bluuebunny/crossref_metadata_2025_split huggingface dataset:
IMPACT OF CHRONIC KIDNEY DISEASE ON HEART FAILURE SEVERITY IN HYPERTENSION AND ATRIAL FIBRILLATION PATIENTS
Authors: Tatar Maria Cristina , Husariu Madalina , German-Sallo Marta , Tilea Ioan 
Published: April 2021

Objective:
Given the frequent association of chronic kidney disease (CKD) to cardiovascular disorders and the coexistence of heart failure (HF) with atrial fibrillation (AF), especially in elderly, hypertension being a contributor, our main objective was to assess the effect of kidney dysfunction on the heart failure progression in hypertension and atrial fibrillation patients.

Design and method:
We conducted a retrospective analytic-observational study that included 258 AF patients, mean age 73.48 yr (SD = 10.4), 51.6% females. In order to classify the CKD, we divided the study population in two groups based on the estimated glomerular filtration rate (eGFR): higher or equal than 60, respectively below 60 ml/min/1.73 square meters, comparing the estimations of Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. We used the NYHA classification to identify the HF severity.

Results:
Of all patients, according to the presence or absence of the hypertension, 210 patients (81.4%) presented high blood pressure values. In terms of the eGFR using the MDRD equation, 117 patients presented a value higher or equal than 60 ml/min/1.73 square meters, while 93 had an eGFR below 60 ml/min/1.73 square meters. The median value of NYHA class was 3 in both groups (SD = 1.03; 0.96) and there was no statistical significance (p = 0.13) between them. By comparison, estimation using the CKD-EPI equation, indicated a statistically significant difference (p = 0.03), 109 patients presented higher than 60 ml/min/1.73 square meters and 101 patients were below this cut off value even though the median NYHA class was 3 as well (SD = 1.04; 0.94).

Conclusions:
These results reinforce the well-known superiority in the accuracy of the CKD-EPI equation. But, in terms of the influence of renal dysfunction severity on the heart failure severeness, our results suggest that decreasing in the eGFR is not correlated with the progression of the heart failure in AF patients. However, given the severity of complications and importance of proper treatment in atrial fibrillation, the development of an estimation equation that relates to the presence of atrial fibrillation should be considered.
SURROGATE CARDIOVASCULAR OUTCOMES WITH SODIUM-GLUCOSE CO-TRANSPORTER-2 INHIBITORS IN WOMEN: AN UPDATED META-ANALYSIS
Authors: Patoulias Dimitrios , Katsimardou Alexandra , Imprialos Konstantinos , Stavropoulos Konstantinos , Toumpourleka Maria , Koutsampasopoulos Konstantinos , Tegou Zoi , Mavridou Maria , Siskos Fotios , Papadopoulos Christodoulos , Doumas Michael 
Published: April 2021

Objective:
Women with type 2 diabetes mellitus (T2DM) experience an increased risk for cardiovascular disease development compared to men. However, they are usually underrepresented in clinical trials assessing treatment strategies to ameliorate excess cardiovascular risk. Previous meta-analyses of cardiovascular outcome trials (CVOTs) demonstrated that sodium-glucose co-transporter-2 (SGLT-2) inhibitors do not decrease the risk for major adverse cardiovascular events (MACEs) among women participants.

Design and method:
We searched PubMed from its inception to 2 October 2020. We sought to determine the effect of SGLT-2 inhibitors on cardiovascular outcomes of interest in women utilizing data from the “hallmark” CVOTs and the recently published trials enrolling patients with heart failure with reduced ejection fraction (HFrEF), extracting data concerning female patients, as reported across the selected studies. We set as primary efficacy outcome the composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke and as secondary efficacy outcome the composite of hospitalization for heart failure (HF) worsening and cardiovascular death.

Results:
SGLT-2 inhibitor treatment resulted in a non-significant decrease in the risk for MACEs (RR = 0.91, 95% CI; 0.80 to 1.04, I2 = 0%). Regarding the secondary efficacy outcome, it was shown that SGLT-2 inhibitor treatment led to a significant decrease equal to 21% (RR = 0.79, 95% CI; 0.69 to 0.91, I2 = 8%), which was primarily driven by the results observed in the dedicated HFrEF trials. More specifically, we demonstrated that SGLT-2 inhibitor treatment did not induce a significant decrease in the risk for heart failure hospitalization or cardiovascular death across the cardiovascular outcome trials (RR = 0.87, 95% CI; 0.73 to 1.03, I2 = 0%), while it produced a significant result when we pooled the data from the DAPA-HF and the EMPEROR-Reduced trials (RR = 0.71, 95% CI; 0.58 to 0.88, I2 = 15%).

