bluuebunny/crossref_metadata_2025_split huggingface dataset:
PREDICTING THE RISK OF FALLS IN PATIENTS WITH AN INDICATION FOR ANTIHYPERTENSIVE TREATMENT: DEVELOPMENT AND VALIDATION OF THE STRATIFY-FALLS PREDICTION MODEL
Authors: Archer Lucinda , Koshiaris Constantinos , Snell Ie Kym , Riley Richard D. , Stevens Richard , Hobbs Fd. Richard , McManus Richard J. , Sheppard James P. 
Published: June 2022

Objective:
Falls are one of the most common side effects associated with antihypertensive medication. In patients at high risk of falls, the additional risk of harm from medication may outweigh the potential benefits in terms of cardiovascular risk reduction. However, it is currently unclear which patients are at high risk of falls. This study aimed to develop and validate a clinical prediction model for risk of hospitalisation or death from falls in adults eligible for antihypertensive treatment.

Design and method:
Eligible patients were aged 40 and above, with at least one blood pressure measurement between 130–179 mm Hg. The outcome was a fall resulting in hospitalisation or death within 10 years of entering the study. Model development was conducted in data from CPRD GOLD using a Fine-Gray approach, accounting for the competing risk of death from other causes, with subsequent recalibration at specific time-points using pseudo-values. External validation was conducted using data from CPRD Aurum, with performance assessed through calibration curves, the Observed/Expected (O/E) ratio, C-statistic, and D-statistic, each pooled across GP practices.

Results:
Analysis included 1,773,224 patients (62,691 events) for model development, and 3,805,322 (206,956 events) for external validation. Conditional on other variables, increasing age, being female, of white ethnicity, being a heavy drinker and living in an area of high social deprivation were associated with an increased risk of falls. Upon external validation, the re-calibrated model showed good discrimination, with pooled C-statistics of 0.843 (95%CI: 0.841 to 0.844) and 0.833 (95%CI: 0.831 to 0.835) at 5 and 10 years respectively. Original model calibration was poor on visual inspection and whilst this improved with re-calibration, under-prediction of risk remained (Observed/Expected ratio 1.839 at 10 years, 95%CI: 1.811 to 1.865) (Figure 1)

Conclusions:
STRATIFY-Falls uses commonly recorded clinical characteristics and shows good discrimination on external validation, accurately distinguishing between patients at high and low risk of falls in the next 5–10 years. This model may be used in routine clinical practice to help identify those at high risk of falls, for whom the benefits of antihypertensive medication may be outweighed by the harms.
STRESSED HEART MORPHOLOGY AND NEUROLOGIC STRESS SCORE EFFECT BEYOND HEMODYNAMIC STRESS ON FOCAL GEOMETRY
Authors: Yalcin Fatih , Melek Ismet , Mutlu Turay 
Published: June 2022

Objective:
Recent work have emphasized the importance of adaptive cardiac emodelling (Plos One, IJCCRP, Am J Cardiovasc Dis., 2021). In addition to hemodynamic stress in hypertension, novel cardiac imaging have shown that stressed heart morphology (SHM: basal septal hypertrophy, the early imaging biomarker in hypertension, J Applied Physiol 2019) could be affected by emotional stress and aortic stenosis (B Press Monitor 2020, ATCS 2021).

Design and method:
The aim of the study was to explore the potential effect of chronic emotional and mental overdrive in addition to chronic hemodynamic stress due to chronic hypertension. Therefore, we planned to determine imaging data as well as neurologic stress scores in SHM and compare them in terms of geometric details and severity of stress scores.

Results:
SHM was diagnosed in 50 chronic patients with systemic hypertension using the universal criteria (thicker than 1.4 cm septal base on the parasternal long axis). Then, we decided to detect quantitative scores of neurologic stress for all patients of the study group. The patients with SHM with irregular septal basal emodelling with septal bulging were associated with high neurologic stress score, while the other SHM patients with regular emodelling had lower score (p < 0.05).

Conclusions:
SHM seems like a quite complex phenomenon which possibly affected by emotional and mental overdrive beyond pure hemodynamic stress due to hypertension. Complex imaging findings also are consistent with adaptive phase SHM (J Clinic Med 2022, J of Hypertension 2022) showing irregular nature of human SHM which is likely to depend on cognitive function compared to regular emodelling in animals.
STRESSED HEART MORPHOLOGY: A SPECIFIC LOCATION FOR VARIETY OF STRESS STIMULI
Authors: Yalcin Fatih , Yalcin Hulya , Abraham M. Rosell , Abraham Theodore P. 
Published: June 2022

Objective:
Myocardial on-specifi is a response to increased stress in acute or chronic situations. Stressed heart morphology (SHM) is a very interesting description representing basal septal hypertrophy (The early Imaging Biomarker in Hypertension, J Aplied Physiol 2019) caused by both acute emotional stress, functional due to increased afterload in hypertension and mechanic in aortic stenosis.

