bluuebunny/crossref_metadata_2025 huggingface dataset:
DO GENES AFFECT METABOLIC AND HORMONAL PARAMETERS IN PATIENTS WITH ESSENTIAL ARTERIAL HYPERTENSION?
Authors: Repchuk Yuliia , Sydorchuk Larysa , Biletsky Semen , Petrynych Oksana , Kasantseva Tetiana , Ivashchuk Serge , Semianiv Marianna , Sokolenko Alina , Voroniuk Kseniia , Yarynych Yuliia , Dzhuryak Valentyna
Published: June 2023

Objective:

The aim of the study was to analyze metabolic and hormonal parameters changes in patients with essential arterial hypertension (EAH) depending on the vitamin D receptor gene (VDR, rs2228570) polymorphism.

Design and method:

The study involved 100 patients suffering from EAH with target-organ damaging, moderate, high or very high cardiovascular risk. Among them were 79.0% (79) women and 21.0% (21) men, an average age was 59.87±8.02 yo. The control group involved 60 practically healthy persons, matched by age and gender distribution. All enrolled/screened patients signed the Informed Consent to participate in the research. The VDR gene (rs2228570) polymorphism was studied by a real-time polymerase chain reaction (RT-PCR) method. The intact parathyroid hormone (intact PTH) and vitamin 25 (OH) D levels in blood serum were determined by chemiluminescence immunoassay (MAGLUMI).

Results:

The decreased level of vitamin 25 (OH) D (<30 ng/ml) was found more often in the A-allele carriers of the VDR gene (rs2228570), than in GG-genotype carriers: in the control group - by 36.84% (x2 = 10.32; p = 0.001), in study group - by 42.42% (x2 = 39.27; p<0.001). Hypocalcemia according to the level of ionized blood calcium (Ca2+ <1.12 mmol/l) was registered only in G-allele carriers, both among practically healthy and hypertensive patients. In the control group, GG-genotype carriers had a lower ionized Ca2+ blood level with a compensatory higher concentration of the intact PTH in comparison with A-allele carriers - by 3.42%, 25.19% and 16.03% (p<0.05), respectively. Secondary hyperparathyroidism due to a compensatory increasing of the intact PTH (>65 pg/ml) was found more often in the G-allele carriers of the VDR gene (rs2228570) than in AA-genotype carriers: in control group - by 55.55% (x2 = 11.11; p<0.001), and in the group of patients with EAH - by 62.5% (x2 = 12.5; p<0.001).

Conclusions:

The GG-genotype of the VDR gene (rs2228570) increases the risk of hypocalcemia by more than 6 times [OR = 6.25; 95% CI: 1.05-37.37; p = 0.046], with the lowest probability in carriers of the A-allele [OR = 0.16; 95% CI: 0.03-0.96].
ANGIOTENSIN II REDUCES THE EXPRESSION OF CX43 AND INHIBITS THE C-SRC /MAPK/ERK PATHWAY VIA CX43 IN CARDIOMYOCYTES
Authors: Fan Xin , Chen Xinrong , Yu Jing
Published: June 2023

Objective:

Hypertension is associated with abnormal renin angiotensin system (RAS). Angiotensin II (AngII), an important substance in RAS, is closely related to cardiomyocyte injury. Connexin43 (Cx43), a key structural protein in cardiomyocyte membrane, takes part in signal transduction and substance transport. Cx43 may cause extracellular interstitial fibrosis. It is known that Cx43 increases collagen I in heart tissue by regulating nuclear factor kappa B and Mechanistic metalloproteinase. However, the relationship between Ang II and Cx43 has been controversial,and how Ang II affects Cx43-related pathway is unclear. Otherwise, the activation and inhibition of the c-SRC /MAPK/ERK pathway may is related to Cx43, but the fact which is the forward is not sure.

Objective:The purpose of this study is to explore whether Ang II affects the expression of Cx43 and inhibits c-Src /MAPK/ERK pathway via Cx43.

Design and method:

First, we given rat cardiomyocytes (H9C2 cells) different concentrations of Ang II (10-5M,10-6M and 10-7M,for 48h), and establish Ang II groups. There is a contral group, which was given normal culture without Ang II. Second,we given H9C2 cells the Gap26,which is the inhibition of Cx43. Proteins of Cx43 and c-SRC /MAPK/ERK pathway from all groups were detected by Western Blot, and mRNA of these proteins were detected by PCR. SPSS was used for statistical analysis to compare the difference between all the groups.

Results:

First, compared with the control group, protein of Cx43, c-SRC, ERK2 and ERK1 were significantly decreased in Ang II group, and when the concentration of Ang II was 10-5M, these proteins were the least. mRNA of Cx43, ERK2 and ERK1 also were cut down after giving Ang II (only 10-5M). Second, the Gap26-intervention group had the lower expression protein and mRNA of Cx43, c-SRC, ERK2 and ERK1.

Conclusions:

We proved that Angiotensin II can reduce the expression of Cx43 and inhibit c-SRC /MAPK/ERK pathway via Cx43 in cardiomyocytes. Based on the role of Cx43 and c-Src /MAPK/ERK pathway, hypertesion may injury the cardiomyocytes via RAS and these pathways.
EXTREME CARDIOVASCULAR RISK IN CARDIOLOGICAL REHABILITATION: PREVALENCE AND IMPACT ON PATIENT'S FUNCTIONAL IMPROVEMENT
Authors: Maloberti Alessandro , Senini Eleonora , Fabbri Saverio , Ciampi Claudio , Regazzetti Matteo , Monticelli Massimiliano , Pirola Roberto , Giannattasio Cristina
Published: June 2023

Objective:

Among patients at very high cardiovascular risk, some are more likely to experience recurrent cardiovascular events. In may 2022, an article was published in the European Heart Journal proposing different definitions of patients at extreme cardiovascular risk. However, the process of defining the patient at extreme cardiovascular risk is still ongoing and more data also on its prevalence are needed. To assess the prevalence of patients at extreme cardiovascular risk in cardiological rehabilitation, to evaluate the clinical features of these patients. Furthermore, we want to establish how the extreme cardiovascular risk condition correlates with the functional improvement obtained during cardiac rehabilitation.

