© 1995 Oxford University Press
research-article |
Serum Total Homocysteine and Coronary Heart Disease
* Institute of Community Medicine, University of Tromsø MH-building, N-9037 Tromso, Norway
** Clinical Pharmacology Unit, Central Laboratory, Haukeland Hospital, University of Bergen Norway
Department of Heart Disease, Haukeland Hospital, University of Bergen Norway
BACKGROUND: Several studies have observed high plasma levels of homocysteine among patients with coronary heart disease (CHD). The only prospective study was based on US physicians, and concluded that homocysteine was associated with subsequent myocardial infarction (Ml). However, the association was limited to those above a threshold level of homocysteine.
METHODS: We conducted a nested case-control study among the 21 826 subjects, aged 12–61 years, who were surveyed in the municipality of Tromsø, Norway. Among those free from Ml at the screening, 123 later developed CHD. Four controls were selected for each case.
RESULTS: Level of homocysteine was higher in cases than in controls (12.7 ± 4.7 versus 11.3 ± 3.7 µmol/l (mean ± SD); P = 0.002). The relative risk for a 4 µmol/l increase in serum homocysteine was 1.41 (95% confidence interval (Cl): 1.16–1.71). Adjusting for possible confounders reduced the relative risk to 1.32 (95% Cl: 1.05–1.65). There was no threshold level above which serum homocysteine is associated with CHD events.
CONCLUSIONS: In the general population serum total homocysteine is an independent risk factor for CHD with no threshold level.
Keywords Coronary heart disease, serum total homocysteine, nested case-control study, cardiovascular risk factors
Revised 1 January 1995
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S. C. Larsson, S. Mannisto, M. J. Virtanen, J. Kontto, D. Albanes, and J. Virtamo Folate, Vitamin B6, Vitamin B12, and Methionine Intakes and Risk of Stroke Subtypes in Male Smokers Am. J. Epidemiol., April 15, 2008; 167(8): 954 - 961. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Atkinson, J. Elmslie, M. Lever, S. T Chambers, and P. M George Dietary and supplementary betaine: acute effects on plasma betaine and homocysteine concentrations under standard and postmethionine load conditions in healthy male subjects Am. J. Clinical Nutrition, March 1, 2008; 87(3): 577 - 585. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. H. Bonaa, I. Njolstad, P. M. Ueland, H. Schirmer, A. Tverdal, T. Steigen, H. Wang, J. E. Nordrehaug, E. Arnesen, K. Rasmussen, et al. Homocysteine Lowering and Cardiovascular Events after Acute Myocardial Infarction N. Engl. J. Med., April 13, 2006; 354(15): 1578 - 1588. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. B.S. Kazemi, K. Eshraghian, G. R. Omrani, K. B. Lankarani, and E. Hosseini Homocysteine Level and Coronary Artery Disease Angiology, January 1, 2006; 57(1): 9 - 14. [Abstract] [PDF]
|
|
|
|
|
|
M. F. Elias, L. M. Sullivan, R. B. D'Agostino, P. K. Elias, P. F. Jacques, J. Selhub, S. Seshadri, R. Au, A. Beiser, and P. A. Wolf Homocysteine and Cognitive Performance in the Framingham Offspring Study: Age Is Important Am. J. Epidemiol., October 1, 2005; 162(7): 644 - 653. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Nakano, F. A. Taiwo, D. Nugent, H. R. Griffiths, S. Aldred, M. Paisi, M. Kwok, P. Bhatt, M. H. E. Hill, S. Moat, et al. Downstream effects on human low density lipoprotein of homocysteine exported from endothelial cells in an in vitro system J. Lipid Res., March 1, 2005; 46(3): 484 - 493. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Voutilainen, J. K Virtanen, T. H Rissanen, G. Alfthan, J. Laukkanen, K. Nyyssonen, J. Mursu, V.