bluuebunny/crossref_metadata_2025_split huggingface dataset:
PREECLAMPSIA COMPLICATED WITH PULMONARY EDEMA IN NEWLY DIAGNOSED PERIPARTUM DILATED CARDIOMYOPATHY: CASE REPORT
Authors: Mitevska Irena , Stanojevic Verdi , Stojcevski Saso , Bosevski Marijan , Jovanova Silvana , Kostovska Elizabeta Srbinovska 
Published: June 2022

Objective:
Pulmonary edema is one of the most serious complications of preeclampsia that should be ruled out in case of dyspnea in a pregnant woman. The prognosis is generally good, however it can indicate underlying unrecognized dilated cardiomyopathy.

Design and method:
We present a case of 30-year-old woman in 34 weeks of pregnancy was hospitalized at the Gynecology Clinic for preeclampsia.

Results:
This was the third pregnancy without any previous known cardiovascular disease or known hypertension. Cardiology examination was requested which showed conscious, severely dispnoic and tachycardic patient, with lower leg edema and bilateral pulmonary rales indicating acute pulmonary edema. Blood pressure was 170/100 mmHg, heart rate 130 bpm and saturation 89% with oxygen nasal mask. She reported the presence of headache. Patient was treated for three days with Metil dopa, Nifedipine and corticosteroid therapy of baby lung maturation. She received magnesium sulfate, Verapamil and intravenous Furosemide of 120 mg and the time of pulmonary edema. The patient was not in labor. The ultrasound revealed a monofetal pregnancy and amniotic fluid in normal quantity. Laboratory tests showed mild anemia with normal renal and liver function results. D-dimers were 1320 ng/ml. After stabilization of the patient, a C-section was performed, with the extraction of healthy newborn with an APGAR at 10/10th. There were no post-operative complications. There was marked disappearance of dyspnea within 72 hours, and stabilization of blood pressure. Patient was transferred to the cardiology clinic. Echocardiography showed signs of dilated cardiomyopathy with EF 30% and absent valvopathy. She was put on heart failure treatment with ACE inhibitor, beta blocker, MRA antagonist, furosemide, bromocriptine and LMWH. We received significant clinical improvement during the hospitalization. She was discharged after 6 days in NYHA class II.

Conclusions:
Acute pulmonary edema is a rare complication, but leading cause of death in women with pre-eclampsia. Diagnosis of peripartum cardiomyopathy requires heightened awareness among multidisciplinary patient care teams and a high degree of suspicion. Many patients with peripartum cardiomyopathy recover within 3 to 6 months of disease onset, but recovery might occur as late as 48 months postpartum
ARTERIAL STIFFNESS IN PATIENTS WITH HYPERTENSIVE CRISIS
Authors: Jug Juraj , Lang Valerija Bralic , Prkacin Ingrid 
Published: June 2022

Objective:
The aim of this study was to determine if patients with the hypertensive crisis have higher pulse wave velocity compared to the patients with arterial hypertension without it.

Design and method:
In this case-control study which lasted from January 2020 to December 2021, 61 patients (36 males, 25 females) with the hypertensive crisis were analyzed at the Emergency department in Clinical Hospital Merkur, Zagreb. The hypertensive crisis was defined as a rapid increase in systolic blood pressure above 180 and/or diastolic above 120mmHg (SBP range 181–208mmHg). On the other hand, in the control group, we analyzed 45 patients (24 males, 21 females) with confirmed arterial hypertension by a 24h-ambulatory blood pressure monitor (BTL Cardiopoint, SBP > 130/80mmHg or taking antihypertensives) without evidence of hypertensive crisis (SBP range 115–156mmHg) in two family medicine practices. Elementary lab results and pulse wave velocity (by Agedio B900) were checked in all patients. Patients were divided into two additional groups by age (51–60, 42 patients and 61–70 years, 64 patients). Mann-Whitney U test was used for the analysis of non-parametric variables in Statistica v.10.0.

