Chromogranin A pathway: from pathogenic molecule to renal disease Background: Chromogranin A (CHGA) is an index granin protein critical for biogenesis and exocytotic release of catecholamine storage granules. It is elevated in plasma of patients with sympathetic over-activity and kidney dysfunction. Several CHGA polymorphisms are associated with hypertensive kidney disease. Previously, we unraveled the molecular mechanism by which CHGA expression is regulated in African Americans carrying a genetic variation associated with hypertensive chronic kidney disease (CKD). Method: Experimental CKD mouse model were created by 5/6th nephrectomy (Npx) using wild-type and Chga−/− knockout mouse strains to delineate the role of CHGA in CKD. Result: Wild-type-Npx mice expressing Chga developed exacerbated azotemia and fibrosis as compared with their knockout-Npx counterparts. Gene expression profiling revealed downregulation of mitochondrial respiratory complexes genes consistent with maladaptive mitochondria in wild-type-Npx mice, contrasted to knockout-Npx. In healthy individuals, an inverse relationship between circulating CHGA levels and glomerular function was observed. In vitro, mesangial cells treated with CHGA-triggered nitric oxide release by a signaling mechanism involving scavenger receptor SR-A. The CHGA-treated and untreated mesangial cells displayed differential expression of cytokine, chemokine, complement, acute phase inflammatory and apoptotic pathway genes. Thus, build-up of plasma CHGA because of kidney injury served as an insult to the mesangial cells resulting in expression of genes promoting inflammation, fibrosis, and progression of CKD. Conclusion: These findings improve understanding of the role of elevated CHGA in the progression of CKD and reveal novel pathways that could be exploited for therapeutic strategies in hypertensive kidney disease. Correspondence to Sucheta M. Vaingankar, PhD, or Saiful A. Mir PhD Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0838, USA. Tel: +1 858 246 0815; fax: +1 858 534 0626; e-mail: svaingankar@ucsd.edu;s1mir@ucsd.edu Received 11 July, 2019 Revised 26 September, 2019 Accepted 30 September, 2019 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 © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Blood pressure dipping and sleep quality in the Wisconsin Sleep Cohort Aims: Nondipping blood pressure (BP) is associated with higher risk for hypertension and advanced target organ damage. Insomnia is the most common sleep complaint in the general population. We sought to investigate the association between sleep quality and insomnia and BP nondipping cross-sectionally and longitudinally in a large, community-based sample. Methods: A subset of the Wisconsin Sleep Cohort (n = 502 for cross-sectional analysis and n = 260 for longitudinal analysis) were enrolled in the analysis. Polysomnography measures were used to evaluate sleep quality. Insomnia symptoms were obtained by questionnaire. BP was measured by 24-h ambulatory BP monitoring. Logistic regression models estimated cross-sectional associations of sleep quality and insomnia with BP nondipping. Poisson regression models estimated longitudinal associations between sleep quality and incident nondipping over a mean 7.4 years of follow-up. Systolic and diastolic nondipping were examined separately. Results: In cross-sectional analyses, difficulty falling asleep, longer waking after sleep onset, shorter and longer total sleep time, lower sleep efficiency and lower rapid eye movement stage sleep were associated with higher risk of SBP and DBP nondipping. In longitudinal analyses, the adjusted relative risks (95% confidence interval) of incident systolic nondipping were 2.1 (1.3–3.5) for 1-h longer waking after sleep onset, 2.1 (1.1–5.1) for 7–8 h total sleep time, and 3.7 (1.3–10.7) for at least 8-h total sleep time (compared with total sleep time 6–7 h), and 1.9 (1.1–3.4) for sleep efficiency less than 0.8, respectively. Conclusion: Clinical features of insomnia and poor sleep quality are associated with nondipping BP. Our findings suggested nondipping might be one possible mechanism by which poor sleep quality was associated with worse cardiovascular outcomes. Correspondence to Paul E. Peppard, PhD, Department of Population Health Sciences, University of Wisconsin School of Medicine and Public Health, WARF Building, #611, 