<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.3 20210610//EN" "JATS-journalpublishing1-3.dtd">
<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">arthyper</journal-id><journal-title-group><journal-title xml:lang="ru">Артериальная гипертензия</journal-title><trans-title-group xml:lang="en"><trans-title>"Arterial’naya Gipertenziya" ("Arterial Hypertension")</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">1607-419X</issn><issn pub-type="epub">2411-8524</issn><publisher><publisher-name>Antihypertensive League</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.18705/1607-419X-2008-14-2-110-115</article-id><article-id custom-type="elpub" pub-id-type="custom">arthyper-1198</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>ОБЗОР</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>REVIEW</subject></subj-group></article-categories><title-group><article-title>Современные представления о гипергомоцистеинемии как факторериска сердечно-сосудистых заболеваний</article-title><trans-title-group xml:lang="en"><trans-title>Hyperhomocystcinemia
as a cardiovascular risk factor. Current concepts</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Родионов</surname><given-names>Р.</given-names></name><name name-style="western" xml:lang="en"><surname>Rodionov</surname><given-names>R.</given-names></name></name-alternatives><email xlink:type="simple">noemail@neicon.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Лентц</surname><given-names>С.</given-names></name><name name-style="western" xml:lang="en"><surname>Lentz</surname><given-names>S.</given-names></name></name-alternatives><email xlink:type="simple">noemail@neicon.ru</email><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Медицинский Факультет Университета Айовы</institution><country>Россия</country></aff><aff xml:lang="en"><institution>University of Iowa Carver College of Medicine</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2008</year></pub-date><pub-date pub-type="epub"><day>28</day><month>04</month><year>2008</year></pub-date><volume>14</volume><issue>2</issue><fpage>110</fpage><lpage>115</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Родионов
                 Р., Лентц
                 С., 2008</copyright-statement><copyright-year>2008</copyright-year><copyright-holder xml:lang="ru">Родионов
                 Р., Лентц
                 С.</copyright-holder><copyright-holder xml:lang="en">Rodionov
                 R., Lentz
                 S.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://htn.almazovcentre.ru/jour/article/view/1198">https://htn.almazovcentre.ru/jour/article/view/1198</self-uri><abstract><p>Резюме
Тяжелая гипергомоцистеинемия, вызванная редкими наследственными нарушениями метаболизма гомоцис-теина, приводит к многократному увеличению риска атеротромбоза. Даже частичная коррекция уровня гомоцис-теина у пациентов с тяжелой гипергомоцистеинемией позволяет существенно уменьшить частоту возникновения сердечно-сосудистых осложнений. Умеренная гипергомоцистеинемия широко распространена в популяции и коррелирует с повышенным риском развития заболеваний сердечно-сосудистой системы. В экспериментальных моделях умеренная гипергомоцистеинемия вызывает эндотелиальную дисфункцию, предрасполагает к тромбозу и ускоряет развитие атеросклероза. На основании эпидемиологических и экспериментальных данных была выдвинута гипотеза, что коррекция умеренной гипергомоцистеинемии может существенно уменьшить риск развития заболеваний сердечно-сосудистой системы. Вопреки ожиданиям, серия крупных клинических исследований показала, что снижение уровня гомоцистеина при умеренной гипергомоцистеинемии не влияет на риск развития сердечнососудистых заболеваний. В данной статье обсуждаются современные представления о гипергомоцистеинемии как факторе риска развития заболеваний сердечно-сосудистой системы в свете отрицательных результатов клинических исследований по коррекции уровня гомоцистеина при умеренной гипергомоцистеинемии.
            </p></abstract><trans-abstract xml:lang="en"><p>Resume
Hyperhomocysteinemia is hypothesized to be a cardiovascular risk factor. Severe hyperhomocysteinemia due to rare genetic impairments of homocysteine metabolism predisposes to atherothrombosis. Even partial correction of homocysteine levels in patients with severe hyperhomocysteinemia leads to significant reduction in cardiovascular risk. Moderate hyperhomocysteinemia is common in the general population and is associated with the increased risk of cardiovascular disease. Moderate hyperhomocysteinemia leads to endothelial dysfunction, increased susceptibility to thrombosis and accelerated progression of atherosclerosis in animal models. Extensive epidemiological and experimental evidence lead to the hypothesis that correction of moderate hyperhomocysteinemia may significantly lower cardiovascular risk. Paradoxically, several large clinical trials failed to demonstrate any benefit from lowering of homocysteine levels in moderate hyperhomocysteinemia. This article discusses the current understanding of hyperhomocysteinemia as a cardiovascular risk factor in light of the negative results of clinical trials of homocysteine lowering therapy in moderate hyperhomocysteinemia.
