From the Department of Clinical Epidemiology, Department of Cardiology,
Hemostasis and Thrombosis Research Center, Leiden University Hospital,
Netherlands.
Correspondence to Prof Dr Frits R. Rosendaal, Department of Clinical Epidemiology, Leiden University Hospital, Bldg 1:CO-P, PO Box 9600, 2300 RC Leiden, Netherlands. E-mail rosendaal{at}rullf2.medfac.leidenuniv.nl
Background—A genetic variation
located in the 3'-untranslated region of the prothrombin gene
(prothrombin 20210 G
Methods and Results—Among 560 men with a first myocardial
infarction before the age of 70 years, 1.8% were heterozygous carriers
of the 20210 variant of the prothrombin gene. The control group
consisted of 646 men who were frequency matched by age. In the latter
group, the frequency of the 20210 AG genotype was 1.2%. The
risk of myocardial infarction in the presence of the AG
genotype was increased by 50% (odds ratio, 1.5; 95%
confidence interval [95% CI], 0.6 to 3.8). The risk of myocardial
infarction for carriership of factor V Leiden mutation was increased by
40% (odds ratio, 1.4; 95% CI, 0.8 to 2.2). When a coagulation defect
was present (ie, the 20210 AG prothrombin genotype or the
factor V Leiden mutation), the risk of myocardial infarction for
carriers versus noncarriers was 1.4 (95% CI, 0.9 to 2.2). This risk
was substantially increased when one of the major
cardiovascular risk factors of smoking, hypertension,
diabetes mellitus, or obesity also was present, with odds ratios
varying between 3 and 6. These risks exceeded those of the single
effects of the cardiovascular risk factors (ie, in the
absence of the coagulation defect).
Conclusions—We conclude that in men the 20210 G
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
Interaction of Coagulation Defects and Cardiovascular Risk Factors
Increased Risk of Myocardial Infarction Associated With Factor V Leiden or Prothrombin 20210A
A) was recently described as a risk factor for
venous thrombosis. We examined how the presence of this mutation
affected the risk of myocardial infarction in a population-based
case-control study. Furthermore, we studied the risk of myocardial
infarction associated with the simultaneous presence of a
coagulation defect (ie, the 20210 AG genotype of prothrombin or
the factor V Leiden mutation) and major cardiovascular
risk factors. A variant of
prothrombin is associated with an increased risk of myocardial
infarction. The combined presence of major
cardiovascular risk factors and carriership of a
coagulation defect increases the risk considerably.
Key Words: myocardial infarction • coagulation • thrombosis • genetics • risk factors
This article has been cited by other articles:
 |
|
 |
|
  O. A. Iakoubova, C. H. Tong, C. M. Rowland, T. G. Kirchgessner, B. A. Young, A. R. Arellano, D. Shiffman, M. S. Sabatine, H. Campos, C. J. Packard, et al. Association of the Trp719Arg polymorphism in kinesin-like protein 6 with myocardial infarction and coronary heart disease in 2 prospective trials: the CARE and WOSCOPS trials. J. Am. Coll. Cardiol., January 29, 2008; 51(4): 435 - 443. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Koestenberger, B. Nagel, A. Gamillscheg, W. Temmel, G. Cvirn, and A. Beitzke Myocardial Infarction in an Adolescent: Anomalous Origin of the Left Main Coronary Artery From the Right Coronary Sinus in Association With Combined Prothrombotic Defects Pediatrics, August 1, 2007; 120(2): e424 - e427. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Stephenson, L. J. Toltl, S. Beaudin, and P. C. Liaw Modulation of Monocyte Function by Activated Protein C, a Natural Anticoagulant J. Immunol., August 15, 2006; 177(4): 2115 - 2122. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. V. Podgoreanu and D. A. Schwinn New Paradigms in Cardiovascular Medicine: Emerging Technologies and Practices: Perioperative Genomics J. Am. Coll. Cardiol., December 6, 2005; 46(11): 1965 - 1977. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. C.M. Jansen, E. S. van Aalst-Cohen, M. W.T. Tanck, S. Cheng, M. R. Fontecha, J. Li, J. C. Defesche, and J. J.P. Kastelein Genetic Determinants of Cardiovascular Disease Risk in Familial Hypercholesterolemia Arterioscler. Thromb. Vasc. Biol., July 1, 2005; 25(7): 1475 - 1481. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. K. MacCallum Markers of Hemostasis and Systemic Inflammation in Heart Disease and Atherosclerosis in Smokers Proceedings of the ATS, April 1, 2005; 2(1): 34 - 43. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Wolak, B. Rogachev, D. Tovbin, Y. Hertzanu, M. Zlotnik, and G. Lugassy Renal vein thrombosis as a presenting symptom of multiple genetic pro-coagulant defects Nephrol. Dial. Transplant., April 1, 2005; 20(4): 827 - 829. [Full Text] [PDF]
