{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T23:03:06Z","timestamp":1768345386870,"version":"3.49.0"},"reference-count":47,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T00:00:00Z","timestamp":1768262400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"Korea government","doi-asserted-by":"publisher","award":["RS-2022-NR070832"],"award-info":[{"award-number":["RS-2022-NR070832"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: Blood renin and electrolyte levels are associated with blood pressure and hypertension. While sex-specific effects of such factors have been investigated, exact comparisons of the factors between the sexes have been scarce. Methods: Using cohort data from the Korean Genome and Environmental Study (KoGES), the study population that did not receive any interventions for blood pressure was determined. Blood levels of renin and electrolytes, including sodium, potassium, chloride, and calcium, were used to test their relationship with hypertension and blood pressure. Confounding variables, including age, body mass index (BMI), waist-to-hip ratio, family history of hypertension, alcohol consumption, smoking, blood urea nitrogen, creatinine, protein, and albumin levels, were used for adjustment in the multiple regression analysis. Results: In the single-variable analysis, sodium levels were significantly higher in the female population, and showed strong associations in the multiple regression analysis. Blood potassium levels showed no significant sex-specific differences. Among these factors, renin showed the greatest significance in both the total population and sex-specific groups. Moreover, in the development of hypertension, the effect size of renin was significantly different between sexes. Additionally, BMI tended to show stronger associations in females. Conclusions: This study identified sex-specific differential effects of renin and other electrolytes that are important in the pathophysiology of blood pressure. These findings provide clues for the more precise management of hypertension.<\/jats:p>","DOI":"10.3390\/jcm15020643","type":"journal-article","created":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T15:52:57Z","timestamp":1768319577000},"page":"643","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Cross-Sectional Study of Sex-Specific Associations of Renin and Electrolytes on the Development of Hypertension"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5734-1645","authenticated-orcid":false,"given":"Seong Beom","family":"Cho","sequence":"first","affiliation":[{"name":"Department of Biomedical Informatics, College of Medicine, Gachon University, 38-13, Dokgeom-ro 3 Street, Namdong-gu, Incheon 21565, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,13]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2023). Global Report on Hypertension: The Race Against a Silent Kille, World Health Organization."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1038\/s41440-024-01622-w","article-title":"The WHO Global report 2023 on hypertension warning the emerging hypertension burden in globe and its treatment strategy","volume":"47","author":"Kario","year":"2024","journal-title":"Hypertens. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.pcad.2016.10.002","article-title":"Renin Angiotensin Aldosterone System Inhibitors in Hypertension: Is There Evidence for Benefit Independent of Blood Pressure Reduction?","volume":"59","author":"Bavishi","year":"2016","journal-title":"Prog. Cardiovasc. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3396","DOI":"10.3748\/wjg.v23.i19.3396","article-title":"Renin angiotensin system in liver diseases: Friend or foe?","volume":"23","author":"Simoes","year":"2017","journal-title":"World J. Gastroenterol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3239057","DOI":"10.1155\/2022\/3239057","article-title":"Role and Mechanism of the Renin-Angiotensin-Aldosterone System in the Onset and Development of Cardiorenal Syndrome","volume":"2022","author":"Ma","year":"2022","journal-title":"J. Renin Angiotensin Aldosterone Syst."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.biopha.2017.07.091","article-title":"Renin-angiotensin-aldosterone (RAAS): The ubiquitous system for homeostasis and pathologies","volume":"94","author":"Patel","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"606S","DOI":"10.1093\/ajcn\/65.2.606S","article-title":"Dietary sodium chloride and potassium have effects on the pathophysiology of hypertension in humans and animals","volume":"65","author":"Tobian","year":"1997","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s40885-023-00259-0","article-title":"Effect of low sodium and high potassium diet on lowering blood pressure and cardiovascular events","volume":"30","author":"Kim","year":"2024","journal-title":"Clin. Hypertens."