bluuebunny/crossref_metadata_2025 huggingface dataset:
EFFECT OF RENAL DENERVATION ON AMBULATORY BLOOD PRESSURE IN PATIENTS WITH UNCONTROLLED HYPERTENSION: A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED, SHAM-CONTROLLED TRIALS
Authors: Stavropoulos Konstantinos , Patoulias Dimitrios , Katsimardou Alexandra , Imprialos Konstantinos , Koutsampasopoulos Konstantinos , Toumpourleka Maria , Sachinidis Alexandros , Dimitriadis Kyriakos , Papademetriou Vassilios , Tsioufis Konstantinos , Doumas Michael
Published: April 2021

Objective:

Untreated and uncontrolled hypertension remains among the most important cardiovascular risk factors worldwide, while hypertension treatment and control rates remain low in many countries. The aim of this study was to meta-analyze the effects of renal denervation (RDN) on ambulatory blood pressure levels in patients with untreated or uncontrolled hypertension.

Design and method:

PubMed and CENTRAL, along with grey literature sources, were searched from their inception to May 2019 for randomized, sham-controlled trials evaluating the efficacy and safety of RDN on the management of hypertension, irrespective of study blinding, setting and sample size.

Results:

Six randomized, sham-controlled trials were identified and included in the meta-analysis. In total, 981 patients with hypertension were randomized in all 6 trials to undergo either RDN (n = 585) or sham-procedure (n = 396). Compared to sham, RDN resulted in a decrease in 24-h systolic ambulatory blood pressure (ABP) by 3.62 mmHg (95% CI: -5.28 to -1.96; I^2 = 0%) and in 24-h diastolic ABP by 1.92 mmHg (95% CI: -3.65 to -0.20; I^2 = 46%). Grade of evidence was rated as low for both outcomes. Further analysis documented that RDN decreased daytime systolic ABP by 5.51 mmHg (95% CI: -7.79 to -3.23; I2 = 0%), nighttime systolic ABP by 3.06 mm Hg (95% CI: -8.69 to 2.56; I^2 = 73%), daytime diastolic ABP by 1.90 mmHg (95% CI: -3.48 to -0.32; I^2 = 4%) and nighttime diastolic ABP by 0.80 mmHg (95% CI: -3.61 to 2.02; I2 = 57%), compared to sham procedure. No major safety issues were identified.

Conclusions:

RDN is associated with a significant reduction in both 24-h systolic and diastolic ABP levels. Importantly, RDN decreases significantly daytime ABP levels, while it does not consistently induce a substantial reduction in nighttime ABP levels.
DIRECT REDUCTIONS IN BLOOD PRESSURE AND NOREPINEPHRINE LEVELS AFTER RENAL DENERVATION OF THE COLLECTING SYSTEM
Authors: Hering Dagmara , Hubbard Brad , Heuser Richard
Published: April 2021

Objective:

Variability in both renal arterial anatomy and distribution of peri-arterial renal efferent and afferent nerves affect the magnitude of blood pressure (BP) response to arterial renal denervation (RDN). No useful markers of procedural success for RDN have yet been identified. This study was performed to examine the effectiveness of RDN of the renal pelvis nerves on BP, norepinephrine (NE) and histopathology of the treated zone in a porcine model.

Design and method:

A total of 74 porcine kidneys obtained from female swine (3.5–5 months old) weighting 60–65 kg underwent bilateral RDN via ureteral access with the catheter-based 4-electode VERVE Medical PhoenixTM system positioned in the renal pelvis. Renal cortical tissue was harvested and NE levels were measured using HPLC directly post procedure and 7, 14, 30 and 90 days after RDN. Intraarterial BP was measured directly throughout RDN and at 14 days follow-up. Pyelograms, direct visual evidence of RDN with ureteroscopy, gross examination and histopathology of the kidneys, and ureters were also performed.

Results:

Using a baseline of 600 ng/g (controls), the porcine kidneys had a mean NE concentration reduction of 76% directly post procedure, 60% at 7 days, 60% at 14 days, 57% at 30 days and 65% at 90 days follow-up. There was an immediate fall in BP for systolic of -20.6 ± 20.5 and diastolic of -6.0 ± 9.3 mmHg during ablation of the renal pelvis which was maintained at follow-up. Histopathological results confirmed nerve ablation of the treated zone with unremarkable kidney, ureter, and peripelvic nerves peripheral to the immediate treatment sites. Pyelograms of renal pelvis showed no remodeling in the renal pelvis related to the device.

Conclusions:

The immediate reduction in BP and NE accompanied by nerve damage of the treated zone suggest a successful ablation of abundance of efferent and afferent nerves residing in the collecting system, providing an encouraging target for RDN. If VERVE clinical studies confirm efficacy and safety, this approach can be widely used for the treatment of hypertension, and alternative therapy for patients with renal artery abnormalities and anatomical ineligibility for arterial approach.
CHANGES IN RENAL HEMODYNAMICS DURING A COLD PRESSURE TEST ARE DETECTABLE BY DOPPLER AND CONTRAST-ENHANCED ULTRASOUND
Authors: Hendriks-Balk M. , Polychronopoulou E. , Brito W. , Pruijm M. , Wuerzner G.
Published: April 2021

Objective:

The cold pressure test (CPT) is a classic cardiovascular stress test known to increase blood pressure and heart rate secondary to an increase in nervous sympathetic activity. Its effect on renal hemodynamics using both Doppler ultrasound (DU) and contrast-enhanced ultrasound (CEUS) has not been reported previously. We hypothesized that a CPT would induce changes in renal hemodynamics detectable by DU and CEUS. The objective was to measure the renal responses during a CPT using DU and CEUS.

Design and method:

This was a single center prospective study in healthy participants. Renal resistive index (RRI) and mean acceleration time (MAT) were measured 4 times during 2 minutes baseline conditions (water at body temperature) and 4 times during 2 minutes CPT conditions (water at 4°C). The same protocol was then repeated after 5 minutes washout period for the measurement of the perfusion index (PI), relative blood volume and mean transit time using CEUS. Renal hemodynamic responses during baseline and CPT were compared using a t-test or a Wilcoxon matched-pair signed-rank test if variables were not normally distributed.

