bluuebunny/crossref_metadata_2025_split huggingface dataset:
THE WHITE MATTER INTEGRITY AND COGNITIVE PERFORMANCES OF HYPERTENSIVE PATIENTS ARE ASSOCIATED TO CIRCULATORY INFLAMMATORY RISK BIOMARKERS AND CIRCULATING WHITE BLOOD CELLS
Authors: Carnevale Lorenzo , Maffei Angelo , Carnevale Daniela , Lembo Giuseppe 
Published: May 2024

Objective:
The role of the immune system and inflammation in establishing target organ damage in cardiovascular diseases and hypertension is widely recognized. While this has been well characterized in hypertension-induced cardiac and renal damage, preclinical studies pointed out its role in cerebral injury, but it is less known whether this can be verified in hypertensive patients. In particular, no study has investigated how inflammatory mediators and circulating immune cells can be used as risk biomarkers for cerebral injury parameters obtained by neuroimaging in hypertensive patients

Design and method:
We have subjected hypertensive patients to cerebral MRI, elaborated with advanced neuroimaging techniques as diffusion tensor imaging (DTI)-MRI to assess white matter injury. We subjected patients to neuropsychological tests such as the Montreal Cognitive Assessment (MoCA) to evaluate cognitive function, measured circulating high sensitivity C-reactive protein (hs-CRP) as a general inflammatory biomarker and counted white blood cells (WBC).

Results:
We found a widespread association between white matter tract loss of integrity and elevation of inflammatory and immune biomarkers (Figure A). Specifically, the regions surrounding and crossing the corpus callosum like Forceps Major and Minor, the Anterior Commissure show a correlation between the microstructural loss of integrity and hs-CRP levels. On the other hand, the integrity of tracts situated across the temporal lobe, as the Superior Longitudinal Fasciculus, the Arcuate Fasciculus and other associative tracts is correlated with the WBC. Finally, tracts connecting the temporal lobe and traversing the white matter near the corpus callosum, and specifically the Frontal Aslant and the Uncinate Fasciculus, show associations with both inflammatory and immune markers (Figure B).

Conclusions:
We leveraged advanced neuroimaging to show that the immunoinflammatory risk in hypertensive patients is associated with white matter alterations in the corpus callosum, associative and projection fibers. Furthermore, our previous work identified that white matter damage in the Forceps Minor and Superior Longitudinal Fasciculus was a typical trait of hypertensive patients. Our data further show that the inflammatory risk associates with lower score at cognitive tests, suggesting a clinical relevance in terms of damage evidenced by advanced MRI in hypertensive patients.
HYPERTENSION AND DEXTROMETHORPHAN POISONING IN PATIENTS AGED BETWEEN 0 TO 18 YEARS- A 7 YEAR RETROSPECTIVE CASE SERIES
Authors: Stratula Andreea- Catalin , Popescu Alexandru- Mihai , Ulmeanu Coriolan Emil , Vivisenco Iolanda , Nitescu Gabriela Viorela 
Published: May 2024

Objective:
Coughing is a common symptom in the pediatric population. The wide variety of preparations available in pharmacies allows easy access to over-the-counter use. Dextromethorphan inhibits the cough reflex through an antagonistic mechanism at the NMDA-glutamate opioid receptor. Its effects are similar to those of drugs of abuse (phencyclidine and ketamine). In high doses, it produces tachycardia, hypertension, altered consciousness to coma, and neurological symptoms (agitation, hallucinations, seizures). According to the literature, patients between the ages of 12 and 20 years account for 50% of all dextromethorphan poisoning emergencies. The aim of our study is to determine the presence of arterial hypertension, its characteristics and the course of its development in dextromethorphan intoxication.

Design and method:
We present a series of 18 cases of acute dextromethorphan poisoning that were admitted to the Pediatric Antitoxic Center in Bucharest between January 2017 and November 2023.

