{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T21:57:45Z","timestamp":1787003865742,"version":"build-2736575974"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,11,21]],"date-time":"2016-11-21T00:00:00Z","timestamp":1479686400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,11,21]],"date-time":"2016-11-21T00:00:00Z","timestamp":1479686400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Little is known about the association between homocysteine (Hcy) and asymptomatic CAS in the healthy population. The purpose of this study was to investigate the relationship between Hcy levels and asymptomatic CAS in a Chinese community population. The current study included 5393 participants who were age of 40 years or older, and free of stroke, transient ischemic attack, and coronary artery disease. Demographic and clinical variables were investigated, and the presence of CAS was assessed by Color Doppler Ultrasound. A multivariate logistic regression was used to examine the association between Hcy levels and asymptomatic CAS. 361 (6.69%) participants were diagnosed with asymptomatic CAS, who had higher Hcy levels compared with those without (p-value for trend\u2009=\u20090.0001). After adjusting other possible risk factors, Hcy\u2009&gt;\u200919.3\u03bcmol\/L was considered as an independent indicator of asymptomatic CAS (OR 1.53, 95%CI 1.05\u20132.23; p-value for trend\u2009=\u20090.0265), but with a difference between participants with diabetes and without [OR (95%CI): 2.89(1.02\u20138.22) vs. 1.42(0.95\u20132.12); P interaction\u2009&lt;\u20090.05]. In this large-population, community-based study, Hcy is an independent indicator of asymptomatic CAS, especially in patients with diabetes.<\/jats:p>","DOI":"10.1038\/srep37361","type":"journal-article","created":{"date-parts":[[2016,11,21]],"date-time":"2016-11-21T06:05:19Z","timestamp":1479708319000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Homocysteine and Its Relationship to Asymptomatic Carotid Stenosis in a Chinese Community Population"],"prefix":"10.1038","volume":"6","author":[{"given":"Jiaokun","family":"Jia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anxin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianwei","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiujuan","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengyun","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingquan","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,11,21]]},"reference":[{"key":"BFsrep37361_CR1","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/S0140-6736(13)61953-4","volume":"383","author":"VL Feigin","year":"2014","unstructured":"Feigin, V. L. et al. Global and regional burden of stroke during 1990\u20132010: findings from the Global Burden of Disease Study 2010. The Lancet 383, 245\u2013255 ( 2014).","journal-title":"The Lancet"},{"key":"BFsrep37361_CR2","doi-asserted-by":"publisher","first-page":"956","DOI":"10.1016\/j.jvs.2013.10.073","volume":"59","author":"SK Kakkos","year":"2014","unstructured":"Kakkos, S. K. et al. Predictors and clinical significance of progression or regression of asymptomatic carotid stenosis. J. Vasc. Surg. 59, 956\u2013967.e951 (2014).","journal-title":"J. Vasc. Surg."