Conclusions:
SGLT-2 inhibitors do not confer significant decrease in the risk for MACEs among women; however, they provide significant results in terms of reduction in the risk for cardiovascular death or hospitalization for heart failure in the HFrEF population. Better representation of women in future trials will provide further insights.
CIRCULATING CERAMIDE AS A POTENTIAL BIOMARKER FOR ISOLATED NOCTURNAL HYPERTENSION
Authors: Zhang Dongyan , Guo Qianhui , Cheng Yibang , Wang Jiguang , Li Yan 
Published: April 2021

Objective:
Isolated nocturnal hypertension (INH) is a subtype of hypertension characterized as an elevated blood pressure (BP) at nighttime only. To identify potential new biomarkers related with INH, we compared serum metabolite profiles between INH and normotensive controls.

Design and method:
Twenty-four-hour ambulatory BP monitoring was performed with Mobil-O-graph (IEM, Germany) monitors in untreated outpatients. INH was defined as a nocturnal BP greater or equal to 120/70 mmHg and daytime BP less than 135/85 mmHg at both two visits within a month. Age-sex matched normotensives (NT) were included as controls. We applied untargeted liquid chromatography tandem mass spectrometry (LC-MS) to detect serum metabolites. Multiple algorithms were first run in a training set (40 INH and 40 NT) and then in a test set (22 INH and 19 NT) to select and verify potential biomarkers. We computed student's P-values corrected by multiple comparison and VIP (Variable Importance in the Projection) score. Based on the results of untargeted LC-MS, we quantified 8 circulating sphingolipids, including sphingomyelin (SM) (d18:1/16:0), SM (d18:1/18:0), SM (d18:1/24:1), ceramide (Cer) (d18:1/16:0), Cer (d18:1/18:0), Cer (d18:1/24:1), sphingosine and sphingosine-1-phosphate in the test set by a targeted LC-MS method.

Results:
Orthogonal partial least squares-discriminant analysis (OPLS-DA) demonstrated a clear separation of metabolite profiles of INH patients from NT controls (R2 = 0.747, Q2 = 0.672). Cer (d18:1/16:0) had significant association with INH (odds ratio (OR) = 0.290 per SD, 95% confidence interval (CI), 0.125–0.715, P trend = 0.0027). The ceramide score, calculated as a sum of concentrations of the three ceramides, was associated with a lower risk of INH across extreme quartiles (OR = 0.592, 95% CI, 0.400–0.875, P trend = 0.0085). Moreover, Cer (18:1/16:0) significantly improved the diagnostic prediction of INH (P = 0.04).

Conclusions:
Our study illustrated a novel association between plasma ceramide concentration and INH. More research on ceramides in hypertensive pathobiology might be warranted.
CORRELATION OF NT-PROBNP CONCENTRATION WITH THE CONDITION OF BLOOD MICROCIRCULATION IN PATIENTS WITH CONTROLLED AND UNCONTROLLED ARTERIAL HYPERTENSION
Authors: Podshibiakina Elizaveta , Nebieridze Natiya , Safronova Tatyana , Podzolkov Valerij 
Published: April 2021

Objective:
To study the relation between NT-proBNP and the condition of blood microcirculation in patients with controlled (CAH) and uncontrolled (UAH) course of hypertension.

Design and method:
A cross-sectional study included 27 patients with essential hypertension: group I (CAH) - 12 patients, group II (UAH) - 15. The average age was 59.6 ± 9.5 years, the average duration of hypertension was 13.6 ± 10.2 years, the function of the left ventricle was normal. The criteria for inclusion in group I were the constant use of correct therapy for hypertension, 24-hour BPM indicators within the reference values, the absence of hypertensive crises over the last year. All patients underwent measurement of NT-proBNP concentration, laser Doppler flowmetry of microvasculature vessels.

