bluuebunny/crossref_metadata_2025 huggingface dataset:
SIGNIFICANCE OF THE NAV 1.8. VOLTAGE-GATED, TETRODOTOXIN-RESISTANT SODIUM CHANNEL FOR THE RENAL SENSORY INNERVATION IN MICE AND RATS
Authors: Rodionova Kristina , Ditting Tilmann , Holzmann Kathrin , Bach Felix , Cordasic Nada , Hilgers Karl -Friederich , Linz Peter , Schiffer Mario , Amann Kerstin , Veelken Roland
Published: May 2024

Objective:

Our previous work repeatedly showed that the sensory innervation of the kidney in rats has a peculiarity containing predominantly (more than 50%) highly active tonic neurons to electrical stimulation. In a previous publication demonstrated an increased mRNA expression of the TTX-resistant sodium channel Nav1.8 in renal sensory neurons. Hence, we tested the hypothesis that tonic firing pattern is related to the specific expression of Nav1.8 on the cell surface of neurons with renal sensoric axons in the dorsal root ganglia (DRG Th12-L2).

Design and method:

Harvested dorsal root ganglion neurons (DRG Th11-L2) from Sprague Dawley (SD) with renal afferents were investigated in neuronal cell culture using current clamp mode to assess action potential generation during current injection and to characterize neurons as tonic highly active and phasic less active neurons using a Nav1.8 blocker (A-803467) before and after stimulation. Further, renal DRG neurons from a Nav1.8 knock out mouse (C57BL6J-Scn10atm1Jwo) were investigated in a current clamp mode. C57BL6 mice were used as controls.

Results:

At a concentration of 0.3μM the maximum AP firing frequency of tonic neurons was blocked from 13+/- 1.1 APs/600ms to 7.6+/-1.4 APs/600ms under superfusion with a Nav1.8 blocker. No blocker effects were seen at a concentration of 0.1 μM and due to superfusion with the solvent methanol alone.

The firing pattern of renal neurons in the C57BL6 mouse was similar to that in the SD rat with a dominance of the tonic highly active neurons. In a Nav1.8 knock out mouse (C57BL6J-Scn10atm1Jwo) in the population of neurons with dendrites from the kidney only a single cell out of 70 showed tonic firing behavior (control vs Nav1.8 KO mouse, z-test, p<0.05).

Conclusions:

Under physiological conditions, renal sensory neurons exhibit predominantly a firing pattern associated with higher excitability. Our findings in this study support the significance of the TTX-resistant sodium channel Nav1.8 for the specific tonic firing pattern of neurons with renal projections. That might be of importance for pharmacological interventions to influence renal nerve activity, which likely plays a crucial role in the regulation of blood pressure and control of cardiovascular function.
PDGFRALPHA ACTIVATION LEADS TO BLOOD PRESSURE INCREASE AND SMALL ARTERIES MEDIAL HYPERTROPHY IN MALE MICE
Authors: Atassi Fabrice , Frisdal Angèle , Roy-vessieres Emilie , Proux Coralyne , Solinc Julien , Trenquier Eva , Suffee Nadine , Dilanian Gille , Balse Elise , Henrion Daniel , Nadaud Sophie
Published: May 2024

Objective:

Arterial remodeling is associated with vascular function alteration and with hypertension development. This remodeling is due to cells reorganization within the vascular wall and in some cases to smooth muscle cells proliferation. PDGF (Platelet-derived Growth Factor) is a major regulator of arterial remodeling and some studies suggest that PDGFRα, one of its receptors, could be activated during hypertension.

Our aim is to determine the role of PDGFRα and of PDGFRα-expressing progenitor cells in vascular remodeling.

Design and method:

We used a tamoxifen-inducible genetic mouse model of PDGFRα constitutive activation. Blood pressure was measured by the tail-cuff method and by carotid catheter. Small mesenteric arteries reactivity was studied using ex vivo arteriography. Vascular remodeling was analyzed by immunofluorescence.

