Associations of awake and asleep blood pressure and blood pressure dipping with abnormalities of cardiac structure: the Coronary Artery Risk Development in Young Adults study Objectives: To evaluate the associations of high awake blood pressure (BP), high asleep BP, and nondipping BP, determined by ambulatory BP monitoring (ABPM), with left ventricular hypertrophy (LVH) and geometry. Methods: Black and white participants (n = 687) in the Coronary Artery Risk Development in Young Adults study underwent 24-h ABPM and echocardiography at the Year 30 Exam in 2015–2016. The prevalence and prevalence ratios of LVH were calculated for high awake SBP (≥130 mmHg), high asleep SBP (≥110 mmHg), the cross-classification of high awake and asleep SBP, and nondipping SBP (percentage decline in awake-to-asleep SBP < 10%). Odds ratios for abnormal left ventricular geometry associated with these phenotypes were calculated. Results: Overall, 46.0 and 49.1% of study participants had high awake and asleep SBP, respectively, and 31.1% had nondipping SBP. After adjustment for demographics and clinical characteristics, high awake SBP was associated with a prevalence ratio for LVH of 2.79 [95% confidence interval (95% CI) 1.63–4.79]. High asleep SBP was also associated with a prevalence ratio for LVH of 2.19 (95% CI 1.25–3.83). There was no evidence of an association between nondipping SBP and LVH (prevalence ratio 0.70, 95% CI 0.44–1.12). High awake SBP with or without high asleep SBP was associated with a higher odds ratio of concentric remodeling and hypertrophy. Conclusion: Awake and asleep SBP, but not the decline in awake-to-asleep SBP, were associated with increased prevalence of cardiac end-organ damage. Correspondence to Natalie A. Bello, MD, MPH, Columbia University Irving Medical Center, 622 West 168th Street, PH 3-342, New York, NY 10032, USA. Tel: +1 212 305 1436; fax: +1 212 305 9049; e-mail: nb338@columbia.edu Received 28 February, 2019 Revised 26 July, 2019 Accepted 27 July, 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.

Women discontinue antihypertensive drug therapy more than men. Evidence from an Italian population-based study Objective: Several factors affect adherence to antihypertensive drug treatment, but whether these factors include a sex difference is unclear. Aim of the study was to compare persistence with antihypertensive drug therapy between men and women in a large cohort of patients. Methods: The 60 526 residents of the Italian Lombardy Region aged 40–80 years newly treated with antihypertensive drugs during 2010 were identified and followed for 1 year after the first prescription. Discontinuation of treatment was defined as lack of prescription renewal for at least 90 days. Log-binomial regression models were fitted to estimate the risk ratio of treatment discontinuation in relation to sex. Other than for the whole population, analyses were stratified according to age, comorbidity status and the initial antihypertensive treatment strategy. Results: Thirty-seven percent of the patients discontinued the drug treatment during follow-up. Compared with women, men had a 10% lower risk of discontinuation of drug treatment (95% confidence interval: 8–12). Persistence on antihypertensive treatment was better in men than in women, this being the case in both younger (40–64 years) and older patients (65–80 years), in patients starting treatment with any major antihypertensive drug and in patients who had a low comorbidity status. There was no evidence that men and women had a different risk of treatment discontinuation when their comorbidity status was worse, or initial antihypertensive treatment was based on drug combinations. Conclusion: Our data show that in a real-life setting, men are more persistent to antihypertensive drug therapy than women. Correspondence to Federico Rea, Dipartimento di Statistica e Metodi Quantitativi, Sezione di Biostatistica, Epidemiologia e Sanità Pubblica, Università degli Studi di Milano-Bicocca, Via Bicocca degli Arcimboldi, 8, Edificio U7, 20126 Milan, Italy. Tel: +39 02 64485859; e-mail: f.rea@campus.unimib.it Received 5 March, 2019 Revised 23 June, 2019 Accepted 29 July, 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.

