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Brief observation| Volume 114, ISSUE 8, P685-688, June 01, 2003

Serum homocysteine levels and mortality in outpatients with or without coronary artery disease: an observational study

DOI:https://doi.org/10.1016/S0002-9343(03)00123-2
Serum homocysteine levels and mortality in outpatients with or without coronary artery disease: an observational study
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      Observational studies have shown that homocysteine is an independent predictor of cardiovascular events—fatal and nonfatal coronary artery disease—in several populations (
      • 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.
      JAMA. 1995; 274: 1049-1057
      ,
      • Eikelboom J.W
      • Lonn E
      • Genest Jr, J
      • et al.
      Homocyst(e)ine and cardiovascular disease a critical review of the epidemiologic evidence.
      Ann Intern Medz. 1999; 131: 363-375
      ,
      • 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.
      JAMA. 1992; 268: 877-881
      ,
      • Arnesen E
      • Refsum H
      • Bonaa K.H
      • et al.
      Serum total homocysteine and coronary heart disease.
      Int J Epidemiol. 1995; 24: 704-709
      ,
      • Wald N.J
      • Watt H.C
      • Law M.R
      • et al.
      Homocysteine and ischemic heart disease results of a prospective study with implications regarding prevention.
      Arch Intern Med. 1998; 158: 862-867
      ,
      • Bostom A.G
      • Silbershatz H
      • Rosenberg I.H
      • et al.
      Nonfasting plasma total homocysteine levels and all-cause and cardiovascular disease mortality in elderly Framingham men and women.
      Arch Intern Med. 1999; 159: 1077-1080
      ,
      • Kark J.D
      • Selhub J
      • Adler B
      • et al.
      Nonfasting plasma total homocysteine level and mortality in middle-aged and elderly men and women in Jerusalem.
      Ann Intern Med. 1999; 131: 321-330
      ,
      • Ridker P.M
      • Manson J.E
      • Buring J.E
      • et al.
      Homocysteine and risk of cardiovascular disease among postmenopausal women.
      JAMA. 1999; 281: 1817-1821
      ). The results of prospective studies have not been uniform, however. Whereas eight studies (
      • Eikelboom J.W
      • Lonn E
      • Genest Jr, J
      • et al.
      Homocyst(e)ine and cardiovascular disease a critical review of the epidemiologic evidence.
      Ann Intern Medz. 1999; 131: 363-375
      ,
      • Wald N.J
      • Watt H.C
      • Law M.R
      • et al.
      Homocysteine and ischemic heart disease results of a prospective study with implications regarding prevention.
      Arch Intern Med. 1998; 158: 862-867
      ,
      • Bostom A.G
      • Silbershatz H
      • Rosenberg I.H
      • et al.
      Nonfasting plasma total homocysteine levels and all-cause and cardiovascular disease mortality in elderly Framingham men and women.
      Arch Intern Med. 1999; 159: 1077-1080
      ,
      • Kark J.D
      • Selhub J
      • Adler B
      • et al.
      Nonfasting plasma total homocysteine level and mortality in middle-aged and elderly men and women in Jerusalem.
      Ann Intern Med. 1999; 131: 321-330
      ,
      • Nygard O
      • Nordrehaug J.E
      • Refsum H
      • et al.
      Plasma homocysteine levels and mortality in patients with coronary artery disease.
      N Engl J Med. 1997; 337: 230-236
      ,
      • Taylor Jr, L.M
      • Moneta G.L
      • Sexton G.J
      • et al.
      Prospective blinded study of the relationship between plasma homocysteine and progression of symptomatic peripheral arterial disease.
      J Vasc Surg. 1999; 29: 8-19
      ,
      • Omland T
      • Samuelsson A
      • Hartford M
      • et al.
      Serum homocysteine concentration as an indicator of survival in patients with acute coronary syndromes.
      Arch Intern Med. 2000; 160: 1834-1840
      ,
      • Anderson J.L
      • Muhlestein J.B
      • Horne B.D
      • et al.
      Plasma homocysteine predicts mortality independently of traditional risk factors and C-reactive protein in patients with angiographically defined coronary artery disease.
