bluuebunny/crossref_metadata_2025_split huggingface dataset:
KIDNEY DNA METHYLATION AS A DRIVER OF HERITABLE PREDISPOSITION TO BLOOD PRESSURE AND HYPERTENSION
Authors: Xu Xiaoguang , Eales James , Jiang Xiao , Guo Hui , Samani Nilesh , Charchar Fadi , Tomaszewski Maciej 
Published: April 2021

Objective:
We aim to bridge the knowledge gap between “sequence” (discoveries from genome-wide association study (GWAS)) and “consequence” (human hypertension) by illuminating the effects of blood pressure (BP)-associated genetic variants on molecular targets operating at epigenome in the renal tissue.

Design and method:
We conducted cis-methylation quantitative trait loci (mQTL) analysis on methylation data from 374,826 CpGs in 195 human kidney samples. Based on the intersection between blood pressure variants from all previous GWAS and mQTLs, we performed a colocalisation analysis to explore whether the overlapping BP GWAS and kidney cis-mQTL signals track the same genetic variant. We then used Mendelian randomisation (MR) to investigate the causal effects of renal methylation signals on BP-defining traits.

Results:
Through examination of the effects of 821 common BP GWAS variants on kidney CpG site methylation in a unique collection of 195 human kidneys, we identified 578 kidney genes as kidney CpG site partners for the BP GWAS variants. For 54% of BP GWAS kidney mGenes, the CpG signal was proximal to the transcription start site (distance < 1500 bp). For example, cg04510874 (the CpG partner of rs4932373 BP GWAS kidney mSNP) mapped onto a CpG island and the promoter sequence of FES (a target for naproxen – a non-steroidal anti-inflammatory medication with high BP known as one of its side effects). The extent of methylation at this CpG site and the renal expression of FES showed opposite directions of association with the rs4932373 genotype. Colocalisation and Mendelian randomisation analyses revealed a total of 99 unique genes with a causal link to BP through kidney DNA methylation.

Conclusions:
Through integration of DNA methylation data from a large collection of human kidney samples we colocalised GWAS association and cis-mQTL signals in known BP GWAS loci and uncovered 99 kidney genes with a causal effect on BP, that acts through DNA methylation.
IMPACT OF SHAM PROCEDURE ON BLOOD PRESSURE LEVELS IN PATIENTS WITH UNCONTROLLED HYPERTENSION: A SYSTEMATIC REVIEW AND META-ANALYSIS OF RENAL DENERVATION TRIALS
Authors: Stavropoulos Konstantinos , Katsimardou Alexandra , Imprialos Konstantinos , Patoulias Dimitrios , Koutsampasopoulos Konstantinos , Tegou Zoi , Alataki Sofia , Bouloukou Sofia , Dimitriadis Kyriakos , Papademetriou Vassilios , Tsioufis Konstantinos , Doumas Michael 
Published: April 2021

Objective:
Renal denervation (RDN) has been studied extensively during the last decade. Its role in the management of resistant hypertension has been placed at the epicenter after the conduction of the second-generation trials. The impact of sham procedure however remains undetermined.

Design and method:
PubMed and CENTRAL, along with grey literature sources, were searched from their inception to May 2019 for randomized, sham-controlled trials primarily evaluating the efficacy and safety of RDN on the management of hypertension, irrespective of study blinding, setting and sample size. We extracted those data concerning the effect of sham procedure on ambulatory and office blood pressure levels (ABP and OBP, respectively).

Results:
Six randomized, sham-controlled trials were identified and included in the meta-analysis. In total, 981 patients with hypertension were randomized in all 6 trials to undergo either RDN (n = 585) or sham-procedure (n = 396). It was documented that the sham procedure did not affect significantly 24-h systolic ABP levels (MD: -1.15, 95% CI: -2.67 to 0.36, I^2 = 0%); however, it induced a significant decrease in 24-h diastolic ABP levels by 1.52 mm Hg (95% CI: -2.53 to -0.51, I^2 = 0%). In addition, it was demonstrated that the sham procedure resulted in a significant decrease in systolic OBP by 3.05 mm Hg (95% CI: -5.30 to -0.81, I^2 = 0%) and a non-significant decrease in diastolic OBP by 0.65 mm Hg (95% CI: -2.03 to 0.73, I^2 = 0%). No major safety issues arose.