Association of serum carbohydrate antigen 19-9 level with arterial stiffness and coronary artery calcification in middle-aged and older adults: a cross-sectional study Objectives: Emerging evidence suggests that serum carbohydrate antigen 19-9 level is elevated in type 2 diabetes and metabolic syndrome, which are closely related with atherosclerotic cardiovascular disease. This study aimed to determine whether serum carbohydrate antigen 19-9 level is related to atherosclerosis as measured by brachial–ankle pulse wave velocity (PWV) and coronary calcium score (CCS). Methods: This cross-sectional study comprised 1732 Korean adults aged at least 45 years who underwent a health examination program. Serum carbohydrate antigen 19-9 level was quantified by chemiluminescence immunoassay and categorized as quartiles, after exclusion of participants with carbohydrate antigen 19-9 levels more than 30 U/ml to rule out hidden malignancy: Q1: 4.5 or less, Q2: 4.6–7.5, Q2: 7.6–12.2, and Q4: at least 12.3 ng/ml. High brachial–ankle PWV was defined as a level greater than 1570 cm/s (>75th percentile), and high CCS was defined as a level over 100. The odds ratios and 95% confidence intervals for high PWV and high CCS were calculated across serum carbohydrate antigen 19-9 quartiles using multiple logistic regression analysis. Results: The prevalence of high PWV and high CCS increased with serum carbohydrate antigen 19-9 quartile. Compared with the lowest quartile, the odds ratios (95% confidence intervals) of the highest carbohydrate antigen 19-9 quartile for high PWV and high CCS were 1.61 (1.05–2.48) and 2.03 (1.17–3.54), respectively, after adjusting for age, sex, BMI, smoking status, alcohol consumption, regular exercise, fasting plasma glucose, total cholesterol, hypertension, type 2 diabetes, and dyslipidemia. Conclusion: We found that serum carbohydrate antigen 19-9 level was positively and independently associated with arterial stiffness and coronary artery calcification. Correspondence to Yong-Jae Lee, Department of Family Medicine, Yonsei University College of Medicine, Gangnam Severance Hospital, 211Eonju-ro, Gangnam-gu, Seoul 06273, Republic of Korea. Tel: +82 2 2019 2630; fax: +82 3463 3882; e-mail: ukyjhome@yuhs.ac Received 26 April, 2019 Revised 3 July, 2019 Accepted 20 July, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Risk stratification in hypertension: NT-proBNP and R wave in aVL lead combination better than echocardiographic left ventricular mass Objectives: Plasma N-terminal pro brain natriuretic peptide (NT-proBNP) and R wave in aVL lead (RaVL) have been associated with mortality in hypertension. The aim of the current study was to compare the prognostic value of their combination to that of the left ventricular mass index (LVMI) assessed by echocardiography. Methods: A total of 1104 hypertensive patients who had at baseline an assessment of plasma NT-proBNP, a 12-lead ECG, and echocardiography were included. LVMI was assessable in 921 patients. After a median (interquartile range) follow-up of 8.5 (5.4–13.3) years, 110 deaths occurred, 62 of which were from a cardiovascular cause. Results: Optimal thresholds of RaVL and plasma NT-proBNP to predict mortality were 0.7 mV and 150 pg/ml, respectively. A three-modality variable based on RaVL and NT-proBNP was built: 0 when none were above the threshold, 1 or 2 when only one or both were above the threshold. After adjustment for all confounders including LVMI indexed to height raised to the allometric power of 2.7 in Cox regression analysis, we observed a significant increased risk for patients having one marker above the threshold for all-cause and cardiovascular mortality [hazard ratio: 1.76; 95% confidence interval (1.08–2.86); 2.18 (1.06–4.46)] and for those having two markers above the threshold [2.76 (1.51–5.03); 3.90 (1.69–9.00)]. The prognostic value of the combination had the highest C-index (0.772 and 0.839, respectively) in comparison with LVMI (0.746 and 0.806, respectively). Conclusion: Risk stratification in hypertension using the combination of NT-proBNP and RaVL is a simple method that may be considered in first line screening. Correspondence to Pierre-Yves Courand, MD, PhD, Cardiology Department, European Society of Hypertension Excellence Center, Hôpital de la Croix-Rousse et Hôpital Lyon Sud, Hospices Civils de Lyon, 103 Grande Rue de la Croix-Rousse, F-69004 Lyon, France. Tel: +33 0 472 071 667; fax: +33 0 472 071 674; e-mail: pierre-yves.courand@chu-lyon.fr Received 10 June, 2019 Revised 28 July, 2019 Accepted 30 July, 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.

