sided 97.5% confidence interval (97.5%CI) for the difference in SBP reduction between treatments at week 8, with a noninferiority margin of 3 mmHg.

Results:

The efficacy endpoint analysis included 167 and 166 in the ALC and A5 groups. After 8 weeks, the ALC and A5 groups showed SBP reductions of -18.3±11.9 and -19.4±12.5, respectively, and DBP reductions of -8.5±7.3 and -9.8±7.0 mmHg, respectively (p>0.025 for both). The unadjusted least-square mean (LSM) difference in SBP reduction was 1.15 mmHg, with a 97.5%CI upper limit of 3.51 mmHg. More female patients were allocated to the A5 than the ALC groups (47.6% vs. 34.1%, p=0.012). Both treatments exhibited greater SBP reduction in women than men (-21.4 vs. -16.8 mmHg, p=0.009 in the ALC group; -21.9 vs -17.1 mmHg, p<0.001 in the A5 group). The sex-adjusted LSM difference in SBP reduction was 0.46 mmHg, with a 97.5%CI upper limit of 2.79 mmHg. The response rates (achieving SBP <140 mmHg and DBP <90 mmHg and/or reduction of SBP >=20 mmHg and/or DBP >=10 mmHg from baseline) were 73.1% for ALC and 75.3% for A5 groups (p=0.633). Adverse drug reactions (ADRs) occurred in 3 patients receiving ALC and 5 patients receiving A5, all being mild.

Conclusions:

The study demonstrated that the single-pill third-dose triple antihypertensive therapy is comparable to standard-dose monotherapy in reducing SBP over 8 weeks without increasing ADRs, providing further support for the low-dose combination antihypertensive drugs in the initial treatment of hypertension. (NCT05362110)
ASSESSING THE CLINICAL IMPACT OF PROTON PUMP INHIBITOR-DIGOXIN INTERACTIONS: A RETROSPECTIVE COHORT STUDY OF HOSPITALIZATION AND MORTALITY RISK
Authors: Qadhi Rawabi , Tran Tran , Lip Stefanie , Team Ogor , Macallum Linsay , Padmanabhan Sandosh
Published: May 2024

Objective:

Digoxin pharmacokinetics are altered by co-administration of proton pump inhibitors (PPI). This may have adverse clinical consequences given digoxin's narrow therapeutic index. Our aim was to investigate whether there was evidence for the association of digoxin-PPI interactions with early adverse clinical events.

Design and method:

A retrospective cohort study was conducted using an anonymised extract of linked routinely collected Greater Glasgow and Clyde hospitals data between 01/01/2014 and 31/12/2022. Patients aged 40 years and over when commencing either a PPI or digoxin were classified into: PPI only, digoxin only, or both PPI and digoxin. Record linkage provided 60-day follow-up data on all-cause, gastrointestinal and arrythmia-related hospitalisations or deaths. Univariate and multivariable Cox proportional hazards models were run applying inverse probability of treatment weighting for age, sex, SIMD, ethnicity, and background conditions to address confounding by indication.

Results:

The cohort comprised 200,769 (92%) patients who commenced on a PPI only, 3,358 (1.5%) on digoxin only, and 14,126 (6.5%) on both. The 53-day crude incidence of all-cause hospitalisation or death was 7.7%, 11.0% and 16.3% respectively. Compared with PPI only, the risk was higher for those taking a PPI plus digoxin (adjusted HR 1.93, 95% CI 1.81;2.07) but not digoxin only. This was explained by gastrointestinal conditions which were the most frequent cause of hospitalisation and death. Arrythmia-related hospitalisations/deaths were more likely among those taking digoxin even if not also taking a PPI.

Conclusions:

Concomitant use of a PPI and digoxin significantly increases the risk of early clinically significant gastrointestinal complications.
ASSESSED OF ANGIOTENSIN-CONVERTING ENZYME INHIBITORS THERAPY ALONE OR ASSOCIATED WITH HYDROCHLOROTHIAZIDE AND/OR CHANNEL CALCIUM BLOCKERS ACCORDING TO APPLANATION TONOMETRY
Authors: Paterno Carlos Alberto
Published: May 2024

Objective:

Angiotensin-converting enzyme inhibitors (ACE-I) are widely accepted as antihypertensive agents with beneficial effects on cardiovascular events. The aim of this study was to know the efficacy of the ACE-I therapy alone or associated with Hydrochlorothiazide (Hctz) and/or Channel Calcium Blockers (CCB) during assessment with the SphygmoCor System.