Results:

PDGFRα constitutive activation for 6 weeks led to a 25% increase in blood pressure (p<0.05) and a 25% decrease in cardiac output in male mice (p<0.05), without changes in other cardiac parameters. In these mice, small mesenteric arteries showed no alteration in contractility or endothelium-dependent and independent relaxation but an increase of media thickness, whereas larger vessels did not show structure or function alteration. Echo-doppler analyses showed an increased resistivity index of the renal artery (+13% p<0.05) but not of the aorta suggesting an increased resistance of small renal arteries. The remodeling of small mesenteric arteries was characterized by an early proliferation of perivascular cells at 4 days but not of medial cells followed by the production of new smooth muscle cells after 2 weeks.

Female mice did not show blood pressure increase following induction of PDGFRα constitutive activation for 6 weeks. Small mesenteric arteries showed a reduced contractility with alteration of endothelium-dependent and independent relaxation.

Conclusions:

These results suggest that PDGFRα activation could participate in arterial hypertension development by leading to increased media thickness and stiffness in small arteries in males. Our results suggest that in females the increased resistance of small vessels is compensated by a decreased contractility.
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.
ASSOCIATION OF OFFICE AND AMBULATORY BLOOD PRESSURE MONITORING WITH COGNITIVE FUNCTION AND DEMENTIA PREVALENCE
Authors: Melgarejo Jesus , Charisis Sokratis , Patil Dhrumil , Vatcheva Kristina , Mejia-arango Silvia , Mena Luis , Garcia Antonio , Alliey-rodriguez Ney , Satizabal Claudia , Chavez Carlos , Gaona Ciro , Silvia Egle , Calmon Gustavo , Mavarez Rosa , Lee Joseph , Terwilliger Joseph , Blangero John , Seshadri Sudha , Maestre Gladys
Published: May 2024

Objective:

Blood pressure (BP) is an important risk factor for cognitive decline and dementia. However, it is unclear which measures of BP obtained from office and ambulatory BP monitoring assessments are better related with cognition and dementia. Therefore, we evaluated the association of office and ambulatory BP measures with cognitive function and dementia at baseline.

Design and method:

We included baseline information of 1435 participants aged 50y or older from a population-based study whom underwent 24-h ambulatory BP monitoring, cognitive function, and neurological assessments. Office and ambulatory BP monitoring measures included systolic BP level and short-term variability quantified using the average real variability (ARV) index. Cognitive function examination included the minimental state examination (MMSE) and selective reminder tests ([SRL], total retrieval, long-term retrieval, and delayed recall). Dementia was a clinical dementia rating scale equal or higher than 1. We performed adjusted logistic and linear regression models to evaluate the association of office and ambulatory BP monitoring measures with cognitive function and dementia.

Results:

The mean age was 63.8±10.3 and 69.1% (n=963) were women. The prevalence of dementia was 3.21 (n=46). In adjusted logistic regression models, only ARV of the 24-h (odds ratios [OR] per +1-standard deviation [SD] increase in ARV, 1.42; 95% confidence interval [CI], 1.07-1.88) and nighttime (OR, 1.37; 95% CI, 1.05-1.78) systolic BP were associated with dementia at baseline. In adjusted linear regression models, only ARV was associated with lower scores in the MMSE and the SRL tests (adjusted-mean scores per +1SD increase in ARV ranged from -0.09 to -0.06 points; P values below 0.027). These associations remained after models were additionally adjusted by the BP level (P values below 0.033)

Conclusions:

Among office and ambulatory BP monitoring measures, higher short-term variability in the 24-h and nighttime systolic BP was associated with lower cognitive function and dementia independent of the BP level. This is the first epidemiological study showing an association between short-term BP variability and dementia. Future longitudinal studies need to address whether short-term BP variability could be a potential marker for cognitive decline and might help in assessing the risk of dementia.
MICRORNA-133A AND MICRORNA-145 AS PROMISING BIOMARKERS OF HYPERTENSION MEDIATED ORGAN DAMAGE IN ADOLESCENTS WITH PRIMARY HYPERTENSION – A PRELIMINARY STUDY
Authors: Szyszka Michal , Skrzypczyk Piotr
Published: May 2024

Objective:

Studies based on data from adults show an important role of microRNAs in the development of hypertension and their impact on hypertension-mediated organ damage (HMOD). The aim was to examine the expression of miR-21, miR-27a, miR-27b, miR-133a, and miR-145 in hypertensive pediatric patients and reveal their correlation with blood pressure parameters, properties of the arteries, and myocardial hypertrophy.

