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      Sex differences in arterial hypertension : A scientific statement from the ESC Council on Hypertension, the European Association of Preventive Cardiology, Association of Cardiovascular Nursing and Allied Professions, the ESC Council for Cardiology Practice, and the ESC Working Group on Cardiovascular Pharmacotherapy

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          Graphical Abstract

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          Sex differences in hypertension. BP, blood pressure; CV, cardiovascular; T2D, type 2 diabetes; OSAS, obstructive sleep apnoea syndrome; LVH, left ventricular hypertrophy; LV, left ventricular; LA left atrial; HFpEF, heart failure with preserved ejection fraction; BB, beta blocker; CCB, calcium channel blocker; HFrEF, heart failure with reduced ejection fraction.

          Abstract

          There is strong evidence that sex chromosomes and sex hormones influence blood pressure (BP) regulation, distribution of cardiovascular (CV) risk factors and co-morbidities differentially in females and males with essential arterial hypertension. The risk for CV disease increases at a lower BP level in females than in males, suggesting that sex-specific thresholds for diagnosis of hypertension may be reasonable. However, due to paucity of data, in particularly from specifically designed clinical trials, it is not yet known whether hypertension should be differently managed in females and males, including treatment goals and choice and dosages of antihypertensive drugs. Accordingly, this consensus document was conceived to provide a comprehensive overview of current knowledge on sex differences in essential hypertension including BP development over the life course, development of hypertension, pathophysiologic mechanisms regulating BP, interaction of BP with CV risk factors and co-morbidities, hypertension-mediated organ damage in the heart and the arteries, impact on incident CV disease, and differences in the effect of antihypertensive treatment. The consensus document also highlights areas where focused research is needed to advance sex-specific prevention and management of hypertension.

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          Most cited references182

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          2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure

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            2018 ESC/ESH Guidelines for the management of arterial hypertension

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              Global burden of 87 risk factors in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

              Summary Background Rigorous analysis of levels and trends in exposure to leading risk factors and quantification of their effect on human health are important to identify where public health is making progress and in which cases current efforts are inadequate. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 provides a standardised and comprehensive assessment of the magnitude of risk factor exposure, relative risk, and attributable burden of disease. Methods GBD 2019 estimated attributable mortality, years of life lost (YLLs), years of life lived with disability (YLDs), and disability-adjusted life-years (DALYs) for 87 risk factors and combinations of risk factors, at the global level, regionally, and for 204 countries and territories. GBD uses a hierarchical list of risk factors so that specific risk factors (eg, sodium intake), and related aggregates (eg, diet quality), are both evaluated. This method has six analytical steps. (1) We included 560 risk–outcome pairs that met criteria for convincing or probable evidence on the basis of research studies. 12 risk–outcome pairs included in GBD 2017 no longer met inclusion criteria and 47 risk–outcome pairs for risks already included in GBD 2017 were added based on new evidence. (2) Relative risks were estimated as a function of exposure based on published systematic reviews, 81 systematic reviews done for GBD 2019, and meta-regression. (3) Levels of exposure in each age-sex-location-year included in the study were estimated based on all available data sources using spatiotemporal Gaussian process regression, DisMod-MR 2.1, a Bayesian meta-regression method, or alternative methods. (4) We determined, from published trials or cohort studies, the level of exposure associated with minimum risk, called the theoretical minimum risk exposure level. (5) Attributable deaths, YLLs, YLDs, and DALYs were computed by multiplying population attributable fractions (PAFs) by the relevant outcome quantity for each age-sex-location-year. (6) PAFs and attributable burden for combinations of risk factors were estimated taking into account mediation of different risk factors through other risk factors. Across all six analytical steps, 30 652 distinct data sources were used in the analysis. Uncertainty in each step of the analysis was propagated into the final estimates of attributable burden. Exposure levels for dichotomous, polytomous, and continuous risk factors were summarised with use of the summary exposure value to facilitate comparisons over time, across location, and across risks. Because the entire time series from 1990 to 2019 has been re-estimated with use of consistent data and methods, these results supersede previously published GBD estimates of attributable burden. Findings The largest declines in risk exposure from 2010 to 2019 were among a set of risks that are strongly linked to social and economic development, including household air pollution; unsafe water, sanitation, and handwashing; and child growth failure. Global declines also occurred for tobacco smoking and lead exposure. The largest increases in risk exposure were for ambient particulate matter pollution, drug use, high fasting plasma glucose, and high body-mass index. In 2019, the leading Level 2 risk factor globally for attributable deaths was high systolic blood pressure, which accounted for 10·8 million (95% uncertainty interval [UI] 9·51–12·1) deaths (19·2% [16·9–21·3] of all deaths in 2019), followed by tobacco (smoked, second-hand, and chewing), which accounted for 8·71 million (8·12–9·31) deaths (15·4% [14·6–16·2] of all deaths in 2019). The leading Level 2 risk factor for attributable DALYs globally in 2019 was child and maternal malnutrition, which largely affects health in the youngest age groups and accounted for 295 million (253–350) DALYs (11·6% [10·3–13·1] of all global DALYs that year). The risk factor burden varied considerably in 2019 between age groups and locations. Among children aged 0–9 years, the three leading detailed risk factors for attributable DALYs were all related to malnutrition. Iron deficiency was the leading risk factor for those aged 10–24 years, alcohol use for those aged 25–49 years, and high systolic blood pressure for those aged 50–74 years and 75 years and older. Interpretation Overall, the record for reducing exposure to harmful risks over the past three decades is poor. Success with reducing smoking and lead exposure through regulatory policy might point the way for a stronger role for public policy on other risks in addition to continued efforts to provide information on risk factor harm to the general public. Funding Bill & Melinda Gates Foundation.
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                Author and article information

