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Plasma total homocysteine levels in postmenopausal women with unstable coronary artery disease

      Abstract

      An elevated plasma total homocysteine (tHcy) level is considered a risk factor for coronary artery disease (CAD), but the relationship between plasma tHcy and well-defined CAD in women is still unclear. Plasma tHcy concentrations and the covariates serum folate, vitamin B12, and creatinine were analysed in 157 angiographically examined postmenopausal women with unstable CAD and in 101 healthy controls. At coronary angiography, 16% had normal vessels and 84% had coronary atherosclerosis. Mean plasma tHcy concentration (μmol/l, 95% confidence interval) did not differ in patients compared to controls (13.1 (12.3–13.8) vs. 12.5 (11.6–13.5)) or in patients with or without coronary atherosclerosis (13.3 (12.4–14.1) vs. 12.0 (10.8–13.2)). A trend to an increasing plasma tHcy with increasing degree of coronary atherosclerosis was attenuated after adjustment for age and the previous mentioned covariates. Odds ratio for the risk of coronary artery disease and coronary atherosclerosis in hyperhomocysteinemic patients (≥90th percentile in controls) was approximately 3. However, the confidence interval included unity in half of the groups and the significance was therefore difficult to judge. Receiver operating characteristics showed age to be the only variable with a significant discriminatory ability regarding the presence of coronary atherosclerosis (area 0.77). Mild hyperhomocysteinemia seems not to be related to the risk of unstable CAD in postmenopausal women. The trend towards higher plasma tHcy with increasing degree of coronary atherosclerosis may be a marker of the disease. In future studies adjustment for age and the other three covariates should be considered.

