{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T06:34:54Z","timestamp":1775025294948,"version":"3.50.1"},"reference-count":34,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2011,2,2]],"date-time":"2011-02-02T00:00:00Z","timestamp":1296604800000},"content-version":"unspecified","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"],"DOI":"10.1371\/journal.pone.0016473","type":"journal-article","created":{"date-parts":[[2011,2,2]],"date-time":"2011-02-02T16:41:49Z","timestamp":1296664909000},"page":"e16473","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":62,"title":["Reconciling the Evidence on Serum Homocysteine and Ischaemic Heart Disease: A Meta-Analysis"],"prefix":"10.1371","volume":"6","author":[{"given":"David S.","family":"Wald","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joan K.","family":"Morris","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas J.","family":"Wald","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2011,2,2]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"2520","DOI":"10.1161\/01.CIR.98.23.2520","article-title":"Common methylenetetrahydrofolate reductase gene mutation leads to hyperhomocysteinemia but not to vascular disease.","volume":"98","author":"L Brattstrom","year":"1998","journal-title":"Circulation"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1136\/bmj.325.7374.1202","article-title":"Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis.","volume":"325","author":"DS Wald","year":"2002","journal-title":"BMJ"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1136\/bmj.39000.486701.68","article-title":"Folic acid, homocysteine and cardiovascular disease: judging causality in the face of inconclusive trial evidence.","volume":"333","author":"DS Wald","year":"2006","journal-title":"BMJ"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"2023","DOI":"10.1001\/jama.288.16.2023","article-title":"MTHFR 677 C to T polymorphism and risk of coronary heart disease.","volume":"288","author":"M Klerke","year":"2002","journal-title":"JAMA"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/j.amjcard.2010.03.064","article-title":"Meta-analysis of Folic acid Supplementation Trials on Risk of Cardiovascular Disease and Risk Interaction with Baseline Homocysteine levels.","volume":"106","author":"ER Miller","year":"2010","journal-title":"Am J Cardiol"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/S0049-3848(03)00379-7","article-title":"The mechanism of action of aspirin.","volume":"110","author":"JR Vane","year":"2003","journal-title":"Thromb Res"},{"key":"ref7","article-title":"Homocysteine, coagulation, platelet function and thrombosis.","author":"A Coppola","year":"2000","journal-title":"Seminars in Thrombosis and HemostasisVolume 26, Number 3"},{"key":"ref8","first-page":"293","article-title":"Relationship of homocysteine to markers of platelet and endothelial activation in \u2018high risk\u2019 hypertensives: a substudy of the Anglo-Scandanavian.","volume":"94","author":"CGC Spencer","year":"2004","journal-title":"Cardiac Outcomes Trial.Int J Cardiol"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1111\/j.1538-7836.2007.02459.x","article-title":"Elevated total homocysteine is associated with increased platelet activation at the site of microvascular injury: effects of folic acid administration.","volume":"5","author":"A Undas","year":"2007","journal-title":"J Thromb Haemost"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.atherosclerosis.2004.02.008","article-title":"Altered platelet activity in peripheral vascular disease complicated with elevated plasma homocysteine levels.","volume":"175","author":"R Riba","year":"2004","journal-title":"Atherosclerosis"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1007\/s001250100581","article-title":"Homocysteine-induced inhibition of nitric oxide production in platelets: a study on healthy and diabetic subjects.","volume":"44","author":"B Mutus","year":"2001","journal-title":"Diabetologica"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1016\/j.thromres.2006.11.008","article-title":"Homocysteine, reactive oxygen species and nitric oxide in type 2 diabetes mellitus.","volume":"120","author":"MG Signorello","year":"2007","journal-title":"Thrombosis Research"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1007\/s380-002-8316-y","article-title":"Effect of homocysteine on the L-arginine\/nitric oxide synthase\/nitric oxide pathway in human platelets.","volume":"16","author":"J Li","year":"2002","journal-title":"Heart Vessels"},{"issue":"7","key":"ref14","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1080\/09537100802308081","article-title":"Comparitive studies on homocysteine and its metabolite \u2013 homocysteine thiolactone action in blood platelets in vitro.","volume":"19","author":"B Olas","year":"2008","journal-title":"Platelets"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1046\/j.1365-2362.2003.01203.x","article-title":"Effects of homocysteine on L-arginine transport and nitric oxide formation in human platelets.","volume":"33","author":"G Leoncini","year":"2003","journal-title":"Eur J Clin Invest"},{"issue":"5B","key":"ref16","doi-asserted-by":"crossref","first-page":"2015","DOI":"10.1111\/j.1582-4934.2008.00200.x","article-title":"Effect of homocysteine on calcium mobilization and platelet function in type 2 diabetes mellitus.","volume":"12","author":"N Alexandru","year":"2008","journal-title":"J Cell Mol