© 1995 Oxford University Press
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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
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J. D. Kark, J. Selhub, B. Adler, J. Gofin, J. H. Abramson, G. Friedman, and I. H. Rosenberg Nonfasting Plasma Total Homocysteine Level and Mortality in Middle-Aged and Elderly Men and Women in Jerusalem Ann Intern Med, September 7, 1999; 131(5): 321 - 330. [Abstract] [Full Text] [PDF]
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J. W. Eikelboom, E. Lonn, J. Genest Jr., G. Hankey, and S. Yusuf Homocyst(e)ine and Cardiovascular Disease: A Critical Review of the Epidemiologic Evidence Ann Intern Med, September 7, 1999; 131(5): 363 - 375. [Abstract] [Full Text] [PDF]
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K. J. Harjai Potential New Cardiovascular Risk Factors: Left Ventricular Hypertrophy, Homocysteine, Lipoprotein(a), Triglycerides, Oxidative Stress, and Fibrinogen Ann Intern Med, September 7, 1999; 131(5): 376 - 386. [Abstract] [Full Text] [PDF]
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P. M. Ridker Evaluating Novel Cardiovascular Risk Factors: Can We Better Predict Heart Attacks? Ann Intern Med, June 1, 1999; 130(11): 933 - 937. [Abstract] [Full Text] [PDF]
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 S. N. Doshi, J. Goodfellow, M. J. Lewis, and I. F.W. McDowell Homocysteine and endothelial function Cardiovasc Res, June 1, 1999; 42(3): 578 - 582. [Full Text] [PDF]
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P. M. Ridker, J. E. Manson, J. E. Buring, J. Shih, M. Matias, and C. H. Hennekens Homocysteine and Risk of Cardiovascular Disease Among Postmenopausal Women JAMA, May 19, 1999; 281(19): 1817 - 1821. [Abstract] [Full Text] [PDF]
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P. F. Jacques, J. Selhub, A. G. Bostom, P. W.F. Wilson, and I. H. Rosenberg The Effect of Folic Acid Fortification on Plasma Folate and Total Homocysteine Concentrations N. Engl. J. Med., May 13, 1999; 340(19): 1449 - 1454. [Abstract] [Full Text] [PDF]
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S. Voutilainen, J. D. Morrow, L. J. Roberts II, G. Alfthan, H. Alho, K. Nyyssonen, and J. T. Salonen Enhanced In Vivo Lipid Peroxidation at Elevated Plasma Total Homocysteine Levels Arterioscler Thromb Vasc Biol, May 1, 1999; 19(5): 1263 - 1266. [Abstract] [Full Text] [PDF]
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J. B. Ubbink, R. Delport, R. Riezler, and W.J. H. Vermaak Comparison of Three Different Plasma Homocysteine Assays with Gas Chromatography–Mass Spectrometry Clin. Chem., May 1, 1999; 45(5): 670 - 675. [Abstract] [Full Text] [PDF]
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K. J. Greenlund, S. R. Srinivasan, J.-H. Xu, E. Dalferes Jr, L. Myers, A. Pickoff, and G. S. Berenson Plasma Homocysteine Distribution and Its Association With Parental History of Coronary Artery Disease in Black and White Children : The Bogalusa Heart Study Circulation, April 27, 1999; 99(16): 2144 - 2149. [Abstract] [Full Text] [PDF]
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S. K. Osganian, M. J. Stampfer, D. Spiegelman, E. Rimm, J. A. Cutler, H. A. Feldman, D. H. Montgomery, L. S. Webber, L. A. Lytle, L. Bausserman, et al. Distribution of and Factors Associated With Serum Homocysteine Levels in Children: Child and Adolescent Trial for Cardiovascular Health JAMA, April 7, 1999; 281(13): 1189 - 1196. [Abstract] [Full Text] [PDF]
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A. Leino Fully Automated Measurement of Total Homocysteine in Plasma and Serum on the Abbott IMx Analyzer Clin. Chem., April 1, 1999; 45(4): 569 - 570. [Full Text] [PDF]
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P. F Jacques, I. H Rosenberg, G. Rogers, J. Selhub, B. A Bowman, E. W Gunter, J. D Wright, and C. L Johnson Serum total homocysteine concentrations in adolescent and adult Americans: results from the third National Health and Nutrition Examination Survey Am. J. Clinical Nutrition, March 1, 1999; 69(3): 482 - 489. [Abstract] [Full Text] [PDF]
