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Clinical Relevance of Hyperhomocysteinaemia in Atherothrombotic Disease

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Abstract

High fasting plasma homocysteine levels (>12 to 15 μmol/L) are commonly encountered in clinical practice and are associated with increased risk of atherothrombotic disease. Treatment with folic acid (1 to 5 mg/day) is inexpensive and effective in normalising plasma homocysteine levels. High plasma homocysteine levels after methionine loading (>40 to 50 μmol/L) are also common and can be treated with pyridoxine-based regimens (50 to 250 mg/day). As compared with fasting plasma homocysteine levels, the association between high postmethionine loading plasma homocysteine levels and atherothrombotic disease has been less extensively studied. There is reasonable, but not clearly definitive, evidence that high plasma homocysteine levels are causally related to atherothrombotic disease. Results of randomised trials of homocysteine-lowering treatment with clinical end-points will be available in 4 to 6 years. At present, a reasonable policy for the practising clinician would be to consider homocysteinelowering treatment in individuals at very high risk of atherothrombotic disease, such as patients with clinically manifest atherothrombotic disease with onset before 55 years of age, patients with end stage renal disease, and healthy subjects with a strong family history of early-onset atherothrombotic disease. Such a policy should be reassessed as the results of randomised trials become available.

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References

  1. McCully KS. Vascular pathology of homocysteinemia: implications for the pathogenesis of arteriosclerosis. Am J Pathol 1969; 56: 111–28

    PubMed  CAS  Google Scholar 

  2. Wilcken DEL, Wilcken B. The pathogenesis of coronary artery disease: a possible role for methionine metabolism. J Clin Invest 1976; 57: 211–5

    Article  Google Scholar 

  3. Boushey CJ, Beresford SAA, Omenn GS, et al. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. JAMA 1995; 274: 1049–57

    Article  PubMed  CAS  Google Scholar 

  4. Refsum H, Ueland PM, Nygård O, et al. Homocysteine and cardiovascular disease. Annu Rev Med 1998; 49: 31–62

    Article  PubMed  CAS  Google Scholar 

  5. Danesh J, Lewington S. Plasma homocysteine and coronary heart disease: systematic review of published epidemiological studies. J Cardiovasc Risk 1998; 5: 229–32

    Article  PubMed  CAS  Google Scholar 

  6. Graham IM, Daly LE, Refsum HM, et al. Plasma homocysteine as a risk factor for vascular disease. JAMA 1997; 277: 1775–81

    Article  PubMed  CAS  Google Scholar 

  7. Homocysteine Lowering Trialists’ Collaboration. Lowering blood homocysteine with folic acid-based supplements: meta-analysis of randomised trials. BMJ 1998; 316: 894–8

    Article  Google Scholar 

  8. Omenn GS, Beresford SAA, Motulsky AG. Preventing coronary heart disease: B vitamins and homocysteine. Circulation 1998; 97: 421–4

    Article  PubMed  CAS  Google Scholar 

  9. Malinow MR, Bostom AG, Krauss RM. Homocyst(e)ine, diet, and cardiovascular diseases: a statement for healthcare professionals from the Nutrition Committee, American Heart Association. Circulation 1999; 99: 178–82

    Article  PubMed  CAS  Google Scholar 

  10. Kuller LH, Evans RW. Homocysteine, vitamins, and cardiovascular disease. Circulation 1998; 98: 196–9

    Article  PubMed  CAS  Google Scholar 

  11. 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: 1449–54

    Article  PubMed  CAS  Google Scholar 

  12. Finkelstein JD. The metabolism of homocysteine: pathways and regulation. Eur J Pediatr 1998; 157: S40–4

    Article  PubMed  CAS  Google Scholar 

  13. Scott JM, Weir DG. Folic acid, homocysteine and one-carbon metabolism: a review of the essential biochemistry. J Cardiovasc Risk 1999; 5: 223–7

    Article  Google Scholar 

  14. Selhub J, Jacques PF, Wilson PWF, et al. Vitamin status and intake as primary determinants of homocysteinemia in an elderly population. JAMA 1993; 270: 2693–8

    Article  PubMed  CAS  Google Scholar 

  15. de Jong SC, Stehouwer CDA, van den Berg M, et al. Determinants of fasting and post-methionine homocysteine levels in families predisposed to hyperhomocysteinemia and premature vascular disease. Arterioscler Thromb Vasc Biol 1999; 19: 1316–24

