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      Sex differences in the renin-angiotensin-aldosterone system and its roles in hypertension, cardiovascular, and kidney diseases

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          Abstract

          Cardiovascular disease is a pathology that exhibits well-researched biological sex differences, making it possible for physicians to tailor preventative and therapeutic approaches for various diseases. Hypertension, which is defined as blood pressure greater than 130/80 mmHg, is the primary risk factor for developing coronary artery disease, stroke, and renal failure. Approximately 48% of American men and 43% of American women suffer from hypertension. Epidemiological data suggests that during reproductive years, women have much lower rates of hypertension than men. However, this protective effect disappears after the onset of menopause. Treatment-resistant hypertension affects approximately 10.3 million US adults and is unable to be controlled even after implementing ≥3 antihypertensives with complementary mechanisms. This indicates that other mechanisms responsible for modulating blood pressure are still unclear. Understanding the differences in genetic and hormonal mechanisms that lead to hypertension would allow for sex-specific treatment and an opportunity to improve patient outcomes. Therefore, this invited review will review and discuss recent advances in studying the sex-specific physiological mechanisms that affect the renin-angiotensin system and contribute to blood pressure control. It will also discuss research on sex differences in hypertension management, treatment, and outcomes.

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          Most cited references190

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          Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study.

          Although more than 80% of the global burden of cardiovascular disease occurs in low-income and middle-income countries, knowledge of the importance of risk factors is largely derived from developed countries. Therefore, the effect of such factors on risk of coronary heart disease in most regions of the world is unknown. We established a standardised case-control study of acute myocardial infarction in 52 countries, representing every inhabited continent. 15152 cases and 14820 controls were enrolled. The relation of smoking, history of hypertension or diabetes, waist/hip ratio, dietary patterns, physical activity, consumption of alcohol, blood apolipoproteins (Apo), and psychosocial factors to myocardial infarction are reported here. Odds ratios and their 99% CIs for the association of risk factors to myocardial infarction and their population attributable risks (PAR) were calculated. Smoking (odds ratio 2.87 for current vs never, PAR 35.7% for current and former vs never), raised ApoB/ApoA1 ratio (3.25 for top vs lowest quintile, PAR 49.2% for top four quintiles vs lowest quintile), history of hypertension (1.91, PAR 17.9%), diabetes (2.37, PAR 9.9%), abdominal obesity (1.12 for top vs lowest tertile and 1.62 for middle vs lowest tertile, PAR 20.1% for top two tertiles vs lowest tertile), psychosocial factors (2.67, PAR 32.5%), daily consumption of fruits and vegetables (0.70, PAR 13.7% for lack of daily consumption), regular alcohol consumption (0.91, PAR 6.7%), and regular physical activity (0.86, PAR 12.2%), were all significantly related to acute myocardial infarction (p<0.0001 for all risk factors and p=0.03 for alcohol). These associations were noted in men and women, old and young, and in all regions of the world. Collectively, these nine risk factors accounted for 90% of the PAR in men and 94% in women. Abnormal lipids, smoking, hypertension, diabetes, abdominal obesity, psychosocial factors, consumption of fruits, vegetables, and alcohol, and regular physical activity account for most of the risk of myocardial infarction worldwide in both sexes and at all ages in all regions. This finding suggests that approaches to prevention can be based on similar principles worldwide and have the potential to prevent most premature cases of myocardial infarction.
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            2020 International Society of Hypertension Global Hypertension Practice Guidelines

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              2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults

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                Author and article information

                Contributors
                Journal
                Front Cardiovasc Med
                Front Cardiovasc Med
                Front. Cardiovasc. Med.
                Frontiers in Cardiovascular Medicine
                Frontiers Media S.A.
                2297-055X
                19 June 2023
                2023
                : 10
                : 1198090
                Affiliations
                [ 1 ]Tulane Hypertension and Renal Center of Excellence, Tulane University School of Medicine , New Orleans, LA, United States
                [ 2 ]Department of Physiology, Tulane University School of Medicine , New Orleans, LA, United States
                [ 3 ]Department of Pharmacology, Tulane University School of Medicine , New Orleans, LA, United States
                Author notes

                Edited by: Hong Wang, Temple University, United States

                Reviewed by: Sarfaraz Ahmad, Wake Forest University, United States Kazutaka Ueda, The University of Tokyo, Japan

                [* ] Correspondence: Jia Long Zhuo jzhuo@ 123456tulane.edu
                Article
                10.3389/fcvm.2023.1198090
                10315499
                37404743
                ea27c40b-180d-437f-8e85-b13e949cc1e2
                © 2023 Nwia, Leite, Li and Zhuo.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 31 March 2023
                : 06 June 2023
                Page count
                Figures: 5, Tables: 0, Equations: 0, References: 192, Pages: 0, Words: 0
                Funding
                Funded by: National Institute of Diabetes and Digestive and Kidney Diseases
                Award ID: 1R01DK123144-01, 2R01DK067299-10A1, 2R01DK102429-03A1
                This work was supported in part by grants from National Institute of Diabetes and Digestive and Kidney Diseases (1R01DK123144-01; 2R01DK067299-10A1; and 2R01DK102429-03A1) to JZ.
                Categories
                Cardiovascular Medicine
                Review
                Custom metadata
                Sex and Gender in Cardiovascular Medicine

                cardiovascular,hypertension,kidney,renin-angiotensin system,sex differences

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