bluuebunny/crossref_metadata_2025_split huggingface dataset:
COUNTERACTING ANGIOTENSINOGEN SMALL INTERFERING RNA-MEDIATED ANTIHYPERTENSIVE EFFECTS WITH REVERSIR
Authors: López Edwyn Cruz , Ye Dien , Van Veghel Richard , Garrelds Ingrid M. , Kasper Anne , Wassarman Kelly , Tu Ho -Chou , Zlatev Ivan , Danser A. H. Jan 
Published: May 2024

Objective:
Administering small interfering RNA (siRNA) targeting liver angiotensinogen (AGT) effectively depletes circulating AGT, leading to a sustained blood pressure reduction for up to six months post-single injection. However, certain situations may require a rapid increase in angiotensin levels. The REVERSIR (reverse siRNA silencing, RVR) technology is being studied as a potential approach to counteract AGT-siRNA effects.

Design and method:
Spontaneously hypertensive rats (SHR) underwent a 3-week AGT-siRNA treatment, followed by AGT-RVR doses at 1, 10, or 20 mg/kg. After a week of AGT-RVR, a re-dose of AGT-siRNA assessed its post-AGR-RVR effectiveness. Additionally, the impact of AGT-RVR with a 3-week valsartan treatment (4 mg/kg per day) was examined. Arterial pressure was measured via radiotelemetry, circulating AGT, and renin by enzyme-kinetic assays, and liver AGT mRNA levels by quantitative PCR.

Results:
: Baseline mean arterial pressure (MAP) was 144±1 mm Hg. AGT-siRNA reduced MAP by ∼16 mm Hg and circulating AGT by >95.9%, with a 25-fold increase in circulating renin. All AGT-RVR doses restored MAP to baseline within a week. Notably, 10 and 20 mg/kg fully restored circulating AGT and renin to baseline, while 1 mg/kg allowed ∼50% AGT restoration with renin above baseline. Liver AGT mRNA changes mirrored circulating AGT alterations. A second AGT-siRNA dose, on top of 1 mg/kg AGT-RVR, replicated the initial dose’s MAP effect. On top of 10 mg/kg AGT-RVR, the second dose resulted in ∼50% of the first dose’s MAP effect. Valsartan, like AGT-siRNA, reduced MAP similarly, inducing a 30-fold renin increase and 39.6% circulating AGT reduction. Adding AGT-RVR to valsartan did not alter this outcome.

Conclusions:
AGT-RVR dose-dependently reversed AGT-siRNA-induced AGT reduction, normalizing MAP. Notably, MAP normalization persisted with partially recovered AGT levels (∼50%), likely due to upregulated renin maintaining normal angiotensin generation. AGT-RVR had no impact on valsartan-induced AGT reduction. Post-AGR-RVR, a second AGT-siRNA dose effectively lowered MAP to the same extent as the initial dose. In summary, AGT-RVR is a highly selective tool for AGT and BP restoration in SHR. These findings support further evaluation of the RVR platform to counteract siRNA-mediated effects.
EFFICACY AND SAFETY OF SACUBITRIL/ALLISARTAN FOR THE TREATMENT OF PRIMARY HYPERTENSION: A PHASE 3 RANDOMIZED, DOUBLE-BLIND STUDY
Authors: Zhang Wei , Zhang Jin , Yan Jie , Ge Qian , Lu Xiaohong , Chen Shaoxing , Xu Wenjie , Sun Jingchao , Li Jinfeng , Liu Zichen , Wang Qiang , Zhou Xiangnan , Li Yan , Wang Jiguang 
Published: May 2024

Objective:
This randomized, double-blind, phase 3 study assessed the efficacy and safety of sacubitril/allisartan, an angiotensin receptor neprilysin inhibitor, compared with olmesartan in Chinese patients with mild to moderate hypertension.

Design and method:
Eligible patients aged 18-75 years (n=1197) with mild to moderate hypertension were randomized to receive sacubitril/allisartan 240 mg (n=399), sacubitril/allisartan 480 mg (n=399), or olmesartan 20 mg (n=399) once daily for 12 weeks. Patients who completed the 12-week treatment then received another 12-week extended treatment (n=1084) and 28-week prolonged treatment (n=189). The primary end point was a reduction in clinic mean sitting systolic blood pressure (msSBP) from baseline with various doses of sacubitril/allisartan versus olmesartan at 12 weeks. Secondary efficacy variables included clinic and 24-h ambulatory blood pressure for the comparison between sacubitril/allisartan and olmesartan at week 12, 24, and 52.

