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Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis

BMJ 2002; 325 doi: https://doi.org/10.1136/bmj.325.7374.1202 (Published 23 November 2002) Cite this as: BMJ 2002;325:1202

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  • References
    1. Zheng YZ, Tong J, Do XP, Pu XQ, Zhou BT. Prevalence of methylenetetrahydrofolate reductase C667T and its association with arterial and venous thrombosis in the Chinese population. Br J Haematol 2000;109:870-4.
    2. Chambers JC, Ireland H, Thompson E, Reilly P, Obeid OA, Refsum H, et al. Methylenetetrahydrofolate reductase 677 C® T mutation and coronary heart disease in UK Indian Asians. Arterioscler Thromb Vasc Biol 2000;20:2448-52.
    3. Fernandez-Arcas N, Diegues-Lucena JL, Munoz-Moran E, Ruiz-Galdon M, Espinosa-Caliani S, Aranda-Lara P, et al. The genotype interactions of methylenetetrahydrofolate reductase and renin-angiotensin system genes are associated with myocardial infarction. Atherosclerosis 1999;145:293-300.
    4. Chao CL, Tsai HH, Lee CM, Hsu SM, Kao JT, Chien KL, et al. The graded effect of hyperhomocysteinemia on the severity and extent of coronary atherosclerosis. Atherosclerosis 1999;147:379-86.
    5. Brulhart MC, Dussoix P, Ruiz J, Passa P, Froguel P, James RW. The (Ala-Val) mutation of methylenetetrahydrofolate reductase as a genetic risk factor for vascular disease in non-insulin-dependent diabetic patients. Am J Hum Genet 1997;60:228-9.
    6. Tsai MY, Welge BG, Hanson NQ, Bignell MK, Vessey J, Schwichtenberg K, et al. Genetic causes of mild hyperhomocysteinemia in patients with premature occlusive coronary artery diseases. Atherosclerosis 1999;143:163-70.
    7. Girelli D, Friso S, Trabetti E, Olivieri O, Russo C, Pessotto R, et al. Methylenetetrahydrofolate reductase C677 mutation, plasma homocysteine, and folate in subjects from northern Italy with and without severe coronary atherosclerotic disease: evidence for an important genetic-environment interaction. Blood 1998;91:4158-63.
    8. Brugada R, Marian AJ. A common mutation in methylenetetrahydrofolate reductase gene is not a major risk of coronary artery disease or myocardial infarction. Atherosclerosis 1997;128:107-12.
    9. Adams M, Smith PD, Martin D, Thomson JR, Lodwick D, Samani NJ. Genetic analysis of thermolabile methylenetetrahydrofolate reductase as a risk factor for myocardial infarction. Q J Med 1996;89:437-44.
    10. Schmitz C, Lindpainter K, Verhoef P, Gaziano JM, Buring J. Genetic polymorphism of methylenetetrahydrofolate reductase and myocardial infarction: a case-control study. Circulation 1996;94:1812-14.
    11. Ardission D, Mannucci PM, Merlini PA, Duca F, Fetiveau R, Tagliabue L, et al. Prothrombotic genetic risk factors in young survivors of myocardial infarction. Blood 1999;94:46-51.
    12. Meisel C, Cascorbi I, Gerloff T, Stangl V, Laule M, Müller J, et al. Identification of six methylenetetrahydrofolate reductase (MTHFR) genotypes resulting from common polymorphisms: impact on plasma homocysteine levels and development of coronary artery disease. Atherosclerosis 2001;154:651-8.
    13. Verhoef P, Rimm EB, Hunter DJ, Chen J, Willett WC, Kelsey K, et al. A common mutation in the methylenetetrahydrofolate reductase gene and risk of coronary heart disease: results among US men. J Am Coll Cardiol 1998;32:253-9.
    14. Ma J, Stampfer MJ, Hennekens CH, Frosst P, Selhub J, Horsford J, et al. Methylenetetrahydrofolate reductase polymorphism, plasma folate, homocysteine and risk of myocardial infarction in US physicians. Circulation 1996;94:2410-6.