Relationship between BMI and aortic stiffness: influence of anthropometric indices in hypertensive men and women Background: Increased aortic stiffness could be one of the mechanisms by which obesity increases cardiovascular risk independently of traditional risk factors. Studies have suggested that anthropometric indices may be predictors of cardiovascular risk but few studies have investigated their relations with aortic stiffness in high cardiovascular risk population. We investigated the strength of correlation between different anthropometric indices with aortic stiffness in hypertensive and diabetic patients. Methods: A cross-sectional study was performed in 474 hypertensive patients. Anthropometric indices were calculated: BMI, waist circumference, waist–hip ratio, and waist–height ratio (WHtR). Aortic stiffness was assessed by measurement of carotid-femoral pulse wave velocity (PWV). Correlations between indices and PWV were investigated by linear regression analyses and hierarchical analyses after adjusting for cardiovascular risk factors. Results: Regional anthropometric indices were more strongly correlated with PWV than BMI in both sexes. In linear regression analyses, WHtR presented the highest correlation with PWV than other indices in our study population. In adjusted hierarchical regression used, WHtR had the highest additive value on top of BMI while there no additive value of BMI on top of WHtR. These differences remained after adjustment on cardiovascular events. In men WHtR was more closely correlated with PWV than others. In women, waist–hip ratio and WHtR were equally correlated with PWV compared with BMI. Conclusion: Regional anthropometric indices are more closely correlated with PWV than BMI in hypertensive patients. WHtR presents the highest correlation with PWV beyond BMI. Registration: The study was registered in the French National Agency for Medicines and Health Products Safety (No. 2013-A00227-38) and was approved by the Advisory Committee for Protection of Persons in Biomedical Research. Correspondence to Jacques Blacher, MD, PhD, Hypertension and Cardiovascular Prevention Unit, Diagnosis and Therapeutic Center, Paris-Descartes University, Hôtel-Dieu Hospital, AP-HP, 1 Place du Parvis de Notre-Dame, Paris, France. E-mail: jacques.blacher@aphp.fr Received 1 July, 2019 Revised 19 July, 2019 Accepted 30 July, 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.

The impact on office blood pressure categories and ambulatory blood pressure discrepancies of the European Society of Hypertension and American Academy of Pediatrics Guidelines for Management of Hypertension in Children and Adolescents Background: The objective was to assess the differences between the 2016 European Society of Hypertension (ESH) and the 2017 American Academy of Pediatrics (AAP) hypertension (HTN) guidelines in the distribution of office blood pressure (BP) categories as well as in the office and ambulatory BP mismatches. Material and methods: The study included 4940 clinical evaluations performed in 2957 youth (5–18 years) of both sexes. BP and anthropometric parameters were measured following standard conditions. The classification of the BP measurements was normotension, high-normal, stages 1 and 2 HTN, following the criteria of both guidelines. In a subgroup of 2467 participants, 3941 office BP assessment was completed with 24-h ambulatory BP monitoring using an oscillometric monitor under standard conditions. The classification on white-coat (WCH) and masked HTN was recorded. Results: The AAP classified more participants, 70 per 1000 BP evaluations in the categories of high-normal and stage 1 HTN, than the ESH did. The differences were greater in obese, but also present in normal weight participants. Likewise, significant discrepancies were observed in the prevalence of WCH and masked HTN. The AAP identified more participants with WCH, with greater differences in older participants, mainly in boys, independent of weight category. In contrast, the ESH identified more participants with masked HTN. The excess of WCH by AAP was three times higher than the excess of masked HTN by ESH. Conclusion: The application of the two guidelines may result in marked differences in the classification of high-normal BP and HTN and in the mismatched conditions when ambulatory BP monitoring is applied. Correspondence to Empar Lurbe, MD, PhD, FAHA, Department of Pediatrics, Consorcio Hospital General, University of Valencia, Valencia, Spain. E-mail: empar.lurbe@uv.es Received 17 July, 2019 Revised 30 July, 2019 Accepted 30 July, 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.

