Hypertension

High blood pressure induced by vitamin D deficiency is associated with renal overexpression and hyperphosphorylation of Na+-K+-2Cl- cotransporter type 2 Objectives: Clinical and epidemiological studies have suggested a correlation between vitamin D deficiency (VDD) and high blood pressure (BP). This study aimed to test the hypothesis that high BP induced by VDD is associated with altered expression and covalent modification of apical sodium transporters along the nephron. The contributions of the intrarenal renin–angiotensin system (RAS) and oxidative stress were also investigated. Methods: Male Wistar rats were fed a vitamin D-free (n = 26) or standard diet (n = 25) for 30 days. BP was recorded using noninvasive and invasive procedures. The expression levels of total and phosphorylated apical sodium transporters in rat renal cortex and medulla were evaluated by immunoblotting. Intrarenal RAS components were assessed by immunoblotting and ELISA. Renal oxidative stress was analyzed by measuring the concentrations of thiobarbituric acid reactive substances and reduced glutathione. Results: Higher BP levels in VDD rats than controls were accompanied by overexpression and hyperphosphorylation of renal cortical and medullary Na+-K+-2Cl- cotransporter type 2, enhanced levels of phosphorylated Na+/H+ exchanger type 3, and reduced expression levels of total and phosphorylated Na+/Cl- cotransporter. Changes in intrarenal RAS induced by VDD vs. controls included the marked elevation of medullary renin expression, higher expression of cortical angiotensinogen, higher urinary angiotensinogen excretion, and higher cortical and medullary angiotensin II content. VDD rats displayed higher thiobarbituric acid reactive substances/glutathione ratios in the renal cortex and medulla than controls. Conclusion: These results suggest that the molecular mechanisms underlying the effects of VDD on BP may include the upregulation of Na+-K+-2Cl- cotransporter type 2 and activation of intrarenal RAS and oxidative stress. Correspondence to Adriana C.C. Girardi, Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of São Paulo Medical School, Avenida Dr Enéas de Carvalho Aguiar, 44, 10° andar, Bloco II, 05403-900 São Paulo, SP, Brazil. Tel: +55 11 2661 5929; fax: +55 11 2661 5022; e-mail: adriana.girardi@incor.usp.br Received 2 April, 2020 Revised 27 October, 2020 Accepted 15 November, 2020 Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Validity of five formulas in estimating 24-h urinary sodium via spot urine sampling in hypertensive patients living in Northeast China Objective: The objective was to evaluate the accuracy of five formulas -- the Kawasaki, Tanaka, INTERSALT, Mage, and Uechi methods -- using spot urinary sampling for 24-h urinary sodium (UNa) prediction in hypertensive patients living in northeast China. Methods: There were 1154 hypertensive patients enrolled from multiple centers. Five different formulas were used to predict 24-h UNa excretion via spot morning urinary samples. Actual UNa excretion was measured from 24-h urine samples. The estimated value was compared with the actual value by examining biases, the intraclass correlation coefficients (ICC), and Bland–Altman plots. Results: The average excretion of sodium was 2.97 ± 1.26 g/day. The formula-produced mean biases for actual UNa were 0.31 g/day for INTERSALT, 0.80 g/day for Mage, 0.88 g/day for Tanaka, 1.14 g/day for Uechi, and 1.95 g/day for Kawasaki. The ICC was 0.511 for Kawasaki, 0.499 for INTERSALT, 0.468 for Tanaka, 0.402 for Mage, and 0.378 for Uechi. The least mean bias in the lower and moderate salt intake subgroups was 1.22 and 0.07 g/day, respectively, which was calculated using the Mage and INTERSALT methods. The least mean bias in the higher salt intake subgroup was 0.10 g/day for the Uechi method. The INTERSALT method was more efficiency at the individual level, with 17.4% of participants having relative differences within 10%, and 22.3% participants having absolute differences within 393 mg. Conclusion: The INTERSALT method may exhibit a good performance in estimating 24-h urinary sodium level for the hypertensive population living in northeast China. Correspondence to Wei Song, Department of Cardiology, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, China. Tel: +86 18098875773; e-mail: songwei8124@163.com Received 1 September, 2020 Revised 10 November, 2020 Accepted 1 December, 2020 Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Incremental value of carotid elasticity modulus