Design and method:

For this cross-sectional retrospective study, we recorded 109 hypertensives with normal kidney function, both sexes, treated with ACE-I alone (41%) and associated with Hctz and/or CCB. Women were 54 with a mean age of 68.5 years, and men 55 with a mean age of 64.3 years. The mean follow-up time for women and men was 33/38 months, respectively. Anthropological data, Systolic/Diastolic Blood Pressure, and Heart Rate were measured. Central Haemodynamic Parameters and the difference between normal levels and observed values of Augmentation Index with SphygmoCor System PVX were assessed, according method's standard by sex and age. The total sample of ACE-I therapy was evaluated, and after were divided into 4 groups: ACE-I alone or associated with Hctz, CCB, or both. The results of the ACE-I therapy alone group were compared with the other 3 groups. Mean and standard deviation were calculated. Statistical tests were two-sided and the alpha level was set at <0.05.

Results:

The systolic diastolic blood pressure (women-men 153.0/86.3-142.5/87.4 mmHg) and Central Haemodynamic Parameters of the total sample during ACE-I therapy were higher than normal, as were the values of the other 4 groups. When the group treated with ACE-I alone was compared with the groups of ACE-I associated with Hctz, BCC, or both, no statistically significant difference was observed. Only in the small group of women, the difference in augmentation index was normal when ACE-I was associated with Hctz and CCB. Probably associating Hctz or CCB with ACE-I could produce the phenomenon of “escape” of aldosterone with the consequent increase of cardiovascular volume and blood pressure.

Conclusions:

The systolic and diastolic blood pressure values and Central Haemodynamic Parameters during ACE-I therapy were higher than normal and when associated with Hctz, CCB, or both no benefit was observed.
FOLLOW-UP OF RENAL DENERVATION IN PATIENTS WITH RESISTANT ARTERIAL HYPERTENSION
Authors: Rekovets Oksana , Sirenko Yuriy , Torbas Olena , Primak Galina , Radchenko Ganna , Granich Volodymyr , Kushnir Svitlana
Published: May 2024

Objective:

Aim. Determining the long-term efficacy and safety of RDN the results of a 10-year follow-up

Design and method:

We selected 1146 patients with resistant arterial hypertension (RAH) who received 3 or more antihypertensive drugs. 16 patients were selected for renal artery denervation. RDN was performed in 8 patients (0.70%). 8 patients refused the procedure. The age was 52.13 ± 3.88 years (40–66), the duration of hypertension was 16.75 ± 2.17 (12–25) years. The number of antihypertensive drugs was 5.5 ± 0.18 (patients was in refractory hypertension). Office SBP/DBP on optimization of therapy was 156.88/95.00 ± 2.98 mm Hg and heart rate - 68.88 ± 3.28 beats/min. 24SBP/DBP was 149.16 ± 5.40/86.98 ± 5.08 mm Hg. 24HR was 70.12 ± 2.94 beats/min. All patients tolerated the procedure well.

Results:

The decrease in office SBP/DBP in the dynamics of 1 month, 12 months, 2 years, 5 years and 10 years were -12,59/-10,0, -11,17/-2,57, -20,31/-11,71, -27,71/-13,33 and -30,21/-16,67 mm Hg, respectively. The office heart rate (HR) decreased, its dynamics were -3.74 bpm, -4.68 bpm, -1.45 bpm, - 2.13 bpm. -4.21 bpm, - 3.88 bpm., respectively. The decrease in 24SBP/DBP was -14,45/-6,95, -8,70/-10,01, -19,45/-12,37, -19,91/-11,24, -29,93/-13,61 and -26,13/-23,35 mm Hg. (p<0.05 for all values). 24HR dynamics: -3.16 bpm, - 4.19 bpm, + 1.43 bpm. -1.51 bpm, -4.46 bpm, and -5.49 bpm, respectively. After 2, 5, and 10 years, all patients reached the target blood pressure level both in the office and with ABPM. Patients reduced the number of antihypertensive drugs from 5.50±0.18 to 3.50±0.30 - after 5 years and 3.67±0.18 - after 10 years after RDN. GFR change over 10 years from 76.10±5.62 to 64.60±1.93 ml/min/1.73m2, p>0.05. One patient died of thyroid cancer 2 years later. All other patients are alive and have not had any cardiovascular event or death during 10 years.