Results:
Patients with hypertensive crisis had a significantly higher heart rate (median 78 vs. 69 bpm, U = 714; p < 0.001), fasting glucose (median 5.5 vs. 6.0 mmol/L, U = 804.5; p < 0.01), body mass index (median 31.0 vs. 27.9 kg/m2, U = 889; p < 0.001), nocturnal SBP drop (median 15.5 vs. 9.8%, U = 386; p < 0.05), and augmentation index (median 42 vs. 19%, U = 686; p < 0.001). In both younger and older group, patients with hypertensive crisis had statistically significantly higher pulse wave velocity (median younger: 9.3 vs. 8.1m/s, U = 65.5; p < 0.001; older: 10.7 vs. 9.0m/s, U = 19; p < 0.001) shown in the Figure 1. In younger group patients with hypertensive crisis have 8.5 times higher chances of having pulse wave velocity above reference value (>8.0m/s; CI = 1.57–46.87, p < 0.001) while in older group that chance was 108 times higher than in controls (reference value >9.5m/s; CI = 13.83–843.33, p < 0.001).

Conclusions:
Patients with hypertensive crisis had statistically higher pulse wave velocity values, heart rate, fasting glucose, body mass index, and nocturnal SBP drop compared to patients with arterial hypertension without crisis.
ANTISENSE OLIGONUCLEOTIDES TARGETING HEPATIC ANGIOTENSINOGEN DOSE-DEPENDENTLY REDUCE ATHEROSCLEROSIS AND LIVER STEATOSIS IN HYPERCHOLESTEROLEMIC MICE
Authors: Ye Dien , Wu Congqing , Cai Lei , Howatt Deborah A. , Liang Ching Ling , Temel Ryan E. , Mullick Adam E. , Danser A.H. Jan , Daugherty Alan , Lu Hong S. 
Published: June 2022

Objective:
Liver-derived angiotensinogen (AGT) is the substrate from which renin and ACE generate angiotensin (Ang) II. Ang II not only increases blood pressure, but also is a major determinant of atherosclerosis in hypercholesteremic mice. Here we investigated the effect of hepatocyte-specific (N-acetylgalactosamine-conjugated) antisense oligonucleotides targeting AGT (GalNAc AGT ASOs) on blood pressure and atherosclerosis in hypercholesterolemic mice.

Design and method:
Eight-week-old male LDL receptor deficient mice were fed a Western diet for 12 weeks, after receiving vehicle, GalNAc control ASO, or 1, 2.5 or 5 mg/kg of GalNAc AGT ASO on day 1, 3, 5 and 7 in the week prior the start of the diet (n = 6–10/group). Treatment was continued thereafter on a weekly basis. Systolic blood pressure (SBP) was monitored by tail cuff. After 12 weeks, mice were euthanized and plasma was collected. Plasma AGT concentration was measured by ELISA kit, and aortic atherosclerotic lesion area was measured by an en face method.

Results:
The 3 GalNAc AGT ASO doses decreased plasma AGT from 10.3 ± 0.8 to 1.4 ± 0.1, 0.9 ± 0.1 and 0.7 ± 0.1 g/mL, respectively. These decreases were paralleled by dose-dependent SBP reductions from 114 ± 3 to 96 ± 2, 92 ± 2, and 84 ± 2 mmHg, respectively, and atherosclerotic lesion area reductions from 27.4 ± 0.9 to 15.1 ± 1.4, 10.8 ± 1.2, and 7.7 ± 1.0%, respectively. Yet, the attenuation of liver steatosis (liver triglyceride/weight from 139.7 ± 35.7 to 26.8 ± 4.5, 19.9 ± 1.2 and 36.0 ± 3.6 g/mg, liver total cholesterol/weight from 19.8 ± 1.6 to 8.6 ± 0.9, 6.1 ± 0.6 and 8.2 ± 0.7 g/mg) was identical for each GalNAc AGT ASO dose. GalNAc control ASO did not have effects on plasma AGT, SBP, atherosclerosis lesion area, or liver steatosis vs. vehicle.

