bluuebunny/crossref_metadata_2025_split huggingface dataset:
HUMAN UMBILICAL MESENCHYMAL STEM CELL-DERIVED MITOCHONDRIA AMELIORATE MATERNAL PHENOTYPE BY IMPROVING PLACENTAL MITOCHONDRIAL FUNCTION IN ANGIOTENSIN II-INDUCED RAT PREECLAMPSIA MO
Authors: Zhang Yin Hua 
Published: May 2024

Objective:
Preeclampsia (PE) is one of the primary contributors of neonatal and maternal morbidity and mortality. Clinical manifestations of PE include elevated blood pressure and renal dysfunction (albuminuria), 20 weeks into the gestation. Presently, preterm labor, intravenous MgSO4 for vasospasm relief or termination of pregnancy remain the treatments for PE. There is an urgent need to develop effective strategies to prevent PE-associated abnormalities to secure maternal and neonatal health. Here, we investigated the efficacy of mitochondrial transplantation (derived from human umbilical cord mesenchymal stem cells, hUC-MSC) on a rat model of PE.

Design and method:
A rat model of PE was established by infusing angiotensin-II (Ang II, 1 microg/kg/min) to pregnancy rats (from gestation day 8 for 2 weeks). Mitochondria from hUC-MSC was administered (100microg / <micro>l) via jugular vein on gestation day 14.

Results:
Blood pressure was increased in Ang II-rats, accompanied by reduced glomerular capillaries, impaired fetal weight and placental vascular development. Soluble fms-like tyrosine kinase 1 (sFlt-1) content was increased in the plasma of Ang II rats, confirming the establishment of PE. Mitochondria from hUC-MSC reversed both fetal and maternal manifestations of PE (fetal weight was increased and blood pressure, glomerular abnormalities and placental vasculature were restored to normal). Mitochondrial biogenesis markers (PGC-1α, NRF1, Tfam) were improved, mitophagy markers (PINK1, BNIP3, BNIP3L, FUNDC 1) and mitochondrial fission markers (DRP1, FIS1) were reduced and mitochondrial fusion markers (OPA1, MFN1, MFN2) were increased in the mitochondria from placental tissue. Reactive oxygen species (ROS) was reduced, activities of ATP synthase and citrate synthase were increased. Further investigations into trophoblast cells and placental tissue revealed elevated sFLT-1 mRNA and protein levels in PE. Additionally, calcineurin protein content and nuclear factor of activated T cells (NFAT) in the nucleus were increased in placental trophoblasts of PE, hUC-MSC reversed the effects.

Conclusions:
In summary, mitochondria from hUC MSC can be an effective therapeutic modality for the treatment of PE in our rat model. This study sheds light on novel therapeutic options for PE targeting angiogenesis.
EFFECTS OF ANGIOTENSIN RECEPTOR-NEPRILYSIN INHIBITOR (ARNI) ON HOME BLOOD PRESSURE AND BAPWV IN ESSENTIAL HYPERTENSIVE PATIENTS
Authors: Yamagishi Toshio 
Published: May 2024

Objective:
Sacubitril/valsartan sodium hydrate (Entresto) is classified as an ARNI and has a novel mechanism of action that simultaneously inhibits neprilysin and angiotensin II receptors. We investigated the effects of Entresto on blood pressure (BP), baPWV, and carotid arterial intima-media thickness (IMT) and elasticity in essential hypertension.

Design and method:
Fifty-two hypertensive patients (twenty-six males, average age 67 years) who had insufficient BP reduction (home systolic 135 or diastolic 85 mmHg or higher) after receiving ARBs (azilsartan 26 or valsartan 26) for more than 6 months, were assigned to receive Entresto for 12 months (200-400mg/day, gradually increase depending on the condition). Changes in home BP, biochemical data, baPWV, central blood pressure (cSBP) were evaluated. The carotid arterial IMT and elastic modulus in the circumferential direction (Eθ) were simultaneously measured by the high-resolution Doppler technique, “Phased Tracking Method”.