      Circulation. 2000; 102: 1227-1232
      ) reported that homocysteine was a predictor of cardiovascular disease, five (
      • 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
      ,
      • Chasan-Taber L
      • Selhub J
      • Rosenberg I.H
      • et al.
      A prospective study of folate and vitamin B6 and risk of myocardial infarction in US physicians.
      J Am Coll Nutr. 1996; 15: 136-143
      ,
      • Evans R.W
      • Shaten B.J
      • Hempel J.D
      • et al.
      Homocyst(e)ine and risk of cardiovascular disease in the Multiple Risk Factor Intervention Trial.
      Arterioscler Thromb Vasc Biol. 1997; 17: 1947-1953
      ,
      • Folsom A.R
      • Nieto F.J
      • McGovern P.G
      • 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
      ,
      • Fallon U
      • Ben-Shlomo Y
      • Elwood P
      • et al.
      Homocysteine and coronary heart disease in the Caerphilly cohort a 10 year follow-up.
      Heart. 2001; 85: 153-158
      ) failed to show this association. Most of the studies consisted of large, primarily healthy populations (
      • 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.
      JAMA. 1992; 268: 877-881
      ,
      • Arnesen E
      • Refsum H
      • Bonaa K.H
      • et al.
      Serum total homocysteine and coronary heart disease.
      Int J Epidemiol. 1995; 24: 704-709
      ,
      • Wald N.J
      • Watt H.C
      • Law M.R
      • et al.
      Homocysteine and ischemic heart disease results of a prospective study with implications regarding prevention.
      Arch Intern Med. 1998; 158: 862-867
      ,
      • Bostom A.G
      • Silbershatz H
      • Rosenberg I.H
      • et al.
      Nonfasting plasma total homocysteine levels and all-cause and cardiovascular disease mortality in elderly Framingham men and women.
      Arch Intern Med. 1999; 159: 1077-1080
      ) or patients whose homocysteine levels were measured at the time of coronary angiography (
      • Nygard O
      • Nordrehaug J.E
      • Refsum H
      • et al.
      Plasma homocysteine levels and mortality in patients with coronary artery disease.
      N Engl J Med. 1997; 337: 230-236
      ,
      • Anderson J.L
      • Muhlestein J.B
      • Horne B.D
      • et al.
      Plasma homocysteine predicts mortality independently of traditional risk factors and C-reactive protein in patients with angiographically defined coronary artery disease.
      Circulation. 2000; 102: 1227-1232
      ) and who were followed for cardiovascular events. Few studies have examined total mortality as the primary endpoint (
      • Wald N.J
      • Watt H.C
      • Law M.R
      • et al.
      Homocysteine and ischemic heart disease results of a prospective study with implications regarding prevention.
      Arch Intern Med. 1998; 158: 862-867
      ,
      • Bostom A.G
      • Silbershatz H
      • Rosenberg I.H
      • et al.
      Nonfasting plasma total homocysteine levels and all-cause and cardiovascular disease mortality in elderly Framingham men and women.
      Arch Intern Med. 1999; 159: 1077-1080
      ,
      • Kark J.D
      • Selhub J
      • Adler B
      • et al.
      Nonfasting plasma total homocysteine level and mortality in middle-aged and elderly men and women in Jerusalem.
      Ann Intern Med. 1999; 131: 321-330
      ,
      • Nygard O
      • Nordrehaug J.E
      • Refsum H
      • et al.
      Plasma homocysteine levels and mortality in patients with coronary artery disease.
      N Engl J Med. 1997; 337: 230-236
      ,
      • Taylor Jr, L.M
      • Moneta G.L
      • Sexton G.J
      • et al.
      Prospective blinded study of the relationship between plasma homocysteine and progression of symptomatic peripheral arterial disease.
      J Vasc Surg. 1999; 29: 8-19
      ,
      • Anderson J.L
      • Muhlestein J.B
      • Horne B.D
      • et al.
      Plasma homocysteine predicts mortality independently of traditional risk factors and C-reactive protein in patients with angiographically defined coronary artery disease.
      Circulation. 2000; 102: 1227-1232
      ).
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      References

