bluuebunny/crossref_metadata_2025_split huggingface dataset:
PREDICTION OF CARDIOVASCULAR EVENTS IN HYPERTENSIVE SUBJECTS WITH ARTIFICIAL INTELLIGENCE TOOLS
Authors: Rodilla Enrique , Iriarte Olast Arrizibita , Serrano Blanca Miranda , Ruilope Luis Miguel , Gil Germán Sedano , Arduán Alberto Ortiz , Costa Jose Antonio , Beristain Onintza Sayar 
Published: May 2024

Objective:
Cardiovascular diseases contribute substantially to morbi-mortality at the global level. To effectively address the increasing incidence of cardiovascular events, advanced preventive strategies are needed. Predictive modeling is a crucial tool to identify individuals at risk and facilitate proactive interventions to improve clinical outcomes.
This study develops and evaluates a model for predicting cardiovascular events (ischemic heart disease and stroke in previously event-free hypertensive subjects) by integrating clinical data, biomarkers and established risk factors. Most importantly, it predicts the likelihood of cardiovascular events after the initial patient visit.

Design and method:
The first step we have performed, enrich the dataset by creating variables using statistical measures, Principal Component Analysis (PCA) and Latent Class Analysis (LCA). Three different prediction algorithms are applied: XGBoost, Random Forest and Logistic Regression. The models were trained with 70% of the dataset and 30% for validation. Each algorithm maintains a balance between predictive accuracy and interpretability. The models predict cardiovascular events in patients with no history of cardiovascular disease after their baseline visit.

Results:
A total of 4,145 consecutive patients were referred to a hospital’s hypertension unit. The population’s mean age is 55.9±14, with 51% women. The average follow-up time is 3,028 days, yielding an incidence density of 1.93 (95% CI: 1.78-2.09) per 100 patient-years. The XGBoost model achieves 85% accuracy, 87% sensitivity, and 71% specificity. When reducing the model to the 30 most influential variables, there is a modest decrease in predictive accuracy (80%). Logistic Regression provides an interpretable model with an accuracy of 80%, sensitivity of 56%, and specificity of 84%. Meanwhile, Random Forest exhibits a high accuracy of 86%, with notably lower sensitivity at 13%.

Conclusions:
Our findings underscore the resilience and stability of the XGBoost model, effectively balancing predictive accuracy and interpretability. The inclusion of the Logistic Regression model, with its interpretative capacity, remains crucial, especially when transparency in model decisions is paramount. This study emphasizes the importance of tailoring predictive models to the specific requirements of applications. Future research could explore possible techniques for the interpretability of the XGBoost model.
PERSONAL BLOOD PRESSURE VARIABILITY IS NOT ASSOCIATED WITH SEASONAL BLOOD PRESSURE EFFECTS: A 4-YEAR PROSPECTIVE COHORT OF 1,151 PARTICIPANTS FROM ELDERLY CENTRES IN HONG KONG
Authors: Tsoi Kelvin Kf , Hao Ziyu , Chen Yize , Chan Howard H , Yiu Karen Kl 
Published: May 2024

Objective:
Personal blood pressure variability (BPV) is demonstrated to be an important risk factor for cardiovascular diseases, but blood pressure fluctuates over the years with seasonal effects. This study aimed to investigate the association between personal BPV and year-round seasonal blood pressure fluctuations among the elderly in Hong Kong.

Design and method:
Elderly participants aged above 55 years were recruited from 76 elderly centres and were prospectively followed up between September 2016 and January 2020. Personal interviews were conducted to assess personal health conditions. Nursing calls and social worker engagement were offered for those with suboptimal BP readings. The inclusion criteria were the participants who reported more than 80% of weekly BP records in at least 2 years of follow-up. Standard deviation (SD) was applied to quantify the personal variability levels of systolic and diastolic BPV. A machine learning classification method, K-means, was used to further classify participants into low, medium, and high levels of overall BPV. The seasonal fluctuations of blood pressure readings were extracted by a time series model. Temperature data were extracted from the Hong Kong Observatory and were correlated with the seasonal blood pressure variability across the participants with different levels of BPV.

Results:
A total of 500,914 blood pressure records were collected from 1,151 elderly participants with a mean age of 79 years. Machine learning classified 588 (51%), 462 (40%), and 101 (9%) participants with low, medium and high levels of BPV, respectively. Seasonal fluctuations were shown to be reversely correlated with the temperature data (r > 85% with all p-values < 0.001) (Figure 1) regardless of the personal BPV levels.