Design and method:
Echocardiography and coronary angiography were used to evaluate underlying mechanism of the symptoms of the particular patient who applied for health care.

Results:
In this case, we detected ampulla shape geometry with chronic stress and hypertension. 72 years old lady with 25 years of hypertension history was examined for exercise intolerance and dyspnea Echocardiography showed a left ventricular dysfunction with 40 % ejection fraction and basal septal hypertrophy. Coronary anjiography was planned and no coronary stenosis detected. The patient gave a typical history for chronic emotional disturbance and was on longstanding antidepressive medication.

Conclusions:
While SHM is associated with acute stress cardiomyopathy, hypertension and aortic stenosis (Blood Press Monitor 2020, Am J Cardiovasc Dis 2021, ATCS 2021), it also could be seen in those with chronic hypertension and emotional disturbance. This support the notion that SHM could be a specific location for variety of on-specific stress stimuli.
EVALUATION OF PLASMA HOMOCYSTEINE LEVELS AND ERYTHROCYTE ANTIOXIDANT ENZYMATIC ACTIVITIES IN TYPE 2 DIABETICS WITH ARTERIAL HYPERTENSION
Authors: Bendiab Nabila Taleb , Bouanane Samira , Baba Ahmed Fatema Zohra 
Published: June 2022

Objective:
Diabetes associated with high blood pressure and hyperhomocysteinemia are both the cause early and rapidly evolving vascular lesions. There are multiple mechanisms behind these lesions and still imperfectly known, but diabetes and hyperhomocysteinemia have many in common deleterious effects affecting hemostasis, and lipid peroxidation, suggesting that there may be a synergistic effect of these two pathologies. Currently, oxidative stress is recognized as an important factor involved in the degenerative complications of diabetes. The objective of our study is to assess the plasma homocysteine level and the activity erythrocyte antioxidant enzymes in hypertensive women with type 2 diabetes.

Design and method:
Blood samples are from hypertensive women with type 2 diabetes (n = 36), and healthy female volunteers (n = 36). A blood sample is taken for the assay of plasma biochemical parameters (glycemia, glycated hemoglobin, plasma assay homocysteine, urea and creatinine) and markers of plasma oxidative stress. Enzyme activity antioxidant erythrocytes (dismutase, glutathione peroxidase and reductase) is also determined.

Results:
Our results show that type 2 diabetes linked to hypertension causes complications metabolic resulting in hyperglycemia and glycated hemoglobin. However, the average of homocysteinemia is very high associated with hypercreatinemia and hyperuremia in diabetic women this can be explained by the marked presence of a hypertension. The activities of antioxidant enzymes: catalase, superoxide dismutase, glutathione peroxidase and reductase are significantly reduced in diabetic patients compared to control values.

Conclusions:
Diabetes mellitus is associated with alterations in the antioxidant defense system which can worsen the complications of diabetes. A diet rich in vitamins (vitamins B - vitamins B6, B12 and B9 or folic acid) and management of the diabetic’s antioxidant status is necessary for avourable assessment of this pathology.
MODULATION OF BIOMARKERS ASSOCIATED WITH LYMPHANGIOGENESIS AND CARDIOVASCULAR RISK BY POLYMORPHIC GENETIC VARIANTS OF AQUAPORINS AND HEPARANASE IN PSORIASIS
Authors: Santos Ana Carolina , Gil Ângela , Da Silva Inês Vieira , Ferreira Joana , Soveral Graça , Bicho Maria Clara , Filipe Paulo , Bicho Manuel 
Published: June 2022

Objective:
Psoriasis is a chronic inflammatory disease associated with cardiovascular risk factors. Aquaporins(AQP) are a family of channels, which can transport: water, urea, hydrogen peroxide and/or glycerol, essential for redox signalling and metabolic skin homeostasis.
Heparanase(HPSE) is an endo--glucuronidase that cleaves heparan sulfate chains of proteoglycans from the extracellular matrix(ECM), an essential step in the neovascularization and cell growth process.
Vascular endothelial growth factor-C(VEGF-C) is an important growth factor regulating lymphatic neovascularization and pathological processes associated with sodium accumulation in ECM in the skin. The VEGF soluble receptors(s-flt1) are decoy receptors present in endothelial cells, hematopoietic stem cells, monocytes, macrophages, and platelets.
This study aims to evaluate the impact of AQP3, AQP7 and HPSE genetic polymorphisms in biomarkers related to cardiovascular risk in patients with psoriasis and their clinical severity determined by Psoriasis Area and Severity Index(PASI).

