bluuebunny/crossref_metadata_2025_split huggingface dataset:
INFLUENCE OF ANTIHYPERTENSIVE MEDICATION STATUS ON THE BLOOD PRESSURE RESPONSES TO DYNAMIC EXERCISE IN HYPERTENSIVE INDIVIDUALS
Authors: Ramirez-Jimenez Miguel , Morales-Palomo Felix , Moreno-Cabañas Alfonso , Alvarez-Jimenez Laura , Ortega Juan F. , Mora-Rodriguez Ricardo 
Published: April 2021

Objective:
To investigate if the blood pressure (BP) response to a maximal graded exercise test (GXT) is influenced by antihypertensive medication (AHM) in monotherapy or in combination.

Design and method:
Thirty-one hypertensive individuals with obesity under AHM treatment targeting the renin-angiotensin-aldosterone system (RAAS) were divided into 3 groups depending on the number of AHM taken: monotherapy (MONO, n = 15), two drugs (DUAL, n = 8) or 3 drugs (TRIPLE, n = 8). By using a randomized, double-blind, placebo-controlled, crossover design, participants completed two trials (i.e. AHM vs PLAC). In each trial, 24-h ambulatory blood pressure (ABP), plasma renin activity (PRA), aldosterone concentration and the BP responses to a GXT were measured and compared among groups.

Results:
In AHM trials, 24-h ABP was significantly lower (127 ± 12 vs 134 ± 10 mmHg, P < 0.001) and PRA higher (4.0 ± 2.7 vs 1.9 ± 1.8 ng/mL/h, P < 0.001) in comparison to PLAC, without differences between groups in any variable (P > 0.05). There was not any group nor trial effect on plasma aldosterone concentration (P > 0.05). During incremental exercise, there were no differences between trials nor among groups in the BP response to incremental exercise, reaching similar peak systolic BP (211 ± 25 vs 206 ± 25 mmHg in AHM and PLAC, respectively, P = 0.118). Regarding the heart rate (HR) response to exercise, the TRIPLE group showed a higher HR at submaximal intensities in AHM vs PLAC (+7 ± 4 bpm, P < 0.005).

Conclusions:
Antihypertensive medication reduces ABP but does not have any effect on systolic BP during exercise, independently of the number of drugs taken. Our data suggest that in chronically treated hypertensives AHM does not reduce the BP response to exercise.
MMP-2 INHIBITION ATTENUATES HYPERTENSIVE ECCENTRIC CARDIAC HYPERTROPHY AND DYSFUNCTION BY PRESERVING TROPONIN I AND DYSTROPHIN
Authors: Parente Juliana Montenegro , de Mello Marcela Maria Blascke , da Silva Pedro Henrique Leite , Omoto Ana Carolina Mieko , Pernomian Laena , de Oliveira Isadora Sousa , Mahmud Zabed , Fazan Rubens , Braga Eliane Candiani Arantes , Schulz Richard , de Castro Michele Mazzaron 
Published: April 2021

Objective:
To verify wether increased matrix metalloproteinase (MMP)-2 activity contributes to the proteolysis of troponin I and dystrophin in the left ventricle (LV) of two kidney-one clip (2K1C) rats thus favoring the transition from concentric (C-LVH) to eccentric hypertrophy (E-LVH) and cardiac dysfunction.

Design and method:
Male 7-week old Wistar rats were sham or 2K1C operated and treated with water or doxycycline (MMP inhibitor, 15 mg/kg/day) by gavage from the tenth to the sixteenth week post-surgery. To establish this aim, tail-cuff plethysmography, echocardiogram, morphological analysis (collagen deposition and cardio myocyte hypertrophy assay), gelatin and in situ zymography, confocal microscopy of MMP-2 and troponin I, troponin I western blotting and mass spectrometry, and dystrophin in silico analysis and immunofluorescence were performed. Results were analyzed by two-way ANOVA or unpaired t test (Ethics Committee approval number: 023/2015-1).