Design and method:

In 22 teenagers (18 boys, 4 girls, 15.1±1.9 years) with primary hypertension, we assessed mentioned above microRNA expression levels before and after one hour of aerobic exercise session, office and 24-hour ambulatory blood pressure and HMOD indicators, such as left ventricle mass index (LVMI), urinary albumin-creatine ratio, pulse wave velocity (PWV), and carotid intima-media thickness (cIMT). Relative microRNA expression was calculated with the 2^-δδCt method with miR-16 as endogenous control and baseline (before exercise session) microRNA expression taken as a control value.

Results:

In the studied children, we observed significant decrease in both office and 24 hour ambulatory diastolic blood pressure after one-hour exercise (82.2±8.5 vs. 78.6±8.8 [mm Hg], p=0.01 and 75.0±8.3 vs. 73.0±7.4 [mm Hg], p=0.02). In the whole group there were no significant changes in expression of the studied microRNA molecules after an exercise session. The post-exercise increase in miR-133a expression level showed a positive correlation with LVMI [g/m2.7] (R=0.491, p=0.02). Conversely, post-exercise increase in miR-145 expression correlated negatively with post-exercise both systolic and diastolic office and 24-hour blood pressure, 24-hour PWV, and cIMT (R=-0.428, p=0.047 and R=-0.430; p=0.046, and R=-0.455, p=0.033, respectively). None of the studied microRNA molecules correlated with age.

Conclusions:

1.MicroRNA-133a might be a marker of left ventricular hypertrophy in children with primary hypertension.

2. Exercise-induced change in microRNA-145 expression may lower post-exercise blood pressure and have a protective effect against arterial damage in children with primary hypertension.

3. Both miR-133a and miR-145 may be involved in epigenetic modifications in pediatric patients with primary hypertension influencing HMOD.
CHILD BLOOD PRESSURE AND RENAL FUNCTION DIFFERENCES BY SUBTYPES OF MATERNAL HYPERTENSIVE DISORDERS OF PREGNANCY
Authors: Ishikuro Mami , Obara Taku , Noda Aoi , Orui Masatsugu , Shinoda Genki , Murakami Keiko , Kikuya Masahiro , Metoki Hirohito , Kuriyama Shinichi
Published: May 2024

Objective:

The objective of this study is to investigate the difference child blood pressure (BP) and renal function by subtypes of maternal hypertensive disorders of pregnancy (HDP).

Design and method:

The Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study is a prospective birth cohort study including pregnant women, children and their families. Using available data of children at 8 years old from December 2022 to March 2023, we analyzed the association between maternal HDP subtypes by extracted from medical record and systolic and diastolic BPs and estimated glomerular filtration rate (eGFR) collected at research facilities. Analysis of covariance adjusted for their sex, body mass index, small for gestational age were performed. Maternal grandparental hypertension and paternal hypertension for child BP, and maternal grandparental chronic nephritis and parental chronic nephritis were additionally adjusted.