},{"key":"BFsrep37361_CR3","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/j.jns.2010.07.013","volume":"298","author":"A Towfighi","year":"2010","unstructured":"Towfighi, A., Markovic, D. & Ovbiagele, B. Pronounced association of elevated serum homocysteine with stroke in subgroups of individuals: a nationwide study. Journal of the Neurological Sciences 298, 153\u2013157 (2010).","journal-title":"Journal of the Neurological Sciences"},{"key":"BFsrep37361_CR4","doi-asserted-by":"publisher","first-page":"e107498","DOI":"10.1371\/journal.pone.0107498","volume":"9","author":"C Zhong","year":"2014","unstructured":"Zhong, C. et al. High homocysteine and blood pressure related to poor outcome of acute ischemia stroke in Chinese population. PLoS ONE 9, e107498 (2014).","journal-title":"PLoS ONE"},{"key":"BFsrep37361_CR5","doi-asserted-by":"publisher","first-page":"2419","DOI":"10.1161\/STROKEAHA.115.009136","volume":"46","author":"Z Shi","year":"2015","unstructured":"Shi, Z. et al. Elevated Total Homocysteine Levels in Acute Ischemic Stroke Are Associated With Long-Term Mortality. Stroke; a journal of cerebral circulation 46, 2419\u20132425 (2015).","journal-title":"Stroke; a journal of cerebral circulation"},{"key":"BFsrep37361_CR6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.vph.2015.06.009","volume":"78","author":"F Santilli","year":"2016","unstructured":"Santilli, F., Dav\u00ec, G. & Patrono, C. Homocysteine, methylenetetrahydrofolate reductase, folate status and atherothrombosis: A mechanistic and clinical perspective. Vascul. Pharmacol. 78, 1\u20139 (2016).","journal-title":"Vascul. Pharmacol"},{"key":"BFsrep37361_CR7","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1161\/01.STR.0000115161.10646.67","volume":"35","author":"FM Faraci","year":"2004","unstructured":"Faraci, F. M. & Lentz, S. R. Hyperhomocysteinemia, oxidative stress, and cerebral vascular dysfunction. Stroke; a journal of cerebral circulation 35, 345\u2013347 (2004).","journal-title":"Stroke; a journal of cerebral circulation"},{"key":"BFsrep37361_CR8","first-page":"1444","volume":"41","author":"O Stanger","year":"2003","unstructured":"Stanger, O. & Weger, M. Interactions of homocysteine, nitric oxide, folate and radicals in the progressively damaged endothelium. Clin. Chem. Lab. Med. 41, 1444\u20131454 (2003).","journal-title":"Clin. Chem. Lab. Med"},{"key":"BFsrep37361_CR9","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1001\/jama.291.5.565","volume":"291","author":"JF Toole","year":"2004","unstructured":"Toole, J. F. et al. Lowering homocysteine in patients with ischemic stroke to prevent recurrent stroke, myocardial infarction, and death: the Vitamin Intervention for Stroke Prevention (VISP) randomized controlled trial. JAMA 291, 565\u2013575 (2004).","journal-title":"JAMA"},{"key":"BFsrep37361_CR10","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1016\/j.ejvs.2006.09.012","volume":"33","author":"A Assadian","year":"2007","unstructured":"Assadian, A. et al. Homocysteine and early re-stenosis after carotid eversion endarterectomy. European Journal of Vascular & Endovascular Surgery 33, 144\u2013148 (2007).","journal-title":"European Journal of Vascular & Endovascular Surgery"},{"key":"BFsrep37361_CR11","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1056\/NEJM199502023320502","volume":"332","author":"J Selhub","year":"1995","unstructured":"Selhub, J. et al. Association between plasma homocysteine concentrations and extracranial carotid-artery stenosis. N. Engl. J. Med. 332, 286\u2013291 (1995).","journal-title":"N. Engl. J. Med."},{"key":"BFsrep37361_CR12","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1161\/STROKEAHA.112.676155","volume":"44","author":"S Alsulaimani","year":"2013","unstructured":"Alsulaimani, S. et al. Elevated homocysteine and carotid plaque area and densitometry in the Northern Manhattan Study. Stroke; a journal of cerebral circulation 44, 457\u2013461 (2013).","journal-title":"Stroke; a journal of cerebral circulation"},{"key":"BFsrep37361_CR13","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1016\/j.jacc.2011.05.028","volume":"58","author":"V Veeranna","year":"2011","unstructured":"Veeranna, V. et al. Homocysteine and reclassification of cardiovascular disease