{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T02:21:28Z","timestamp":1755224488807,"version":"3.43.0"},"reference-count":31,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T00:00:00Z","timestamp":1754956800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Currently, some studies have investigated the relationship between homocysteine (Hcy) levels and hypertension. However, within the population of individuals with hypertension, there is still a lack of relevant research data. Therefore, we utilized data from the National Health and Nutrition Examination Survey (NHANES) to explore the associations between Hcy levels and hypertension prevalence, all-cause mortality, and cardiovascular mortality, in order to understand the role of Hcy levels in the control, assessment, and treatment of hypertension.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>In this study, the data utilized were derived from NHANES, which collected data from 1999 to 2006. A total of 7680 eligible participants were ultimately included. To explore the associations between Hcy levels and hypertension prevalence as well as blood pressure, a weighted multivariate linear regression model and restricted cubic splines were employed to adjust for confounding factors. Additionally, we conducted subgroup analyses to observe the associations between Hcy levels and hypertension prevalence, systolic blood pressure(SBP), and diastolic blood pressure (DBP) in different subgroups. Lastly, we employed Kaplan-Meier estimates and Cox proportional hazards regression models for survival analysis, elucidating the relationship between hyperhomocysteinemia (HHcy) and the risks of all-cause mortality and cardiovascular mortality among hypertensive patients.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>The average age of all participants was 44.82 years, with 51.8% being female. After adjusting for relevant covariates, a positive correlation between Hcy and the risk of hypertension was identified (OR=1.04, 95% <jats:italic>CI<\/jats:italic>: 1.02\u20131.07, <jats:italic><jats:italic>P<\/jats:italic><\/jats:italic>\u2009&lt;\u20090.001). Multivariate linear regression results indicated a positive correlation between HHcy and blood pressure levels (SBP: \u03b2\u2009=\u20090.2, 95% <jats:italic>CI<\/jats:italic>: 0.10\u20130.30, <jats:italic><jats:italic>P<\/jats:italic><\/jats:italic>\u2009&lt;\u20090.001; DBP: \u03b2\u2009=\u20090.09, 95% <jats:italic>CI<\/jats:italic>: 0.01\u20130.17, <jats:italic><jats:italic>P<\/jats:italic><\/jats:italic>\u2009&lt;\u20090.05). Furthermore, restricted cubic spline(RCS) curve analysis revealed a nonlinear positive correlation between SBP and DBP with Hcy levels. Survival analysis results demonstrated that when blood Hcy concentrations exceeded 10 \u03bcmol\/L, patients with hypertension experienced significantly increased all-cause and cardiovascular mortality rates (P\u2009&lt;\u20090.001).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>Our research validates Hcy as an independent risk factor for hypertension, further confirming a nonlinear positive correlation between blood pressure and Hcy levels. HHcy was associated with small increases SBP and DBP proportional to the degree of homocysteine elevation. Additionally, HHcy was a high-risk factor for all-cause and cardiovascular mortality in hypertensive patients. This may provide new insights into the management and treatment of hypertension.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0330267","type":"journal-article","created":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T17:31:44Z","timestamp":1755019904000},"page":"e0330267","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Association between homocysteine levels and hypertension prevalence as well as all-cause mortality and cardiovascular mortality among hypertensive patients: A population-based study"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-7662-5494","authenticated-orcid":true,"given":"Wenna","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peng","family":"Pu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huan","family":"Yin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linlin","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,8,12]]},"reference":[{"issue":"10304","key":"pone.0330267.ref001","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1016\/S0140-6736(21)01330-1","article-title":"Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants","volume":"398","author":"NCD Risk Factor Collaboration (NCD-RisC)","year":"2021","journal-title":"Lancet"},{"key":"pone.0330267.ref002","doi-asserted-by":"crossref","first-page":"1109445","DOI":"10.3389\/fcvm.2022.1109445","article-title":"Mechanism of homocysteine-mediated endothelial injury and its consequences for atherosclerosis","volume":"9","author":"D Yuan","year":"2023","journal-title":"Front Cardiovasc Med"},{"issue":"6","key":"pone.0330267.ref003","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1161\/01.CIR.96.6.1745","article-title":"High homocysteine levels are