Conclusions:
Sham procedure is a safe procedure, providing significant or marginally non-significant decrease in both ABP and OBP levels.
THE PREVALENCE OF DRUG-RELATED ADVERSE REACTIONS AMONG HYPERTENSIVE PATIENTS
Authors: Stolarz-Skrzypek Katarzyna , Bijak Magdalena , Olszanecka Agnieszka , Wojciechowska Wiktoria , Czarnecka Danuta 
Published: April 2021

Objective:
Drug-related side effects are one of the main causes of patients non-adherence to antihypertensive treatment. Therapeutic challenge concerns mainly patients with multiple drug intolerance syndrome, defined as history of side effects after three or more classes of medications. The aim of the current study was to assess the prevalence of drug-related adverse events in hypertensive patients.

Design and method:
We recruited for the study regular patients followed at the Outpatient Hypertensive Clinic. The standardized questionnaire was administered, comprising of 23 questions, inquiring about patient medical history including drug related side effects. Patient's answers were adjudicated against archived medical history. Database management a statistical analyses were provided using STATISTICA 13.1.

Results:
The study group included 600 patients (57,66 % women, age = 64 (54–71) years, BMI = 26,7 (24,2–30,5) kg/m2; 42,33% men, age = 60 (49–68) years, BMI = 27,5 (24,7–30,9) kg/m2). Of all patients, 184 (30,67%) reported experiencing drug-related side effect(s) anytime in their life. 56 patients (9,33%) complained of side effects of 2 drug classes, and 24 patients (4,00%) reported side effects from three or more drug classes, fulfilling the definition of the Multiple Drug Intolerance Syndrome (MDIS). Patients with a history of drug-related adverse events as compared to patients never reporting them were more often women (68 % vs 32 %, p = 0,001). No difference was observed between the groups in terms of age (64 (51–71) vs 62 (52–69) years old, p = 0,370) or BMI (26,7 (24,3–30,4) vs 27,3 (24,4–3,1, p = 0,359). Patients with MDIS were older (65 (54–72 vs 59 (50–67 years old, p = 0,018) and more often women (70% vs 30 %, p = 0,001) as compared to patients without MDIS.

Conclusions:
History of drug-related side effects is common among hypertensive patients and concerns one-third of outpatients. Women report drug-related side effect more often then men. Four percent of hypertensive patients fulfills the definition of the multiple drug intolerance syndrome. Older age and female sex are determinants of multiple drug intolerance syndrome in hypertensive patients.
GENDER DIFFERENCES IN PATIENTS WITH TYPE 2 DIABETES MELLITUS AND HEART FAILURE WITH REDUCED EJECTION FRACTION: ARE AGE, HYPERTENSION AND ATRIAL FIBRILLATION THE ANSWER?
Authors: Gaman Mihnea -Alexandr , Dobrica Elena Codruta , Cozma Matei Alexandru , Diaconu Camelia Cristina 
Published: April 2021

Objective:
Gender differences may exist in heart failure with reduced ejection fraction (HFrEF) patients, but little research has been conducted on this topic so far, mainly because women are underrepresented in clinical trials. The addition of type 2 diabetes mellitus (T2DM) to HFrEF might have an influence on gender differences as well. Our objective was to evaluate and report gender differences in a group of patients with HFrEF and T2DM.

Design and method:
Observational, retrospective study using the medical records of patients with HFrEF and T2DM hospitalized in the Internal Medicine Department of an emergency referral hospital in Romania between January-June 2017.