Design and method:
Sixty-three psoriasis patients with a mean age of 52.50 ± 12.81years. Sociodemographic, hemodynamic and routine blood laboratory data were collected. Biochemical parameters were determined in serum according to standardized methods. Genetic polymorphisms were determined by endpoint analysis and s-flt1 and VEGF-C by ELISA. Patients were stratified based on PASI:< 5(G1) and > or equal to 5(G2). For statistical analysis, SPSS program was used with a p-value < 0.05.

Results:
Comparing the genotypic and allelic frequencies of the studied polymorphisms, no differences were found between G1 and G2.
In general, patients with genotype AA of AQP3 had higher levels of s-flt1(p = 0.005) and VEGF-C(p = 0.048). For AQP7, genotype TT was associated with higher levels of mean platelet volume(p = 0.049) and lower levels of creatinine(Cr)(p = 0.023).
Elevated levels of neutrophils(N)(p = 0.017) and potassium(p = 0.001) was observed in genotype AA of HPSE.
For G1 was observed an increased level of: s-flt1(p = 0.022) and VEGF-C(p = 0.044) associated with genotype AA of AQP3; Cr in allele C of AQP7(p = 0.018), N in genotype CC of AQP7(p = 0.017). For G2 was observed: higher levels of leucocytes in allele C of AQP3(p = 0.016) and angiotensin-converting enzyme activity(ACE1) in allele T of AQP7(p = 0.033).

Conclusions:
AQP3, AQP7 and HPSE polymorphisms appear to modulate some biochemical parameters relevant to lymphangiogenesis associated with cardiovascular risk in a sample of patients with psoriasis.
COMBINED EXOSOMAL AND PLASMA NON-CODING RNA SIGNATURE ASSOCIATED WITH URINARY ALBUMIN EXCRETION IN HYPERTENSION
Authors: Ortega Ana , Martinez-Arroyo Olga , Riffo-Campos Angela Leticia , Perez-Hernandez Javier , Flores-Chova Ana , Redon Josep , Cortes Raquel 
Published: June 2022

Objective:
Non-coding RNA (ncRNA), released into circulation or packaged into exosomes, play important roles in many biological processes in the kidney. The purpose of the present study is to identify a common ncRNA signature associated with early renal damage and its related molecular pathways by constructing a RNA-based transcriptional network.

Design and method:
This is an observational case-control study which included 43 hypertensives, twenty-one patients with essential hypertension and twenty-two without persistent elevated urinary albuminuria (UAE) (higher or equal to 30 mg/g urinary creatinine). Three individual libraries (plasma and urinary exosomes and total plasma) were prepared from each hypertensive patient for ncRNA sequencing analysis. Next, a RNA-based transcriptional regulatory network was constructed.

Results:
The three RNA biotypes with the greatest number of differentially expressed transcripts were long-ncRNA (lncRNA), microRNA (miRNA) and piwi-interacting RNA (piRNA). We identified a common 24 ncRNA molecular signature related to hypertension-associated albuminuria, of which lncRNA was the most representative. In addition, the transcriptional regulatory network analysis showed five lncRNA (LINC02614, BAALC-AS1, FAM230B, LOC100505824 and LINC01484), and the miR-301a-3p to play a significant role in network organization and to target critical pathways regulating filtration barrier integrity, tubule reabsorption and systemic endothelial dysfunction.

Conclusions:
Our study found a combined ncRNA signature associated with albuminuria, independently of biofluid origin (urine or plasma, circulating or in exosomes) that identifies a handful of potential targets involved in filtration barrier, tubule reabsorption and endothelial function that may be utilized to treating hypertension-associated albuminuria and cardiovascular damage progression.
ANALYSIS OF RAAS BIOMARKERS TO CLASSIFY ANTI-HYPERTENSIVE DRUG TREATMENTS IN THE GENERAL POPULATION: THE CHRIS STUDY
Authors: Arisido Maeregu Woldeyes , Foco Luisa , Gögele Martin , Melotti Roberto , Pramstaller Peter , Poglitsch Marko , Pattaro Cristian 
Published: June 2022

Objective:
Hypertension is a leading cause of death worldwide. Large-scale population-based epidemiological studies are an opportunity to assess the effectiveness of anti-hypertensive drug (AHD) treatment. However, these studies often lack treatment documentation, especially in situations where linkage to electronic health records is not established, with consequent recall and classification biases. When relevant biomarkers are measured, it should however be possible to attribute individuals to the most likely AHD treatment, limiting information loss.
We investigate whether unsupervised cluster analysis applied to measured RAAS biomarkers may help to classify different AHD treatments in a general population sample.