        • 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.
        JAMA. 1995; 274: 1049-1057
        View in Article
        • Eikelboom J.W
        • Lonn E
        • Genest Jr, J
        • et al.
        Homocyst(e)ine and cardiovascular disease.
        Ann Intern Medz. 1999; 131: 363-375
        View in Article
        • 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.
        JAMA. 1992; 268: 877-881
        View in Article
        • Arnesen E
        • Refsum H
        • Bonaa K.H
        • et al.
        Serum total homocysteine and coronary heart disease.
        Int J Epidemiol. 1995; 24: 704-709
        View in Article
        • Wald N.J
        • Watt H.C
        • Law M.R
        • et al.
        Homocysteine and ischemic heart disease.
        Arch Intern Med. 1998; 158: 862-867
        View in Article
        • Bostom A.G
        • Silbershatz H
        • Rosenberg I.H
        • et al.
        Nonfasting plasma total homocysteine levels and all-cause and cardiovascular disease mortality in elderly Framingham men and women.
        Arch Intern Med. 1999; 159: 1077-1080
        View in Article
        • Kark J.D
        • Selhub J
        • Adler B
        • et al.
        Nonfasting plasma total homocysteine level and mortality in middle-aged and elderly men and women in Jerusalem.
        Ann Intern Med. 1999; 131: 321-330
        View in Article
        • Ridker P.M
        • Manson J.E
        • Buring J.E
        • et al.
        Homocysteine and risk of cardiovascular disease among postmenopausal women.
        JAMA. 1999; 281: 1817-1821
        View in Article
        • Nygard O
        • Nordrehaug J.E
        • Refsum H
        • et al.
        Plasma homocysteine levels and mortality in patients with coronary artery disease.
        N Engl J Med. 1997; 337: 230-236
        View in Article
        • Taylor Jr, L.M
        • Moneta G.L
        • Sexton G.J
        • et al.
        Prospective blinded study of the relationship between plasma homocysteine and progression of symptomatic peripheral arterial disease.
        J Vasc Surg. 1999; 29: 8-19
        View in Article
        • Omland T
        • Samuelsson A
        • Hartford M
        • et al.
        Serum homocysteine concentration as an indicator of survival in patients with acute coronary syndromes.
        Arch Intern Med. 2000; 160: 1834-1840
        View in Article
        • Anderson J.L
        • Muhlestein J.B
        • Horne B.D
        • et al.
        Plasma homocysteine predicts mortality independently of traditional risk factors and C-reactive protein in patients with angiographically defined coronary artery disease.
        Circulation. 2000; 102: 1227-1232
        View in Article
        • 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
        View in Article
        • Chasan-Taber L
        • Selhub J
        • Rosenberg I.H
        • et al.
        A prospective study of folate and vitamin B6 and risk of myocardial infarction in US physicians.
        J Am Coll Nutr. 1996; 15: 136-143
        View in Article
        • Evans R.W
        • Shaten B.J
        • Hempel J.D
        • et al.
        Homocyst(e)ine and risk of cardiovascular disease in the Multiple Risk Factor Intervention Trial.
        Arterioscler Thromb Vasc Biol. 1997; 17: 1947-1953
        View in Article
        • Folsom A.R
        • Nieto F.J
        • McGovern P.G
        • et al.
        Prospective study of coronary heart disease incidence in relation to fasting total homocysteine, related genetic polymorphisms, and B vitamins.
        Circulation. 1998; 98: 204-210
        View in Article
        • Fallon U
        • Ben-Shlomo Y
        • Elwood P
        • et al.
        Homocysteine and coronary heart disease in the Caerphilly cohort.
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      Article Info

      Publication History

      Accepted: December 16, 2002
      Received in revised form: December 6, 2002
      Received: November 13, 2001

      Identification

      DOI: https://doi.org/10.1016/S0002-9343(03)00123-2

      Copyright

      © 2003 Excerpta Medica Inc. Published by Elsevier Inc. All rights reserved.

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