Results:
The study group (70.81 ± 9.49 years, range 38–92 years) included 100 patients with HFrEF and T2DM: 47 women (47.00%, 73.02 ± 8.47 years, range 57–92 years), 53 men (53.00%, 68.85 ± 9.90 years, range 38–86 years). NYHA class: 63 (63.00%) patients NYHA class II, 18 (18.00%) patients NYHA class III and 19 (19.00%) patients NYHA class IV. Women with HFrEF and T2DM were older (p = 0.0283) and were more likely to be hypertensive (p = 0.002) vs. men with HFrEF and T2DM who were more likely to have atrial fibrillation (p = 0.05) vs. women. NYHA class II was the most frequent functional class in both genders (61.70% in women vs. 64.15% in men). NYHA class III was more common in men vs. women (22.64% vs. 12.77%), whereas NYHA class IV was more common in women vs. men (25.51% vs. 13.21%). Women with HFrEF and T2DM were more likely to have hypertension, dyslipidemia, obesity, anemia, nephropathy, dyselectrolytemia, neuropathy or retinopathy vs. men. As compared to women, men with HFrEF and T2DM were more likely to be diagnosed with valvulopathy, coronary heart disease, atrial fibrillation, chronic kidney disease, hepatic steatosis, chronic venous insufficiency or peripheral arterial disease.

Conclusions:
Our study reinforces that gender differences in HFrEF and T2DM patients exist: women were more likely to be older, have a more severe NYHA functional class or suffer from hypertension, obesity, dyslipidemia, microvascular complications and dyselectrolytemia. Men with HFrEF and T2DM were younger, had a less severe NYHA functional class and often had more macrovascular complications.
THE GLOBAL AMBULATORY BLOOD PRESSURE MONITORING (ABPM) IN HEART FAILURE WITH PRESERVED EJECTION FRACTION (HF-PEF) REGISTRY. RATIONALE, DESIGN AND OBJECTIVES
Authors: Camafort Miguel , Adeseye Akintunde , Barroso Weimar Sebba , Coca Antonio , Damasceno Albertino , Medina Angel R. González , Jhund Pardeep , Kario Kazuomi , Komori Takahiro , Lee Hae -Young , Lip Stefanie , López-Jaramillo Patricio , Mccallum Linsay , Ogah Okechukwu , Padmanabhan Sandosh , Pascual Domingo , Pyun Wook -Bum , Renna Nicolas F. , Sierra Cristina , Valdez Osiris , Wyss Fernando , Barbosa Eduardo , Okazaki Osamu , Yoshida Tetsuro , Sani Mahmoud 
Published: April 2021

Objective:
The prognosis of patients with heart failure and preserved ejection fraction (HFpEF), depends on multiple factors such as frailty and functional capacity, the presence of comorbidities and haemodynamic parameters including blood pressure (BP). Detailed definition of these prognostic factors may help identify effective management strategies. Our primary objective is to identify measures of BP recorded by ambulatory blood pressure monitoring (ABPM) that associated with hospital readmission due to HF or cardiovascular (CV) death, or functional decline in patients with HFpEF. Secondary objectives will be to examine the association between these measures and each of the components of the primary outcome separately and on non-CV death and all cause death, cognitive impairment and frailty.

Design and method:
In this prospective observational cohort of patients with stable HFpEF, ABPM will be obtained at baseline and at one year of follow-up. Inclusion criteria will be previous diagnosis of stable HFpEF defined as stable treatment or functional class for at least 4 weeks before study admission. A diagnosis of HFpEF (LVEF > 45%) will be made according to the European Society of Cardiology guidelines. In addition to data on demographics and clinical examination, doppler echocardiography, office BP measurement, ABPM recordings, home BP measurement (HBPM), ECG, laboratory tests (serum creatinine, eGFR, Albumin/Creatinine/Ratio, lipid parameters, glucose, HbA1c, liver biology, albumin, prealbumin, blood cell count, ferritin and transferrin saturation rate, natriuretic peptides) will all be recorded. Functional and cognitive capacity will be assessed using the Barthel index and MOCA test, while frailty will be assessed using the Short Physical Performance Battery, and Frail Phenotype questionnaires.