using shear wave elastography for identifying coronary artery disease in patients without carotid plaque Background: Shear wave elastography (SWE) directly quantifies the local arterial wall stiffness by calculating the elastic modulus. However, whether carotid wall elastic modulus can predict obstructive coronary artery disease (CAD) is not well known. We aimed to investigate the value of carotid wall elastic modulus measured using SWE in identifying obstructive CAD. Materials and methods: We prospectively enrolled 61 patients without carotid plaque referred for clinically indicated coronary angiography. Twenty-seven (44.3%) patients were diagnosed with obstructive CAD (≥50% coronary stenosis). The elastic modulus of common carotid artery was quantified using SWE. Ankle--brachial index (ABI) and echocardiographic global cardiac calcium score (GCCS) were measured. Results: Patients with obstructive CAD had significantly higher elastic modulus than those without obstructive CAD. The maximum elastic modulus (EMmax) was independently associated with obstructive CAD after adjusting for the Framingham risk score, ABI, and GCCS. EMmax had the highest area under the curve (AUC) to identify obstructive CAD (AUC 0.70; P = 0.003). In the nested models, the model based on the Framingham risk score and ABI (χ2 = 3.74) improved by adding GCCS (χ2 = 9.95) and further improved by adding EMmax (χ2 = 15.86). Adding EMmax to the combined ABI and GCCS model increased integrated discrimination index from 0.10 to 0.19. Conclusion: Carotid wall elastic modulus measured using SWE is a useful predictor of obstructive CAD in patients without carotid plaque. We demonstrated the incremental and independent value of carotid wall elastic modulus in identifying obstructive CAD compared with clinical risk factors and other imaging predictors, including ABI and GCCS. Video abstract: Please see the video, in Supplemental Digital Content 1, http://links.lww.com/HJH/B551 for more insights from the authors. Correspondence to Chunyan Ma, First Hospital of China Medical University, No. 155 Nanjingbei Street, Shenyang, Liaoning 110001, China. Tel/fax: +86 24 83282114; e-mail: cmu1h_mcy@126.com Received 20 August, 2020 Revised 14 November, 2020 Accepted 6 December, 2020 Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://www.jhypertension.com). This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0 Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Targeting persistent normal left ventricular geometry in the general population: a 25-year follow-up study Aim: Findings regarding the extent of persistence over time of normal left ventricular (LV) geometry, a reference healthy echocardiographic phenotype, in the community are scanty. We sought to assess this issue in members of the general population enrolled in the Pressioni Arteriose Monitorate e Loro Associazioni study. Methods: The study included 433 participants who attended the second and third survey of the Pressioni Arteriose Monitorate e Loro Associazioni study performed after 10 and 25 years from the initial evaluation. Data collection included medical history, anthropometric parameters, office, home, ambulatory blood pressure, routine blood examinations and echocardiography. Results: During 25-year follow-up 167 participants showed persistently normal LV mass (LVM) and LV geometry pattern, whereas 266 participants exhibited LV hypertrophy or LV concentric remodelling at any point during study. Compared with participants developing, maintaining or regressing from LV hypertrophy and LV concentric remodelling those with a persistently normal LVM index and geometry were younger (−8 years) and more frequently female (63 vs. 45%), exhibited baseline (and follow-up) lower office and out-of-office blood pressure, BMI, serum creatinine, fasting blood glucose total serum cholesterol and rate of antihypertensive treatment. In multivariate regression analysis age [odds ratio (OR): 0.93, confidence interval (CI): 0.91–0.96, P < 0.0001] BMI (OR: 0.90, CI: 0.83–0.97, P = 0.008), office SBP (OR: 0.97, CI: 0.95–0.99, P = 0.005) and fasting blood glucose (OR: 0.96, CI: 0.93–0.99, P = 0.007) were independently associated with persistent normal LVM index and geometry. Conclusion: The current long-term longitudinal study suggests that persistence of normal LV geometry is associated with normal/optimal SBP, BMI and blood glucose. Thus, a closer control of these risk factors in midlife may increase the likelihood of maintaining normal ventricular geometry and, in turn, reduce the burden of subclinical cardiac organ damage and related complications in advanced age. Correspondence to Cesare Cuspidi, Clinical Research Unit, Istituto Auxologico Italiano, Viale della Resistenza 23, 20036 Meda, Italy. Tel: +39 0362 772433; fax: +39 0362 772416; e-mail: cesare.cuspidi@unimib.it Received 26 September, 2020 Revised 3 November, 2020 Accepted 15 November, 2020 Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://www.jhypertension.com). Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Neck-to-height ratio and arterial stiffness in Chinese adults: cross-sectional associations in a community-based cohort Objectives: The aim of this study was to investigate the association between neck-to-height ratio (NHR) and arterial stiffness in adults from a community-based Chinese cohort in a cross-sectional study. Methods: We conducted cross-sectional analysis using data from the Kailuan study, a population-based cohort research. Altogether, 18 972 individuals were included in the analysis. Brachial ankle pulse wave velocity (baPWV), anthropometric indexes and cardiovascular risk factors were recorded. Data were analyzed by multiple lineal regression model. Results: NHR was positively associated with baPWV after adjusted for age, sex, blood pressure, heart rate, BMI, waist–hip ratio, current smoking, fasting blood glucose, serum cholesterol, uric acid, high-sensitivity C reactive protein and creatinine clearance (β = 5.76, P < 0.001), while the association of neck circumference and baPWV was NS after adjusting the variables mentioned above. In subgroups analysis, the association between NHR and baPWV did not reach statistical significance in female, while in males, the association was significant. Interaction effects were observed among BMI stratifications and the individuals with metabolic syndrome and history of cardiovascular events (P for intereaction = 0.002, 0.038 and 0.003, respectively). Conclusion: The current study demonstrated for the first time that NHR was positively associated with baPWV in community-based population, NHR might be a promising independent predictor for cardiovascular disease. Correspondence to Jun Tao, Department of Hypertension and Vascular Disease, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China. E-mail: taojungz123@163.com Received 4 August, 2020 Revised 27 October, 2020 Accepted 22 November, 2020 Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://www.jhypertension.com). This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0 Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Association between arterial stiffness and the clustering of metabolic syndrome risk factors: a systematic review and meta-analysis Objectives: Metabolic syndrome (MetS) is a cluster of different cardiometabolic risk factors (CMRFs), and its different combinations with other CMRFs, such as arterial stiffness have been hypothesized to explain, at least partially, increased risk of cardiovascular disease. Thus, in this systematic review and meta-analysis, we aimed to synthesize the evidence regarding the association between the clustering of MetS-related CMRFs and arterial stiffness measured using pulse wave velocity (PWV). Methods: Original studies analysing the association between arterial stiffness, measured using PWV, and MetS were systematically searched. Pooled effect size estimates and their respective 95% confidence intervals (CI) were calculated using the DerSimonian and Laird method for two separate analyses: the diagnosis of MetS and PWV values and the number of CMRFs and PWV values. Results: Moderate effect size estimates were observed between MetS and PWV (0.68, 95% CI: 0.54–0.82) with a slightly higher effect size for the low-risk compared with the high-risk population group (0.75, 95% CI: 0.58–0.92; and 0.51, 95% CI: 0.32–0.82, respectively). A trend between the number of MetS-related CMRFs and PWV was found with the pooled effect size nearly doubling as the number of MetS-related CMRFs increased, 0.11 (95% CI: 0.04–0.17) for one MetS-related CMRF, 0.26 (95% CI: 0.13–0.4) for two, and 0.4 (95% CI: 0.2–0.6) for three or more. Conclusion: These results demonstrated a clinically relevant association between MetS and PWV and an increasing trend in PWV values, such as a MetS-related CMRF increase. Although these results should be considered cautiously because of the considerable heterogeneity, our findings reinforce the rationale of MetS as an aggregation of risk factors with common causes, which could provide additional useful information to guide clinical management. Correspondence to Iván Cavero-Redondo, PhD, Universidad de Castilla-La Mancha, Edificio Melchor Cano, Centro de Estudios Socio-Sanitarios, Santa Teresa Jornet s/n, 16071 Cuenca, Spain. E-mail: Ivan.Cavero@uclm.es Received 8 September, 2020 Revised 31 October, 2020 Accepted 22 November, 2020 Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://www.jhypertension.com). Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Effect of frequency and pattern of night shift on hypertension risk in female nurses: a cross-sectional study Objectives: Understanding the effect of night shift on hypertension risk in nurses is important to improve the health of nurses and ensure patient safety. This study aimed to evaluate the effect of the frequency and pattern of night shift on hypertension risk and the interaction of them in female nurses. Methods: This cross-sectional study constituted 84 697 female nurses in 13 cities in China. The main contents of the survey included SBP, DBP, the frequency and pattern of night shift, and some other factors that might be associated with hypertension. Logistic regression analyses were used to calculate ORs and 95% CIs to estimate the effect of the frequency and pattern of night shift on hypertension risk and the interaction of them in relation to hypertension risk. Results: Having more than 5 to 10 or more than 10 night shifts per month were significantly more likely to be hypertensive (OR 1.19, 95% CI 1.10–1.28; OR 1.32, 95% CI 1.13–1.54), whereas having less than or equal to 5 night shifts per month was not (OR 1.05, 95% CI 0.95–1.16). The patterns of night shift were all associated with a higher probability of hypertension and participants engaging in rapidly rotating night shift had a lower OR (1.14) than those having slowly rotating night shift (1.23) and permanent night shift (1.46). No significant interaction was observed between the frequency and the pattern of night shift (Pinteraction = 0.281). Conclusion: The frequency and pattern of night shift were associated with hypertension risk in female nurses and no significant interaction was observed between them. Correspondence to Wei Cui, Department of Cardiology, The Second Hospital of Hebei Medical University, No. 215, Heping West Road, Shijiazhuang city, Hebei Province, China. E-mail: cuiwei21c@163.com Received 25 February, 2020 Revised 15 November, 2020 Accepted 22 November, 2020 Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Hemodynamic profiles in treatment-naive arterial hypertension and their clinical implication for treatment choice: an exploratory post hoc analysis Objective: Noninvasive thoracic bioimpedance by the HOTMAN System estimates hemodynamic modulators and expresses them as hemodynamic profiles. Aims of this analysis were to describe hemodynamic profiles among treatment-naive hypertensive patients compared with normotensive controls and to investigate whether a hemodynamic-guided choice of therapy improves blood pressure (BP) control within 4 weeks. Method: This exploratory post hoc analysis used data of a randomized parallel-group trial including 80 outpatients with newly diagnosed arterial hypertension (AHT), randomized to four antihypertensive first-line monotherapies, and 20 age-matched and sex-matched normotensive controls. Hemodynamic profiles were measured at baseline and after four weeks of treatment. On the basis of the hemodynamic profiles, the most appropriate pharmacological treatment was determined retrospectively and patients were categorised to have received concordant (ConTG) or discordant treatment (DisTG). Results: In the hypertensive group, hypervolemia with vasoconstriction was the predominant hemodynamic profile in 48% of patients and hypervolemia without vasoconstriction in 45%, compared with 15 and 50%, respectively, in the control group. After 4 weeks of treatment, the mean (±SD) 24-h BP was 129.9 (±11.0)/81.5 (±8.0) mmHg in the DisTG vs. 133.9 (±12.3)/84.0 (±9.1) mmHg in the ConTG (P = 0.158/0.222). The mean 24-h BP reductions were −9.7 (±10.1)/−5.0 (±6.2) mmHg in the DisTG and −12.4 (±14.8)/−6.9(±6.9) mmHg in the ConTG (P = 0.353/0.223). After 4 weeks of treatment, the BP control rate was 53.7% (43/80) among all, 55.7% (29/52) in the DisTG and 48% (12/25) in the ConTG (P = 0.628). Conclusion: Our findings do not support the hypothesis that personalized treatment initiation based on hemodynamic profiles improves BP control in newly diagnosed hypertensive outpatients. Correspondence to Thilo Burkard, Medical Outpatient and Hypertension Clinic, ESH Hypertension Centre of Excellence, University Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland. E-mail: thilo.burkard@usb.ch Received 6 October, 2020 Revised 29 November, 2020 Accepted 29 November, 2020 Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://www.jhypertension.com). This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0 Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