Design and method:

The study included 938 patients suffering from atherosclerosis who attended the cardiological rehabilitation of Niguarda Hospital in Milan. Patients diagnosed with non-ischemic heart failure or congenital heart disease have been excluded. Patients classified as at extreme cardiovascular risk were compared with the remaining patients and a multivariate linear regression was performed with absolute functional improvement as the dependent variable.

Results:

Among 938 patients, 26.9% belong to the category of extreme cardiovascular risk. Patients at extreme cardiovascular risk showed a higher average age (67.8 ± 10.4 vs 64.1 ± 11.1 years; p <0.001), a higher prevalence of significant comorbidities (peripheral arterial disease, cerebrovascular disease, chronic kidney disease, dyslipidemia, diabetes, hypertension) and a lower functional improvement during cardiac rehabilitation (102.9 ± 68.6 vs 138.1 ± 86.5 m; p < 0.001). At multivariate analysis extreme cardiovascular risk remains a significant determinant of the absolute functional improvement at Six-Minute Walking Test obtained during cardiac rehabilitation with b = -0.137 and p = 0.035, together with female sex (b = -0.136; p = 0.035).

Conclusions:

Extreme cardiovascular risk is a widespread condition among patients with chronic coronary syndrome and adversely affects the patient's functional improvement during cardiac rehabilitation. The identification of patients at extreme cardiovascular risk is a goal to be pursued in order to intensify secondary prevention strategies.
SIMULTANEOUS RECORDING OF CENTRAL BP AND ARTERIAL STIFFNESS DURING ECHO CORRELATES BETTER WITH LV DIASTOLIC FUNCTION THAN ROUTINE EXAMINE
Authors: Torbas Olena , Botsiuk Yurii , Sirenko Yuriy
Published: June 2023

Objective:

ASE guidelines for the diagnostics of the left ventricle (LV) of diastolic dysfunction in 2016 suggested using the method of non-invasive assessment of central blood pressure (CBP) and the augmentation index (Aix) in order to obtain more detailed information in patients with arterial hypertension (AH). Routine determination of CBP does not allow the procedure to be performed simultaneously with ultrasound, so that can affect the results of the study because hemodynamics can change significantly during this time. The BAT 41-2 device, developed in Ukraine, allows the performing of two studies at the same time. The purpose of this analysis was to determine whether this approach is better than routine research.

Design and method:

We included 37 patients with AH grade 2. An echocardiographic examination was done according to ASE guidelines for the diagnosis of diastolic dysfunction of the left ventricle in 2016, including evaluation of transmitral E/A and E/e’ ratios, deceleration time (Dt) and isovolumic relaxation time (IVRT). Routine examination of CBP and Aix standardized for heart rate 75 (Aix@75) was measured with Sphygmocor (ArCor, Australia) according to a standardized protocol. Simultaneous measurement of CBP and Aix@75 was done with BAT41-2 device (IKS-Techno, Ukraine). Simultaneous measurement was done during standard echo views were recorded while the routine examination was done 30-90 min after the ultrasound diagnostic was done. To evaluate associations we used Spearman correlation analysis with the IBM SPSS 26.0 software package.

Results:

In our analysis, we did not find any correlations of E/A with any of the other parameters. Both routine and simultaneous CBP measurement were associated with LV IVRT but for simultaneous CBP measurement, this association was greater (R = 0.197, P = 0.043, and R = 0.340, P = 0.049 respectively). E/e’ significantly correlated with routine Aix@75 and simultaneous Aix@75, but again the last association was more strong (R = 0.495, P = 0.037 and R = 0.504, P = 0.014 respectively). Simultaneous Aix@75 was also more associated with IVRT (R = 0.438, P = 0.010) than routine (R = 0.210, P = 0.038).

Conclusions:

Simultaneous registration of CBP and AiX during echocardiography is more associated with LV diastolic function parameters than a routine examination.
SEX DIFFERENCES IN PULSE WAVE AND SUBENDOCARDIAL VIABILITY RATIO IN HYPERTENSIVE PATIENTS
Authors: Barbato Vincenzo , Grillo Andrea , Pierro Giuliano Di , Rovina Matteo , Puato Massimo , Parati Gianfranco , Salvi Paolo , Bernardi Stella , Fabris Bruno
Published: June 2023

Objective:

Myocardial ischemia represents the main cause of morbidity and mortality in hypertensive patients in both women and men, although some difference in pathophysiology and in the exposure to risk factors may explain the lower global cardiovascular risk of women. Sex differences in the structure and function of the cardiovascular system may affect the aortic pressure wave and the functional balance in myocardial perfusion determined by central aortic pressure, which may lead to myocardial ischemia and type 2 myocardial infarction.

Design and method:

In a population of 318 treated hypertensive patients (162 females, 156 males) referring to a single Hypertension centre (University of Trieste, Italy), we measured peripheral blood pressure and performed arterial applanation tonometry (PulsePen, DiaTecne, Italy) to determine central blood pressure waveform, aortic pulse wave velocity (PWV), augmentation index (AIx), pulse wave separation analysis with timing and amplitude of forward (fT, fP) and backward reflected (bT, bP) waves, and the subendocardial viability ratio (SEVR), i.e. the ratio between diastolic and systolic pressure-time index, as a risk marker of myocardial ischemia.

Results:

Despite similar peripheral systolic and diastolic blood pressure values, heart rate and PWV between sexes, females showed a longer forward pressure wave duration (119.8±38.6 vs 105.0±30.4 ms, p<0.0001) and lower amplitude (52.7±19,4 vs 57.1±19.3 mmHg, p = 0.039) compared to males. Backward pressure waved were similar in timing and amplitude between males and females. The difference in forward wave caused a marked higher AIx (19.5±12.4 vs 11.9±14.9, p<0.0001) and a lower SEVR (101.6±24.4 vs 108.5±27.7, p = 0.018) in women compared to men.