    15. Dilley A, Hooper WC, El-Jamil M, Renshaw M, Wenger NK, Evatt BL. Mutations in the genes regulating methylenetetrahydrofolate reductase (MTHFR C® T677) and cystathione β -synthase (CBS G® A919, CBS T® c833) are not associated with myocardial infarction in African Americans. Thromb Res 2001;103:109-15.
    16. Schwartz SM, Siscovick DS, Malinow MR, Rosendaal FR, Beverly RK, Hess DL, et al. Myocardial infarction in young women in relation to plasma total homocysteine, folate, and a common variant in the methylenetetrahydrofolate reductase gene. Circulation 1997;96:412-7.
    17. Hsu L-A, Jo Y-L, Wand S-M, Chang C-J, Hsu T-S, Chiang C-W, et al. The C677T mutation of the methylenetetrahydrofolate reductase gene is not associated with the risk of coronary artery disease or venous thrombosis among Chinese in Taiwan. Hum Hered 2001;51:41-5.
    18. van Bockxmeer FM, Mamotte CDS, Vasikaran SD, Taylor RR. Methylenetetrahydrofolate reductase gene and coronary artery disease. Circulation 1997;95:21-3.
    19. Abbate R, Sardi I, Pepe G, Marcucci R, Brunelli T, Prisco D, et al. The high prevalence of the thermolabile 5,10-methylenetetrahydrofolate reductase (MTHFR) in Italians is not associated with an increased risk for coronary artery disease (CAD). Thromb Haemost 1998;79:727-30.
    20. Wilcken DEL, Wang XL, Sim AS, McCredie M. Distribution in healthy and coronary populations of the methylenetetrahydrofolate reductase (MTHFR) C677T mutation. Arterioscler Thromb Vasc Biol 1996;16:878-82.
    21. Pintó X, Vilaseca MA, Garcia-Giralt N, Ferrer I, Palá M, Meco JF, et al. Homocysteine and the MTHFR 677C® T allele in premature coronary artery disease. Case control and family studies. Eur J Clin Invest 2001;31:24-30.
    22. Kim C-H, Hwang K-Y, Choi T-M, Shin W-Y, Hong S-Y. The methylenetetrahydrofolate reductase gene polymorphism in Koreans with coronary artery disease. Int J Cardiol 2001;78:13-17.
    23. Anderson JL, King GJ, Thomson MJ, Todd M, Bair TL, Muhlestein JB, et al. A mutation in the methylenetetrahydrofolate reductase gene is not associated with increased risk for coronary artery disease or myocardial infarction. J Am Coll Cardiol 1997;30:1206-11.
    24. Kluijtmans LAJ, Kastelein JJP, Lindemans J, Boers GHJ, Heil SG, Bruschke AVG, et al. Thermolabile methylenetetrahydrofolate reductase in coronary artery disease. Circulation 1997;96:2573-7.
    25. Fowkes FG, Lee AJ, Hau CM, Cooke A, Connor JM, Lowe GD. Methylenetetrahydrofolate reductase (MTHFR) and nitric oxide synthase (ecNOS) genes and risks of peripheral and arterial disease and coronary heart disease: Edinburgh Artery Study. Atherosclerosis 2000;150:179-85.
    26. Christensen B, Frosst P, Lussier-Cacan S, Selhub J, Goyette P, Rosenblatt DS, et al. Correlation of a common mutation in the methylenetetrahydrofolate reductase gene with plasma homocysteine in patients with premature coronary artery disease. Arterioscler Thromb Vasc Biol 1997;17:569-73.
    27. Gardemann A, Weidemann H, Philpp M, Katz N, Tillmanns H, Wilhelm Herlein F, et al. The TT genotype of the methylenetetrahydrofolate reductase C677T gene polymorphism is associated with the extent of coronary atherosclerosis in patients at high risk of coronary artery disease. Eur Heart J 1999;20:584-92.
    28. Todesco L, Angst C, Litynski P, Loehrer F, Fowler B, Haefeli WE. Methylenetetrahydrofolate reductase polymorphism, plasma homocysteine and age. Eur J Clin Invest 1999;29:1003-9.
    29. Reinhardt D, Sigush HH, Vogt SF, Farker K, Muller S, Hoffman A. Absence of association between common mutation in the methylenetetrahydrofolate reductase gene and the risk of coronary artery disease. Eur J Clin Invest 1998;28:20-3.