The adrenal medulla in cardiovascular medicine: an untold story Unlike noradrenaline, the sympathetic neurotransmitter which overflows to the circulation, adrenaline (ADR) is a secreted hormone, with a low plasma concentration, and plasma concentration for biological action a log order lower than that of noradrenaline. The venous drainage of the left adrenal medulla into the left renal vein does expose this vein to uniquely high plasma ADR concentrations and possible risk of thrombosis at high rates of ADR secretion. There is typically a different timeframe for adrenal medullary and sympathetic nervous system responses: ADR release is short term in contrast with sympathetic activation persisting for years in heart failure and hypertension. The historic view of Walter Cannon, subject to recent review, that the sympathoadrenal system is a unified biological system, was deconstructed further with demonstration of frequent mismatching of adrenal medullary and sympathetic nervous responses. Under gravity stimulation with standing, there is prompt sympathetic activation without ADR release. In many diseases, notably obesity, hypertension, heart failure and depressive illness, an activated sympathetic nervous system and silent adrenal medulla coexist. The therapeutic corollary of this is that ADR blockade is much less commonly needed clinically than pharmacological antagonism of the sympathetic nervous system. Correspondence to Murray D. Esler, Baker Heart and Diabetes Institute, PO Box 6492, Melbourne 3004, VIC, Australia. Tel: +61 409 178 058; fax: +61 3 8532 1100; e-mail: murray.esler@baker.edu.au Received 19 October, 2020 Revised 15 November, 2020 Accepted 16 November, 2020 Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Uterine fibroids increase the risk of hypertensive disorders of pregnancy: a prospective cohort study Objective: It is unclear whether uterine fibroids are associated with the occurrence of hypertensive disorders of pregnancy (HDP). Thus, this study aimed to evaluate the association between uterine fibroids and HDP in a prospective cohort. Methods: Overall, 2404 pregnant women who received antenatal care were enrolled in a prospective cohort in China between 2014 and 2016; 2277 women met the inclusion criteria of this study. The clinical characteristics of participants were assessed via questionnaires and physical examinations at baseline (before the 20th week of gestation), 21st–27th, 28th–34th, and 35th–39th gestational weeks. Ultrasound examination was performed before the 20th week of pregnancy to determine the presence of uterine fibroids. Linear mixed-effect and Cox proportional hazard regression models were used to analyze the association of uterine fibroids with blood pressure and HDP. Results: Of 2277 pregnant women, 242 (10.6%) had uterine fibroids, and 45 (2.0%) subsequently developed HDP. The incidence of HDP in women with and without uterine fibroids was 5% (n = 12) and 1.6% (n = 33), respectively. The longitudinal SBPs and DBPs were significantly higher in women with uterine fibroids than in those without. The multivariable Cox model showed that the presence of uterine fibroids was associated with increased HDP risk (adjusted hazard radio: 2.95, 95% confidence interval: 1.35–6.44). Conclusion: Uterine fibroids in early pregnancy were associated with an increased HDP risk. Blood pressure of women with uterine fibroids should be closely monitored, and HDP preventive measures are crucial. Correspondence to Xuerui Tan, The First Affiliated Hospital of Shantou University Medical College, 57 Changping Road, Shantou, Guangdong 515041, China. Tel: +86 754 88611690; fax: +86 754 88259850; e-mail: doctortxr@126.com. Received 26 July, 2020 Revised 8 October, 2020 Accepted 2 November, 2020 Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://www.jhypertension.com). This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0 Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

#

Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

Telephone consultation 11855 int 1193,