Conclusions:

Hypertensive women and men showed significant differences in forward pressure wave, causing a significant increase in AIx and a decreased SEVR in women compared to men. This may have important implications in sex-specific risk and myocardial ischemia.
EVALUATION IN REAL LIFE OF ‘SUIVI-HTA’, A FREE APPLICATION FOR HOME BLOOD PRESSURE MONITORING
Authors: Jeune Sylvain Le , Sautenet Bénédicte , Duband Benjamin , Feit Bertrand , Lequeux Benoît , Artifoni Mathieu , Ledieu Guillaume , Deliege Pierre-Guillaume , Delsart Pascal , Girerd Xavier , Lamirault Guillaume
Published: June 2023

Objective:

Home Blood Pressure Monitoring (HBPM) is key to improve blood pressure control. To help hypertensive patients adopt HBPM and doctors use the results in their practice, the French ‘Fondation de Recherche en Hypertension Artérielle’ has developed the Suivi-HTA application, available since September 2020. We therefore aimed at carrying out a first real-life evaluation of the utilization of this application among hypertension specialists and their patients.

Design and method:

The survey was carried out in France between October 2020 and March 2021 in 8 hospitals and 2 private practices based on a standardized questionnaire assessing the acceptability and effective use of the application, as well as the doctor's opinion on patient satisfaction.

Results:

The survey included 135 hypertensive patients, 38% were women, 57% were over 55 years old. Only 27% regularly performed HBPM. If the application was offered, it was well accepted (women 65%, men 80%) with a more important rejection rate in hypertensives over 55 years old (26% vs. 3%, p<0.0003) and with more comorbidities (31% vs. 7%, p = 0.0005). Rejection was mainly related to digital technology (no smartphone or tablet, lack of knowledge on downloading or using applications). Among the 113 patients who agreed to test the application, 98 (87%) effectively performed HBPM, 77 (67%) did so using Suivi-HTA, of which 60 (53%) generated and transmitted a HBPM report. According to the doctor's opinion, 88% patients who have used Suivi-HTA will be future users of the application. Patient satisfaction with the application was assessed as “good” for 93% patients.

Conclusions:

This national survey shows that the Suivi-HTA application has a good rate of acceptance and effective use among hypertensives. It also generates a very positive opinion in the medical community. However, age and presence of comorbidities were risk factors for reduced acceptance, in connection with the difficulties to digital accessibility. It would therefore be interesting, while globally promoting the use of HBPM in hypertensive patients, to develop specific strategies targeting patients with more comorbidities and/or at higher cardiovascular risk.
CORRELATION BETWEEN HOME AND AMBULATORY BLOOD PRESSURE MEASUREMENT: DIAGNOSIS AND MONITORING OF HYPERTENSION
Authors: Hamdani Achref , Ajra Zaineb , Bayar Mohamed Fehmi , Gheni Refaat , Rashikou Lamia , Hmida Riadh Ben , Ounissi Taha , Elhadj Zied Ibn
Published: June 2023

Objective:

Home Blood Pressure Measurement (HBPM) and Ambulatory Blood Pressure Measurement (ABPM) are 2 valid approaches to measure out of office blood pressure to confirm and monitor hypertension. The objective of our study was to compare the results of HBPM to ABPM considered as the reference technique and to determine its contribution in the management of hypertension

Design and method:

An analytical cross-sectional study including 100 patients aged > 18 years, followed at the outpatient cardiology clinic of the Mohamed Taher Maamouri university hospital in Nabeul over a six months period (July-December 2021). Patients were asked to measure blood pressure (BP) at home as instructed by the physician using validated blood pressure self-measurement devices (MICROLIFE BP A3 PLUS, MICROLIFE BP A2 Basic and Beurer BM 40 ). Laying of ABPM was performed immediately after the HBPM using a Bravo Mini validated device from Sun Tech Medical. The correlation was analyzed using Pearson correlation coefficient (r).

Results:

Our population was composed of 47 women and 53 men. The mean age was 59.14±13.12 years. HBPM and ABPM were realized in 84% of cases for monitoring hypertensive patients and in 16% of cases to confirm newly diagnosed. The diagnosis of hypertension was confirmed in 75% by HBPM and in 62.5% by ABPM. White coat uncontrolled hypertension (WCUH) was noted in 31% of cases by HBPM and in 25% by ABPM and masked uncontrolled hypertension (MUCH) was noted in 6% of cases by HBPM and in 8.3% by ABPM. The difference between HBPM and ABPM was not statistically significant for the detection of MUCH (p = 0.320) and WCUH (p = 0.198). A strong correlation was found between HBPM and ABPM of systolic BP (P <0.001; r = 0.728; Curve A) as well as of diastolic BP (P <0.001; r = 0.773; Curve B).

Conclusions:

HBPM has a value very close to ABPM. So, it's important to increase its availability in clinics, outpatient clinics and even in private practice given its lower cost and better availability compared to ABPM for the diagnosis of hypertension and its monitoring.
BLOOD PRESSURE CONTROL IN PUBLIC AND PRIVATE BRAZILIAN HEALTHCARE SERVICES
Authors: Amorim Kecia , Vitorino Priscila Valverde O , Feitosa Audes Diogenes M. , Lopes Lais Rocha , Camafort Miguel , Sousa Ana Luiza Lima , Barroso Weimar Kunz Sebba
Published: June 2023

Objective:

To compare office and home blood pressure (BP) measurements of treated hypertensive patients followed in public and private healthcare in a Brazilian multicenter study.

Design and method:

A cross-sectional study. The datas were exported from TeleMRPA plataform to an excel file containing the variables to be analyzed. Public and private healthcare units were coordinated by same cardiologists and followed same guidelines concerning BP treatment. Descriptive statistics were used through the measure of central tendency (mean), measure of dispersion (standard deviation) and measure of frequency (percentage). For inferential statistics, the unpaired t-student test was used. A 95% confidence interval and a significance level of p<0.05 were considered.

Results:

The sample consisted of 3.043 study patients: 1.842 (60.5%) of them at private and 1,201 (39.5%) at public healthcare services with a mean age of 58± 12.2 years [public = 59±11.3; private = 58±12.8, p = 0.18], BMI of 28.9±5.2 Kg/m2 [public = 29.4±5.7; private = 28.6±4.8, p<0.001]. Concerning office BP values, Systolic BP [public = 144±25.5mmHg; private = 130±17.2mmHg, p<0.001] and Diastolic BP [public = 87±14.4mmHg; private = 81±10.2mmHg, p<0.001] and at home BP the average Systolic BP[public = 134±20.8mmHg and private = 123±13.6mmHg, p<0.001] and Diastolic BP [public = 82±13mmHg; private = 76±8.9mmHg, p<0.001].