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      References

        • Mudd S.
        • Levy H.
        • Skovby F.
        Disorders of transulfuration.
        in: Scriver C.R.B.A. Sly W.S. Valle D. The Metabolic Basis of Inherited Disease. 7th ed. McGraw-Hill, New York1995: 1279-1327
        • Ueland P.
        • Refsum H.
        • Brattström L.
        Plasma homocysteine and cardiovascular disease.
        in: Francis Jr R.B. Atherosclerotic Cardiovascular Disease, Hemostasis, and Endothelial Function. Marcel Dekker Inc, New York, NY1992: 183-236
        • Stampfer M.J.
        • Malinow M.R.
        • Willett W.C.
        • et al.
        A prospective study of plasma homocyst(e)ine and risk of myocardial infarction in US physicians.
        J. Am. Med. Assoc. 1992; 268: 877-8781
        • Arnesen E.
        • Refsum H.
        • Bonaa K.H.
        • Ueland P.M.
        • Forde O.H.
        • Nordrehaug J.E.
        Serum total homocysteine and coronary heart disease.
        Int. J. Epidemiol. 1995; 24: 704-709
        • Graham I.M.
        • Daly L.E.
        • Refsum H.M.
        • et al.
        Plasma homocysteine as a risk factor for vascular disease. The European Concerted Action Project.
        J. Am. Med. Assoc. 1997; 277: 1775-1781
        • Boushey C.J.
        • Beresford S.A.
        • Omenn G.S.
        • Motulsky A.G.
        A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakes.
        J. Am. Med. Assoc. 1995; 274: 1049-1057
        • Robinson K.
        • Mayer E.L.
        • Miller D.P.
        • et al.
        Hyperhomocysteinemia and low pyridoxal phosphate. Common and independent reversible risk factors for coronary artery disease.
        Circulation. 1995; 92: 2825-2830
        • Wu L.L.
        • Wu J.
        • Hunt S.C.
        • et al.
        Plasma homocyst(e)ine as a risk factor for early familial coronary artery disease.
        Clin. Chem. 1994; 40: 552-561
        • Mendis S.
        • Athauda S.B.
        • Takashi K.
        Association between hyperhomocysteinemia and ischemic heart disease in Sri Lankans.
        Int. J. Cardiol. 1997; 62: 221-225
        • Schwartz S.M.
        • Siscovick D.S.
        • Malinow M.R.
        • et al.
        Myocardial infarction in young women in relation to plasma total homocysteine, folate, and a common variant in the methylenetetrahydrofolate reductase gene.
        Circulation. 1997; 96: 412-417
        • Murphy-Chutorian D.
        • Alderman E.
        The case that hyperhomocysteinemia is a risk factor for coronary artery disease.
        Am. J. Cardiol. 1994; 73: 705-707
        • Aronow W.S.
        • Ahn C.
        Association between plasma homocysteine and coronary artery disease in older persons.
        Am. J. Cardiol. 1997; 80: 1216-1218
        • Malinow M.
        • Sexton G.
        • Averbuch M.
        • Grossman M.
        • Wilson D.
        • Upson B.
        Homocyst(e)inemia in daily practice: levels in coronary artery disease.
        Coron. Artery Dis. 1990; 1: 215-220
        • Verhoef P.
        • Kok F.J.
        • Kruyssen D.A.
        • et al.
        Plasma total homocysteine, B vitamins, and risk of coronary atherosclerosis.
        Arterioscler. Thromb. Vasc. Biol. 1997; 17: 989-995
        • Bots M.L.
        • Launer L.J.
        • Lindemans J.
        • Hofman A.
        • Grobbee D.E.
        Homocysteine, atherosclerosis and prevalent cardiovascular disease in the elderly: the Rotterdam study.
        J. Int. Med. 1997; 242: 339-347
        • Dalery K.
        • Lussier-Cacan S.
        • Selhub J.
        • Davignon J.
        • Latour Y.
        • Genest J.
        Homocysteine and coronary artery disease in French Canadian subjects: relation with vitamins B12, B6, pyridoxal phosphate, and folate.
        Am. J. Cardiol. 1995; 75: 1107-1111
        • Nygard O.
        • Nordrehaug J.E.
        • Refsum H.
        • Ueland P.M.
        • Farstad M.
        • Vollset S.E.
        Plasma homocysteine levels and mortality in patients with coronary artery disease.
        N. Engl. J. Med. 1997; 337: 230-236
        • Wald N.J.
        • Watt H.C.
        • Law M.R.
        • Weir D.G.
        • McPartlin J.
        • Scott J.M.
        Homocysteine and ischemic heart disease: results of a prospective study with implications regarding prevention.
        Arch. Intern. Med. 1998; 158: 862-867
        • Selhub J.
        • Jacques P.F.
        • Bostom A.G.
        • et al.
        Association between plasma homocysteine concentrations and extracranial carotid-artery stenosis.
        N. Engl. J. Med. 1995; 332: 286-291
        • Perry I.J.
        • Refsum H.
        • Morris R.W.
        • Ebrahim S.B.
        • Ueland P.M.
        • Shaper A.G.
        Prospective study of serum total homocysteine concentration and risk of stroke in middle-aged British men.
        Lancet. 1995; 346: 1395-1398
        • den Heijer M.
        • Blom H.J.
        • Gerrits W.B.
        • et al.
        Is hyperhomocysteinaemia a risk factor for recurrent venous thrombosis.
        Lancet. 1995; 345: 882-885
        • Alfthan G.
        • Pekkanen J.
        • Jauhiainen M.
        • et al.
        Relation of serum homocysteine and lipoprotein(a) concentrations to atherosclerotic disease in a prospective Finnish population based study.
        Atherosclerosis. 1994; 106: 9-19
        • Verhoef P.
        • Hennekens C.H.
        • Allen R.H.
        • Stabler S.P.
        • Willett W.C.
        • Stampfer M.J.
        Plasma total homocysteine and risk of angina pectoris with subsequent coronary artery bypass surgery.
        Am. J. Cardiol. 1997; 79: 799-801
        • Evans R.W.
        • Shaten B.J.
        • Hempel J.D.
        • Cutler J.A.
        • Kuller L.H.
        Homocyst(e)ine and risk of cardiovascular disease in the Multiple Risk Factor Intervention Trial.
        Arterioscler. Thromb. Vasc. Biol. 1997; 17: 1947-1953
        • Donner M.G.
        • Klein G.K.
        • Mathes P.B.
        • Schwandt P.
        • Richter W.O.
        Plasma total homocysteine levels in patients with early-onset coronary heart disease and a low cardiovascular risk profile.
        Metabolism. 1998; 47: 273-279
        • Folsom A.
        • Nieto J.
        • McGovern P.
        • et al.
        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
      1. CASS Study Group. National Heart, Lung and Blood Institute Coronary Artery Surgery Study (CASS), Circulation 1981;63 (Monography 79).

        • Metz C.E.
        Some practical issues of experimental design and data analysis in radiological ROC studies.
        Invest. Radiol. 1989; 24: 234-245
        • Grover S.A.
        • Palmer C.S.
        • Coupal L.
        Serum lipid screening to identify high-risk individuals for coronary death. The results of the Lipid Research Clinics prevalence cohort.
        Arch. Int. Med. 1994; 154: 679-684
        • Grover S.A.
        • Coupal L.
        • Hu X.P.
        Identifying adults at increased risk of coronary disease. How well do the current cholesterol guidelines work.
        J. Am. Med. Assoc. 1995; 274: 801-806
        • Avins A.L.
        • Browner W.S.
        Improving the prediction of coronary heart disease to aid in the management of high cholesterol levels: what a difference a decade makes.
        J. Am. Med. Assoc. 1998; 279: 445-449
        • Zweig M.H.
        Apolipoproteins and lipids in coronary artery disease. Analysis of diagnostic accuracy using receiver operating characteristic plots and areas.
        Arch. Pathol. Lab. Med. 1994; 118: 141-144
      2. Nielsen NE, Olsson A, Swahn E. Plasma lipoprotein particle concentrations in postmenopausal women with unstable coronary artery disease. Analysis of diagnostic accuracy using receiver operating characteristics, J. Int. Med. 1999;in press.