            </p></trans-abstract><kwd-group xml:lang="ru"><kwd>гипергомоцистеинемия</kwd><kwd>гомоцистеин</kwd><kwd>сердечно-сосудистые заболевания</kwd><kwd>фактор риска</kwd></kwd-group><kwd-group xml:lang="en"><kwd>hyperhomocysteinemia</kwd><kwd>homocysteine</kwd><kwd>cardiovascular disease</kwd><kwd>risk factor</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Jacques P.F., Rosenberg I.H., Rogers G., et al., Serum total homocysteine concentrations in adolescent and adult Americans: results from the third National Health and Nutrition Examination Survey. Am J Clin Nutr, 1999. 69: 482-489.</mixed-citation><mixed-citation xml:lang="en">Jacques P.F., Rosenberg I.H., Rogers G., et al., Serum total homocysteine concentrations in adolescent and adult Americans: results from the third National Health and Nutrition Examination Survey. Am J Clin Nutr, 1999. 69: 482-489.</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru"></mixed-citation><mixed-citation xml:lang="en"></mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Selhub J., Homocysteine metabolism. Annu Rev Nutr, 1999. 19: p. 217-46.</mixed-citation><mixed-citation xml:lang="en">Selhub J., Homocysteine metabolism. Annu Rev Nutr, 1999. 19: p. 217-46.</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru"></mixed-citation><mixed-citation xml:lang="en"></mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Lentz S.R. and Haynes W.G., Homocysteine: is it a clinically important cardiovascular risk factor? Cleve Clin J Med, 2004. 71(9): 729-734.</mixed-citation><mixed-citation xml:lang="en">Lentz S.R. and Haynes W.G., Homocysteine: is it a clinically important cardiovascular risk factor? Cleve Clin J Med, 2004. 71(9): 729-734.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru"></mixed-citation><mixed-citation xml:lang="en"></mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Mudd S.H., Finkelstein J.D., Refsum H., et al., Homocysteine and its disulfide derivatives: a suggested consensus terminology. Arterioscler Thromb Vase Biol, 2000. 20(7): 1704-1706.</mixed-citation><mixed-citation xml:lang="en">Mudd S.H., Finkelstein J.D., Refsum H., et al., Homocysteine and its disulfide derivatives: a suggested consensus terminology. Arterioscler Thromb Vase Biol, 2000. 20(7): 1704-1706.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru"></mixed-citation><mixed-citation xml:lang="en"></mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">McCully K.S., Vascular pathology of homocysteinemia: implications for the pathogenesis of arteriosclerosis. Am J Pathol, 1969.56:111-128.</mixed-citation><mixed-citation xml:lang="en">McCully K.S., Vascular pathology of homocysteinemia: implications for the pathogenesis of arteriosclerosis. Am J Pathol, 1969.56:111-128.</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru"></mixed-citation><mixed-citation xml:lang="en"></mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Kang S.S., Wong P.W., and Malinow M.R., Hyperhomocyst(e)inemia as a risk factor for occlusive vasculardisease. Annu Rev Nutr, 1992. 12:279-298.</mixed-citation><mixed-citation xml:lang="en">Kang S.S., Wong P.W., and Malinow M.R., Hyperhomocyst(e)inemia as a risk factor for occlusive vasculardisease. Annu Rev Nutr, 1992. 12:279-298.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru"></mixed-citation><mixed-citation xml:lang="en"></mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Mudd S.H., Skovby F., Levy H.L., et al., The natural history of homocystinuria due to cystathionine beta-synthase deficiency. Am J Hum Genet, 1985. 37(1): p. 1-31.</mixed-citation><mixed-citation xml:lang="en">Mudd S.H., Skovby F., Levy H.L., et al., The natural history of homocystinuria due to cystathionine beta-synthase deficiency. Am J Hum Genet, 1985. 37(1): p. 1-31.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru"></mixed-citation><mixed-citation xml:lang="en"></mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Yap S., Boers G.H., Wilcken В., et al., Vascular outcome in patients with homocystinuria due to cystathionine beta-synthase deficiency treated chronically: a multicenter observational study. Arterioscler Thromb Vase Biol, 2001. 21(12):2080-2085.</mixed-citation><mixed-citation xml:lang="en">Yap S., Boers G.H., Wilcken В., et al., Vascular outcome in patients with homocystinuria due to cystathionine beta-synthase deficiency treated chronically: a multicenter observational study. Arterioscler Thromb Vase Biol, 2001. 21(12):2080-2085.