Family patterns of arterial stiffness across three generations in the Malmö Offspring Study Background: Central haemodynamics have in recent years emerged as a promising predictor of cardiovascular health and risk of cardiovascular disease (CVD). Central haemodynamics are affected early in the development of vascular aging and contributes to target organ damage. Carotid–femoral pulse wave velocity (c-f PWV), augmentation index (Aix) and central SBP (cSBP) are variables that reflect arterial stiffness and central haemodynamics. Aim: To study the association between patterns of central haemodynamics across three related generations focusing on c-f PWV. Methods: In all, 1131 participants from the Malmö Diet Cancer Study (MDCS) and Malmö Offspring Study (MOS) were included. c-f PWV was measured (Sphygmocor) in grandparents and in all offsprings. Correlation analyses of c-f PWV between offspring and c-f PWV in parents and grandparents were conducted. Parents and grandparents were stratified into quartiles by c-f PWV. Offspring c-f PWV means were compared with one-way ANOVA analyses. Multiple regression analyses were adjusted for age, sex, BMI, SBP and fasting glucose. Bonferroni corrections were used. Results: c-f PWV in offsprings was positively correlated with c-f PWV in parents (r = 0.26, P < 0.001) and in grandparents (r = 0.29, P < 0.001). Parents with high c-f PWV had offspring with significantly higher means of c-f PWV. Conclusion: A measure of aortic stiffness (c-f PWV) is positively correlated across three related generations in this population-based study. Correspondence to Peter M. Nilsson, MD, PhD, Department of Clinical Sciences, Lund University, Skane University Hospital, Jan Waldenstroms gata 15, 5th floor, S-20502 Malmo, Sweden. Tel: +46 40 33 24 15; e-mail: Peter.Nilsson@med.lu.se Received 30 January, 2019 Revised 24 September, 2019 Accepted 25 September, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Association of increased arterial stiffness with diastolic dysfunction in ischemic stroke patients: the Norwegian Stroke in the Young Study Background: Young and middle-aged ischemic stroke survivors have a high prevalence of hypertension, increased arterial stiffness and abnormal left ventricular (LV) geometry, which all are associated with the presence of LV diastolic dysfunction. However, the prevalence and covariates of diastolic dysfunction in these patients have not been reported. Objectives: To explore diastolic dysfunction in ischemic stroke patients aged 15–60 years included in the Norwegian Stroke in the Young Study. Methods: Data from 260 patients with acute ischemic stroke was analyzed. Diastolic dysfunction was assessed by combining transmitral peak early flow (E), early diastolic mitral annular velocity (e′), E/e′ ratio, left atrial volume index and peak tricuspid regurgitant jet velocity, following current European guidelines. Carotid–femoral pulse wave velocity at least 10 m/s by aplanation tonometry was defined as increased arterial stiffness. Results: Prevalent diastolic dysfunction was found in 20% of patients (13% with diastolic dysfunction grade 1 and 7% with diastolic dysfunction grades 2–3). Patients with diastolic dysfunction were older and more likely to have hypertension, overweight, increased arterial stiffness, higher LV mass and less percentage nightly reduction in mean blood pressure (BP) (all P < 0.001). In a multivariable logistic regression analysis, diastolic dysfunction was associated with increased arterial stiffness [odds ratio 2.86 (95% confidence interval 1.05–7.79), P < 0.05] independent of age more than 45 years, overweight, hypertension, night-time BP reduction and LV mass. Conclusion: Among young and middle-aged ischemic stroke survivors, diastolic dysfunction was found in 20%. The presence of diastolic dysfunction was associated with increased arterial stiffness independent of higher age, overweight, hypertension, night-time BP reduction and LV mass. Correspondence to Sahrai Saeed, MD, PhD, FESC, Department of Heart Disease, Haukeland University Hospital, Jonas Lies veg, 5021 Bergen, Norway. Tel: +47 55972196; fax: +47 55975150; e-mail: sahrai.saeed@helse-bergen.no Received 13 June, 2019 Revised 24 September, 2019 Accepted 7 October, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

The role of insomnia in the association between posttraumatic stress disorder and hypertension Objective: Posttraumatic stress disorder (PTSD) is associated with incident hypertension. Although this relationship is poorly understood, PTSD is also associated with insomnia symptoms, which increases the risk for hypertension. Whether insomnia contributes to PTSD-associated risk for hypertension is unknown. Methods: We examined self-report survey and electronic health record data from 1109 participants in the Women Veterans Cohort Study (mean age: 43.8 ± 10.9 years; 52% women, 81% white) to assess the cross-sectional associations between PTSD symptom severity, recent symptoms of insomnia, and hypertension, defined as self-reported treatment for high blood pressure in the last year. Structural equation modeling was used to examine whether insomnia symptoms mediate the association between PTSD and hypertension. Results: PTSD symptom severity was associated with hypertension (r = 0.09, P < 0.001). PTSD symptom severity and hypertension were each associated with the insomnia symptoms difficulty falling asleep, difficulty staying asleep, and worry/distress about sleep problems (PTSD: rs = 0.58--0.62, P <  0.001; hypertension: rs = 0.07--0.10, P <  0.001). A latent variable derived from those symptoms mediated 9% of the association between PTSD symptom severity and hypertension (P = 0.02). Conclusion: In this study of young and middle-aged Veterans, insomnia symptoms mediated the association between PTSD and hypertension. Difficulties falling asleep and maintaining sleep and related distress may be particularly deleterious for cardiovascular health in Veterans. Longitudinal data is required to further investigate the associations between PTSD, insomnia, and hypertension. Correspondence to Allison E. Gaffey, PhD, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA. Tel: +1 203 932 5711 ext. 3268; fax: +1 203 937 3884, e-mail: Allison.Gaffey@yale.edu Received 26 July, 2019 Revised 24 September, 2019 Accepted 14 October, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

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.