Conclusions:

Hypertensive patients followed at public healthcare services have greater BMI and higher level of BP than private services. Better care is suggested and necessary for public health care, including actions to reviewing the classes of anti-hypertensive drugs and their fixed or non-fixed combinations in order to reduce cardiovascular outcomes.
HOME BLOOD PRESSURE MONITORING WITH A DIGITAL BLOOD PRESSURE COACH. A PROSPECTIVE ANALYSIS OF INDIVIDUAL USER DATA
Authors: Beger Christian , Rüegger Dominik , Lenz Anna , Wagner Steffen , Haller Hermann , Schmidt-Ott Kai -Martin , Volland Dirk , Limbourg Florian P.
Published: June 2023

Objective:

The influence of baseline BP category and measurement duration on home blood pressure monitoring (HBPM) are still poorly defined, particularly when used in conjunction with a digital application.

Design and method:

This is a prospective analysis of real-world user data from a digital BP-coach (Manoa app ) in the period from April 2020 (release of the Manoa app) to November 2021 in Germany. The app was freely available in Germany during this period in all major app stores (iOS, Android).

We analysed temporal BP changes and performed BP classification tracking in users with self-reported hypertension performing HBPM with a digital and interactive blood pressure coach.

Results:

Of 3175 users who enrolled in HBPM, 74.1% completed the first measurement period. Overall, mean systolic BP dropped significantly after the first day, but stratification by BP category demonstrated that initial category influenced BP course. BP classification tracking revealed that time to reach final BP category was dependent on baseline category, with users in categories high-normal and grade 1 hypertension requiring more days to decrease BP class volatility and to reach their definitive BP class. This was driven by an intense switching between directly neighbouring categories until the middle phase of the HBPM period, while more distant class switching occurred less often and only early on. Overall, > 90% of users maintained their category by day 5. Omitting the first day from analysis lead to therapeutically relevant reclassification in 3.8% of users. Users who completed at least two HBPM periods (n = 864) showed a mean SBP/DBP decrease of 2.6/1.6 mmHg, which improved hypertension control from 55.6% to 68.1%.

Conclusions:

With a digital HBPM-protocol, five consecutive measurement days are required for a reliable diagnosis and BP categorization. However, especially at therapeutic thresholds, additional measurement days are often required. Excluding day 1 from the protocol resulted in blood pressure reclassifications in 8.4% of all cases, with therapeutic relevance in 3.8% of cases.

The optimal length of HBPM period depends on BP category. HBPM with a digital coach is associated with a reduction in average BP and improvement in BP control.
CHANGE IN ARTERIAL STIFFNESS AND AMBULATORY BLOOD PRESSURE IN PATIENTS WITH RHEUMATOID ARTHRITIS: THE JOINTHEART STUDY
Authors: Linde Anja , Gerdts Eva , Fevang Bjørg Tilde Svanes , Eilertsen Rune , Kringeland Ester , Alsing Christian Lillebø , Midtbø Helga
Published: June 2023

Objective:

Use of disease modifying antirheumatic drugs (DMARDs) has been associated with reduction in blood pressure (BP) and arterial stiffness in clinical trials, but real-word data is lacking. We investigated change in ambulatory BP and arterial stiffness in outpatients with rheumatoid arthritis (RA) eligible for initiation or change in targeted synthetic (ts) or biological (b) DMARDs.

Design and method:

Eighty-nine consecutive RA patients (age 53±13, 68% women) were examined at initiation of ts/bDMARDs and repeated after 22 months. Ambulatory BP, carotid-femoral-pulse wave velocity (cfPWV) and Disease Activity Score in 28 joints using C-reactive protein (DAS28) were measured at baseline and at follow-up. High cfPWV was defined as cfPWV > 10 m/s in accordance with guidelines.

Results:

At follow-up, 20% used tsDMARDs, 57% bDMARDs and 67% had achieved remission or low disease activity. DAS28 decreased from 3.9±1.3 at baseline to 2.8±1.2 at follow-up (p<0.001).

The ambulatory systolic BP increased (116±11 mmHg vs 120±13 mmHg, p = 0.010), while the ambulatory diastolic BP decreased (76±7 mmHg vs. 73±8 mmHg, p = 0.001) from baseline to follow-up. Body mass index (BMI) increased from 26.5±5.2 kg/m2 to 27.1±4.9 kg/m2, p = 0.009. Changes in ambulatory systolic and diastolic BP were associated with presence of diabetes at baseline, but not DAS28 or use of ts or bDMARDs. Mean cfPWV increased from 7.8±1.6 m/s at baseline to 8.5±1.8 m/s at follow-up (p<0.001). The prevalence of high cfPWV increased from 10.8% to 16.3 %, p = 0.03. DAS28 (beta = 0.32, p = 0.01) and diabetes at baseline (beta = 0.39, p = 0.001) were associated with increase in cfPWV, independent of achieved remission/low disease activity at follow-up, baseline systolic BP, BMI, age, sex and use of antihypertensive drugs.

Conclusions:

In outpatients with RA, higher disease activity at baseline was associated with an increase in arterial stiffness during follow-up, despite DMARD therapy and significant decrease in disease activity.
THE SYNERGISTIC EFFECTS OF PROINFLAMMATORY CYTOKINES ON CARDIOVASCULAR FUNCTION AND SYMPATHETIC OUTFLOW IN RAT
Authors: Wei Shunguang , Cao Yiling , Yu Yang
Published: June 2023

Objective:

Inflammation has been implicated in the pathophysiology of cardiovascular dysfunction and neurohumoral activation in cardiovascular diseases. Our previous work has demonstrated that proinflammatory cytokines (PICs) in cardiovascular/autonomic brain regions contribute significantly to the sympathetic excitation and cardiac dysfunction in heart failure and hypertension. Notably, the chronic inflammatory conditions in these disease settings are caused by numerous inflammatory cytokines and chemokines. Given that the elevated levels of a single effector cytokine in the pathophysiological condition are insufficient to cause a significant change in hemodynamic and sympathetic responses, how PIC-driven neuroinflammation promotes sympathetic activation remains unclear. This work sought to determine whether PICs in the brain have a synergistic action to exaggerate their inflammatory effects on hemodynamic and sympathetic responses in rats.