</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru"></mixed-citation><mixed-citation xml:lang="en"></mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Selhub J., Jacques P.F., Wilson P.W., et al., Vitamin status and intake as primary determinants of homocysteinemia in an elderly population. Jama, 1993. 270(22): 2693-2698.</mixed-citation><mixed-citation xml:lang="en">Selhub J., Jacques P.F., Wilson P.W., et al., Vitamin status and intake as primary determinants of homocysteinemia in an elderly population. Jama, 1993. 270(22): 2693-2698.</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru"></mixed-citation><mixed-citation xml:lang="en"></mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Selhub J., Jacques P.F., Rosenberg I.H., et al., Serum total homocysteine concentrations in the third National Health and Nutrition Examination Survey (1991-1994): population reference ranges and contribution of vitamin status to high serum concentrations. Ann Intern Med, 1999. 131:331-339.</mixed-citation><mixed-citation xml:lang="en">Selhub J., Jacques P.F., Rosenberg I.H., et al., Serum total homocysteine concentrations in the third National Health and Nutrition Examination Survey (1991-1994): population reference ranges and contribution of vitamin status to high serum concentrations. Ann Intern Med, 1999. 131:331-339.</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru"></mixed-citation><mixed-citation xml:lang="en"></mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Homocysteine Studies Collaboration, Homocysteine and risk of ischemic heart disease and stroke: a meta-analysis. Jama, 2002. 288: 2015-2022.</mixed-citation><mixed-citation xml:lang="en">Homocysteine Studies Collaboration, Homocysteine and risk of ischemic heart disease and stroke: a meta-analysis. Jama, 2002. 288: 2015-2022.</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru"></mixed-citation><mixed-citation xml:lang="en"></mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">Den Heijer M., Lewington S., and Clarke R., Homocysteine, MTHFR and risk of venous thrombosis: a meta-analysis of published epidemiological studies. J Thromb Haemost, 2005.3(2): 292-299.</mixed-citation><mixed-citation xml:lang="en">Den Heijer M., Lewington S., and Clarke R., Homocysteine, MTHFR and risk of venous thrombosis: a meta-analysis of published epidemiological studies. J Thromb Haemost, 2005.3(2): 292-299.</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru"></mixed-citation><mixed-citation xml:lang="en"></mixed-citation></citation-alternatives></ref><ref id="cit25"><label>25</label><citation-alternatives><mixed-citation xml:lang="ru">Dayal S. and Lentz S.R., Role of Redox Reactions in the Vascular Phenotype of Hyperhomocysteinemic Animals. Antioxid Redox Signal, 2007.18:189-195.</mixed-citation><mixed-citation xml:lang="en">Dayal S. and Lentz S.R., Role of Redox Reactions in the Vascular Phenotype of Hyperhomocysteinemic Animals. Antioxid Redox Signal, 2007.18:189-195.</mixed-citation></citation-alternatives></ref><ref id="cit26"><label>26</label><citation-alternatives><mixed-citation xml:lang="ru"></mixed-citation><mixed-citation xml:lang="en"></mixed-citation></citation-alternatives></ref><ref id="cit27"><label>27</label><citation-alternatives><mixed-citation xml:lang="ru">Kanani P.M., Sinkey C.A., Browning R.L., et al., Role of oxidant stress in endothelial dysfunction produced by experimental hyperhomocyst(e)inemia in humans. Circulation, 1999. 100: 1161-1168.</mixed-citation><mixed-citation xml:lang="en">Kanani P.M., Sinkey C.A., Browning R.L., et al., Role of oxidant stress in endothelial dysfunction produced by experimental hyperhomocyst(e)inemia in humans. Circulation, 1999. 100: 1161-1168.</mixed-citation></citation-alternatives></ref><ref id="cit28"><label>28</label><citation-alternatives><mixed-citation xml:lang="ru"></mixed-citation><mixed-citation xml:lang="en"></mixed-citation></citation-alternatives></ref><ref id="cit29"><label>29</label><citation-alternatives><mixed-citation xml:lang="ru">Toole J.F., Malinow M.R., Chambless L.E., 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.</mixed-citation><mixed-citation xml:lang="en">Toole J.F., Malinow M.R., Chambless L.E., 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.</mixed-citation></citation-alternatives></ref><ref id="cit30"><label>30</label><citation-alternatives><mixed-citation xml:lang="ru"></mixed-citation><mixed-citation xml:lang="en"></mixed-citation></citation-alternatives></ref><ref id="cit31"><label>31</label><citation-alternatives><mixed-citation xml:lang="ru">Lonn E., Yusuf S., Arnold M.J., et al., Homocysteine lowering with folic acid and В vitamins in vascular disease. N Engl J Med, 2006. 