Conclusions:
In hypercholesterolemic mice, inhibition of hepatic AGT reduces systolic blood pressure and atherosclerosis dose-dependently, while liver steatosis was prevented in dose-independent manner.
THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM IN THE PREGNANT RAT
Authors: Speth Robert , West Crystal 
Published: June 2022

Objective:
Preeclampsia is the leading cause of maternal and fetal morbidity and mortality in the United States, affecting ~2–5% of all pregnancies. Women with a history of preeclampsia have a 4-fold increased risk for developing hypertension, 2-fold increased risk for developing stroke, and 2-fold increased risk for developing ischemic heart disease later in life. Although it is known that intact renin-angiotensin-aldosterone system (RAAS) signaling is critical to a healthy pregnancy and that the RAAS is altered in preeclampsia the pathogenic mechanisms are largely unknown and a comprehensive examination of RAAS metabolism and receptor expression is lacking in the literature. The purpose of this study is to understand how the vasculature becomes refractory to the reported high circulating angiotensin II (ANGII) during pregnancy. This work provides basic information needed to understand blood pressure regulation and volume expansion in normal pregnancy, and why it fails to occur in women with preeclampsia, resulting in hypertension and fetal growth restriction.

Design and method:
We performed AT1 receptor autoradiography in kidneys of virgin (V) and late pregnant (LP) rats. We also performed equilibrium RAAS Fingerprinting in the plasma and kidneys of LP rats and V rats using a new LC/MS technique.

Results:
Using this new method, ANGII levels were decreased in the plasma and unchanged in the kidney of LP animals. This was surprising as it is inconsistent with historical data, however, other methods of measuring ANGII are problematic and often unreliable. There was a very high Aldosterone/ANGII-ratio (AA2) in both plasma and kidney of LP animals. The AA2-ratio provides information about the adrenal aldosterone-releasing response to ANGII. We also found that AT1R expression is decreased in the kidneys of LP compared to V rats.

Conclusions:
These results suggest a systemic down regulation of renal ANGII signaling with increased adrenal signaling. Continuing studies are assessing the RAAS signaling cascade to further validate these data, which may revolutionize the way we think about the RAAS in pregnancy, leading to improved treatment of women with preeclampsia.
THE EXPLORATION OF THE RENINE ANGIOTENSIN SYSTEM IN NEPHROLOGY: EXPERIENCE OF THE NEPHROLOGY DEPARTMENT OF THE HEDI CHAKER UNIVERSITY HOSPITAL CENTER OF SFAX
Authors: El Atigh Aminetou , Dammak Najla , Agrebi Ikram , Chaabouni Khanssa , Toumi Salma , Chaker Hanen , Yaich Soumeya , Kammoun Khawla , Ayedi Fatma , Hmida Mohamed Ben 
Published: June 2022

Objective:
Plasma renin and aldosterone assays are useful in clinical practice for the aetiological assessment of arterial hypertension (hypertension) and / or a disturbance of the electrolyte balance. The objective of our work is to describe the main indications exploration of the renin aldosterone system, its results, its diagnostic and etiological impact.

Design and method:
We conducted a retrospective study of 40 patients who received a renin / aldosterone dosage, collected in the Nephrology department at the Hédi Chaker CHU in Sfax for a period of 6 years from January 2014 until December 2020.

Results:
These are 21 women and 19 men with a sex ratio of 1.1. Hypertension was present in 82.5% of cases. The dosage indication was: hypertension with hypokalaemia in 52.5%, hypertension in young subjects in 20%, resistant hypertension and hypertension with incidentaloma in each 7, 5% of cases, and incidentaloma without HTA in each 5% of cases and in one case hypokalaemia without HTA. Aldosterone was elevated in 52.5% of cases. Renin was normal in 67.5% of cases, low in 25% and high in 7.5% of cases. The aldosterone / renin ratio was normal in 60% of cases, elevated, decreased and invalid in respectively 27.5%, 2.5% and 10%. The etiological investigation revealed: primary hyperaldosteronism in 42.5% of cases secondary to a Conn adenoma in 20% of cases, to adrenal hyperplasia in 17.5% of cases and with normal imaging in 5% of cases. Secondary hyperaldosteronism was confirmed in association with Liddle syndrome and renal artery stenosis in 2.5% of cases each. The other etiologies were pheochromocytoma in 12.5% of cases, Takayusu’s disease, tubulopathy in 2.5% of cases each. The dosage was non-contributory in 7.5% of cases and normal in 25% of cases.