    30. Verhoef P, Kok FJ, Kluijtmans LAJ, Blom HJ, Refsum H, Ueland PM, et al. The 677C® T mutation in the methylenetetrahydrofolate reductase gene: associations with plasma total homocysteine levels and risk for coronary atherosclerotic disease. Atherosclerosis 1997;132:105-13.
    31. Kihara T, Abe S, Saigo M, Kaieda H, Obata H, Eto H, et al. Methylenetetrahydrofolate reductase gene polymorphism and premature myocardial infarction. Circulation 1997;96:101-I.
    32. Araujo F, Lopes M, Goncalves L, Maiciel MJ, Cunha-Ribeiro LM. Hyperhomocysteinemia, MTHFR C667T genotype and low folate levels: a risk combination for acute coronary disease in a Portuguese population. Thromb Haemost 2000;83:517-8.
    33. Tokgozoglu SL, Alikasifoglu M, Unsal I, Atalar E, Aytemir K, Ozer N, et al. Methylenetetrahydrofolate reductase genotype and the risk and extent of coronary artery disease in a population with low plasma folate. Heart 1999;81:518-22.
    34. Malik NM, Syrris P, Schwartsman R, Kaski JC, Crossman DC, Francis SE, et al. Methylenetetrahydrofolate reductase polymorphism (C-677T) and coronary artery disease. Clin Sci 1998;95:311-5.
    35. Thögersen AM, Nilsson TK, Dahlen G, Jansson J-H, Boman K, Huhtasaari F, et al. Homozygosity for the C677® T mutation of 5,10-methylenetetrahydrofolate reductase and total plasma homocyst(e)ine are not associated with greater than normal risk of a first myocardial infarction in northern Sweden. Coron Artery Dis 2001;12:85-90.
    36. Izumi M, Iwai N, Ohmichi N, Nakamura Y, Shimoike H, Kinoshita M. Molecular variant of 5,10-methylenetetrahydrofolate reductase is a risk factor of ischaemic heart disease in the Japanese population. Atherosclerosis 1996;121:293-4.
    37. Nakai K, Fusazaki T, Suzuki T, Ohsawa M, Kamata J, Kawazoe K, et al. Genetic polymorphism of 5,10-methylenetetrahydrofolate increases risk of myocardial infarction and is correlated to elevated levels of homocysteine in the Japanese general population. Coron Artery Dis 2000;11:47-51.
    38. Morita H, Taguchi J, Kurihara H, Kitaoka M, Kaneda H, Kurihara Y, et al. Genetic polymorphism of 5,10-methylenetetrahydrofolate reductase (MTHFR) as a risk factor for coronary artery disease. Circulation 1997;95:2032-6.
    39. Szczeklik A, Sanak M, Jankowski M, Dropinski J, Czachór R, Musial L, et al. Mutation A1298C of methylenetetrahydrofolate reductase: risk for early coronary disease not associated with hyperhomocysteinemia. Am J Med Genet 2001;101:36-9.
    40. Ou T, Kobayashi Y, Yamakawa K, Arinami T, Amemiya H, Fujiwara H, et al. Methylenetetrahydrofolate reductase and apolipoprotein E polymorphisms are independent risk factors for coronary heart disease in Japanese: a case control study. Atherosclerosis 1998;137:23-8.
    41. Malinow MR, Nieto FJ, Kruger WD, Duell PB, Hess DL, Gluckman RA, et al. The effects of folic acid supplementation on plasma total homocysteine are modulated by multivitamin use and methylenetetrahydrofolate reductase genotypes. ArteriosclerThromb Vasc Biol 1997;17:1157-62.
    42. Kawashiri M, Kajinami K, Nohara A, Yagi K, Inazu A, Koizumi J, et al. Effect of common methylenetetrahydrofolate reductase gene mutation on coronary artery disease in familial hypercholesterolaemia. Am J Cardiol 2000;86:840-5.
    43. Gallagher PM, Meleady R, Shields DC, Soon Tan K, McMaster D, Rozen R, et al. Homocysteine and risk of premature coronary heart disease: evidence for a common gene mutation. Circulation 1996;94:2154-8.