|
|
|
|
 |
|
 C. M. Johnson, L. Mureebe, and D. Silver Hypercoagulable States: A Review Vascular and Endovascular Surgery, March 1, 2005; 39(2): 123 - 133. [Abstract] [PDF]
|
|
|
|
 |
|
 A. Pezzini, M. Grassi, E. D. Zotto, S. Archetti, R. Spezi, V. Vergani, D. Assanelli, L. Caimi, and A. Padovani Cumulative Effect of Predisposing Genotypes and Their Interaction With Modifiable Factors on the Risk of Ischemic Stroke in Young Adults Stroke, March 1, 2005; 36(3): 533 - 539. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M S Mahonen, P McElduff, A J Dobson, K A Kuulasmaa, and A E Evans Current smoking and the risk of non-fatal myocardial infarction in the WHO MONICA Project populations Tob. Control, September 1, 2004; 13(3): 244 - 250. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. D Walker Masterclass series in peripheral arterial disease: Inherited thrombophilia Vascular Medicine, August 1, 2004; 9(3): 219 - 221. [PDF]
|
|
|
|
|
|
N. Carano, A. Agnetti, D. J. Hagler, B. Tchana, U. Squarcia, and S. Bernasconi Acute Myocardial Infarction in a Child: Possible Pathogenic Role of Patent Foramen Ovale Associated With Heritable Thrombophilia Pediatrics, August 1, 2004; 114(2): e255 - e258. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Pullmann Jr, M. Skerenova, J. Lukac, J. Hybenova, V. Melus, P. Kubisz, J. Rovensky, and R. Pullmann Factor V Leiden and Prothrombin G20210A Mutations and the Risk of Atherothrombotic Events in Systemic Lupus Erythematosus Clinical and Applied Thrombosis/Hemostasis, July 1, 2004; 10(3): 233 - 238. [Abstract] [PDF]
|
|
|
|
|
|
B. Voetsch and J. Loscalzo Genetic Determinants of Arterial Thrombosis Arterioscler. Thromb. Vasc. Biol., February 1, 2004; 24(2): 216 - 229. [Abstract] [Full Text]
|
|
|
|
 |
|
 B Granel, J Serratrice, N Ene, P E Morange, P Disdier, and P-J Weiller Juvenile temporal arteritis and activated protein C resistance Ann Rheum Dis, February 1, 2004; 63(2): 215 - 216. [Full Text] [PDF]
|
|
|
|
 |
|
 N. von Ahsen and M. Oellerich The intronic prothrombin 19911A>G polymorphism influences splicing efficiency and modulates effects of the 20210G>A polymorphism on mRNA amount and expression in a stable reporter gene assay system Blood, January 15, 2004; 103(2): 586 - 593. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F Burzotta, K Paciaroni, V De Stefano, F Crea, A Maseri, G Leone, and F Andreotti G20210A Prothrombin gene polymorphism and coronary ischaemic syndromes: a phenotype-specific meta-analysis of 12 034 subjects Heart, January 1, 2004; 90(1): 82 - 86. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Colussi, S. W. Hall, and E. G. Nabel Cardiovascular Genomics N. Engl. J. Med., October 2, 2003; 349(14): 1387 - 1388. [Full Text] [PDF]
|
|
|
|
|
|
P. M. Mannucci, D. Ardissino, P. A. Merlini, F. Peyvandi, Y.-G. Xie, C. Butt, and E. Randell Vagaries of genetic association studies in myocardial infarction Blood, August 15, 2003; 102(4): 1558 - 1560. [Full Text] [PDF]
|
|
|
|
 |
|
 M. Erali, B. Schmidt, E. Lyon, and C. Wittwer Evaluation of Electronic Microarrays for Genotyping Factor V, Factor II, and MTHFR Clin. Chem., May 1, 2003; 49(5): 732 - 739. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Butt, H. Zheng, E. Randell, D. Robb, P. Parfrey, and Y.-G. Xie Combined carrier status of prothrombin 20210A and factor XIII-A Leu34 alleles as a strong risk factor for myocardial infarction: evidence of a gene-gene interaction Blood, April 15, 2003; 101(8): 3037 - 3041. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B.C Tanis Oral contraceptives and the risk of myocardial infarction Eur. Heart J., March 1, 2003; 24(5): 377 - 380. [Full Text] [PDF]
