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Finkelstein JD. The metabolism of homocysteine: pathways and regulation. Eur J Pediatrics 1998; 157 (Suppl 2):S40-S44.
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Eikelboom JW, Lonn E, Genest J, et al. Homocyst(e)ine and cardiovascular disease: a critical review of the epidemiologic evidence. Ann Intern Med 1999; 131:363-375.
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5
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Kaul S, Zadeh AA, Shah PK. Homocysteine hypothesis for atherothrombotic cardiovascular disease: not validated. J Am Coll Cardiol 2006; 48:914-923. This is a comprehensive review of experimental, observational and clinical trials data on this topic. The authors conclude that, to date, it is unclear whether there is a causal relationship between homocysteine and cardiovascular risk or if homocysteine is related to other confounding cardiovascular risk factors or if it is a marker of existing disease burden. In addition, the authors conclude that currently there is no evidence that vitamin B supplementation prevents cardiovascular events.
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Kaul S, Zadeh AA, Shah PK. Homocysteine hypothesis for atherothrombotic cardiovascular disease: not validated. J Am Coll Cardiol 2006; 48:914-923. This is a comprehensive review of experimental, observational and clinical trials data on this topic. The authors conclude that, to date, it is unclear whether there is a causal relationship between homocysteine and cardiovascular risk or if homocysteine is related to other confounding cardiovascular risk factors or if it is a marker of existing disease burden. In addition, the authors conclude that currently there is no evidence that vitamin B supplementation prevents cardiovascular events.
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The effect of folic acid fortification on plasma folate and total homocysteine concentrations
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Jacques PF, Selhub J, Bostom AG, et al. The effect of folic acid fortification on plasma folate and total homocysteine concentrations. N Engl J Med 1999; 340:1449-1454.
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Boushey CJ, Beresford SA, Omenn GS, Motulsky AG. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease: probable benefits of increasing folic acid intakes. JAMA 1995; 274:1049-1057.
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The Homocysteine Studies Collaboration. Homocysteine and risk of ischemic heart disease and stroke. JAMA 2002; 288:2015-2022.
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Wald DS, Law M, Morris JK. Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis. BMJ 2002; 325:1202-1206.
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MTHFR 677C→T polymorphism and risk of coronary heart disease: A meta-analysis
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and the MTHFR Studies Collaboration Group
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Klerk M, Verhoef P, Clarke R, et al., and the MTHFR Studies Collaboration Group. MTHFR 677C→T polymorphism and risk of coronary heart disease: a meta-analysis. JAMA 2002; 228:2023-2031.
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Meta-analysis of MTHFR 677C→T polymorphism and coronary heart disease: Does totality of evidence support causal role for homocysteine and preventive potential of folate?
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Lewis SJ, Ebrahim S, Smith GD. Meta-analysis of MTHFR 677C→T polymorphism and coronary heart disease: does totality of evidence support causal role for homocysteine and preventive potential of folate? BMJ 2005; 331:1053-1058.
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A meta-analysis of hyperhomocyst(e)inemia and the risk of venous thromboembolic disease
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den Heÿer M, Lewington S, Clarke E. Homocysteine, MTHFR and risk of venous thrombosis: a meta-analysis of published epidemiological studies. J Thromb Haemost 2005; 3:292-299.
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Dose-dependent effects of folic acid on blood concentrations of homocysteine: A meta-analysis of the randomized trials
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Homocysteine Lowering Trialists' Collaboration
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Homocysteine Lowering Trialists' Collaboration. Dose-dependent effects of folic acid on blood concentrations of homocysteine: a meta-analysis of the randomized trials. Am J Nutr 2005; 82:806-812.
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Yap S, Boers GH, Wilcken B, et al. Vascular outcome in patients with homocystinuria due to cystathionine beta-synthase deficiency treated chronically: a multicenter observational study. Arterioscler Thromb Vasc Biol 2001; 21:2080-2085.
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85136359716
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6 on clinical outcome after percutaneous coronary intervention: the Swiss Heart study: a randomized controlled trial. JAMA 2002; 288:973-979.
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6 on clinical outcome after percutaneous coronary intervention: the Swiss Heart study: a randomized controlled trial. JAMA 2002; 288:973-979.
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26
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2942752021
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Folate therapy and in-stent restenosis after coronary stenting
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Lange, H.1
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27
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1342309318
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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
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Toole JF, Malinow MR, Chambless LE, 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 2004; 291:565-575.
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Toole, J.F.1
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28
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33645796222
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6 therapy. There was no treatment effect on cancer.
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6 therapy. There was no treatment effect on cancer.
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33645753544
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12 therapy versus placebo. There was no treatment benefit for the primary outcome, which was a composite of cardiovascular death, MI and stroke. A 25% reduction in stroke was noted, however, more patients in the active treatment group were hospitalized for unstable angina. There was no treatment benefit for cancer.