Results:
The age range in the series of 18 patients is from 1 to 17 years. Voluntary intoxication was recorded in 13 cases (72.22%) Hypertension was noted in 15 cases (83.33%). Hypertension was present at the onset of symptoms. The poisoning severity score(PSS) showed that most of the cases were moderate (77.77%)

Conclusions:
Hypertension is a common symptom of dextromethorphan intoxication in patients between 0 and 18 years of age and may be accompanied by palpitations and precordialgia. It is mild to moderate in severity and does not require any specific treatment, as general management of the intoxication is sufficient. Severe cases or death are a rare event, while moderate cases are the most common.
DETERMINATION OF WAIST CIRCUMFERENCE IN ADOLESCENTS AS A PREDICTION TOOL OF CARDIOVASCULAR RISK FACTORS
Authors: Ospanova Ainur , Kerimkulova Aiman , Veber Viktor , Markabayeva Akbayan , Nurpeissova Riza , Adiyeva Madina 
Published: May 2024

Objective:
to assess the efficiency of WC at teenagers in prognostication of cardiovascular risk factors

Design and method:
Cross-sectional study developed with 1519 adolescents aged 12-13 years (average age, standard deviation 12.3 + 0.46 years). The prevalence of hypertension was assessed and its relationship with waist circumference. Criteria for assessing blood pressure of adolescents are identified by the following data: normal blood pressure (systolic and dyastolic blood pressure <89 percentile); high normal blood pressure (systolic and dyastolic blood pressure < 90 and 94 percentile); hypertension (systolic and dyastolic blood pressure 95 percentile). The analysis and processing of statistical data were carried out using the SPSS (version 22) program. The Pearson Chi squared test was used for comparison between groups and the presence of relationships between them or Fisher test for the difference between the proportions. The criterion for the statistical significance of the obtained results was considered the value of p <0.05. ROC analysis was used to study the relationship between waist circumference and overweight/obesity. The distinctive impact of waist circumference on the development of these states was expressed as the area under the curve (AUC 95% CI)

Results:
From 1519 studied teenagers of 12-13 years, boys were 49.1% (n=745), girls 50.9% (n=774) respectively. Population with normal BP composed 62.7%, normal raised blood pressure - 24.8%, Hypertension-12.4%. There were conducted measurements of waist circumference as a method of indirect assessment of abdominal obesity. There was revealed WC 90P 98.5% (n=939) of teenagers that shows insignificant number of the adolescents suffering from abdominal obesity. The distribution by sex was: with a normal waist circumference value 98.8% among boys, 94.7% girls respectively, girls are more likely to have abdominal obesity than boys, (Chi squared test = 19.940, df = 1, P 0.001)

Conclusions:
waist circumference rates are not as popular among children and adolescents in comparison with adults. According the obtained data of high sensitivity and specificity, it is possible to recommend active use of waist circumference in clinical practice for the early detection for the assessment of the risk of developing cardiovascular diseases regarding maturity
LONG TERM FOLLOW-UP OF ADOLESCENTS WITH WHITE COAT HYPERTENSION
Authors: Obrycki Lukasz , Podymniak-grzeszykowska Malgorzata , Pac Michal , Skoczynski Krzysztof , Koziej Jan , Mitoraj Kacper , Pilip Jakub , Wierzbicka-rucinska Aldona , Swiader-lesniak Anna , Swiderska Marta , Feber Janusz , Litwin Mieczyslaw 
Published: May 2024

Objective:
White coat hypertension (WCH) defined as elevated office blood pressure (BP) with normal ambulatory blood pressure monitoring (ABPM) is diagnosed in up to 43% of adolescents referred for hypertension based on office BP. Prospective data on adults show that WCH may be associated with the development of sustained hypertension (SH), hypertension-mediated organ damage (HMOD), and consequently, a higher cardiovascular risk. The aim of our study was to re-evaluate a group of young adults who were diagnosed with WCH in their adolescence.