Results:
We plan to include data from more than 80 investigators from more than 17 countries around the world during the next 5 years. This study has been registered at https://clinicaltrials.gov/ct2/show/NCT04065620

Conclusions:
The Global Ambulatory Blood Pressure Monitoring (ABPM) in Heart Failure with Preserved Ejection Fraction (HFpEF) registry will allow us to assess the association between blood pressure and frailty in a global population of patients with HFPEF
ANALYSIS OF PLASMA PROTEIN AGGREGATION FROM PATIENTS WITH HEART FAILURE WITH PRESERVED EJECTION FRACTION
Authors: Gouveia Marisol , Schmidt Cristine , Teixeira Manuel , Magalhães Sandra , Nunes Alexandra , Lopes Mário , Ferreira Rita , Vitorino Rui , Santos Mário , Vieira Sandra , Ribeiro Fernando 
Published: April 2021

Objective:
To compare the structural conformation of circulating protein aggregates and the levels of SDS-resistant protein aggregates between patients with heart failure with preserved ejection fraction (HFpEF) and age-matched individuals.

Design and method:
Ten adults were recruited, five patients with HFpEF (age: 70.0 ± 3.2 years, FEVE: 58.0 ± 7.5%, NT-proBNP: 1039.4 ± 530.7 pg/mL, BMI: 33.2 ± 5.6 kg/m2, SBP: 142.0 ± 23.5 mmHg, DBP: 74.6 ± 9.3 mmHg) and five age-matched individuals with cardiovascular risk factors (70.6 ± 2.7 years, BMI: 32.8 ± 2.8 kg/m2, SBP: 38.5 ± 13.8 mmHg, DBP: 81.6 ± 6.6 mmHg). SDS detergent-insoluble protein aggregates were analysed in plasma pre-cleared from albumin and immunoglobulin, by diagonal two-dimensional electrophoresis. Fourier-transform infrared spectroscopy (FTIR) was used to assess plasma proteins’ secondary structures, particularly the ones related with high aggregation propensity.

Results:
Our results indicate that HFpEF patients have similar plasma levels of SDS-resistant protein aggregates to those of age-matched participants (29.6 ± 6.4 vs. 35.0 ± 3.9%, p = 0.153). However, HFpEF patients with lower VO2peak and higher NT-proBNP generally presented higher level of protein aggregates. FTIR multivariate analysis of the amide region I (1700–1600 cm-1), which is directly related to proteins secondary structures, allowed to discriminate HFpEF from age-matched group. Partial Least Square Regression (PLS-R) to this spectra region showed that HFpEF patients exhibited strong vibrational peaks characteristic of protein aggregates (intermolecular beta-sheet (1625 cm-1), anti-parallel beta-sheet (1693 cm-1) and aggregate strands (1611 cm-1)); the age-matched individuals were characterized by a band containing alpha-helix structures (1653 cm-1), characteristic of a more stable conformation with less susceptibility to aggregation.

Conclusions:
The analysis of the protein aggregation profile by FTIR revealed that the plasma from HFpEF patients was characterized by the presence of secondary structures typical of protein aggregates. Although the fraction of detergent-insoluble aggregates was not different from the one of age-matched participants, our ongoing identification of proteins present in the aggregates, by mass spectrometry, will allow us to infer main molecular pathways involved in the progression of HFpEF.
RELATIONSHIP BETWEEN PCSK9 PLASMA LEVELS AND CAROTID ATEROSCLEROSIS IN HYPERTENSIVE PATIENTS
Authors: Galvez Juan Manuel Urbano , Frederico Ana Coelho , Ronderos Eduardo Carvajal , Bolaños Cristina Carrera 
Published: April 2021

Objective:
The objective of our study is to assess whether serum PSCK9 levels are associated with AT by measuring the CIMT, which allows the identification of an analytically independent risk factor in hypertensive patients, with the aim of improving early cardiovascular risk detection in these patients.