Design and method:
In the Cooperative Health Research in South Tyrol (CHRIS) study, automated drug barcode scans allowed classification of AHD specific treatment among participants. We measured angiotensin I, angiotensin II and aldosterone levels on 800 participants using liquid chromatography combined with tandem mass spectrometry (LC-MS/MS) analysis, as implemented in the RAAS Triple-A assay. Age and sex matched participants (age: 43–90 years; 54% females) were split into 8 balanced groups: normotensive (n = 101); untreated hypertensive (n = 100); non-AHD (n = 100); ACEi (n = 99); ARB (n = 98); ACEi+diuretic (n = 100); ARB+diuretic (n = 102); and beta-blockers (n = 100).
We performed unsupervised cluster analysis based on the three biomarkers ignoring the known AHD treatment. We evaluated the extent of agreement between the automated drug recognition system and RAAS based classification.

Results:
We identified three clinically heterogeneous clusters. Cluster 1 (n = 444) was characterized by participants not receiving any AHD and having high systolic blood pressure. Cluster 2 (n = 235) identified the use of ARB with or without diuretics. These individuals were more likely to present diabetes. Cluster 3 (n = 121) identified ACEi with or without diuretics and included older and overweight participants. The inter-classification agreement between the automated recognition system and RAAS clusters was highest for ACEi and ARB.

Conclusions:
In the absence of specific information, unsupervised cluster analysis applied to RAAS biomarkers can reliably identify individuals under ACEi and ARB treatment.
ROLE OF SERUM URIC ACID LEVELS AND CRP IN THE EXISTENCE OF ATRIAL FIBRILLATION IN HYPERTENSIVE PATIENTS
Authors: Papavasileiou M.V. , Karamanou A. , Aravantinos D. , Moustakas G. , Patsianis S. , Pittaras A. 
Published: June 2022

Objective:
The inflammatory effect of the serum uric acid and C-reactive protein (CRP) is evident, as well as the role and significance, of inflammation in the presence of atrial fibrillation.
The aim of this study was to investigate a possible association between the serum uric acid levels with the existence of atrial fibrillation in hypertensive patients and the possible role of CRP in this status.

Design and method:
We studied 1196 hypertensive patients (45,1% female), treated or newly diagnosed untreated, of mean age: 63,1 ± 13,3 years, without any known cardiovascular disease and with mean office systolic/diastolic arterial blood pressure (S/DBPo): 142,1 ± 19.3/86.5 ± 12,6 mmHg, mean office heart rate (HRo): 73,7 ± 10,7 bpm, average body mass index (BMI): 28.5 ± 5,8 kg/m2and average waist circumference (WC) 96.1 ± 12.9 cm
The levels of serum uric acid (SUA), C-reactive protein (CRP), urea, creatinine,were recorded. eGFR was calculated according Cockcroft-Gault Equation and the atrial fibrillation (AF) status was recorded. The study population was separated in two groups, according the existence or not of any evidence for AF
Group A: with PAF or PEAF
Group B: without AF
By using the ANOVA statistic method we registered the SUA and CRP values in both groups.
Using Pearson correlation method we correlated SUA with CRP serum levels.

Results:
Table 1: Differences of serum uric acid and CRP levels between group A and group B

Table 2: Correlation between serum uric acid levels with C-reactive protein levels

SUA: serum uric acid
CRP: C-reactive protein

Conclusions:
In hypertensive patients treated or not, the presence of PAF or PEAF was associated with significantly higher serum uric acid levels and CRP levels, while a significant positive correlation exists between SUA and CRP levels in this population. possibly indicating their importance in the inflammatory status of hypertensive patients with atrial fibrillation.
PROGNOSTIC SIGNIFICANCE OF RISK FACTORS AND BIOMARKERS IN PATIENTS HOSPITALIZED FOR CARDIORENAL SYNDROMES
Authors: Vordoni Aikaterini , Theofilis Panagiotis , Nakas Nikos , Kotsakis Athanasios , Kranidis Athanasios , Makryniotou Ioanna , Kalaitzidis Rigas 
Published: June 2022

Objective:
Cardiorenal syndromes (CRS), involving the heart-kidney cross-talk and the activation of neurohumoral and inflammatory pathways, is an entity characterized by high morbidity and mortality. Our study aimed to evaluate the prognostic role of risk factors and biomarkers in patients ospitalised for CRS.