Conclusions:
Blood pressure variability is a personal risk factor that is irrelevant to seasonal blood pressure fluctuations. Early intervention to control for suboptimal blood pressure variability would provide additional benefits to patients with a higher risk of cardiovascular diseases.
PEAK NOCTURNAL HOME BLOOD PRESSURE AS AN EARLY AND STRONG NOVEL RISK FACTOR FOR STROKE: THE PRACTITIONER-BASED NATIONWIDE J-HOP NOCTURNAL BP STUDY
Authors: Kario Kazuomi , Okawara Yukie , Kanegae Hiroshi , Tomitani Naoko , Hoshide Satoshi 
Published: May 2024

Objective:
Recent evidence suggests a correlation between nighttime blood pressure BP) measured through ambulatory BP monitoring (ABPM), the nocturnal BP dipping phenotype, and cardiovascular risk. However, the clinical implications of elevated peak nighttime home BP are currently unknown. This analysis investigated the association between peak nighttime home systolic BP (SBP) and cardiovascular events in outpatients with one or more cardiovascular risk factors.

Design and method:
In the Japan Morning Surge-Home Blood Pressure (J-HOP) study, nighttime home BP was automatically measured three times every night for 14 days using a nighttime home BP monitoring device (HEM-5001, Omron Healthcare) at baseline. Peak nighttime home SBP was defined as average of the highest three values recoded during the 14-night measurement period. Cardiovascular events (stroke, coronary artery disease, heart failure, aortic dissection) were tracked over a mean 7.1 years’ follow-up period.

Results:
This analysis included 2545 individuals (mean age 63.3±10.3 years, 49% male) with their nighttime home BPs. After adjustment for covariates (including age, sex, and average office, morning, evening, and nighttime home SBP), individuals with peak nighttime home systolic blood pressure (SBP) in the highest quintile (Q5, >=149.0 mmHg) demonstrated a significantly elevated risk of stroke compared to those in the lowest quintile (Q1, <119.3 mmHg) (hazard ratio [HR] 4.24, 95% confidence interval [CI] 1.07–16.77; p=0.039 overall and 8.92, 1.49–53.43; p=0.017 in the subgroup with >=6 nighttime home SBP measurements). Even when controlling for average real variability of nighttime BP, peak nighttime home SBP remained an independent predictor of stroke risk. On spline regression analysis, the average peak nighttime home SBP cut-off value for predicting an increased risk of incident stroke was 136 mmHg.

Conclusions:
We propose exaggerated peak nighttime home SBP determined from >=6 measurements as a novel risk factor for stroke, independent of conventional office and home BP values.
SIGNIFICANT INCREASES IN PERIPHERAL AND CENTRAL BLOOD PRESSURE IN CHILDREN AT MUCH LOWER BODY MASS INDEX THAN EXPECTED
Authors: Wilmsmeier Lisa , Von Der Born Jeannine , Sugianto Rizky I , Grabitz Carl , Schmidt Bernhard Mw , Braun Ana Celine , Homeyer Denise , Tegtbur Uwe , Melk Anette 
Published: May 2024

Objective:
Cardiovascular (CV) complications are the most common causes of death worldwide. Increased body weight and higher blood pressure (BP) are known risk factors for CV disease with a known association of higher body mass index (BMI) with higher BP. Our study intended to describe at which BMI-level significant increases in either central (cBP) or peripheral BP (pBP) can be detected in young children.

Design and method:
We measured cBP and pBP in 1,183 schoolchildren (first/second graders; mean age 7.9±0.6 years; 51% male). pBP measurements were performed with a validated oscillometric device (Dinamap-VC150-GE). cBP was measured noninvasively with the Mobil-O-Graph (IEM). Multivariable linear regression models (corrected for age, sex, height) were used to compare pBP/cBP values of children with a BMI<50th percentile (pct) with children separated in five groups according to BMI pct (>=50th-<65thpct; >=65th-<75thpct; >=75th-<85thpct; >=85th-<95thpct; >=95thpct).