354(15):1567-1577.</mixed-citation><mixed-citation xml:lang="en">Lonn E., Yusuf S., Arnold M.J., et al., Homocysteine lowering with folic acid and В vitamins in vascular disease. N Engl J Med, 2006. 354(15):1567-1577.</mixed-citation></citation-alternatives></ref><ref id="cit32"><label>32</label><citation-alternatives><mixed-citation xml:lang="ru"></mixed-citation><mixed-citation xml:lang="en"></mixed-citation></citation-alternatives></ref><ref id="cit33"><label>33</label><citation-alternatives><mixed-citation xml:lang="ru">Bonaa K.H., Njolstad I., Ueland P.M., et al., Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med, 2006. 354(15):1578-1588.</mixed-citation><mixed-citation xml:lang="en">Bonaa K.H., Njolstad I., Ueland P.M., et al., Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med, 2006. 354(15):1578-1588.</mixed-citation></citation-alternatives></ref><ref id="cit34"><label>34</label><citation-alternatives><mixed-citation xml:lang="ru"></mixed-citation><mixed-citation xml:lang="en"></mixed-citation></citation-alternatives></ref><ref id="cit35"><label>35</label><citation-alternatives><mixed-citation xml:lang="ru">den Heijer M., Willems H.P., Blom H.J., et al., Homocysteine lowering by В vitamins and the secondary prevention of deep vein thrombosis and pulmonary embolism: A randomized, placebo-controlled, double-blind trial. Blood, 2007. 109(1): 139-144.</mixed-citation><mixed-citation xml:lang="en">den Heijer M., Willems H.P., Blom H.J., et al., Homocysteine lowering by В vitamins and the secondary prevention of deep vein thrombosis and pulmonary embolism: A randomized, placebo-controlled, double-blind trial. Blood, 2007. 109(1): 139-144.</mixed-citation></citation-alternatives></ref><ref id="cit36"><label>36</label><citation-alternatives><mixed-citation xml:lang="ru"></mixed-citation><mixed-citation xml:lang="en"></mixed-citation></citation-alternatives></ref><ref id="cit37"><label>37</label><citation-alternatives><mixed-citation xml:lang="ru">Jamison R.L., Hartigan P., Kaufman J.S., et al., Effect of homocysteine lowering on mortality and vascular disease in advanced chronic kidney disease and end-stage renal disease: a randomized controlled trial. Jama, 2007. 298(10): 1163-1170.</mixed-citation><mixed-citation xml:lang="en">Jamison R.L., Hartigan P., Kaufman J.S., et al., Effect of homocysteine lowering on mortality and vascular disease in advanced chronic kidney disease and end-stage renal disease: a randomized controlled trial. Jama, 2007. 298(10): 1163-1170.</mixed-citation></citation-alternatives></ref><ref id="cit38"><label>38</label><citation-alternatives><mixed-citation xml:lang="ru"></mixed-citation><mixed-citation xml:lang="en"></mixed-citation></citation-alternatives></ref><ref id="cit39"><label>39</label><citation-alternatives><mixed-citation xml:lang="ru">Albert C.M., Cook N.R., Gaziano J.M., et al., Effect of Folic Acid and В Vitamins on Risk of Cardiovascular Events and Total Mortality Among Women at High Risk for Cardiovascular Disease: A Randomized Trial. 2008:2027-2036.</mixed-citation><mixed-citation xml:lang="en">Albert C.M., Cook N.R., Gaziano J.M., et al., Effect of Folic Acid and В Vitamins on Risk of Cardiovascular Events and Total Mortality Among Women at High Risk for Cardiovascular Disease: A Randomized Trial. 2008:2027-2036.</mixed-citation></citation-alternatives></ref><ref id="cit40"><label>40</label><citation-alternatives><mixed-citation xml:lang="ru"></mixed-citation><mixed-citation xml:lang="en"></mixed-citation></citation-alternatives></ref><ref id="cit41"><label>41</label><citation-alternatives><mixed-citation xml:lang="ru">Malinow M.R., Bostom A.G., and Krauss R.M., Homocysteine, diet, and cardiovascular diseases: a statement forhealthcare professionals from the Nutrition Committee, AmericanHeart Association. Circulation, 1999. 99(1):178-182.</mixed-citation><mixed-citation xml:lang="en">Malinow M.R., Bostom A.G., and Krauss R.M., Homocysteine, diet, and cardiovascular diseases: a statement forhealthcare professionals from the Nutrition Committee, AmericanHeart Association. Circulation, 1999. 99(1):178-182.