610 Walnut St., Madison, WI 53726, USA. Tel: +1 608 262 2680; e-mail: ppeppard@wisc.edu Received 24 March, 2019 Revised 30 August, 2019 Accepted 21 September, 2019 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 © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Real-world efficacy and safety of nebivolol in Korean patients with hypertension from the BENEFIT KOREA study Objective: The efficacy and safety of nebivolol in patients with hypertension is well established, but its effect in Asian patients with essential hypertension in the real world has not been studied. Methods: Adult South Korean patients with essential hypertension, with or without comorbidities, were enrolled to participate in this prospective, single-arm, open, observational study; 3011 patients received nebivolol either as monotherapy or add-on therapy. Changes in SBP, DBP and heart rate (HR) at 12 and 24 weeks were evaluated. Subgroup analysis for BP changes in newly diagnosed (de novo) patients and those receiving other antihypertensives at study entry were also conducted. Results: Nebivolol significantly decreased mean SBP and DBP at 12 and 24 weeks compared with baseline (P < 0.0001). A significant reduction in HR was also observed at 12 and 24 weeks (P < 0.0001). The reductions of SBP and DBP were notably greater when nebivolol was used as monotherapy in de novo patients (P < 0.0001) and as add-on therapy to existing antihypertensives (angiotensin II receptor blockers, angiotensin-converting enzyme inhibitors and calcium channel blockers; P < 0.0001). Majority of the reported adverse events were mild; the most common adverse events were dizziness (1.3%), headache (1.0%) and dyspnea (0.9%). Conclusion: Despite the limitations associated with observational studies, this real-world study in Asian patients with essential hypertension with and without comorbidities, demonstrated the efficacy and safety of once daily nebivolol, either as monotherapy or add-on therapy. Clinical trial registration number: NCT 03847350. SDC Callout: Video Abstract, http://links.lww.com/HJH/B172 Correspondence to Dae-Hyeok Kim, MD, PhD, Division of Cardiology, Department of Internal Medicine, Incheon Regional Cardiovascular Center, Inha University Hospital, 27, Inhang-Ro, Jung-Gu, Incheon 22332, Korea. Tel: +82 32 890 2440; +82 32 890 2451; fax: +82 32 890 2447; e-mail: kdhmd@inha.ac.kr Received 2 July, 2019 Revised 25 September, 2019 Accepted 5 October, 2019 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 © 2019 Wolters Kluwer Health, Inc. All rights reserved.

STRIDE BP: an international initiative for accurate blood pressure measurement The diagnosis and management of hypertension is dependent upon accurate blood pressure (BP) measurement. Despite intense efforts over several decades by the international medical community worldwide, the use of inaccurate devices has resulted in the misdiagnosis and poor management of hypertension, which remains a largely unresolved public health problem. STRIDE BP (www.stridebp.org) is an international nonprofit organization the mission of which is to improve the accuracy of BP measurement and the diagnosis of hypertension. STRIDE BP comprises a group of 24 recognized experts in BP monitoring from across the world and operates in affiliation with the European Society of Hypertension, the International Society of Hypertension, and the World Hypertension League. In the first stage, STRIDE BP has reviewed 419 validations of 260 devices and approved 69% of them, providing recommendations on accurate devices for office, ambulatory and home BP measurement in adults, children and during pregnancy. At the next stage, STRIDE BP intends to develop programs for on-line training and tools for use in clinical practice leading to improved measurement of BP and better diagnosis of hypertension world-wide. Correspondence to Professor George S. Stergiou, MD, FRCP, Hypertension Center STRIDE-7, National and Kapodistrian University of Athens, School of Medicine, Third Department of Medicine, Sotiria Hospital, 152 Mesogion Avenue, Athens 11527, Greece. Tel: +30 2107763117; fax: +30 2107719981; e-mail: gstergi@med.uoa.gr Received 18 August, 2019 Accepted 24 September, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Prognostic value of office blood pressure measurement in patients with atrial fibrillation on anticoagulation