Results:

A total of 684 children (357 male and 327 female) at 8 years old was included in this study. Among them, 56 children had mothers with HDP (24 gestational hypertension, 11 preeclampsia, 9 superimposed preeclampsia, 12 chronic hypertension). The mean (standard deviation) systolic/diastolic BPs and eGFR were 106.90 (10.51)/64.68 (8.77) mmHg and 110.91 (16.23) mL/min/1.73m2, respectively. Estimated systolic/diastolic BPs (standard error) of children with normotensive mothers, those with gestational hypertension mothers, those with preeclampsia mothers, those with superimposed preeclampsia mothers, and those with chronic hypertension mothers were: 106.44 (0.76)/64.58 (0.64) mmHg, 108.38 (2.11)/64.80 (1.78) mmHg, 107.59 (3.10)/64.70 (2.61) mmHg, 108.38 (3.38)/63.64 (2.85) mmHg, 112.19 (2.98)/64.58 (2.51) mmHg, respectively. Upon classification of HDP subtypes, estimated eGFR were as follows: 110.11 (1.23) mL/min/1.73m2, 111.61 (3.40) mL/min/1.73m2, 118.20 (4.99) mL/min/1.73m2, 105.13 (5.43) mL/min/1.73m2, and 119.42 (4.82) mL/min/1.73m2, respectively. The p-values were above 0.05 for the systolic and diastolic BPs and eGFR among HDP subtypes.

Conclusions:

The follow-up measurement is ongoing until 2026; therefore, further study with updated dataset is necessary and will be provided.
DIAGNOSTIC VALUE OF SERUM IRISIN LEVELS IN HYPERTENSIVE PATIENTS WITH SEVERE OBSTRUCTIVE SLEEP APNEA SYNDROME
Authors: Yili Jina , Yao Xiaoguang , Li Nanfang
Published: May 2024

Objective:

To observe the diagnostic value of serum irisin level in patients with hypertension for severe obstructive sleep apnea syndrome.

Design and method:

A total of 156 hypertensive patients were selected from the Hypertension Center of the People 's Hospital of Xinjiang Uygur Autonomous Region from September 2019 to January 2020. Baseline data, PSG and ABPM were collected and serum irisin levels were measured. According to AHI, the patients were divided into severe OSAS group (n=79 cases) and non-severe OSAS group (n=77 cases).

Results:

Male patients in severe OSAS group were significantly more than those in non-severe OSAS group, and abdominal circumference and neck circumference in severe OSAS group were greater than those in non-severe OSAS group. Serum irisin concentration in severe OSAS patients was lower than that in non-severe OSAS group, and the difference was statistically significant(14.94 ng/ml vs 42.34 ng/ml, p < 0.001). Serum irisin concentration was negatively correlated with AHI (r=-0.359, p < 0.01). The critical value of serum irisin concentration was 38.07 mg/ml by ROC curve, the AUC is 0.761, the sensitivity was 86.07%, the specificity was 61.07%, the positive predictive value was 69.38%, and the negative predictive value was 81.03%.

Conclusions:

In hypertensive population, the serum irisin concentration of OSA patients was negatively correlated with the severity of OSAS. Serum irisin level can be used as a diagnostic index for severe OSAS patients.
EVALUATION OF EFFICACY OF ANTIHYPERTENSIVE THERAPY FOR PSYCHOEMOTIONAL STATUS IN PATIENTS WITH ARTERIAL HYPERTENSION
Authors: Makhkamova Nargiza , Xasanova Kamola
Published: May 2024

Objective:

To evaluate the effectiveness of antihypertensive therapy on the level of personal, reactive anxiety and depression in patients with hypertension (AH).

Design and method:

The study included 75 patients with AH aged 39-69 years (average age 54 ± 3 years). During the study, the causes of symptomatic AH, baseline antihypertensive therapy was optimized. AH was diagnosed by daily monitoring of blood pressure (DMBP) using the TONOPORT device (Germany) according to the standard method. At baseline and in the course of 3-month antihypertensive therapy (AHT) with valsartan (160 mg per day) and indapamide 2.5 mg per day, the level of personal and reactive anxiety on the State-Trait Anxiety Inventory, STAI and depression on the Zung Self-Rating Depression Scale were determined.