                Contributors
                Journal
                Eur Heart J
                Eur Heart J
                eurheartj
                European Heart Journal
                Oxford University Press (US )
                0195-668X
                1522-9645
                07 December 2022
                22 September 2022
                22 September 2022
                : 43
                : 46 , Focus Issue on Epidemiology, Prevention, and Healthcare Policies
                : 4777-4788
                Affiliations
                Center for Research on Cardiac Disease in Women, University of Bergen , Bergen, Norway
                University Hospital Zurich University Heart Center, Cardiology, University Hospital and University of Zurich , Zurich, Switzerland
                Department of Cardiology, Cardiovascular Center Aalst, OLV Clinic Aalst , Aalst, Belgium
                Department of Experimental Pharmacology, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel , Brussels, Belgium
                Department of Medical and Surgical Sciences, University of Bologna , Bologna, Italy
                Université de Paris Cité, Inserm, PARCC , Paris, France
                Service de Pharamcologie, AP-HP, Hôpital Européen Georges Pompidou , Paris, France
                University of Cardiologia, ASST Garda , Desenzano del Garda, Italy
                Department of Rehabilitation Sciences, KU Leuven , Leuven, Belgium
                Clinique Villette , Dunkerque, France
                Department of Cardiology and Vascular Pathology, CH Saint Joseph and Saint Luc , Lyon, France
                Karolinska Institutet, Department of Clinical Sciences, Danderyd Hospital, Division of Cardiovascular Medicine , Stockholm, Sweden
                Department of Community Medicine, UiT The Arctic University of Norway , Tromsø, Norway
                Department of Cardiology, Radboudumc , Nijmegen, The Netherlands
                Department of Internal Medicine III, Cardiology, Angiology and Intensive Care Medicine, Saarland University Hospital , Homburg/Saar, Germany
                Department of Cardiology and Kolling Institute, Royal North Shore Hospital , St Leonards, UK
                Faculty of Medicine and Health Sciences, Macquarie University , Sydney, Australia
                Department of Circulation and Medical Imaging, Norwegian University of Science and Technology , Trondheim, Norway
                Department of Cardiac, Neural and Metabolic Sciences, Instituto Auxologico Italiano, IRCCS , Milan, Italy
                Department of Medicine and Surgery, University of Milano-Bicocca , Milan, Italy
                Hypertension Research Center and Department of Advanced Biomedical Sciences, Federico II University , Naples, Italy
                Author notes
                Corresponding author. Tel: +4792086505, Email: eva.gerdts@ 123456uib.no

                Conflict of interest: E.G.: Bayer Health, NOKLUS, Fürst laboratories; I.S. Amgen, Astra Zeneca, Daiichi Sankio, Medtronic, Merck Sharpe & Dohme, Novartis, Recordati, Sanofi and Servier; SB Daiichi Sankyo; Merck, Sanofi, Menarini and Servier; C.B. Menarini Corporate, Servier, Novo Nordisk and Novartis; R.M.B. Medtronic; C.C.: none; V.C.: none; F.D.: none; M.F.: none; T.K.: TK Medtronics, and ReCor Medical; M.L.L.: Bayer Health, Sanofi, Bristol Myers Squibb and Pfizer; AHEMM: Organon, Novartis, Abbott and Omron; F.M.: Medtronic, ReCor Medical, Astra-Zeneca, Bayer, Boerhringer-Ingelheim, Medtronic, Merck and ReCor Medical; A.S.M.: Servier and SCAI; T.M.: none; G.P.: none; G.d.S.: none.

                Author information
                https://orcid.org/0000-0003-4109-2311
                https://orcid.org/0000-0001-8197-8892
                https://orcid.org/0000-0002-7081-4881
                https://orcid.org/0000-0001-8039-8781
                https://orcid.org/0000-0002-6107-3356
                https://orcid.org/0000-0002-6381-1404
                https://orcid.org/0000-0002-0578-4954
                https://orcid.org/0000-0001-6102-8494
                https://orcid.org/0000-0002-2595-2433
                https://orcid.org/0000-0001-9909-4956
                https://orcid.org/0000-0002-8532-6573
                https://orcid.org/0000-0001-5782-9926
                https://orcid.org/0000-0002-4425-549X
                https://orcid.org/0000-0001-6435-0411
                https://orcid.org/0000-0003-1024-8088
                https://orcid.org/0000-0001-9402-7439
                https://orcid.org/0000-0001-8567-9881
                Article
                ehac470
                10.1093/eurheartj/ehac470
                9726450
                36136303
                65f77f00-6239-4843-b677-c97c871aac5b
                © The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License ( https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 29 March 2022
                : 17 July 2022
                : 11 August 2022
                Page count
                Pages: 12
                Categories
                Special Article
                Hypertension
                AcademicSubjects/MED00200
                Eurheartj/30

                Cardiovascular Medicine
                hypertension,sex,blood pressure regulators,hypertension-mediated organ damage,pharmacological treatment,adverse events,cardiovascular disease,sex hormones

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