Results:
All 2K1C rats had increased systolic blood pressure when compared to controls (p < 0.05) and doxycycline did not decrease it (p > 0.05). About 25% of 2K1C rats had E-LVH followed by reduced ejection fraction and fractional shortening (p < 0.05). The remaining had C-LVH with preserved cardiac function (p < 0.05). Doxycycline prevented the transition from C-LVH to E-LVH. Both C-LVH and E-LVH rats had cardio myocyte hypertrophy (p < 0.05) and doxycycline reverted it (p < 0.05). E-LVH was the only group who had more collagen deposition in the LV (p < 0.05). MMP-2 activity increased in C- and E-LVH hearts when compared to controls (p < 0.05) and doxycycline inhibited it (p < 0.05). MMP-2 and troponin I co-localize in the LV of control rats (p < 0.05). This was associated with an increase in troponin I cleavage products in E-LVH when compared to C-LVH (p < 0.05) confirmed by western blotting and mass spectrometry. Moreover, about ten putative MMP-2 cleavage sites in rat dystrophin were found and, in fact, a decline in dystrophin levels was observed in E-LVH when compared to controls (p < 0.05) which was prevented by doxycycline (p < 0.05).

Conclusions:
Hypertension causes increased cardiac MMP-2 activity which reduces both troponin I and dystrophin levels and contributes to the transition from C-LVH to E-LVH.
CARBOXYLATED OSTEOCALCIN LEVELS CORRELATE WITH EARLY CHANGE OF ARTERIAL STIFFNESS PARAMETERS IN PATIENTS WITH TYPE 2 DIABETES MELLITUS
Authors: Marinova Elena , Dimova-Mileva Maria , Gancheva Silviya , Boyadzhieva Mila , Kanazirev Branimir 
Published: April 2021

Objective:
Osteocalcin (OC) is a bone derived protein with a recently discovered hormonal nature with a putative target organ the arterial wall. Under pathological conditions, OC synthesized locally by vascular smooth muscle cells. Arterial stiffness measurement is a modern method for diagnosing subclinical atherosclerosis. Of particular importance is to find a biomarker for early vascular damage in patients with Type 2 diabetes (T2DM).

Aim:
To evaluate the correlation of carboxylated (cOC) and uncarboxylated (ucOC) osteocalcin levels with parameters of arterial stiffness (AS) in patients with T2DM without cardio-vascular diseases.

Design and method:
46 patients with T2DM (mean age 58 ± 7.6 men 45.6%) and 18 healthy age- and sex-matched controls were included in the study and examined for cOC and ucOC with ELISA kits (Takara Bio, Japan). One-point Echo-tacking measuring by Aloka Hitachi were performed on the common carotid artery (CA) with measuring Pulse Wave Velocity (PWV), Beta-stiffness index (BSI) and Modulus of elasticity (Ep).

Results:
We found significant correlations of cOC with the BSI (r = 0.31; p = 0.03) and the Ep (r = 0.29; p = 0.05), and lack of correlation with PWV (r = 0.23; p = 0.12). After adjusting confounding factors such as blood pressure, waist circumference, cOC significant and independently correlated with BSI (B = -0.34; P = 0.04). No correlations were found for ucOC. We additionally established correlations of cOC with HDL (r = 0.3; p = 0.01), BMI (r = -0.32; p = 0.007) and waist (r = -0.4; p = 0.0009). cOC were lower in patients with T2DM 7.84 ± 2.41 ng/ml than in controls 10.05 ± 4.57 ng/ml (p = 0.01). unOC levels were lower in patients with T2DM without significance 3.81 ± 5.12 ng/ml vs. 4.37 ± 3.0 ng/ml (p = 0.08).

Conclusions:
Our patients with T2DM had lower unOC and cOC levels. For cOC were observed a significant correlation with the arterial stiffness parameters BSI and Ep and therefore with subclinical atherosclerosis. Osteocalcin is involved in the process of vascular calcification and can be considered as a potential biomarker for vascular damage.
PULSE PRESSURE SIGNIFICANTLY AND INDEPENDENTLY CORRELATES WITH CAROTID PULSE WAVE VELOCITY AND BETA-STIFFNESS INDEX IN PATIENTS WITH TYPE 2 DIABETES MELLITUS
Authors: Marinova Elena , Dimova-Mileva Maria , Kanazirev Branimir 
Published: April 2021

Objective:
Introduction: Pulse wave velocity (PWV) and beta-stiffness index (BSI) are the most popular echo-tracking parameters indicating increased carotid stiffness. Pulse pressure (PP) values turns out to be higher in patients with increased indices of arterial stiffness and is an independent predictor of cardiovascular disease and mortality. This is of greater importance for patients with type 2 Diabetes Mellitus (T2DM).