Results:
Home morning BP (mmHg) after administration of Entresto significantly (p<0.05) decreased from 142.9±11.3/80.0±12.1 to 125.7±7.4/70.9±12.0, and home heart rate (HR, bpm) also significantly decreased from 75.1±11.3 to 72.2±11.9. There were no differences in BP and HR changes between ARBs. Furthermore, baPWV (m/sec) significantly decreased from 1542.4±259.8 to 1438.4±222.41, and cSBP (mmHg) significantly decreased from 141.0±9.1 to 133.2±8.4. Urine protein (mg/g/Cr) decreased significantly from 319.6±473.6 to 213.1±376.4, but there were no significant changes in eGFR (45.6±14.1 to 44.5±14.5 mL/min/1.73m2) nor serum potassium (4.2±0.4 to 4.0±0.9mEq/L). Eθ (kPa) was reduced significantly from 301±141 to 163±41 without changes in IMT. The histogram analysis of the Eθ data revealed the drug decreased harder components of the elasticity distribution, suggesting improvement of endothelial dysfunction.

Conclusions:
These data demonstrate that the ARNI, Entresto provides potent antihypertensive and antiatherosclerotic effects.
SINGLE-PILL, TRIPLE ANTIHYPERTENSIVE THERAPY IN RURAL SUB-SAHARAN AFRICA: PRELIMINARY EXPERIENCE
Authors: Muggli Franco , Parati Gianfranco , Hunjan Isabella , Stroppa Clara , Bianchetti Mario , Muvunyi Bienvenu , Ntaganda Evariste , Umulisa Alice , Sinabubaraga Vincent , Radovanovic Dragana 
Published: May 2024

Objective:
Arterial hypertension is worldwide the leading modifiable cardiovascular risk factor. Beside life-style changes, strong evidence supports the efficacy of pharmacological treatment in reducing the complications of hypertension. International guidelines have recommended single-pill, low-dose combinations as initial treatment strategy. We investigated whether management of hypertension through this approach is feasible and effective in a rural sub-Saharan Africa setting.

Design and method:
Diagnosis of hypertension was established over three sets of blood pressure measurements: during a community-based, house-to-house screening in 2020 and in 2022, and at the hypertension outpatient clinic. Blood pressure measurements were performed according to the ESH recommendations by trained personnel, using a validated, oscillometric device OMRON M7 IT-HEM-7322-E. In 98 individuals diagnosed to have arterial hypertension, once-daily, single-pill combination of olmesartan, amlodipine, and hydrochlorothiazide was prescribed at a dose suitable to their blood pressure values and clinical characteristics. They were instructed on its administration and potential side effects and encouraged towards lifestyle modifications. Treatment regimen was adjusted, if needed, at each outpatient clinic visit scheduled after 4, 8, 12, and 16 weeks

Results:
79 patients (aged 61 [53-70] years; median and interquartile range) strictly adhered to the treatment schedule, while overall 19 individuals dropped-out (aged 70 [65-80] years) because of different reasons. About 20% were tobacco smokers and nearly all consumed alcohol. Blood pressure was <140/90 mm Hg after 4 weeks in 44 (56%), after 8 weeks in 62 (78%), after 12 weeks in 69 (87%), and after 16 weeks in 74 (94%) participants. Excellent tolerance was widely reported.

Conclusions:
Management of hypertension with once-daily, single-pill combination of olmesartan, amlodipine, and hydrochlorothiazide as initial treatment was feasible and effective also in a rural sub-Saharan setting, with very high rate of hypertension control in patients adherent to treatment. Our results provide real life evidence in favor of extensive implementation of single-pill combination therapy also in low- and middle-income countries where local Health Care Systems should include recommendation on their usage in national guidelines and should make them available also in rural and remote areas at low or no cost as reliable first-line treatment strategy
EVENING DOSING VERSUS MORNING DOSING OF ANTI-HYPERTENSIVE MEDICATIONS FOR NOCTURNAL HYPERTENSION: A SYSTEMATIC REVIEW AND META-ANALYSIS OF 107 RANDOMIZED CONTROLLED TRIALS
Authors: Lee Eric Kam-pui , Poon Paul Km , Tse Emily Tsui-yee , Wang Shuqi , Ramdzan Siti Nurkamilla , Sit Regina , Ng Wei Leik , Chan Linda , Yu Chun -Pong 
Published: May 2024