    44. Mager A, Lalezari S, Shohat T, Birnbaum Y, Adler Y, Magal N, et al. Methylenetetrahydrofolate reductase genotypes and early onset coronary artery disease. Circulation 1999;100:2406-10.
    45. Ferrer-Antunes C, Palmeiro A, Morais J, Lourenço M, Freitas M, Providência L. The mutation C677T in the methylenetetrahydrofolate reductase gene as a risk factor for myocardial infarction in the Portuguese population. Thromb Haemost 1998;80:521-2.
    46. Güleç S, Aras Ö, Akar E, Tutar E, Ömürlü K, Avci F, et al. Methylenetetrahydrofolate reductase gene polymorphism and risk of premature myocardial infarction. Clin Cardiol 2001;24:281-4.
    47. Dilley A, Austin H, Hooper WC, Lally C, Ribeiro MJA, Wenger NK, et al. Relation of three genetic traits to venous thrombosis in an African-American population. Am J Epidemiol 1998;147:30-5.
    48. Brown K, Luddington R, Baglin T. Effect of the MTHFRC677 T variant on risk of venous thromboembolism: interaction with factor V Leiden and prothrombin (F2G20212A) mutations. Br J Haematol 1998;103:42-4.
    49. Angchaisuksiri P, Pingsuthiwong S, Sura T, Aryichai K, Busabaratana M, Atichartakarn A. Prevalence of C677T methylenetetrahydrofolate reductase mutation in Thai patients with deep vein thrombosis. Acta Haematol 2000;103:191-6.
    50. Toydemir PB, Elhan AH, Tukun A, Toydemir R, Gurler A, Tuzuner A, et al. Effects of factor V gene G1691A, methylenetetrahydrofolate reductase gene C677T, and prothrombin gene G20210A mutations on deep vein thrombogenesis in Behcet’s disease. J Rheumatol 2000;27:2849-54.
    51. Cattaneo M, Tsai MY, Bucciarelli P, Taioli E, Zighetti ML, Bignell M, et al. A common mutation in the methylenetetrahydrofolate reductase gene (C677) increases the risk for deep-vein thrombosis in patients with mutant factor V (factor V:Q506). Arterioscler Thromb Vasc Biol 1997;17:1662-6.
    52. Alhenc-Gelas M, Arnaud E, Nicaud V, Aubry M-L, Flessinger JN, Aiach M, et al. Venous thromboembolic disease and the prothrombin, methylene tetrahydrofolate reductase and factor V genes. Thromb Haemost 1999;81:506-10.
    53. Tosetto A, Missiaglia E, Frezzato M, Rodeghiero F, the VITA Project. C677T mutation in the methylenetetrahydrofolate reductase gene and risk of venous thromboembolism. Br J Haematol 1997;97:804-6.
    54. Akar N, Akar E, Akcay R, Avcu F, Yalci A, Cin S. Effect of methylenetetrahydrofolate reductase 677 C-T, 1294 A-C, and 1317 T-C on factor 1691 mutation in Turkish deep vein thrombosis patients. Thromb Res 2000;97:163-7.
    55. Legnani C, Gualtiero P, Grauso F, Sassi S, Grossi G, Piazzi S, et al. Hyperhomocyst(e)inemia and a common methylenetetrahydrofolate reductase mutation (Ala223Val MTHFR) in patients with inherited thrombophilia coagulation defects. Arterioscler Thromb Vasc Biol 1997;17:2924-9.
    56. Kluitjmans LAJ, den Heijer M, Reitsma PH, Heil SG, Blom HJ, Rosendaal FR. Thermolabile methylenetetrahydrofolate reductase and factor V Leiden in the risk of deep-vein thrombosis. Thromb Haemost 1998;79:254-8.
    57. Salden A, Keeney S, Hay CRM, Cumming AM. The C677T MTHFR variant and the risk of venous thrombosis. Br J Haematol 1997;99:464-72.
    58. Rintelen C, Mannhalter C, Lechner K, Eichinger S, Kyrle PA, Papagiannopoulos M, et al. No evidence for an increased risk of venous thrombosis in patients with factor V Leiden by the homozygous 677 C to T mutation in the methylenetetrahydrofolate-reductase gene. Blood Coagul Fibrinolysis 1999;10:101-5.