Aim:
To find out correlation between the pulse pressure and carotid stiffness indices.

Design and method:
100 patients with T2DM without overt cardio-vascular diseases and 30 healthy age and sex matched controls were included in the study. All participants underwent carotid examination of PWV and BSI, by echo-tracking method with Aloka Hitachi Prosound alfa-7. Patients with uncontrolled blood pressure and history of CV diseases were excluded from the study.

Results:
Pulse pressure significantly correlated with left carotid artery PWV (r = 0.43; p = 0.0001) and BSI (r = 0.44; p = 0.001) and right carotid artery PWV (r = 0.38; p = 0.001), BSI (r = 0.39; p = 0.001). Multivariate regression analysis with independent variable PWV, revealed that PP remained a significant and independent determinant (B = 5.78; p < 0.0001), similar to systolic blood pressure (B = 2.97; p = 0.003).

Conclusions:
PP is among the most important independent determinants associated with increased carotid stiffness in patients with T2DM without cardiovascular complications and with well controlled blood pressure. PP may serve as an early marker of increased cardiovascular risk in patients with T2DM.
PREDIALYSIS SYSTOLIC PRESSURE AND MORTALITY
Authors: Hajri Malika , Mannai Khouloud , Jbeli Hela , Khedher Rania , Smaoui Wided , Krid Madiha , Ghabi Hiba , Mami Insaf , Kaab Badr , Fatma Lilia Ben , Raies Lamia , Beji Soumaya , Zouaghi Mohamed Karim 
Published: April 2021

Objective:
This study aimed to verify the impact of predialysis systolic pressure (PDSP) on patients’ mortality.

Design and method:
We reviewed files of incident patients, in one reference center of hemodialysis, between January 2009 and June 2010. Arterial pressure was measured by sphygmomanometer before initiating the patient's first dialysis session. We considered: as “high PDSP” a SP equals or over 180 mmHg; as “low PDSP” a PS equals or less than 100 mmHg. Univariate and multivariate analysis were performed to study PDSP association with absolute mortality at five years. Odds ratio (OR) was subject to a 95% confidence interval. We used Kaplan Meier method for survival curves.

Results:
One hundred eleven patients were included. Sex ratio was 1.7 M/W. At dialysis initiation: mean age was 55 ± 14.9 years. Sixty nine patients (62%) were hypertensive; all of them were under antihypertensive agents. MAP, SP and DP were respectively 98.8 ± 16.3 mmHg, 139.4 ± 25.4 mmHg and 79.1 ± 14 mmHg. Mean urinary output was 1156 ± 542 ml/day and initial serum creatinine 887 ± 271 μmol/l.
In univariate analysis, absolute mortality at five years was associated with low PDSP (p = 0.001, OR = 4.8). This association was pronounced among orderlies (p = 0.001) and diabetic patients (p = 0.001). High PDSP was also associated with absolute mortality at five years (p = 0.03; OR = 1.67). In multivariate study, neither low nor high PDSP were associated to mortality.
Survival was decreased for patients with low PDSP (log-rank p = 0.001) (Figure 1) and high PDSP (log-rank p = 0.03) (Figure 2).

