Donate Help Contact The AHA Sign In Home
American Heart Association
Circulation
Search: search_blue_button Advanced Search
« Previous Article | Table of Contents | Next Article »
Circulation. 1999;99:2361-2363

This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bostom, A. G.
Right arrow Articles by Selhub, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bostom, A. G.
Right arrow Articles by Selhub, J.
Related Collections
Right arrow Carotid Stenosis
Right arrow Genomics
Right arrow Risk Factors for Stroke

(Circulation. 1999;99:2361-2363.)
© 1999 American Heart Association, Inc.

Editorial

Homocysteine and Arteriosclerosis

Subclinical and Clinical Disease Associations

Andrew G. Bostom, MD, MS; Jacob Selhub, PhD

From the Division of General Internal Medicine, Memorial Hospital of Rhode Island (A.G.B.), Providence, and Vitamin Bioavailability Laboratory, Jean Mayer USDA Human Nutrition Research Center (A.G.B., J.S.), Boston, Mass.

Correspondence to Andrew G. Bostom, MD, General Internal Medicine, Memorial Hospital of Rhode Island, 111 Brewster St, Pawtucket, RI 02860. E-mail abostom{at}loa.com


Key Words: Editorials • arteriosclerosis • homocysteine • risk factors

In 1969, the clinical observations of McCully1 first linked marked hyperhomocysteinemia (ie, equivalent to total homocysteine [tHcy] levels of 100 to 450 µmol/L by current assays) to precocious arteriosclerotic disease in autopsied children who died from distinct metabolic forms of homocystinuria. Intermittent reports of severe thrombotic outcomes specifically involving the extracranial carotid arteries in homocystinuric patients have been reported dating back at least 20 years.2 3 4 Excepting 2 small but notable studies,5 6 overall a rather consistent body of published data has emerged linking plasma tHcy levels to extracranial carotid artery wall thickening in young adults homozygous7 or heterozygous8 for cystathionine synthase deficiency, among young heterozygotes for familial hypercholesterolemia,9 and in general population samples of middle-aged, asymptomatic individuals free of clinical cardiovascular disease (CVD).10 11 12 13 In addition, tHcy levels have also been associated with more advanced extracranial carotid artery arteriosclerosis (ie, percentage of luminal stenosis) in elderly subjects14 15 16 17 and those with prevalent cerebrovascular disease.18

Thirty years after McCully's initial report,1 a burgeoning amount of clinical evidence has accumulated that indicates that mild to moderate fasting, nonfasting, or post–methionine loading (PML) hyperhomocysteinemia (ie, tHcy levels >=12 to <=100 µmol/L fasting or nonfasting or >=50 to <=140 µmol/L 6 hours PML) is an independent risk factor for hard, arteriosclerotic outcomes. A recent series of pooled observational studies examining the relationship between homocysteine and CVD19 20 21 has been updated through the end of 1998 (Dr S.A.A. Beresford, personal communication). These meta-analyses indicated that the best estimate for the increased risk of arteriosclerotic coronary heart disease morbidity and mortality comparing fasting and or nonfasting tHcy levels of >=15 to <=10 µmol/L, after adjustment for established CVD risk factors, was 1.4. This estimate is unaffected when only prospective studies are analyzed (7 studies, {approx}1400 incident events), including the recently reported Atherosclerosis Risk in Communities22 and British United Provident Association23 cohort studies. More recent prospective data not included in these meta-analyses from the Scottish Heart Health Study24 and US Nurses Health Study25 indicate that tHcy levels were independently predictive of incident coronary heart disease in Scottish women and men, as well as of incident total CVD among middle-aged US women. Three additional prospective studies also not included in these meta-analyses examined the potential association between tHcy levels and CVD mortality. The first 2 of these reports found strong, independent links between tHcy levels and subsequent CVD death in patients with angiographically confirmed coronary artery disease26 or symptomatic peripheral vascular disease,27 whereas the third study found a more modest but significant independent association between tHcy levels and CVD mortality in the elderly population–based Framingham cohort.28 Furthermore, a large, multicenter, European case-control study has confirmed that PML hyperhomocysteinemia confers a risk for prevalent CVD equal in magnitude to and independent of fasting hyperhomocysteinemia.29 Initial prospective follow-up ({approx}4.5 years) of this cohort with prevalent CVD has revealed that postload hyperhomocysteinemia may independently predict subsequent CVD death.30 Finally, 3 prospective studies31 32 33 conducted among persons with end-stage renal disease have yielded concordant findings indicating a significant independent association between baseline tHcy levels and subsequent CVD occurrence in this high-CVD-risk population.