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12 therapy versus placebo. There was no treatment benefit for the primary outcome, which was a composite of cardiovascular death, MI and stroke. A 25% reduction in stroke was noted, however, more patients in the active treatment group were hospitalized for unstable angina. There was no treatment benefit for cancer.
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85136420591
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Bazzano LA, Reynolds K, Holder KN, He J. Effect of folic acid supplementation on risk of cardiovascular disease: a meta-analysis of randomized controlled trials. JAMA 2006; 296:2720-2726. This is a meta-analysis of randomized controlled trials of folic acid supplementation in cardiovascular disease prevention. The authors conclude that folic acid supplementation has not been shown to date to reduce the risk of cardiovascular diseases or all-cause mortality among participants with prior history of vascular disease.
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Bazzano LA, Reynolds K, Holder KN, He J. Effect of folic acid supplementation on risk of cardiovascular disease: a meta-analysis of randomized controlled trials. JAMA 2006; 296:2720-2726. This is a meta-analysis of randomized controlled trials of folic acid supplementation in cardiovascular disease prevention. The authors conclude that folic acid supplementation has not been shown to date to reduce the risk of cardiovascular diseases or all-cause mortality among participants with prior history of vascular disease.
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34249730020
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Wang X, Qin X, Demitras H, et al. Efficacy of folic acid supplementation in stroke prevention: a meta-analysis. Lancet 2007; 369:1876-1882. This meta-analysis of eight randomized controlled trials concludes that folic acid supplementation reduced the risk of stroke by 18%. Treatment benefits appear more significant in regions without folate food fortification and in patients who have not had a previous stroke.
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Wang X, Qin X, Demitras H, et al. Efficacy of folic acid supplementation in stroke prevention: a meta-analysis. Lancet 2007; 369:1876-1882. This meta-analysis of eight randomized controlled trials concludes that folic acid supplementation reduced the risk of stroke by 18%. Treatment benefits appear more significant in regions without folate food fortification and in patients who have not had a previous stroke.
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34250658841
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12. While the study lacks statistical power to conclusively exclude a possible treatment benefit, it is the largest randomized controlled trial of the effects of B vitamin supplements on VTEs published to date.
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12. While the study lacks statistical power to conclusively exclude a possible treatment benefit, it is the largest randomized controlled trial of the effects of B vitamin supplements on VTEs published to date.
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85117739329
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den Heijer M, Willems HPJ, Blom HJ, et al. Homocysteine lowering by B vitamins and the secondary prevention of deep vein thrombosis and pulmonary embolism: a randomized, placebo-controlled, double-blind trial. Blood 2007; 109:139-144. The VITRO trial reported that homocysteine lowering with B vitamin supplementation did not prevent recurrent venous thrombosis in patients with previous deep vein thrombosis or pulmonary embolism and with elevated homocysteine concentrations.
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den Heijer M, Willems HPJ, Blom HJ, et al. Homocysteine lowering by B vitamins and the secondary prevention of deep vein thrombosis and pulmonary embolism: a randomized, placebo-controlled, double-blind trial. Blood 2007; 109:139-144. The VITRO trial reported that homocysteine lowering with B vitamin supplementation did not prevent recurrent venous thrombosis in patients with previous deep vein thrombosis or pulmonary embolism and with elevated homocysteine concentrations.
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35
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33645777279
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Homocysteine trials: Clear outcomes for complex reasons
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Loscalzo J. Homocysteine trials: clear outcomes for complex reasons. N Engl J Med 2006; 354:1629-1632.
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(2006)
N Engl J Med
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Loscalzo, J.1
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31344459617
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B-Vitamin Treatment Trialist's Collaboration. Homocysteine-lowering trials for prevention of cardiovascular events: a review of the design and power of the large randomized trials. Am Heart J 2006; 151:282-287. This is a useful overview of completed and ongoing randomized controlled trials of homocysteine lowering in cardiovascular prevention. Important study design features and statistical issues are discussed. The authors emphasize the need for additional large trials and a prespecified individual patient data meta-analysis to conclusively determine the role of homocysteine-lowering B vitamins in cardiovascular prevention.
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B-Vitamin Treatment Trialist's Collaboration. Homocysteine-lowering trials for prevention of cardiovascular events: a review of the design and power of the large randomized trials. Am Heart J 2006; 151:282-287. This is a useful overview of completed and ongoing randomized controlled trials of homocysteine lowering in cardiovascular prevention. Important study design features and statistical issues are discussed. The authors emphasize the need for additional large trials and a prespecified individual patient data meta-analysis to conclusively determine the role of homocysteine-lowering B vitamins in cardiovascular prevention.
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