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(Circulation. 2000;101:372.)
© 2000 American Heart Association, Inc.

Clinical Investigation and Reports

Relationships Between Homocysteine, Factor VIIa, and Thrombin Generation in Acute Coronary Syndromes

Mohamed K. Al-Obaidi, MRCP; Helen Philippou, PhD; Peter J. Stubbs, MD, MRCP; Antonella Adami, BSc; Rajiv Amersey, MRCP; Mark M. Noble, DSc, PhD; David A. Lane, PhD

From the National Heart and Lung Institute, Cardiology and Haematology departments, Charing Cross Campus, Imperial College School of Medicine, London, UK.

Correspondence to Dr M Al-Obaidi, National Heart and Lung Institute, Royal Brompton Hospital, Sydney Street, London, SW3 6NP, UK. E-mail m.al-obaidi{at}rbh.nthames.nhs.uk

Background—It has been suggested by clinical, epidemiological, and experimental in vitro studies that homocysteine potentiates thrombin generation. This prothrombotic effect however has not previously been demonstrated in patients presenting with acute coronary syndromes (ACS).

Methods and Results—Patients with ACS (n =117) presenting with confirmed acute myocardial infarction (MI) (n =57) or unstable angina pectoris (UAP) (n =60) were consecutively recruited together with patients (n =18) in whom the presenting chest pain was not of cardiac origin (NCP), included as controls. Plasma samples were collected on admission and before clinical intervention. Homocysteine was assayed by high performance liquid chromatography, and both Factor VIIa and prothrombin fragment F1+2 were analyzed by ELISA. There were significant elevations in F1+2 in MI (P<0.001) and UAP (P=0.003), and modest elevations in Factor VIIa in UAP (P<0.05) compared with NCP but no differences in homocysteine levels among those groups. On dividing patients with ACS into quartiles of homocysteine, there was a stepwise increase in F1+2 (P<0.0001) and of Factor VIIa (P<0.05). There were significant correlations in ACS between homocysteine and F1+2 (r=0.46, P<0.0001), homocysteine and Factor VIIa (r=0.24, P<0.01), and F1+2 and Factor VIIa (r=0.41, P<0.0001). There was no correlation between homocysteine and either F1+2 (r=-0.15, P=0.57) or Factor VIIa (r=0.22, P=0.37) in the NCP patients.

Conclusions—Elevated plasma homocysteine is associated with and may cause elevated Factor VIIa and thrombin generation in patients presenting with ACS. These findings suggest an explanation for the prothrombotic effect of homocysteine in ACS.

Key Words: coagulation • risk factors • heart disease • endothelium

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