Design and method:

Blood pressure (BP, mmHg), heart rate (HR, beats/min) and renal sympathetic nerve activity (RSNA, % change) were continuously recorded for 4-5 hours in urethane anesthetized male Sprague Dawley rats. The inflammatory cytokines tumor necrosis factor-↑ (TNF-↑), interleukin (IL)-1↓, IL-6 and vehicle were injected intracerebroventricularly (ICV).

Results:

We found that while ICV injection of TNF-↑, IL-1↓ or IL-6 alone at a low dose (10 ng, respectively) did not induce significant changes in BP, HR and RSNA, the combined injection of all three cytokines at the same dose (10 ng) elicited a substantial (*p<0.05) increase in BP (18.2 ± 2.1*), HR (62 ± 7*) and RSNA (94.5 ± 5.2 %*), that began within 15-20 mins. These responses peaked at 2-3 hours after ICV injection and remained elevated for the rest of the recording period. Additionally, ICV injection of TNF-↑, IL-1↓ or IL-6 alone at a high dose (50 ng, respectively), produced a dramatic and long-lasting increase in BP, HR and RSNA, that closely resembles the time course and response pattern induced by ICV injection of all three cytokines concurrently at the low dose (10 ng).

Conclusions:

These data suggest a synergistically excitatory action of PICs in the brain on sympathetic outflow. Interventions that simultaneously target multiple cytokines may have an extended anti-inflammatory effect of reducing sympathetic excitation in hypertension and heart failure.
BLOOD PRESSURE PROFILE IN PATIENTS WITH CHRONIC KIDNEY DISEASE
Authors: Triqui Chifa , Khadhar Mariem , Jerbi Mouna , Hadded Sarra , Aoudia Raja , Gaied Hanene , Goucha Rim
Published: June 2023

Objective:

High blood pressure (HBP) is often associated with chronic kidney disease (CKD). It can be a cause or a complication of the latter.

The aim of this work was studying the clinical characteristics and the therapeutic modalities prescribed in our hypertensive patients monitored in nephrology consultation.

Design and method:

It was a retrospective descriptive study conducted at the nephrology consultation from January 2020 to January 2022. The stage of chronic kidney disease was defined according to the KDIGO classification. A therapeutic target achieved was defined by a Systolic Blood pressure<140 mmHg and a Disyslotic Blood Pressure<90 mmHg.

Results:

Our population included 53 hypertensive patients who were followed for chronic kidney disease. The mean age was 70.16 [46-90] with a M/F sex ratio of 1.3. The stage of chronic kidney disease was 1,2,3,4 and 5 in 2 patients (3.77%), 7 patients, (13.2%), 25 patients (47.16%), 8 patients (15.09%) and 11 patients (20.75%) respectively. Hypertension was classified as grade 1, 2 and 3 in 18 (33.16%), 6 (11.32%) and 3(5.6%) patients respectively.

The mean systolic blood pressure in our patients was 137.55+/-21.54 mmHg and the mean diastolic was 78.62+/-11.37mmHg.

Left ventricular hypertrophy on ultrasound was found in 4 patients (7.54%).

Blood pressure was balanced in 42 (79.4%) patients, of whom 29 were on a calcium channel blocker alone or in dual therapy, 27 patients were on a combination containing a blocker of the rennin angiotensin aldosterone system, 17 patients were on beta blocker,14 patients were on dual therapy containing a loop diuretic and 13 patients were on a central antihypertensive.

The therapeutic target was not reached in 11 patients, among whom there was a dietary deviation in 4 patients, nonadherence to treatment in 6 patients and sleep apnea in 1 patient. Five patients were in stage 4 and 5 of chronic kidney disease.

Conclusions:

Blood pressure control is an important part of the follow-up of hypertensive patients in nephrology. Hypertension can increase the morbidity and mortality of the chronic kidney disease.
LONGER TELOMERE LENGTH IN BALKAN ENDEMIC NEPHROPATHY PATIENTS UNDERGOING CHRONIC HEMODIALYSIS IS ASSOCIATED WITH LOWER CARDIOVASCULAR MORTALITY
Authors: Toupance Simon , Premuzic Vedran , Hollander Allyson , Stipancic Zelimir , Bukal Nikolina , Jelakovic Ana , Brzic Ivan , Benetos Athanase , Jelakovic Bojan
Published: June 2023

Objective:

Balkan endemic nephropathy (BEN) is characterized with later onset, milder forms of hypertension and lower pulse wave velocity (PWV) than other end-stage kidney disease (ESKD). We hypothesized that telomere length (TL) would be longer in BEN patients and associated with lower PWV and less cardiovascular (CV) mortality.

Design and method:

124 patients undergoing hemodialysis (HD) (68 BEN, 56 non-BEN; 48.4% men; 65±14 years) were enrolled and followed-up for 72 months. Blood pressure and PWV were determined before mid-week dialysis. TL was measured in leukocytes by Southern blot.

Results:

Age and sex-adjusted TL was significantly longer in the BEN group (7.19 kb vs 6.79 kb; p<0.001). TL was associated in the BEN group with PWV, and in the non-BEN group with age. BEN patients presented significantly lower CV mortality than non-BEN patients (p<0.001). In the BEN group shorter TL was the only determinant of shorter survival (HR 0.11 [95% CI 0.03, 0.35]). To analyze the diagnostic value of TL for CV mortality we used ROC analysis that revealed TL < 6.21 kb to be useful for prediction of CV mortality in patients undergoing chronic HD.