Design and method:
27 patients diagnosed with WCH at the age of 14.5±2.5 years, with full diagnostic assessment (anthropometry, biochemistry, office BP, ABPM, central systolic blood pressure (cSBP) and augmentation pressure (AugPress), carotid intima media thickness – cIMT, left ventricular mass – LVMi and pulse wave velocity – PWV) were re-evaluated after 8.3±1.2 years.

Results:
At the time of WCH diagnosis, left ventricular hypertrophy (LVH) was diagnosed in 3/27 (11%), increased cIMT in 3/27 (11%), and increased PWV in 19/27 (70%). At the 2nd measurement 8 years after, 20/27 (74%) normalized BP or maintained their WCH status, whereas 7/27 (26%) developed SH. Waist circumference, total and LDL-cholesterol, fasting glycemia, cSBP, PWV, cIMT and LVMI increased in normal BP/WCH and SH subjects, not significantly different between WCH and SH subjects except for LVMI (higher increase in SH). At the 2nd measurement LVH was diagnosed in 3/20 (15%), increased cIMT in 0/20 and increased PWV in 4/20 (20%) WCH patients and in 2/7 (29%), 0/7, and 2/7 (29%) of SH patients, respectively. Despite having lower 24h BP values (p<0.05), patients who normalized BP/maintained WCH had lower LDL cholesterol values at the time of WCH diagnosis (85±27 vs 103±30 mg/dL; p<0.05). LVMi was significantly higher at follow-up in patients who developed SH (p=0.001).

Conclusions:
Children with WCH are at risk of developing SH and HMOD, therefore, this group should be closely monitored. The presence of lipid disorders may be an additional parameter assessing the risk of developing SH in this group.
PREDICTIVE VALUE OF CARDIOMETABOLIC INDEX IN CHINESE ADOLESCENTS AGED 12–18 YEARS OLD FOR METABOLICALLY UNHEALTHY PHENOTYPE IN NORMAL WEIGHT POPULATION
Authors: Ma Xiaoyan , Tan Mei , Liu Jianxi , Tong Lingling , Ding Wenqing 
Published: May 2024

Objective:
There are few studies on the predictive value of Cardiometabolic index (CMI) on metabolically unhealthy normal weight (MUNW) phenotype in adolescents. Hence, the aim of this study was to investigate the relationship between CMI and MUNW phenotype in Chinese adolescents and to assess the predictive value of CMI for MUNW phenotype.

Design and method:
Using stratified cluster sampling method, 1009 adolescents (605 males, 60%) aged 12-18 years old in Ningxia were randomly selected from October 2017 to September 2020 for questionnaire survey, physical measurements, body composition measurements and laboratory examinations. The relationship between MUNW phenotype and CMI was analyzed using binary logistic regression, and the predictive ability of relevant indicators for MUNW phenotype was assessed by constructing receiver operating characteristic (ROC) curves.

Results:
There were 913 cases of metabolically healthy weight normal (MHNW) phenotype and 96 cases of metabolically abnormal weight normal (MUNW) phenotype. The CMI level of the MUNW phenotype was higher than that of the MHNW phenotype (P<0.001). After adjusting for confounders such as age and gender, the risk of MUNW in the highest quartile group (Q4) of CMI was 3.37 times (95% CI: 1.66-6.83) higher than that of the lowest quartile group (Q1), and the risk of MUNW was at a gradually increasing (P<0.001). The MUNW risk of CMI in male and female students in Q4 group was 3.18 times (95% CI: 1.11-9.14) and 3.90 times (95% CI: 1.45-10.50) higher than that in Q1 group (all P < 0.05). Compared with BMI, TG/HDL-C, WC and WHtR, CMI was the best predictor of MUNW phenotype in both sexes (boys:AUC=0.686,95%CI:0.581∼0.792; girls: AUC=0.696,95%CI: 0.607∼0.785) (P<0.001).