In light of all these data, one could reasonably infer that homocysteine appears to be an independent risk factor for arteriosclerosis across the continuum from subclinical to clinical disease. However, it has been proposed that clinical or even subclinical arteriosclerosis itself somehow raises tHcy levels, resulting in a spurious association between mild hyperhomocysteinemia and clinical CVD due to reverse causality.22 34 35 Devoid of any plausible biological mechanism, this reverse causality hypothesis is not supported by the pooled epidemiological evidence from all published observational studies reviewed above (as opposed to the highly selective citation methods exercised in the studies reported in References 22, 34, and 3522 34 35 ) and the following reported findings from additional human and animal studies:

1. Despite the absence of any traditional CVD risk factors, 50% of untreated children and young adults with homocystinuria due to cystathionine synthase deficiency experience a major atherothrombotic event by the age of 30 years.36 Furthermore, strategies designed solely to reduce tHcy levels in these patients have been shown to decrease atherothrombotic event rates.36 37

2. In adults (n=38; mean age, 58±12 years) with mild hyperhomocysteinemia, tHcy-lowering treatment may have reduced the rate of progression of ultrasound-determined extracranial carotid artery plaque area.38

3. Young, healthy subjects free of clinical arteriosclerosis or CVD risk factors who have normal baseline flow-mediated brachial artery reactivity experience a dramatic "dose-response" reduction in their flow-mediated brachial artery reactivity after acute hyperhomocysteinemia produced by an oral L-methionine load.39

4. Randomized, controlled studies have revealed that mild, dietary-induced hyperhomocysteinemia resulted in abnormal vascular reactivity among nonhuman primates,40 as well as increased arterial stiffness and frank atherothrombotic sequelae in minipigs.41

Although we do not believe the reverse causality hypothesis is tenable, we certainly agree that simultaneous pursuit of 2 related areas of investigation will be required to confirm a causal relationship between hyperhomocysteinemia and CVD: (1) randomized, placebo-controlled trials of the effect of tHcy lowering on recurrent (and perhaps, de novo) CVD outcomes and (2) elucidation of the basic biological mechanism linking hyperhomocysteinemia to arteriosclerosis.

As described in detail elsewhere, well-designed tHcy-lowering trials for secondary CVD outcome prevention are currently under way42 in Europe as well as the United States. The data of McQuillan et al13 in this issue of Circulation suggest the potential use of changes in extracranial carotid artery intimal-medial thickness score as a surrogate end point to gauge the efficacy of tHcy-lowering treatment in clinical trials conducted among individuals free of symptomatic cerebrovascular disease. Analogous studies of lipid lowering that used this noninvasive surrogate end point have added to our understanding of the role of dyslipidemia in the progression of asymptomatic carotid arteriosclerosis.43 Currently, however, in the absence of any data from randomized, controlled trials demonstrating a reduction in CVD outcomes or the progression of subclinical carotid arteriosclerosis with successful treatment of mild hyperhomocysteinemia, we do not believe screening and treatment recommendations for mild hyperhomocysteinemia can or should be provided. This suggestion is concordant with the recently published American Heart Association position paper on homocysteine,44 which emphasized that screening and treatment recommendations for hyperhomocysteinemia in the general population were premature and must await the results of clinical trials of tHcy lowering for secondary or primary CVD outcome prevention.

Acknowledgments

Support for this work was provided in part by the National Heart, Lung, and Blood Institute (grant No. RO1-HL-56908-01A1) and the US Department of Agriculture, Agricultural Research Service contract 53-3KO6-01.