Results:

At baseline, the indicators of personal and reactive anxiety in patients with AH were noticeably higher (27 ± 1 point and 26 ± 2 points). At the same time, the indicators of reactive and especially personal anxiety closely correlated with the average daily indicators of systolic BP (r - 0.47 at p < 0.05 and 0.54 at p < 0.01). Insufficient decrease in BP at night was more clearly associated with the severity of depression and anxiety detected on the Zung Self-Rating Depression Scale (r -0.39, at p < 0.05). The increase in personal anxiety was clearly associated with an increase in the average daily variability of systolic BP.

As a result of the combined AHT, a significant decrease in the scores on the used scales was observed. The measures of personal and reactive anxiety were 22 ± 2 and 21 ± 1 point, respectively, (p < 0.01 from baseline). The increase in personal anxiety was clearly associated with an increase in the average daily variability of systolic BP (r -0.46, p < 0.05).

Conclusions:

The degree of arterial hypertension and daily variability is associated with an increase in the level of anxiety and severity of depressive disorders in patients with AH. Adequate AHT contributes to the improvement of psychoemotional status indicators in patients with AH.
A COMPARISON BETWEEN THE TWO METHODS OF MAGNESIUM SULFATE ADMINISTRATION FOR DURATION OF 12 VERSUS 24 H AFTER DELIVERY IN PATIENTS WITH SEVERE PREECLAMPSIA
Authors: Kashanian Maryam , Sahraian Ghazal
Published: May 2024

Objective:

Preeclampsia is one of the very serious and important complications of pregnancy which may culminate in serious maternal mortality and morbidity. For preventing eclampsia and convulsions, magnesium sulfate (Mg So4) is the medication of choice. As a standard method, it will be continued up to 24 hours after delivery of the baby. Shortening the duration of its administration can reduce the duration of hospital stay, risk of magnesium sulfate (Mg sulfate) toxicity and adverse effects, cost, duration of treatment, and patient satisfaction.

The purpose of the present study was to compare the 2 methods of magnesium sulfate administration for a duration of 12 VS 24 hours after delivery in patients with severe preeclampsia.

Design and method:

The study was performed as a randomized clinical trial on 182 cases of severe preeclampsia. They were randomly assigned into the 2 groups. In one group, Mg sulfate was prescribed for 12 hours after delivery and in the other group, it was prescribed for 24 hours after delivery. The dosage of Mg sulfate was similar in both groups and only the duration of administration was different.

Both groups were compared for the occurrence of convulsions and other adverse effects.

Results:

The women of the 2 groups did not have significant differences according to age, BMI, Parity, gravidity, or gestational age at the time of delivery. Also, systolic blood pressure, diastolic blood pressure, antihypertensive use, previous diabetes and renal disorders, gestational diabetes, and proteinuria were similar in both groups before treatment. One woman had a convulsion in the 12 hours group and Mg SO4 was continued for 24 hours in this case. Blood pressure, urine volume, and laboratory indexes did not show significant differences between the 2 groups before and after treatment. Also, adverse effects were similar in both groups. Pain at the injection site was less in the 12-hour group (P=0.048).

Conclusions:

Administration of Mg sulfate for 12 hours after delivery should be considered somehow as effective as 24 24-hour prescription for preventing convulsion after delivery.
PREVALENCE AND OUTCOME OF PRIMARY ALDOSTERONISM IN PBMAH: A SINGLE CENTER STUDY AND A SYSTEMATIC REVIEW OF THE LITERATURE
Authors: Panarelli Annalisa , Nowak Elisabeth , Adam Pia , Schweizer Junia , Stuefchen Isabel , Zopp Stephanie , Reincke Martin
Published: May 2024

Objective:

Primary bilateral macronodular adrenocortical hyperplasia (PBMAH), characterized by benign adrenocortical macronodules and variable levels of cortisol excess, can also lead to an excess of mineralocorticoids, although there is only anecdotal evidence.

To assess the prevalence and characteristics of primary aldosteronism (PA) in patients with PBMAH.