Conclusions:
CMI is a risk factor for the risk of developing theMUNW phenotype in Chinese adolescents, and CMI has strong predictive efficacy as a valid tool for identifying the MUNW phenotype in a normal weight population.
CYSTATIN C BASED EGFR IS SUPERIOR FOR THE ASSESSMENT OF CARDIOVASCULAR RISK IN PRETERM CHILDREN
Authors: Chainoglou Athanasia , Sarafidis Kosmas , Taparkou Anna , Farmaki Evangelia , Chrysaidoy Katerina , Gidaris Dimos , Kollios Konstantinos , Kotsis Vasilios , Stabouli Stella 
Published: May 2024

Objective:
Preterm birth is a risk factor for hypertension (HTN), chronic kidney disease (CKD) and adverse cardiovascular (CV) outcomes. The aims of the study were to evaluate the utility of eGFR based on cystatin C (Cys C) compared to creatinine in regard to associations with office blood pressure (BP) and central systolic BP (cSBP).

Design and method:
This case-control study included 52 children and adolescents born prematurely (ex-preterms) and 26 at full term (controls) matched for age in 2:1 ratio. All participants underwent office BP and cSBP measurement and laboratory evaluation including assessment of CysC values at the same visit.

Results:
Mean age of the population was 10.74±3.55 years. There were no significant differences in BP levels, eGFR(creatinine) and eGFR(CysC) between ex-preterm and control group. CysC levels were similar between the ex-preterm and the control group. CysC significantly correlated with cSBP z score (r=0.32, p=0.02, Spearman test). This association remained significant after adjustment for age, sex and BMI z score in the ex-preterm group (B=1.003, 95%CI 1.001-0.005, p=0.006). 42% (n=22) of the ex-preterm children presented cSBP levels greater than the 95th percentile. eGFR(CysC) presented positive association with office DBP (r=-0.37, p= 0.006, Spearman test) and cSBP z score (r= -0.32, p=0.022, Spearman test) in the ex-preterm group, but not in the control group (Figure). eGFR(creatinine) did not associate with BP parameters. eGFR(creatinine) overestimated eGFR levels in ex-preterm group (mean difference 20.56±22.66, p <0.001). Two (3%) and 17(32.6%) ex preterm children had GFR < 90 ml/min/1.73m2 by creatinine-based eGFR compared by eGFR(CysC).

Conclusions:
eGFR(CysC) presents apositive association with cSBP and thus, may better classify future cardiovascular risk in ex-preterm children. cSBP elevation and its association with CysC maybe a target for future studies to elucidate the role of central hemodynamic alterations in the development of HTN and CV disease in the ex-preterm individuals.
EARLY BLOOD PRESSURE AND MEDICATION CHANGES AFTER DELIVERY IN PATIENTS WITH POSTPARTUM HYPERTENSION
Authors: Jalanthiran Subeedhja , Socrates Thenral , Wenker Céline , Rana Alessandro , Piattini Leana , Strobel Noémie , Schumacher Christina , Vischer Annina , Mayr Michael , Mosimann Beatrice , Lapaire Olav , Burkard Thilo 
Published: May 2024

Objective:
Postpartum Hypertension (PPHT) is defined as elevated blood pressure (BP) (systolic >= 140 mmHg, diastolic >= 90 mmHg) after delivery. PPHT is frequent and has various etiologies. In addition, several factors including hemodynamic fluctuations, sodium homeostasis, and stress attribute to dynamic changes in blood pressure. In this analysis, we focused on early BP trends and therapeutic intensity scores (TIS) trajectories during the first three months after delivery.