Footnotes

The opinions expressed in this editorial are not necessarily those of the editors or of the American Heart Association. The contents of this article do not necessarily reflect the views or policies of the US Department of Agriculture, nor does mention of trade names, commercial products, or organizations imply endorsement by the US government.

References

  1. McCully KS. Vascular pathology of homocysteinemia. Am J Pathol. 1969;56:111–128.[Medline] [Order article via Infotrieve]
  2. Vandresse JH, de Saint Hubert E, Evrard P. Homocystinuria and carotid arteriography. Neuroradiology. 1978;17:57–58.[Medline] [Order article via Infotrieve]
  3. Wicherink-Bol HF, Boers GH, Drayer JI, Rosenbusch G. Angiographic findings in homocystinuria. Cardiovasc Intervent Radiol. 1983;6:125–128.[Medline] [Order article via Infotrieve]
  4. Lu CY, Hou JW, Wang PJ, Chiu HH, Wang TR. Homocystinuria presenting as fatal common carotid artery occlusion. Pediatr Neurol. 1996;15:159–162.[Medline] [Order article via Infotrieve]
  5. Rubba P, Mercuri M, Faccenda F, Ianuzzi A, Irace C, Strisciuglio P, Gnasso A, Tang R, Andria G, Bond G, Mancini M. Premature carotid atherosclerosis: does it occur in both familial hypercholesterolemia and homocystinuria? Ultrasound assessment of arterial intimal-medial thickness and blood flow velocity. Stroke. 1994;25:943–950.[Abstract]
  6. Smilde TJ, van den Berkmortel FW, Boers GH, Wollersheim H, de Boo T, van Langen H, Stalenhoef AF. 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;18:1958–1963.[Abstract/Free Full Text]
  7. Megnien JL, Gariepy J, Saudubray JM, Nuoffer JM, Denarie N, Levenson J, Simon A. Evidence of carotid artery wall hypertrophy in homozygous homocystinuria. Circulation. 1998;98:2276–2281.[Abstract/Free Full Text]
  8. Clarke R, Fitzgerald D, O'Brien C, O'Farrell C, Roche G, Parker RA, Graham I. Hyperhomocysteinemia: a risk factor for extracranial carotid artery atherosclerosis. Ir J Med Sci. 1992;161:61–65.[Medline] [Order article via Infotrieve]
  9. Tonstad S, Joakimsen O, Stensland-Bugge E, Leren TP, Ose L, Russel D, Bonaa KH. Arterioscler Thromb Vasc Biol. 1996;16:984–991.[Abstract/Free Full Text]
  10. Malinow MR, Nieto FJ, Szklo M, Chambless LE, Bond MG. Carotid artery intimal-medial wall thickening and plasma homocysteine in asymptomatic adults: the Atherosclerosis Risk in Communities Study. Circulation. 1993;87:1107–1113.[Abstract/Free Full Text]
  11. Voutilainen S, Alfthan G, Nyyssonen K, Salonen R, Salonen JT. Association between elevated plasma total homocysteine and increased common carotid artery wall thickness. Ann Med. 1998;30:300–306.[Medline] [Order article via Infotrieve]
  12. Demuth K, Moatti N, Hanon O, Benoit MO, Safar M, Girerd X. Opposite effects of plasma homocysteine and the methylenetetrahydrofolate reductase C677T mutation on carotid artery geometry in asymptomatic adults. Arterioscler Thromb Vasc Biol. 1998;18:1838–1843.[Abstract/Free Full Text]
  13. McQuillan BM, Beilby JP, Nidorf M, Thompson PL, Hung J. The risk of carotid atherosclerosis with hyperhomocysteinemia and the C677T mutation of methylenetetrahydrofolate reductase: the Perth Carotid Ultrasound Assessment Study (CUDAS). Circulation. 1999;99:2383-2388.[Abstract/Free Full Text]
