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.

Left-versus-right-adrenal-volume ratio as a screening index before adrenal venous sampling to identify unilateral primary aldosteronism patients Objectives: The current study aimed to investigate the value of the computed tomography-based left-versus-right adrenal gland volume ratio (L/Rv) in screening patients with unilateral primary aldosteronism. Methods: The current study recruited 114 patients who underwent successful adrenal venous sampling (AVS) and adrenal computed tomography at West China Hospital of Sichuan University. The patients were divided into three groups according to the AVS results: AVS-left, AVS-bilateral, and AVS-right primary aldosteronism. The volumes of the left and right adrenal glands were semiautomatically calculated. The L/Rv of each patient was computed, and its value in identifying unilateral primary aldosteronism was analyzed. Results: The mean value of the L/Rv was larger in AVS-left patients and smaller in AVS-right patients than that in AVS-bilateral patients. In AVS-left primary aldosteronism patients, the cutoff value of the L/Rv with the highest Youden index was 1.344 [area under the curve (AUC) 0.851, sensitivity 80.0%, specificity 78.1%]. The optimal cutoff value was 1.908, of which 46.0% (23/50) of AVS-left primary aldosteronism patients could be identified (specificity 100.0%). In AVS-right primary aldosteronism patients, the cutoff value of the L/Rv with the highest Youden index was 1.267 (AUC 0.868, specificity 72.8%, sensitivity 87.9%). The optimal cutoff value was 0.765, of which 27.3% (9/33) of AVS-right primary aldosteronism patients could be identified (specificity 100.0%). Patients with L/Rv more than 1.908 or less than 0.765 had higher complete success rate postsurgery. Conclusion: Although not perfect, the L/Rv is an applicable index to screen unilateral primary aldosteronism patients for surgery. Primary aldosteronism patients, even those aged more than 35 years, with an L/Rv more than 1.908 or less than 0.765 can be spared AVS before surgery. Correspondence to Tao Chen, Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, 37 GuoXue Lane, Chengdu 610041, Sichuan, PR China. Tel: 86 18980606758; e-mail: dr.chentao@qq.com Received 3 March, 2019 Revised 1 September, 2019 Accepted 7 September, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Muscle strength is a major determinant of the blood pressure response to isometric stress testing: the Asklepios population study Aim: Maximal handgrip strength is a strong predictor of cardiovascular mortality in economically and socioculturally diverse countries, yet the main determinants of cardiovascular response to change in afterload during handgrip are not well known. We examined the blood pressure (BP) responses during submaximal handgrip (at 25% of grip strength) and the determinants of grip strength. Methods: We studied 2215 participants from a population-based random sample without overt clinical disease (Asklepios Study; mean age 56.2 years). Handgrip testing was performed using a modified Jamar dynamometer with direct visual feedback. Simultaneously, a validated finger plethysmographic device measured continuous BP and heart rate. Results: During handgrip, SBP and DBP rose by, respectively, 20 ± 13 and 10 ± 6 mmHg. These changes were normally distributed and consistently higher in men. The main independent determinants of mean arterial pressure response during handgrip were: grip strength (F = 191.4; P < 0.001), baseline pulse pressure (F = 32.0; P < 0.001), height (F = 16.4; P < 0.001) and age (F = 12.8; P < 0.001). Grip strength was associated with muscle mass, better metabolic health, but also with higher baseline DBP. There was a significant graded increase in maximum pressure achieved and in the magnitude of pressure change during handgrip with increasing BP categories (P for trend <0.001). Conclusion: The population BP response to handgrip is variable and its predominant determinant turned out to be grip strength itself, which should be accounted for in future analyses. Higher baseline BP, even within the normotensive range, acted as an independent and graded predictor of BP increase during handgrip. Correspondence to Caroline M. Van daele, Department of Cardiovascular Diseases, Ghent University and Ghent University Hospital, Corneel Heymanslaan 10, Building 10K12IE, 9000 Ghent, Belgium. Tel: +32 93320127; e-mail: Ernst.Rietzschel@Ugent.be Received 14 March, 2019 Revised 20 August, 2019 Accepted 9 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.