</mixed-citation></citation-alternatives></ref><ref id="cit42"><label>42</label><citation-alternatives><mixed-citation xml:lang="ru"></mixed-citation><mixed-citation xml:lang="en"></mixed-citation></citation-alternatives></ref><ref id="cit43"><label>43</label><citation-alternatives><mixed-citation xml:lang="ru">Nygard O., Nordrehaug J.E., Refsum H., et al., Plasma homocysteine levels and mortality in patients with coronary artery disease. N Engl J Med, 1997. 337(4): p. 230-6.</mixed-citation><mixed-citation xml:lang="en">Nygard O., Nordrehaug J.E., Refsum H., et al., Plasma homocysteine levels and mortality in patients with coronary artery disease. N Engl J Med, 1997. 337(4): p. 230-6.</mixed-citation></citation-alternatives></ref><ref id="cit44"><label>44</label><citation-alternatives><mixed-citation xml:lang="ru"></mixed-citation><mixed-citation xml:lang="en"></mixed-citation></citation-alternatives></ref><ref id="cit45"><label>45</label><citation-alternatives><mixed-citation xml:lang="ru">Astor B.C., Muntner P., Levin A., et al., Association of kidney function with anemia: the Third National Health and Nutrition Examination Survey (1988-1994). Arch Intern Med, 2002. 162(12): 1401-1408.</mixed-citation><mixed-citation xml:lang="en">Astor B.C., Muntner P., Levin A., et al., Association of kidney function with anemia: the Third National Health and Nutrition Examination Survey (1988-1994). Arch Intern Med, 2002. 162(12): 1401-1408.</mixed-citation></citation-alternatives></ref><ref id="cit46"><label>46</label><citation-alternatives><mixed-citation xml:lang="ru"></mixed-citation><mixed-citation xml:lang="en"></mixed-citation></citation-alternatives></ref><ref id="cit47"><label>47</label><citation-alternatives><mixed-citation xml:lang="ru">Bellamy M.F., McDowell I.F., Ramsey M.W., et al., Hyperhomocysteinemia after an oral methionine load acutely impairs endothelial function in healthy adults. Circulation, 1998. 98(18): 1848-1852.</mixed-citation><mixed-citation xml:lang="en">Bellamy M.F., McDowell I.F., Ramsey M.W., et al., Hyperhomocysteinemia after an oral methionine load acutely impairs endothelial function in healthy adults. Circulation, 1998. 98(18): 1848-1852.</mixed-citation></citation-alternatives></ref><ref id="cit48"><label>48</label><citation-alternatives><mixed-citation xml:lang="ru"></mixed-citation><mixed-citation xml:lang="en"></mixed-citation></citation-alternatives></ref><ref id="cit49"><label>49</label><citation-alternatives><mixed-citation xml:lang="ru">Chambers J.C., McGregor A., Jean-Marie J., et al., Acute hyperhomocysteinaemia and endothelial dysfunction. Lancet, 1998. 351(9095): 36-37.</mixed-citation><mixed-citation xml:lang="en">Chambers J.C., McGregor A., Jean-Marie J., et al., Acute hyperhomocysteinaemia and endothelial dysfunction. Lancet, 1998. 351(9095): 36-37.</mixed-citation></citation-alternatives></ref><ref id="cit50"><label>50</label><citation-alternatives><mixed-citation xml:lang="ru"></mixed-citation><mixed-citation xml:lang="en"></mixed-citation></citation-alternatives></ref><ref id="cit51"><label>51</label><citation-alternatives><mixed-citation xml:lang="ru">Wald D.S., Law M., and Morris J.K., Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis. Bmj, 2002. 325(7374): 1202.</mixed-citation><mixed-citation xml:lang="en">Wald D.S., Law M., and Morris J.K., Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis. Bmj, 2002. 325(7374): 1202.</mixed-citation></citation-alternatives></ref><ref id="cit52"><label>52</label><citation-alternatives><mixed-citation xml:lang="ru"></mixed-citation><mixed-citation xml:lang="en"></mixed-citation></citation-alternatives></ref><ref id="cit53"><label>53</label><citation-alternatives><mixed-citation xml:lang="ru">Wald D.S., Wald N.J., Morris J.K., et al., Folic acid, homocysteine, and cardiovascular disease: judging causality in the face of inconclusive trial evidence. Bmj, 2006. 333(7578): 1114-1117.</mixed-citation><mixed-citation xml:lang="en">Wald D.S., Wald N.J., Morris J.K., et al., Folic acid, homocysteine, and cardiovascular disease: judging causality in the face of inconclusive trial evidence. Bmj, 2006. 333(7578): 1114-1117.</mixed-citation></citation-alternatives></ref><ref id="cit54"><label>54</label><citation-alternatives><mixed-citation xml:lang="ru"></mixed-citation><mixed-citation xml:lang="en"></mixed-citation></citation-alternatives></ref><ref id="cit55"><label>55</label><citation-alternatives><mixed-citation xml:lang="ru">Klerk M., Verhoef P., Clarke R., et al., MTHFR 677C→T polymorphism and risk of coronary heart disease: a meta-analysis. Jama, 2002. 288(16): 2023-20231.</mixed-citation><mixed-citation xml:lang="en">Klerk M., Verhoef P., Clarke R., et al., MTHFR 677C→T polymorphism and risk of coronary heart disease: a meta-analysis. Jama, 2002. 