Conclusions:
These results suggest the presence of a “U” curve relationship between PDSP and mortality. Further studies, with larger populations, are needed to determine the potential use of low PDSP as a mortality risk factor.
COMPARISON OF PARTIAL SEATED SALINE INFUSION TEST AND SEATED SALINE INFUSION TEST FOR THE DIAGNOSIS OF PRIMARY ALDOSTERONISM
Authors: Li Keli , Qin Luo , Li Nanfang 
Published: April 2021

Objective:
Seated saline infusion test (SSIT) has proved to be much more sensitive to recumbent saline infusion test (RSIT) in confirmation of primary aldosteronism (PA), highly specific, much cheaper and less complicated than fludrocortisone suppression testing (FST). However, SSIT requires the subjects to keep sitting position for 4.5 h, which is not comfortable for all patients, especially for the elderly. The purpose of this study was to explore the diagnostic consistency between more free and comfortable partial seated saline infusion test (PSSIT) and SSIT.

Design and method:
The current study involved 89 hypertensive patients who had positive results in the screening test and underwent both PSSIT and SSST for the confirmation of PA. For SSIT, patients remained sitting posture for 4.5 hours (0.5 h before the basal measurement of PAC at 9am local time and during the whole process of saline infusion). For PSSIT, patients remained sitting posture for 0.5 h before the measurement of basal PAC and 0.5 h before the completion of saline infusion, for the rest of the time in the process of infusion, subjects were permitted to adopted more free and comfortable posture. Two liters of 0.9% NaCl was administered intravenously over 4 h during SSIT or PSSIT. The diagnostic consistency between PSSIT and SSIT was analyzed.

Results:
The plasma aldosterone concentration (PAC) after PSSIT was significantly lower than that of SSIT (6.06 vs 7.07ng/dL, P < 0.001). Eight patients (9%) who had post-PSSIT PAC less than 10ng/dl had post-SSIT PAC greater than 10ng/dl. The two saline infusion tests had lower correlation coefficient (r = 0.246, P = 0.02) and intra group correlation coefficient (ICC = 0.194, P = 0.015). ROC analysis predicted optimal cut-off aldosterone levels of 5.385 ng/dl for PSSIT with high sensitivity (80%) but low specificity (50%) when use 6 ng/dl for SSIT according to the Endocrine Society Guideline.

Conclusions:
The optimal cut-off values of PAC for PSSIT were lower than that of SSIT with high sensitivity but low specificity, which need to be noted in clinical application.
HYPERTENSION IS A RISK FACTOR FOR ACUTE KIDNEY INJURY AND A PREDICTOR OF MORTALITY IN HOSPITALIZED PATIENTS WITH COVID-19
Authors: Khruleva Yulia , Mubayazvamba Tapiwa , Troitskaya Elena , Efremovtseva Marina , Kobalava Zhanna 
Published: April 2021

Objective:
Initial reports indicate a high incidence of acute kidney injury(AKI) in the novel coronavirus infection (COVID-19). Hypertension(HTN) frequently coexists with COVID-19 and may be a possible risk factor for AKI. The aim of the study was to investigate the contribution of HTN for the AKI development in patients hospitalized with COVID-19.

Design and method:
A retrospective analysis of the register of patients with COVID-19 was performed. COVID-19 was defined as the laboratory-confirmed infection and/or presence of the typical CT picture. AKI definition was based on KDIGO criteria. P value < 0.05 was considered statistically significant.

Results:
The register included 721 patients(49.6% male, age 64 ± 15.7 years, HTN in 66%, controlled in 80%, obesity in 50.8%, diabetes mellitus(DM) in 24.2%, chronic kidney disease(CKD) in 6%). The median length of stay was 11[9;15] days, in the ICU – 4[2;9] days. 18.9% of patients died. Mean blood pressure at admission was 130 ± 17/80 ± 11 mmHg in the hypertensive group. 40.3% of patients received angiotensin-converting enzyme inhibitors(ACEi) or angiotensin II-receptors blockers(ARBs) regularly before admission. In 79% therapy was continued, in 21% - withdrawn. The AKI incidence in the register was 27.2%, in hypertensive patients– 30.1%. ACEi /ARBs intake wasn‘t associated with AKI. Hypertensive patients compared to normotensives were older (69 ± 12vs50 ± 15, p < 0.0001), more often had DM (31.7%vs10%, p < 0.0001), CKD (8%vs2%, p = 0.01). History of HTN was associated with higher mortality (23.6%vs10.7%, p = 0.001). HTN incidence was higher in patients with AKI (80%vs61%, p < 0.0001) and HTN was a risk factor for AKI development (OR 2.45, 95% CI 1.49–4.13, p = 0.0002). Hypertensive patients with AKI compared to patients without AKI had longer duration of hospitalization (13 ± 7vs12 ± 6 days, p = 0.003), were more likely to be treated with mechanical ventilation (50%vs13%, p < 0.0001), more often were in the ICU (46.5%vs16.4%, p < 0.001 and had higher in-hospital mortality (48%vs9.7%, respectively, p < 0.0001).The AKI development and history of HTN were predictors of mortality: OR 8.90 (95%CI 5.7–13.78, p < 0.0001) and OR 2.58 (95%CI 1.46–4.75, p = 0.0006), respectively.

