American Journal of Clinical Nutrition, Vol 59, 940-948, Copyright © 1994 by The American Society for Clinical Nutrition, Inc

ORIGINAL RESEARCH COMMUNICATIONS

Plasma homocyst(e)ine, folate, and vitamin B-12 concentrations and risk for early-onset coronary artery disease [published erratum appears in Am J Clin Nutr 1996 Apr;63(4):609]

N Pancharuniti, CA Lewis, HE Sauberlich, LL Perkins, RC Go, JO Alvarez, M Macaluso, RT Acton, RB Copeland and AL Cousins
Department of Epidemiology, School of Public Health, University of Alabama at Birmingham 35294-0008.

High plasma homocyst(e)ine (Hcy) concentrations may be a determinant of coronary artery disease (CAD). Folate and vitamin B-12 are required for the primary metabolic pathway to reduce Hcy concentrations. The interrelationships of Hcy and these two vitamin cofactors were investigated in a case-control study of 101 white males aged 30-50 y with angiographically demonstrated CAD, and 108 white male, similarly aged, control subjects living in the same community as the patients. The odds ratio (OR) of CAD per quartile increase of plasma Hcy concentration based on control values was 1.6 (95% CI: 1.3, 2.1). After age, HDL and LDL cholesterol, body mass index, smoking, hypertension, and diabetes were controlled for, Hcy remained an independent risk factor (OR: 1.4; 95% CI: 1.0, 2.0). The OR change per quartile increase of folate concentration was 0.8 (95% CI: 0.6, 1.0). This difference was reduced (OR: 0.9; 95% CI: 0.7, 1.2) after Hcy adjustment. No difference in the geometric mean of vitamin B-12 concentration was found between patients and control subjects, both 5.8 nmol/L. However, after Hcy and the other CAD risk factors were controlled for, the OR per quartile increase in vitamin B-12 concentration was 1.5 (95% CI: 1.0, 1.8). Reduction in plasma Hcy by interventions to increase plasma folate concentration may decrease CAD risk.

This article has been cited by other articles:

				D. Vanuzzo, L. Pilotto, R. Lombardi, G. Lazzerini, M. Carluccio, S. Diviacco, F. Quadrifoglio, G. Danek, D. Gregori, P. Fioretti, et al. Both vitamin B6 and total homocysteine plasma levels predict long-term atherothrombotic events in healthy subjects Eur. Heart J., February 2, 2007; 28(4): 484 - 491. [Abstract] [Full Text] [PDF]

				V. Ganji and M. R Kafai Population reference values for plasma total homocysteine concentrations in US adults after the fortification of cereals with folic acid. Am. J. Clinical Nutrition, November 1, 2006; 84(5): 989 - 994. [Abstract] [Full Text] [PDF]

				H.-K. Kuo, F. A. Sorond, J.-H. Chen, A. Hashmi, W. P. Milberg, and L. A. Lipsitz The Role of Homocysteine in Multisystem Age-Related Problems: A Systematic Review J. Gerontol. A Biol. Sci. Med. Sci., September 1, 2005; 60(9): 1190 - 1201. [Abstract] [Full Text] [PDF]

				V. Ganji and M. R. Kafai Population References for Plasma Total Homocysteine Concentrations for U.S. Children and Adolescents in the Post-Folic Acid Fortification Era J. Nutr., September 1, 2005; 135(9): 2253 - 2256. [Abstract] [Full Text] [PDF]

				V. Ganji and M. R Kafai Frequent consumption of milk, yogurt, cold breakfast cereals, peppers, and cruciferous vegetables and intakes of dietary folate and riboflavin but not vitamins B-12 and B-6 are inversely associated with serum total homocysteine concentrations in the US population Am. J. Clinical Nutrition, December 1, 2004; 80(6): 1500 - 1507. [Abstract] [Full Text] [PDF]

				M. Chandalia, N. Abate, A. V. Cabo-Chan Jr., S. Devaraj, I. Jialal, and S. M. Grundy Hyperhomocysteinemia in Asian Indians Living in the United States J. Clin. Endocrinol. Metab., March 1, 2003; 88(3): 1089 - 1095. [Abstract] [Full Text] [PDF]

				X. Wang and M. Fenech A comparison of folic acid and 5-methyltetrahydrofolate for prevention of DNA damage and cell death in human lymphocytes in vitro Mutagenesis, January 1, 2003; 18(1): 81 - 86. [Abstract] [Full Text] [PDF]