Conclusions:
The exploration of the renin angiotensin aldosterone system has several indications, mainly in hypertension with hypokalaemia. It can help make the etiological diagnosis and guide therapeutic management.
ANGIOTENSIN PROFILES IN PATIENTS WITH HYPERTENSION AND TYPE 2 DIABETES WITH COMBINATION THERAPY OF EMPAGLIFLOZIN AND LINAGLIPTIN VERSUS METFORMIN AND INSULIN GLARGINE
Authors: Bosch Agnes , Poglitsch Marko , Kannenkeril Dennis , Ott Christian , Pietschner Robert , Striepe Kristina , Schiffer Mario , Schmieder Roland E. 
Published: June 2022

Objective:
The renin-angiotensin system (RAS) plays a key role in the physiological regulation of blood pressure. Patients with type-2-diabetes-mellitus (T2DM) and hypertension are known to have increased RAS activity. However, the precise role of RAS activation after SGLT2-inhibitor therapy is unknown. The classic RAS comprises the ACE-AngII-AT1R-axis (classic-axis) that promotes vasoconstriction. The Angiotensin-converting-enzyme-2-angiotensin-(1–7)-Mas axis (Mas-axis) with its components Angiotensin-(1–7) (Ang-1–7) and Angiotensin-(1–5) (Ang-1–5) is an endogenous negative regulatory pathway of the classic-axis, which can reduce its harmful effects.

Design and method:
Angiotensin profiles were determined in 55 patients with hypertension and T2DM from our double blind, randomized, placebo controlled clinical trial “Effects of Empagliflozin+Linagliptin (E+L) vs Metformin+Insulin Glargine (M+I) on Renal and Vascular Changes in Type 2 Diabetes’’ (ELMI) at baseline and three months after application of either E+L or M+I. An LC-MS/MS based approach was used to simultaneously quantify individual angiotensin metabolites (Attoquant Diagnostics, Vienna, Austria).

Results:
In the E+L group medication induced a rise in Ang-I, Ang-(1–7) and a trend to a rise in Ang-II between baseline and treatment, which was not present in the M+I group (table).
Comparison between the E+L and M+I group revealed that change between baseline and treatment was significantly different for Ang I (p = 0.002) and Ang-(1–7) (p = 0.002) between the groups. No difference in change between baseline and treatment was found for Ang II (p = 0.182) and Ang-(1–5) (p = 0.224) between the E+L and M+I group.

Conclusions:
In patients with hypertension and T2DM three months of therapy with E+L led to a rise of classic and protective components of the RAS, which was not present in the M+I group. The biological consequence of this complex RAS activation remains to be elucidated.
THE RENIN-ANGIOTENSIN SYSTEM INHIBITORS IN HAEMODIALYSIS: CARDIOPROTECTIVE? TO WHAT EXTENT?
Authors: Dammak Najla , Ben Brahim Rimeh , Agrebi Ikram , Chaker Hanen , Ghabi Faten , Toumi Salma , Yaich Soumaya , Jarraya Fayçal , Chaabouni Khanssa , Kammoun Khawla , Ayedi Fatma , Ben Hmida Mohammed 
Published: June 2022

Objective:
The renin-angiotensin-aldosterone (RAAS) system is one of the most important systems in the pathogenesis of coronary heart disease. Its blockage constitutes a central pillar of cardiovascular therapeutics. Patients in end-stage renal disease or on dialysis are almost invariably excluded from trials evaluating antihypertensive treatments. Angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) are more cardioprotective than other antihypertensive agents in patients with chronic renal disease but whether this applies also to patients on dialysis is unknown.
This study followed a cohort of haemodialysis patients over a median of three years, we analysed all-cause mortality and cardio-vascular admissions for patients under RAAS inhibitors.