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G. B. Anker, H. Refsum, P. M. Ueland, D. C. Johannessen, E. A. Lien, and P. E. Lonning Influence of Aromatase Inhibitors on Plasma Total Homocysteine in Postmenopausal Breast Cancer Patients Clin. Chem., February 1, 1999; 45(2): 252 - 256. [Abstract] [Full Text] [PDF]
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M. R. Malinow, A. G. Bostom, and R. M. Krauss Homocyst(e)ine, Diet, and Cardiovascular Diseases : A Statement for Healthcare Professionals From the Nutrition Committee, American Heart Association Circulation, January 12, 1999; 99(1): 178 - 182. [Full Text] [PDF]
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M. L. Bots, L. J. Launer, J. Lindemans, A. W. Hoes, A. Hofman, J. C. M. Witteman, P. J. Koudstaal, and D. E. Grobbee Homocysteine and Short-term Risk of Myocardial Infarction and Stroke in the Elderly: The Rotterdam Study Arch Intern Med, January 11, 1999; 159(1): 38 - 44. [Abstract] [Full Text] [PDF]
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L. Brattstrom, D. E. L. Wilcken, J. Ohrvik, and L. Brudin Common Methylenetetrahydrofolate Reductase Gene Mutation Leads to Hyperhomocysteinemia but Not to Vascular Disease : The Result of a Meta-Analysis Circulation, December 8, 1998; 98(23): 2520 - 2526. [Abstract] [Full Text] [PDF]
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C. D. A. Stehouwer, M. P. Weijenberg, M. van den Berg, C. Jakobs, E. J. M. Feskens, and D. Kromhout Serum Homocysteine and Risk of Coronary Heart Disease and Cerebrovascular Disease in Elderly Men : A 10-Year Follow-Up Arterioscler Thromb Vasc Biol, December 1, 1998; 18(12): 1895 - 1901. [Abstract] [Full Text] [PDF]
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T. J. Smilde, F. W. P. J. van den Berkmortel, G. H. J. Boers, H. Wollersheim, T. de Boo, H. van Langen, and A. F. H. Stalenhoef Carotid and Femoral Artery Wall Thickness and Stiffness in Patients at Risk for Cardiovascular Disease, With Special Emphasis on Hyperhomocysteinemia Arterioscler Thromb Vasc Biol, December 1, 1998; 18(12): 1958 - 1963. [Abstract] [Full Text] [PDF]
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J.-L. Megnien, J. Gariepy, J.-M. Saudubray, J.-M. Nuoffer, N. Denarie, J. Levenson, and A. Simon Evidence of Carotid Artery Wall Hypertrophy in Homozygous Homocystinuria Circulation, November 24, 1998; 98(21): 2276 - 2281. [Abstract] [Full Text] [PDF]
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 Z. Chen and R. Banerjee Purification of Soluble Cytochrome b5 as a Component of the Reductive Activation of Porcine Methionine Synthase J. Biol. Chem., October 2, 1998; 273(40): 26248 - 26255. [Abstract] [Full Text] [PDF]
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P. W. Siri, P. Verhoef, and F. J. Kok Vitamins B6, B12, and Folate: Association with Plasma Total Homocysteine and Risk of Coronary Atherosclerosis J. Am. Coll. Nutr., October 1, 1998; 17(5): 435 - 441. [Abstract] [Full Text] [PDF]
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D. W. Jacobsen Homocysteine and vitamins in cardiovascular disease Clin. Chem., August 1, 1998; 44(8): 1833 - 1843. [Abstract] [Full Text] [PDF]
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A. R. Folsom, F. J. Nieto, P. G. McGovern, M. Y. Tsai, M. R. Malinow, J. H. Eckfeldt, D. L. Hess, and C. E. Davis 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, July 21, 1998; 98(3): 204 - 210. [Abstract] [Full Text] [PDF]
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D. A. J. Brouwer, H. T. M. E. Welten, D.-J. Reijngoud, J. J. van Doormaal, and F. A. J. Muskiet Plasma folic acid cutoff value, derived from its relationship with homocyst(e)ine Clin. Chem., July 1, 1998; 44(7): 1545 - 1550. [Abstract] [Full Text] [PDF]
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J. H. Stein and P. E. McBride Hyperhomocysteinemia and Atherosclerotic Vascular Disease: Pathophysiology, Screening, and Treatment Arch Intern Med, June 22, 1998; 158(12): 1301 - 1306. [Abstract] [Full Text] [PDF]
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N. J. Wald, H. C. Watt, M. R. Law, D. G. Weir, J. McPartlin, and J. M. Scott Homocysteine and Ischemic Heart Disease: Results of a Prospective Study With Implications Regarding Prevention Arch Intern Med, April 27, 1998; 158(8): 862 - 867. [Abstract] [Full Text] [PDF]
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