Objective:
Although nocturnal blood pressure (BP) is consistently a stronger predictor to cardiovascular events and death than daytime BP, specific treatment for nocturnal hypertension (HT) is lacking. As effects of one-daily anti-hypertensive (HT) medications are more pronounced within first few hours of ingestion, evening administration of anti-HT medications can be a feasible treatment for nocturnal HT. However, a relevant meta-analysis in patients with nocturnal HT has yet been conducted.

Design and method:
This is a systematic review and meta-analysis. Randomized-controlled trials that included patients with elevated mean nocturnal BP, compared evening anti-HT administration versus morning administration and reported nocturnal BP were included. Multiple databases were searched using search terms developed with a medical librarian. Grey literature search included reference lists of previous related reviews and clinicaltrial.gov. Studies selection and data extraction were conducted by 2 independent authors. Risk of bias assessment and overall quality of evidence were conducted using Cochrane risk-of-bias tool and GRADE by 2 independent authors. Meta-analyses were conducted using a random effect model.

Results:
A total of 107 studies were included and 76 Chinese studies were identified, which had never been included in previous reviews. Only a few studies investigated effects of beta-blockers (n=3) and diuretics (n=1). Evening administration of anti-HT medications were effective in reducing nocturnal systolic BP (4.12-9.1mmHg; I2 = 80.5-95.2%) and diastolic BP (3.38-5.87mmHg; I2=87.4-95.6%). Subgroup analyses found that effectiveness of evening administration was contributed by data from Hermida group and from China. Effectiveness of nocturnal BP reduction was similar with different types, doses, and half-lives of medications. Evening administration of anti-HT medications may reduce proteinuria, left ventricular hypertrophy (LVH), non-dipper and morning surge. The overall quality of evidence was ranked low to moderate. There is a lack of long-term RCT which reported clinically relevant cardiovascular outcomes (i.e. >1 year).

Conclusions:
Evening administration of anti-HT can further reduce nocturnal BP, non-dipping and excessive morning surge when compared to morning administration and can be a useful strategy for treatment of nocturnal HT. Evening administration may also be more effective to reverse surrogate cardiovascular outcomes such as proteinuria and LVH.
THE CHANGE IN QUALITY OF LIFE IN DRUG-TREATED HYPERTENSIVE PATIENTS AFTER 10 YEARS OF ANTIHYPERTENSIVE TREATMENT
Authors: Kantola Ilkka , Kantola Taru -Tuuli 
Published: May 2024

Objective:
To clarify the change in quality of life in Finnish drug-treated hypertensive patients after ten years of antihypertensive treatment.

Design and method:
Earlier non-treated patients participated during the years 1999-2002 in a six-month study where their antihypertensive treatment was titrated either by using home or 24 hour ambulatory measurement. Thereafter they have been in the ordinary out-patient care,
The patients filled the SF-36 questionnaire before the start of antihypertensive therapy and after 10-13 years of use of antihypertensive therapy.

Results:
SF-36 questionnaire was filled out by 44 patients (23 females and 21 males, aged 66.1 (6.1), 55-77 years) after 10.6 (2.9) (6-13) years of antihypertensive treatment. All of them used at least one antihypertensive agent.
The mean (SD) SF-36 questionnaire scores after about 10 years of antihypertensive treatment were (maximum 100): Physical functioning 78.5 (19.9), role-physical 72.6 (34.0), bodily pain 68.1 (22.2), general health 64.5 (16.2), vitality 68.6 (15.8), social functioning 90.1 (19.0), role-emotional 76.0 (35.9), mental health 84.5 (14.4) and general health 3.2 (0.7). The mean of all the scores was 75.4 (17.8).
During the titration period (in the years 1999-2002) physical functioning decreased nearly significantly from 87.1 (12.4) to 83.3 (15.7), p=0.053. Other parameters did not change significantly.
During 10 years of antihypertensive treatment physical functioning decreased significantly from 84.5 to 79.8 (p=0.039). Instead, vitality (63.4 (22.2) to 69.6 (14.5), p=0.032), social functioning (85.8 (21.1) to 91.7 (14.9), p=0.028) and mental health (81.7 (14.4) to 85.7 (12.4), p=0.030) increased significantly. Other parameters did not change significantly.