-P. Valkonen, T.-P. Tuomainen, G. A Kaplan, et al. Serum folate and homocysteine and the incidence of acute coronary events: the Kuopio Ischaemic Heart Disease Risk Factor Study Am. J. Clinical Nutrition, August 1, 2004; 80(2): 317 - 323. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-C. Fruchart, M. C. Nierman, E. S. G. Stroes, J. J. P. Kastelein, and P. Duriez New Risk Factors for Atherosclerosis and Patient Risk Assessment Circulation, June 15, 2004; 109(23_suppl_1): III-15 - III-19. [Abstract] [Full Text]
|
|
|
|
 |
|
 R. H Boger When the endothelium cannot say 'NO' anymore: ADMA, an endogenous inhibitor of NO synthase, promotes cardiovascular disease Eur. Heart J., November 1, 2003; 24(21): 1901 - 1902. [Full Text] [PDF]
|
|
|
|
 |
|
 S. Matetzky, D. Freimark, S. Ben-Ami, I. Goldenberg, J. Leor, R. Doolman, I. Novikov, M. Eldar, and H. Hod Association of Elevated Homocysteine Levels With a Higher Risk of Recurrent Coronary Events and Mortality in Patients With Acute Myocardial Infarction Arch Intern Med, September 8, 2003; 163(16): 1933 - 1937. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Must, P. F. Jacques, G. Rogers, I. H. Rosenberg, and J. Selhub Serum Total Homocysteine Concentrations in Children and Adolescents: Results from the Third National Health and Nutrition Examination Survey (NHANES III) J. Nutr., August 1, 2003; 133(8): 2643 - 2649. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. K. Kim, J. M. Ordovas, J. Selhub, and H. Campos B Vitamins and Plasma Homocysteine Concentrations in an Urban and Rural Area of Costa Rica J. Am. Coll. Nutr., June 1, 2003; 22(3): 224 - 231. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Lokk News and Views on Folate and Elderly Persons J. Gerontol. A Biol. Sci. Med. Sci., April 1, 2003; 58(4): M354 - 361. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Meleady, P. M Ueland, H. Blom, A. S Whitehead, H. Refsum, L. E Daly, S. E. Vollset, C. Donohue, B. Giesendorf, I. M Graham, et al. Thermolabile methylenetetrahydrofolate reductase, homocysteine, and cardiovascular disease risk: the European Concerted Action Project Am. J. Clinical Nutrition, January 1, 2003; 77(1): 63 - 70. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
References Circulation, December 17, 2002; 106(25): 3373 - 3421. [Full Text]
|
|
|
|
|
|
U. Lim and P. A. Cassano Homocysteine and Blood Pressure in the Third National Health and Nutrition Examination Survey, 1988-1994 Am. J. Epidemiol., December 15, 2002; 156(12): 1105 - 1113. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Haulrik, S. Toubro, J. Dyerberg, S. Stender, A. R Skov, and A. Astrup Effect of protein and methionine intakes on plasma homocysteine concentrations: a 6-mo randomized controlled trial in overweight subjects Am. J. Clinical Nutrition, December 1, 2002; 76(6): 1202 - 1206. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. De Bree, W. M. M. Verschuren, D. Kromhout, L. A. J. Kluijtmans, and H. J. Blom Homocysteine Determinants and the Evidence to What Extent Homocysteine Determines the Risk of Coronary Heart Disease Pharmacol. Rev., December 1, 2002; 54(4): 599 - 618. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. De Bree, W. M. Verschuren, D. Kromhout, L. I Mennen, H. J Blom, E. S Ford, S J. Smith, D. F Stroup, K. K Steinberg, P. W Mueller, et al. Homocysteine and coronary heart disease: the importance of a distinction between low and high risk subjects Int. J. Epidemiol., December 1, 2002; 31(6): 1268 - 1272. [Full Text] [PDF]
|
|
|
|
 |
|