Results:
Sacubitril/allisartan 240 mg/day provided a greater reduction in msSBP than olmesartan at 12 weeks (between-group difference: -1.9 mmHg [95% confidence interval -4.2 to 0.4 mmHg], P=0.0007, for non-inferiority). Sacubitril/allisartan 480 mg/day provided a significantly greater reduction in msSBP than olmesartan at 12 weeks (between-treatment difference: -5.0 mmHg [95% confidence interval -7.3 to -2.8 mmHg], P<0.001, for superiority). Greater reductions in 24-h, daytime and nighttime systolic and diastolic blood pressure were also observed with both doses of sacubitril/allisartan compared with olmesartan (P<=0.001 for 480 mg/day). The blood pressure reductions tended to be dose-dependent for sacubitril/allisartan. Sacubitril/allisartan was well tolerated, and no cases of angioedema or death were reported.

Conclusions:
Sacubitril/allisartan is effective for the treatment of hypertension and well tolerated in Chinese patients.
LONG-TERM SYSTOLIC BLOOD PRESSURE VARIABILITY AS AN INDEPENDENT RISK FACTOR FOR CARDIOVASCULAR EVENTS IN KIDNEY TRANSPLANT RECIPIENTS
Authors: Picciotto Daniela , Bussalino Elisabetta , Macciò Lucia , Parodi Angelica , Gandolfo Maria Teresa , Viazzi Francesca 
Published: May 2024

Objective:
Cardiovascular (CV) events represent the main cause of death in patients undergoing renal transplantation. Several studies have described the role of blood pressure variability (BPV) in predicting all-cause mortality and fatal and non-fatal CV events in the general population and in diabetic patients. Systolic blood pressure variability (SBPV) has recently been proposed as a predictor of clinical outcomes in patients with chronic kidney disease.
However, evidence is still scarce about the prognostic role of BPV in the setting of renal transplantation.
The aim of our study was to evaluate the role of long-term SBPV in the development of fatal and non-fatal CV events (myocardial infarction, unstable angina or revascularization, stroke and hospitalization for heart failure) in subjects undergoing kidney transplantation.

Design and method:
We performed a single-center retrospective observational analysis in a cohort of 272 kidney transplant patients (mean age 64±13 years, 66% men), with a transplant duration beyond 12 months and with at least 6 blood pressure measurements at defined intervals (3 months ± 15 days) over an assessment period of 18 months.
BPV was expressed as standard deviation of ambulatory systolic blood pressure (SBP) and patients were accordingly classified in tertiles (low <9.3 mmHg, medium 9.3-13 mmHg, high >13 mmHg).
The role of SBPV was analyzed by Kaplan-Meier (logrank) and its independent effect by Cox Regression.

Results:
Over a mean follow-up of 58.7±17.2 months, 27 subjects (9.9%) developed CV events. For each increase of 2.7 mmHg in SBP standard deviation, the risk for fatal or non-fatal CV events increased almost 3-folds (P=0.02) and patients in the highest tertile of SBP standard deviation showed a 4-fold increased risk (P= 0.01) (Figure 1). This relationship was maintained even after incremental adjustment for time-averaged pulse pressure, age, diabetes, prior CV event, and dialysis vintage (HR 3.2, 95% CI 1.1–10.0, p 0.04) (Table 1).

Conclusions:
Long-term BPV represents an independent risk factor for CV events in kidney transplant patients. It is therefore essential to seek for stable long-term blood pressure levels in this population in order to minimize the residual CV risk.
THE EFFECT OF TREATMENT ON THE INFLAMMATION PROFILE AMONG PATIENTS WITH PRIMARY ALDOSTERONISM
Authors: Kantauskaite Marta , Duvnjak Blanka , Schmidt Claudia , Königshausen Eva , Zierhut Ulf , Rump Lars Christian , Stegbauer Johannes 
Published: May 2024

Objective:
Due to direct and indirect effects of aldosterone various pathways of inflammation cascade are activated leading to further end organ damage and higher cardiovascular risk among patients with primary aldosteronism (PA). To what extent the pro-inflammatory effects occur and, more importantly, if they are affected by the PA treatment remain unclear. Therefore, we aimed to analyze the inflammation profile among patients with PA before and after the treatment.

Design and method:
46 patients with PA (43% with adrenal adenoma and 57% with bilateral hyperplasia) were included into this study. Patient serum samples were collected at the study entry and 6 months after the treatment of PA was initiated. Demographic, clinical and laboratory data were collected retrospectively. Inflammatory cytokines and proteins were measured in patient’s serum using proximity extension assay (O-link Inflammation panel, Olink Proteomics, Uppsala, Sweden).