therapy: systematic review and meta-analysis Objective: In patients with atrial fibrillation (AF), the clinical relevance of office blood pressure (OBP) measurement in terms of predicting morbidity and mortality is questionable, mainly because such measurements in these patients are variable and uncertain. This study reviewed the evidence on the prognostic value of OBP in AF. Methods: A systematic PubMed/Embase search was performed for prospective trials in AF patients on oral anticoagulants, reporting OBP measurements or hypertension diagnosis and outcome. A meta-analysis of the predictive ability of OBP values or hypertension diagnosis for stroke/systemic embolism, major haemorrhage and all-cause mortality was performed. Results: The meta-analysis included nine studies (n = 65 637; 126 926 person-years). There was considerable heterogeneity in the OBP methodology, which was not standardized in most studies. Five studies reported baseline OBP or hypertension diagnosis, two average OBP control during follow-up, and two both baseline and follow-up OBP control. Meta-analysis of six studies (n = 61 055; 105 373 person-years) showed elevated vs. low OBP or hypertension vs. normotension to predict stroke and/or systemic embolism [hazard ratio (HR) 1.29; 95% confidence intervals (CI) 1.12, 1.47]. Meta-analysis of three studies (n = 29 233, 51 528 person-years) showed a worse follow-up OBP control to predict higher stroke/systemic embolism risk (HR 1.79, 95% CI 1.38, 2.32). OBP and hypertension diagnosis did not appear to predict major haemorrhagic events (HR 1.10; 95% CI 0.97, 1.25) or all-cause mortality (HR 0.96; 95% CI 0.89, 1.05). Conclusion: In AF patients, OBP and hypertension diagnosis predict stroke or systemic embolism, and follow-up OBP control appears to have even stronger predictive ability. Correspondence to Prof. George S. Stergiou, MD, FRCP, Hypertension Center STRIDE-7, National and Kapodistrian University of Athens, School of Medicine, Third Department of Medicine, Sotiria Hospital, 152 Mesogion Avenue, Athens 11527, Greece. Tel: +30 2107763117; fax: +30 2107719981; e-mail: gstergi@med.uoa.gr Received 8 June, 2019 Revised 11 August, 2019 Accepted 13 August, 2019 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 © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Dissociation between hypertrophy and fibrosis in the left ventricle early after experimental kidney transplantation Objective: Left ventricular (LV) hypertrophy is the most common cardiac alteration in patients with chronic kidney disease (CKD). Normalization of hypertension in CKD patients receiving a healthy kidney allograft often reverses LV hypertrophy, but effects on LV fibrosis remain unclear. To study causal interactions between graft and environment on LV hypertrophy, fibrosis and inflammation, we applied cross-kidney transplantation Methods: Orthotopic transplantation was performed after inducing CKD in rats by two-third bilateral ablation of kidney mass: Healthy kidney (K) donor to healthy heart (H) recipient (healthy-K→healthy-H); CKD-K→healthy-H; healthy-K→CKD-H; CKD-K→CKD-H; N= 6 per group. Results: At week 6 after transplantation, mean arterial pressure (MAP) and LV mass index (LVMI) increased in CKD-K versus healthy-K irrespective of recipient. Contrarily, LV fibrosis was more severe in CKD-H versus healthy-H recipients irrespective of graft. Indeed, MAP and plasma creatinine correlated with LVMI but not with LV fibrosis. Increased LVMI in CKD-K→CKD-H not accompanied by cardiomyocyte cross-sectional area gain is consistent with eccentric remodelling. Cardiac RNA sequencing found a strong transcriptional response associated with LV fibrosis but only sparse changes associated with LV hypertrophy. This response was, among others, characterized by changes in extracellular matrix (ECM) and inflammatory gene expression. Conclusion: LVMI reversed and MAP and renal function were normalized early after transplantation of a healthy kidney. However, LV fibrosis persisted, dissociating LV hypertrophy from LV fibrosis within 6 weeks. Elucidating cardiac ECM dynamics in CKD patients, although challenging, appears promising. Correspondence to Jaap A. Joles, DVM, PhD, Department of Nephrology & Hypertension, University Medical Center Utrecht, Heidelberglaan 100, PO Box 85500, 3508 GA Utrecht, Netherlands. Tel: +31 88 75 69020; fax: +31 88 755 