Homocysteine and hemostatic disorder as a risk factor for myocardial infarction at a young age.
BACKGROUND
Hyperhomocysteinemia is a coronary risk factor, but its pathophysiologic mechanism remains unclear.


METHODS
The importance of hyperhomocysteinemia in the pathogenesis of early myocardial infarction, was determined in case-control study of 127 men with a first early myocardial infarction <or=45 years and 150 age-matched male controls. We measured plasma concentrations of homocysteine, fibrinogen, antithrombin, tissue factor, tissue factor pathway inhibitor, tissue plasminogen activator, plasminogen activator inhibitor-I, plasminogen, alpha(2)-antiplasmin, lipoprotein(a), protein C, protein S, factor VII, and activated factor VII.


RESULTS
Homocysteine concentrations were higher in patients with early myocardial infarction than in controls (11.2+/-5.3 and 8.3+/-5.0 micromol/l, respectively, P<0.001). Hyperhomocysteinemia was associated with early myocardial infarction (odds ratio=2.22, P<0.001) by multivariate logistic regression analysis. Tissue factor, antithrombin, plasminogen, tissue plasminogen activator, plasminogen activator inhibitor-I, lipoprotein(a), diabetes, and smoking also had associations. In a stepwise logistic regression analysis, hyperhomocysteinemia was the strongest predictor of early myocardial infarction (R(2)=0.19, P<0.001). Hyperhomocysteinemia also had positive correlations with tissue factor (rho=0.26, P=0.009), tissue factor pathway inhibitor (rho=0.23, P=0.020), and tissue plasminogen activator (rho=0.25, P=0.011) in patients with early myocardial infarction, but not in controls.


CONCLUSIONS
Hyperhomocysteinemia is an independent risk factor for early myocardial infarction, and is associated with a hypercoagulable state mediated by the extrinsic coagulation cascade.
Ogawa
Masakazu
M
First Department of Internal Medicine, Faculty of Medicine, Kagoshima University, 8-35-1 Sakuragaoka, 890-8520, Kagoshima, Japan.
Abe
Satoshi
S
Saigo
Masahiko
M
Biro
Sadatoshi
S
Toda
Hitoshi
H
Matsuoka
Tatsuru
T
Torii
Hiroyuki
H
Minagoe
Shinichi
S
Maruyama
Ikuro
I
Tei
Chuwa
C
D000328:Adult; D017668:Age of Onset; D001798:Blood Proteins / Q000032:analysis; D003920:Diabetes Mellitus / Q000453:epidemiology; D006487:Hemostasis; D006801:Humans; D006937:Hypercholesterolemia / Q000453:epidemiology; D020138:Hyperhomocysteinemia / Q000097:blood / Q000150:complications / Q000453:epidemiology*; D007564:Japan / Q000453:epidemiology; D016015:Logistic Models; D008297:Male; D009203:Myocardial Infarction / Q000097:blood / Q000453:epidemiology* / Q000209:etiology; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects / Q000453:epidemiology; D019851:Thrombophilia / Q000097:blood / Q000453:epidemiology* / Q000209:etiology
D001798:Blood Proteins