Results:
The concentration of NT-proBNP exceeded normal values in 4 patients (14.8%) in group I and in 1 patient (3.7%) in II, in group I this indicator was lower - 27.6 [21.4; 47.9] pg/ml than in group II - 45.15 [36.2; 102.0] pg/ml (p < 0.05).
According to the 24-BPM, the average daily (119.5 [112.0; 123.5]) and nocturnal (105.0 [99.5; 108.0]) SBP, as well as daily DBP (76 [64; 83]) in group I was lower than the similar indicators (136.0 [125.0; 164.0]), (122.5 [107.0; 144.0]) and (81 [75; 90]) in group II (p < 0.05). During the study of the microvasculature state, there was found an improvement in the microcirculation index (MI) in group I (30.55 [26.64; 34.37] compared to group II (22.19 [18.25; 26.05] (p < 0.05).
During the correlation analysis, the concentration of NT-proBNP in group I was correlated with the coefficient of variation of MI (r = 0.6; p < 0.05), the indicator of blood shunt (r = 0.59; p < 0.05), the maximum amplitude of the pulse factor regulating microcirculation (r = 0.71; p < 0.05), the contribution of the pulse factor to the total perfusion of tissues (r = 0.68; p < 0.05). In group II, the concentration of NT-proBNP had correlation with pulse BP (r = 0.54; p < 0.05).

Conclusions:
In patients with CAH there was detected a lower concentration of NT-proBNP along with lower values of SBP and DBP and better indicators of the state of blood microcirculation as compared with patients with UAH.
LOWER CIRCULATING MIR-191-5P AND LET-7G-5P ARE INDEPENDENT BIOMARKERS OF RENAL INJURY
Authors: Paradis Pierre , Berillo Olga , Huo Ku -Geng , Fraulob-Aquino Julio C. , Richer Chantal , Briet Marie , Boutouyrie Pierre , Lipman Mark L. , Sinnett Daniel , Schiffrin Ernesto L. 
Published: April 2021

Objective:
Hypertension is associated with subclinical target organ damage including cardiac, vascular and kidney injury. Circulating microRNAs have been investigated as biomarkers of cardiovascular disease, but few studies have examined them as target organ damage biomarkers in hypertension. We aimed to identify circulating microRNAs that could serve as biomarkers of hypertension-induced target organ damage using an unbiased approach.

Design and method:
Normotensive subject, hypertensive patients (HTN) and patients with HTN associated with at least 2 other features of the metabolic syndrome (MetS) or with chronic kidney disease (CKD) grades 3–4 were studied (n = 15–16). Blood pressure was determined by automated office measurement (AOBP). Blood and urine were collected for determination of blood cell count, blood biochemistry and urinalysis. Platelet-free plasma (6 mL) was isolated from blood collected on EDTA, and RNA extracted for small RNA deep sequencing using Illumina HiSeq-2500. Differentially expressed (DE) genes were identified with a threshold of false discovery rate < 0.1. The most abundant DE miRNAs were confirmed by reverse transcription-quantitative PCR (RT-qPCR). Right common carotid artery remodeling and stiffness were assessed by ultrasound and aorta stiffness by carotid to femoral pulse wave velocity.

Results:
We found 4 up-regulated and 4 down-regulated miRNAs uniquely associated with the HTN group, 1 up-regulated uniquely associated with the MetS group, 1 up-regulated and 12 down-regulated miRNAs uniquely associated with the CKD group and 8 were found similarly DE in different groups (P < 0.01 and q < 0.1). Two down-regulated miRNAs, let-7g-5p and miR-191–5p of 11, the most abundant DE miRNAs, were validated by RT-qPCR. Correlation analysis revealed that let-7g-5p was associated with large vessel stiffening, miR-191–5p with diabetes, and both microRNAs with estimated glomerular filtration rate (eGFR) and inflammatory markers. Using let-7g-5p and miR-191–5p and parameters that correlated with eGFR as candidate variables, stepwise multiple linear regression generated a model showing that let-7g-5p, miR-191–5p and urinary albumin/creatinine ratio predicted eGFR with an adjusted R2 of 0.40 (P = 1.1e-5).

Conclusions:
Circulating let-7g-5p and miR-191–5p were identified as independent biomarkers of chronic kidney disease among patients with hypertension, which could have pathophysiological and therapeutic implications.
INFLAMMATORY MARKERS AND REFRACTORY HYPERTENSION
Authors: Alves Hugo Farah Affonso , Santo Bruno Dussoni Moreira Dos , Vallap João Gabriel Rega Do Nascimento , Silva João Gabriel Bezerra Da , Gonçalves Larissa De Oliveira , Kimura Lucca Hiroshi De Sá , Nolasco Vitor De Melo , Carl Fernanda Oliveira De Carvalho , Cortez Arthur Fernandes , Chedier Bernardo , Muxfeldt Elizabeth 
Published: April 2021

Objective:
Introduction: Refractory hypertension (RfHT) is defined as an uncontrolled blood pressure (BP) despite the use of 5 or more antihypertensives, including spironolactone and it is considered an extreme phenotype of resistant hypertension (RHT). High BP levels lead to RAAS stimulation, sympathetic hyperactivity and endothelial dysfunction with consequent production of pro-inflammatory cytokines.