Neonatal effects of intrauterine metoprolol/bisoprolol exposure during the second and third trimester: a cohort study with two comparison groups Objectives: Our aim was to evaluate the effects of beta-blockers during the second and third trimester on fetal growth, length of gestation and postnatal symptoms in exposed infants. Methods: The current prospective observational cohort study compares 294 neonates of hypertensive mothers on metoprolol or bisoprolol during the second and/or third trimester with 225 methyldopa-exposed infants and 588 infants of nonhypertensive mothers. The risks for reduced birth weight, prematurity, neonatal bradycardia, hypoglycaemia and respiratory disorders were analysed. Results: The rate of small-for-gestational-age children was significantly higher in long-term beta-blocker exposed infants (24.1%) compared with the methyldopa cohort [10.2%, odds ratio (OR)adj 2.5, 95% confidence interval (CI) 1.2–5.2] and the nonhypertensive cohort (9.9%, ORadj 4.3, 95% CI 2.6–7.1). The risk for preterm birth was significantly increased compared with nonhypertensive pregnancies (ORadj 2.2, 95% CI 1.3–3.8) but not compared with the methyldopa cohort. Neonatal adverse outcomes occurred more frequently in the study cohort (11.5%) compared with the nonhypertensive comparison group (6.5%) and the methyldopa cohort (8.4%), but without statistical significance (ORadj 1.5, 95% CI 0.7–3.0 and ORadj 1.5, 95% CI 0.7–3.3, respectively). Conclusion: Long-term intrauterine exposure to metoprolol or bisoprolol may increase the risk of being born small-for-gestational-age. It is still a matter of debate to which extent maternal hypertension contributes to the lower birth weight. Serious neonatal symptoms are rare. Altogether, metoprolol and bisoprolol are well tolerated treatment options, but a case-by-case decision on close neonatal monitoring is recommended. Correspondence to Dr. med. Angela Kayser, Pharmakovigilanzzentrum Embryonaltoxikologie, Institut für Klinische Pharmakologie und Toxikologie, Charité – Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany. Tel: +49 30 450525702; fax: +49 30 4507525920; e-mail: angela.kayser@charite.de Received 27 March, 2019 Revised 19 August, 2019 Accepted 23 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.

Redefining hypertension in children and adolescents: A review of the evidence considered by the European Society of Hypertension and American Academy of Pediatrics guidelines No abstract available

Biological convergence of three human and animal model quantitative trait loci for blood pressure Objectives: Blood pressure (BP) is comparable among different mammalian orders, despite their evolution divergence. Because of it, fundamental mechanisms should connect humans and rodents by their shared BP physiology. We hypothesized that similar quantitative trait loci (QTLs) function in both humans and rodents in controlling BP. Methods: We utilized inbred hypertensive Dahl salt-sensitive rats (DSS) as a functional proxy to evaluate the relevance of human genome-wide association studies (GWAS) genes in BP regulation. Results: First, three DSS BP QTLs functionally captured three specific human GWAS genes. Each QTL has a major biological impact, not a miniscule effect, on BP, in causation by function. Second, noncoding single-nucleotide polymorphisms (SNPs) found in GWAS are by products of primate evolution, instead of mechanistic drivers in regulating BP, because their absence did not impact on BP of mammals. Third, a missense mutation, rather than a noncoding GWAS SNP marking it nearby, is the priority functional basis for a given QTL. Depleting such a noncoding GWAS SNP had no impact, whereas eliminating the muscarinic cholinergic receptor 3 (M3R) signaling decreased BP. Finally, epistatic modularity biologically organizes multiple QTLs with redundant functions, and is the genetic mechanism that modulates the BP homeostasis when QTLs function collectively. Conclusions: Two pathogenic pathways of hypertension biologically unify mechanisms of BP regulations for humans and their functional surrogates. The mechanism-based biology for the M3R-mediated pathway in raising BP has established M3R as a novel pathogenesis-driven target for antihypertension therapies. Correspondence to Alan Y. Deng, Research Centre, Centre hospitalier de l’Université de Montréal (CHUM), 900 rue St. Denis Street, R08-432, Montréal, Québec H2X 0A9, Canada. Tel: +1 514 890 8000 ext. 23614; fax: +514 412 7655; e-mail: alan.deng@umontreal.ca Received 24 April, 2019 Revised 21 August, 2019 Accepted 4 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.

Use of simulated patients to assess hypertension case management at public healthcare facilities in South Africa Objective: Our study aims to evaluate hypertensive case management in South Africa's public health sector using simulated patients. Method: Our study describes interactions between hypertensive simulated patients and primary healthcare workers at 39 public sector healthcare facilities in two metropolitan centres in the Eastern and Western Cape Provinces of South Africa. Our analysis focus on 97 interactions where our eight simulated patients tested within range for stage 1 hypertension, that is with SBP 140–159 mmHg and/or DBP 90–99 mmHg. For this subset, we describe how healthcare workers communicated the outcome of the blood pressure test, and whether they follow government guidelines on risk assessment and lifestyle advice. Results: Healthcare workers highlighted the risks associated with hypertension in one out of three cases and stressed the importance of regular monitoring of blood pressure in less than half of cases. Hypertensive patients received advice on all six lifestyle risk factors in 8% of cases. 39% of patients received no lifestyle advice at all. In one out of four cases, hypertensive patients left the facility without a hypertension diagnosis and with no prospect of a follow-up visit. Conclusion: Simulated patients can assess the quality of hypertension case management, yielding granular and comprehensive information that can help mobilize resources to improve care. The management of hypertension patients in South African public healthcare facilities is critically insufficient. Given that hypertension is responsible for a rising share of deaths in South Africa and many of these deaths are preventable, urgent intervention is needed. Correspondence to Ronelle Burger, Economics Department, Stellenbosch University, Stellenbosch, South Africa. Tel: +27 21 808 3106; fax: +27 21 808 4637; e-mail: rburger@sun.ac.za Received 30 April, 2019 Revised 23 August, 2019 Accepted 26 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.