288(16): 2023-20231.</mixed-citation></citation-alternatives></ref><ref id="cit56"><label>56</label><citation-alternatives><mixed-citation xml:lang="ru"></mixed-citation><mixed-citation xml:lang="en"></mixed-citation></citation-alternatives></ref><ref id="cit57"><label>57</label><citation-alternatives><mixed-citation xml:lang="ru">Casas J.P., Bautista L.E., Smeeth L., et al., Homocysteine and stroke: evidence on a causal link from mendelian randomisation. Lancet, 2005. 365(9455): 224-232.</mixed-citation><mixed-citation xml:lang="en">Casas J.P., Bautista L.E., Smeeth L., et al., Homocysteine and stroke: evidence on a causal link from mendelian randomisation. Lancet, 2005. 365(9455): 224-232.</mixed-citation></citation-alternatives></ref><ref id="cit58"><label>58</label><citation-alternatives><mixed-citation xml:lang="ru"></mixed-citation><mixed-citation xml:lang="en"></mixed-citation></citation-alternatives></ref><ref id="cit59"><label>59</label><citation-alternatives><mixed-citation xml:lang="ru">Lewis S.J., Ebrahim S., and Davey Smith G., 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(7524): p. 1053.</mixed-citation><mixed-citation xml:lang="en">Lewis S.J., Ebrahim S., and Davey Smith G., 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(7524): p. 1053.</mixed-citation></citation-alternatives></ref><ref id="cit60"><label>60</label><citation-alternatives><mixed-citation xml:lang="ru"></mixed-citation><mixed-citation xml:lang="en"></mixed-citation></citation-alternatives></ref><ref id="cit61"><label>61</label><citation-alternatives><mixed-citation xml:lang="ru">Cronin S., Furie K.L., and Kelly P.J., Dose-relatedassociation of MTHFR 677T allele with risk of is chemic stroke: evidence from a cumulative meta-analvsis. Stroke, 2005. 36(7):1581-1587.</mixed-citation><mixed-citation xml:lang="en">Cronin S., Furie K.L., and Kelly P.J., Dose-relatedassociation of MTHFR 677T allele with risk of is chemic stroke: evidence from a cumulative meta-analvsis. Stroke, 2005. 36(7):1581-1587.</mixed-citation></citation-alternatives></ref><ref id="cit62"><label>62</label><citation-alternatives><mixed-citation xml:lang="ru"></mixed-citation><mixed-citation xml:lang="en"></mixed-citation></citation-alternatives></ref><ref id="cit63"><label>63</label><citation-alternatives><mixed-citation xml:lang="ru">Ashfield-Watt P.A., Pullin C.H., Whiting J.M., et al., Methylenetetrahydrofolate reductase 677C→T genotype modulate shomocysteine responses to a folate-rich diet or a low-dose folicacid supplement: a randomized controlled trial. Am J Clin Nutr, 2002.76(1):180-186.</mixed-citation><mixed-citation xml:lang="en">Ashfield-Watt P.A., Pullin C.H., Whiting J.M., et al., Methylenetetrahydrofolate reductase 677C→T genotype modulate shomocysteine responses to a folate-rich diet or a low-dose folicacid supplement: a randomized controlled trial. Am J Clin Nutr, 2002.76(1):180-186.</mixed-citation></citation-alternatives></ref><ref id="cit64"><label>64</label><citation-alternatives><mixed-citation xml:lang="ru"></mixed-citation><mixed-citation xml:lang="en"></mixed-citation></citation-alternatives></ref><ref id="cit65"><label>65</label><citation-alternatives><mixed-citation xml:lang="ru">Boushey C.J., Beresford S.A., Omenn G.S., et al., Aquantitative assessment of plasma homocysteine as a risk factor forvascular disease. Probable benefits of increasing folic acid intakes. Jama, 1995.274:1049-1057.</mixed-citation><mixed-citation xml:lang="en">Boushey C.J., Beresford S.A., Omenn G.S., et al., Aquantitative assessment of plasma homocysteine as a risk factor forvascular disease. Probable benefits of increasing folic acid intakes. Jama, 1995.274:1049-1057.</mixed-citation></citation-alternatives></ref><ref id="cit66"><label>66</label><citation-alternatives><mixed-citation xml:lang="ru"></mixed-citation><mixed-citation xml:lang="en"></mixed-citation></citation-alternatives></ref><ref id="cit67"><label>67</label><citation-alternatives><mixed-citation xml:lang="ru">Clarke R., Armitage J., Lewington S., et al., Homocysteine-lowering trials for prevention of vascular disease: protocol for a collaborative meta-analysis. Clin Chem Lab Med, 2007. 45(12): p. 1575-8151.</mixed-citation><mixed-citation xml:lang="en">Clarke R., Armitage J., Lewington S., et al., Homocysteine-lowering trials for prevention of vascular disease: protocol for a collaborative meta-analysis. Clin Chem Lab Med, 2007. 