{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T10:08:01Z","timestamp":1790935681679,"version":"4.1.0"},"reference-count":28,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"18","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[1999,5,11]]},"abstract":"<jats:p>\n            <jats:italic>Background<\/jats:italic>\n            \u2014Hyperhomocysteinemia has been identified as a potential risk factor for atherosclerosis. This study examined whether a modest elevation of plasma total homocysteine (tHcy) was an independent risk factor for increased carotid artery intimal-medial wall thickness (IMT) and focal plaque formation in a large, randomly selected community population. We also examined whether vitamin cofactors and the C677T genetic mutation of the methylenetetrahydrofolate reductase (\n            <jats:italic>MTHFR<\/jats:italic>\n            ) enzyme were major contributors to elevated plasma tHcy and carotid vascular disease.\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Methods and Results<\/jats:italic>\n            \u2014In 1111 subjects (558 men, 553 women) 52\u00b113 years old (mean\u00b1SD; range, 27 to 77 years) recruited from a random electoral roll survey, we measured fasting tHcy and performed bilateral carotid B-mode ultrasound. For the total population, mean tHcy was 12.1\u00b14.0 \u03bcmol\/L. Plasma tHcy levels were correlated with IMT (Spearman rank\n            <jats:italic>r<\/jats:italic>\n            <jats:sub>s<\/jats:sub>\n            =0.31,\n            <jats:italic>P<\/jats:italic>\n            =0.0001). After adjustment for age, sex, and other conventional risk factors, subjects in the highest versus the lowest quartile of tHcy had an odds ratio of 2.60 (95% CI, 1.51 to 4.45) for increased IMT and 1.76 (95% CI, 1.10 to 2.82) for plaque. Serum and dietary folate levels and the C677T mutation in\n            <jats:italic>MTHFR<\/jats:italic>\n            were independent determinants of tHcy (all\n            <jats:italic>P<\/jats:italic>\n            =0.0001). The mutant homozygotes (10% of the population) had higher mean tHcy than heterozygotes or those without the mutation (14.2 versus 12.3 versus 11.6 \u03bcmol\/L, respectively,\n            <jats:italic>P<\/jats:italic>\n            =0.0001). The inverse association of folate levels with tHcy was steeper in the mutant homozygotes. Despite this, the C677T\n            <jats:italic>MTHFR<\/jats:italic>\n            mutation was not independently predictive of increased carotid IMT or plaque formation.\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Conclusions<\/jats:italic>\n            \u2014Mild hyperhomocysteinemia is an independent risk factor for increased carotid artery wall thickness and plaque formation in a general population. Lower levels of dietary folate intake and the C677T mutation in\n            <jats:italic>MTHFR<\/jats:italic>\n            are important causes of mild hyperhomocysteinemia and may therefore contribute to vascular disease in the community.\n          <\/jats:p>","DOI":"10.1161\/01.cir.99.18.2383","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:42:29Z","timestamp":1339461749000},"page":"2383-2388","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":155,"title":["Hyperhomocysteinemia but Not the C677T Mutation of Methylenetetrahydrofolate Reductase Is an Independent Risk Determinant of Carotid Wall Thickening"],"prefix":"10.1161","volume":"99","author":[{"given":"Brendan M.","family":"McQuillan","sequence":"first","affiliation":[{"name":"From the Sir Charles Gairdner Hospital Campus of the Heart Research Institute of Western Australia (B.McQ., M.N., P.L.T., J.H.); the Department of Clinical Biochemistry, PathCentre, QEII Medical Centre (J.P.B.); and the Department of Medicine, University of Western Australia (J.H.), Nedlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John P.","family":"Beilby","sequence":"additional","affiliation":[{"name":"From the Sir Charles Gairdner Hospital Campus of the Heart Research Institute of Western Australia (B.McQ., M.N., P.L.T., J.H.); the Department of Clinical Biochemistry, PathCentre, QEII Medical Centre (J.P.B.); and the Department of Medicine, University of Western Australia (J.H.), Nedlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Nidorf","sequence":"additional","affiliation":[{"name":"From the Sir Charles Gairdner Hospital Campus of the Heart Research Institute of Western Australia (B.McQ., M.N., P.L.T., J.H.); the Department of Clinical Biochemistry, PathCentre, QEII Medical Centre (J.P.B.); and the Department of Medicine, University of Western Australia (J.H.), Nedlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter L.","family":"Thompson","sequence":"additional","affiliation":[{"name":"From the Sir Charles Gairdner Hospital Campus of the Heart Research Institute of Western Australia (B.McQ., M.N., P.L.T., J.H.); the Department of Clinical Biochemistry, PathCentre, QEII Medical Centre (J.P.B.); and the Department of Medicine, University of Western Australia (J.H.), Nedlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Hung","sequence":"additional","affiliation":[{"name":"From the Sir Charles Gairdner Hospital Campus of the Heart Research Institute of Western Australia (B.McQ., M.N., P.L.T., J.H.); the Department of Clinical Biochemistry, PathCentre, QEII Medical Centre (J.P.B.); and the Department of Medicine, University of Western Australia (J.H.), Nedlands."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1995.03530130055028"},{"key":"e_1_3_3_2_2","unstructured":"Ueland PM Refsum H Brattstrom L. Plasma homocysteine and cardiovascular disease. In: Francis RB ed. Atherosclerotic Cardiovascular Disease Hemostasis and Endothelial Function. New York NY: Marcel Dekker; 1992:183\u2013236."},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0496-386"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.87.4.1107"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199502023320502"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2796.1997.00239.x"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1993.03510220049033"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2796.1994.tb00856.x"},{"key":"e_1_3_3_9_2","first-page":"414","volume":"43","year":"1988","unstructured":"Kang SS, Zhou J, Wong PW, Kowalisyn J, Strokosch G. Intermediate homocysteinemia: a thermolabile variant of methylenetetrahydrofolate reductase. 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Canberra Australia: National Heart Foundation of Australia and Australian Institute of Health; 1990:141."},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-4347(87)80438-3"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1177\/000456329903600107"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/18.6.499"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1753-6405.1984.tb00419.x"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/0301-5629(91)90043-V"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.74.6.1399"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.92.8.2127"},{"key":"e_1_3_3_19_2","unstructured":"SAS. SAS\/STAT User\u2019s Guide Vol 1. 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