Design and method:
In a population of 166 patients with high blood pressure (HBP), the CIMT was evaluated and correlated with the analytical values of PCSK9. The age of the participants ranges between 30 and 86 years, with an average age of 59.5 years and a standard deviation of 11.4 years (CV-19.2%). 55.4% were men. Ultrasound variables related to the carotid arteries, specifically the CIMT and the presence of unstable plaques, were analysed.

Results:
We analyse the possible relationship between the plasma value of PCSK9 and the CIMT considering two situations: that the CIMT is normal or altered. The average PCSK9 levels for both situations are high, observing that the average value for people with altered CIMT is significantly higher (p = 0.001). If we calculate the mean values of CIMT for individuals with normal and altered PCSK9, it is observed that it is significantly higher in individuals with altered PCSK9 (p = 0.000). We also relate the percentage of individuals with altered CIMT with the presence of normal / altered PCSK9 values. The relationship between the variables is statistically significant (p = 0.000), indicating that the proportion of subjects with alteration of the PCSK9 is clearly higher in the group with altered CIMT (75.5% versus 39.3%). With respect to the relationship between PCSK9 values and the presence or absence of unstable carotid plaques, in individuals with this type of plaque, the average level of PCSK9 is clearly higher. However, since the group with this situation is very small, the difference cannot be considered significant (p = 0.170).

Conclusions:
The serum levels of PSCK9 are positively correlated with an early CV risk factor (CIMT). Therefore, we can conclude that PSCK9 can become an independent risk factor for AT in hypertensive patients. More studies are needed to confirm our preliminary results
RELATIONSHIP BETWEEN PSCK9 PLASMA LEVELS AND BLOOD PRESSURE LEVELS REGISTERED BY AMBULATORY BLOOD PRESSURE MONITORING (ABPM)
Authors: Gálvez Juan Manuel Urbano , Ronderos Eduardo Carvajal , Bolaños Cristina Carrera , Frederico Ana Coelho 
Published: April 2021

Objective:
Establish a correlation between values and circadian patterns of 24-hour BP measured by ABPM and serum PCSK9 values to try identify an early CVR biomarker.

Design and method:
In a sample of 166 patients (without treatment with statins) followed in an HBP medical office, 24-hour BP was evaluated by ABPM and correlated with the plasma analytical values of PCSK9. The mean age of the participants was 59.5 years The mean values of daytime and nocturnal systolic and diastolic BP and its relationship with the circulating values of PSCK9 were analyzed. For all variables, the mean, median, standard deviation and coefficient of variation were calculated, as well as their minimum and maximum values and their asymmetry coefficient.

Results:
There is a significant correlation of PCSK9 values with daytime SBP (r = 0.240; p = 0.002; R2 = 0.06), and also weaker with nocturnal SBP (r = 0.153; p = 0.049), in both cases with positive correlation. No positive correlation of PCSK9 values was observed with the mean values of DBP (p = 0.587 and p = 0.081), although it should be taken into account that at the sample level the sign of the coefficient is negative. When grouping the sample by type of AT, it is observed that in general, the positive relationship between daytime systolic BP and PSCK9 remains both in patients with a standard dipper (r = 0.206) and in those with a non-dipper (r = 0.387). On the contrary, for nocturnal systolic BP, it is only observed in dippers (r = 0.420) and in extreme dippers but with a negative sign (r = -0.515). The correlation is not significant among the dippers (p = 0.191).