Objective:
To evaluate the relationship between inflammatory markers and refractory hypertension in a large cohort of patients with RHT.

Design and method:
A cross-sectional study that evaluated 423 resistant hypertensives (30.5% male, mean age 63.9 ± 10.8 years), of which 62 (14.6%) diagnosed as RfHT. All of them were submitted to the dosage of inflammatory markers: TNF-alpha, MCP-1, E-selectin and PAI-1. Socio-demographic and anthropometric characteristics and cardiovascular risk factors (CV) were recorded. Variance analysis compared serum levels of the 4 inflammatory markers and bivariate analysis compared patients with RHT versus RfHT.

Results:
Patients with RfHT are younger, with higher prevalence of smoking, higher levels of albuminuria and higher prevalence of chronic cerebrovascular and renal disease stages 4 and 5. PAI-1 values (126 [108–162] vs 118 [94–153] were higher in those with RfHT, although they did not reach statistical significance. The other biomarkers evaluated showed no association with the diagnosis of RfHT.

Conclusions:
Among inflammatory markers, PAI-1 was the one that correlated most strongly with refractory hypertension. Our study is the first one to demonstrate PAI-1 association with treatment refractoriness
BIOMARKERS OF GLOMERULAR FILTRATION, BUT NOT TUBULAR DYSFUNCTION, ARE ASSOCIATED WITH UNCONTROLLED HYPERTENSION IN THE GENERAL POPULATION. THE TROMSØ STUDY
Authors: Brobak Karl Marius , Melsom Toralf , Norvik Jon Viljar , Andreassen Runa Marie , Solbu Marit Dahl 
Published: April 2021

Objective:
Uncontrolled hypertension (UHT) and chronic kidney disease (CKD) are common and frequently overlapping entities with considerable health consequences. Little is known about the relationship between low-grade kidney dysfunction and UHT. The importance of tubular in contrast to glomerular dysfunction in cardiovascular disease and hypertension has been recognised, but tubular biomarkers have not been examined in population-based studies of UHT. We assessed the associations between biomarkers of low-grade kidney dysfunction and UHT in treated hypertensive individuals from a general population.

Design and method:
In a cross-sectional design, we included all participants of the Tromsø Study 2007–08, second visit, who reported the use of two ore more blood pressure (BP) lowering drugs. The cohort was dichotomised into controlled hypertension or UHT; UHT was defined as systolic BP >=140 mmHg and/or diastolic BP >=90 mmHg. We used logistic regression to examine the associations between cardiovascular risk factors and UHT. In multivariable models we added estimated glomerular filtration rate (eGFR), urate, two urinary biomarkers of glomerular dysfunction (albumin-creatinine ratio [U-ACR] and orosomucoid-creatinine ratio [U-OCR]) and one biomarker of tubular dysfunction (N-acetyl-beta -D-glucosaminidase -creatinine ratio [U-NAG-Cr]).

Results:
Of the 7308 participants, 1189 persons (mean age 68.0 [8.9] years), fulfilled the inclusion criterion. Among these, 65% had UHT. Subjects with UHT were older and more frequently non-smokers than subjects with controlled hypertension. They had lower eGFR and higher U-ACR and U-OCR, whereas the level of U-NAG-Cr was similar between the groups. In multivariable analyses, higher U-OCR was associated with UHT (OR 1.17; 95% CI 1.02, 1.34 per log unit), whereas U-NAG-Cr was not. U-ACR was significantly associated UHT in models that did not include U-OCR (OR 1.14; 95% CI 1.03, 1.25 per log unit ACR).

Conclusions:
Although tubulointerstitial function is important in BP regulation, and tubulointerstitial damage appears early in CKD, we found no independent association between U-NAG-Cr and UHT. However, biomarkers of glomerular dysfunction, including U-ACR and U-OCR, were independently associated with UHT in treated subjects from the general population. The cross-sectional design limits conclusions about cause and effect, and prospective studies should be undertaken.
VALIDATION OF THE VITA-D1 NONINVASIVE CONTINUOUS BLOOD PRESSURE MONITOR WITH PHOTOPLETHYSMOGRAPHY-ONLY TECHNOLOGY FOR SELF-MEASUREMENT AND CLINIC USE
Authors: Ang Jianning Zh , Tong Xinzhu , Qiu Yumin , Tao Jun 
Published: April 2021

Objective:
Hypertension is still a prevalent health burden without adequate population awareness. As a diagnostic footstone and prognostic indicator, it is of great importance to precisely measure blood pressure (BP). The referenced methods to date for BP measurements are based on inflated cuff. However, stress may contribute to unanticipated BP increasements. Hence, conventional methods limit the efficiency of BP management. A promising BP measuring device with no cuff inflation is clinic practical. Yet, no robust devices with beat-to-beat photoplethysmography (PPG)-only technique have been validated.