    Article  PubMed  Google Scholar 

  16. Brattstrom L, Wilcken DEL, Ohrvik J, et al. Common methylenetetrahydrofolate reductase gene mutation leads to hyper-homocysteinemia but not to vascular disease: the result of a meta-analysis. Circulation 1998; 98: 2520–6

    Article  PubMed  CAS  Google Scholar 

  17. Wouters MG, Moorrees MT, van der Mooren MJ, et al. Plasma homocysteine and menopausal status. Eur J Clin Invest 1995; 25: 801–5

    Article  PubMed  CAS  Google Scholar 

  18. Giltay EJ, Hoogeveen EK, Elbers JMH, et al. Effects of sex steroids on plasma total homocysteine levels: a study in trans-sexual males and females. J Clin Endocrinol Metab 1998; 83: 550–3

    Article  PubMed  CAS  Google Scholar 

  19. Bostom AG, Lathrop AG. Hyperhomocysteinemia in end-stage renal disease: prevalence, etiology, and potential relationship to arteriosclerotic outcomes. Kidney Int 1997; 52: 10–20

    Article  PubMed  CAS  Google Scholar 

  20. Guttormsen AB, Ueland PM, Svarstad E, et al. Kinetic basis of hyperhomocysteinemia in patients with chronic renal failure. Kidney Int 1997; 52: 495–502

    Article  PubMed  CAS  Google Scholar 

  21. van Guldener C, Donker AJM, Jakobs C, et al. No net renal extraction of homocysteine in fasting humans. Kidney Int 1998; 54: 166–9

    Article  PubMed  Google Scholar 

  22. van Guldener C, Kulik W, Berger R, et al. Homocysteine and methionine metabolism in end-stage renal disease — a stable isotope study. Kidney Int 1999; 56: 1064–71

    Article  PubMed  Google Scholar 

  23. Wollesen F, Brattström L, Refsum H, et al. Plasma total homocysteine and cysteine in relation to glomerular filtration rate in diabetes mellitus. Kidney Int 1999; 55: 1028–35

    Article  PubMed  CAS  Google Scholar 

  24. Malinow MR. Homocyst(e)ine and arterial occlusive diseases. J Intern Med 1994; 236: 603–17

    Article  PubMed  CAS  Google Scholar 

  25. Nygård O, Vollset SE, Refsum H, et al. Total plasma homocysteine and cardiovascular risk profile: the Hordaland Homocysteine Study. JAMA 1995; 274: 1526–33

    Article  PubMed  Google Scholar 

  26. Nygård O, Refsum H, Ueland PM. Major lifestyle determinants of plasma total homocysteine distribution: the Hordaland Homocysteine Study. Am J Clin Nutr 1998; 67: 263–70

    PubMed  Google Scholar 

  27. Sutton-Tyrrell K, Bostom A, Selhub J, et al. High homocysteine levels are independently related to isolated systolic hypertension in older adults. Circulation 1997; 96: 1745–9

    Article  PubMed  CAS  Google Scholar 

  28. Giltay EJ, Hoogeveen EK, Elbers JMH, et al. Insulin resistance is associated with elevated plasma total homocysteine levels in healthy, non-obese subjects. Atherosclerosis 1998; 139: 197–8

    Article  PubMed  CAS  Google Scholar 

  29. Mudd SH, Levy HL, Skovby F. Disorders of transsulfuration. In: Scriver CR, Beaudet AL, Sly WS, et al., editors. The metabolic and molecular basis of inherited disease. 7th ed. New York: McGraw-Hill, 1995: 1279–327

    Google Scholar 

  30. Wilcken DEL, Wilcken B. The natural history of vascular disease in homocystinuria and the effects of treatment. J Inher Metab Dis 1997; 20: 295–300

    Article  PubMed  CAS  Google Scholar 

  31. Stampfer MJ, Malinow MR, Willett WC, et al. A prospective study of plasma homocyst(e)ine and risk of myocardial infarction in US physicians. JAMA 1992; 268: 877–81

    Article  PubMed  CAS  Google Scholar 

  32. Arnesen E, Refsum H, Bonaa KH, et al. Serum total homocysteine and coronary heart disease. Int J Epidemiol 1995; 24: 704–9

    Article  PubMed  CAS  Google Scholar 

  33. Perry IJ, Refsum H, Morris RW, et al. Prospective study of serum homocysteine concentration and risk of stroke in middle-aged British men. Lancet 1995; 346: 1395–8