6283; e-mail: j.a.joles@umcutrecht.nl Received 10 December, 2018 Revised 12 September, 2019 Accepted 24 September, 2019 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 © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Increased detection of suspected atrial fibrillation in elderly and female hypertensive patients through home blood pressure monitoring: the HOME-AF study Background: Episodes of suspected atrial fibrillation are particularly frequent in essential hypertension. This study aimed to investigate the incidence of new suspected atrial fibrillation cases detected through home blood pressure (BP) screening among hypertensive patients. Association of new suspected atrial fibrillation cases with arterial hypertension (AH) phenotypes and the CHA2DS2-VASc score was also investigated. Methods: The prospective study recruited hypertensive patients at least 50 years old from private and hospital hypertensive clinics. An ECG was performed during the first visit. Microlife BP A6 PC was used to measure office and home BP for at least 3 and preferably 7 consecutive days. Results: A total of 2408 AH patients were recruited. Suspected atrial fibrillation was detected by BP monitor in 12.5% of patients. CHA2DS2-VASc was greater in hypertensive patients with suspected atrial fibrillation detection, as compared with all other hypertensive patients (3.3 ± 1.4 vs. 2.8 ± 1.4, P < 0.0001). Suspected atrial fibrillation detection was associated with advanced age (≥ 75 years, P < 0.0001) and female sex (P = 0.01). A nonsignificant association between suspected atrial fibrillation detection and history of chronic heart failure/left ventricular dysfunction was observed (P = 0.06). In the multivariate analysis, age and sex were the only independent risk factors with patients at least 75 years old having more than twice the risk of suspected atrial fibrillation compared with patients less than 64 years old. No differences between new suspected atrial fibrillation cases and AH phenotype (white coat/uncontrolled/masked hypertension) were identified. Conclusion: In our cohort of hypertensive patients, suspected atrial fibrillation was common particularly among elderly and female patients. These results underline the need for early suspected atrial fibrillation detection to minimize the increased thromboembolic risk associated with hypertension. Correspondence to Paraskevi Savvari, Medical Department of Internal Medicine, Pfizer Hellas S.A, 243 Messoghion Ave., 15451 Neo Psychiko, Athens, Greece. Tel: +30 2106785937; fax: +30 2106785553; e-mail: Paraskevi.Savvari@pfizer.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 Received 13 March, 2019 Revised 5 September, 2019 Accepted 25 September, 2019 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 © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Serum uric acid and fatal myocardial infarction: detection of prognostic cut-off values: The URRAH (Uric Acid Right for Heart Health) study Objective: The Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension conceived and designed an ad-hoc study aimed at searching for prognostic cut-off values of serum uric acid (SUA) in predicting fatal myocardial infaction (MI) in women and men. Methods: The URic acid Right for heArt Health study is a nationwide, multicentre, observational cohort study involving data on individuals aged 18–95 years recruited on a regional community basis from all the territory of Italy under the patronage of the Italian Society of Hypertension with a mean follow-up period of 122.3 ± 66.9 months. Results: A total of 23 467 individuals were included in the analysis. Cut-off values of SUA able to discriminate MI status were identified by mean of receiver operating characteristic curves in the whole database (>5.70 mg/dl), in women (>5.26 mg/dl) and in men (>5.49 mg/dl). Multivariate Cox regression analyses adjusted for confounders (age, arterial hypertension, diabetes, chronic kidney disease, smoking habit, ethanol intake, BMI, haematocrit, LDL cholesterol and use of diuretics) identified an independent association between SUA and fatal MI in the whole database (hazard ratio 1.381, 95% confidence intervals, 1.096–1.758, P = 0.006) and in women (hazard ratio 1.514, confidence intervals 1.105–2.075, P < 0.01), but not in men. Conclusion: The results of the current study confirm that SUA is an independent risk