  14. Selhub J, Jacques PF, Bostom AG, D'Agostino RB, Wilson PWF, Belanger AJ, O'Leary DH, Wolf PA, Schaefer EJ, Rosenberg IH. Association between plasma homocysteine concentrations and extracranial carotid-artery stenosis. N Engl J Med. 1995;332:286–291.[Abstract/Free Full Text]
  15. Aronow WS, Ahn C, Schoenfeld MR. Association between plasma homocysteine and extracranial carotid arterial disease in older persons. Am J Cardiol. 1997;79:1432–1433.[Medline] [Order article via Infotrieve]
  16. Sutton-Tyrrell K, Bostom A, Selhub J, Zeigler-Johnson C. High homocysteine levels are independently related to isolated systolic hypertension in older adults. Circulation. 1997;96:1745–1749.[Abstract/Free Full Text]
  17. Bots ML, Launer LJ, Lindemans J, Hofman A, Grobbee DE. Homocysteine, atherosclerosis and prevalent cardiovascular disease in the elderly: the Rotterdam Study. J Intern Med. 1997;242:339–347.[Medline] [Order article via Infotrieve]
  18. Kostulas K, Crisby M, Huang WX, Lannfelt L, Hagenfeldt L, Eggertsen G, Kostulas V, Hillert J. A methylenetetrahydrofolate reductase gene polymorphism in ischemic stroke and in carotid stenosis. Eur J Clin Invest. 1998;28:285–289.[Medline] [Order article via Infotrieve]
  19. Boushey CJ, Beresford SA, Omenn GS, Motulsky A. 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.[Abstract]
  20. Beresford SA, Boushey CJ. Homocysteine, folic acid, and cardiovascular disease risk. In: Bendich A, Deckelbaum RJ, eds. Preventive Nutrition: The Comprehensive Guide for Health Professionals. Totowa, NJ: Humana Press; 1997:193–224.
  21. Omenn GS, Beresford SAA, Motulsky AG. Preventing coronary heart disease: B vitamins and homocysteine. Circulation. 1998;97:421–424.[Free Full Text]
  22. Folsom AR, Nieto FJ, McGovern PG, Tsai MY, Malinow MR, Eckfeldt JH, Hess DL, Davis C. 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;98:204–210.[Abstract/Free Full Text]
  23. Wald NJ, Watt HC, Law MR, Weir DG, McPartlin J, Scott JM. Homocysteine and ischemic heart disease: results of a prospective study with implications regarding prevention. Arch Intern Med. 1998;158:862–867.[Abstract/Free Full Text]
  24. A'Brook R, Tavendale R, Tunstall-Pedoe H. Homocysteine and coronary risk in the general population: analysis from the Scottish Heart Health Study and Scottish MONICA Surveys. Eur Heart J. 1998;19(suppl):8. Abstract.
  25. Ridker PM, Buring JE, Manson JE, Hennekens CH. A prospective study of total plasma homocysteine and the risk of future cardiovascular events among apparently healthy women. Circulation. 1998;98(suppl I):I-810. Abstract.
  26. 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;337:230–236.[Abstract/Free Full Text]
  27. Taylor LM Jr, Moneta GL, Sexton GJ, Schuff RA, Porter JM. Prospective blinded study of the relationship between plasma homocysteine and progression of symptomatic peripheral vascular disease. J Vasc Surg. 1999;29:8–19.[Medline] [Order article via Infotrieve]
  28. Bostom AG, Silbershatz H, Rosenberg IH, Selhub J, D'Agostino RB, Wolf PA, Jacques PF, Wilson PWF. Non-fasting plasma total homocysteine levels and all-cause and cardiovascular disease mortality in elderly Framingham men and women. Arch Intern Med. In press.
  29. Graham IM, Daly LE, Refsum HM, Robinson K, Brattstrom LE, Ueland PM, Palman-Reis FJ, Boers GHJ, Sheahan RG, Israelsson B, Uiterwaal CS, Meleady R, McMaster D, Verhoef P, Witterman J, Rubba P, Bellet H, Wautrecht JC, de Valk HW, Luis ACS, Parrot-Toulaud P, Tan KS, Higgins I, Garcon D, Medrano J, Candito M, Evans AE, Andria G. Plasma homocysteine as a risk factor for vascular disease: the European Concerted Action Project. JAMA. 1997;277:1775–1781.[Abstract]