Results:

24 healthy participants (15 women, 9 men) were included. Mean age and body mass index were respectively (mean ± standard deviation) 33.9 ± 11.8 years and 24.3 ± 3.4 kg/m2. The CPT increased mean blood pressure by 19.8 ± 4.4 mmHg, heart rate by 14.0 ± 3.8 beats per min. The CPT decrease RRI from 0.60 ± 0.04 to 0.58 ± 0.04 (p = 0.018). This decrease was associated with the systolic blood pressure (rho: -0.43, p = 0.038) and heart rate response (rho = -0.52, p = 0.009). Mean acceleration time did not change. Perfusion index (median and interquartile range) increased from 2578 UI (1789; 4901) to 4148UI (2499; 6739) (p < 0.001). Relative blood volume increased, but mean transit time did not change.

Conclusions:

This is the first demonstration that the CTP induces detectable changes in renal hemodynamics using both DU and CEUS. The CPT combined to DU and CEUS may be a valuable tool to assess the renal response to increased sympathetic drive in hypertensive or chronic kidney disease patients.
N-METHYL-D-ASPARTATE (NMDA) RECEPTORS IN THE CONNECTING TUBULE INDUCE RENAL VASODILATION AND REGULATES BLOOD PRESSURE
Authors: Romero Cesar , Wang Hong , Ren Yiling , Wynne Brandi , Wall Susan
Published: April 2021

Objective:

N-methyl-D-aspartate (NMDA) receptors are expressed throughout the nephron, including distal nephron principal cells (PC), and induce renal vasodilation through an unknown mechanism. Connecting tubule-glomerular feedback (CNTGF) is a vasodilator feedback mechanism producing afferent arteriole (AfA) vasodilatation and promote sodium excretion. We hypothesized that NMDA receptors activation stimulate CNTGF and that the inhibition of NMDA receptors decrease CNTGF inducing hypertension.

Design and method:

To determine the effect of NMDA receptor on CNTGF-mediated AfA dilation, we measured CNTGF-mediated AfA dilation in the presence or absence of NMDA receptor antagonists with and without NMDA antagonist (MK801), using a double-perfusion method of the AfA and CNT ex vivo in rabbits and stop-flow pressure (SFP) technique in vivo in rats. To evaluate the effect of the NMDA receptor in blood pressure regulation, we use the NMDA inhibitor MK801 infused by osmotic minipumps for 7 days in liddle syndrome mouse (βENaC mutated allele on129/Sv background) on normal salt diet. Under normal salt diet, blood pressure (BP) is not different from wild type despite evidence for increased sodium reabsorption in distal colon and low plasma aldosterone, suggesting chronic hypervolemia. BP was measure using tail cuff methods.

Results:

In pre-constricted AfA, in vitro NMDA agonist application to the connecting tubule lumen increased AfA dilation (p < 0.001). This amino-acid-induced dilation was blocked with the CNTGF inhibitor benzamil and blunted with the NMDA receptor blocker MK-801. In vivo, NMDA agonist increase CNTGF (P < 0.01). Basal BP was similar in both mice group (p = 0.4). The infusion of NMDA inhibitor (Mk-801) during 7 days induces hypertension (SBP 146 ± 8 mmHg) while the vehicle infused mice remained normotensives (110.7 ± 7.7 mmHg; p < 0.01).

Conclusions:

NMDA receptor activation induced renal vasodilation by increasing CNTGF responses. NMDA inhibition decrease CNTGF induced-vasodilation and promote hypertension. These results provide evidence on the role of NMDA receptors on renal hemodynamic and blood pressure regulation.
ACID-BASE BALANCE IN HYPERTENSIVE PATIENTS WITH CHRONIC KIDNEY DISEASE: INFLUENCE OF DIABETES
Authors: Mule’ Giuseppe , Carollo Caterina , Sorce Alessandra , Giambrone Marta , Ferrara Alida , Giarratana Carmen , Sinatra Nicola , Vaccaro Francesco , Guarneri Marco , Cottone Santina
Published: April 2021

Objective:

Metabolic acidosis is a common complication of advanced CKD and it has been associated with an increased risk of death and faster renal function decline. Diabetes mellitus is one of the most crucial cause of CKD. The dysregulation of glucose homeostasis may lead to many acid–base balance disorders.

Our study was aimed to compare the acid-base status in diabetic patients with severe CKD with non diabetic CKD subjects.

Design and method:

Study population included 143 consecutive CKD hypertensive subjects attending our Nephrology unit with advanced renal failure. To be included on the study, patients were required to have an estimated eGFR of less than 30 mL/min, no intake of alkali within the previous 30 days, and the absence of pulmonary diseases and other clinical conditions at the time of the study that could explain an acute imbalance of the acid-base status, such as heart failure, hemorrhage, or sepsis. Patients were divided into two groups on the basis of the presence (n = 73) or the absence of Type 2 diabetes mellitus (n = 70) Arterial blood samples were drawn in all the subjects.

Results:

Age, sex distribution, serum creatinine, eGFR and proteinuria were not different in the two groups. Blood pH [7.406 (7.35–7.43) vs 7.384 (7.32–7.41), p = 0.02], bicarbonate levels [22 (19.1–23.7) vs 20.5 (17.4–23.1); p = 0.05] were higher and the prevalence of metabolic alkalosis (16.8 vs 8.4 %) was greater in diabetic patients as compared to non diabetic ones. The positive associations between diabetes and pH values (beta: 0.186; p = 0.02) and between diabetes and metabolic alkalosis (odds ratio 2.68; p < 0.05), were confirmed respectively in linear multiple regression analyses and in logistic multivariate models even after adjustment for potential confounders.