 C. D. Bushnell and L. B. Goldstein Homocysteine testing in patients with acute ischemic stroke Neurology, November 26, 2002; 59(10): 1541 - 1546. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Stangl, G. Baumann, and K. Stangl Coronary atherogenic risk factors in women Eur. Heart J., November 2, 2002; 23(22): 1738 - 1752. [Full Text] [PDF]
|
|
|
|
 |
|
 Homocysteine Studies Collaboration Homocysteine and Risk of Ischemic Heart Disease and Stroke: A Meta-analysis JAMA, October 23, 2002; 288(16): 2015 - 2022. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. O'Callaghan, R. Meleady, T. Fitzgerald, I. Graham, and European COMAC group Smoking and plasma homocysteine Eur. Heart J., October 2, 2002; 23(20): 1580 - 1586. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A Heuberger, A. I Fisher, P. F Jacques, R. Klein, B. E. Klein, M. Palta, and J. A Mares-Perlman Relation of blood homocysteine and its nutritional determinants to age-related maculopathy in the third National Health and Nutrition Examination Survey Am. J. Clinical Nutrition, October 1, 2002; 76(4): 897 - 902. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Dose-dependent effects of folic acid on plasma homocysteine in a randomized trial conducted among 723 individuals with coronary heart disease Eur. Heart J., October 1, 2002; 23(19): 1509 - 1515. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.L. SHEEN, J.F. DILLON, D.N. BATEMAN, K.J. SIMPSON, and T.M. MACDONALD Paracetamol toxicity: epidemiology, prevention and costs to the health-care system QJM, September 1, 2002; 95(9): 609 - 619. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Q. Hanson, J. H. Eckfeldt, K. Schwichtenberg, O. Aras, and M. Y. Tsai Interlaboratory Variation of Plasma Total Homocysteine Measurements: Results of Three Successive Homocysteine Proficiency Testing Surveys Clin. Chem., September 1, 2002; 48(9): 1539 - 1545. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Weiss, C. Keller, U. Hoffmann, and J. Loscalzo Endothelial dysfunction and atherothrombosis in mild hyperhomocysteinemia Vascular Medicine, August 1, 2002; 7(3): 227 - 239. [Abstract] [PDF]
|
|
|
|
 |
|
 A. E. van Ede, R. F. J. M. Laan, H. J. Blom, G. H. J. Boers, C. J. Haagsma, C. M. G. Thomas, T. M. de Boo, and L. B. A. van de Putte Homocysteine and folate status in methotrexate-treated patients with rheumatoid arthritis Rheumatology, June 1, 2002; 41(6): 658 - 665. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Koyama, T. Usami, O. Takeuchi, K. Morozumi, and G. Kimura Efficacy of methylcobalamin on lowering total homocysteine plasma concentrations in haemodialysis patients receiving high-dose folic acid supplementation Nephrol. Dial. Transplant., May 1, 2002; 17(5): 916 - 922. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. S Ford, S J. Smith, D. F Stroup, K. K Steinberg, P. W Mueller, and S. B Thacker Homocyst(e)ine and cardiovascular disease: a systematic review of the evidence with special emphasis on case-control studies and nested case-control studies Int. J. Epidemiol., February 1, 2002; 31(1): 59 - 70. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Rydlewicz, J.A. Simpson, R.J. Taylor, C.M. Bond, and M.H.N. Golden The effect of folic acid supplementation on plasma homocysteine in an elderly population QJM, January 1, 2002; 95(1): 27 - 35. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M Kerins, M. J Koury, A. Capdevila, S. Rana, and C. Wagner Plasma S-adenosylhomocysteine is a more sensitive indicator of cardiovascular disease than plasma homocysteine Am. J. Clinical Nutrition, December 1, 2001; 74(6): 723 - 729. [Abstract] [Full Text]
|
|
|
|
|
|