  30. Meleady R, Lindgren A, Boers GHJ, Reis R, Wautrscht JC, Medrano M-J, Daly L, Graham IM. Plasma homocysteine as a prognostic risk factor for vascular disease. Eur Heart J. 1998;19(suppl):8. Abstract.
  31. Bostom AG, Shemin D, Verhoef P, Nadeau MR, Jacques PF, Selhub J, Dworkin L, Rosenberg IH. Elevated fasting total plasma homocysteine levels and cardiovascular disease outcomes in maintenance dialysis patients: a prospective study. Arterioscler Thromb Vasc Biol. 1997;17:2554–2558.[Abstract/Free Full Text]
  32. Jungers P, Chauveau P, Bandin O, Chadefaux B, Aupetit J, Labrunie M, Descamps-Latscha B, Kamoun P. Hyperhomocysteinemia is associated with atherosclerotic occlusive arterial accidents in predialysis chronic renal failure patients. Miner Electrolyte Metab. 1997;23:170–173.[Medline] [Order article via Infotrieve]
  33. Moustapha A, Naso A, Nahlawi M, Gupta A, Arheart KL, Jacobsen DW, Robinson K, Dennis VW. Prospective study of hyperhomocysteinemia as an adverse cardiovascular risk factor in end-stage renal disease. Circulation. 1998;97:138–141.[Abstract/Free Full Text]
  34. 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;17:1947–1953.[Abstract/Free Full Text]
  35. Brattstrom L, Wilcken DE, Ohrvik J, Brudin L. Common methylenetetrahydrofolate reductase gene mutation leads to hyperhomocysteinemia but not to vascular disease: the result of a meta-analysis. Circulation. 1998;98:2520–2526.[Abstract/Free Full Text]
  36. Mudd SH, Skovby F, Levy HL, Pettigrew KD, Wilcken B, Pyeritz RE, Andria G, Boers GH, Bromberg IL, Cerone R. Natural history of homocystinuria due to cystathionine beta synthase deficiency. Am J Hum Genet. 1985;37:1–25.[Medline] [Order article via Infotrieve]
  37. Wilcken DE. The natural history of vascular disease in homocystinuria and the effects of treatment. J Inherit Metab Dis. 1997;20:295–300.[Medline] [Order article via Infotrieve]
  38. Peterson JC, Spence JD. Vitamins and progression of atherosclerosis in hyperhomocysteinemia. Lancet. 1998;351:263. Letter.[Medline] [Order article via Infotrieve]
  39. Chambers JC, McGregor A, Jean-Marie J, Kooner JS. Acute hyperhomocysteinemia and endothelial dysfunction. Lancet. 1998;351:36–37.[Medline] [Order article via Infotrieve]
  40. Lentz SR, Sobey CG, Piegors DJ, Bhopatkar MY, Faraci FM, Malinow MR, Heistad DD. Vascular dysfunction in monkeys with diet-induced hyperhomocysteinemia. J Clin Invest. 1996;98:328–329.
  41. Rolland PH, Friggi A, Barlaiter A, Piquet P, Latrille V, Faye MM, Guillou J, Charpiot P, Bodard H, Ghiringhelli O, Calaf R, Luccioni R, Garcon D. Hyperhomocysteinemia-induced vascular damage in the minipig. Circulation. 1995;91:1161–1174.[Abstract/Free Full Text]
  42. 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;5:249–255.[Medline] [Order article via Infotrieve]
  43. Hodis HN, Mack WJ, LaBree L, Selzer RH, Liu C, Liu C, Alaupovic P, Kwong-Fu H, Azen SP. Reduction in carotid arterial wall thickness using lovastatin and dietary therapy: a randomized controlled clinical trial. Ann Intern Med. 1996;15:124:548–556.
  44. 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;99:178–182.[Free Full Text]