Design and method:
Starting in June 2020, patients were enrolled in the Basel-PPHT Cohort. Those with chronic hypertension (CH), hypertensive disorders of pregnancy (HDP), and de novo PPHT were eligible. This analysis included all patients with both a mobile App, which leads patients through guideline conform home BP measurements (HBPM), and a 24-hour ambulatory BP measurement 3 months after delivery. Therapy adjustments were done at the discretion of the treating physician via telemedicine consultations based on HBPM. BP and TIS trajectories were evaluated. TIS as quantification of treatment was defined as seen in Figure 1. Normotensive values were defined as systolic/diastolic <135mmHg/<85mmHg (HBPM and mean awake ABPM). BP comparisons between baseline visit (BV) defined as BP at enrollment to first post-baseline visit (FPBV) and landmark visit at 3 months post-delivery (LV).

Results:
41 participants were included in this analysis. The mean (SD) age was 33(±4.9). BV, FPBV, and LV were conducted at a median (IQR)) of 3(3), 18(7), and 112 (28) days after delivery, respectively. Figure 1 shows BP and TIS trajectories. Mean systolic/diastolic BP decreased by 13(0.6)/2(1.7) mmHg between BV and FPBV, p=0.00/p=0.09, without a significant change of TIS. Whereas, changes in BP were not significant between FPBV and LV, but TIS significantly decreased (p<0.00). At LV median awake systolic/diastolic BP was 127(14)/ 82(9) mmHg, with 17% of participants on antihypertensive treatment, compared to 95% at BV.

Conclusions:
This analysis shows a significant decrease in BP during the transition period to ambulatory care. BP medication could be down-titrated in a relevant proportion of patients. These trends indicate the need for close monitoring of these patients in the early postpartum period.
ASSOCIATION BETWEEN THE WEIGHT ADJUSTED WAIST INDEX AND INCIDENT STROKE
Authors: Hu Junli , Cai Xintian , Li Nanfang 
Published: May 2024

Objective:
The association between weight-adjusted-waist index (WWI) and stroke is unclear. We aimed to determine the relationship of the WWI and stroke among the elderly patients with hypertension.

Design and method:
The Cox regression model was used to evaluate the relationship between baseline WWI and the risk of new-onset stroke. Restricted cubic splines were performed to explore the shape of the association between baseline WWI and stroke. Besides, we conducted subgroup analyses and interaction tests.

Results:
A total of 4962 hypertensive participants aged more than 60 years without a history of stroke were recruited in our study. During a median follow-up of 3.2 years, 547 incidents of new-onset stroke occurred. After adjusted for covariates, cox regression models showed the positive relationship between the baseline WWI and first stroke event. The hazard ratios (HRs) gradually increases, along with augment in WWI. Compared to the lowest quartile of WWI (Q1), HR and 95% confidence interval (CI) for stroke in the Q4 were 1.87 (1.44, 2.42). In stratified analyses, the association between WWI and the risk of stroke maintained.

Conclusions:
High WWI showed a positive association with new on-set stroke among elderly patients with hypertension. The rising prevalence of WWI may increase the future burden of stroke in elderly hypertensive cases.
ASSOCIATIONS OF THE CARDIOMETABOLIC INDEX WITH THE RISK OF CARDIOVASCULAR DISEASE IN PATIENTS WITH HYPERTENSION AND OBSTRUCTIVE SLEEP APNEA: RESULTS OF A LONGITUDINAL COHORT STUDY
Authors: Cai Xintian , Hu Junli , Li Nanfang 
Published: May 2024

Objective:
We aimed to explore the relationship between the cardiometabolic index (CMI) and cardiovascular disease (CVD) and its subtypes (coronary artery disease and stroke) in patients with hypertension and obstructive sleep apnea (OSA).

Design and method:
We conducted a retrospective cohort study enrolling 2067 participants from the Urumqi Research on Sleep Apnea and Hypertension study. The CMI was calculated as triglyceride to high-density lipoprotein cholesterol ratio × waist-to-height ratio. Participants were divided into three groups (T1, T2, and T3) according to the tertile of CMI. The Kaplan-Meier method helped to calculate the cumulative incidence of CVD in different groups. We assessed the association of CMI with the risk of CVD and CVD subtypes by estimating hazard ratios (HRs) and 95% confidence intervals (CIs) using Cox models.