    59. Isotalo PA, Donnelly JG. Prevalence of methylenetetrahydrofolate reductase mutations in patients with venous thrombosis. Mol Diagn 2000;5:59-66.
    60. Ordóňez AJG, Alvarez CRF, Rodrigues JMM, Garcia EC, Alvarez MV. Genetic polymorphism of methylenetetrahydrofolate reductase and venous thromboembolism: a case-control study. Haematologica 1999;84:190-1.
    61. Philipp CS, Dilley A, Saidi P, Evatt B, Austin H, Zawadsky J, et al. Deletion Polymorphism in the angiotensin-converting enzyme gene as a thrombophilic risk factor after hip arthroplasty. Thromb Haemost 1998;80:869-73.
    62. Quéré I, Chassé JF, Dupuy E, Bellet E, Molho-Sabatier P, Tobelem G, et al. Homocysteine, 5-10-methylenetetrahydrofolate reductase et thrombose veineuse profonde. Enquete aupres de 120 patients en medecine interne. Rev Med Interne 1998;19:29-33
    63. Franco RF, Morelli V, Lourenco D, Maffei FH, Tavella MH, Piccinato CE, et al. A second mutation in the methylenetetrahydrofolate reductase gene and the risk of venous thrombotic disease. Br J Haematol 1999;105:556-9.
    64. Vargas M, Soto I, Pinto CR, Urgelles MF, Coto E. Mild hyperhomocysteinemia and MTHFR C677T do not increase the risk for venous thrombosis in a Spanish population. Blood Coagul Fibrinolysis 1998;9:555-6.
    65. Hsu T-S, Hsu L-A, Chang C-J, Sun C-F, Ko Y-L, Kuo C-T, et al. Importance of hyperhomocysteinemia as a risk factor for venous thromboembolism in a Taiwanese population. Thromb Res 2001;102:387-95.
    66. Margaglione M, D’Andrea G, d’Addedda M, Giuliani N, Cappucci G, Iannaccone L, et al. The methylenetetrahydrofolate reductase TT677 genotype is associated with venous thrombosis independently of the coexistence of the FV Leiden and the prothrombin A20210 mutation. Thromb Haemost 1998;79:907-11.
    67. Fujimura H, Kawasaki T, Sakata T, Ariyoshi H, Kato H, Monden M, et al. Common C677 polymorphism in the methylenetetrahydrofolate reductase gene increases the risk for deep vein thrombosis in patients with predisposition of thrombophilia. Thromb Res 2000;98:1-8.
    68. Balta G, Gürgey A. Methylenetetrahydrofolate reductase MTHFR C677T mutation in Turkish patients with thrombosis. Turk J Pediatr 1999;41:197-9.
    69. Gemmati D, Previati M, Serino ML, Moratelli S, Guerra S, Capitani S, et al. Low folate levels and thermolabile methylenetetrahydrofolate reductase as primary determinant of mild homocysteinemia in normal and thromboembolic subjects. Arterioscler Thromb Vasc Biol 1999;19:1761-7.
    70. Akar N, Akar E, Misirlioglu M, Avcu F, Talcin A, Cin S. Search for genetic factors favoring thrombosis in Turkish populations. Thromb Res 1998;92:79-82.
    71. Arruda VR, von Zuben PM, Chiaparini LC, Annichino-Bizzacchi JM, Costa FF. The mutation Ala677-Val in the methylenetetrahydrofolate reductase gene: a risk factor for arterial disease and venous thrombosis. Thromb Haemost 1997;77:818-21.
    72. Eikelboom JW, Hankey GJ, Anand SS, Lofthouse E, Staples N, Baker RI. Association between high homocyst(e)ine and ischemic stroke due to large- and small-artery disease but not other etiologic subtypes of ischemic stroke. Stroke 2000;31:1069-75.
    73. Press RD, Beamer N, Evans A, DeLoughery TG, Coull BM. Role of a common mutation in the homocysteine regulatory enzyme methylenetetrahydrofolate reductase in ischemic stroke. Diagn Mol Pathol 1999;8:54-8.
    74. Salooja N, Catto A, Carter A, Tudenham EG, Grant PJ. Methylenetetrahydrofolate reductase C677T genotype and stroke. Clin Lab Haematol 1998;20:357-61.