Conclusions:
According to our results physical functioning decreased and vitality, social functioning and mental health increased during about 10 years of antihypertensive treatment. The decrease in physical functioning is probably explained by aging, because physical function decreases in normal population about 0.5/lifeyear. Perhaps, good antihypertensive treatment explains the increase in those three mental parameters. All three parameters and also physical functioning were better than in the normal population. Thus, it seems that according to the SF 36 questionnaire quality of life in Finnish treated hypertensive patients is quite good and do not decrease significantly during aging.
DECLINING RATES OF FIXED-DOSE COMBINATION PILLS FOR HYPERTENSION IN GERMANY FROM 2016 TO 2023
Authors: Götzinger Felix , Kieble Marita , Laufs Ulrich , Mahfoud Felix , Schulz Martin 
Published: May 2024

Objective:
Current guidelines recommend the usage of fixed-dose combination (FDC) pills in primary and secondary prevention of cardiovascular diseases. Current data on the implementation of these recommendations in German clinical practice are scarce. The objective was to assess the use of antihypertensive FDCs in Germany from 2016-2023.

Design and method:
We analysed claims data from the German Institute for Drug Use Evaluation from January of 2016 to September of 2023, containing information on dispensed drugs in an outpatient care setting of approx. 87% of the German population (excluding private insurance) and evaluated the use of antihypertensive FDC pills according to time, age of the insured persons, and active substances contained in the FDC.

Results:
The use of FDC pills decreased from 2016 to 2022 from 22.2 million packages to 15.6 million packages, while the absolute number of antihypertensives prescribed increased from 143.8 million packages to 155.9 million packages. Consequently, the proportion of FDC pills in all antihypertensives decreased from 15.4% in 2016 to 10.0% in 2022. The amount of hydrochlorothiazide (HCT) containing FDC pills decreased from 2016 to 2022 (from 18.9 million packages to 11.0 million packages), while the amount of FDC pills that do not contain HCT increased from 2016 to 2022 (from 3.3 million packages to 4.7 million packages). Use of FDC pills has been declining in all age groups. FDC pills are used infrequently in patients over 80 years of age.

Conclusions:
Despite guideline recommendations, use of antihypertensive FDC pills in Germany is declining, showing continuing guideline inertia. The decrease is mainly driven by decreased prescriptions of HCT-containing FDC pills. Assumed higher medication cost for FDC compared to single pills and fear of non-melanoma skin cancer for HCT are potential reasons. Use of FDC pills should be advised and implemented in outpatient care in Germany.
RATIONALE AND DESIGN OF PHASE 3 TRIAL FOR BAXDROSTAT, A NOVEL HIGHLY SELECTIVE ALDOSTERONE SYNTHETASE INHIBITOR
Authors: Perl Shira , Azizi Michel , Bakris George , Brown Jenifer M. , Flack John M. , Jones Erika , Shibata Hirotaka , Wittes Janet , Wilderäng Ulrica , Olsson Daniel S. , Williams Bryan 
Published: May 2024

Objective:
Aldosterone is a key driver of cardiorenal disease as well as hard-to-treat hypertension. Highly selective aldosterone synthase inhibitors (ASI) are a new class of anti-hypertensive therapy that hold great promise for management of blood pressure (BP), having demonstrated BP lowering in a proof-of-concept study. The rationale for and design of a phase 3 trial with the novel ASI baxdrostat are described here.

