Homocysteinämie und B-Vitamine - Rationeller Umgang mit einem neuen Risikofaktor

Zusammenfassung

Homocystein ist heute als ein unabhängiger Risikofaktor für kardiovaskuläre Erkrankungen zu betrachten. Eine Homocysteinämie wird für etwa 10 % des kardiovaskulären Gesamtrisikos verantwortlich gemacht. Diskutiert wird aber auch ein negativer Einfluss auf das Zentralnervensystem. Im Mittelpunkt steht dabei neben der Depression vor allem die Demenz. Somit besteht ein enger Zusammenhang zu solchen chronischen Erkrankungen, die sich meist im fortgeschrittenen Lebensalter finden und ein hohes Invalidisierungspotenzial aufweisen. Neben dem Leid, das diese Erkrankungen dem Einzelnen und seinen Familien bereitet, sind immense Kosten für die erforderliche Behandlung und Pflege zu berück-sichtigen. Andererseits gibt es bisher keinen Risikofaktor, der so kostengünstig beeinflussbar ist. Denn durch Substitution mit den Vitaminen B₆, B₁₂ und Folsäure lässt sich Homocystein zuverlässig senken. Theoretisch sollen hierdurch über 20 % aller kardiovas-kulären Ereignisse vermeidbar sein. Eine generelle Empfehlung zur Senkung einer Homocysteinämie auch bei Gesunden wird möglich sein, sobald die Ergebnisse von randomisierten kontrollierten Behandlungsstudien vorliegen.

Summary

Homocysteine is now generally considered an independent risk factor for cardiovascular diseases. About 10 per cent of cardiovascular problems are assumed to be caused by homocysteinaemia which furthermore seems to adversely affect the central nervous system. Apart from depressions, this disorder most probably can cause dementia. It is thus closely related to chronic diseases which are mainly affecting elderly people and which entail a high risk of invalidity. Apart from the distress afflicting individual patients and their families, the costs for medical attention and care must be considered. On the other hand, we are so far not aware of another risk factor that can be so easily influenced at low costs. In fact, blood homocysteine levels can be positively lowered by B₆, B₁₂ or folic acid supplements. In theory, more than 20 per cent of all cardiovascular diseases can be avoided. General recommendations for therapies liable to prevent or cure homocysteinaemia will be available as soon as randomised, controlled medication studies have been performed.

Schlüsselwörter

Homocystein - Vitamin B₆ - Vitamin B₁₂ - Folsäure - Risikofaktoren - Herz-Kreislauf-Erkrankungen - Demenz - chronische Krankheiten

Key words

Homocysteine - vitamin B₆ - vitamin B₁₂ - folic acid - risk factors - cardivascular diseases - dementia - chronical disease

