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

      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.
      ,
      • Eikelboom J.W
      • Lonn E
      • Genest Jr, J
      • et al.
      Homocyst(e)ine and cardiovascular disease a critical review of the epidemiologic evidence.
      ,
      • 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.
      ,
      • Arnesen E
      • Refsum H
      • Bonaa K.H
      • et al.
      Serum total homocysteine and coronary heart disease.
      ,
      • 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.
      ,
      • 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.
      ,
      • 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.
      ,
      • Ridker P.M
      • Manson J.E
      • Buring J.E
      • et al.
      Homocysteine and risk of cardiovascular disease among postmenopausal women.
      ). 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.
      ,
      • 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.
      ,
      • 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.
      ,
      • 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.
      ,
      • Nygard O
      • Nordrehaug J.E
      • Refsum H
      • et al.
      Plasma homocysteine levels and mortality in patients with coronary artery disease.
      ,
      • 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.
      ,
      • Omland T
      • Samuelsson A
      • Hartford M
      • et al.
      Serum homocysteine concentration as an indicator of survival in patients with acute coronary syndromes.
      ,
      • 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.
      ) 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.
      ,
      • 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.
      ,
      • 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.
      ,
      • 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.
      ,
      • Fallon U
      • Ben-Shlomo Y
      • Elwood P
      • et al.
      Homocysteine and coronary heart disease in the Caerphilly cohort a 10 year follow-up.
      ) 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.
      ,
      • Arnesen E
      • Refsum H
      • Bonaa K.H
      • et al.
      Serum total homocysteine and coronary heart disease.
      ,
      • 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.
      ,
      • 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.
      ) 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.
      ,
      • 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.
      ) 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.
      ,
      • 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.
      ,
      • 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.
      ,
      • Nygard O
      • Nordrehaug J.E
      • Refsum H
      • et al.
      Plasma homocysteine levels and mortality in patients with coronary artery disease.
      ,
      • 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.
      ,
      • 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.
      ).
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