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1161\/HYPERTENSIONAHA.123.19487","article-title":"Modifying Dietary Sodium and Potassium Intake: An End to the \u2018Salt Wars\u2019?","volume":"81","author":"Little","year":"2024","journal-title":"Hypertension"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2983","DOI":"10.1161\/CIRCULATIONAHA.112.117333","article-title":"Body mass index and risk of incident hypertension over the life course: The Johns Hopkins Precursors Study","volume":"126","author":"Shihab","year":"2012","journal-title":"Circulation"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Landi, F., Calvani, R., Picca, A., Tosato, M., Martone, A.M., Ortolani, E., Sisto, A., D\u2019Angelo, E., Serafini, E., and Desideri, G. (2018). Body Mass Index is Strongly Associated with Hypertension: Results from the Longevity Check-up 7+ Study. Nutrients, 10.","DOI":"10.3390\/nu10121976"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"410","DOI":"10.33314\/jnhrc.v16i41.1560","article-title":"Correlation of Blood Pressure with Body Mass Index, Waist Circumference and Waist by Hip Ratio","volume":"16","author":"Chaudhary","year":"2019","journal-title":"J. Nepal Health Res. Counc."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e28297","DOI":"10.1016\/j.heliyon.2024.e28297","article-title":"Waist-to-height ratio is a better predictor of hypertension in women during recovery from anesthesia compared to BMI, waist-to-hip ratio, and waist circumference","volume":"10","author":"Cao","year":"2024","journal-title":"Heliyon"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1161\/HYPERTENSIONAHA.122.17952","article-title":"Salt Sensitivity of Blood Pressure in Women","volume":"80","author":"Barris","year":"2023","journal-title":"Hypertension"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"F406","DOI":"10.1152\/ajprenal.00222.2024","article-title":"Modulation of blood pressure by dietary potassium and sodium: Sex differences and modeling analysis","volume":"328","author":"Stadt","year":"2025","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Jiang, X., Zhao, Y., Yang, Q., Wang, W., Lin, T., and Qiu, Y. (2025). Gender differences in associations between obesity and hypertension, diabetes, dyslipidemia: Evidence from electronic health records of 3.5 million Chinese senior population. BMC Public Health, 25.","DOI":"10.1186\/s12889-025-21534-9"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1007\/s40292-015-0106-3","article-title":"Associations Between Hypertension and Body Mass Index and Waist Circumference in U.S. Adults: A Comparative Analysis by Gender","volume":"22","author":"Roka","year":"2015","journal-title":"High Blood Press. Cardiovasc. Prev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e20","DOI":"10.1093\/ije\/dyv316","article-title":"Cohort Profile: The Korean Genome and Epidemiology Study (KoGES) Consortium","volume":"46","author":"Kim","year":"2017","journal-title":"Int. J. Epidemiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2867","DOI":"10.1093\/eurheartj\/ehac313","article-title":"Sex-specific associations between potassium intake, blood pressure, and cardiovascular outcomes: The EPIC-Norfolk study","volume":"43","author":"Wouda","year":"2022","journal-title":"Eur. Heart J."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Gan, L., Zhao, B., Inoue-Choi, M., Liao, L.M., Graubard, B.I., Weinstein, S.J., Albanes, D., and Huang, J. (2024). Sex-specific associations between sodium and potassium intake and overall and cause-specific mortality: A large prospective U.S. cohort study, systematic review, and updated meta-analysis of cohort studies. BMC Med., 22.","DOI":"10.1186\/s12916-024-03350-x"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"16519","DOI":"10.1038\/s41598-025-01040-z","article-title":"Sex difference in the relationship between 24-h sodium-potassium ratio and prevalence of metabolic syndromes: A cross-sectional study","volume":"15","author":"Wang","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/S0895-7061(01)02293-2","article-title":"Serum potassium is not associated with blood pressure tracking in the Framingham Heart Study","volume":"15","author":"Walsh","year":"2002","journal-title":"Am. J. Hypertens."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.atherosclerosis.2021.12.006","article-title":"Serum potassium concentration and its association with hypertension among Ghanaian migrants and non-migrants: The RODAM study","volume":"342","author":"Ndong","year":"2022","journal-title":"Atherosclerosis"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1111\/j.1751-7176.2011.00503.x","article-title":"Serum calcium levels and hypertension among U.S. adults","volume":"13","author":"Sabanayagam","year":"2011","journal-title":"J. Clin. Hypertens."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Hua, Y., Liu, H.L., Sun, J.Y., Kong, X.Q., Sun, W., and Xiong, Y.Q. (2021). Association Between Serum Calcium and the Prevalence of Hypertension Among US Adults. Front. Cardiovasc. Med., 8.","DOI":"10.3389\/fcvm.2021.719165"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1161\/HYPERTENSIONAHA.113.01793","article-title":"Serum chloride is an independent predictor of mortality in hypertensive patients","volume":"62","author":"McCallum","year":"2013","journal-title":"Hypertension"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1136\/hrt.2006.107706","article-title":"Renin: Friend or foe?","volume":"93","author":"Brown","year":"2007","journal-title":"Heart"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Zhang, H., Singal, P.K., Ravandi, A., and Rabinovich-Nikitin, I. (2025). Sex-Specific Differences in the Pathophysiology of Hypertension. Biomolecules, 15.","DOI":"10.3390\/biom15010143"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s13293-017-0128-8","article-title":"Sex differences in the aging pattern of renin-angiotensin system serum peptidases","volume":"8","author":"Izagirre","year":"2017","journal-title":"Biol. Sex Differ."