risk. Journal of the American College of Cardiology 58, 1025\u20131033 (2011).","journal-title":"Journal of the American College of Cardiology"},{"key":"BFsrep37361_CR14","doi-asserted-by":"publisher","first-page":"1777","DOI":"10.1161\/STROKEAHA.115.009111","volume":"46","author":"L Han","year":"2015","unstructured":"Han, L. et al. Homocysteine, Ischemic Stroke, and Coronary Heart Disease in Hypertensive Patients: A Population-Based, Prospective Cohort Study. Stroke; a journal of cerebral circulation 46, 1777\u20131786 (2015).","journal-title":"Stroke; a journal of cerebral circulation"},{"key":"BFsrep37361_CR15","doi-asserted-by":"publisher","first-page":"912","DOI":"10.1179\/1743132813Y.0000000228","volume":"35","author":"W-J Tu","year":"2013","unstructured":"Tu, W.-J., Zhao, S.-J., Liu, T.-G., Yang, D.-G. & Chen, H. Combination of high-sensitivity C-reactive protein and homocysteine predicts the short-term outcomes of Chinese patients with acute ischemic stroke. Neurol. Res. 35, 912\u2013921 (2013).","journal-title":"Neurol. Res."},{"key":"BFsrep37361_CR16","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1016\/j.ejim.2013.01.015","volume":"24","author":"X-Q Wu","year":"2013","unstructured":"Wu, X.-Q. et al. Acute phase homocysteine related to severity and outcome of atherothrombotic stroke. European Journal of Internal Medicine 24, 362\u2013367 (2013).","journal-title":"European Journal of Internal Medicine"},{"key":"BFsrep37361_CR17","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/j.jash.2014.12.020","volume":"9","author":"C Catena","year":"2015","unstructured":"Catena, C., Colussi, G., Url-Michitsch, M., Nait, F. & Sechi, L. A. Subclinical carotid artery disease and plasma homocysteine levels in patients with hypertension. Journal of the American Society of Hypertension: JASH 9, 167\u2013175 (2015).","journal-title":"Journal of the American Society of Hypertension: JASH"},{"key":"BFsrep37361_CR18","doi-asserted-by":"publisher","first-page":"734","DOI":"10.1161\/STROKEAHA.110.595546","volume":"42","author":"SJ Kim","year":"2011","unstructured":"Kim, S. J. et al. Biomarkers of Asymptomatic Carotid Stenosis in Patients Undergoing Coronary Artery Bypass Grafting. Stroke; a journal of cerebral circulation 42, 734\u2013739 (2011).","journal-title":"Stroke; a journal of cerebral circulation"},{"key":"BFsrep37361_CR19","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1159\/000090209","volume":"21","author":"H-J Bae","year":"2006","unstructured":"Bae, H.-J. et al. Correlation of coronary and cerebral atherosclerosis: difference between extracranial and intracranial arteries. Cerebrovascular Diseases 21, 112\u2013119 (2006).","journal-title":"Cerebrovascular Diseases"},{"key":"BFsrep37361_CR20","doi-asserted-by":"publisher","first-page":"e94935","DOI":"10.1371\/journal.pone.0094935","volume":"9","author":"X Yang","year":"2014","unstructured":"Yang, X. et al. Homocysteine and carotid plaque stability: a cross-sectional study in Chinese adults. PLoS ONE 9, e94935 (2014).","journal-title":"PLoS ONE"},{"key":"BFsrep37361_CR21","doi-asserted-by":"publisher","first-page":"1205","DOI":"10.1161\/STROKEAHA.109.573410","volume":"41","author":"M Lee","year":"2010","unstructured":"Lee, M., Hong, K. S., Chang, S. C. & Saver, J. L. Efficacy of homocysteine-lowering therapy with folic Acid in stroke prevention: a meta-analysis. Stroke; a journal of cerebral circulation 41, 1205\u20131212 (2010).","journal-title":"Stroke; a journal of cerebral circulation"},{"key":"BFsrep37361_CR22","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1007\/s10545-010-9151-1","volume":"34","author":"YM Smulders","year":"2011","unstructured":"Smulders, Y. M. & Blom, H. J. The homocysteine controversy. Journal of inherited metabolic disease 34, 93\u201399 (2011).","journal-title":"Journal of inherited metabolic disease"},{"key":"BFsrep37361_CR23","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1016\/j.cca.2005.10.025","volume":"366","author":"E-J Huang","year":"2006","unstructured":"Huang, E.