B. G. Nedrebo, O. Nygard, P. M. Ueland, and E. A. Lien Plasma Total Homocysteine in Hyper- and Hypothyroid Patients before and during 12 Months of Treatment Clin. Chem., September 1, 2001; 47(9): 1738 - 1741. [Full Text] [PDF]
|
|
|
|
|
|
J. A. Tice, E. Ross, P. G. Coxson, I. Rosenberg, M. C. Weinstein, M. G. M. Hunink, P. A. Goldman, L. Williams, and L. Goldman Cost-effectiveness of Vitamin Therapy to Lower Plasma Homocysteine Levels for the Prevention of Coronary Heart Disease: Effect of Grain Fortification and Beyond JAMA, August 22, 2001; 286(8): 936 - 943. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. McKinley, J.J. Strain, J. McPartlin, J. M. Scott, and H. McNulty Plasma Homocysteine Is Not Subject to Seasonal Variation Clin. Chem., August 1, 2001; 47(8): 1430 - 1436. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Knekt, A. Reunanen, G. Alfthan, M. Heliovaara, H. Rissanen, J. Marniemi, and A. Aromaa Hyperhomocystinemia: A Risk Factor or a Consequence of Coronary Heart Disease? Arch Intern Med, July 9, 2001; 161(13): 1589 - 1594. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. E. Vollset, H. Refsum, A. Tverdal, O. Nygard, J. E. Nordrehaug, G. S Tell, and P. M. Ueland Plasma total homocysteine and cardiovascular and noncardiovascular mortality: the Hordaland Homocysteine Study Am. J. Clinical Nutrition, July 1, 2001; 74(1): 130 - 136. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Aras, M. Y. Tsai, N. Q. Hanson, R. Bailey, G. Rao, and D. B. Hunninghake Cystatin C Is an Independent Predictor of Fasting and Post-Methionine Load Total Homocysteine Concentrations among Stable Renal Transplant Recipients Clin. Chem., July 1, 2001; 47(7): 1263 - 1268. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Thambyrajah, M. J. Landray, H. J. Jones, F. J. McGlynn, D. C. Wheeler, and J. N. Townend A randomized double-blind placebo-controlled trial of the effect of homocysteine-lowering therapy with folic acid on endothelial function in patients with coronary artery disease J. Am. Coll. Cardiol., June 1, 2001; 37(7): 1858 - 1863. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. A.-B. Badawy Moderate alcohol consumption as a cardiovascular risk factor: the role of homocysteine and the need to re-explain the 'French Paradox' Alcohol Alcohol., May 1, 2001; 36(3): 185 - 188. [Full Text] [PDF]
|
|
|
|
|
|
V. Cavalca, G. Cighetti, F. Bamonti, A. Loaldi, L. Bortone, C. Novembrino, M. De Franceschi, R. Belardinelli, and M. D. Guazzi Oxidative Stress and Homocysteine in Coronary Artery Disease Clin. Chem., May 1, 2001; 47(5): 887 - 892. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. G. Federman and R. S. Kirsner An Update on Hypercoagulable Disorders Arch Intern Med, April 23, 2001; 161(8): 1051 - 1056. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Q. Hanson, O. Aras, F. Yang, and M. Y. Tsai C677T and A1298C Polymorphisms of the Methylenetetrahydrofolate Reductase Gene: Incidence and Effect of Combined Genotypes on Plasma Fasting and Post-Methionine Load Homocysteine in Vascular Disease Clin. Chem., April 1, 2001; 47(4): 661 - 666. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U B Fallon, P Elwood, Y Ben-Shlomo, J B Ubbink, R Greenwood, and G D. Smith Homocysteine and ischaemic stroke in men: the Caerphilly study J. Epidemiol. Community Health, February 1, 2001; 55(2): 91 - 96. [Abstract] [Full Text]
|
|
|
|
|
|