Design and method:

We conducted a systematic review according to the PRISMA guidelines. We reviewed single case reports and case series of patients with PBMAH and PA in Pubmed, Embase and Cochrane from database inception to December 2023. PBMAH was defined radiologically as at least 1 bilateral adrenal nodule of at least 10 mm. Findings were compared to patients with PBMAH without PA derived from LMU Hospital and literature.

Results:

1018 articles were screened, and 36 articles were assessed for eligibility. We identified 18 articles (8 single case reports and 10 case series), resulting in 68 cases with PBMAH with PA. Of those, 12 had cosecretion of cortisol. The prevalence of PA in PBMAH, in six studies (166 patients), ranged from 2-44%. The median age at diagnosis was 51.5 (47.5-56.2). The majority of patients with PBMAH and PA were male compared to patients with PBMAH without PA (59% vs 39%, p= 0.0295).

At baseline, the mean arterial pressure was 112 mmHg (113-133) and the median duration of hypertension was 108 months (48-135). The serum aldosterone concentration and plasma renin activity were 253 ng/l (159-436) and 0.23 ng/ml/h (0.16-0.44), respectively. Adrenal nodules were smaller in patients with PBMAH with PA compared to patients with PBMAH without PA (22 vs 30 mm, p=0.0498).

Treatment modality was reported in 30 cases: 28 patients underwent adrenalectomy (two bilateral, two subtotal, and 24 unilateral) and two received mineralocorticoid receptor antagonists (MRA). In comparison, fewer patients with PBMAH without PA underwent adrenalectomy (54/106, p=0.0005).

Conclusions:

PA in PBMAH appears to be more frequent than previously thought. Multicenter studies will help to clarify the association between these conditions and the most appropriate treatment modality.
PREVALENCE AND CLINICAL CHARACTERISTICS OF COMORBID HYPERTENSION AND CORONARY ARTERY DISEASE IN CHINA, 2008-2018
Authors: Xue Hao , Wang Chi , Xin Qian
Published: May 2024

Objective:

Data on the prevalence of patients with comorbid hypertension and coronary artery disease (HT-CAD) in Chinese population is sparse. The current study aims to investigate the prevalence of hypertension in patients with CAD, clinical characteristics of patients with HT-CAD, and their temporal change during 2008 to 2018 in Chinese population.

Design and method:

This cross-sectional study was conducted in Chinese PLA General Hospital, a tertiary hospital that gathering nationwide patients in Beijing, China. A total of 32,355 CAD patients with and without hypertension admitted from 5 August 2008 to 22 July 2018 were identified in the current study. Among these patients, 29.57% were local residents in Beijing and 70.43% were from other 30 provinces of China (Figure 1). The demographic characteristics, diagnosis records, relevant examinations, and treatment patterns were obtained from the hospital information system. We analyzed the prevalence, blood pressure control, clinical characteristics, and their temporal change of patients with HT-CAD.

Results:

The overall prevalence of HT-CAD in patients with CAD was 64.12% (n=20,747) and did not significantly change during 2008 to 2018 (Figure 2). Higher comorbidity rate was observed in elderly and women. Among patients with HT-CAD, the blood pressure was controlled at <140/90 mmHg in 52.39% and <130/80 mmHg in 27.03%. The control rate of <130/80 mmHg increased during 2008 to 2018 (P for trend =0.02), whereas the control rate of <140/90 mmHg did not change significantly (P for trend =0.84) (Figure 2). Compared with CAD patients without hypertension, patients with HT-CAD had higher prevalences of cardiovascular-related risk factors and comorbidities, including diabetes mellitus, anemia, hyperuricemia, stroke, chronic kidney disease, peripheral arterial disease, and atrial fibrillation (Figure 3). Most of these cardiovascular-related comorbidities showed an rising trend over the study period (Figure 4), indicating worse prognosis in patients with HT-CAD and higher financial burden for health care system.

Conclusions:

Hypertension is the most common comorbidity in Chinese patients with CAD. Patients with HT-CAD have an increasing health burden and should be paid with special attention on the intensive blood pressure control and targeted management for risk factors and comorbidities.