Literatur

• 1 Becker A, Kostense PJ, Bos G. et al. . Hyperhomocysteinaemia is associated with coronary events in type 2 diabetes.  J Intern Med. 2003;  253 293-300
• 2 Beitz R, Mensink GB, Fischer B, Thamm M. Vitamins - dietary intake and intake from dietary supplements in Germany.  Eur J Clin Nutr. 2002;  56 539-545
• 3 Bostom AG, Garber C. Endpoints for homocysteine-lowering trials.  Lancet. 2000;  335 511-512
• 4 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 1077-1080
• 5 Bots ML, Launer LJ, Lindemans J. et al. . Homocysteine and short-term risk of myocardial infarction and stroke in the elderly.  Arch Intern Med. 1999;  159 38-44
• 6 Boushey CJ, Beresford SAA, 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
• 7 Chen P, Poddar R, Tipa EV. et al. . Homo-cysteine metabolism in cardiovascular cells and tissues: implications for hyperhomocysteinemia and cardiovascular disease.  Adv Enzyme Regul. 1999;  39 93-109
• 8 Clarke R, Smith D, Jobst KA. et al. . Folate, vitamin B₁₂, and serum total homocysteine levels in confirmed Alzheimer disease.  Arch Neurol. 1998;  55 1449-1455
• 9 De Bree A, van Dusseldorp M, Brouwer IA. et al. . Folate intake in Europe: recommended, actual and desired intake.  Eur J Clin Nutr. 1997;  51 643-660
• 10 De Bree A, Verschuren WM, Kromhout D, Mennen LI, Blom HJ. Homocysteine and coronary heart disease: the importance of distinction between low and high risk subjects.  Int J Epidemiol. 2002;  31 1268-1272
• 11 Durand P, Prost M, Loreau N, Lussier-Cacan S. Impaired homocysteine metabolism and atherothrombotic disease.  Lab Invest. 2001;  81 645-672
• 12 Erbel R, Siffert W, Mohlenkamp S, Schmermund A. Prävention durch Risikostratifizierung.  Dtsch Med Wochenschr. 2003;  128 330-336
• 13 Foody JM, Milberg JA, Robinson K. et al. . Homocysteine and lipoprotein(a) interact to increase CAD risk in young men and women.  Arterioscler Thromb Vasc Biol. 2000;  20 493-499
• 14 Genest J. Hyperhomocyst(e)inemia - determining factors and treatment.  Can J Cardiol. 1999;  15 35-38
• 15 Graham I. Homocysteine in health and disease.  Ann Intern Med. 1999;  131 387-388
• 16 Henning BF, Tepel M, Riezler R, Naurath HJ. Long-term effects of vitamin B₁₂, folate, and vitamin B₆ supplements in elderly people with normal serum vitamin concentrations.  Gerontology. 2001;  47 30-35
• 17 Homocysteine Lowering Trialists' Collaboration . Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomised trials.  BMJ. 1998;  316 894-898
• 18 Jacques PF, Bostom AG, Williams RR. et al. . Relation between folate status, a common mutation in methylenetetrahydrofolate reductase, and plasma homocysteine concentrations.  Circulation. 1996;  93 7-9
• 19 Jacques PF, Selhub J, Bostom AG, Wilson PWF, Rosenberg IH. The effect of folic acid fortification on plasma folate and total homocysteine concentrations.  N Engl J Med. 1999;  340 1449-1454
• 20 Joosten E, van A den Berg, Riezler R. et al. . Metabolic evidence that deficiencies of vitamin B-12 (cobalamin), folate, and vitamin B-6 occur commonly in elderly people.  Am J Clin Nutr. 1993;  58 468-476
• 21 Klerk M, Verhoef P, Clarke R, Blom HJ, Kok FJ, Schouten EG. MTHFR Studies Collaboration Group: MTHFR 677C->T polymorphism and risk of coronary heart disease: a meta-analysis.  JAMA. 2002;  288 2023-2031
• 22 Kluijtmans LA, Boers GH, Kraus JP. et al. . The molecular basis of cystathionine beta-synthase deficiency in Dutch patients with homocystinuria: effect of CBS genotype on biochemical and clinical phenotype and on response to treatment.  Am J Hum Genet. 1999;  65 59-67
• 23 Law M, Wald DS. Risk factor thresholds: their existence under scrutiny.  BMJ. 2002;  324 1576
• 24 Lipton SA, Kim WK, Choi YB. et al. . Neuro-toxicity associated with dual actions of homocysteine at the N-methyl-D-aspartate receptor.  Proc Natl Acad Sci USA. 1997;  94 5923-5928
• 25 Lloyd-Jones DM, Larson MG, Beiser A, Levy D. Lifetime risk of developing coronary heart disease.  Lancet. 1999;  353 89-92