    75. Morita H, Kurihara H, Tsubaki S, Sugiyama T, Hamada C, Kurihara Y, et al. Methylenetetrahydrofolate reductase gene polymorphism and ischaemic stroke in Japanese. Arterioscler Thromb Vasc Biol 1998;18:1465-9.
    76. Lalouschek W, Aull S, Serles W, Schnider P, Mannhalter C, Lang T, et al. Genetic and nongenetic factors influencing plasma homocysteine levels in patients with ischaemic cerebrovascular disease and in healthy control subjects. J Lab Clin Med 1999;133:575-82.
    77. Markus H, Kapozsta Z, Ditrich R, Wolfe C, Powell AN, Mendell M, et al. Increased common carotid intima-media thickness in UK African Caribbeans and its relation to chronic inflammation and vascular candidate gene polymorphisms. Stroke 2001;32:2465-71.
    78. Kostulas K, Crisby M, Huang WX, Lannfelt L, Hagenfeldt L, Eggertsen G, et al. A methylenetetrahydrofolate reductase gene polymorphism in ischaemic stroke and in carotid artery stenosis. Eur J Clin Invest 1998;28:285-9.
    79. Chango A, Potier de Courcy G, Boisson F, Guilland JC, Barbé F, Perrin MO, et al. 5,10-methylenetetrahydrofolate reductase common mutations, folate status and plasma homocysteine in healthy French adults of the supplementation en vitamines et meneraux antioxydants (SU.VI.MAX) cohort. Br J Nutr 2000;84:891-6.
    80. Dekou V, Whincup P, Papacosta O, Ebrahim S, Lennon L, Ueland PM, et al. The effect of the C677T and A1298C polymorphisms in the methylenetetrahydrofolate reductase gene on homocysteine levels in elderly men and women from the British regional heart study. Atherosclerosis 2001;154:659-66.
    81. D’Angelo A, Coppola A, Madinna P, Fermao I, Pagnano A, Mazzola G, et al. The role of vitamin B12 in fasting hyperhomocysteinaemia and its interaction with homozygous C677T mutation of the methylenetetrahydrofolate reductase (MTHFR) gene. Thromb Haemost 2000;83:563-70.
    82. Deloughery TG, Evans RW, Sadeghi A, McWilliams J, Henner WD, Taylor LM, et al. Common mutation in methylenetetrahydrofolate reductase: correlation with homocysteine metabolism and late-onset vascular disease. Circulation 1996;94:3074-8.
    83. Rassoul F, Richter V, Janke C, Purschwitz K, Klotzer B, Geisel J, et al. Plasma homocysteine and lipoprotein profiles in patients with peripheral arterial occlusive disease. Angiology 2000;51:189-96.
    84. Mazza A, Motti C, Nulli A, Marra G, Gnasso A, Psatore A, et al. Lack of association between carotid intima-media thickness and methylenetetrahydrofolate reductase gene polymorphism or serum homocysteine in non-insulin-dependent diabetes mellitus. Metabolism 2000;49:718-23.
    85. Kluijtmans LAJ, van den Heuvel PWJ, Boers GHJ, Frosst P, Stevens EMB, van Oost BA, et al. Molecular genetics analysis in mild hyperhomocysteinemia: a common mutation in methylenetetrahydrofolate reductase gene is a genetic risk factor for cardiovascular disease. Am J Hum Genet 1996;58:35-41.
    86. Arai K, Yamasaki Y, Kajimoto Y, Watada H, Umayahara Y, Kodama M et al. Association of methylenetetrahydrofolate reductase gene polymorphism with carotid arterial wall thickening and myocardial infarction risk in NIDDM. Diabetes 1997;46:2102-4.
    87. Chango A, Boisson F, Barbe F, Quilliot D, Droesch S, Pfister M, et al. The effect of 677C--> and 1298A--> C mutations on plasma homocysteine and 5,10-methylenetetrahydrofolate reductase activity in healthy subjects. Br J Nutr 2000;83:593-6.
    88. Saw S, Yuan J, Ong C, Arakawa K, Lee H, Coetzee GA, et al. Genetic, dietary, and other lifestyle determinants of plasma homocysteine concentrations in middle-aged and older Chinese men and women in Singapore. Am J Clin Nutr 2001;73:232-9.