Conclusions:
AKI is common among patients hospitalized with COVID-19 and is associated with the presence of HTN. HTN and AKI development are the significant predictors of in-hospital mortality in this population.
THE ASSOCIATION BETWEEN ARTERIAL STIFFNESS MARKERS AND THE SEVERITY OF CORONARY ARTERY DISEASE AS ASSESSED BY SYNTAX II SCORE IN HYPERTENSIVE PATIENTS WITH INSULIN RESISTANCE
Authors: Khalil Wael 
Published: April 2021

Objective:
The Endothelial dysfunction and the arterial stiffness are the signs of cardiovascular diseases especially in the hypertensive patients with insulin resistance. The endothelial dysfunction were assessed by the brachial flow mediated dilatation. The arterial stiffness markers which are expected to be early increased in hypertensive patients with insulin resistance were assessed for detection of coronary artery disease. The aim of this study: to detect the association between arterial stiffness markers and the presence of coronary artery disease and the assessment of CAD severity by syntax II score in hypertensive patients with insulin resistance.

Design and method:
A total of 120 hypertensive patients who underwent coronary angiography in catheterization unit from January 2019 to October 2020 by using the (homesostatic model assessment of insulin resistance) were divided into (Group A) sixty patients with insulin resistance and CAD (Group B) sixty patients without insulin resistance and no CAD. The brachial flow mediated dilatation was measured. The Mobil O Graph blood pressure device was used to measure the PWV and Aix at rest and three min after isometric handgrip exercise at 40% of the maximal handgrip power. The inter-arm systolic blood pressure difference from both arms was calculated. The severity of the coronary artery diseases were assessed by the syntax II risk score.

Results:
In our study the predictive value of FMD for the detection of CAD in group A with a cutoff value >0.448 (P < 0.0001), (sensitivity of 88.9% and specificity of 91.8%). After isometric exercise handgrip for 3 min, the Aix was increased significantly in patients with CAD (before 16.7% vs. 3 min after 23.6%, P = 0.001). PWV was increased significantly in patients with CAD (before 11.5 vs. 3 min after 12.2 m/s,P = 0.001). The Inter Arm Blood Pressure Difference more than 10mmHg were associated with a high syntax II risk score compared to the patients with values less than 10 mmHg (p < 0.001).

Conclusions:
FMD and after isometric handgrip exercise (PWV and Aix), are independent predictors for CAD. The Inter Arm Blood Pressure Difference more than 10mmHg was associated with a higher syntax II risk score.
MICROVASCULAR DYSFUNCTION IN NON-DIABETIC HYPERTENSIVE PATIENTS IS RELATED TO DYSLIPIDAEMIA AND GLUCOSE INTOLERANCE: RESULTS FROM THE DOXAZOSIN RAMIPRIL STUDY
Authors: Jekell Andreas , Kahan Thomas 
Published: April 2021

Objective:
Microvascular dysfunction relates to increased cardiovascular risk in type 2 diabetes and in the metabolic syndrome. Disturbances in microvascular function are multifactorial, and both low HDL-cholesterol (HDL) and glucose intolerance are important mediators. However, their importance in relation to microvascular function in non-diabetic hypertension is not well studied.