				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]

				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]

				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]

				J. Bryan, E. Calvaresi, and D. Hughes Short-Term Folate, Vitamin B-12 or Vitamin B-6 Supplementation Slightly Affects Memory Performance But Not Mood in Women of Various Ages J. Nutr., June 1, 2002; 132(6): 1345 - 1356. [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]

				M.C. Verhaar, E. Stroes, and T.J. Rabelink Folates and Cardiovascular Disease Arterioscler Thromb Vasc Biol, January 1, 2002; 22(1): 6 - 13. [Abstract] [Full Text] [PDF]

				P. Madonna, V. de Stefano, A. Coppola, F. Cirillo, A. M. Cerbone, G. Orefice, and G. Di Minno Hyperhomocysteinemia and Other Inherited Prothrombotic Conditions in Young Adults With a History of Ischemic Stroke Stroke, January 1, 2002; 33(1): 51 - 56. [Abstract] [Full Text] [PDF]

				N. Matsuyama, M. Yamaguchi, M. Toyosato, M. Takayama, and K. Mizuno New Enzymatic Colorimetric Assay for Total Homocysteine Clin. Chem., December 1, 2001; 47(12): 2155 - 2156. [Full Text] [PDF]

				E. Calvaresi and J. Bryan B Vitamins, Cognition, and Aging: A Review J. Gerontol. B. Psychol. Sci. Soc. Sci., November 1, 2001; 56(6): P327 - 339. [Abstract] [Full Text] [PDF]

				K. G Rowley, Q. Su, M. Cincotta, M. Skinner, K. Skinner, B. Pindan, G. A White, and K. O'Dea Improvements in circulating cholesterol, antioxidants, and homocysteine after dietary intervention in an Australian Aboriginal community Am. J. Clinical Nutrition, October 1, 2001; 74(4): 442 - 448. [Abstract] [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]

				K. K. A. Witte, A. L. Clark, and J. G. F. Cleland Chronic heart failure and micronutrients J. Am. Coll. Cardiol., June 1, 2001; 37(7): 1765 - 1774. [Abstract] [Full Text] [PDF]

				G. Liaugaudas, P. F. Jacques, J. Selhub, I. H. Rosenberg, and A. G. Bostom Renal Insufficiency, Vitamin B12 Status, and Population Attributable Risk for Mild Hyperhomocysteinemia Among Coronary Artery Disease Patients in the Era of Folic Acid-Fortified Cereal Grain Flour Arterioscler Thromb Vasc Biol, May 1, 2001; 21(5): 849 - 851. [Abstract] [Full Text] [PDF]

				K. M Koehler, R. N Baumgartner, P. J Garry, R. H Allen, S. P Stabler, and E. B Rimm Association of folate intake and serum homocysteine in elderly persons according to vitamin supplementation and alcohol use Am. J. Clinical Nutrition, March 1, 2001; 73(3): 628 - 637. [Abstract] [Full Text] [PDF]

				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]

				Y. Jang, J. H. Lee, E. Y. Cho, N. S. Chung, D. Topham, and B. Balderston Differences in body fat distribution and antioxidant status in Korean men with cardiovascular disease with or without diabetes Am. J. Clinical Nutrition, January 1, 2001; 73(1): 68 - 74. [Abstract] [Full Text] [PDF]

				R. M. Krauss, R. H. Eckel, B. Howard, L. J. Appel, S. R. Daniels, R. J. Deckelbaum, J. W. Erdman Jr, P. Kris-Etherton, I. J. Goldberg, T. A. Kotchen, et al. AHA Scientific Statement: AHA Dietary Guidelines: Revision 2000: A Statement for Healthcare Professionals From the Nutrition Committee of the American Heart Association J. Nutr., January 1, 2001; 131(1): 132 - 146. [Full Text]

				C. M. Loria, D. D. Ingram, J. J. Feldman, J. D. Wright, and J. H. Madans Serum Folate and Cardiovascular Disease Mortality Among US Men and Women Arch Intern Med, November 27, 2000; 160(21): 3258 - 3262. [Abstract] [Full Text] [PDF]

				R. M. Fleming and L. B. Boyd The Effect of High-Protein Diets on Coronary Blood Flow Angiology, October 1, 2000; 51(10): 817 - 826. [Abstract] [PDF]