    89. Kosokabe T, Olumura K, Sone T, Kondo J, Tsuboi H, Mukawa H, et al. Relation of a common methylenetetrahydrofolate reductase mutation and plasma homocysteine with intimal hyperplasia after coronary stenting. Circulation 2001;103:2048-54.
    90. Anderson JL, Muhlestein JB, Horne BD, Carlquist JF, Bair TL, Madsen TE, et al. Plasma homocysteine predicts mortality independently of traditional risk factors and C-reactive protein in patients with angiographically defined coronary artery disease. Circulation 2000;102:1227-32.
    91. Yoo J-H. A thermolabile variant of methylenetetrahydrofolate reductase is a determinant of hyperhomocyst(e)inemia in the elderly. Ann N Y Acad Sci 2001;928:344.
    92. Voutilainen S, Lakka TA, Hämelahti P, Lehtimäki T, Poulsen HE, Salonen JT. Plasma total homocysteine concentration and the risk of acute coronary events: the Kuopio ischaemic heart disease risk factor study. J Intern Med 2000;248:217-22.
    93. Mazza A, Motti C, Nulli A, Marra G, Gnasso A, Pastore A, et al. Lack of association between carotid intima-media thickness and methylenetetrahydrofolate reductase gene polymorphism or serum homocysteine in non-insulin-dependent diabetes mellitus. Metabolism 2000;49:718-23.
    94. Vulapalli R, Liang C, Sareba W, Moss AJ. Recurrent coronary events are not increased in postinfarction patients with methylenetetrahydrofolate reductase patients with methylenetetrahydrofolate reductase gene C677T polymorphism. Am J Cardiol 2001;87:1289-92.
    95. Evans RW, Shaten BJ, Hempel JD, Cutler JA, Kuller LH. Homocysteine and risk of cardiovascular disease in the multiple risk factor intervention trial. Arterioscler Thromb Vasc Biol 1997;17:1947-53.
    96. Knekt P, Alfthan G, Aromaa A, Heliovaara M, Marniemi J, Rissanen H, et al. Homocysteine and major coronary events: a prospective population study amongst women. J Intern Med 2001;249:461-5.
    97. Knekt P, Reunanen A, Alfthan G, Heliovaara M, Rissanen H, Marniemi J, et al. Hyperhomocysteinaemia: a risk factor or a consequence of coronary heart disease? Arch Intern Med 2001;161:1589-94.
    98. Alfthan G, Pekkanen J, Jauhiainen M, Pitkaniemi J, Karvonen M, Tuomilehto J, et al. Relations of serum homocysteine and lipoprotein concentrations to atherosclerotic disease in a prospective Finnish population based study. Atherosclerosis 1994;106:9-19.
    99. Fallon UB, Ben-Shlomo YB, Elwood P, Ubbink JB, Davey Smith G. Homocysteine and coronary heart disease in the Caerphilly cohort: a 10 year follow up. Heart 2001;85:153-8.
    100. Fallon UB, Ben-Shlomo Y, Davey Smith G. Homocysteine and coronary heart disease—Authors’ reply. Heart (14 Mar 2001) http://heart.bmjjournals.com/cgi/eletters/85/2/153#EL1 (accessed 26 Sep 2002).
    101. Whincup PH, Refsum H, Perry IJ, Morris R, Walker M, Lennon L, et al. Serum total homocysteine and coronary heart disease: prospective study in middle aged men. Heart 1999;82:448-54.
    102. Stehouwer CD, Weijenberg MP, van den Berg M, Jakobs C, Feskens EJ, Kromhout D. Serum homocysteine and risk of coronary heart disease and cerebrovascular disease in elderly men: a 10 year follow up. Arterioscler Thromb Vasc Biol 1998;18:1895-901.
    103. Folsom AR, Nieto J, McGovern PG, Tsai MY, Mallinow MR, Eckfeldt JH, et al. Prospective study of coronary heart disease incidence in relation to fasting total homocysteine, related genetic polymorphisms, and B vitamins: the atherosclerosis risk in communities (ARIC) study. Circulation 1998;98:204-10.