Med"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1203\/00006450-198206000-00018","article-title":"Effect of homocysteine and homocystine on platelet and vascular arachidonic acid metabolism.","volume":"16","author":"JE Graeber","year":"1982","journal-title":"Pediatr Res"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.1172\/JCI116715","article-title":"Abnormally high thromboxane biosynthesis in homozygous homocystinuria.","volume":"92","author":"G Di Minno","year":"1999","journal-title":"J Clin Invest"},{"issue":"4","key":"ref19","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/0090-6980(84)90098-4","article-title":"Urinary excretion of 2,3-dinor-thromboxane B2 in man under normal conditions, following drugs and during some pathological conditions.","volume":"27","author":"O Vesterqvist","year":"1984","journal-title":"Prostaglandins"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1111\/j.1538-7836.2005.01708.x","article-title":"Activation of p38 MAPKinase\/cPLA2 pathway in homocysteine-treated patients.","volume":"4","author":"G Leoncini","year":"2006","journal-title":"J Thromb Haemost"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1046\/j.1365-2362.2002.00971.x","article-title":"Effect of homocysteine on arachiodonic acid release in human platelets.","volume":"32","author":"MG Signorello","year":"2002","journal-title":"Eur J Clin Invest"},{"issue":"3","key":"ref22","first-page":"349","article-title":"Homocysteine thiolactone, N-homocysteine thiolactonyl retinamide, and platelet aggregation.","volume":"56","author":"KS McCully","year":"1987","journal-title":"Research Communications in Chemical Pathology and Pharmacology"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1172\/JCI116187","article-title":"Adverse vascular effects of homocysteine are modulated by endothelium-derived relaxing factor and related oxides of nitrogen.","volume":"91","author":"JS Stamler","year":"1993","journal-title":"J Clin Invest"},{"issue":"7336","key":"ref24","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1016\/S0140-6736(64)92852-1","article-title":"Homocystinuria, thrombosis, and the blood-platelets.","volume":"1","author":"L McDonald","year":"1964","journal-title":"Lancet Apr 4;"},{"issue":"11","key":"ref25","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1056\/NEJM197409122911101","article-title":"Homocystinemia: Vascular injury and arterial thrombosis.","volume":"291","author":"LA Harker","year":"1974","journal-title":"New Engl J Med"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.nut.2005.04.012","article-title":"Effect of homocysteine on platelet activation induced by collagen.","volume":"22","author":"F Luo","year":"2006","journal-title":"Nutrition"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1002\/jcb.21123","article-title":"A role for PLCy2 in platelet activation by homocysteine.","volume":"100","author":"G Leoncini","year":"2007","journal-title":"J Cell Biochem"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1001\/archpedi.1975.02120460010003","article-title":"Amino acids and collagen-induced platelet aggregation.","volume":"129","author":"JW Davis","year":"1976","journal-title":"Am J Dis Child"},{"issue":"1","key":"ref29","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1177\/1076029607308390","article-title":"Homocysteine activates platelets in vitro.","volume":"14","author":"IV Mohan","year":"2008","journal-title":"Clin Appl Thromb Hemost"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/S0140-6736(05)70152-5","article-title":"Homocysteine and stroke: evidence on a causal link from mendelian randomisation.","volume":"365","author":"JP Casas","year":"2005","journal-title":"Lancet"},{"key":"ref31","first-page":"1","article-title":"The natural history of homocystinuria due to cystathionine \u03b2synthase deficiency.","volume":"37","author":"SH Mudd","year":"1985","journal-title":"Am J Hum Genet"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1086\/302439","article-title":"The molecular basis of cystathionine \u03b2synthase deficiency in Dutch patients with homocystinuria: effect of SBS genotype on biochemical and clinical phenotype and on response to treatment.","volume":"65","author":"LAJ Kluijtmans","year":"1999","journal-title":"Am J Hum Genet"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1023\/A:1005445132327","article-title":"Homocysteinemia due to cystathionine \u03b2synthase deficiency in Ireland: 25 years experience of newborn screened and treated population with reference to a clinical outcome and biochemical control.","volume":"21","author":"S Yap","year":"1998","journal-title":"J Inherit Metab Dis"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"1876","DOI":"10.1016\/S0140-6736(07)60854-X","article-title":"Efficacy of folic acid supplementation in stroke prevention: a meta-analysis.","volume":"369","author":"X Wang","year":"2007","journal-title":"Lancet"}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0016473","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,10,23]],"date-time":"2018-10-23T04:58:49Z","timestamp":1540270729000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0016473"}},"subtitle":[],"editor":[{"given":"Adrian","family":"Hernandez","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2011,2,2]]},"references-count":34,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2011,2,2]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0016473","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,2,2]]}}}