This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Al-Obaidi, M. K. Articles by Lane, D. A. Search for Related Content PubMed PubMed Citation Articles by Al-Obaidi, M. K. Articles by Lane, D. A. Related Collections Risk Factors Acute coronary syndromes Coagulation and fibronolysis Endothelium/vascular type/nitric oxide

(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

This article has been cited by other articles:

				N. Tyagi, K. C. Sedoris, M. Steed, A. V. Ovechkin, K. S. Moshal, and S. C. Tyagi Mechanisms of homocysteine-induced oxidative stress Am J Physiol Heart Circ Physiol, December 1, 2005; 289(6): H2649 - H2656. [Abstract] [Full Text] [PDF]

				R. H. Samson, Z. Yungst, and D. P. Showalter Homocysteine, a Risk Factor for Carotid Atherosclerosis, Is Not a Risk Factor for Early Recurrent Carotid Stenosis Following Carotid Endarterectomy Vascular and Endovascular Surgery, July 1, 2004; 38(4): 345 - 348. [Abstract] [PDF]

				M. Soinio, J. Marniemi, M. Laakso, S. Lehto, and T. Ronnemaa Elevated Plasma Homocysteine Level Is an Independent Predictor of Coronary Heart Disease Events in Patients with Type 2 Diabetes Mellitus Ann Intern Med, January 20, 2004; 140(2): 94 - 100. [Abstract] [Full Text] [PDF]

				S. Matetzky, D. Freimark, S. Ben-Ami, I. Goldenberg, J. Leor, R. Doolman, I. Novikov, M. Eldar, and H. Hod Association of Elevated Homocysteine Levels With a Higher Risk of Recurrent Coronary Events and Mortality in Patients With Acute Myocardial Infarction Arch Intern Med, September 8, 2003; 163(16): 1933 - 1937. [Abstract] [Full Text] [PDF]

				A. Maseri and D. Cianflone Inflammation in acute coronary syndromes Eur. Heart J. Suppl., March 1, 2002; 4(suppl_B): B8 - B13. [Abstract] [PDF]

				B Chandrasekaran and A S Kurbaan Myocardial infarction with angiographically normal coronary arteries J R Soc Med, January 8, 2002; 95(8): 398 - 400. [Full Text] [PDF]

				M K Al-Obaidi, P J Stubbs, R Amersey, and M I M Noble Acute and convalescent changes in plasma homocysteine concentrations in acute coronary syndromes Heart, April 1, 2001; 85(4): 380 - 384. [Abstract] [Full Text]

				N. H. Badner, W. S. Beattie, D. Freeman, and J. D. Spence Nitrous Oxide-Induced Increased Homocysteine Concentrations Are Associated with Increased Postoperative Myocardial Ischemia in Patients Undergoing Carotid Endarterectomy Anesth. Analg., November 1, 2000; 91(5): 1073 - 1079. [Abstract] [Full Text] [PDF]

				M. K. Al-Obaidi, P. J. Stubbs, P. Collinson, R. Conroy, I. Graham, and M. I. M. Noble Elevated homocysteine levels are associated with increased ischemic myocardial injury in acute coronary syndromes J. Am. Coll. Cardiol., October 1, 2000; 36(4): 1217 - 1222. [Abstract] [Full Text] [PDF]

				P. J. Stubbs, M. K. Al-Obaidi, R. M. Conroy, MusB, P. O. Collinson, MRCPath, I. M. Graham, FRCPI, and M. I. M. Noble Effect of Plasma Homocysteine Concentration on Early and Late Events in Patients With Acute Coronary Syndromes Circulation, August 8, 2000; 102(6): 605 - 610. [Abstract] [Full Text] [PDF]