bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.