Results:
BMI was 17±3 kg/m2 (M±SD), 275 children (22.8%) were overweight (BMI>=85th pct), 126 (10.5%) obese (BMI>=95thpct). Peripheral systolic blood pressure (pSBP) was 104±8mmHg (M±SD), peripheral diastolic blood pressure (pDBP) 61±6mmHg (M±SD); 5% of the cohort displayed hypertensive pBP values >=95thpct. In the unadjusted analysis, we saw an increase in pSBP (Fig.1A) and cSBP (Fig.1B) already at a BMI around 60thpct. Further analysis comparing the corrected means revealed that pSBP showed already a significant increase for children with a BMI>=75thpct (ß=1.8, p=0.026) when compared to children with a BMI<50thpct. For the model including pDBP no significant effects were seen. cSBP significantly increased already in children with a BMI >=65thpct. (ß=1.7, p=0.031), while cDBP increased significantly in children with a BMI >=75thpct (ß=1.5; p=0.012) when compared to children with a BMI<50thpct.

Conclusions:
Our findings suggest that increases in body weight affect pBP and particularly cBP at much lower BMI pct level than expected. These results are alarming as pediatricians usually get concerned at BMI levels above the 85thpct (defined as cut-off for overweight in children based on WHO growth reference values). Given the important interaction between both risk factors and their track from childhood to adulthood, effective overweight prevention must take place in early childhood.
NIGHTTIME BLOOD PRESSURE ASSESSED USING HOME OR AMBULATORY BLOOD PRESSURE MONITORS IN YOUNG ADULTS WITH TYPE 1 DIABETES: RELATIONSHIP WITH PRECLINICAL TARGET-ORGAN DAMAGE
Authors: Theodosiadi Aikaterini , Kollias Anastasios , Vakali Elena , Destounis Antonios , Tsiroukidou Kyriaki , Karypidou Erieta , Menti Ariadni , Vazeou Andriani , Zografou Ioanna , Doumas Michael , Stergiou George 
Published: May 2024

Objective:
To investigate the association between nighttime blood pressure (BP) measured with home (HBPM) versus ambulatory monitors (ABPM) with indices of preclinical target-organ damage in adolescents and young adults with type 1 diabetes (T1D).

Design and method:
Individuals aged 12-30 years with T1D underwent 24h ABPM (20-min intervals, Microlife WatchBP O3), home monitoring (duplicate morning and evening measurements for 7 days; 3 measurements/night for 3 nights; Microlife WatchBP Home-N) and assessment of indices of preclinical target-organ damage [left ventricular mass index (LVMI), intima-media thickness of common carotid artery and bulb (IMT), albumin-to-creatinine ratio (ACR) in two different morning urine samples].

Results:
Data from 93 individuals were analyzed (57% males, mean age 21±5.5 years, BMI 24±4 kg/m2, HbA1c 7.2±1.0%, T1D duration 11.2±6.5 years, 24-hour systolic/diastolic ambulatory BP 112±9.3/67±5.6 mmHg, 24h ambulatory hypertension 3.2%). LVMI measurements were available in 79 participants, IMT in 65, and ACR in 88 participants. Nighttime ambulatory and home BP were correlated with LVMI (r=0.35/0.31 for systolic and r=0.26/0.25 for diastolic BP, respectively, p<0.05) and IMT (r=0.34/0.46 for systolic and r=0.29/0.42, for diastolic BP, respectively, p<0.01). ACR was correlated with HbA1c (r=0.24, p<0.05), and inversely with nighttime systolic BP dip in ABPM (r=-0.23, p<0.05). Results of multivariable regression analysis are presented in Table 1.

Conclusions:
In adolescents and young adults with T1D, nighttime BP measured at home and in ABPM appear to exhibit similar correlations with indices of asymptomatic target-organ damage.
APOCYNIN PREVENTS BLOOD PRESSURE RISING AND IMPROVES KIDNEY FUNCTION IN RATS WITH 5/6 NEPHRECTOMY
Authors: Vukovic Andrija , Karanovic Danijela , Mihailovic-stanojevic Nevena , Miloradovic Zoran , Nesovic-ostojic Jelena , Brkic Predrag , Ivanov Milan , Kovacevic Sanjin , Vajic Una -JOVANA , Jovovic Djurdjica , De Luka Silvio R. 
Published: May 2024

Objective:
High blood pressure and proteinuria play major roles in chronic kidney disease (CKD), a high-mortality condition that affects millions of people. Reactive oxygen species (ROS) produced by NADPH oxidases are implicated in many pathophysiological processes including hypertension and CKD. Apocynin (APO) shows the anti-oxidative activity by inhibiting the assembly of NADPH oxidase and overproduction of ROS. The aim of this study was to investigate the effects of apocynin on oxidative stress, blood pressure and kidney function in normotensive rats with CKD induced by 5/6 nephrectomy through ligation of renal poles (Nx-L).