Results:
There were 52% woman and 48% men with a mean age of 50.2±12 years. The median aldosterone-renin-quotient (ARQ) was 96 and the blood pressure values were ranging between 142±17/89±12 mmHg. 6 months following the treatment a significant reduction in blood pressure and ARQ was achieved. Analysis of association between clinical factors and biomarker expression has shown that patients with adrenal adenoma have significantly higher levels of FGF21, whereas female gender was associated with lower expression of pro-inflammatory cytokines such as IL-18, TNFRSF9, CXCL9 and higher expression of protective cytokines such as TWEAK and MCP-4, especially among females with bilateral hyperplasia. According to proteomic analysis at study entry, we have identified 4 patient clusters. Interestingly, young females with adrenal adenoma have composed a separate cluster with significantly higher levels of IL-6, IFN-gamma, MCP-1, MMP1 and FGF21 and robust reduction of these parameters following the treatment. In general, volcano plot analysis of whole study cohort has demonstrated the significant reduction in expression of pro-inflammatory cytokines (EN-RAGE, CCL23, OPG, IL-10, FGF21 etc).

Conclusions:
The treatment of primary aldosteronism leads to reduced expression of pro-inflammatory proteins. The extent of inflammatory activation as well as response to treatment is highly associated with gender and the cause of aldosterone excess.
DEEP LEARNING MODELS FOR PREDICTING THE RISK OF CARDIOVASCULAR INCIDENTS BASED ON THE WISCONSIN LONGITUDINAL STUDY
Authors: Kvan Valerii , Artomov Mykyta 
Published: May 2024

Objective:
Existing models use only a limited number of well-known factors such as age, sex, cholesterol level, glucose level, and heart rate, while there is no general pipeline, which could give better overall prediction power, for an automatic pooling of the most correlated with heart disease predictors from the large-scale datasets. They often require preprocessing, and dimensionality reduction and has many missing data.

Design and method:
To address such challenges, we implemented data processing pipeline and several predictive models based on the Wisconsin Longitudinal Study dataset, which has both epidemiological and genetic data. We used univariate Cox Proportional Hazard models to estimate the effect of each variable, Hyperimpute to impute missing data, DeepSurv neural network and Autoprognosis 2.0 to develop final models.
Fig. 1 The research pipeline, where MI – Myocardial Infarction, HA – Heart Attack.

Results:
The pipeline showed high predictive power (approx. 80% under the ROC curves) to predict risks of heart incidents such as heart attack, myocardial infarction, and stroke within a 5–10-year time window. Furthermore, we estimated the effect of various polygenic risk scores like subjective well-being, neuroticism, and depression on heart incidents.

Conclusions:
We implemented an effective pipeline of accurate model development to predict risks of heart incidents, which, as a result, can be used to build different models to estimate other risks correlated with heart incidents and could be used on other biobanks’ datasets. Therefore, this opens more ways to explore the causalities of heart diseases better and improve treatments of such conditions.
HOME BLOOD PRESSURE TELEMONITORING IN THE NETHERLANDS: A PILOT STUDY IN GENERAL PRACTICES
Authors: Steenkiste Job Van , Verberk-jonkers Iris , Versmissen Jorie , Dohmen Daan , Jainandunsing Sjaam 
Published: May 2024

Objective:
Home Blood Pressure Telemonitoring (HBPT) has been proposed to improve blood pressure (BP) control, and efficient care delivery in patients with hypertension. Its adoption in GP practices however remains low. In this pilot study we evaluated barriers and facilitators for successful implementation, patient satisfaction, clinical effectiveness, and efficiency for a HBPT project in Dutch GP practices by means of the Quadruple Aim Model.

Design and method:
GP practices included patients with hypertension that were part of their regular cardiovascular disease program. The hospital would initially support the HBPT program followed by a period in which the GP practices were primarily responsible for the telemonitoring (figure 1, procedures A and B). We conducted semi-structured interviews at 3- and 6-months (figure 2) to identify barriers and facilitators for successful implementation. Patient satisfaction was measured with Telehealth Usability (TUQ) - and MHealth App Usability (MAUQ) Questionnaires. A Systolic Blood Pressure Intervention Trial (SPRINT) -protocol BP measurement was performed after the pilot project to assess clinical effectiveness. Efficiency data were collected on the number of registered consultations during the 6-month project.