Conclusions:
In our study, we found a positive correlation between serum PSCK9 levels and 24-hour BP values with different degrees of positivity according to the circadian pattern and type of HBP. This assumes that the plasma level of PSCK9 could be a possible early biomarker of CVR in these hypertensive patients. More studies are needed to confirm our preliminary results.
ASSOCIATION BETWEEN TUMOR NECROSIS FACTOR, BRAIN NATRIURETIC PEPTIDE AND POLYMORPHISM OF THE M235T OF THE ATG GENE IN HYPERTENSIVE PATIENTS WITH HEART FAILURE
Authors: Medentseva Olena , Udovychenko M. , Rudyk I. , Ovrakh T. , Gasanov I. , Babichev D. , Galchinskaya V. 
Published: April 2021

Objective:
To investigate the association between tumor necrosis factor alfa (TNFa), N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and polymorphism of the M235T of the ATG gene in hypertensive patients with heart failure with preserved ejection fraction (HFpEF).

Design and method:
The main group of eighty-four patients (51 females and 33 males; mean age 62,7 ± 8,0 years) with HFpEF and arterial hypertension. Sixty-eight patients and eighteen healthy persons were carriers of 235T allele (MT+TT genotypes), sixteen patients had MM genotype of M235T polymorphism of ATG, determined by using of polymerase chain reaction. Levels of NTproBNP and TNFa were determined by enzyme-linked immunosorbent assay (ELISA) using «NTproBNP-BEST-ELISA» (Russia) and «TNFa-ELISA-BEST» (Russia), respectively. All statistical tests were 2-tailed and p < 0,05 was considered statistically significant and performed in Statistica 10.0.

Results:
The significant difference in the level of TNFa in hypertensive patients with HFpEF depending on the different genotypes of M235T polymorphism of ATG was not found. Although the serum NTproBNP level increased in patients with MT+TT genotypes compared with patients with MM genotype (Table 1).

Conclusions:
The presence of T allele of M235T polymorphism of ATG in hypertensive patients with HFpEF was independently associated with increased level of NTproBNP
VASCULAR ENDOTHELIAL GROWTH FACTOR-A AND THE POLYMORPHISM OF THE GENE (RS 2010963) IN ONE YEAR PROGNOSIS IN HYPERTENSIVE PATIENTS WITH ST-ELEVATION MYOCARDIAL INFARCTION
Authors: Kobets Alla , Kutya Inna , Rodionova Iuliia , Kopytsya Mykola 
Published: April 2021

Objective:
The objective was to study the role of vascular endothelial growth factor (VEGF-A) and the polymorphism of the VEGF-A gene (rs 2010963) in prognosis hypertensive patients with ST-elevation myocardial infarction (STEMI) within 12-months.

Design and method:
91 patients with STEMI were enrolled into the study, 70 (76.9%) men and 21 (23.1%) women, with an average age of 59.21 ± 8.92 years. The VEGF-A concentration was measured by the ELISA. The allelic polymorphism of the G634C of the VEFR-A gene (rs 2010963) was performed by a real-time polymerase chain reaction (PCR) method. Blood examination was done on 5–7 days and 12 months after the STEMI.

Results:
Results: The baseline levels of VEGF-A was significantly higher - 194.10 [115.02–398.86] pg/ml in patients with the GG genotype compared with those who had the GC genotype - 148.44 [68, 84–221.28] pg / ml, p = 0.047. After 12 months the level of VEGF-A significantly increased from 148.44 [68.84–221.28] pg/ml to 467.18 [351.34–697.29] pg/ml (p = 0.001) in patients with the GC group of polymorphic variant of the G634C gene. The peptide increased also in the patients with the GG gene but it was less significant. After one year examination, there were significant reduction in the level of systolic blood pressure (SBP) (p = 0,015) and diastolic blood pressure (DBP), (p = 0,031) in the patients with the genotype GC, at the same time in those with the GG genotype this reduction was characterized by p = 0,039 and p = 0,033 respectively.

Conclusions:
Conclusion: The STEMI patients with GC genotype are predisposed for the best blood pressure control in the one year follow-up period compared to the GG genotype.