-J. et al. Homocysteine and other biochemical parameters in Type 2 diabetes mellitus with different diabetic duration or diabetic retinopathy. Clinica Chimica Acta 366, 293\u2013298 (2006).","journal-title":"Clinica Chimica Acta"},{"key":"BFsrep37361_CR24","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1007\/s12199-008-0024-2","volume":"13","author":"Y Masuda","year":"2008","unstructured":"Masuda, Y. et al. Factors associated with serum total homocysteine level in type 2 diabetes. Environ Health Prev Med 13, 148\u2013155 (2008).","journal-title":"Environ Health Prev Med"},{"key":"BFsrep37361_CR25","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1016\/j.jjcc.2012.11.009","volume":"61","author":"N Mahalle","year":"2013","unstructured":"Mahalle, N., Kulkarni, M. V., Garg, M. K. & Naik, S. S. Vitamin B12 deficiency and hyperhomocysteinemia as correlates of cardiovascular risk factors in Indian subjects with coronary artery disease. J Cardiol 61, 289\u2013294 (2013).","journal-title":"J Cardiol"},{"key":"BFsrep37361_CR26","doi-asserted-by":"publisher","first-page":"808","DOI":"10.1111\/j.1464-5491.2006.01809.x","volume":"23","author":"G Ferretti","year":"2006","unstructured":"Ferretti, G. et al. Homocysteinylation of low-density lipoproteins (LDL) from subjects with Type 1 diabetes: effect on oxidative damage of human endothelial cells. Diabet. Med. 23, 808\u2013813 (2006).","journal-title":"Diabet. Med."},{"key":"BFsrep37361_CR27","doi-asserted-by":"publisher","first-page":"595","DOI":"10.4093\/dmj.2011.35.6.595","volume":"35","author":"HC Cho","year":"2011","unstructured":"Cho, H. C. The Relationship among Homocysteine, Bilirubin, and Diabetic Retinopathy. Diabetes Metab J 35, 595\u2013601 (2011).","journal-title":"Diabetes Metab J"},{"key":"BFsrep37361_CR28","first-page":"1","volume":"9","author":"C Xu","year":"2014","unstructured":"Xu, C. et al. Relationship between homocysteine level and diabetic retinopathy: a systematic review and meta-analysis. Diagnostic Pathology 2014 9:1 9, 1\u20139 (2014).","journal-title":"Diagnostic Pathology 2014 9:1"},{"key":"BFsrep37361_CR29","doi-asserted-by":"publisher","first-page":"407452","DOI":"10.1155\/2013\/407452","volume":"2013","author":"T Wang","year":"2013","unstructured":"Wang, T. et al. Diagnostic value of the combined measurement of serum hcy, serum cys C, and urinary microalbumin in type 2 diabetes mellitus with early complicating diabetic nephropathy. ISRN Endocrinol 2013, 407452 (2013).","journal-title":"ISRN Endocrinol"},{"key":"BFsrep37361_CR30","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1016\/S0021-9150(01)00531-7","volume":"159","author":"MC Audelin","year":"2001","unstructured":"Audelin, M. C. & Genest, J. Homocysteine and cardiovascular disease in diabetes mellitus. Atherosclerosis 159, 497\u2013511 (2001).","journal-title":"Atherosclerosis"},{"key":"BFsrep37361_CR31","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/S0021-9150(02)00386-6","volume":"167","author":"VA Fonseca","year":"2003","unstructured":"Fonseca, V. A., Fink, L. M. & Kern, P. A. Insulin sensitivity and plasma homocysteine concentrations in non-diabetic obese and normal weight subjects. Atherosclerosis 167, 105\u2013109 (2003).","journal-title":"Atherosclerosis"},{"key":"BFsrep37361_CR32","first-page":"1947","volume":"31","author":"AC Pinheiro Volp","year":"2015","unstructured":"Pinheiro Volp, A. C., Santos Silva, F. C. & Bressan, J. Hepatic inflammatory biomarkers