        • Lijmer J.
        • Hunink M.
        • van den Dungen J.
        • Loonstra J.
        • Aj S.
        ROC analysis of noninvasive tests for peripheral arterial disease.
        Ultrasound Med. Biol. 1996; 22: 391-398
      3. Fragmin during Instability in Coronary Artery Disease (FRISC) study group. Low-molecular-weight heparin during instability in coronary artery disease, Lancet 1996;347:561–568.

        • Andersson A.
        • Isaksson A.
        • Brattstrom L.
        • Hultberg B.
        Homocysteine and other thiols determined in plasma by HPLC and thiol-specific postcolumn derivatization.
        Clin. Chem. 1993; 39: 1590-1597
        • Swets J.A.
        Measuring the accuracy of diagnostic systems.
        Science. 1988; 240: 1285-1293
        • Karlsson J.
        • Bjorkholm A.
        • Nylander E.
        • Ohlsson J.
        • Swahn E.
        • Wallentin L.
        ST-changes in ECG at rest or during exercise indicate a high risk of severe coronary lesions after an episode of unstable coronary artery disease.
        Int. J. Cardiol. 1993; 42: 47-55
        • Egerton W.
        • Silberberg J.
        • Crooks R.
        • Ray C.
        • Xie L.
        • Dudman N.
        Serial measures of plasma homocyst(e)ine after acute myocardial infarction.
        Am. J. Card. 1996; 77: 759-761
        • Landgren F.
        • Israelsson B.
        • Lindgren A.
        • Hultberg B.
        • Andersson A.
        • Brattström L.
        Plasma homocysteine in acute myocardial infarction: homocysteine-lowering effect of folic acid.
        J. Int. Med. 1995; 237: 381-388
        • Refsum H.
        • Ueland P.M.
        • Nygard O.
        • Vollset S.E.
        Homocysteine and cardiovascular disease.
        Ann. Rev. Med. 1998; 49: 31-62
      4. Refsum H, Guttormsen A, Fiskerstrand T, Ueland PM. Hyperhomocysteinemia in terms of steady-state kinetics, Eur. J. Pediatr. 1998;157:S45–S49.

      5. Task Force of the European Society of Cardiology. Management of stable angina pectoris. Recommendations of the Task Force of the European Society of Cardiology, Eur. Heart. J. 1997;18:394–413.

        • Brattstrom L.
        • Lindgren A.
        • Israelsson B.
        • Andersson A.
        • Hultberg B.
        Homocysteine and cysteine: determinants of plasma levels in middle-aged and elderly subjects.
        J. Int. Med. 1994; 236: 633-641
        • Frosst P.
        • Blom H.J.
        • Milos R.
        • et al.
        A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase.
        Nat. Genet. 1995; 10 (Letter): 111-113
        • Jacques P.F.
        • Bostom A.G.
        • Williams R.R.
        • et al.
        Relation between folate status, a common mutation in methylenetetrahydrofolate reductase, and plasma homocysteine concentrations.
        Circulation. 1996; 93: 7-9
        • Harmon D.L.
        • Woodside J.V.
        • Yarnell J.W.
        • et al.
        The common ‘thermolabile’ variant of methylene tetrahydrofolate reductase is a major determinant of mild hyperhomocysteinaemia.
        Q. J. Med. 1996; 89: 571-577
        • Ma J.
        • Stampfer M.J.
        • Hennekens C.H.
        • et al.
        Methylenetetrahydrofolate reductase polymorphism, plasma folate, homocysteine, and risk of myocardial infarction in US physicians.
        Circulation. 1996; 94: 2410-2416
        • Verhoef P.
        • Kok F.J.
        • Kluijtmans L.A.
        • et al.
        The 677C-->T mutation in the methylenetetrahydrofolate reductase gene: associations with plasma total homocysteine levels and risk of coronary atherosclerotic disease.
        Atherosclerosis. 1997; 132: 105-113
        • Kluijtmans L.A.
        • Kastelein J.J.
        • Lindemans J.
        • et al.
        Thermolabile methylenetetrahydrofolate reductase in coronary artery disease.
        Circulation. 1997; 96: 2573-2577
        • Brattström L.
        • Wilcken D.
        • Öhrvik 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
        • Brattström L.
        • Zhang Y.
        • Hurtig M.
        • et al.
        A common methylenetetrahydrofolate reductase gene mutation (C677T/MTHFR) and longevity.
        Atherosclerosis. 1998; 141: 315-319