Visit-to-visit blood pressure variation and outcomes in heart failure with reduced ejection fraction: findings from the Eplerenone in Patients with Systolic Heart Failure and Mild Symptoms trial Background: Visit-to-visit office blood pressure (BP) variability (BPV) has been associated with morbidity and mortality outcomes in several cardiovascular conditions. The aim of this study was to evaluate the association between BPV and outcomes in patients with heart failure and reduced ejection fraction and the effect of eplerenone on BPV. Methods and results: We evaluated the associations between BPV, calculated as SBP coefficient of variation (SBP-CoV = SD/mean × 100%), and the primary composite endpoint of cardiovascular mortality or heart failure hospitalization (HFH), and its components, in 2549 patients from the Eplerenone in Patients with Systolic Heart Failure and Mild Symptoms trial. Lower SBP-CoV was independently associated with a higher risk of all the studied outcomes, while higher as well as lower SBP-CoV were associated with a higher risk of cardiovascular death. After a median follow-up period of 21 months the risk of the composite outcome of cardiovascular death or HFH was almost double in the lower SBP-CoV tertile as compared with the intermediate tertile [adjusted hazard ratio: 2.01, 95% confidence interval (1.62–2.51), P < 0.001]. The relationship between SBP-CoV and outcomes was not modified by eplerenone (P value for interaction = 0.48). An interaction was detected between mean SBP and SBP-CoV for the primary outcome (P = 0.048) and for HFH (P = 0.018). The effect modification was slight, but lower SBP-CoV was associated with worse outcomes in patients with both low and high SBP, while this interaction was less clear for patients with SBP in the ‘normal’ range. Conclusion: In our patients with heart failure and reduced ejection fraction and mild symptoms, both a lower and higher SBP-CoV were associated with worse outcomes. SBP-CoV did not modify the benefit of eplerenone. Further studies are warranted to clarify the role of BPV in heart failure. ClinicalTrials.gov identifier: NCT00232180. Correspondence to Patrick Rossignol, MD, PhD, Centre d’Investigation Clinique 1433 Module Plurithématique, CHRU Nancy – Hopitaux de Brabois, Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu, 4 Rue Du Morvan, 54500 Vandoeuvre-les-Nancy, France. Tel: +33 0 3 83 15 73 15; fax: +33 0 3 83 15 73 24; e-mail: p.rossignol@chru-nancy.fr Received 11 May, 2019 Revised 11 September, 2019 Accepted 12 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.

Lack of a significant legacy effect of baseline blood pressure ‘treatment naivety’ on all-cause and cardiovascular mortality in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial Objectives: To investigate legacy effects at 14-year follow-up of all-cause and cardiovascular disease (CVD) mortality in ‘treatment-naive’ or ‘previous treatment’ groups based on blood pressure (BP)-lowering treatment status at baseline. Methods: A post-hoc observational study of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. We excluded participants with a previous history of CVD events. Cox proportional hazard model and 95% confidence interval were used to estimate the effects of treatment naive on mortality outcomes. Moreover, a subgroup analysis by estimated 10-year Framingham risk score was performed. Results: In multivariable models adjusting for baseline and in-trial characteristics (BP values and number of BP medications as time-dependent variables), there was no statistically significant difference in 5 and 14-year all-cause mortality with a hazard ratio of 0.93 (95% confidence interval 0.80–1.09) and hazard ratio 0.95 (0.88–1.03) and in 5 and 14-year CVD mortality hazard ratio 0.94 (0.72–1.23) and hazard ratio 0.93 (0.80–1.08). In subgroup by absolute CVD risk, no heterogeneity of the association between treatment naive and short-term or long-term all-cause or CVD mortality were found. All comparisons are between the treatment-naive and previous treatment groups. Conclusion: Physicians are concerned about ‘legacy effects’ of not treating individuals with a BP of 140 mmHg or over and low absolute risk. When treatment intensification was taken into consideration in the primary prevention population in this study, no adverse legacy effect as a result of baseline BP ‘treatment naivety’ was evident in 14 years of follow-up. The nonsignificant associations were consistent across the CVD risk subgroups. However, the results may be biased due to unobserved residual confounding and therefore should be interpreted with caution. Correspondence to Chau L.B. Ho, Menzies Institute for Medical Research, University of Tasmania, Private Bag 23, Hobart 7001, TAS, Australia. Tel: +61 61406656898; fax: +61 362264734; e-mail: chau.ho@utas.edu.au Received 2 June, 2019 Revised 17 September, 2019 Accepted 18 September, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.