S.-M. Saw, J.-M. Yuan, C.-N. Ong, K. Arakawa, H.-P. Lee, G. A Coetzee, and M. C Yu Genetic, dietary, and other lifestyle determinants of plasma homocysteine concentrations in middle-aged and older Chinese men and women in Singapore Am. J. Clinical Nutrition, February 1, 2001; 73(2): 232 - 239. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. de Jong, M. J. C. A Paw, L. C. de Groot, R. A. Rutten, D. W Swinkels, F. J Kok, and W. A van Staveren Nutrient-dense foods and exercise in frail elderly: effects on B vitamins, homocysteine, methylmalonic acid, and neuropsychological functioning Am. J. Clinical Nutrition, February 1, 2001; 73(2): 338 - 346. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U B Fallon, Y Ben-Shlomo, P Elwood, J B Ubbink, and G D. Smith Homocysteine and coronary heart disease in the Caerphilly cohort: a 10 year follow up Heart, February 1, 2001; 85(2): 153 - 158. [Abstract] [Full Text]
|
|
|
|
 |
|
 D. J. Meiklejohn, M. A. Vickers, R. Dijkhuisen, and M. Greaves Plasma Homocysteine Concentrations in the Acute and Convalescent Periods of Atherothrombotic Stroke Stroke, January 1, 2001; 32(1): 57 - 62. [Abstract] [Full Text]
|
|
|
|
|
|
B. K. Nallamothu, A. M. Fendrick, M. Rubenfire, S. Saint, R. R. Bandekar, and G. S. Omenn Potential Clinical and Economic Effects of Homocyst(e)ine Lowering Arch Intern Med, December 11, 2000; 160(22): 3406 - 3412. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. S. Morris, P. F. Jacques, I. H. Rosenberg, J. Selhub, B. A. Bowman, E. W. Gunter, J. D. Wright, and C. L. Johnson Serum Total Homocysteine Concentration Is Related to Self-Reported Heart Attack or Stroke History among Men and Women in the NHANES III J. Nutr., December 1, 2000; 130(12): 3073 - 3076. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Anderson, J. B. Muhlestein, B. D. Horne, J. F. Carlquist, T. L. Bair, T. E. Madsen, and R. R. Pearson Plasma Homocysteine Predicts Mortality Independently of Traditional Risk Factors and C-Reactive Protein in Patients With Angiographically Defined Coronary Artery Disease Circulation, September 12, 2000; 102(11): 1227 - 1232. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. A. McCullough, S. S. Soman, S. S. Shah, S. T. Smith, K. R. Marks, J. Yee, and S. Borzak Risks associated with renal dysfunction in patients in the coronary care unit J. Am. Coll. Cardiol., September 1, 2000; 36(3): 679 - 684. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
J. Thambyrajah, M. J. Landray, F. J. McGlynn, H. J. Jones, D. C. Wheeler, and J. N. Townend Does Folic Acid Decrease Plasma Homocysteine and Improve Endothelial Function in Patients With Predialysis Renal Failure? Circulation, August 22, 2000; 102(8): 871 - 875. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. J. Stubbs, M. K. Al-Obaidi, R. M. Conroy, MusB, P. O. Collinson, MRCPath, I. M. Graham, FRCPI, and M. I. M. Noble Effect of Plasma Homocysteine Concentration on Early and Late Events in Patients With Acute Coronary Syndromes Circulation, August 8, 2000; 102(6): 605 - 610. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. M Ueland, H. Refsum, S. A. Beresford, and S. E. Vollset The controversy over homocysteine and cardiovascular risk Am. J. Clinical Nutrition, August 1, 2000; 72(2): 324 - 332. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. LAIVUORI, R. KAAJA, O. YLIKORKALA, T. HILTUNEN, and K. KONTULA 677 C->T Polymorphism of the Methylenetetrahydrofolate Reductase Gene and Preeclampsia Obstet. Gynecol., August 1, 2000; 96(2): 277 - 280. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. L. Booth, E. E.L. Wang, and with the Canadian Task Force on Preventive Health Preventive health care, 2000 update: screening and management of hyperhomocysteinemia for the prevention of coronary artery disease events Can. Med. Assoc. J., July 1, 2000; 163(1): 21 - 29. [Abstract] [Full Text] [PDF]
|
|