Conclusions:

Long-term results of renal artery denervation showed no cardiovascular events or cardiovascular death over 10 years. RDN contributed to a reduction in the number of antihypertensive drugs from 5.5 to 3.67 after 10 years of therapy. All patients achievement of the target BP level.
EVALUATION OF THE EFFICACY AND TOLERABILITY OF A FIXED DOSE COMBINATION OF AMLODIPINE AND INDAPAMIDE IN PATIENTS OLDER THAN 55 YEARS
Authors: Islam Quazi Tarikul , Haq Kmhs Sirajul , Moula Kaniz , Ah H.A.M. Nazmul , Kalam Khan Abul , Rahman Mujibur , Patwary Ismail , Hossain Zakir , Miah Titu , Kalam Azad Abul
Published: May 2024

Objective:

There is very limited real-life data on hypertension management in Bangladeshi population. Considering this fact, this study evaluated the effectiveness of treatment with an indapamide/amlodipine single-pill combination (SPC) in Bangladeshi patients over the age of 55 years, in an OPD setting with uncontrolled systolic hypertension in real-life clinical practice.

Methods: This was a 3-month, multicenter, observational, open-label study conducted in 3 divisional cities of Bangladesh among patients with grade I or II hypertension who were either uncontrolled on previous antihypertensive treatment or treatment-naïve. The effectiveness of indapamide/amlodipine SPC was assessed by the change in office systolic blood pressure (SBP) and the rate of target SBP (< 140 mmHg) achievement at 2 weeks, 1 month and 3 months, in four age groups: 55-59 years, 60-69 years, 70-79 years, and 80 years or older.

Design and method:

The COMBINE study recruited 213 patients, of whom 185 took indapamide/amlodipine 1.5/5 mg SPC fora full three-month course of therapy. Mean age was 62.4±7.4 years, 76 men [41.1%] and 109 women [58.9%]. The absolute decrease of SBP during 3 months of taking indapamide/amlodipine single-pill combination (SPC) was 29.3 mm Hg, DBP - 12.9 mm Hg. After 3 months of treatment significant SBP decreases from baseline were observed in each age group: ? 31.8 mmHg (from 156.7 to 124.9), ? 26.4 mmHg (from 152.7 to 126.3), ? 29.5 mmHg (from 152.8 to 123.3), and ? 25.8 mmHg (from 151.7 to 125.9) in the 55-59, 60-69, 70-79, and 80 years and older age groups, respectively. Leg edema was observed in 3 patients (1.62%), electrolyte imbalance was observed in 4 patients (2.16%) and 1 patients observed sudden fall of blood pressure.

Conclusion: This COMBINE study results showed that indapamide/amlodipine SPC was associated with significant and rapid reductions in BP even in a different age range of Bangladeshi patients in routine clinical practice. This study result is consistent with already achieved data of this SPC globally.
INCREASED INTAKE OF TABLE SALT AS A RISK FACTOR FOR THE DEVELOPMENT OF ARTERIAL HYPERTENSION
Authors: Khamidullaeva Gulnoz , Ataniyazov Khurshid , Yusupova Khafiza , Fozilov Khurshid , Abdullaeva Saodat
Published: May 2024

Objective:

to study association of high table salt intake with hypertension among hypertensive patients of Aral Sea region of Uzbekistan.

Design and method:

The results of screening of the population over 40 years of age (total 2430 respondents) in family clinics of the region were analyzed, according to the modified (for the region of Central Asia and Transcaucasia) PEN WHO protocol. From the total number of respondents, individuals with high blood pressure (BP) 140/90 mm Hg or more were selected. Taking into account the Aral Sea region, characterized by an unfavorable climate and salinity of soil and water, all subjects were tested according to the method of R. Henkin to determine the threshold of taste sensitivity to table salt.

Results:

The 2019 STEPS Uzbekistan study shows that more than a third (36.6%) of residents always or often add or directly during meals and more than a third (36.2%) always or often eat processed foods high in salt. Hypertensive patients in the Aral region were characterized by a pronounced prevalence of a high threshold of taste sensitivity to table salt: in the general group - 85.6%, women 83.7%, men 88.7%, which on average required more than 0.32% NaCl concentration to assess the threshold. At the same time, there was a noticeable direct correlation between hemodynamic parameters – systolic and diastolic BP, mean BP and NaCl concentration in the test for determining the taste sensitivity to table salt threshold (r = 0.646; r = 0.610; r = 0.645, respectively). A survey on proper nutrition, according to the PEN protocol, also showed that 68% of those surveyed added salt to their food and/or consumed saltiness in their diet, with a slight difference between women and men: women 61.2%, men 72.6%, which is significantly more similar indicators identified.