Conclusions:

Our results, in agreement with those obtained in a previous study (Caracava F et al, Am J Kidney Dis 1999), seem to suggest that metabolic alkalosis is more common than metabolic acidosis in diabetic patients with severe CKD. Further studies are needed in order to provide the pathophysiological explanations of these findings.
AORTIC STIFFNESS AND AORTIC TO ARTERIAL MISMATCH AS MARKERS OF KIDNEY INJURY IN HYPERTENSION
Authors: Lundwall Kristina , Jekell Andreas , Jacobson Stefan , Kahan Thomas , Desta Liyew , Spaak Jonas
Published: April 2021

Objective:

Vascular stiffening is an important feature of the cardiorenal syndrome. Which hemodynamic and vascular parameters that are of most importance, and thereby best might serve as predictive markers for kidney failure in a hypertensive population, remains unclear. We therefore investigated a broad spectrum of hemodynamic parameters in a hypertensive population with kidney function ranging from normal to severe dysfunction, and then studied their independent relation to eGFR.

Methods:

Individuals with hypertension and varying degree of kidney dysfunction from two RCTs (DoRa and SOLID) were studied. Carotid to femoral (CF) pulse wav velocity (PWV), carotid to radial PWV, aortic (CF) to arterial (CR) mismatch (CF/CRPWV ratio), flow mediated vasodilation (FMD), subendocardial viability ratio (SEVR), central pulse pressure, central blood pressure, and echocardiographic measures of stiffness (left atrial volume index, E/é, left ventricular mass index) were measured. Hemodynamic parameters were correlated to kidney function, and for significant correlations, independence was investigated with multivariate regression.

Design and method:

107 participants were investigated, with eGFR ranging from 130 to 21 ml/min, mean eGFR of 73.8 ml/min. Mean age was 58 years, 9.3% had experienced a cardiovascular event, and 30.8% were on antihypertensive treatment. Mean BP was 150/87mmHg. CFPWV, a measure of aortic stiffness, and CF/CRPWV, a measure of the mismatch between aortic and arterial stiffness, showed independent correlations with eGFR (−coeff −0,159, p = 0.01 and −coeff −0.123, p = 0.04 respectively), whereas neither measures of endothelial dysfunction nor measures of ventricular stiffness showed significant correlations.

Conclusion:

Our results imply a profound importance of aortic stiffness in chronic kidney disease related vascular dysfunction, and suggest that measures of aortic PWV and the mismatch to arterial PWV might serve as risk markers of kidney injury in the hypertensive population.
URINARY PLASMIN PLAYS PATHOGENIC ROLES FOR THE DEVELOPMENT OF HYPERTENSION IN SALT-SENSITIVE HYPERTENSION WITH PROTEINURIA
Authors: Kakizoe Yutaka , Deng Qinyuan , Iwata Yasunobu , Adachi Masataka , Nakagawa Terumasa , Izumi Yuichiro , Kuwabara Takashige , Mukoyama Masashi
Published: April 2021

Objective:

The epithelial sodium channel (ENaC) in the renal collecting duct plays pivotal roles in the regulation of sodium homeostasis and blood pressure. The proteolytic cleavage of γENaC by extracellular serine proteases is an important process for the full activation of this channel and is physiologically regulated by aldosterone. In the setting of proteinuria, plasminogen/plasmin filtered through damaged glomeruli could activate ENaC leading to hypertension, independently of aldosterone. We reported that Dahl salt-sensitive (DS) rats with high-salt (HS) diet developed severe hypertension together with aberrant activation of γENaC by serine proteases. However, the role of plasmin in the hypertension of DS rats remain to be elucidated. In this study, we evaluated the relationship of proteinuria, urinary plasmin activity and hypertension, and the antihypertensive effect of a serine protease inhibitor camostat mesilate (CM) in DS rats.

Design and method:

Five-week-old DS rats were divided into normal-salt (NS) diet, HS and HS+CM (0.1% diet) groups. After systolic BP (SBP) measurement and 24h urine collection were performed for 5 weeks, rats were sacrificed for biochemical examination. Urinary plasmin activities were evaluated by zymography and Western blotting (WB). The proteolytic cleavage of γENaC in urinary exosome was evaluated by WB.

Results:

HS diet induced severe hypertension, marked proteinuria and urinary plasmin activation, as well as the cleavage of urinary exosomal γENaC. The treatment with CM suppressed these changes, together with significantly reduced BP and proteinuria [SBP (mmHg): NS, 141.1 ± 5.8; HS, 222.3 ± 15.4; HS + CM, 199.5 ± 5.0. urinary protein (mg/day): NS, 23.8 ± 12.1; HS 272.3 ± 79.9; HS ± CM, 135.1 ± 27.4].

Conclusions:

In conclusion, plasmin is associated with the pathogenesis of hypertension in DS rats, and serine protease inhibition could be a potential therapeutic strategy against salt-sensitive hypertension with proteinuria.
UP-REGULATION OF SGLT-5 AS A CAUSE OF FRUCTOSE-INDUCED VOLUME-DEPENDENT HYPERTENSION
Authors: Hara Hiroaki , Takayanagi Kaori , Terao Masaaki , Kurosawa Akira , Iwasita Takatugu , Simizu Taisuke , Ogawa Tonari , Kanozawa Kouichi , Hasegawa Hajime
Published: April 2021

Objective:

Excessive intake of fructose causes a variety of adverse conditions including obesity, hepatic steatosis, insulin resistance, uric acid overproduction and hypertension which is the most common and significant pathological setting. Cause of the hypertension is not known at present. This study aimed to elucidate the underlying mechanism of fructose-induced hypertension by rat model.

Design and method:

Male SD rats (7 weeks old) were fed by food containing 60% glucose (GLU) and 60% fructose (FRU) for 3, 6 and 12 weeks. Histological, immunohistological and molecular biological analysis, and gene chip study were applied. No difference of calorie and salt intake of individual animal was daily checked by the measured weight of remaining food.