Acute vascular effects of vascular endothelial growth factor inhibition in the forearm arterial circulation Objective: Although vascular endothelial growth factor inhibition (VEGFi) represents a major therapeutic advance in oncology, it is associated with hypertension and adverse vascular thrombotic events. Our objective was to determine whether VEGFi caused direct vascular dysfunction through increased endothelin-1 (ET-1) activity or impaired endothelial vasomotor or fibrinolytic function. Methods: Using forearm venous occlusion plethysmography, we measured forearm blood flow during intra-arterial infusions of bevacizumab (36–144 μg/dl forearm volume per minute) administered for 15–60 min in healthy volunteers (n = 6–8). On two separate occasions in 10 healthy volunteers, we further measured forearm blood flow and tissue plasminogen activator (t-PA) release during intra-arterial bradykinin infusion (100 and 1000 pmol/min) in the presence and absence of bevacizumab (144 μg/dl forearm volume per minute), and the presence and absence of endothelin A receptor antagonism with BQ-123 (10 nmol/min). Plasma t-PA and plasminogen activator inhibitor-1 (PAI-1) concentrations were measured at baseline and with each dose of bradykinin. Results: Baseline blood flow and plasma ET-1, t-PA and PAI-1 concentrations were unaffected by bevacizumab. Bradykinin caused dose-dependent vasodilatation (P < 0.0001) and t-PA release (P < 0.01) but had no effect on plasma PAI-1 concentrations. Neither bevacizumab nor BQ-123 affected bradykinin-induced vasodilatation and t-PA release. Conclusion: Acute exposure to bevacizumab does not directly cause endothelial vasomotor or fibrinolytic dysfunction in healthy young volunteers. Correspondence to Dr Alan C. Cameron, BSc (Hons), MB ChB, MRCP, BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, 126 University Place, Glasgow G12 8TA, United Kingdom. Tel: +44 141 330 8271; fax: +44 141 330 3360; e-mail: alan.cameron.2@glasgow.ac.uk. Received 4 June, 2019 Revised 1 August, 2019 Accepted 1 August, 2019 This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Clinical characteristics, antihypertensive medication use and blood pressure control among patients with treatment-resistant hypertension: the Survey of PatIents with treatment ResIstant hyperTension study Objective: We evaluated the characteristics of patients with treatment-resistant hypertension (TRH) and the prevalence of TRH in a large multicountry sample of specialist tertiary centres. Methods: The Survey of PatIents with treatment ResIstant hyperTension (SPIRIT) study was a retrospective review of medical records of patients seen at tertiary centres located in Western Europe, Eastern Europe, North America, South America, Australia and Asia. Data on demographics, medical history and medication use were extracted from medical records. Prevalence and incidence of TRH were based upon estimated catchment populations. Results: On thousand, five hundred and fifty-five patients from 76 centres were included, mostly from centres that specialize in hypertension (55%), cardiology (11%) or nephrology (19%). Mean age was 64, 60% were men, 62% were Caucasian, 36% had chronic kidney disease, 41% had diabetes, 12% were smokers and 31% had a previous cardiovascular event. Daytime and night-time ambulatory blood pressure (BP) was the most frequently used measurement for diagnosis (82%). Ninety-five percent of patients were prescribed diuretics, 93% an inhibitor of the renin–angiotensin system, 86% a calcium channel blocker, 74% a beta-blocker and 36% an aldosterone antagonist. The overall estimated mean incidence of TRH was 5.8 per 100 000 per year (ranging between 2.3 and 14.0 across regions) and the corresponding estimated mean prevalence of TRH was 23.9 per 100 000 (ranging between 7.6 and 90.5 across regions). Conclusion: Observed variation likely reflects real differences in patient characteristics and physician management practices across regions and specialities but may also reflect differences in patient selection and errors in estimation of catchment population across participating centres. Correspondence to Professor John Chalmers, MD, PhD, The George Institute for Global Health, Level 10, King George V Building, 83-117 Missenden Road, Camperdown, NSW 2050, Australia. E-mail: chalmers@georgeinstitute.org.au Received 14 December, 2018 Revised 16 May, 2019 Accepted 6 June, 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.