Design and method:
Male Wistar rats were divided into three groups. One group was control (sham surgery) and two other groups underwent two-step surgical procedure of 5/6 nephrectomy induced by ligation of renal poles. Unlike conventional Nx which leads to high mortality due to hemorrhage in or after surgery, here we induced Nx by ligation of the upper and lower poles (leads to necrosis of these poles) of left kidney after removal the right kidney one week later. After 4 weeks from this procedure, control and model group (Nx-L) received vehicle, while Nx-L+APO received apocynin 20 mg/kg/day (i.p.) for 4-week-period. Mean blood pressure (MAP), proteinuria, and oxidative stress marker (thiobarbituric acid reactive species-TBARS) in plasma and urine were measured.

Results:
In model group we observed significantly increased MAP (121,13±2,01vs.94,88±4,13mmHg, p<0.001), plasma creatinine (55,4±1,3vs. 41,3±2,3μmol/l, p<0.001), and proteinuria (0,036±0,006vs.0,017±0,001mg/min/kg, p<0.01) levels compared to those in control. Furthermore, significant increase of plasma TBARS level (5,47±0,77vs.2,75±0,52nmol/ml, p<0.01) and urine TBARS excretion (1,10±0,06vs.0,86±0,04nmol/min/kg, p<0.01) were detected in model compared to control. Interestingly, APO treatment significantly reduced blood pressure to the level of control (83,88±5,14vs.94,88±4,13mmHg). APO significantly reduced urine protein loss (0,024±0,002vs.0,036±0,006mg/min/kg, p<0.05) and plasma creatinine level (49,9±1,5vs.55,4±1,3μmol/l, p<0.05) as well as reduced plasma lipid peroxidation (2,19±0,26vs.5,47±0,77nmol/ml, p<0.001) in comparison to model group.

Conclusions:
Our results show that APO treatment prevents blood pressure rising and ameliorates kidney function in rats with 5/6 nephrectomy trough improvement of systemic oxidative status. Therefore, NADPH oxidase presents a potential therapeutic target in this form of kidney disease.
CLINICAL SIGNIFICANCE OF NIGHTTIME BLOOD PRESSURE: EXPLORING THE ASSOCIATION OF NOCTURNAL HYPOTENSIVE PHENOTYPE AND HISTORY OF FALLS IN ELDERLY HYPERTENSIVE PATIENTS
Authors: Croce Alessandro , Bilo Grzegorz , Pengo Martino F. , Ornago Alice Margherita , Ricco Alice , Bellelli Giuseppe , Parati Gianfranco 
Published: May 2024

Objective:
falls are a major health problem in elderly, approximately 28–35% of individuals aged > 65 years’ experience falls each year. Previous studies suggested that unexplained falls may mask a syncope or pseudo-syncope in almost 50% of cases, and that patients with reflex syncope have a higher prevalence of systolic blood pressure (SBP) drops on ambulatory blood pressure monitoring (ABPM), the so-called hypotensive phenotype. However, it is not clear whether hypotensive phenotype may be itself associated with falls. We investigate if hypotensive phenotype is associated with history of falls in elderly hypertensive.

Design and method:
a cross-sectional study that included treated hypertensive patients aged >=75 years evaluated at the Hypertension Center of Istituto Auxologico Italiano IRCCS in Milan. We excluded patients with a life expectancy of less than 6 months. All participants underwent ABPM. History of falls within the last year was recorded and multidimensional geriatric assessment to estimate frailty using Frailty accumulation index was performed. Daytime and night-time hypotensive phenotypes were defined as at least one SBP drops <90 mmHg on ABPM during daytime and night-time, respectively. The same analysis was repeated by considering cut-off of SBP <80 mmHg both during day and night-time.

Results:
we enrolled 105 patients, mainly females (n=80, 76%) with a mean age of 82 (± 4) years.
In 74 (70%) patients day-time hypotensive phenotype was present at ABPM, while nighttime hypotensive phenotype was present in 24 of them (23%). Among participants 21 (20%) experienced a fall in the last 12 months; compared for age, sex, BMI, frailty index and BP patients with falls and not have no significant differences. Regardless of SBP cut-off, nocturnal hypotensive phenotype was associated with history of falls while daytime hypotensive phenotype was not. (Figure 1).

Conclusions:
In our study, nighttime but not daytime BP drops were associated with falls in treated hypertensive elderly patients. The mechanistic role of nighttime hypotensive phenotype and its association with syncope and falls will need to be evaluated in larger prospective studies to better clarify the utility of ABPM in falls prediction in elderly.
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.