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1007\/s11906-002-0039-9","article-title":"Effects of gender on the renin-angiotensin system, blood pressure, and renal function","volume":"4","author":"Kang","year":"2002","journal-title":"Curr. Hypertens. Rep."},{"key":"ref_31","first-page":"266","article-title":"Interactions between oestrogen and the renin angiotensin system-potential mechanisms for gender differences in Alzheimer\u2019s disease","volume":"1","author":"Wharton","year":"2012","journal-title":"Am. J. Neurodegener. Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.genm.2012.06.005","article-title":"Sex differences in hypertension: Contribution of the renin-angiotensin system","volume":"9","author":"Manigrasso","year":"2012","journal-title":"Gend. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1161\/01.CIR.95.1.39","article-title":"Effects of estrogen replacement therapy on the renin-angiotensin system in postmenopausal women","volume":"95","author":"Schunkert","year":"1997","journal-title":"Circulation"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4296","DOI":"10.1210\/en.2014-1416","article-title":"GPER-1 and estrogen receptor-beta ligands modulate aldosterone synthesis","volume":"155","author":"Caroccia","year":"2014","journal-title":"Endocrinology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.6118\/jmm.2014.20.1.1","article-title":"Postmenopausal hypertension and sodium sensitivity","volume":"20","author":"Kim","year":"2014","journal-title":"J. Menopausal. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1161\/HYPERTENSIONAHA.117.11087","article-title":"Biological Sex Modulates the Adrenal and Blood Pressure Responses to Angiotensin II","volume":"71","author":"Shukri","year":"2018","journal-title":"Hypertension"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1161\/HYPERTENSIONAHA.119.12802","article-title":"Progesterone Predisposes Females to Obesity-Associated Leptin-Mediated Endothelial Dysfunction via Upregulating Endothelial MR (Mineralocorticoid Receptor) Expression","volume":"74","author":"Faulkner","year":"2019","journal-title":"Hypertension"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Goto, K., and Kitazono, T. (2022). Chloride Ions, Vascular Function and Hypertension. Biomedicines, 10.","DOI":"10.3390\/biomedicines10092316"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.kint.2021.03.025","article-title":"A small molecule inhibitor of the chloride channel TMEM16A blocks vascular smooth muscle contraction and lowers blood pressure in spontaneously hypertensive rats","volume":"100","author":"Cil","year":"2021","journal-title":"Kidney Int."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2263","DOI":"10.1093\/cvr\/cvaa271","article-title":"Oestrogen inhibits salt-dependent hypertension by suppressing GABAergic excitation in magnocellular AVP neurons","volume":"117","author":"Jin","year":"2021","journal-title":"Cardiovasc. Res."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Kato, M., Takayama, Y., and Sunagawa, M. (2021). The Calcium-Activated Chloride Channel TMEM16A is Inhibitied by Liquiritigenin. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.628968"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Kosami, K., Kuwabara, M., Okayama, A., and Ae, R. (2024). Body Mass Index and Weight Change as Predictors of Hypertension Development: A Sex-Specific Analysis. Nutrients, 17.","DOI":"10.3390\/nu17010119"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1360328","DOI":"10.1155\/2019\/1360328","article-title":"The Investigation of Sex Differences in the Effect of Body Mass Index","volume":"2019","author":"Xiao","year":"2019","journal-title":"Int. J. Hypertens."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.orcp.2014.07.001","article-title":"Gender differences in the relationship between blood pressure and body mass index during adolescence","volume":"9","author":"Kawada","year":"2015","journal-title":"Obes. Res. Clin. Pract."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"245","DOI":"10.4330\/wjc.v6.i5.245","article-title":"Alcohol-induced hypertension: Mechanism and prevention","volume":"6","author":"Husain","year":"2014","journal-title":"World J. Cardiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1177\/1747493016641961","article-title":"Interactive effects of physical fitness and body mass index on risk of stroke: A national cohort study","volume":"11","author":"Crump","year":"2016","journal-title":"Int. J. Stroke"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1016\/j.joca.2016.01.008","article-title":"Multiple P-values and Bonferroni correction","volume":"24","author":"Ranstam","year":"2016","journal-title":"Osteoarthr. Cartil."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/2\/643\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T16:07:30Z","timestamp":1768320450000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/2\/643"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,13]]},"references-count":47,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["jcm15020643"],"URL":"https:\/\/doi.org\/10.3390\/jcm15020643","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,13]]}}}