Results:
During a median follow-up of 6.83 years (interquartile range: 5.92-8.00 years), 326 incident CVD were identified, including 121 incident stroke and 205 incident coronary heart disease (CHD). Overall, after adjusting for confounding variables, CMI was positively associated with the risk of new-onset CVD (per SD increment, adjusted HR: 1.31; 95% CI: 1.20, 1.43), new-onset CHD (per SD increment, adjusted HR: 1.33; 95% CI: 1.20, 1.48), and new-onset stroke (per SD increment, adjusted HR: 1.27; 95% CI: 1.10, 1.47). Similar results were obtained in various subgroup and sensitivity analyses. Adding CMI to the baseline risk model for CVD improved the C-index (P < 0.001), continuous net reclassification improvement (P < 0.001), and integrated discrimination index (P < 0.001). Similar results were observed for CHD and stroke.

Conclusions:
There was a positive association between CMI levels and the risk of new-onset CVD in patients with hypertension and OSA. This finding suggests that CMI may help identify people at high risk of developing CVD.
KARDIA-3 STUDY DESIGN: ZILEBESIRAN AS ADD-ON THERAPY IN PATIENTS WITH HIGH CARDIOVASCULAR RISK AND HYPERTENSION INADEQUATELY CONTROLLED BY STANDARD OF CARE ANTIHYPERTENSIVES
Authors: Havasi Andrea , Pagidipati Neha , Bakris George , Weber Michael , Bengus Monica , Daga Shruti , Xiang Zhihua , Zee Tiffany , Bhan Ishir , Granger Christopher Bull 
Published: May 2024

Objective:
Zilebesiran is an investigational subcutaneous (SC) RNA interference therapeutic that targets synthesis of hepatic angiotensinogen, the most upstream precursor of the renin-angiotensin system. In the phase 2 KARDIA-1 (NCT04936035) study, a single dose of zilebesiran monotherapy significantly reduced 24-hr mean ambulatory and office systolic blood pressure (SBP) from baseline to 3 and 6 months versus placebo in patients with mild to moderate hypertension. KARDIA-3, a phase 2 randomized, double-blind, placebo-controlled study (NCT06272487) will evaluate the efficacy and safety of zilebesiran as add-on therapy in patients with established cardiovascular (CV) disease or at high CV risk, with uncontrolled hypertension despite treatment with at least 2 standard-of-care antihypertensives.

Design and method:
KARDIA-3 will enroll adults with seated automated mean office SBP 140-170 mmHg on stable therapy with 2-4 antihypertensives and prior documented CV history or 10-year atherosclerotic CV disease risk >15% or estimated glomerular filtration rate (eGFR) 30-60 mL/min/1.73m2 at screening in 2 cohorts: Cohort A (∼270 patients, eGFR at least 45 mL/min/1.73m2) and Cohort B (up to 120 patients, eGFR 30 to <45 mL/min/1.73m2). Patients will be randomized 1:1:1 to receive a single SC dose of zilebesiran 300 or 600 mg or placebo in Cohort A, or 1:1:1:1 to receive a single SC dose of zilebesiran 150, 300, or 600 mg or placebo in Cohort B. The primary endpoint is change in mean seated office SBP from baseline to month 3, assessed as the mean difference between each zilebesiran dose and placebo separately for Cohorts A and B. Secondary and exploratory endpoints include other measures of blood pressure response, pharmacodynamics, and safety and tolerability through month 6.

Results:
KARDIA-3 will initiate enrollment in early 2024.

Conclusions:
There remains a substantial unmet need to treat uncontrolled hypertension in patients at high CV risk, including those with advanced chronic kidney disease. This novel phase 2 KARDIA-3 study will evaluate efficacy and safety of zilebesiran in patients with or at high risk for CV disease, building on previous phase 1 and 2 studies of this innovative therapeutic.