Hypertensive emergencies and urgencies: a single-centre experience in Northern Italy 2008–2015 Background: An increasing attention is given to emergency departments (EDs) admissions for an acute and severe rise in blood pressure (BP). Data on epidemiology and treatment of hypertensive emergencies and urgencies admitted to ED are still limited. The aim of our study was to evaluate the prevalence, clinical presentation and treatment of patients admitted for hypertensive emergencies or hypertensive urgencies. Methods: Medical records of consecutive patients aged at least 18 years, admitted to the ED of the Spedali Civili in Brescia in 2008 and in 2015 and presenting with SBP at least 180 mmHg and/or DBP at least 120 mmHg were prospectively collected and analysed. Results: The prevalence of patients admitted with acute BP rise was 2.0% (n = 1551, age 70 ± 14 years) in 2008 and 1.75% (n = 1214, age 69.7 ± 15 years) in 2015. According to the clinical presentation and the presence of acute organ damage, patients were defined hypertensive emergencies (20.4 and 15.4%, respectively, in 2008 and 2015) or as hypertensive urgencies (79.6 and 84.5%, respectively, in 2008 and 2015). SBP and DBP values were higher in patients with emergencies than in those with urgencies (BP 193 ± 15/102 ± 15 vs. 189 ± 13/96 ± 13 mmHg in 2008 and 192 ± 17/98 ± 15 vs. 189 ± 12/94 ± 15 mmHg in 2015, P < 0.001 for both). Among hypertensive emergencies, the different forms of organ damage were 25% acute coronary syndromes and 1% aortic dissection in both periods, 34 and 38% acute heart failure, 40 and 37% stroke. Conclusion: Admission to the ED for hypertensive emergencies and hypertensive urgencies is still high. Diagnosis and treatment are still not appropriate and require the rapid application of recently published guidelines. Correspondence to Maria Lorenza Muiesan, Department of Clinical & Experimental Sciences, University of Brescia, Department of Internal Medicine, ASST Spedali Civili di Brescia, Piazzale Spedali Civili n 1, Brescia 25123, Italy. Tel: +39 030 3998721; fax: +39 030 3388147; e-mail: marialorenza.muiesan@unibs.it Received 23 May, 2019 Revised 3 July, 2019 Accepted 15 July, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Blood pressure measurement in atrial fibrillation: review and meta-analysis of evidence on accuracy and clinical relevance Atrial fibrillation (AF) often coexists with hypertension in the elderly and multiplies the risk of stroke and death. Blood pressure (BP) measurement in patients with AF is difficult and uncertain and has been a classic exclusion criterion in hypertension clinical trials leading to limited research data. This article reviews the evidence on the accuracy of BP measurement in AF performed using different methods (office, ambulatory, home) and devices (auscultatory, oscillometric) and its clinical relevance in predicting cardiovascular damage. The current evidence suggests the following: (i) Interobserver and intra-observer variation in auscultatory BP measurement is increased in AF because of increased beat-to-beat BP variability and triplicate measurement is required; (ii) The evidence from validation studies of automated electronic BP monitors in AF is limited and methodologically heterogeneous and suggests reasonable accuracy in measuring SBP and a small yet consistent overestimation of DBP; (iii) 24-h ambulatory BP monitoring is feasible in AF, with similar proportion of errors as in individuals without AF; (iv) both auscultatory and automated oscillometric BP measurements appear to be clinically relevant in AF, providing similar associations with intra-arterial BP measurements and with indices of preclinical cardiac damage as in patients without AF, and predict cardiovascular events and death; (v) Screening for AF in the elderly using an AF-specific algorithm during routine automated office, home or ambulatory BP measurement has high diagnostic accuracy. In conclusion, in AF patients, BP measurement is important, reliable, and clinically relevant and should not be neglected in clinical research and in practice. 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 8 June, 2019 Accepted 3 July, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.