    Article  PubMed  CAS  Google Scholar 

  34. Petri M, Roubenoff R, Dallal GE, et al. Plasma homocysteine as a risk factor for atherothrombotic events in systemic lupus erythematosus. Lancet 1996; 348: 1120–4

    Article  PubMed  CAS  Google Scholar 

  35. Nygård O, Nordrehaug JE, Refsum H, et al. Plasma homocysteine levels and mortality in patients with coronary artery disease. N Engl J Med 1997; 337: 230–6

    Article  PubMed  Google Scholar 

  36. Bostom AG, Shemin D, Verhoef P, et al. Elevated fasting total plasma homocysteine levels and cardiovascular disease outcomes in maintenance dialysis patients: a prospective study. Arterioscler Thromb Vasc Biol 1997; 17: 2554–8

    Article  PubMed  CAS  Google Scholar 

  37. Jungers P, Chauveau P, Bandin O, et al. Hyperhomocysteinemia is associated with atherosclerotic occlusive arterial accidents in predialysis chronic renal failure patients. Miner Electrolyte Metab 1997; 23: 170–3

    PubMed  CAS  Google Scholar 

  38. Moustapha A, Naso A, Nahlawi M, et al. Prospective study of hyperhomocysteinemia as an adverse cardiovascular risk factor in end-stage renal disease. Circulation 1998; 97: 138–141

    Article  PubMed  CAS  Google Scholar 

  39. Stehouwer CDA, Weijenberg MP, van den Berg M, et al. Serum homocysteine and risk of coronary heart disease and cerebrovascular disease in elderly men: a ten-year follow-up. Arterioscler Thromb Vasc Biol 1998; 18: 1895–901

    Article  PubMed  CAS  Google Scholar 

  40. Wald NJ, Watt HC, Law MR, et al. Homocysteine and ischemic heart disease: results of a prospective study with implications regarding prevention. Arch Intern Med 1998; 158: 862–7

    Article  PubMed  CAS  Google Scholar 

  41. Hoogeveen EK, Kostense PJ, Jacobs C, et al. Hyperhomocysteinaemia increases risk of death, especially in type 2 diabetes mellitus. Circulation. In press

  42. Stehouwer CDA, Gall MA, Hougaard P, et al. Plasma homocysteine concentration predicts mortality in non-insulin-dependent diabetic patients with and without albuminuria. Kidney Int 1999; 55: 308–14

    Article  PubMed  CAS  Google Scholar 

  43. Bots ML, Launer LJ, Lindemans J, 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

    Article  PubMed  CAS  Google Scholar 

  44. Taylor LM, Moneta GL, Sexton GJ, et al. Prospective blinded study of the relationship between plasma homocysteine and progression of symptomatic peripheral arterial disease. J Vasc Surg 1999; 29: 8–21

    Article  PubMed  Google Scholar 

  45. Ridker PM, Manson JE, Buring JE, et al. Homocysteine and risk of cardiovascular disease among postmenopausal women. JAMA 1999; 281: 1817–21

    Article  PubMed  CAS  Google Scholar 

  46. Bostom AG, Silbershatz H, Rosenberg IH, 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

    Article  PubMed  CAS  Google Scholar 

  47. Kark JD, Selhub J, Bostom A, et al. Plasma homocysteine and all-cause mortality in diabetes. Lancet 1999; 353: 1936–7

    Article  PubMed  CAS  Google Scholar 

  48. Stehouwer CDA, Jakobs C. Abnormalities of vascular function in hyperhomocysteinaemia: relationship to atherothrombotic disease. Eur J Pediatrics 1998; 157Suppl. 2: S107–11

    Article  CAS  Google Scholar 

  49. Welch GN, Loscalzo J. Mechanisms of disease: homocysteine and atherothrombosis. N Engl J Med 1998; 338: 1042–50

    Article  PubMed  CAS  Google Scholar 

  50. Lentz SR. Homocysteine and vascular dysfunction. Life Sci 1997; 61: 1205–15

    Article  PubMed  CAS  Google Scholar 

  51. Perna AF, Ingrosso D, Galletti P, et al. Membrane protein damage and methylation reactions in chronic renal failure. Kidney Int 1996; 50: 358–66

    Article  PubMed  CAS  Google Scholar 

  52. Verhoef P, Hennekens CH, Malinow R, et al. A prospective study of plasma homocyst(e)ine and risk of ischemic stroke. Stroke 1994; 25: 1924–30