Results:
Three GP practices included 19 patients. Barriers for implementation (table 1) were a lack of a reimbursement structure, lack of information technology system integration and increased experienced workload when using HBPT. Facilitators (table 1) included the positive effects on BP control, increased sense of safety for patient and care provider, and increased disease-insight. Median satisfaction scores for TUQ and MAUQ questionnaires (scale 1-7) were 6 (IQR 5-6) and 6 (IQR 5-7). At baseline, 16% of the patients had a BP <140/90 mmHg. Based on the performed SPRINT measurements, 68% had a well-controlled BP (<140/90 mmHg) after 6 months. Average BP improved from 151/89 mmHg to 132/81 mmHg (p=0.0004). On average, one monthly contact moment related to hypertension between patient and GP practice was registered.

Conclusions:
We found positive results following the introduction of HBPT in GP practices on clinical outcomes and patients’ satisfaction, however for large-scale implementation improvements with regards to organizational efficiency and a clear reimbursement structure are needed.
CAN A DAYTIME PROFILE OF HOME BLOOD PRESSURE MONITORING PREVENT HYPOTENSION DUE TO OVERDOSING OR INTERACTION WITH OTHER DRUGS?
Authors: Muzik Jan , Peleska Jan , Camek Rene , Fiala Dominik , Doksansky Marek , Hana Karel , Vranka Jakub , Dolezil David , Jozifova Marie 
Published: May 2024

Objective:
Hypotension occurs during treatment for hypertension relatively rarely, but the new BP thresholds and targets support its more frequent occurrence. It concerns mainly the time of peak effect of antihypertensive and all the medication reducing BP, respectively.
Office BP measurements are falsely higher. HBPM is more objective, especially when HBP telemonitoring (HBPTM) and checking of the rest before BPM is used.

Design and method:
Personal BP monitors wirelessly connected to mobile phones for data transfer were used. The required 5 minutes of physical inactivity before BPM were checked in by smart wristbands. 112 predominantly treated patients with essential hypertension aged 24-85 years, 61% males, were referred as well controlled.
A daytime profile of HBPM (triplets of BPM each hour during one daytime) was a part of the study comparing HBPTM and ABPM. Medication was taken immediately after the first morning BPM.
Based on several cases of hypotension in patients treated with perindopril/indapamide/amlodipine and perindopril/indapamide reported to a hypertension consultation website, the time of the peak effect 5 hours was chosen.

Results:
The average systolic BP (SBP) was 132.2 mmHg before taking medication and 126.5 mmHg after 5 hours (n=95).
Decrease of SBP in mmHg (difference between the starting level and that after 5 hours) was preliminary analyzed by paired t-test: 0.92+12.78, p=0.799, (untreated, n=13); 2.18+10.8, p=0.248 (1 drug, n=34), 8.04+12.28, p= 0.002, (2 drugs, n=28), 12.15+18.87, p=0.031 (3-5 drugs, n=13). One patient with SBP value even below 100 mmHg, did not report spontaneously any symptoms of hypotension.

Conclusions:
Decrease of SBP was statistically significant after 5 hours from drug taking in groups treated with 2 and more antihypertensive drugs. Though we did not find any problems associated with hypotension, it is necessary to be careful especially in patients with sedentary occupation whose working activity can be at least suppressed. Under the unfavorable constellation of other BP decreasing factors hypotension can cause a fall due to vertigo or even car accident. Therefore, HBPM with a daytime profile seems to be a suitable tool to identify hypotension.
IS IT NECESSARY TO MEASURE 2 TIMES OR 3 TIMES IN A ROW TO CATEGORIZE A PATIENT'S BLOOD PRESSURE LEVEL?
Authors: Girerd Xavier , De Buyer Paul , Hanon Olivier , Wimart Marie , Pathak Atul 
Published: May 2024

Objective:
The ESH 2023 guidelines stipulate that to measure a patient's blood pressure, 3 measurements should be taken at 1-minute intervals, and the last two should be kept for averaging to assess whether 2 consecutive 1-minute blood pressure measurements classify blood pressure levels in the same way as 3 measurements.

Design and method:
The French Fundation and Hypertension Comitee health data warehouse contains 4172 medical records of subjects aged 35 years who volunteered to participate in nationwide health surveys conducted in France between 2015 and 2022 (French League Against Hypertension Survey). Blood pressure was measured with an automatic blood pressure monitor in the morning in a seated position with 1 minute between each measurement. Each subject was categorized according to the systolic and diastolic blood pressure of measurement 2 and the mean of measurement 2 and 3. The subject was classified as H if SBP > 140 or DBP >90. Subject was N if SBP <= 130 or DBP <= 90. Concordance in classifications between measure 2 and the mean of measure 2 and 3 was performed for each subject.