Conclusions:

As our results showed, among patients with hypertension in the Aral region, high consumption of table salt prevails, which is confirmed by a high threshold of taste sensitivity to NaCl. A correlation was revealed between a high threshold of taste sensitivity to table salt and blood pressure in hypertensive patients.
THE ASSOCIATION BETWEEN SODIUM AND POTASSIUM ON DIFFERENCES IN RENIN AND ALDOSTERONE LEVELS AMONG GHANAIAN POPULATIONS IN RURAL GHANA, URBAN GHANA AND AMSTERDAM
Authors: Tonkin-hill Gina , Appiah Lt , Shafer La , Van Der Linden El , Vriend Emc , Danser Ah , Vogt Liffert , Agyemang Charles , Van Den Born Bert -Jan
Published: May 2024

Objective:

To identify if differences in dietary, and serum, sodium and potassium levels are associated with differences in aldosterone, renin and the aldosterone-renin ratio. Secondly, to assess the contribution of confounders, and site-specific factors.

Design and method:

A multi-site analytical cross-sectional study using baseline data from the RODAM (Research on Obesity and Diabetes among African Migrants). Adult Ghanaians (aged over 25 years) were recruited across rural Ghana, urban Ghana and Amsterdam, the Netherlands. Both food questionnaires and renin and aldosterone measurements occurred in a subset of the baseline RODAM population: rural Ghana (n=193), urban Ghana (n=199) and Amsterdam (n= 69). Dietary behaviour was collected by a RODAM-specific Food Propensity Questionnaire (FPQ) which assessed the usual intake of 134 food items over the preceding 12 months. Three outcomes were investigated: aldosterone (pg/mL), renin (pg/mL) and the ARR, aldosterone-renin ratio (pg/mL/pg/mL).

Results:

Sodium intake was highest in urban Ghana (2.9g/day) and Amsterdam (2.8g/day), followed by rural Ghana (2.5g/day). Potassium intake was highest in rural Ghana (4.8g/day) and Amsterdam (4.7g/day), followed by urban Ghana (3.9g/day). Sites had similar renin levels; however, differences in aldosterone, led to a median ARR of 13.2, 12.2 and 22.0 pg/mL/pg/mL in rural, urban Ghana and Amsterdam respectively. Generalised linear models both with and without covariates, revealed no significant associations between dietary or serum sodium and potassium levels with either aldosterone, renin nor ARR. Associations were more pronounced in subgroup analyses among participants not taking blood pressure medication, although they remained weak or non-significant.

Conclusions:

Unlike previous research, no clear association between salt and hormone levels was found. However, bias from missingness, a possible healthy volunteer effect and medication use may have masked results. The findings may suggest that increased medication usage could benefit these populations in reducing blood pressure-related issues. These findings encourage the development of further longitudinal and intervention studies in people of African descent, to investigate the interaction of specific medications on dietary intake and renin, aldosterone levels.
DEPRESSION AND ANXIETY IN HYPERTENSIVE PATIENTS UNDER THE CONDITIONS OF WAR IN UKRAINE: COHORT STUDY
Authors: Sydorchuk Andrii , Lytvyn Bohdan , Sydorchuk Larysa , Yarynych Yulia , Voronyuk Ksenia , Sydorchuk Ruslan
Published: May 2024

Objective:

The prevalence of hypertension in Ukraine is 29.6% among city residents and 36.3% in rural areas. Currently, the situation with hypertension in Ukraine has worsened due to the full-scale military aggression of the russian federation. Acute and chronic stress provoke a more frequent crisis course of hypertension, way more difficult control of elevated blood pressure (BP). Therefore, the aim of the study was to assess anxiety and depression value in the Ukrainian population before and during the war to establish the life quality changes in essential arterial hypertensive (EAH) patients.

Design and method:

100 EAH patients with hypertensive-mediated organ damage (moderate-very high cardiovascular risks, aged 45-65 years) participated in the cohort study. All participant underwent a complex of clinical and laboratory examinations and determined the frequency of EAH exacerbations, crisis course, the Charlson comorbidity index, anxiety and depression level after GAD-7 and PHQ-9 tests, the Cumulative Illness Rating Scale CIRS, life quality (SF-36) compared to the pre-war period. Additionally, 191 respondents preferably from the western part of Ukraine, filled out an online questionnaire form that included tests for depression, anxiety and life quality.

Results:

The war significantly affected the life quality of Ukrainians with EAH: both the physical and mental health of patients according to the SF-36 test (by 19.65% and 23.01%), as well as social activity (by 19.71%) worsened. The frequency of EAH exacerbations and crises course against the background of military aggression increased 2.25 times (χ2=14.25; p<0.001 and χ2=4.42; p=0.035), as well as the reactive and personal anxiety levels – by 13.37% (p=0.002) and 19.80% (p=0.042), respectively; 29% of respondents show symptoms of moderate, severe and very severe depression (PHQ-9); 37% had generalized anxiety disorder (GAD-7).