    Article  PubMed  CAS  Google Scholar 

  53. Alfthan G, Pekkanen J, Jauhiainen M, et al. Relation of serum homocysteine and lipoprotein (a) concentrations to atherosclerotic disease in a prospective Finnish population-based study. Atherosclerosis 1994; 106: 9–19

    Article  PubMed  CAS  Google Scholar 

  54. Chasan-Taber L, Selhub J, Rosenberg IH, 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

    PubMed  CAS  Google Scholar 

  55. Evans RW, Shaten BJ, Hempel JD, et al. Homocyst(e)ine and risk of cardiovascular disease in the Multiple Risk Factor Intervention Trial. Arterioscler Thromb Vasc Biol 1997; 17: 1947–53

    Article  PubMed  CAS  Google Scholar 

  56. Verhoef P, Hennekens CH, Allen RH, et al. Plasma total homocysteine and risk of angina pectoris with subsequent coronary artery bypass surgery. Am J Cardiol 1997; 79: 799–801

    Article  PubMed  CAS  Google Scholar 

  57. Folsom AR, Nieto FJ, McGovern PG, 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

    Article  PubMed  CAS  Google Scholar 

  58. Robinson K, Arheart K, Refsum H, et al. Low circulating folate and vitamin B6 concentrations: risk factors for stroke, peripheral vascular disease, and coronary artery disease. Circulation 1998; 97: 437–43

    Article  PubMed  CAS  Google Scholar 

  59. Giles WH, Kittner SJ, Anda RF, et al. Serum folate and risk for ischemic stroke. Stroke 1995; 26: 1166–70

    Article  PubMed  CAS  Google Scholar 

  60. Selhub J, Jacques PF, Bostom AG, et al. Association between plasma homocysteine concentrations and extracranial carotid-artery stenosis. N Engl J Med 1995; 332: 286–91

    Article  PubMed  CAS  Google Scholar 

  61. Rimm EB, Willett WC, Hu FB, et al. Folate and vitamin B6 from diet and supplements in relation to risk of coronary heart disease among women. JAMA 1998; 279: 359–64

    Article  PubMed  CAS  Google Scholar 

  62. Nygård O, Refsum H, Ueland PM, et al. Plasma homocysteine levels and mortality in patients with coronary artery disease [letter]. N Engl J Med 1997; 332: 1632

    Google Scholar 

  63. den Heijer M, Koster T, Blom HJ, et al. Hyperhomocysteinemia as a risk factor for deep-vein thrombosis. N Engl J Med 1996; 334: 759–62

    Article  Google Scholar 

  64. Hoogeveen EK, Kostense PJ, Jager A, et al. Serum homocysteine level and protein intake are related to risk of microalbuminuria: the Hoorn Study. Kidney Int 1998; 54: 203–9

    Article  PubMed  CAS  Google Scholar 

  65. Hofmann MA, Kohl B, Zumbach MS, et al. Hyperhomocyst(e)inemia and endothelial dysfunction in IDDM. Diabetes Care 1998; 21: 841–8

    Article  PubMed  CAS  Google Scholar 

  66. Refsum H, Ueland PM. Recent data are not in conflict with homocysteine as a cardiovascular risk factor. Curr Opin Lipidol 1998; 9: 533–9

    Article  PubMed  CAS  Google Scholar 

  67. Hoogeveen EK, Kostense PJ, Beks PJ, et al. Hyperhomocysteinemia is associated with an increased risk of cardiovascular disease, especially in non-insulin-dependent diabetes mellitus. Arterioscler Thromb Vasc Biol 1998; 18: 133–8

    Article  PubMed  CAS  Google Scholar 

  68. Wang H, Yoshizumi M, Lai K, et al. Inhibition of growth and p21ras methylation in vascular endothelial cells by homocysteine but not cysteine. J Biol Chem 1997; 272: 25380–5

    Article  PubMed  CAS  Google Scholar 

  69. Upchurch GRJ, Welch GN, Fabian AJ, et al. Homocyst(e)ine decreases bioavailable nitric oxide by a mechanism involving glutathione peroxidase. J Biol Chem 1997; 272: 17012–7

    Article  PubMed  CAS  Google Scholar 

  70. Ubbink JB, Vermaak WJ, Bennett JM, et al. The prevalence of homocysteinemia and hypercholesterolemia in angiographically defined coronary heart disease. Klin Wochenschrift 1991; 69: 527–34