Design and method:
Participants were recruited among out- and inpatients at the Department of Hypertension and Vascular Disease, from May 2019 to November 2019. Exclusive criteria mainly included age below 25 years old, pregnancy, arrythmia and poor quality Korotkoff sounds. Before initiation, an entrance BP measurement based on calibrated mercury sphygmomanometer was needed for each participant for test device calibration. The validation procedure was prospectively conducted following the European Society of Hypertension International Protocol (ESH-IP) revision 2010 in adults.

Results:
A total of 48 participants were screened and final 33 were enrolled (10 females, mean age 52.1 ± 11.3 years). 99 pairs of comparisons were obtained from 33 enrollees. The number of measurements within a difference range of up to 5 mmHg were 80 for systolic blood pressure (SBP) and 94 for diastolic blood pressure (DBP). All of the 99 SBP and DBP recordings were in a difference range of up to 15 mmHg. Mean observer-test device differences were −1.1 ± 4.2 mmHg for SBP and −1.3 ± 3.0 mmHg for DBP. Meanwhile, 28 and 32 enrollees had at least 2 out of 3 device-observers differences no more than 5 mmHg for SBP and DBP, respectively.

Conclusions:
The VITA-D1 passed the validation criteria according to the ESH-IP revision 2010 and may be recommended for clinical or self BP monitoring. Being innovative for its cuffless and user-friendly design, VITA-D1 is a promising device for reliable, convenient, and comfortable BP measurements.
COMPARISON OF BLOOD PRESSURE PARAMETERS WITH LEFT VENTRICULAR MASS IN YOUNGER MEN WITH GRADE 1 HYPERTENSION
Authors: Williams Bryan , Lacy Peter , Jedrzejewski Dawid , Mcfarlane Ewan 
Published: April 2021

Objective:
Non-invasive measurement of central aortic systolic pressure (CASP) has been claimed to confer advantage over conventional clinic blood pressure (BP) in predicting cardiovascular risk, particularly in younger patients where amplification is variable. This study aimed to compare relationships between clinic BP, CASP and ambulatory BP (ABPM) with left ventricular (LV) mass in younger men with grade 1 hypertension and low cardiovascular risk.

Design and method:
155 men aged < 55 years with grade 1 hypertension confirmed by ABPM, underwent a cardiac magnetic resonance imaging (cMRI) scan. BP was assessed by clinic and 24-hour ABPM. CASP was evaluated using a high fidelity tonometer (BProâ) to capture radial artery waveforms calibrated to clinic systolic and diastolic or mean and diastolic (fixed form factor) and processed using a n-point moving average. LV mass indexed to body surface area (LVMI), was assessed by manual segmentation of the LV image stack acquired using a 1.5T cMRI scanner. Linear regression and receiver operator curve (ROC) analysis was used to evaluate the relationship between LVMI and BP measurement mode and whether relationships between CASP and LVMI were influenced by calibration mode.

Results:
In 155 men recruited from the general community (mean age 45 years) with grade 1 hypertension and low cardiovascular risk (10-year QRISKâ 5.4%), increasing BP was positively associated with LVMI. Relationships with LVMI was similar between BP measurement modes (clinic systolic BP r = 0.27, p < 0.001, 24-hour ABPM systolic BP r = 0.28 p < 0.001). The relationship of LVMI with CASP differed little for pressure waves calibrated using systolic and diastolic BP (r = 0.25, p < 0.001) or mean and diastolic BP at a form factor of 0.33 (r = 0.30, p < 0.001). ROC analysis for high LV mass detection (highest 20%), showed similar predictive value between BP modes.

Conclusions:
Carefully measured clinic BP confirmed by ABPM, is as good at predicting LVMI as 24-hour ABPM or CASP, irrespective of the calibration mode in younger men with grade 1 hypertension where amplification is variable. Furthermore recalibration of radial waveforms to mean and diastolic BP at a commonly used form factor (0.33) does not significantly improve this relationship.