Results:
Agreement between measurement 2 and the mean of measurements 2 and 3 was 98% for SBP and 95% for DBP for category H. Agreement for category N was 92.3% for SBP and 94% for DBP.
These results are explained by the increased variability observed as early as measurement 2.

Conclusions:
Measuring blood pressure 2 times in a row with an automatic blood pressure monitor is sufficient to categorize a patient's blood pressure and to identify blood pressure variability.
AMBULATORY AND HOME BLOOD PRESSURE MONITORING FOR CARDIOVASCULAR DISEASE RISK EVALUATION: A SYSTEMATIC REVIEW AND META-ANALYSIS OF PROSPECTIVE COHORT STUDIES
Authors: Panagiotakos Demosthenes , Antza Christina , Kotsis Vasilios 
Published: May 2024

Objective:
The aim of this work was to systematically review the level of evidence based on prospective cohort studies investigating the role of 24-hour ABPM and HBPM on cardiovascular disease (CVD) risk prediction.

Design and method:
Eight studies were included in the meta-analysis. The Der Simonian and Laird's random-effects model with standard error adjustment using the Knapp-Hartung method was used.

Results:
Systolic BP from ABPM and HBPM were significantly, positively associated with CVD risk (combined HR per 1-SD systolic BP, 95%CI; 1.32, 1.19-1.45, I2 = 35.8%, and 1.30, 95%CI;1.11-1.49, I2 = 79.1%, respectively), after adjusting for office BP levels and other potential confounders. Diastolic BP from both ABPM and HBPM were positively associated with CVD risk (combined HR per 1-SD diastolic BP, 95%CI; 1.15, 1.01-1.29, I2 = 73.1% and 1.21, 1.05-1.37, I2 = 84.5%, respectively).

Conclusions:
BP either from ABPM or HBPM could predict CVD risk. As so, at least one of out-of-office BP measurements has to be taken into account during the evaluation of the hypertensive population.
VITAMIN D AND INDICATORS OF AMBULATORY BLOOD PRESSURE MONITORING IN WOMEN WITH ARTERIAL HYPERTENSION IN THE EARLY POSTMENOPAUSAL PERIOD
Authors: Kezhun Liudmila 
Published: May 2024

Objective:
To assess plasma 25(OH)D levels and indicators of ambulatory blood pressure monitoring (ABPM) in women with arterial hypertension (AH) stage II risk 3 in the early postmenopausal period.

Design and method:
We investigated 52 women with AH stage II risk 3 aged 52 (50; 54) years of age who are in the early postmenopausal period - group I. Serum level of 25(OH)D was determined by the immunoenzymatic assay. The level of 25(OH)D in the blood plasma was determined by enzyme immunoassay. In group I we identified subgroup IB (n=21) with vitamin D deficiency/insufficiency - level of 25(OH)D<30ng/ml and subgroup IA (n=31) without vitamin D deficiency. ABPM was carried out with a Watch BP 03. Statistical analysis was performed by means of «STATISTICA 10.0».

Results:
The level of 25(OH)D was lower (p<0,05) in subgroup IB (18,2±9,5 ng/ml) than in the comparable to subgroup IA (27,4±10,5 ng/ml). In subgroup IB, compared with subgroup IA, the values of mean night diastolic (DBP) were higher (p<0,05) (73,0 (69,0;79,0) mm Hg versus 68,8±7,4 mm Hg), time index (TI) DBP at night (14,3 (12,5; 33,4)%, versus 12.5 (0,0;12,5)%,), speed of morning rise DBP (16,5(11,0;22,0) mm Hg/hour versus 10,0(8,5;17,3) mm Hg/hour), systolic variability (SBP) during the day (36,0(29,0;43,0) mm Hg versus 25,0(22,0; 38,0) mmHg). TI DBP at night exceeded the threshold value in 42,9% of women in subgroup IB versus 17,2% (p< 0,05) of subjects in subgroup IA. Morning rise speed DBP in subgroup IB did not correspond to the norm in 81% of cases compared to subgroup IA – 37,9% (p = 0,004). Inverse moderate correlations were established in subgroup IB between the level of 25(OH)D in the blood plasma and a number of ABPM indicators: average night SBP (R =-0,37, p=0,004), TI SBP night (R=-0,42, p=0,04), average night DBP (R=-0,43, p=0,03), TI DBP night (R=-0,39, p=0,05).

Conclusions:
In women with AH stage II risk 3 in the early postmenopausal period, with a deficiency/insufficiency of the level of 25(OH)D in the blood plasma, excess of a number of ABPM indicators was more common than with its optimal level.