Design and method:
Twenty-seven HD patients were cross-sectionally analysed in the following groups: G1: patients with hypertension under ACE or ARB treatment (n = 10), G2: patients with hypertension under another class (n = 7), G3: non-hypertensive patients (n = 10). Associations with all-cause and cardiovascular mortality were assessed over a median of 3 years of follow-up.

Results:
Overall we had three homogeneous groups, there was no significant difference between median ages (46,3 vs52,7 vs49,9), initial nephropathy or dialysis vintage (5,9 years vs 5,1 vs 11,4). In G1: 4 patients experienced cardiovascular events (40%), but none of them died of cardiovascular causes/complications. In G2: 4 patients had cardiovascular events (57%) amongst whom two died of its complications. In G3: two patients had cardiovascular events (20%) amongst whom one died. There was statistically no significant difference between our groups in terms of cardiovascular morbidity or mortality and in all-causes mortality. Nevertheless, patients under SRA inhibitors presented the lowest number of cardiovascular mortalities.

Conclusions:
In the study, we observed that patients with SRA inhibitors experienced less cardio-vascular related death, although it is not enough to conclude its cardioprotective status. Larger studies need to be carried to unveil its utility among haemodialysis patients.
COMPOUND 21 STIMULATES THE ACTIVATION OF AKT AND ERK1/2 IN MOUSE ADIPOSE TISSUE IN VIVO
Authors: Dominici Fernando , Quiroga Diego 
Published: June 2022

Objective:
To analyze signaling events triggered by in vivo stimulation of the AT2 receptor.

Design and method:
Male B57Bl/6 mice were used as model at the age of 3 month. Mice were subjected to a bolus in vivo intravenous injection (cava vein) of saline buffer containing either the AT2 agonist compound 21 (0.25 mg/Kg), a mixture of C21 (0.25 mg/Kg) and the AT2 antagonist PD123319 (2.5 mg/Kg) or saline for baseline assesment under anesthesia. A group of animals that received insulin (0.25 mg/Kg) were used as positive control. The heart and the inguinal adipose tissue were removed after 1 and 3 min respectively, flash-frozen and kept at -70 C until analysis. Proteins from heart and adipose tissue were solubilized in a buffer containing 1% Triton together withprotease and phosphatase inhibitors. Protein content was measured by the BCA method and homogenates were subjected to Western Blotting using specific anti-phospho Akt or anti-phospho ERK1/2 antibodies. The content of Akt and ERK content was detected through incubation with either anti-Akt or anti-ERK1/2 antibodies. Specific bands were detected by chemiluminescence. Protein loading control was checked by coomassie blue staining of every PVDF membrane employed.

Results:
Injection of C21 resulted in the activation of both Akt and ERK1/2 in mouse adipose tissue. The extent of activation of Akt and ERK1/2 attained was equivalent to approximately 30–40% of the levels of activation of these enzymes obtained after an injection of a dose of insulin known to generate maximum activation of these signaling components.
Co-infusion of C21 and PD123319 abolished the in vivo activation of Akt and ERK1/2, indicating that these events were mediated by the AT2 receptor.

Conclusions:
In vivo administration of the AT2 receptor agonist C21 resulted in the stimulation of the phosphorylation of both Akt and ERK1/2 at stimulatory sites indicative of activation of these enzymes. Co-infusion of C21 with the specific AT2 receptor antangonist blunted this effect.
It is concluded that the AT2 receptor is capable of recruiting both Akt as ERK1/2 as signaling molecules in mouse adipose tissue in vivo.
DISTURBANCES OF THE CIRCADIAN RHYTHM AND BLOOD PRESSURE LEVELS IN OBESE PATIENTS WITH TRUE AND PSEUDO-RESISTANT HYPERTENSION
Authors: Shalimova Anna , Isayeva Ganna , Buriakovska Olena , Vovchenko Maryna , Komir Iryna , Prosolenko Kostyantyn 
Published: June 2022

Objective:
The aim was to conduct a comparative assessment of the circadian rhythm abnormalities and blood pressure (BP) levels between pseudo-resistant and true resistant hypertension (RH) in obesity.