Conclusions:

Shorter TL is associated with CV mortality in patients undergoing chronic HD. BEN patients had longer TL and longer survival than other ESKD patients. In BEN patients, TL was negatively associated with PWV. This study confirmed our hypothesis that BEN is associated with slower vascular aging and that longer TL may partially explain this phenomenon.
EFFECTS OF SODIUM-GLUCOSE CO-TRANSPORTER 2 INHIBITORS ON CARDIOVASCULAR MORTALITY IN CHRONIC KIDNEY DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Alexandrou Maria Eleni , Pella Eva , Tsitouridis Alexandros , Theodorakopoulou Marieta , Sampani Erasmia , Georgiou Areti , Kamperidis Vasileios , Papagianni Aikaterini , Sarafidis Pantelis
Published: June 2023

Objective:

In studies of patients with chronic kidney disease (CKD), recommended nephroprotective therapy with ACE-inhibitors or ARBs has not been shown to reduce cardiovascular (CV) events or mortality. Sodium-glucose co-transporter 2 (SGLT-2) inhibitors reduce cardiovascular events and death in patients with diabetes and established CV disease; evidence from studies in populations with CKD has been inconsistent. The aim of this meta-analysis was to evaluate the effect of SGLT-2 inhibitors on cardiovascular (CV) mortality in patients with CKD.

Design and method:

Studies were identified by search in major electronic databases (PubMed/MEDLINE, Scopus, Cochrane Library and Web of Science) (PROSPERO ID: CRD42022382863). We included randomized controlled trials assessing the effect of SGLT-2 inhibitors on the primary outcome, time to cardiovascular death, in patients with CKD at baseline. Secondary outcomes included all-cause mortality and major adverse cardiac events (MACE).

Results:

Eleven studies with 83,203 participants with CKD were eligible for inclusion in the meta-analysis. Treatment with SGLT-2 inhibitors, compared to placebo, reduced the risk of CV death by 14% (hazard ratio [HR] 0.86; 95%CI 0.79-0.94), of all-cause death by 15% (HR 0.85; 95%CI 0.79-0.91) and of MACE by 13% (HR 0.87; 95%CI 0.81-0.93). A consistent treatment effect on the primary outcome was observed with all SGLT-2 inhibitors (canagliflozin: HR 0.84; 95%CI 0.69-1.02, dapagliflozin: HR 0.89; 95%CI 0.78-1.01, empagliflozin: HR 0.82; 95%CI 0.69-0.97 sotagliflozin: HR 0.90; 95%CI 0.73-1.12) studied (p-subgroup-differences = 0.85). Sensitivity analysis pooling data from studies including only diabetic patients with CKD yielded similar results (HR 0.86; 95%CI 0.77-0.97).

Conclusions:

Treatment with SGLT-2 inhibitors led to a significant reduction in the risk for CV and all-cause mortality in CKD patients. These findings support the use of these agents also for protection against cardiovascular events and death in CKD.
HOW TO INTERPRET URINARY PROTEINURIA AS A MARKER OF HYPERTENSIVE NEPHROPATHY?
Authors: Nawal Habak , Nadjet Rouibah , Ammar Chikouche
Published: June 2023

Objective:

Proteinuria may be the first sign of underlying nephropathy. It is pathological when the value is higher than 0.15 g/24h.

The gold standard of quantification is the determination of proteinuria on the collection of urine for 24 hours, however, in view of the errors related to the collection and storage, we adopted another mode of expression.

The objective of our work is to evaluate the correlation between the results of the 24 hours proteinuria and the proteinuria calculated by ratio (proteinuria/creatinuria).

Design and method:

Our prospective comparative study was performed on 100 24-hour urine samples (100 patients).

We recorded the 24h diuresis and we determined the proteinuria by the pyrogallol red method (Advia 1800) and the urinary creatinine by the compensated jaffa method (Cobas 6000). Statistical evaluation was performed using GraphPad Prism software7

Results:

Our results show: the average proteinuria of 24 h is 309.7 mg/24H (the norms lower than 150 mg/24H) and the average proteinuria/creatinine ratio is 283.7 mg/g (the norms lower than 300 mg/g).

Of the 100 samples, only 5 patients (5%) showed pathological 24-hour proteinuria with a proteinuria/creatinuria ratio within the norms, and one patient (1%) had 24-hour proteinuria within the norms and a high proteinuria/creatinuria ratio, 25 patients (25%) had a simultaneous increase in 24-hour proteinuria and in the proteinuria/creatinuria ratio The remaining 69 patients (69%) had 24-hour proteinuria and a proteinuria/creatinuria ratio within the physiological norms

The comparative study found a significant difference p<0.0001 with a significant positive Pearson correlation R 2 = 0.92. The agreement of the 24 h proteinuria tests and the Proteinuria/creatinuria ratio is modelled by the Bland and Altman diagram which finds a bias of 1.02 and a Confidence interval 95%] 0.046-1.36 [.

Conclusions:

Therefore it is not necessary to carry out a 24-hour urine collection, preferring measurements on urine samples from the first morning micturition. In order to overcome the numerous false positives and negatives linked to the collection of 24-hour urine, this examination is a good alternative.
INTRARENAL RESISTANCE INDEXES AND NONALCOHOLIC FATTY LIVER DISEASE IN UNTREATED HYPERTENSIVE PATIENTS
Authors: Bulfone Luca , Vacca Antonio , Catena Cristiana , Cicco Sebastiano , Soardo Giorgio , Donnini Debora , Bortolin Giulia , Candusso Giulia , Baiano Valeria , Comand Jacopo , Sechi Leonardo
Published: June 2023

Objective:

Nonalcoholic Fatty Liver Disease (NAFLD) is reaching epidemic proportions with a prevalence in the adult population of approximately 25%. A continuum of hepatic conditions is embraced by NAFLD, from plain steatosis to liver fibrosis that can be assessed by use of surrogate clinical/biochemical scores. Recent studies have reported an association of NAFLD with chronic renal failure and its progression in the general population. Because increasing of intrarenal resistance indexes (IRI) anticipate worsening of renal function in hypertension we investigated their relationships with liver steatosis and fibrosis scores in never treated hypertensive patients.