    Article  CAS  Google Scholar 

  71. von Eckardstein A, Malinow MR, Upson B, et al. Effects of age, lipoproteins, and hemostatic parameters on the role of homocyst(e)inemia as a cardiovascular risk factor in men. Arterioscler Thromb 1994; 14: 460–4

    Article  Google Scholar 

  72. Verhoef P, Kok FJ, Kruyssen DA, et al. Plasma total homocysteine, B vitamins, and risk of coronary atherosclerosis. Arterioscler Thromb Vasc Biol 1997; 17: 989–95

    Article  PubMed  CAS  Google Scholar 

  73. Yoo JH, Chung CS, Kang SS. Relation of plasma homocyst(e)ine to cerebral infarction and cerebral atherosclerosis. Stroke 1998; 29: 2478–83

    Article  PubMed  CAS  Google Scholar 

  74. van den Berg M, Stehouwer CD, Bierdrager E, et al. Plasma homocysteine and severity of atherosclerosis in young patients with lower-limb atherosclerotic disease. Arterioscler Thromb Vasc Biol 1996; 16: 165–71

    Article  PubMed  Google Scholar 

  75. Demuth K, Moatti N, Hanon O, et al. Opposite effects of plasma homocysteine and the methylenetetrahydrofolate reductase C677T mutation on carotid artery geometry in asymptomatic adults. Arterioscler Thromb Vasc Biol 1998; 18: 1838–43

    Article  PubMed  CAS  Google Scholar 

  76. Tonstad S, Joakimsen O, Stensland-Bugge E, et al. Risk factors related to carotid intima-media thickness and plaque in children with familial hypercholesterolemia and control subjects. Arterioscler Thromb Vasc Biol 1996; 16: 984–91

    Article  PubMed  CAS  Google Scholar 

  77. Bots ML, Launer LJ, Lindemans J, et al. Homocysteine, atherosclerosis and prevalent cardiovascular disease in the elderly: the Rotterdam Study. J Intern Med 1997; 242: 339–47

    Article  PubMed  CAS  Google Scholar 

  78. de Jong SC, Stehouwer CD, Mackaay AJ, et al. High prevalence of hyperhomocysteinemia and asymptomatic vascular disease in siblings of young patients with vascular disease and hyperhomocysteinemia. Arterioscler Thromb Vasc Biol 1997; 17: 2655–62

    Article  PubMed  Google Scholar 

  79. Malinow MR, Nieto FJ, Szklo M, et al. Carotid artery intimalmedial wall thickening and plasma homocyst(e)ine in asymptomatic adults: the Atherosclerosis Risk in Communities Study. Circulation 1993; 87: 1107–13

    Article  PubMed  CAS  Google Scholar 

  80. Smilde TJ, van den Berkmortel FWPJ, Boers GHJ, et al. Carotid and femoral artery wall thickness and stiffness in patients at risk for cardiovascular disease, with special emphasis on hyperhomocysteinemia. Arterioscler Thromb Vasc Biol 1998; 18: 1958–63

    Article  PubMed  CAS  Google Scholar 

  81. Tawakol A, Omland T, Gerhard M, et al. Hyperhomocyst(e)inemia is associated with impaired endothelium-dependent vasodilation in humans. Circulation 1997; 95: 1119–21

    Article  PubMed  CAS  Google Scholar 

  82. Woo KS, Chook P, Lolin YI, et al. Hyperhomocyst(e)inemia is a risk factor for arterial endothelial dysfunction in humans. Circulation 1997; 96: 2542–4

    Article  PubMed  CAS  Google Scholar 

  83. Bellamy MF, Mcdowell IFW, Ramsey MW, et al. Hyperhomocysteinemia after an oral methionine load acutely impairs endothelial function in healthy adults. Circulation 1998; 98: 1848–52

    Article  PubMed  CAS  Google Scholar 

  84. Chambers JC, McGregor A, Jean-Marie J, et al. Demonstration of rapid onset vascular endothelial dysfunction after hyperhomocysteinemia: an effect reversible with vitamin C therapy. Circulation 1999; 99: 1156–60

    Article  PubMed  CAS  Google Scholar 

  85. Usui M, Matsuoka H, Miyazaki H, et al. Endothelial dysfunction by acute hyperhomocyst(e)inaemia: restoration by folic acid. Clin Sci 1999; 96: 235–9