This article has been cited by other articles:


Home page
 JAMAHome page
R. S. Vasan, A. Beiser, R. B. D'Agostino, D. Levy, J. Selhub, P. F. Jacques, I. H. Rosenberg, and P. W. F. Wilson
Plasma Homocysteine and Risk for Congestive Heart Failure in Adults Without Prior Myocardial Infarction
JAMA, March 12, 2003; 289(10): 1251 - 1257.
[Abstract] [Full Text] [PDF]

Home page
 Diabetes CareHome page
A. N. Friedman, L. G. Hunsicker, J. Selhub, A. G. Bostom, and The Collaborative Study Group
Proteinuria as a Predictor of Total Plasma Homocysteine Levels in Type 2 Diabetic Nephropathy
Diabetes Care, November 1, 2002; 25(11): 2037 - 2041.
[Abstract] [Full Text] [PDF]

Home page
 StrokeHome page
H. Adachi, Y. Hirai, Y. Fujiura, H. Matsuoka, A. Satoh, and T. Imaizumi
Plasma Homocysteine Levels and Atherosclerosis in Japan: Epidemiological Study by Use of Carotid Ultrasonography
Stroke, September 1, 2002; 33(9): 2177 - 2181.
[Abstract] [Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
A. G. Bostom, P. F. Jacques, G. Liaugaudas, G. Rogers, I. H. Rosenberg, and J. Selhub
Total Homocysteine Lowering Treatment Among Coronary Artery Disease Patients in the Era of Folic Acid-Fortified Cereal Grain Flour
Arterioscler. Thromb. Vasc. Biol., March 1, 2002; 22(3): 488 - 491.
[Abstract] [Full Text] [PDF]

Home page
 J Am Coll CardiolHome page
M. G. Shlipak, J. A. Simon, D. Grady, F. Lin, N. K. Wenger, C. D. Furberg, and for the Heart and Estrogen/progestin Replacement S
Renal insufficiency and cardiovascular events in postmenopausal women with coronary heart disease
J. Am. Coll. Cardiol., September 1, 2001; 38(3): 705 - 711.
[Abstract] [Full Text] [PDF]

Home page
 Eur Heart J SupplHome page
M. de Lorgeril, P. Salen, F. Laporte, and J. de Leiris
Alpha-linolenic acid in the prevention and treatment of coronary heart disease
Eur. Heart J. Suppl., June 1, 2001; 3(suppl_D): D26 - D32.
[Abstract] [PDF]

Home page
 CirculationHome page
S. R. Lentz, D. J. Piegors, M. R. Malinow, and D. D. Heistad
Supplementation of Atherogenic Diet With B Vitamins Does Not Prevent Atherosclerosis or Vascular Dysfunction in Monkeys
Circulation, February 20, 2001; 103(7): 1006 - 1011.
[Abstract] [Full Text] [PDF]

Home page
 J Am Coll CardiolHome page
L. M. Title, P. M. Cummings, K. Giddens, J. J. Genest Jr, and B. A. Nassar
Effect of folic acid and antioxidant vitamins on endothelial dysfunction in patients with coronary artery disease
J. Am. Coll. Cardiol., September 1, 2000; 36(3): 758 - 765.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
A. G. BOSTOM
Homocysteine: "Expensive Creatinine" or Important,Modifiable Risk Factor for Arteriosclerotic Outcomes in Renal TransplantRecipients?
J. Am. Soc. Nephrol., January 1, 2000; 11(1): 149 - 151.
[Full Text]

Home page
 Circ. Res.Home page
S. Dayal, T. Bottiglieri, E. Arning, N. Maeda, M. R. Malinow, C. D. Sigmund, D. D. Heistad, F. M. Faraci, and S. R. Lentz
Endothelial Dysfunction and Elevation of S-Adenosylhomocysteine in Cystathionine {beta}-Synthase-Deficient Mice
Circ. Res., June 8, 2001; 88(11): 1203 - 1209.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bostom, A. G.
Right arrow Articles by Selhub, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bostom, A. G.
Right arrow Articles by Selhub, J.
Related Collections
Right arrow Carotid Stenosis
Right arrow Genomics
Right arrow Risk Factors for Stroke

Circulation Home | Subscriptions | Archives | Feedback | Authors | Help | AHA Journals Home | Search
Copyright © 1999 American Heart Association, Inc. All rights reserved. Unauthorized use prohibited.