and its link with obesity and chronic diseases. Nutr Hosp 31, 1947\u20131956 (2015).","journal-title":"Nutr Hosp"},{"key":"BFsrep37361_CR33","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1186\/1475-2840-11-71","volume":"11","author":"X An","year":"2012","unstructured":"An, X. et al. Insulin resistance predicts progression of de novo atherosclerotic plaques in patients with coronary heart disease: a one-year follow-up study. Cardiovasc Diabetol 11, 71 (2012).","journal-title":"Cardiovasc Diabetol"},{"key":"BFsrep37361_CR34","doi-asserted-by":"publisher","first-page":"2245","DOI":"10.1161\/ATVBAHA.113.301585","volume":"33","author":"W Karrowni","year":"2013","unstructured":"Karrowni, W. et al. Insulin resistance is associated with significant clinical atherosclerosis in nondiabetic patients with acute myocardial infarction. Arteriosclerosis, Thrombosis, and Vascular Biology 33, 2245\u20132251 (2013).","journal-title":"Arteriosclerosis, Thrombosis, and Vascular Biology"},{"key":"BFsrep37361_CR35","doi-asserted-by":"publisher","first-page":"908","DOI":"10.1100\/tsw.2006.179","volume":"6","author":"JF Navarro","year":"2006","unstructured":"Navarro, J. F. & Mora, C. Diabetes, inflammation, proinflammatory cytokines, and diabetic nephropathy. ScientificWorldJournal 6, 908\u2013917 (2006).","journal-title":"ScientificWorldJournal"},{"key":"BFsrep37361_CR36","doi-asserted-by":"publisher","first-page":"1474","DOI":"10.1016\/j.ajpath.2013.01.010","volume":"182","author":"DP Hajjar","year":"2013","unstructured":"Hajjar, D. P. & Gotto, A. M. Biological relevance of inflammation and oxidative stress in the pathogenesis of arterial diseases. Am. J. Pathol. 182, 1474\u20131481 (2013).","journal-title":"Am. J. Pathol."},{"key":"BFsrep37361_CR37","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1161\/CIRCOUTCOMES.111.963694","volume":"5","author":"S Wu","year":"2012","unstructured":"Wu, S. et al. Prevalence of ideal cardiovascular health and its relationship with the 4-year cardiovascular events in a northern Chinese industrial city. Circ Cardiovasc Qual Outcomes 5, 487\u2013493 (2012).","journal-title":"Circ Cardiovasc Qual Outcomes"},{"key":"BFsrep37361_CR38","doi-asserted-by":"publisher","first-page":"e84685","DOI":"10.1371\/journal.pone.0084685","volume":"8","author":"Y Zhou","year":"2013","unstructured":"Zhou, Y. et al. Asymptomatic Polyvascular Abnormalities in Community (APAC) Study in China: Objectives, Design and Baseline Characteristics. PLoS ONE 8, e84685 (2013).","journal-title":"PLoS ONE"},{"key":"BFsrep37361_CR39","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1148\/radiol.2292030516","volume":"229","author":"EG Grant","year":"2003","unstructured":"Grant, E. G. et al. Carotid artery stenosis: gray-scale and Doppler US diagnosis--Society of Radiologists in Ultrasound Consensus Conference. Radiology 229, 340\u2013346 (2003).","journal-title":"Radiology"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep37361.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep37361","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep37361.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T19:17:36Z","timestamp":1672859856000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep37361"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,11,21]]},"references-count":39,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,12,23]]}},"alternative-id":["BFsrep37361"],"URL":"https:\/\/doi.org\/10.1038\/srep37361","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,11,21]]},"assertion":[{"value":"21 July 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 October 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 November 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"37361"}}