				L. Brattstrom and D. E. Wilcken Homocysteine and cardiovascular disease: cause or effect? Am. J. Clinical Nutrition, August 1, 2000; 72(2): 315 - 323. [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]

				L. J Riddell, A. Chisholm, S. Williams, and J. I Mann Dietary strategies for lowering homocysteine concentrations Am. J. Clinical Nutrition, June 1, 2000; 71(6): 1448 - 1454. [Abstract] [Full Text] [PDF]

				W. G. Christen, U. A. Ajani, R. J. Glynn, and C. H. Hennekens Blood Levels of Homocysteine and Increased Risks of Cardiovascular Disease: Causal or Casual? Arch Intern Med, February 28, 2000; 160(4): 422 - 434. [Abstract] [Full Text] [PDF]

				H. H. Yu, R. Joubran, M. Asmi, T. Law, A. Spencer, M. Jouma, and N. Rifai Agreement among Four Homocysteine Assays and Results in Patients with Coronary Atherosclerosis and Controls Clin. Chem., February 1, 2000; 46(2): 258 - 264. [Abstract] [Full Text] [PDF]

				K. ROBINSON Homocysteine, B vitamins, and risk of cardiovascular disease Heart, February 1, 2000; 83(2): 127 - 130. [Full Text]

				H. W. Wilmink, E. S. G. Stroes, W. D. Erkelens, W. B. Gerritsen, R. Wever, J.-D. Banga, and T. J. Rabelink Influence of Folic Acid on Postprandial Endothelial Dysfunction Arterioscler Thromb Vasc Biol, January 1, 2000; 20(1): 185 - 188. [Abstract] [Full Text] [PDF]

				A. Chait, M R. Malinow, D. N Nevin, C. D Morris, R. L Eastgard, P. Kris-Etherton, F X. Pi-Sunyer, S. Oparil, L. M Resnick, J. S Stern, et al. Increased dietary micronutrients decrease serum homocysteine concentrations in patients at high risk of cardiovascular disease Am. J. Clinical Nutrition, November 1, 1999; 70(5): 881 - 887. [Abstract] [Full Text] [PDF]

				P H Whincup, H Refsum, I J Perry, R Morris, M Walker, L Lennon, A Thomson, P M Ueland, and S B J Ebrahim Serum total homocysteine and coronary heart disease: prospective study in middle aged men Heart, October 1, 1999; 82(4): 448 - 454. [Abstract] [Full Text] [PDF]

				A. G. Bostom, L. Bausserman, P. F. Jacques, G. Liaugaudas, J. Selhub, and I. H. Rosenberg Cystatin C as a Determinant of Fasting Plasma Total Homocysteine Levels in Coronary Artery Disease Patients With Normal Serum Creatinine Arterioscler Thromb Vasc Biol, September 1, 1999; 19(9): 2241 - 2244. [Abstract] [Full Text] [PDF]

				S L Tokgözoglu, M Alikasifoglu, I Ünsal, E Atalar, K Aytemir, N Özer, K Övünç, O Usal, S Kes, and E Tunçbilek Methylene tetrahydrofolate reductase genotype and the risk and extent of coronary artery disease in a population with low plasma folate Heart, May 1, 1999; 81(5): 518 - 522. [Abstract] [Full Text]

				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]

				R. Z Stolzenberg-Solomon, E. R Miller III, M. G Maguire, J. Selhub, and L. J Appel Association of dietary protein intake and coffee consumption with serum homocysteine concentrations in an older population Am. J. Clinical Nutrition, March 1, 1999; 69(3): 467 - 475. [Abstract] [Full Text] [PDF]

				I. A Brouwer, M. van Dusseldorp, C. M. Thomas, M. Duran, J. G. Hautvast, T. K. Eskes, and R. P. Steegers-Theunissen Low-dose folic acid supplementation decreases plasma homocysteine concentrations: a randomized trial Am. J. Clinical Nutrition, January 1, 1999; 69(1): 99 - 104. [Abstract] [Full Text] [PDF]

				W. H. Giles, J. B. Croft, K. J. Greenlund, E. S. Ford, and S. J. Kittner Total Homocyst(e)ine Concentration and the Likelihood of Nonfatal Stroke : Results From the Third National Health and Nutrition Examination Survey, 1988–1994 Stroke, December 1, 1998; 29(12): 2473 - 2477. [Abstract] [Full Text] [PDF]