Results:

Mean blood pressure and fractional sodium excretion (FENa) of FRU were both significantly higher (BP 12w-GLU: 94.8 ± 3.4 vs 12w-FRU: 103.7 ± 1.2 mmHg; FENa 12w-GLU: 0.084 ± 0.011 vs 12w-FRU: 0.059 ± 0.08%), suggesting that fructose caused ECF volume-dependent hypertension. Glomerular expansion in FRU (glomerular surface area in 12w-GLU: 7495 ± 181 vs 12w-FRU: 9831 ± 164 square micrometer) was agreed with the increase in the ECF volume. The expression of GLUT-5, fructose entry pathway, and ketohexokinase, phosphatase of fructose, in the proximal tubule were both up-regulated by fructose. As a candidate of fructose-induced salt reabsorption pathway, NHE3 was focused first because it is principal salt reabsorption pathway of proximal tubule. However, gene expression analysis, immunohistochemistry and immunoblotting of whole and phosphorylated NHE3 indicated negative results. To explore salt transporting molecules responding to fructose, gene chip analysis was conducted, and Slc5a10, corresponding to SGLT-5, showed significant up-regulation. The result was confirmed by RT-PCR (12w-GLU: 75.0 ± 5.8% vs 12w-FLU: 230.1 ± 16.0%) and in-situ hybrydization.

Conclusions:

Excess intake of fructose caused volume-dependent hypertension due to increased salt reabsorption through fructose-induced up-regulation of SGLT-5.
DIVERSIFIED RENAL TUBULAR EPITHELIAL REMODELING AND WATER BALANCE IN GITELMAN'S SYNDROME AND THIAZIDE-TREATED HYPERTENSIVE PATIENTS
Authors: Verzicco Ignazio , Tedeschi Stefano , Perlini Stefano , Graiani Gallia , Coghi Pietro , Merla Simona , Montanari Alberto , Musiari Luisa , Brusasco Irene , Gerra Luigi , Savona Ambra , Figus Giuliano , Cannone Valentina , Negro Aurelio , Vignali Alessandro , Volpi Riccardo , Cabassi Aderville
Published: April 2021

Objective:

Mutations leading to loss of function of NaCl cotransporter (NCC) in the distal convoluted tubule is the basis defect of Gitelman's Syndrome (GS), which is clinically characterized by hypokaliemic metabolic alkalosis, hypomagnesemia, hypocalciuria and normal or low blood pressure with increased renin activity and high aldosterone levels. NCC is the target of thiazide diuretics (TZ) and clinical and laboratory findings of GS patients resemble those on chronic thiazide diuretics treatment. From a physiopathological perspective, this similarity in term of site of defect or site of action (NCC in distal convoluted tubule) for GS or TZ-treated patients respectively, should not alter their urine-concentrating or diluting ability. We aimed to study water balance pathways in these 2 clinical settings.

Design and method:

We investigated two groups of patients: 1) GS (n = 5, age range 21–43, 2 females and 3 males, mean concentration of blood potassium 2.9 mmol/L, bicarbonate 34 mmol/L and magnesium 1.2 mg/dl, normotensive) and 2) TZ hypertensive patients (n = 11, age range 26–48, 4 female and 7 males, blood pressure normalized with chronic thiazide type or like diuretics including hydrochlorothiazide, chlortalidone and indapamide maintained for at least 2 months) to evaluate their water balance pathway by determining plasma and urine osmolarity and to assess through urine aquaporin 2 (AQP2)/creatinine ratio their sensitivity to antidiuretic hormone. These measurements were repeated three times in the same patients.

Results:

Four out of five GS patients showed a urinary AQP2/creatinine ratio lower than TZ-treated patients (mean value of AQP2/creatinine of GS vs TZ-treated p < .05), associated with lower urine osmolarity (p = 0.03).

Conclusions:

Our study shows that water balance in these two groups may be differently handled: A diversified renal tubular epithelial remodeling of medullary collecting duct cells related to TZ treatment could be suggested, leading to an increased prevalence of principal cells on intercalated cells, thus increasing free water reabsorption.
RELATIONSHIP BETWEEN ARTERIAL STIFFNESS AND RENAL FUNCTION DETERMINED BY CKD-EPI AND MDRD EQUATIONS IN A CHINESE COHORT UNDERGOING HEALTH ASSESSMENT
Authors: Tang Biwen , Zhao Jiehui , Deng Xueqin , Tan Isabella , Butlin Mark , Avolio Alberto , Zuo Junli
Published: April 2021

Objective:

The relationship between the renal function and large arteries remains to be determined. Our study investigated the relationship between carotid-femoral pulse wave velocity (c-fPWV) as a measure of arterial stiffness and renal function in healthy participants.

Design and method:

Our cross-sectional study was conducted in healthy individuals in China. We enrolled participants from January 2017 to June 2019. c-fPWV and blood pressure were measured and blood samples taken in all participants. Estimated glomerular filtration rate (eGFR) was evaluated by four different formulae using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Modification of Diet in Renal Disease (MDRD) equations: (i) CKD-EPICr formula based on Cr, (ii) CKD-EPICysC formula based on CysC, (iii) CKD-EPICrCysC formula based on Cr andCysC, (iv) MDRD.

Results:

Average age of 431 study participants was 53.1 ± 13.0 years (68.1% male), 23.7% had diabetes mellitus, 66.6% had hypertension. The average eGFR values of CKD-EPICr, CKD-EPICysC, CKD-EPICrCysC and MDRD equations were respectively 91.9 ± 15.6, 86.8 ± 21.4, 89.6 ± 18.3 and 90.7 ± 16.6 ml/min·1.73m2. c-fPWV was significantly and negatively correlated with eGFR of CKD-EPICr (r = -0.336), CKD-EPICysC (r-0.385), CKD-EPICrcysC (r = -0.378) and MDRD (r = 0.219) equations. After adjusting for confounding factors, c-fPWV remained significantly and negatively correlated with eGFR evaluated by CKD-EPICysC equation (β=-0.118), and significantly and positively correlated with age (β = 0.347), SBP (β= 0.275), HR (β = 0.086), FPG (β= 0.098).