Design and method:
The study included 302 patients with uncontrolled hypertension and obesity. Initial treatment efficacy was assessed 3 months after dual therapy was administered. Those patients who did not reach target BP in dual therapy were transferred to triple therapy. Among patients who received triple therapy, 69 people did not reach target BP. All patients were additionally examined 6 months after the initiation of antihypertensive therapy.

Results:
In the absence of a difference in BP, patients who subsequently become resistant, already at the stage of inclusion, significantly more often had a violation of the circadian rhythm with a predominance of the non-dipper rhythm. Despite the achievement of target BP after 6 months of therapy, in the majority (91.42%) of patients without resistance, the circadian rhythm normalized, while resistant patients had a normal circadian rhythm only in 60.87%.
At the stage of enrolling patients into the study and 3 months of therapy there was no significant difference in BP between true and pseudo-resistance, then after 6 months of therapy, patients with true resistance had significantly higher office SBP (p < 0.01) and 24 h average SBP according to ABPM data (p < 0.05) compared with pseudo-resistant patients. Already at the stage of inclusion in the study, the normal circadian rhythm in true resistance was significantly less common than in pseudo-resistance; during the prescribed therapy, a similar trend persisted: after 6 months of therapy, 71.05% of pseudo-resistant patients had a normal circadian rhythm, while with true resistance only about half of the patients had a normal circadian rhythm.

Conclusions:
Even when target BP levels in antihypertensive therapy are achieved, obese patients with RH are characterized by more pronounced disturbances of the circadian rhythm (most often non-dipper) and higher levels of office and out-of-office BP, compared with non-resistant patients. Compared with pseudo-resistant patients, the presence of true resistance in obesity is associated with higher SBP levels and a higher incidence of circadian rhythm disturbances.
CHANGES IN CLINICAL PROFILE OF REFRACTORY HYPERTENSIVES AFTER THE INTRODUCTION OF SPIRONOLACTONE
Authors: de Carvalho Fortes Carolina , Chedier Bernardo , Roderjan Christian Nejm , Viegas Bianca , Carlos Fernanda O. Carvalho , Santos Taissa Lorena dos , Alves Hugo Farah Affonso , Nemer Camila Bello , Silva Marcus Vinicius Serejo Borges V. da , de Sá Kimura Lucca Hiroshi , Lobo Sofia Luz Coutinho Botelho , de M. Barreto Bianca Zattar , de Melo Nolasco Vitor , Silva João Gabriell Bezerra da , do N. Vallaperde João Gabriel Rega , Muxfeldt Elizabeth Silaid 
Published: June 2022

Objective:
To characterize prevalence and clinical profile of patients with RfHTN among a historical cohort of patients with RHTN in 2 moments: before and after the introduction of spironolactone.

Design and method:
A cross-sectional analysis was performed during the pre-spironolactone period (before 2005) with 1,048 participants with RHTN (72.3% women, average age: 61.2 ± 11.3 years). All of them were submitted to a standard protocol including clinical and laboratory tests, 24-hour ABPM, echocardiogram, and pulse wave velocity. In a second analysis, refractory patients were evaluated after the introduction of spironolactone (post-spironolactone period – after 2005). The statistical analysis included bivariate comparisons between patients with RHTN and those with RfHTN, as well as logistic regressions to assess independent correlations of RfHTN pre- and post-spironolactone.

Results:
In the initial cross-sectional analysis (pre-spironolactone), RfHTN prevalence was 14%. Age < 60 years, smoking, obesity and left ventricular hypertrophy (LVH) were independently correlated with RfHTN. After the introduction of spironolactone, prevalence increased to 17.6%. It was observed that refractory patients using spironolactone presented less aortic stiffness, lower prevalence of LVH, cerebrovascular disease and peripheral arterial disease (PAD), what might indicate a reduced cardiovascular risk despite the lack of blood pressure control. Refractory patients have also presented higher magnitude of white-coat effect, reflecting an exacerbated sympathetic activity. Age < 60 years and lower prevalence of PAD were correlated with RfHTN in the post-spironolactone period.

Conclusions:
The use of spironolactone seems to reduce cardiovascular risk despite the lack of blood pressure control.