				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]

				H. Morita, H. Kurihara, S.-i. Tsubaki, T. Sugiyama, C. Hamada, Y. Kurihara, T. Shindo, Y. Oh-hashi, K. Kitamura, and Y. Yazaki Methylenetetrahydrofolate Reductase Gene Polymorphism and Ischemic Stroke in Japanese Arterioscler Thromb Vasc Biol, September 1, 1998; 18(9): 1465 - 1469. [Abstract] [Full Text] [PDF]

				D. W. Jacobsen Homocysteine and vitamins in cardiovascular disease Clin. Chem., August 1, 1998; 44(8): 1833 - 1843. [Abstract] [Full Text] [PDF]

				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]

				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]

				G. N. Welch and J. Loscalzo Homocysteine and Atherothrombosis N. Engl. J. Med., April 9, 1998; 338(15): 1042 - 1050. [Full Text] [PDF]

				K. Robinson, K. Arheart, H. Refsum, L. Brattstrom, G. Boers, P. Ueland, P. Rubba, R. Palma-Reis, R. Meleady, L. Daly, et al. Low Circulating Folate and Vitamin B6 Concentrations : Risk Factors for Stroke, Peripheral Vascular Disease, and Coronary Artery Disease Circulation, February 10, 1998; 97(5): 437 - 443. [Abstract] [Full Text] [PDF]

				E. B. Rimm, W. C. Willett, F. B. Hu, L. Sampson, G. A. Colditz, J. E. Manson, C. Hennekens, and M. J. Stampfer Folate and Vitamin B6 From Diet and Supplements in Relation to Risk of Coronary Heart Disease Among Women JAMA, February 4, 1998; 279(5): 359 - 364. [Abstract] [Full Text] [PDF]

				M. H. Moghadasian, B. M. McManus, and J. J. Frohlich Homocyst(e)ine and Coronary Artery Disease: Clinical Evidence and Genetic and Metabolic Background Arch Intern Med, November 10, 1997; 157(20): 2299 - 2308. [Abstract] [PDF]

				K. Kottke-Marchant, R. Green, D. W. Jacobsen, A. Gupta, S. R. Savon, M. Secic, and K. Robinson High Plasma Homocysteine: A Risk Factor for Arterial and Venous Thrombosis in Patients with Normal Coagulation Profiles Clinical and Applied Thrombosis/Hemostasis, October 1, 1997; 3(4): 239 - 244. [Abstract] [PDF]

				P. Durand, M. Prost, and D. Blache Folic Acid Deficiency Enhances Oral Contraceptive-Induced Platelet Hyperactivity Arterioscler Thromb Vasc Biol, October 1, 1997; 17(10): 1939 - 1946. [Abstract] [Full Text]

				O. Nygard, J. E. Nordrehaug, H. Refsum, P. M. Ueland, M. Farstad, and S. E. Vollset Plasma Homocysteine Levels and Mortality in Patients with Coronary Artery Disease N. Engl. J. Med., July 24, 1997; 337(4): 230 - 237. [Abstract] [Full Text] [PDF]

				S. M. Schwartz, D. S. Siscovick, M. R. Malinow, F. R. Rosendaal, R. K. Beverly, D. L. Hess, B. M. Psaty, W. T. Longstreth Jr, T. D. Koepsell, T. E. Raghunathan, et al. Myocardial Infarction in Young Women in Relation to Plasma Total Homocysteine, Folate, and a Common Variant in the Methylenetetrahydrofolate Reductase Gene Circulation, July 15, 1997; 96(2): 412 - 417. [Abstract] [Full Text]

				A. D'Angelo and J. Selhub Homocysteine and Thrombotic Disease Blood, July 1, 1997; 90(1): 1 - 11. [Full Text] [PDF]

				I. M. Graham, L. E. Daly, H. M. Refsum, K. Robinson, L. E. Brattstrom, P. M. Ueland, R. J. Palma-Reis, G. H. J. Boers, R. G. Sheahan, B. Israelsson, et al. Plasma Homocysteine as a Risk Factor for Vascular Disease: The European Concerted Action Project JAMA, June 11, 1997; 277(22): 1775 - 1781. [Abstract] [PDF]