Design and method:
71 patients with untreated hypertension (mean BP 154/93 mm Hg) without coronary heart disease were included. The subendocardial viability ratio (SEVR) was calculated by pulse wave analysis (SphygmoCor). Skin microvascular function was assessed by laser Doppler fluxmetry and iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP), and by local heating. Glucose tolerance was estimated by the triglyceride (TG) glucose index (TyG, ln [fasting plasma glucose (mg/dL) x triglycerides (mg/dL)/2]), and by the TG/HDL ratio.

Results:
Fasting LDL-cholesterol (LDL), HDL and TG 3.48 ± 0.92, 1.40 ± 0.40 and 0.96 [0.61–1.33] mmol/L, respectively. Mean glucose was 5.40 ± 0.55 mmol/L, TyG 6.74 ± 0.59, and median TG/HDL ratio 0.65 [0.43–1.18]. Ach peak flux (mean 42.4 ± 29.8 PU) related to HDL (r = 0.27, P = 0.025). Peak flux by local heating (85.4 ± 43.7 PU) related to HDL (r = 0.29, P = 0.017) and inversely to the LDL/HDL ratio (r = –0.29, P = 0.019). Ach peak flux was inversely related to log(TG/HDL) ratio (r = –0.29, P = 0.016) and tended to relate to TyG (r = –0.23, P = 0.065), while responses to SNP and local heating did not. SEVR (mean 169 ± 29 %) was inversely related to LDL (r = –0.25; P = 0.041), but not to HDL (r = –0.05; P = 0.69). SEVR did not relate to TyG or to log(TG/HDL) ratio.

Conclusions:
Skin microvascular dysfunction was related to low HDL and to glucose intolerance, whereas coronary microvascular dysfunction was related to increased LDL. Maximum reactive hyperaemia by local heating is a robust method to evaluate skin microvascular function in non-diabetic hypertension. As for patients with type 2 diabetes and the metabolic syndrome, early microvascular dysfunction can be detected in non-diabetic hypertensive patients, and predict cardiovascular risk.
PATIENTS’ PERCEPTIONS ON THE USE OF RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM INHIBITORS DURING THE FIRST WAVE OF THE COVID-19 PANDEMIC
Authors: Ioannidis Antonios , Paraskelidou Maria , Pechlevanis Apostolos , Fragkiskou Afroditi 
Published: April 2021

Objective:
Since the outbreak of the SARS-COV-2 pandemic, concerns have been raised that renin-angiotensin-aldosterone system inhibitors (RAAS-i) may increase the susceptibility to the coronavirus and the likelihood of severe COVID-19 illness. Aim of this study was to assess the patients’ perceptions on the risk or benefit of RAAS-I use in the COVID-19 era.

Design and method:
Patients visiting the emergency (non-COVID) department or the outpatient clinics of a tertiary hospital in Northern Greece were invited to participate by completing a short questionnaire. This observational study was conducted during the first wave of the COVID-19 (April to June 2020) and would restart at an imminent second wave. Analyses included only questionnaires from the first wave (which was apparently well controlled in Greece) and were performed by IBM SPSS Statistics.

Results:
In total 178 patients (94 women, 52.8%) taking angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor type 1 blockers (ARBs) participated (mean age 63.8 ± 10.2 years). About half (97, 54.4%) were taking RAAS-i for hypertension, while the rest for other indications. The vast majority (160, 92.1%) were aware of the issue that some antihypertensive drugs might be harmful (mainly from TV reports), although almost one third (51, 31.9%) were not sure if they were prescribed such drugs. One fifth of the patients had contacted their doctor inquiring if they were taking such drugs and if, in that case, they could replace it. Only three patients altered their therapeutic regimen. Of note, the majority of patients (151, 84.8%) reported that the chances of getting COVID-19 were low or somewhat low, though they feel more susceptible to catch it (128, 65.7%) or that they will have a more severe disease course (136, 76.4%). Disturbingly, none of the patients had been informed of the position of major scientific societies that patients should not stop taking RAAS-i.

Conclusions:
Greek patients appear to be aware of the issue relating the RAAS-i with the COVID-19 pandemic. Nevertheless they seem lacking information from their healthcare providers or from scientific bodies. Further research is warranted to assess whether patient oriented informative campaigns could comfort the concerns.