Conclusions:

This study presents unique experience. The russian invasion in Ukraine greatly affected well-being of the general population: the frequency of persons with moderate and significant deterioration of health (according to SF-36) increased by 18%, as well as the number of those with moderate and severe depression and anxiety disorders symptoms; the frequency of the EAH crisis course increased by 10%.
ASSOCIATION BETWEEN HYPERHOMOCYSTEINEMIA AND VITAMIN D DEFICIENCY AND THE RISK OF HYPERTENSION
Authors: Smiljic Sonja , Ilic Aleksandra , Stevanovic Angelina , Nestorovic Vojkan , Sapic Srna
Published: May 2024

Objective:

Cardiovascular risk factors simultaneously affect the premature onset of hypertension. The aim of our study was to indicate the frequency of cardiovascular risk factors and coherency of dyslipidemia, elevated values of homocysteine and vitamin D deficiency with the arterial hypertension.

Design and method:

In a prospective study, we have included 230 respondents, of which 199 are being treated for hypertension, and 31 had normal blood pressure. All patients were divided into three groups, patients between 22-39 years old, 40-49 years old and 50-59 years old. We have processed socio-epidemiological data, clinical exam, and biochemical analyses.

Results:

In the group of patients between 22 and 39 years of age were significantly less female respondents, and younger patients significantly less had HTA (p >0.05). Compared to people with normal blood pressure, patients treated for HTA are physically inactive (p >0.17), smokers (0.002) and have BMI above 25 kg/m2 (p>0.02). Total cholesterol and triglycerides were elevated at patients with hypertension, and the value of HDL cholesterol was significantly higher in patients with normal blood pressure (P>0.05). Vitamin D deficiency and hyperhomocisteinemia were more common in people with hypertension and between 50-59 years of age (p<0.001).

Conclusions:

Patients with arterial hypertension have association of more cardiovascular risk factors at the same time. Association of arterial hypertension, dyslipidemia, hyperhomocisteinemia and vitamin D deficiency, speeds up the process of atherosclerosis, leads to coronary heart disease and premature death. Prevention has an important place in the early diagnosis of hypertension and prevention of complications.
PREVALENCE OF RISK FACTORS AND TARGET ORGAN DAMAGE CAUSED BY HYPERTENSION IN RESIDENTS OF THE ARAL SEA REGION OF UZBEKISTAN
Authors: Khamidullaeva Gulnoz , Ataniyazov Khurshid , Fozilov Khurshid , Abdullaeva Saodat
Published: May 2024

Objective:

Analysis of the results of screening the population over 40 years of age for early detection of risk factors and target organ damage caused by hypertension in real clinical practice of family clinics in the Aral Sea region.

Design and method:

The results of screening of 2430 respondents were analyzed according to the modified PEN WHO protocol, which 1020 people with blood pressure (BP) 140/90 mm Hg or more included in the study. The average age was 57.68±8.06 years, women 61.4%, men 38.6%. Additionally, we determined echocardiography, ultrasound examination of the brachiocephalic arteries, microalbuminuria, creatinine and uric acid in blood serum. Statistical data are presented as M±SD.

Results:

Among the patients with high BP, 24 (2.4%) were under 40 years old, 847 (81%) were aged 40-65 years, 169 (16.6%) were over 65 years old. Obesity was detected in 46.2% of patients, left ventricular hypertrophy in 96%, microalbuminuria in 76%, proteinuria in 21%, thickening of the intima-media of the common carotid artery >0.9 mm in 92% of the examined. It was revealed that low cardiovascular risk was 2 times more common among women compared to men: 11.3% versus 5.6% (χ2=8.990; p=0.003); almost 4 times fewer patients with coronary artery disease: 7.4% versus 28.9% (χ2=14.939; p=0.0001); there are no tobacco users or regular alcohol drinkers, whereas among men these risk factors were identified in 59.4% (χ2=178.848; p=0.0001) and 35% (χ2=82.238; p=0.0001), respectively. Hyperuricemia prevailed in men compared to women: 23.3% versus 6.4% (χ2=60.243; p=0.0001) but the incidence of type 2 diabetes is 2 times higher in women compared to men: 13.7% versus 7.4% (χ2=9.205; p=0.002)

Conclusions:

The study showed a wide distribution of CVD risk factors among the hypertensive population of the Aral Sea region and significant target organ damage caused by hypertension. Among hypertensive men, there was a significant prevalence of tobacco and alcohol use, a significantly frequent detection of coronary artery disease, and hyperuricemia compared to women; type 2 diabetes mellitus is significantly more frequently detected in the female population.