45(12): p. 1575-8151.</mixed-citation></citation-alternatives></ref><ref id="cit68"><label>68</label><citation-alternatives><mixed-citation xml:lang="ru"></mixed-citation><mixed-citation xml:lang="en"></mixed-citation></citation-alternatives></ref><ref id="cit69"><label>69</label><citation-alternatives><mixed-citation xml:lang="ru">Yang Q., Botto L.D., Erickson J.D., et al., Improvement in stroke mortality in Canada and the United States, 1990 to 2002. Circulation. 2006. 113(10): p. 1335-1343.</mixed-citation><mixed-citation xml:lang="en">Yang Q., Botto L.D., Erickson J.D., et al., Improvement in stroke mortality in Canada and the United States, 1990 to 2002. Circulation. 2006. 113(10): p. 1335-1343.</mixed-citation></citation-alternatives></ref><ref id="cit70"><label>70</label><citation-alternatives><mixed-citation xml:lang="ru"></mixed-citation><mixed-citation xml:lang="en"></mixed-citation></citation-alternatives></ref><ref id="cit71"><label>71</label><citation-alternatives><mixed-citation xml:lang="ru">Wang X., Qin X., Demirtas H., et al., Efficacy of folic acid supplementation in stroke prevention: a meta-analysis. Lancet, 2007. 369(9576): p. 1876-1882.</mixed-citation><mixed-citation xml:lang="en">Wang X., Qin X., Demirtas H., et al., Efficacy of folic acid supplementation in stroke prevention: a meta-analysis. Lancet, 2007. 369(9576): p. 1876-1882.</mixed-citation></citation-alternatives></ref><ref id="cit72"><label>72</label><citation-alternatives><mixed-citation xml:lang="ru"></mixed-citation><mixed-citation xml:lang="en"></mixed-citation></citation-alternatives></ref><ref id="cit73"><label>73</label><citation-alternatives><mixed-citation xml:lang="ru">Schnyder G., Roffi M., Pin R., et al., Decreased rate of coronary restenosis after lowering of plasma homocysteine levels. N Engl J Med, 2001. 345(22): 1593-1600.</mixed-citation><mixed-citation xml:lang="en">Schnyder G., Roffi M., Pin R., et al., Decreased rate of coronary restenosis after lowering of plasma homocysteine levels. N Engl J Med, 2001. 345(22): 1593-1600.</mixed-citation></citation-alternatives></ref><ref id="cit74"><label>74</label><citation-alternatives><mixed-citation xml:lang="ru"></mixed-citation><mixed-citation xml:lang="en"></mixed-citation></citation-alternatives></ref><ref id="cit75"><label>75</label><citation-alternatives><mixed-citation xml:lang="ru">Friedman A.N., Bostom A.G., Selhub J., et al., The kidney and homocysteine metabolism. J Am Soc Nephrol, 2001. 12(10): 2181-2819.</mixed-citation><mixed-citation xml:lang="en">Friedman A.N., Bostom A.G., Selhub J., et al., The kidney and homocysteine metabolism. J Am Soc Nephrol, 2001. 12(10): 2181-2819.</mixed-citation></citation-alternatives></ref><ref id="cit76"><label>76</label><citation-alternatives><mixed-citation xml:lang="ru"></mixed-citation><mixed-citation xml:lang="en"></mixed-citation></citation-alternatives></ref><ref id="cit77"><label>77</label><citation-alternatives><mixed-citation xml:lang="ru">Schiffrin E.L., Lipman M.L., and Mann J. F., Chronic kidney disease: effects on the cardiovascular system. Circulation, 2007. 116(1): 85-97.</mixed-citation><mixed-citation xml:lang="en">Schiffrin E.L., Lipman M.L., and Mann J. F., Chronic kidney disease: effects on the cardiovascular system. Circulation, 2007. 116(1): 85-97.</mixed-citation></citation-alternatives></ref><ref id="cit78"><label>78</label><citation-alternatives><mixed-citation xml:lang="ru"></mixed-citation><mixed-citation xml:lang="en"></mixed-citation></citation-alternatives></ref><ref id="cit79"><label>79</label><citation-alternatives><mixed-citation xml:lang="ru">Bostom A.G., Bausserman L., Jacques P.F., et al., Cystatin С as a determinant of fasting plasma total homocysteine levels in coronary artery disease patients with normal serum creatinine. Arterioscler Thromb Vase Biol, 1999. 19(9): 2241-2244.</mixed-citation><mixed-citation xml:lang="en">Bostom A.G., Bausserman L., Jacques P.F., et al., Cystatin С as a determinant of fasting plasma total homocysteine levels in coronary artery disease patients with normal serum creatinine. Arterioscler Thromb Vase Biol, 1999. 19(9): 2241-2244.</mixed-citation></citation-alternatives></ref><ref id="cit80"><label>80</label><citation-alternatives><mixed-citation xml:lang="ru"></mixed-citation><mixed-citation xml:lang="en"></mixed-citation></citation-alternatives></ref><ref id="cit81"><label>81</label><citation-alternatives><mixed-citation xml:lang="ru">Bostom A.G., Homocysteine: "expensive creatinine" or important modifiable risk factor for arteriosclerotic outcomes in renal transplant recipients? J Am Soc Nephrol, 2000. 