|
|
|
|
|
|
I Y Tiong, M L Alkotob, and S Ghaffari Protein C deficiency manifesting as an acute myocardial infarction and ischaemic stroke Heart, February 1, 2003; 89(2): e7 - 7. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. L Ruberg and J. Loscalzo Prothrombotic determinants of coronary atherothrombosis Vascular Medicine, November 1, 2002; 7(4): 289 - 299. [Abstract] [PDF]
|
|
|
|
 |
|
 F-J Munoz-Rodriguez, J-C Reverter, J Font, D Tassies, G Espinosa, R Cervera, F Carmona, J Balasch, M Ingelmo, and A Ordinas Clinical significance of acquired activated protein C resistance in patients with systemic lupus erythematosus Lupus, November 1, 2002; 11(11): 730 - 735. [Abstract] [PDF]
|
|
|
|
|
|
E. Sehnal and J. Slany Fibrinogen--the key to familial CHD or just another shadow in Plato's Allegory? Eur. Heart J., August 2, 2002; 23(16): 1231 - 1233. [PDF]
|
|
|
|
|
|
K. Juul, A. Tybjarg-Hansen, R. Steffensen, S. Kofoed, G. Jensen, and B. G. Nordestgaard Factor V Leiden: The Copenhagen City Heart Study and 2 meta-analyses Blood, June 17, 2002; 100(1): 3 - 10. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F.R. Rosendaal, F.M. Helmerhorst, and J.P. Vandenbroucke Female Hormones and Thrombosis Arterioscler. Thromb. Vasc. Biol., February 1, 2002; 22(2): 201 - 210. [Abstract] [Full Text] [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]
|
|
|
|
|
|
F. Burzotta, K. Paciaroni, V. De Stefano, P. Chiusolo, A. Manzoli, I. Casorelli, A.M. Leone, E. Rossi, G. Leone, A. Maseri, et al. Increased prevalence of the G20210A prothrombin gene variant in acute coronary syndromes without metabolic or acquired risk factors or with limited extent of disease Eur. Heart J., January 1, 2002; 23(1): 26 - 30. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Boekholdt, N. R. Bijsterveld, A. H.M. Moons, M. Levi, H. R. Buller, and R. J.G. Peters Genetic Variation in Coagulation and Fibrinolytic Proteins and Their Relation With Acute Myocardial Infarction: A Systematic Review Circulation, December 18, 2001; 104(25): 3063 - 3068. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. Herrington and K. P. Klein Genome and Hormones: Gender Differences in Physiology: Invited Review: Pharmacogenetics of estrogen replacement therapy J Appl Physiol, December 1, 2001; 91(6): 2776 - 2784. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D.M. Herrington Effects of oestrogen on cardiovascular events in postmenopausal women Eur. Heart J. Suppl., October 1, 2001; 3(suppl_M): M7 - M11. [Abstract] [PDF]
|
|
|
|
|
|
A. Sramek, J.H.C. Reiber, W.B.J. Gerrits, and F.R. Rosendaal Decreased Coagulability Has No Clinically Relevant Effect on Atherogenesis: Observations in Individuals With a Hereditary Bleeding Tendency Circulation, August 14, 2001; 104(7): 762 - 767. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Mira, J. Todoli, R. Alonso, M. L. Mico, A. Vaya, F. Ferrando, A. Estelles, P. Villa, and J. Aznar Factor V Leiden and Prothrombin G20210A in Relation to Arterial and/or Vein Rethrombosis: Two Cases Clinical and Applied Thrombosis/Hemostasis, July 1, 2001; 7(3): 234 - 237. [Abstract] [PDF]
|
|
|
|
|
|
C. Russo, D. Girelli, O. Olivieri, P. Guarini, F. Manzato, F. Pizzolo, B. Zaia, A. Mazzucco, and R. Corrocher G20210A Prothrombin Gene Polymorphism and Prothrombin Activity in Subjects With or Without Angiographically Documented Coronary Artery Disease Circulation, May 22, 2001; 103(20): 2436 - 2440. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. S. Williams and P. F. Bray Genetics of Arterial Prothrombotic Risk States Experimental Biology and Medicine, May 1, 2001; 226(5): 409 - 419. [Abstract] [Full Text]
|
|
|
|
|
|
P. W. Kamphuisen, J. C. J. Eikenboom, and R. M. Bertina Elevated Factor VIII Levels and the Risk of Thrombosis Arterioscler. Thromb. Vasc. Biol., May 1, 2001; 21(5): 731 - 738. [Full Text] [PDF]
|
|
|
|
 |
|