Conclusions:

In normal individuals in China, c-fPWV is negatively correlated with eGFR evaluated in different four equations, however only the equation of CKD-EPICysC showed an independent relation with c-fPWV.
EVOLUTION OF RESERVOIR-WAVE ANALYSIS PARAMETERS AFTER KIDNEY TRANSPLANTATION
Authors: Côté Nadège , Philibert Emy , Paré Mathilde , Goupil Rémi , Fortier Catherine , Schultz Martin G. , Sharman James E. , Agharazii Mohsen
Published: April 2021

Objective:

According to reservoir-wave analysis (RWA) arterial pressure is the sum of a reservoir pressure (RP) accounting for dynamic storage and release of blood from arteries, and an excess pressure (XSP) analogous to flow. RP is the minimal left ventricular work required to generate aortic flow, while XSP corresponds to surplus cardiac workload. We have previously shown that kidney transplantation (KTx) improves aortic stiffness. We now aim to determine how the improvement of aortic stiffness after kidney transplantation will translate on the reservoir-wave analysis parameters. We hypothesize that kidney transplantation will result in a decrease of excess pressure and of its integral.

Design and method:

This is a longitudinal observational study involving patients with kidney failure who were undergoing KTx. Before, 3, 6 and 24 months after KTx, carotid pressure waves were recorded using applanation tonometry, calibrated using brachial diastolic and mean blood pressure. Using pressure only approach, reservoir-wave analysis was used to derive RP, XSP and their integrals (RPI, XSPI).

Results:

75 patients (69% male, mean age 51 ± 13 years) were assessed. Post-KTx, PR (121.4 ± 2.4 vs. 98.1 ± 1.5; P < 0.001) and PRI (11,192.5[10,515.7–11,869.4] P < 0.001) decrease significantly and continuously. XSP (18.8 ± 1.1 vs. 18.6 ± 1.5; P = 0.898) doesn’t decrease significantly. XSPI (390.9[331.4–450.4] P = 0.023) decreases significantly at 6 months post KTx but increases after.

Conclusions:

Kidney transplantation results in a continuous decrease of reservoir pressure and of its integral (RP and RPI). As opposed to our hypothesis, the excess pressure (XSP) does not decrease. XSP is analogous to flow. Therefore, it is possible that adding renal vessels to existing vascular network during KTx increases cardiac output. This could explain why we do not see a decrease of excess pressure post KTx despite reduced arterial stiffness.
ASSOCIATION OF PARATHYROID HORMONE WITH PULSE WAVE VELOCITY PROGRESSION
Authors: Cheng Yi-Bang , Guo Qian-Hui , Zhang Dong-Yan , Wang Ying , Huang Jian-Feng , Huang Qi-Fang , Sheng Chang-Sheng , Xu Ting-Yan , Wang Ji-Guang , Li Yan
Published: April 2021

Objective:

We recently demonstrated that carotid-femoral pulse wave velocity (cfPWV) was independently associated with both blood pressure and the serum level of parathyroid hormone (PTH) in untreated Chinese. We investigated in the same cohort whether baseline serum PTH predicted cfPWV and its progression at a 5-year follow-up.

Design and method:

Consecutive untreated outpatients referred for ambulatory blood pressure monitoring were recruited and followed-up. Serum PTH was measured with electrochemiluminescence immunoassay. cfPWV was measured using the SphygmoCor (AtCor, Australia) device. Pearson's correlation, single and multiple regressions were applied for analyses.

Results:

Totally 549 patients (mean age, 51.5 years; 49.2% women) had a follow-up at a median of 5 years. The prevalence of hypertension increased from 39.5% to 79.3%, and cfPWV from 7.79 m/s to 7.83 m/s, with an averaging progression rate of 0.01 m/s/y. With adjustments applied for sex, age, body mass index, heart rate and fasting plasma glucose, serum PTH predicted higher cfPWV at follow-up. Each double of serum PTH was associated with 0.20 m/s higher cfPWV at follow-up (P = 0.035). The association remained significant after further adjusted for eGFR, total-to-HDL cholesterol ratio and systolic blood pressure (P = 0.019). However, with similar adjustment applied, serum PTH was associated with neither cfPWV progression nor the progression rate (P > = 0.17).

Conclusions:

Serum PTH was positively associated with cfPWV both at baseline and 5-year follow-up, but not with PTH progression, indicating that PTH might be a marker but not a main culprit for arterial stiffening.
EARLY LEFT VENTRICULAR GLOBAL LONGITUDINAL STRAIN DETERIORATION AFTER AORTIC ANEURYSM REPAIR IN HYPERTENSIVE PATIENTS: IMPACT OF AORTIC STIFFNESS
Authors: Marketou Maria , Papadopoulos George , Kontopodis Nikolaos , Patrianakos Alexandros , Nakou Elenh , Maragkoudakis Spyros , Stratakis Stavros , Tavlas Emmanuel , Ioannou Christos , Parthenakis Fragiskos
Published: April 2021

Objective:

Invasive abdominal aortic aneurysm (AAA) replacement with an endograft interposes between the normal arterial tree which may acutely reduce overall systemic compliance. As a result, the input impedance is significantly increased, as are central systolic and pulse pressures. We evaluated changes in left ventricular global longitudinal peak strain (GLPS) in hypertensive patients undergoing repair of AAA in relation with the changes in arterial stiffness.

Design and method:

This was a single-center, nonrandomized, prospective, observational cohort study. Consecutive AAA hypertensive patients who underwent open or endovascular repair (EVAR) were enrolled. All patients were asymptomatic from their AAA and were admitted for elective treatment; there were no planned adjunctive procedures at the time of repair. A standard M-mode and 2-dimensional (2D) echocardiographic study was performed in all participants Left ventricular global longitudinal strain (GLS), and carotid-femoral pulse wave velocity (cf-PWV) were estimated 1 week preoperatively, as well as 1 and 6 months postoperatively. Left ventricular global longitudinal strain (GLS), and carotid-femoral pulse wave velocity (cf-PWV) were estimated 1 week preoperatively, as well as 1 and 6 months postoperatively.