independently related to isolated systolic hypertension in older adults","volume":"96","author":"K Sutton-Tyrrell","year":"1997","journal-title":"Circulation"},{"issue":"4","key":"pone.0330267.ref004","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1515\/jtim-2015-0027","article-title":"H-type hypertension and risk of stroke in chinese adults: a prospective, nested case-control study","volume":"3","author":"J Li","year":"2015","journal-title":"J Transl Int Med"},{"issue":"4","key":"pone.0330267.ref005","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1515\/jtim-2015-0027","article-title":"H-type hypertension and risk of stroke in chinese adults: a prospective, nested case-control study","volume":"3","author":"J Li","year":"2015","journal-title":"J Transl Int Med"},{"issue":"13","key":"pone.0330267.ref006","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1001\/jama.2015.2274","article-title":"Efficacy of folic acid therapy in primary prevention of stroke among adults with hypertension in China: the CSPPT randomized clinical trial","volume":"313","author":"Y Huo","year":"2015","journal-title":"JAMA"},{"issue":"20","key":"pone.0330267.ref007","doi-asserted-by":"crossref","first-page":"2101","DOI":"10.1212\/WNL.0000000000004648","article-title":"Association between percent decline in serum total homocysteine and risk of first stroke","volume":"89","author":"X Huang","year":"2017","journal-title":"Neurology"},{"issue":"1","key":"pone.0330267.ref008","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1186\/s12872-024-04317-9","article-title":"Association between homocysteine levels and mortality in CVD: a cohort study based on NHANES database","volume":"24","author":"D Liu","year":"2024","journal-title":"BMC Cardiovasc Disord"},{"issue":"1","key":"pone.0330267.ref009","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1186\/s12940-024-01103-0","article-title":"Association between brominated flame retardants (PBDEs and PBB153) exposure and hypertension in U.S. adults: results from NHANES 2005-2016","volume":"23","author":"D Cheng","year":"2024","journal-title":"Environ Health"},{"issue":"13","key":"pone.0330267.ref010","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1001\/jama.1995.03530130055028","article-title":"A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. 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hyperlipidemia: NHANES 1999-2018","volume":"24","author":"K Cheng","year":"2024","journal-title":"BMC Geriatr"},{"issue":"9","key":"pone.0330267.ref014","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1093\/eurjpc\/zwae022","article-title":"Homocysteine, hyperhomocysteinemia, and H-type hypertension","volume":"31","author":"D-F Wu","year":"2024","journal-title":"Eur J Prev Cardiol"},{"key":"pone.0330267.ref015","first-page":"8438602","article-title":"Abnormal homocysteine metabolism: an insight of Alzheimer\u2019s disease from DNA methylation","volume":"2020","author":"T Pi","year":"2020","journal-title":"Behav Neurol"},{"issue":"2","key":"pone.0330267.ref016","doi-asserted-by":"crossref","first-page":"197","DOI":"10.3390\/biom12020197","article-title":"Folic acid, folinic acid, 5 methyl tetrahydrofolate supplementation for mutations that affect epigenesis through the folate and one-carbon cycles","volume":"12","author":"Y Menezo","year":"2022","journal-title":"Biomolecules"},{"issue":"5","key":"pone.0330267.ref017","doi-asserted-by":"crossref","first-page":"1771","DOI":"10.1007\/s00394-017-1461-8","article-title":"The effectiveness of daily supplementation with 400 or 800 \u00b5g\/day folate in reaching protective red blood folate concentrations in non-pregnant women: a randomized trial","volume":"57","author":"R Obeid","year":"2018","journal-title":"Eur J Nutr"},{"key":"pone.0330267.ref018","doi-asserted-by":"crossref","DOI":"10.1093\/jn\/132.8.2466S","article-title":"Folic acid fortification, folate status and plasma homocysteine","volume":"132","author":"JI Rader","year":"2002","journal-title":"J Nutr"},{"issue":"14","key":"pone.0330267.ref019","doi-asserted-by":"crossref","first-page":"2199","DOI":"10.3390\/nu16142199","article-title":"A comparative study evaluating the effectiveness of folate-based B vitamin intervention on cognitive function of older adults under mandatory folic acid fortification 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B12, and dietary folate intake and hypertension in a cross-sectional study","volume":"10","author":"T Tamura","year":"2020","journal-title":"Sci Rep"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0330267","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T17:31:48Z","timestamp":1755019908000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0330267"}},"subtitle":[],"editor":[{"given":"Mar\u00eda Teresa","family":"Llin\u00e1s,","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2025,8,12]]},"references-count":31,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,8,12]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0330267","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,12]]}}}