 D. G. Federman and R. S. Kirsner An Update on Hypercoagulable Disorders Arch Intern Med, April 23, 2001; 161(8): 1051 - 1056. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. M. Psaty, N. L. Smith, R. N. Lemaitre, H. L. Vos, S. R. Heckbert, A. Z. LaCroix, and F. R. Rosendaal Hormone Replacement Therapy, Prothrombotic Mutations, and the Risk of Incident Nonfatal Myocardial Infarction in Postmenopausal Women JAMA, February 21, 2001; 285(7): 906 - 913. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T C F Sykes, C Fegan, and D Mosquera Thrombophilia, polymorphisms, and vascular disease Mol. Pathol., December 1, 2000; 53(6): 300 - 306. [Abstract] [Full Text]
|
|
|
|
|
|
N. S. Van de Water, J. K. French, M. Lund, T. A. Hyde, H. D. White, and P. J. Browett Prevalence of factor v leiden and prothrombin variant g20210a in patients age <50 years with no significant stenoses at angiography three to four weeks after myocardial infarction J. Am. Coll. Cardiol., September 1, 2000; 36(3): 717 - 722. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Nguyen State-of-the-Art Review : Review and Management of Patients With the Prothrombin G20210A Polymorphism Clinical and Applied Thrombosis/Hemostasis, April 1, 2000; 6(2): 94 - 99. [Abstract] [PDF]
|
|
|
|
|
|
A. Vaya, R. Trenor, S. Molla, A. Estelles, Y. Mira, P. Villa, and J. Aznar Acute Myocardial Infarction Associated With the Prothrombin G20210A Mutation Clinical and Applied Thrombosis/Hemostasis, April 1, 2000; 6(2): 111 - 112. [PDF]
|
|
|
|
|
|
D. A. Lane and P. J. Grant Role of hemostatic gene polymorphisms in venous and arterial thrombotic disease Blood, March 1, 2000; 95(5): 1517 - 1532. [Full Text] [PDF]
|
|
|
|
|
|
G. Kunz, H. A. Ireland, P. J. Stubbs, M. Kahan, G. C. Coulton, and D. A. Lane Identification and characterization of a thrombomodulin gene mutation coding for an elongated protein with reduced expression in a kindred with myocardial infarction Blood, January 15, 2000; 95(2): 569 - 576. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Butenas, C. van't Veer, and K. G. Mann "Normal" Thrombin Generation Blood, October 1, 1999; 94(7): 2169 - 2178. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R. Meinardi, P. M. Pelsma, H. Koning, J. van der Meer, and K. Hamulyak Double-Homozygosity for Factor V Leiden and the Prothrombin Gene G20210A Variant in a Young Patient With Idiopathic Venous Thrombosis Blood, September 1, 1999; 94(5): 1828 - 1829. [Full Text] [PDF]
|
|
|
|
|
|
A. J. Moss, R. E. Goldstein, V. J. Marder, C. E. Sparks, D. Oakes, H. Greenberg, H. J. Weiss, W. Zareba, M. W. Brown, C.-S. Liang, et al. Thrombogenic Factors and Recurrent Coronary Events Circulation, May 18, 1999; 99(19): 2517 - 2522. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Redondo, H. H. Watzke, B. Stucki, I. Sulzer, F. D. Biasiutti, B. R. Binder, M. Furlan, B. Lammle, and W. A. Wuillemin Coagulation Factors II, V, VII, and X, Prothrombin Gene 20210G->A Transition, and Factor V Leiden in Coronary Artery Disease : High Factor V Clotting Activity Is an Independent Risk Factor for Myocardial Infarction Arterioscler. Thromb. Vasc. Biol., April 1, 1999; 19(4): 1020 - 1025. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Inbal, D. Freimark, B. Modan, A. Chetrit, S. Matetzky, N. Rosenberg, R. Dardik, Z. Baron, and U. Seligsohn Synergistic Effects of Prothrombotic Polymorphisms and Atherogenic Factors on the Risk of Myocardial Infarction in Young Males Blood, April 1, 1999; 93(7): 2186 - 2190. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. M. Ridker, C. H. Hennekens, and J. P. Miletich G20210A Mutation in Prothrombin Gene and Risk of Myocardial Infarction, Stroke, and Venous Thrombosis in a Large Cohort of US Men Circulation, March 2, 1999; 99(8): 999 - 1004. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. L. Amowitz, A. L. Komaroff, J. P. Miletich, P. M. Ridker;, F.R. Rosendaal, and D.S. Siscovick Factor V Leiden Is Not a Risk Factor for Myocardial Infarction Among Young Women Blood, February 15, 1999; 93(4): 1432 - 1433. [Full Text] [PDF]
|
|
|
|
 |
|
 P. C. Y. Liaw, T. Mather, N. Oganesyan, G. L. Ferrell, and C. T. Esmon Identification of the Protein C/Activated Protein C Binding Sites on the Endothelial Cell Protein C Receptor. IMPLICATIONS FOR A NOVEL MODE OF LIGAND RECOGNITION BY A MAJOR HISTOCOMPATIBILITY COMPLEX CLASS 1-TYPE RECEPTOR J. Biol. Chem., March 9, 2001; 276(11): 8364 - 8370. [Abstract] [Full Text] [PDF]
|
|