Results:

A total of 70 men, mean age 70 ± 7 years, were evaluated. Of these, 58 underwent EVAR and 12 open repair. A significant time effect was found on cf-PWV, which showed an increase at 1 month and remained thereafter (p = 0.006). Additionally, a deterioration in GLS values was revealed, with a significant increase at 1 month that persisted 5 months later (p < 0.001). No significant group effect was observed between EVAR and open repair (p = 0.98) and there was no significant interaction (p = 0.96). Notably, the difference of global longitudinal strain (DGLS) between baseline and 6 months significantly correlated with the corresponding changes in cf-PWV (r = 0.494, p < 0.0001).

Conclusions:

AAA repair may have detrimental effects in cardiac systolic function. Our findings highlight the need a more intense cardiac surveillance program after aortic reconstruction. Further studies are needed to investigate how this may translate into long-term manifestations of cardiovascular complications and symptomatology.
MIXED-METHOD PROCESS EVALUATION PROTOCOL OF A RANDOMIZED CONTROLLED TRIAL OF AN APP-BASED EDUCATION PROGRAM TO REDUCE SALT INTAKE IN SCHOOL CHILDREN AND THEIR FAMILIES IN CHINA
Authors: Sun Yuewen , Luo Rong , Li Yuan , He Fengjun , Zhang Puhong
Published: April 2021

Objective:

Dietary salt intake is a major risk factor for high blood pressure. It is extremely challenging to reduce salt intake in China, with about 80% being added by the consumers. In recognition this challenge, an innovated salt reduction intervention package (AppSalt) based on smartphone application with functional modules of education, evaluation, target setting and monitoring, decision support and management, was developed and applied among school children and their family members. Process evaluations are crucial for understanding how and why the interventions resulted in its observed effect in this setting, but also inform transferability and future implementation in many other countries. This protocol is to describe the methodology of the process evaluation of AppSalt program, to promote transparency and share the approach, which can be adapted for use in other complex interventions.

Design and method:

We describe the pragmatic methods on five process evaluation dimensions: The fidelity of the implementation, intervention dose delivered and received, reach of the intervention strategies, and the contextual factors influencing the intervention, informed by the theoretical framework of process evaluation proposed by Linnan and Steckler. Quantitative and qualitative data will be triangulated to provide a clearer picture of the AppSalt implementation in the real world.

Mixed methods will be used for collecting and analysis the process data. The APP usage log, activity logs, routinely collected monitoring data and mid-term survey will be the major quantitative process data source to analyse the fidelity, reach and dose of intervention strategies. To understand participants’ experiences and the causal mechanism of the intervention strategies, semi-structured interview will be used for purposively selected intervention participants and key stakeholders from local health and education authorities.

Results:

This is a protocol paper. Data collection is still ongoing. Therefore, there is no results in this abstract.

Conclusions:

This protocol provides a good example of how to integrate process evaluation into public health interventions. It will be helpful for other researchers and policy-makers to replicate the evidence of AppSalt program and design their own salt reduction program.
TISSUE NA+ EXCESS UPON EXPERIMENTAL SALT-LOADING IS SYSTEMIC AND REFLECTS ISOTONIC OEDEMA
Authors: Rossitto Giacomo , Mary Sheon , Chen Jun Yu , Boder Philipp , Neves Karla B. , Alves Rheure L. , Montezano Augusto , Petrie Mark C. , Graham Delyth , Touyz Rhian M. , Delles Christian
Published: April 2021

Objective:

Skin was identified as a large depot for Na+ accumulation. Its proposed water-independent (hypertonic) nature has the potential to induce local pathogenic changes, including activation of the osmotic stress sensor TonEBP-mediated lymphangiogenic signalling. Blockade of this response led to salt-sensitive hypertension. Our study tested the hypertonic nature and organ-specific distribution of tissue Na+ accumulation upon salt-loading.

Design and method:

Twelve weeks-old male and female stroke-prone spontaneously hypertensive (SHRSP) and control Wistar-Kyoto (WKY) rats were treated with 1% NaCl in drinking water (high salt, HS) or normal water (NS) for 3 weeks (n = 8–10/sex/group). Tissue water and Na+/K+ content, as well as TonEBP gene expression in abdominal skin, liver, lung, myocardium and skeletal muscle were measured by gravimetric approach (wet–dry weight), flame photometry and qRT-PCR, respectively. The functional effects of in-vivo and ex-vivo exposure of resistance arteries to salt excess (HS treatment and incubation in +15 mM NaCl, respectively) were assessed and compared by wire myography.

Results:

Tissue Na+ increased in skin (+20.7%), but also liver (+10.3%), lungs (+14.8%) and skeletal muscle (+23.6%) in HS-SHRSP compared to NS; apart from skeletal muscle, it was consistently paralleled by water (skin: +14.1%; liver: +4.8%; lungs: +9.0%; p < 0.05 for all). Patterns were similar between males and females and absent in WKY. In both strains and all organs, K+ + Na+ concentration was not affected by HS and sat within physiological limits, thus pointing against hypertonicity. Nevertheless, TonEBP gene expression changes matched Na+ and water isotonic accumulation in SHRSP-HS skin, liver and lungs.

Hypertonic incubation did not induce hypercontractile responses but exacerbated the sensitivity to NO-mediated relaxation in arteries from both strains (δIC50, p < 0.001). The effect of in-vivo HS, in keeping with classic hypertensive vascular changes, was opposite (p < 0.001, in SHRSP only).