Design and method:

In a cross-sectional study of 111 treatment-naïve, essential hypertensive patients we measured IRI and calculated scores of liver steatosis (LFS: liver fatty score; FLI: fatty liver index; HIS: hepatic steatosis index) and liver fibrosis (NFS: NAFLD fibrosis score; APRI: aminotransferase to platelet ratio index; FIB-4: fibrosis 4).

Results:

IRI were significantly and directly correlated with the LFS (r = 0.240, P = 0.025) while a borderline correlation was observed with NFS (r = 0.206, P = 0.052). No significant relationships were observed with the remaining liver steatosis and fibrosis scores. Multivariate analysis indicated an independent association of IRI and LFS (B = 0.309, P = 0.030).

Conclusions:

In treatment-naïve hypertensive patients IRI are independently associated with a score of liver steatosis suggesting that NAFLD might contribute to worsening of renal function in these patients.
RELATIONSHIP BETWEEN BMI IN ADOLESCENCE, BMI TRAJECTORIES IN ADULTHOOD AND CHRONIC KIDNEY DISEASE OUTCOMES: POPULATION-BASED COHORT STUDY
Authors: Vitkauskaite Monika , Stankevicius Rytis , Macioniene Ernesta , Miglinas Marius , Brunström Mattias
Published: June 2023

Objective:

We aimed to investigate the association of BMI in late adolescence and BMI trajectories in adulthood with chronic kidney disease (CKD), end-stage kidney disease (ESKD) and acute kidney injury (AKI) later in life.

Design and method:

Two cohort analyses were performed, firstly evaluating the link between adolescent BMI and CKD, ESKD and AKI throughout life, secondly assessing the link between BMI change from adolescence to midlife, and the risk of CKD, ESKD and AKI thereafter. Data from the Swedish Conscription Register, the Northern Sweden Health and Disease Study, the Swedish National Patient Register and the Cause of Death Register were included. Patients were stratified into quintiles of BMI in adolescence and BMI change until midlife. Data were analysed using Cox proportional hazards model.

Results:

1 324 831 subjects met the inclusion criteria for BMI evaluation in late adolescence. The mean age at conscription was 18.3±0.8 years and the average BMI was 21.6±2.6 kg/m2. 5593 subjects developed CKD, 2358 developed ESKD and 8029 developed AKI. In the adjusted analyses, an increased risk of developing CKD and ESKD was seen from the fourth BMI quintile (HR 1.25, 95% CI 1.15-1.36 for BMI 21.9-23.6 kg/m2; HR 2.13, 95% CI 1.97-2.31 for BMI >23.6 kg/m2, for CKD), whereas the risk of AKI was increased already from the third BMI quintile (HR 1.15, 95%CI 1.15-1.24 for BMI 20.7-21.9 kg/m2). 32 221 subjects in a regional cohort had an additional BMI evaluation at mean age 42.1±8.6 years. The mean change in BMI between assessments was 4.8±3.2 kg/m2. We found that BMI increase of >7 kg/m2 from late adolescence to mid-life was associated with higher risk of CKD (HR 2.78, 95%CI 1.45-5.30) and AKI (3.49, 2.23-5.47) in non-adjusted analyses; only AKI persisted after adjustment (HR 2.60, 95%CI 1.58-4.28).

Conclusions:

To conclude, BMI in late adolescence is associated with CKD and ESKD, with increased risk from BMI levels >21.9 kg/m2. BMI increase during adulthood was only associated with an increased risk of AKI after covariate-adjustment, suggesting that adolescence is a critical period for the association between BMI and future kidney disease.
C-ATRIAL NATRIURETIC PEPTIDE (ANP)4-23 ATTENUATES RENAL FIBROSIS IN DEOXYCORTICOSTERONE-ACETATE-SALT HYPERTENSIVE MICE
Authors: Lu Yuanyuan , Li Shijin , Li Xiaodong , Gao Pingjin
Published: June 2023

Objective:

Epithelial-mesenchymal transition (EMT) plays a critical role in hypertension-induced renal fibrosis, a final pathway that leads to end-stage renal failure. C-Atrial natriuretic peptide (ANP)4-23, a specific agonist of natriuretic peptide receptor-C (NPR-C), has been reported to have protective effects against hypertension. However, the role of C-ANP4-23 in hypertension-associated renal fibrosis has not yet been elucidated.

Design and method:

In this study, mice were randomly divided into SHAM group, DOCA-salt group, DOCA-salt + C-ANP4-23 group and C-ANP4-23 group. Renal morphology changes, renal function and fibrosis were detected. Human proximal tubular epithelial cells (HK2) stimulated by aldosterone were used for cell function and mechanism study.

Results:

The DOCA-salt treated mice exhibited hypertension, kidney fibrosis and renal dysfunction, which was attenuated by C-ANP4-23. Moreover, C-ANP4-23 inhibited DOCA-salt treatment-induced renal EMT as evidenced by decrease of the mesenchymal marker alpha-smooth muscle actin (ACTA2) and vimentin and increase of epithelial cell marker E-cadherin. In HK2 cells, aldosterone induced EMT response, which was also suppressed by C-ANP4-23. The key transcription factors (twist, snail, slug and ZEB1) involved in EMT were increased in the kidney of DOCA-salt-treated mice, which were also suppressed by C-ANP4-23. Mechanistically, C-ANP4-23 inhibited the aldosterone-induced translocation of MR from the cytosol to the nucleus without change of MR expression. Furthermore, C-ANP4-23 prevented the enhanced expression of NADPH oxidase (NOX) 4 and oxidative stress after aldosterone stimulation. Aldosterone-induced Akt and Erk1/2 activation was also suppressed by C-ANP4-23.

Conclusions:

Our data suggest that C-ANP4-23 attenuates renal fibrosis, likely through inhibition of MR activation, enhanced oxidative stress and Akt and Erk1/2 signaling pathway.
A CROSS-SECTIONAL STUDY OF SERUM OSTEOCALCIN LEVEL ASSOCIATED WITH PERIPHERAL ARTERIAL STIFFNESS BY BRACHIAL-ANKLE PULSE WAVE VELOCITY IN HYPERTENSIVE PATIENTS
Authors: Wang Yung-Hsuan , Wang Hui-Sheng , Wang Ji-Hung , Hsu Bang-Gee
Published: June 2023

Objective:

Brachial-ankle pulse wave velocity (baPWV) is recognized as an independent risk factor for cardiovascular events, cardiovascular mortality, and all-cause mortality. Osteocalcin (OC) is associated with vascular function. The aim of this study was to evaluate the relationship between serum OC levels and peripheral arterial stiffness (PAS) in hypertensive patients measuring by baPWV.

