Plasma homocyst(e)ine, folate, and vitamin B-12 concentrations and risk for early-onset coronary artery disease.

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.

[1]  J. Mason,et al.  The Effects of Vitamins B12, B6, and Folate on Blood Homocysteine Levels a , 1992, Annals of the New York Academy of Sciences.

[2]  W. Willett,et al.  A prospective study of plasma homocyst(e)ine and risk of myocardial infarction in US physicians. , 1992, JAMA.

[3]  D. Wilcken,et al.  Homocystinuria and Atherosclerosis , 1992 .

[4]  R. Clarke,et al.  Hyperhomocysteinemia: an independent risk factor for vascular disease. , 1991, The New England journal of medicine.

[5]  P. Wilson,et al.  Plasma homocyst(e)ine levels in men with premature coronary artery disease. , 1990, Journal of the American College of Cardiology.

[6]  M. Malinow Hyperhomocyst(e)inemia. A common and easily reversible risk factor for occlusive atherosclerosis. , 1990, Circulation.

[7]  M. Malinow,et al.  Elevated plasma homocyst(e)ine concentration as a possible independent risk factor for stroke. , 1990, Stroke.

[8]  L. Taylor,et al.  Prevalence of hyperhomocyst(e)inemia in patients with peripheral arterial occlusive disease. , 1989, Circulation.

[9]  S. S. Kang,et al.  Intermediate homocysteinemia: a thermolabile variant of methylenetetrahydrofolate reductase. , 1988, American journal of human genetics.

[10]  D. Wilcken,et al.  Folic acid lowers elevated plasma homocysteine in chronic renal insufficiency: possible implications for prevention of vascular disease. , 1988, Metabolism: clinical and experimental.

[11]  S. S. Kang,et al.  Thermolabile methylenetetrahydrofolate reductase in patients with coronary artery disease. , 1988, Metabolism: clinical and experimental.

[12]  B. Israelsson,et al.  Homocysteine and myocardial infarction. , 1988, Atherosclerosis.

[13]  D. Heimburger,et al.  Improvement in bronchial squamous metaplasia in smokers treated with folate and vitamin B12. Report of a preliminary randomized, double-blind intervention trial. , 1988, JAMA.

[14]  A. Olszewski,et al.  Homocysteine content of plasma proteins in ischemic heart disease. , 1988, Atherosclerosis.

[15]  E. Podell,et al.  Elevation of total homocysteine in the serum of patients with cobalamin or folate deficiency detected by capillary gas chromatography-mass spectrometry. , 1988, The Journal of clinical investigation.

[16]  L. A. Smolin,et al.  Measurement of total plasma cysteamine using high-performance liquid chromatography with electrochemical detection. , 1988, Analytical biochemistry.

[17]  A. Chait,et al.  The role of sulfur-containing amino acids in superoxide production and modification of low density lipoprotein by arterial smooth muscle cells. , 1987, The Journal of biological chemistry.

[18]  M. Norusis,et al.  Homocysteinemia due to folate deficiency. , 1987, Metabolism: clinical and experimental.

[19]  S. Parthasarathy Oxidation of low-density lipoprotein by thiol compounds leads to its recognition by the acetyl LDL receptor. , 1987, Biochimica et biophysica acta.

[20]  K.,et al.  Protein-bound homocyst(e)ine. A possible risk factor for coronary artery disease. , 1986, The Journal of clinical investigation.

[21]  G. Starkebaum,et al.  Endothelial cell injury due to copper-catalyzed hydrogen peroxide generation from homocysteine. , 1986, The Journal of clinical investigation.

[22]  F. Feit,et al.  Methionine intolerance: a possible risk factor for coronary artery disease. , 1985, Journal of the American College of Cardiology.

[23]  A. Chait,et al.  Iron and copper promote modification of low density lipoprotein by human arterial smooth muscle cells in culture. , 1984, The Journal of clinical investigation.

[24]  D. Wilcken,et al.  Homocysteinemia, ischemic heart disease, and the carrier state for homocystinuria. , 1983, Metabolism: clinical and experimental.

[25]  G. Striker,et al.  Homocysteine-induced endothelial cell injury in vitro: a model for the study of vascular injury. , 1980, Thrombosis research.

[26]  T. Grove Effect of reagent pH on determination of high-density lipoprotein cholesterol by precipitation with sodium phosphotungstate-magnesium. , 1979, Clinical chemistry.

[27]  H. Kondo,et al.  Cobalamin analogues are present in human plasma and can mask cobalamin deficiency because current radioisotope dilution assays are not specific for true cobalamin. , 1978, The New England journal of medicine.

[28]  M. Lopes-Virella,et al.  Cholesterol determination in high-density lipoproteins separated by three different methods. , 1977, Clinical chemistry.

[29]  R. Ross,et al.  Homocystine-induced arteriosclerosis. The role of endothelial cell injury and platelet response in its genesis. , 1976, The Journal of clinical investigation.

[30]  D. Wilcken,et al.  The pathogenesis of coronary artery disease. A possible role for methionine metabolism. , 1976, The Journal of clinical investigation.

[31]  R. Levy,et al.  Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. , 1972, Clinical chemistry.

[32]  W. Vermaak,et al.  Vitamin B-12, vitamin B-6, and folate nutritional status in men with hyperhomocysteinemia. , 1993, The American journal of clinical nutrition.

[33]  M. Malinow,et al.  Hyperhomocyst(e)inemia as a risk factor for occlusive vascular disease. , 1992, Annual review of nutrition.

[34]  L. Taylor,et al.  The association of elevated plasma homocyst(e)ine with progression of symptomatic peripheral arterial disease. , 1991, Journal of vascular surgery.

[35]  K. Hatch,et al.  Evaluation of the deoxyuridine suppression test by using whole blood samples from folic acid-supplemented subjects. , 1990, American Journal of Clinical Nutrition.

[36]  E. Stokstad,et al.  Folic Acid Metabolism In Health And Disease , 1990 .

[37]  Charles R.scriver The Metabolic basis of inherited disease , 1989 .

[38]  S. Mudd Disorders of transsulfuration , 1989 .

[39]  R. Cotran,et al.  The pathogenesis of atherosclerosis: atherogenesis and inflammation. , 1988, Laboratory investigation; a journal of technical methods and pathology.

[40]  A. J. Barr,et al.  SAS user's guide , 1979 .

[41]  V. Vigneaud A trail of research in sulfur chemistry and metabolism, and related fields , 1952 .