Conclusions:

If water independent, interstitial Na accumulation is unlikely to underpin the development of experimental hypertension via a direct impact on vascular function. Tissue Na+ excess upon HS rather reflects isotonic oedema accumulation and systemic changes in tissue architecture, not solely confined to skin, and sensed by TonEBP.
THE EFFECTS OF ADDING EXERCISE TO USUAL CARE ON BLOOD PRESSURE IN PATIENTS WITH HYPERTENSION, TYPE II DIABETES MELLITUS, AND/OR CARDIOVASCULAR DISEASE (PRELIMINARY RESULT)
Authors: Rijal Anupa , Nielsen Emil Eik , Neupane Dinesh , Olsen Michael Hecht , Jacokbsen Janus Christian
Published: April 2021

Objective:

Exercise is one of the most commonly recommended interventions for hypertension, type II diabetes, and/or cardiovascular disease. However, previous reviews have shown conflicting evidence on the effects of exercise and especially the effects in low- and middle-income countries (LMICs) is debated. Our objective was to assess the beneficial and harmful effects of adding exercise to usual care for people with hypertension, type II diabetes, and/or cardiovascular disease in high-income countries (HICs) and LMICs.

Design and method:

We searched CENTRAL, MEDLINE, EMBASE, LILACS from inception to present time, and further searched the bibliography of retrieved articles and reviews. We included relevant randomised clinical trials and cluster randomised trials irrespective of trial duration, publication status, publication year, and language. Two independent investigators assessed each trial for methodological quality. A random-effects model was used to meta-analyse data, we used test of interaction to compare the effects of exercise in HIC and LMIC, and heterogeneity (I2) was assessed by the χ2 test on Cochran's Q statistic. Our protocol was registered with PROSPERO, number CRD42019142313 and published before our literature search was conducted.

Results:

We included 96 trials randomising 6002 participants with type II diabetes (34 trials), hypertension (26 trials), and rest were trials on CVDs. The mean follow-up for the trials was 5.21 (SD: ± 4.07) months. Meta-analysis including all trials showed that exercise compared with control decreased the systolic blood pressure (SBP) 4.66 mmHg (95% CI: -6.24 -3.07; I2 93.6, p < 0.001). Test of interaction showed that the decrease in SBP was higher in LMICs (-8.69; 95% CI -11.95 -5.43; I2 89.73, p < 0.001) compared to HICs (-3.315; 95% CI -5.002 -1.62; I2 93.05, p = 0.000) and the difference was significant (Q = 8.25 p < 0.001). Likewise, exercise decreased the overall diastolic blood pressure (DBP) 2.98 (95% CI; -4.04 -1.93; I2 = 93.35, p < 0.001) however the difference was not significant between LMICs and HICs (Q = 1.66 p = 0.198).

Conclusions:

This reiterates the possibility of implementing exercise on population level as a cheap, low risk, non-pharmacological cardiovascular prevention.
EFFICACY OF CINNAMON CONSUMPTION FOR REDUCING BLOOD PRESSURE IN ADULT HYPERTENSIVE MALES
Authors: Patil Mansi , Patil Vishal
Published: April 2021

Objective:

To assess the efficacy of cinnamon consumption on change in weight, blood pressure, blood glucose levels and anthropometry [waist circumference (WC), Waist to hip ratio (WHR), Body mass Index (BMI)] after 30 days in obese, diabetic hypertensive males.

Design and method:

A cross-sectional study on 200 male patients with uncontrolled hypertension was conducted to assess the effect of consuming 2 gms of home ground cinnamon powder on blood pressure, weight and anthropometry. Patients (n = 200) were advised a 1800 kcals diet with 60% carbohydrates, 20% proteins and 20% fats. Patients (n = 100) were provided dietary advice including cinnamon and 100 patients (control group) were advised to continue the same advised diet without cinnamon. Diet diary was maintained by patients and monitored weekly. Clinic blood pressure, height, Weight, WC and hip circumference measured using the NHANES standard procedures. BMI and WHR were calculated.

Results:

At the commencement of the trial 68% (136/200) patients were obese and 22% (44/200) overweight. Significant weight loss was observed in both groups- cases (p < 0.0001) and control group (p < 0.05). The group ingesting cinnamon, after adjusting for other parameters, was associated with significant reduction in WC, WHR (p < 0.001) and both SBP and DBP (p < 0.0001). Significant reduction in SBP in group consuming cinnamon with reduction in WC and BMI (p < 0.001). Significant reduction in DBP associated with reduction in WHR, WC and BMI (p < 0.001). Change in BSL (F,PP) were not found to be significant in both groups.

Conclusions:

Cinnamon was found to be effective in weight loss and reduction of systolic and diastolic blood pressure in patients with uncontrolled hypertension. Weight loss, reduced WC and WHR in group ingesting cinnamon was positively correlated with a reduction in SBP and DBP.
THE EFFECT OF PLANT-BASED DIETS ON BLOOD PRESSURE: A SYSTEMATIC REVIEW AND META-ANALYSIS OF CONTROLLED CLINICAL TRIALS
Authors: Gibbs Joshua , Gaskin Eleanor , Ji Chen , Miller Michelle , Cappuccio Francesco
Published: April 2021

Objective:

Strict vegetarian diets with no animal products are associated with low blood pressure (BP). It is not clear whether less strict plant-based diets (PBD) exert similar effects. We assessed whether less strict PBDs reduce BP in controlled clinical trials.

Design and method:

We carried out a systematic review and a meta-analysis of all published intervention trials assessing the effects of PBDs on BP according to PRISMA guidelines (PROSPERO: CRD42019153716). On 14 June 2019 we performed a systematic search of publications using MEDLINE (1966–2019), EMBASE (from 1980), CINHAL, WoS and manual searches without language restrictions. Inclusion criteria were age > 18 years, PBD as an intervention, defined as dietary patterns that support high consumption of fruits, vegetables, whole grains, legumes, nuts and seeds, and avoid the consumption of most or all animal products, mean differences in systolic/diastolic BP between PBD and control diet, controlled clinical trial. Standardised mean differences in BP and 95% C.I. were pooled using a random effect model. Quality, sensitivity, heterogeneity and publication bias were assessed.