Design and method:
The international, multicenter, randomized, double-blind, placebo-controlled phase 3 BaxHTN trial (NCT06034743) will enroll approximately 720 adults with uncontrolled or resistant hypertension defined as seated office systolic BP greater than/equal to 135 mmHg despite 2+ antihypertensives including a diuretic, serum potassium 3.5-5.0 mmol/L, and eGFR greater than/equal to 45mL/min/1.73m2. Given the need to address long-term efficacy but limit placebo use due to the risks of uncontrolled hypertension, the study will have 4 sequential parts following placebo run-in: 1) 12-week double-blind period, 1:1:1 randomization to baxdrostat 2 mg, baxdrostat 1 mg, or placebo; 2) 12-week open label period, re-randomization of the placebo and 1 mg arms to 2 mg or standard-of-care; 3) 8-week randomized withdrawal period to 2 mg or placebo; and 4) 20-week open label period. The primary endpoint will be the change in office systolic BP from baseline to 12 weeks. Adverse events will be evaluated under independent data monitoring committee supervision.

Results:
Results are expected in late 2025.

Conclusions:
The phase 3 BaxHTN trial design will allow assessing the safety of baxdrostat and its effect on BP in patients with uncontrolled or resistant hypertension. Results are expected in late 2025.
EFFECT OF CHRONIC FUROSEMIDE THERAPY ON SERUM FREE LIGHT CHAIN IN CHRONIC KIDNEY DISEASE PATIENTS
Authors: Bisht Khushboo , Sinha Nishant 
Published: May 2024

Objective:
Chronic kidney disease (CKD) is an important cause of morbidity and mortality worldwide.
There is a lack of information on the epidemiology and progression of CKD in low-middle-income countries. Chronic use of diuretics is considered to further decrease renal clearance, a pathophysiology not very clearly understood. Free light chains renal deposition is precipitated by loop diuretics. This study attempted to determine whether chronic diuretic usage was associated with increase serum free light chain and a reduction in renal clearance among CKD patients.

Design and method:
A single-center, record-based study of 84 CKD patients with an established diagnosis of CKD, loop diuretic therapy, between June 2019 and December 2019 was conducted after ethical approval by institutional ethics committee ((RIMS/2018/32). The study included participants with age above 18 years of age, never dialysed, non-neoplastic (specifically plasma cell disorder), non-pregnant, and those on loop diuretic were divided into 3 groups: group 1 with Furosemide exposure more than 6 months; Group 2 with furosemide exposure between 3 months to 6 months but less than 6 months; and Group 3 with furosemide exposure less than 3 months.

Results:
46 out of 84 patients were of group 1, 20 belonged to group 2 and 18 were in group 3. In group 1, mean eGFR of 103.6, mean free kappa of 100.98 and mean lambda of 126.65.2 was observed. Group 2 patients had mean eGFR of 125.6 with mean free kappa of 80.98 and mean lambda of 1002.2, whereas group 3 had mean eGFR of 15 5.5, mean free kappa of 79.8 and mean lambda of 96.65.2. It was also observed that 98% patients with stage 5 CKD had high serum free lambda level.

Conclusions:
This study revealed a strong association of serum free light chain level with stage of CKD in patients on diuretic therapy. Therefore, monitoring of Serum Free Light Chain among CKD patients on diuretic therapy can be an indirect evidence of furosemide induced renal function worsening.
ORTHOSTATIC HYPOTENSION IN PATIENT WITH HYPERTENSION AND THE ASSOCIATION OF ANTIHYPERTENSIVE PHARMACOLOGY TREATMENT
Authors: Doan Long , Nguyen Thi Lan Nhi 
Published: May 2024

Objective:
This study aims to assess the prevalence of orthostatic hypotension (OH) and investigate potential associations between OH and specific antihypertensive medication treatments.