11(1): p. 149-151.</mixed-citation><mixed-citation xml:lang="en">Bostom A.G., Homocysteine: "expensive creatinine" or important modifiable risk factor for arteriosclerotic outcomes in renal transplant recipients? J Am Soc Nephrol, 2000. 11(1): p. 149-151.</mixed-citation></citation-alternatives></ref><ref id="cit82"><label>82</label><citation-alternatives><mixed-citation xml:lang="ru"></mixed-citation><mixed-citation xml:lang="en"></mixed-citation></citation-alternatives></ref><ref id="cit83"><label>83</label><citation-alternatives><mixed-citation xml:lang="ru">Potter K., Hankey G.J., Green D.J., et al., Homocysteine or Renal Impairment. Which Is the Real Cardiovascular Risk Factor? Arterioscler Thromb Vase Biol, 2008.(in press)</mixed-citation><mixed-citation xml:lang="en">Potter K., Hankey G.J., Green D.J., et al., Homocysteine or Renal Impairment. Which Is the Real Cardiovascular Risk Factor? Arterioscler Thromb Vase Biol, 2008.(in press)</mixed-citation></citation-alternatives></ref><ref id="cit84"><label>84</label><citation-alternatives><mixed-citation xml:lang="ru"></mixed-citation><mixed-citation xml:lang="en"></mixed-citation></citation-alternatives></ref><ref id="cit85"><label>85</label><citation-alternatives><mixed-citation xml:lang="ru">Riccioni G., Bucciarelli Т., Mancini В., et al., Antioxidant vitamin supplementation in cardiovascular diseases. Ann Clin Lab Sci, 2007. 37(l):89-95.</mixed-citation><mixed-citation xml:lang="en">Riccioni G., Bucciarelli Т., Mancini В., et al., Antioxidant vitamin supplementation in cardiovascular diseases. Ann Clin Lab Sci, 2007. 37(l):89-95.</mixed-citation></citation-alternatives></ref><ref id="cit86"><label>86</label><citation-alternatives><mixed-citation xml:lang="ru"></mixed-citation><mixed-citation xml:lang="en"></mixed-citation></citation-alternatives></ref><ref id="cit87"><label>87</label><citation-alternatives><mixed-citation xml:lang="ru">Rossouw J.E., Anderson G.L., Prentice R.L., et al., Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. Jama, 2002. 288(3): 321-333.</mixed-citation><mixed-citation xml:lang="en">Rossouw J.E., Anderson G.L., Prentice R.L., et al., Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. Jama, 2002. 288(3): 321-333.</mixed-citation></citation-alternatives></ref><ref id="cit88"><label>88</label><citation-alternatives><mixed-citation xml:lang="ru"></mixed-citation><mixed-citation xml:lang="en"></mixed-citation></citation-alternatives></ref><ref id="cit89"><label>89</label><citation-alternatives><mixed-citation xml:lang="ru">Rossi R., Grimaldi Т., Origliani G., et al., Menopause and cardiovascular risk. Pathophvsiol Haemost Thromb, 2002.32(5-6): 325-328.</mixed-citation><mixed-citation xml:lang="en">Rossi R., Grimaldi Т., Origliani G., et al., Menopause and cardiovascular risk. Pathophvsiol Haemost Thromb, 2002.32(5-6): 325-328.</mixed-citation></citation-alternatives></ref><ref id="cit90"><label>90</label><citation-alternatives><mixed-citation xml:lang="ru"></mixed-citation><mixed-citation xml:lang="en"></mixed-citation></citation-alternatives></ref><ref id="cit91"><label>91</label><citation-alternatives><mixed-citation xml:lang="ru">Kris-Etherton P.M., Lichtenstein A.H., Howard B.V., et al., Antioxidant vitamin supplements and cardiovascular disease. Circulation, 2004. 110(5):637-641.</mixed-citation><mixed-citation xml:lang="en">Kris-Etherton P.M., Lichtenstein A.H., Howard B.V., et al., Antioxidant vitamin supplements and cardiovascular disease. Circulation, 2004. 110(5):637-641.</mixed-citation></citation-alternatives></ref><ref id="cit92"><label>92</label><citation-alternatives><mixed-citation xml:lang="ru"></mixed-citation><mixed-citation xml:lang="en"></mixed-citation></citation-alternatives></ref><ref id="cit93"><label>93</label><citation-alternatives><mixed-citation xml:lang="ru">Mosca L., Banka C.L., Benjamin E.J., et al., Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. J Am Coll Cardiol, 2007.49(11): 1230-1250.</mixed-citation><mixed-citation xml:lang="en">Mosca L., Banka C.L., Benjamin E.J., et al., Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. J Am Coll Cardiol, 2007.49(11): 1230-1250.</mixed-citation></citation-alternatives></ref><ref id="cit94"><label>94</label><citation-alternatives><mixed-citation xml:lang="ru"></mixed-citation><mixed-citation xml:lang="en"></mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