    104. Ridker PM, Manson JE, Buring JE, Shih J, Matias M, Hennekens CH. Homocysteine and risk of cardiovascular disease among postmenopausal women. JAMA 1999;281:1817-21.
    105. Wald NJ, Watt HC, Law MR, Weir DG, McPartlin J, Scott JM. Homocysteine and ischaemic heart disease: results of a prospective study with implications regarding prevention. Arch Intern Med 1998;158:862-7.
    106. Stampfer MJ, Malinow R, Willett WC, Newcomer LM, Upson B, Ullmann D, et al. A prospective study of plasma homocysteine and risk of myocardial infarction in US physicians. JAMA 1992;268:877-81.
    107. Kark JD, Selhub J, Adler B, Gofin J, Abramson JH, Friedman G, et al. Nonfasting plasma total homocysteine level and mortality in middle-aged and elderly men and women in Jerusalem. Ann Intern Med. 1999;131:321-30.
    108. Bots ML, Launer LJ, Lindemans J, Hoes AW, Hofman A, Witteman JC, et al. Homocysteine and short-term risk of myocardial infarction and stroke in the elderly: the Rotterdam study. Arch Intern Med 1999;159:38-44.
    109. Arnesen E, Refsum H, Bonaa KJ, Ueland PM, Forde OH, Nordrehaug JE. Serum total homocysteine and coronary heart disease. Int J Epidemiol 1995;24:704-9.
    110. Vollset SE, Refsum H, Tvwrdal A, Nygard O, Nordrehaug JE, Tell GS, et al. Plasma homocysteine and cardiovascular and noncardiovascular mortality: the Hordaland homocysteine study. Am J Clin Nutr 2001;74:130-6.
    111. Nygard O, Nordrehaug JE, Refsum H, Ueland PM, Farstad M, Vollset SE. Plasma homocysteine levels and mortality in patients with coronary artery disease. N Engl J Med 1997;337:230-6.
    112. Fallon UB, Elwood P, Ben-Shlomo Y, Ubbink JB, Greenwood R, Smith GD. Homocysteine and ischaemic stroke in men: the Caerphilly study. J Epidemiol Community Health 2001;55:91-6.
    113. Bostom AG, Rosenberg IH, Silbershatz H, Jacques PF, Selhub J, D’Agostino RB, et al. Nonfasting plasma total homocysteine levels and stroke incidence in elderly persons: the Framingham study. Ann Intern Med 1999;131:352-5.
    114. Petri M, Roubenoff R, Dallal GE, Nadeau MR, Selhub J, Rosenberg IH. Plasma homocysteine as a risk factor for atherothrombotic events in systemic lupus erythematosus. Lancet 1996;348:1120-4.
    115. Perry IJ, Refsum H, Morris RW, Ebrahim SB, Ueland PM, Shaper AG. Prospective study of serum total homocysteine concentration and risk of stroke in middle-aged British men. Lancet 1995:346:1395-8.
    116. Verhoef P, Hennekens CH, Malinow R, Kok FJ, Willett WC, Stampfer MJ. A prospective study of plasma homocyst(e)ine and risk of ischemic stroke. Stroke 1994;25:1924-30.
    117. Chasen-Taber L, Selhub J, Rosenberg IH, Malinow R, Terry P, Tishler PV, et al. A prospective study of folate and vitamin B6 and risk of myocardial infarction in US physicians. J Am Coll Nutr 1996;15:136-43.
    118. Bostom AG, Silbershatz W, Rosenberg IH, Selhub J, D’Agostino RB, Wolf PA, et al. Nonfasting plasma total homocysteine levels and all-cause and cardiovascular disease mortality in elderly Framingham men and women. Arch Intern Med 1999;159:1077-80.
    119. Stehouwer CDA, Gall M-A, Hougaard P, Jakobs C, Parving H-H. Plasma homocysteine concentration predicts mortality in non-insulin-dependent diabetic patients with and without albuminuria. Kidney Int 1999;55:308-14.
    120. Malinow MR, Ducimetiere P, Luc G, Evans AE, Arveiler D, Cambien F, et al. Plasma homocysteine levels and graded risk for myocardial infarction: findings in two populations at contrasting risk for coronary disease. Atherosclerosis 1996;126:27-34.

     

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