Results:

Thirty-nine studies met the inclusion criteria. They included 8,203 participants (4,333 in intervention; 3,870 control groups). Median sample size was n = 65 (range 11–4,717) and mean age of the participants 50.5 yrs (range 25.6–71.0). All were controlled trials (duration 1.4 to 208 wks, median 12 wks). Of the 39 trials, 36 were randomised. Seven were crossover. Two were single-blinded. The interventions were DASH diet (n = 11), Mediterranean diet (MD, n = 8), vegan diet (VD, n = 8), lacto-ovo vegetarian diet (LOVD, n = 5), healthy Nordic diet (ND, n = 3), high fiber diet (HFD, n = 3), and high fruit and vegetables diet (FVD, n = 2). In the pooled analysis, PBDs were associated with lower systolic BP (DASH 5.53 mmHg [-7.95,-3.12], MD -0.95 mmHg [-1.70,-0.20], VD -1.61 mmHg [-4.53,1.31], LOVD -5.47 mmHg [-7.60,-3.34], ND -4.47 mmHg [-7.14,-1.81], HFD -0.65 mmHg [-1.83,053], FVD -0.57 mmHg [-7.45,6.32]. Similar effects were seen on diastolic BP. There was no evidence of publication bias and some heterogeneity was detected.

Conclusions:

PBDs with limited or no animal products lower both systolic and diastolic BP, across sex, age and body mass index.
THE EFFECT OF HEALTH CLASS ON BLOOD PRESSURE STATUS IN TARUMIZU CITY, KAGOSHIMA PREFECTURE OBTAINED FROM HOME BLOOD PRESSURE MEASUREMENT
Authors: Akasaki Yuichi , Kubozono Takuro , Higuchi Koji , Kawasoe Shin , Tokushige Akio , Sakoda Takashi , Ikeda Yoshiyuki , Ohishi Mitsuru
Published: April 2021

Objective:

The mortality rate of cerebrovascular disease is 1.5 times higher than that of the whole country and the second highest treatment rate in Tarumizu City, Kagoshima, Japan. It is a region where the proportion of elderly people exceeds 40%, which is higher than the average of 27% in Japan. The average value of systolic blood pressure in Japan has been decreasing year by year, but in 2016, the treatment rate of hypertension was 50–60% or more, and the management rate of hypertension was only about 40% for men and about 45% for women.

In this study, we investigated the effects of home blood pressure measurement, and dietary and exercise guidance on blood pressure.

Design and method:

The blood pressure at the time of consultation of the prospective cohort study (Tarumizu Study) participants was measured, and home blood pressure was measured by using home sphygmomanometer (OMRON, HEM-9700T). The subjects were 342 people who measured home blood pressure for 4 months. After measuring for two months, home sphygmomanometer data was collected. At the same time, health care classroom about exercise, diet and salt reduction was given. Thereafter, home blood pressure was measured in the same manner for 2 months, and changes in blood pressure were examined.

Results:

The blood pressure was categorized by home blood pressure measurement for 2 months. As a result, 114 patients with hypertension and 64 patients with masked hypertension had an average blood pressure of 143.6 / 84.5 mmHg. The hypertension treatment rate was 48%. The average blood pressure after 2 months in the hypertensive group was 139.6 / 82.5 (-4.0 / -2.0) mmHg, indicating an improvement in blood pressure. The blood pressure management rate improved from 37% to 42%.

Conclusions:

The treatment rate for hypertension and blood pressure management rate were comparable to those reported in Japan. Measurement of home blood pressure, explanation of results, guidance on exercise, diet and salt reduction, improved blood pressure which was confirmed by home blood pressure measurement. This results confirmed that blood pressure measurement and guidance on hypertension were important.
N-3 POLYUNSATURATED FATTY ACIDS ENRICHED HEN EGGS CONSUMPTION ENHANCES MICROVASCULAR ENDOTHELIAL FUNCTION IN PROFESSIONAL ATHLETES
Authors: Stupin Marko , Kolar Luka , Stupin Ana , Jukic Ivana , Susnjara Petar , Mihaljevic Zrinka , Matic Anita , Drenjancevic Ines
Published: April 2021

Objective:

We reported previously that consumption of n-3 polyunsaturated fatty acids (n-3 PUFAs) enriched hen eggs (777 mg of n-3 PUFAs per day for three weeks) enhances forearm skin microvascular reactivity to vascular occlusion (post occlusion reactive hyperemia; PORH), and decreases arterial blood pressure (BP), serum triglycerides and high sensitivity C reactive protein (hsCRP) level in healthy individuals. Present study aimed to determine the effect of n-3 PUFAs enriched hen eggs consumption on microvascular reactivity in professional athletes.

Design and method:

23 young healthy professional athletes (3 women and 20 men, age ranged 18–28 years) have consumed three standard hen eggs per day (249 mg of n-3 PUFAs/day) (Control group) or three n-3 PUFAs enriched hen eggs per day (1053 mg of n-3 PUFAs/day) (n-3 PUFA group) for three weeks. Forearm skin microvascular blood flow in response to vascular occlusion (PORH) and iontophoresis of acetylcholine (ACh) (endothelium-dependent vasodilation) and sodium nitroprusside (SNP) (endothelium-independent vasodilation) were assessed using laser Doppler flowmetry before and after diet protocols. Body mass index (BMI), waist-to-hip ratio (WHR), BP, fasting lipid panels, fasting blood glucose (fBG) and hsCRP were measured in all subjects before and after diet protocols.

Results:

BMI, WHR, BP, fasting lipid panels, fBG and hsCRP were not significantly changed after consumption of either eggs compared to baseline measurements within n-3 PUFAs or Control group. Consumption of n-3 PUFAs eggs significantly improved PORH and ACh-induced dilation (AChID) compared to baseline measurement within n-3 PUFAs group. Contrary, consumption of standard eggs did not induce any significant change in PORH and AChID compared to baseline in Control group. SNP-induced dilation was similar before and after respective diet protocol in both Control and n-3 PUFA groups.

Conclusions:

This is the first study to demonstrate that consumption of n-3 PUFAs enriched functional food (hen eggs) for three weeks enhances skin endothelium-dependent microvascular reactivity in professional athletes. This result provides foundation for future investigation of potential mechanisms by which n-3 PUFAs could improve endothelial function, and overall vascular adaptation to regular physical activity in professional athletes.