    Article  PubMed  CAS  Google Scholar 

  86. Lambert J, van den Berg M, Steyn M, et al. Familial hyperhomocysteinemia and endothelium-dependent vasodilation and arterial distensibility of large arteries. Cardiovasc Res 1999; 42: 743–51

    Article  PubMed  CAS  Google Scholar 

  87. van Guldener C, Lambert J, Janssen MJ, et al. Endotheliumdependent vasodilatation and distensibility of large arteries in chronic haemodialysis patients. Nephrol Dial Transplant 1997; 12Suppl. 2: 14–8

    PubMed  Google Scholar 

  88. van Guldener C, Janssen MJFM, Lambert J, et al. No change in impaired endothelial function after long-term folic acid therapy of hyperhomocysteinaemia in haemodialysis patients. Nephrol Dial Transplant 1998; 13: 106–12

    Article  PubMed  Google Scholar 

  89. Hanratty CG, McAuley DF, McGurk C, et al. Homocysteine and endothelial vascular function [letter]. Lancet 1998; 351: 1288–9

    Article  PubMed  CAS  Google Scholar 

  90. van den Berg M, Boers GH, Franken DG, et al. Hyperhomocysteinaemia and endothelial dysfunction in young patients with peripheral arterial occlusive disease. Eur J Clin Invest 1995; 25: 176–81

    Article  PubMed  Google Scholar 

  91. de Jong SC, Stehouwer CD, van den Berg M, et al. Endothelial marker proteins in hyperhomocysteinemia. Thromb Haemost 1997; 78: 1332–7

    PubMed  Google Scholar 

  92. de Valk-de Roo GW, Stehouwer CDA, Lambert J, et al. Plasma homocysteine is weakly correlated with plasma endothelin and von Willebrand factor, but not with endothelium-dependent vasodilatation in healthy postmenopausal women. Clin Chem 1999; 45: 1200–5

    PubMed  Google Scholar 

  93. Majors A, Ehrhart LA, Pezacka EH. Homocysteine as a risk factor for vascular disease: enhanced collagen production and accumulation by smooth muscle cells. Arterioscler Thromb Vasc Biol 1997; 17: 2074–81

    Article  PubMed  CAS  Google Scholar 

  94. Kang AH, Trelstad RL. A collagen defect in homocystinuria. J Clin Invest 1973; 52: 2571–8

    Article  PubMed  CAS  Google Scholar 

  95. Blacher J, Demuth K, Guerin AP, et al. Influence of biochemical alterations on arterial stiffness in patients with end-stage renal disease. Arterioscler Thromb Vasc Biol 1998; 18: 535–41

    Article  PubMed  CAS  Google Scholar 

  96. Vermeulen EGJ, Stehouwer CDA, Twisk JWR, et al. Effect of homocysteine-lowering treatment with folic acid plus vitamin B6 on progression of subclinical atherosclerosis: a randomised, placebo-controlled trial. Lancet 2000; 355: 517–22

    Article  PubMed  CAS  Google Scholar 

  97. Verhaar MC, Wever RM, Kastelein JJ, et al. 5-methyltetrahydrofolate, the active form of folic acid, restores endothelial function in familial hypercholesterolemia. Circulation 1998; 97: 237–41

    Article  PubMed  CAS  Google Scholar 

  98. Clarke R, Collins R. Can dietary supplements with folic acid or vitamin B6 reduce cardiovascular risk? Design of clinical trials to test the homocysteine hypothesis of vascular disease. J Cardiovasc Risk 1998; 5: 249–55

    Article  PubMed  CAS  Google Scholar 

  99. Brattstrom L. Vitamins as homocysteine-lowering agents. J Nutr 1996; 126 Suppl.: 1276–80

    Google Scholar 

  100. van den Berg M, Franken DG, Boers GHJ, et al. Combined vitamin B6 plus folic acid therapy in young patients with arteriosclerosis and hyperhomocy steinemia. J Vasc Surg 1994; 20: 933–40

    Article  PubMed  Google Scholar 

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Part of the author’s work cited in this paper was supported by a fellowship from the Netherlands Organisation for Scientific Research (NWO).

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Stehouwer, C.D.A. Clinical Relevance of Hyperhomocysteinaemia in Atherothrombotic Disease. Drugs & Aging 16, 251–260 (2000). https://doi.org/10.2165/00002512-200016040-00001

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