				P. Verhoef, F. J. Kok, D. A.C.M. Kruyssen, E. G. Schouten, J. C.M. Witteman, D. E. Grobbee, P. M. Ueland, and H. Refsum Plasma Total Homocysteine, B Vitamins, and Risk of Coronary Atherosclerosis Arterioscler Thromb Vasc Biol, May 1, 1997; 17(5): 989 - 995. [Abstract] [Full Text]

				H. Morita, J.-i. Taguchi, H. Kurihara, M. Kitaoka, H. Kaneda, Y. Kurihara, K. Maemura, T. Minamino, M. Ohno, K. Yamaoki, et al. Genetic Polymorphism of 5,10-Methylenetetrahydrofolate Reductase (MTHFR) as a Risk Factor for Coronary Artery Disease Circulation, April 15, 1997; 95(8): 2032 - 2036. [Abstract] [Full Text]

				I. Graham and R. Meleady Heart attacks and homocysteine BMJ, December 7, 1996; 313(7070): 1419 - 1420. [Full Text]

				P. M. Gallagher, R. Meleady, D. C. Shields, K. S. Tan, D. McMaster, R. Rozen, A. Evans, I. M. Graham, and A. S. Whitehead Homocysteine and Risk of Premature Coronary Heart Disease: Evidence for a Common Gene Mutation Circulation, November 1, 1996; 94(9): 2154 - 2158. [Abstract] [Full Text]

				H. I. Morrison, D. Schaubel, M. Desmeules, and D. T. Wigle Serum Folate and Risk of Fatal Coronary Heart Disease JAMA, June 26, 1996; 275(24): 1893 - 1896. [Abstract] [PDF]

				M. J. Stampfer and E. B. Rimm Folate and Cardiovascular Disease: Why We Need a Trial Now JAMA, June 26, 1996; 275(24): 1929 - 1930. [Abstract] [PDF]

				F. M.T. Loehrer, C. P. Angst, W. E. Haefeli, P. P. Jordan, R. Ritz, and B. Fowler Low Whole-Blood S-Adenosylmethionine and Correlation Between 5-Methyltetrahydrofolate and Homocysteine in Coronary Artery Disease Arterioscler Thromb Vasc Biol, June 1, 1996; 16(6): 727 - 733. [Abstract] [Full Text]

				K. Robinson, E. L. Mayer, D. P. Miller, R. Green, F. van Lente, A. Gupta, K. Kottke-Marchant, S. R. Savon, J. Selhub, S. E. Nissen, et al. Hyperhomocysteinemia and Low Pyridoxal Phosphate : Common and Independent Reversible Risk Factors for Coronary Artery Disease Circulation, November 15, 1995; 92(10): 2825 - 2830. [Abstract] [Full Text]

				C. J. Boushey, S. A. A. Beresford, G. S. Omenn, and A. G. Motulsky A Quantitative Assessment of Plasma Homocysteine as a Risk Factor for Vascular Disease: Probable Benefits of Increasing Folic Acid Intakes JAMA, October 4, 1995; 274(13): 1049 - 1057. [Abstract] [PDF]

				P. N. Hopkins, L. L. Wu, J. Wu, S. C. Hunt, B. C. James, G. M. Vincent, and R. R. Williams Higher Plasma Homocyst(e)ine and Increased Susceptibility to Adverse Effects of Low Folate in Early Familial Coronary Artery Disease Arterioscler Thromb Vasc Biol, September 1, 1995; 15(9): 1314 - 1320. [Abstract] [Full Text]

				C. Gardner, M. A. Winkleby, and F. E. Viteri Dietary Intake Patterns and Acculturation Levels of Hispanic Immigrant Men: A Pilot Study Hispanic Journal of Behavioral Sciences, August 1, 1995; 17(3): 347 - 361. [Abstract]

				A. Lindgren, L. Brattstrom, B. Norrving, B. Hultberg, A. Andersson, and B. B. Johansson Plasma Homocysteine in the Acute and Convalescent Phases After Stroke Stroke, May 1, 1995; 26(5): 795 - 800. [Abstract] [Full Text]

				M. W. Gillman, L. A. Cupples, D. Gagnon, B. M. Posner, R. C. Ellison, W. P. Castelli, and P. A. Wolf Protective Effect of Fruits and Vegetables on Development of Stroke in Men JAMA, April 12, 1995; 273(14): 1113 - 1117. [Abstract] [PDF]