Design and method:
In this observational cohort study, 100 consecutive patients ospitalised for CRS were enrolled. Socio-demographic characteristics, personal medical history, and prior medication use were recorded upon admission, and echocardiography was performed. Moreover, an array of blood markers was measured. The endpoint of interest was a composite of death or dialysis dependence at discharge.

Results:
Patients were classified into two groups; Group 1 (N = 52): discharged being dialysis-independent, Group 2 (N = 48): death/dialysis dependence at discharge. No significant differences were detected in baseline characteristics between the two groups. Group 2 patients used ospit-angiotensin-aldosterone system blockers (RAASb) less often (Group 1: 71.2% vs. Group 2: 41.7%, p = .003) and more frequently presented with oliguria/anuria (Group 1: 28.8% vs. Group 2: 66.7%, p < .001). Group 2 patients had significantly lower hemoglobin, serum albumin, and 25-hydroxy-vitamin D [25(OH)D] (Figure). At the same time, serum phosphate, potassium, N-terminal-pro hormone brain natriuretic peptide, and parathyroid hormone (PTH) were significantly higher in Group 2 patients (Figure). In a multivariate regression analysis, lack of prior RAASb (Odds ratio: 22.0, 95% confidence interval: 2.7–179.5, p = .004) and lower 25(OH)D levels (Odds ratio: 0.90, 95% confidence interval: 0.82–0.99, p = .03) were independently associated with an increased risk of death or dialysis dependence at discharge. 25(OH)D/PTH ratio was the most accurate predictor of the composite endpoint (area under receiver operating characteristics curve: 0.81), with a cutoff of equal or less than 97.9 having a sensitivity and specificity of 79.4% and 70.4%, respectively.

Conclusions:
Lack of prior RAASb use, high PTH, low 25(OH)D levels, and low 25(OH)D/PTH ratio are associated with a poor prognosis in patients ospitalised for CRS.
AMBULATORY BLOOD PRESSURE MONITORING IN HEART FAILURE WITH PRESERVED EJECTION FRACTION PATIENTS
Authors: Yarosh Vitalina , Yepanchinceva Olga , Babenko Vasyl , Yena Larysa 
Published: June 2022

Objective:
120 hypertensive patients (pts) aged 67,8 ± 1,2 years. 30 pts with essential hypertension (EH), 90 pts with EH complicated by heart failure with preserved ejection fraction (HFpEF), NYHA class II.

Design and method:
Doppler echocardiography, office BP measuring and ambulatory BP monitoring, 6 -minute walk test.

Results:
The increased values of office systolic BP (SBP) were determined in both groups (154,3 ± 1,4 mm Hg in HFpEF pts and 145,5 ± 2,3 mm Hg in EH pts, p < 0,01). But mean 24-h (141,0 ± 1,5 mm Hg vs 131,6 ± 1,9 mm Hg, p < 0,001), daytime (144,6 ± 1,5 mm Hg vs 136,7 ± 2,0 mm Hg, p < 0,01) and nighttime (134,0 ± 1,8 mm Hg vs 121,5 ± 3,2 mm Hg, p < 0,05) BP values were significantly higher in HFpEF patients. There is no limiting impact of high blood pressure (in the range up to 154,3 ± 1,4 mm Hg) on physical activity in patients with initial stages of HFpEF.
Office DBP values were comparable in two groups and did not exceed the recommended range. Mean 24-h DBP values slightly exceeded the upper limits in both groups. 24-h pulse BP in HFpEF pts was 63,2 ± 0,9 mm Hg compared to 54,9 ± 1,4 mm Hg in EH pts, (p < 0,05).
54 HFpEF pts (60,0%) demonstrated abnormal pattern of day/night SBP dynamics and 37 pts (41,1%) - abnormal pattern of DBP, in case of EH - 43,3 % and 20,0 %, respectively.
The normal BP circadian rhythm was recorded in 12 (40,0 %) EH pts compared to 16 (17,8 %) HFpEF pts (x2 = 6,21; p < 0,05).

Conclusions:
HFpEF patients demonstrated insufficient control of office and 24-h BP. 82,2% of HFpEF patients were characterized by pathological types of BP circadian rhythm with dominating non-dipper type confirming the increased risk of cardiovascular events in HFpEF patients. Inadequate control of blood pressure is an important factor in the development of chronic heart failure with preserved ejection fraction. Mean ambulatory systolic BP level, unlike the office systolic BP, is independently associated with the development of HFpEF.