Design and method:
A prospective study with a 1-month follow-up in all hypertension patients being treated with antihypertensive medication, who were manifesting symptoms of suspect OH (lightheadedness, visual disturbances, and presyncope…) at the outpatient clinic of Hue University Hospital. Patients with too high or too low SBP (>180mmHg or <90mmHg); patients with a history or be diagnosed in this visit with ischemic or hemorrhagic stroke; patients with a history of any vestibular disorder; patients with cognitive dysfunction or pregnancy were excluded from the study. Patients with a history of diagnosed OH or postural orthostatic tachycardia syndrome were also excluded. All participants were taken medical history, clinical examination, laboratory tests, and orthostatic BP measure by upper arm automated oscillometric device (OMRON HEM-7600T) seated to standing with a 3-minute delay. OH is diagnosed when a decrease in SBP equal or more than 20 mmHg or DBP equal or more than 10 mmHg. Patients had routine consults and treatment at baseline. After 1 month, all OH patients were re-examined and taken orthostatic BP measurements.

Results:
Among 642 participants (mean age 61.4 ± 11.4), 122 (19.0%) patients were diagnosed for OH. There were no significant differences between age, sex, history of comorbidities. There are no association between OH and the uncontrolled hypertension ratio as well as the strict of BP control. In antihypertensive agents, the use of CCB (Amlodipine, Lercanidipine in the study) appears to reduce the risk of OH (p <0.001) and vice versa, the use of diuretics (Hydrochlorothiazide; Indapamide in the study) appears to increase the prevalence of OH (p<0.001). These associations were also demonstrated again through multivariate analysis (p=0.041, p=0.003, respectively). The use of 3 antihypertensive agents were also increase the prevalence of OH (p<0.001), although this was not significant in multivariate analysis (p=0.083).

Conclusions:
Orthostatic hypotension is a common condition in people treated for hypertension with medication. The choice and change of antihypertensive classes should be considered in patients with suspected orthostatic hypotension.
VISCERAL FAT TISSUE AS A SIGNIFICANT CARDIOVASCULAR RISK FACTOR IN CORRELATION WITH SUBCLINICAL ORGAN DAMAGE IN POSTMENOPAUSAL WOMEN
Authors: Woznicka-leskiewicz Lucyna , Posadzy-malaczynska Anna 
Published: May 2024

Objective:
Postmenopausal women are a special group of the cardiological patients. Every effort should be made to search for subclinical organ damage in this group, the presence of which correlates with the amount of visceral fat tissue.

Design and method:
We examined 156 postmenopausal women. The average age of them was 65,3 years old. 41% of them had type 2 diabetes; 46% of them were taking statins. Pulse wave velocity (PWV), systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI) and lipid profile were evaluated. Visceral fat tissue, body weight and fat mass were performed by Tanita MC980 MA Plus analyzer. We assessed cardiovascular risk according to: SCORE2 and SCORE2- OP scales. Statistical calculations were performed in the StatSoft Statistica 10: ?Spearmana was taken to analyze the correlation of statistically significant values.

Results:
We revealed following results [∗for p<= 0,05; ∗∗for p<0,001].
People with higher body weight characterized by higher SBP and DBP. Lower fat mass and BMI resulted with lower DBP. The lower fat mass, BMI and the amount of visceral fat tissue, the higher HDL cholesterol level. People with higher fat mass, BMI and the amount of visceral fat tissue were more likely to have type 2 diabetes.Patients with higher amount of visceral fat tissue characterized by greater aortic stiffness and more often required lipid-lowering therapy. The amount of visceral fat tissue correlated with age of the patients and their cardiovascular risk assessed by SCORE2/SCORE2OP scales.

Conclusions:
The amount of visceral fat tissue should be taken into account in assessing the patient‘s cardiovascular risk and occurrence of cardiological subclinical organ damage. Weight loss must be considered as an important factor in the reducing of blood pressure. The likelihood of developing type 2 diabetes is correlated with higher BMI and fat mass. Reduction of BMI, fat mass and the amount of visceral fat tissue results with better lipid profile. Greater amount of visceral fat tissue results in more frequent need of starting lipid-lowering therapy.