factor for fatal MI after adjusting for potential confounding variables, and demonstrate that a prognostic cut-off value associated to fatal MI can be identified at least in women. Correspondence to Edoardo Casiglia, Studium Patavinum, Department of Medicine, University of Padua, Via Giustiniani 2, Via Vergerio 10, 35128 Padua, Italy. Tel: +0 39 8020005; fax: +0 39 8218541; e-mail: edoardo.casiglia@unipd.it Received 28 July, 2019 Revised 2 September, 2019 Accepted 24 September, 2019 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 © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Laparoscopic Roux-en-Y gastric bypass versus laparoscopic sleeve gastrectomy for 5-year hypertension remission in obese patients: a systematic review and meta-analysis Controversial results exist on mid-term effects of Roux-en-Y gastric bypass and sleeve gastrectomy on hypertension remission. The aim of the present systematic review was to study 5-year hypertension remission after both procedures. One-year hypertension remission and SBP and DBP pressure change at 1 and 5 years after both surgical techniques were also evaluated. We searched MEDLINE, EMBASE and The Cochrane Central Register of Controlled Trials (CENTRAL). Thirty-two articles were included (six randomized controlled trials, 18 cohort and eight case–control studies). The proportion of patients with hypertension remission was greater for those treated with gastric bypass compared with sleeve gastrectomy at 5 years (RR = 1.26, 95% CI = 1.07–1.48) and 1 year (RR = 1.14, 95% CI = 1.06–1.21). Gastric bypass and sleeve gastrectomy did not differ in terms of SBP or DBP change. Patients treated with gastric bypass present a higher hypertension remission rate at 1 and 5 years. Correspondence to Dr David Benaiges, PhD, Department of Endocrinology, Hospital del Mar, Paseo Marítimo, 25-29, E-08003 Barcelona, Spain. Tel: +34 932483902; fax: +34 932483254; e-mail: 96002@parcdesalutmar.cat Received 20 June, 2019 Revised 2 August, 2019 Accepted 21 August, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Does early life programming influence arterial stiffness and central hemodynamics in adulthood? Objectives: We aimed to investigate possible associations between birth weight and adult life carotid–femoral pulse wave velocity (cfPWV) and augmentation pressure index (AIx). Design and method: This study included 1598 participants, that is, 340 elderly individuals from the Malmö Birth Data Cohort (MBDC) and 1258 young-middle aged individuals from the Malmö Offspring Study (MOS) with full data on birth weight and gestational age. Participants underwent cfPWV and AIx measurements with Sphygmocor (AtCor, Australia). Analysis of data was performed with multiple linear regression models including adjustments for age, sex, gestational age and risk factors. Furthermore, comparisons were made between participants born prematurely or at term or born small-for-gestational age (SGA) or appropriate-for-gestational age (AGA). Results: Birth weight was positively associated with cfPWV after full adjustment (β = 0.057; P < 0.001), a finding that remained significant in the younger age group 18–27 years (β = 0.138, P = 0.008). Furthermore, birth weight was inversely associated with AIx (β = −0.058, P = 0.001). Participants born SGA had significantly higher AIx (P = 0.007) and MAP (P = 0.037) compared with AGA born. Preterm-born participants showed significantly higher SBP compared with term-born (P = 0.034). Finally, birth weight was inversely associated with MAP (β = −0.058, P = 0.017) and SBP (β = −0.047, P = 0.031), respectively. Conclusion: Birth weight is positively associated with cfPWV, shown strongest in the youngest individuals, a finding that could possibly be explained by increasing trends for maternal overweight/obesity in recent decades. Furthermore, birth weight is inversely associated with AIx, a risk marker of cardiovascular disease. This calls for screening of risk factors in subjects with adverse conditions at birth. Correspondence to Peter M. Nilsson, MD, PhD, Professor, Internal Medicine Research Group, Department of Clinical Sciences, Skane University Hospital, Lund University, S-20502 Malmö, Sweden. Tel: +46 40 33 24 15; e-mail: Peter.Nilsson@med.lu.se Received 28 June, 2019 Revised 17 September, 2019 Accepted 25 September, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.