• 26 Meleady R, Ueland PM, Blom H. et al. . Thermolabile methylenetetrahydrofolate reductase, homocysteine, and cardiovascular disease risk: The European Concerted Action Project.  Am J Clin Nutr. 2003;  77 63-70
• 27 Mudd SH, Skovby F, Levy HL. et al. . The natural history of homocystinuria due to cystathionine beta-synthase deficiency.  Am J Hum Genet. 1985;  37 1-31
• 28 Naurath HJ, Joosten E, Riezler R. et al. . Effects of vitamin B₁₂, folate, and vitamin B₆ supplements in elderly people with normal serum vitamin concentrations.  Lancet. 1995;  346 85-89
• 29 Nedrebo BG, Ericsson UB, Nygard O. et al. . Plasma total homocysteine levels in hyperthyroid and hypothyroid patients.  Metabolism. 1998;  47 89-93
• 30 Nurk E, Tell GS, Vollset SE. et al. . Plasma total homocysteine and hospitalizations for cardiovascular disease: The Hordaland Homocysteine Study.  Arch Intern Med. 2002;  162 1374-1381
• 31 Nygard O, Nordrehaug JE, Refsum H. et al. . Plasma homocysteine levels and mortality in patients with coronary artery disease.  N Engl J Med. 1997;  337 230-236
• 32 Nygard O, Vollset SE, Refsum H. et al. . Total homocysteine and cardiovascular disease.  J Intern Med. 1999;  246 425-454
• 33 Quinlivan EP, McPartlin J, McNulty H. et al. . Importance of both folic acid and vitamin B₁₂ in reduction of risk of vascular disease.  Lancet. 2002;  359 227-228
• 34 Refsum H, Ueland PM, Nygard O, Vollset SE. Homocysteine and cardiovascular disease.  Annu Rev Med. 1998;  49 31-62
• 35 Riggs KM, Spiro IA, Tucker K, Rush D. Relations of vitamin B-12, vitamin B-6, folate, and homocysteine to cognitive performance in the Normative Aging Study.  Am J Clin Nutr. 1996;  63 306-314
• 36 Rosenberg IH, Selhub J, Jacques PF. et al. .Blood homocysteine levels in the National Health and Nutrition Examination Survey (NHANES III) in the United States: preliminary findings by age and sex. In: Graham I, Refsum H, Rosenberg IH, Ueland PM (eds.): Homocysteine Metabolism: From Basic Science to Clinical Medicine. Boston: Kluver Acad Pub 1997: 184-187
• 37 Schnyder G, Roffi M, Flammer Y, Pin R, Hess OM. Effect of homocysteine-lowering therapy with folic acid, vitamin B₁₂, and vitamin B₆ on clinical outcome after percutaneous coronary intervention. The Swiss Heart Study: a randomized controlled trial.  JAMA. 2002;  288 973-979
• 38 Seshadri S, Beiser A, Selhub J. et al. . Plasma homocysteine as a risk factor for dementia and Alzheimer's disease.  N Engl J Med. 2002;  346 476-483
• 39 Stanger O, Herrmann W, Pietrzik K. et al. . Konsensuspapier der D.A.CH.-Liga Homo-cystein über den rationellen klinischen Umgang mit Homocystein, Folsäure und B-Vitaminen bei kardiovaskulären und thrombotischen Erkrankungen - Richtlinien und Empfehlungen.  Journal für Kardiologie. 2003;  10 190-199
• 40 Stanger O, Weger M, Renner W, Konetschny R. Vascular dysfunction in hyperhomo-cyst(e)inemia. Implications for atherothrombotic disease.  Clin Chem Lab Med. 2001;  39 725-733
• 41 Tice JA, Ross E, Coxson PG. et al. . Cost-effectiveness of vitamin therapy to lower plasma homocysteine levels for the prevention of coronary heart disease: effect of grain fortification and beyond.  JAMA. 2001;  286 936-943
• 42 Ueland PM, Refsum H, Beresford SA, Vollset SE. The controversy over homocysteine and cardiovascular risk.  Am J Clin Nutr. 2000;  72 324-332
• 43 Vollset SE, Nygard O, Kvale G, Ueland PM, Refsum H. The Hordaland Homocysteine Study: Lifestyle and total plasma homo-cysteine in Western Norway. In: Graham I, Refsum H, Rosenberg IH, Ueland PM (eds.): Homocysteine Metabolism: From Basic Science to Clinical Medicine. Boston: Kluver Acad Pub 1997: 177-182
• 44 Wald DS, Law M, Morris JK. Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis.  BMJ. 2002;  325 1202-1206
• 45 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;  158 862-867
• 46 Wilcken DE, Wilcken B. The natural history of vascular disease in homocystinuria and the effects of treatment.  J Inherit Metab Dis. 1997;  20 295-300
• 47 Willett WC, Stampfer MJ. Clinical practice. What vitamins should I be taking, doctor?.  N Engl J Med. 2001;  345 1819-1824