Design and method:

Fasting blood samples were obtained from 120 hypertensive patients. Peripheral arterial stiffness was measured by baPWV device. Serum total OC levels were measured using a commercial enzyme-linked immunosorbent assay kit. Left or right brachial-ankle pulse wave velocity (baPWV) > 18.0 m/s defined the PAS group.

Results:

Twenty-four patients (20.0%) were included in the PAS group in hypertensive patients. Hypertensive patients with PAS had a significantly higher percentage of diabetes (P = 0.010), older age (P = 0.011), higher systolic blood pressure (P = 0.019), serum fasting glucose (P = 0.003), blood urea nitrogen (P = 0.024), creatinine (P = 0.004), C-reactive protein (P = 0.007), and OC level (P = 0.002), while lower estimated glomerular filtration rate (P = 0.004) than those without PAS. After multivariable logistic regression analysis, serum OC level (Odds ratio [OR]: 1.797, 95% confidence interval (CI): 1.077–3.000, P = 0.025), and age (OR: 1.076, 95% CI: 1.004–1.153, P = 0.037) are independently associated with PAS in hypertensive patients.

Conclusions:

Serum OC levels and older age are positively associated with PAS in hypertensive patients.
MUSCLE OXYGENATION AND MICROVASCULAR REACTIVITY ACROSS DIFFERENT STAGES OF CHRONIC KIDNEY DISEASE: A NEAR-INFRARED SPECTROSCOPY STUDY
Authors: Theodorakopoulou Marieta , Zafeiridis Andreas , Dipla Konstantina , Faitatzidou Danai , Koutlas Aggelos , Doumas Michael , Papagianni Aikaterini , Sarafidis Pantelis
Published: June 2023

Objective:

Previous studies in chronic kidney disease(CKD) showed that vascular dysfunction in different circulatory beds is progressively deteriorating with CKD severity. This study evaluated muscle oxygenation and microvascular reactivity at rest, during an occlusion-reperfusion maneuver, and during exercise in patients with pre-dialysis CKD versus controls, as well as between different CKD stages

Design and method:

This observational controlled study included 90 participants (18 per CKD stage 2, 3a, 3b, 4 and 18 controls). Continuous measurement of muscle oxygenation [tissue saturation index (TSI%)] via near-infrared-spectroscopy at rest, during occlusion-reperfusion, and during a 3-min handgrip exercise(at 35% of maximal-voluntary-contraction). Aortic pulse wave velocity (PWV) and carotid intima-media thickness (cIMT) were also recorded.

Results:

Resting muscle oxygenation did not differ among the study groups (controls: 64.3±2.9 stage-2: 63.8±4.2 stage-3a: 64.1±4.1 stage-3b: 62.3±3.3 stage-4: 62.7±4.3%; p = 0.6). During occlusion, no significant differences among groups were detected in TSIocl magnitude- and occlusion-slope. However, during reperfusion, the TSImax and the hyperemic response were significantly lower in groups of patients with more advanced CKD stages (controls: 11.2±3.7 stage-2: 8.3±4.6 stage-3: 7.8±5.5 stage-3b: 7.3±4.4 stage-4: 7.2±3.3; p = 0.04). During handgrip exercise, muscle oxygenation (TSIaverage-decline) was marginally lower in CKD patients than controls, but no significant differences were detected between CKD stages.

Conclusions:

Although no differences were observed in muscle oxygenation at rest and during occlusion, the microvascular hyperemic response during reperfusion was significantly impaired in CKD and deteriorated in more advanced CKD stages. This impaired ability of microvasculature to respond to stimuli may be a crucial component of the adverse vascular profile of CKD patients and may contribute to exercise intolerance
FACTORS RELATED TO SKIN MICROVASCULAR DYSFUNCTION IN INDIVIDUALS WITH DIFFERENT RANGE OF GLUCOSE LEVELS
Authors: Lamprou Stamatina , Koletsos Nikolaos , Zografou Ioanna , Mintziori Gesthimani , Lazaridis Antonios , Doumas Michael , Gkaliagkousi Eugenia , Triantafyllou Areti
Published: June 2023

Objective:

Existing data confirm the presence of microvascular dysfunction in hypertension and diabetes mellitus (DM). Prediabetes is recognized as a significant metabolic status, being a key factor in the occurrence of DM and there is increasing evidence concerning microvascular complications in prediabetes. Laser speckle contrast analysis (LASCA) is a non-invasive technique that can be used to evaluate skin microvascular function. The aim of our study was to assess cardiovascular factors that are possibly associated with microvascular reactivity in a population from normoglycaemia to DM.

Design and method:

Individuals with normoglycemia, prediabetes and diabetes without established cardiovascular disease were included in the study. In all participants, forearm skin blood flow was recorded under standardized conditions using a laser speckle contrast imager (PeriCam PSI NR System, Perimed). Post-occlusive reactive hyperaemia (PORH) was assessed following a standardized protocol and data were analyzed with a signal processing software (PIMSoft, Perimed). Skin microvascular reactivity was expressed as a percentage increase between baseline and peak perfusion (%). Office BP was measured in each participant according to a standard methodology and aortic blood pressure was assessed using the Sphygmocor device.

Results:

Fifty individuals (18 patients with prediabetes, 16 patients with DM and 16 controls) were included in the study. In the univariate model both glucose levels and aortic systolic blood pressure (aSBP) correlated inversely with microvascular reactivity (r = -0.382 and r = -0.349, p<0.01 for both comparisons) However, in the multivariate model only the association with aSBP remained statistically significant (beta = -0.363, p<0.05).

Conclusions:

Only central SBP, but not glucose predicted skin microvascular dysfunction in individuals with normoglycemia, prediabetes and diabetes and without established cardiovascular disease.