Factor V Q506 (Resistance to Activated Protein C) and Prognosis after Acute Coronary Syndrome

Johan Holm; Andreas Hillarp; Bengt Zöller; Leif Erhardt; Erik Berntorp; Björn Dahlbäck

doi:10.1055/s-0037-1614587

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 1999; 81(06): 857-860
DOI: 10.1055/s-0037-1614587

Letters to the Editor

Schattauer GmbH

Factor V Q⁵⁰⁶ (Resistance to Activated Protein C) and Prognosis after Acute Coronary Syndrome

Johan Holm

¹From the Department of Cardiology and Coagulation Disorders, University Hospital, Malmö, Sweden

,

Andreas Hillarp

²Department of Clinical Chemistry and Coagulation Disorders, University Hospital, Malmö, Sweden

,

Bengt Zöller

²Department of Clinical Chemistry and Coagulation Disorders, University Hospital, Malmö, Sweden

,

Leif Erhardt

¹From the Department of Cardiology and Coagulation Disorders, University Hospital, Malmö, Sweden

,

Erik Berntorp

²Department of Clinical Chemistry and Coagulation Disorders, University Hospital, Malmö, Sweden

,

Björn Dahlbäck

²Department of Clinical Chemistry and Coagulation Disorders, University Hospital, Malmö, Sweden

› Institutsangaben

Abstract

Summary

Factor V:Q⁵⁰⁶ causing resistance to activated protein C (APC-resistance), is a risk factor for venous thrombosis. Some studies have indicated an association with arterial disease, especially in women. We investigated the prevalence of the FV:Q⁵⁰⁶ allele prospectively in 295 patients with acute coronary syndrome. Mortality and myocardial infarction rate were evaluated after 30 days and after 2 years. The FV:Q⁵⁰⁶ allele was found in 38 patients. In a Cox proportional hazards model, smokers carrying FV:Q⁵⁰⁶ had a higher risk of infarction or death within 30 days, compared to non-smokers with a normal genotype (relative risk 2.9 [95% CI 1.2-7.0]). The difference remained significant after 2 years (relative risk 2.8 [95% CI 1.2-6.5]). The effect of the FV:Q⁵⁰⁶ allele on clinical outcome in acute coronary syndrome has not previously been described. Our results demonstrate a gene-environment interaction between smoking and the FV:Q⁵⁰⁶ allele, with an increased risk of early complications after an acute ischemic event.

Volltext

Referenzen

References
1 Dahlbäck B, Carlsson M, Svensson P. Familial thrombophilia due to a previously unrecognised mechanism characterised by poor anticoagulant response to activated protein C: prediction of a cofactor to activated protein C. Proc Natl Acad Sci USA 1993; 90: 1004-8.
2 Dahlbäck B, Hildebrand B. Inherited resistance to activated protein C is corrected by anticoagulant cofactor activity found to be a property of factor V. Proc Natl Acad Sci USA 1994; 81: 1396-400.
3 Bertina RM, Koeleman BP, Koster T. et al Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994; 369: 64-7.
4 Dahlbäck B. Pro- and anticoagulant properties of coagulation factor V. Factor V Leiden (APC resistance) causes hypercoagulability by dual mechanisms. J Lab Clin Med 1999. in press
5 Zöller B, Svenson PJ, He X, Dahlbäck B. Identification of the same factor V gene mutation in 47 out of 50 thrombosis prone families with inherited resistance to activated protein C. J Clin Invest 1994; 94: 2521-4.
6 Rosendaal F, Koster T, Vandenbroucke J, Reitsma P. High risk of thrombosis in patients homozygous for factor V Leiden (activated protein C resistance). Blood 1995; 85: 1504-8.
7 Holm J, Zöller B, Berntorp E, Erhardt L, Dahlbäck B. Prevalence of factor V gene mutation among myocardial infarction patients and healthy controls higher in Sweden than in other countries. J Int Med 1996; 239: 221-6.
8 Lindqvist PG, Svensson PJ, Dahlbäck B, Marsál K. Factor V Q 506 mutation (activated protein C resistance) associated with reduced impartum blood loss – a possible evolutionary selection mechanism. Thromb Haemost 1998; 79: 69-73.
9 Svensson P, Dahlbäck B. Resistance to activated protein C as a basis for venous thrombosis. N Engl J Med 1994; 330: 517-21.
10 Kontula K, Ylikorkala A, Miettinen H. et al Arg506Gln factor V mutation (factor V Leiden) in patients with ischemic cerebrovascular disease and survivors of myocardial infarction. Thromb Haemost 1995; 73: 558-60.
11 März W, Seydewitz H, Winkelmann B, Chen M, Nauck M, Witt I. Mutation in coagulation factor V associated with resistance to activated protein C in patients with coronary heart disease. Lancet 1995; 345: 526-7.
12 Samani NJ, Lodwick D, Martin D, Kimber P. Resistance to activated protein C and risk of premature myocardial infarction. Lancet 1994; 344: 1709-10.
13 Emmerich J, Poirier O, Evans A. et al Myocardial infarction, Arg 506 to Gln factor V mutation, and activated protein C resistance. Lancet 1995; 345: 321.
14 van Bockxmeer FM, Baker I R, Taylor RR. Premature ischemic heart disease and the gene for coagulation factor V. Nature Medicine 1995; 1 (03) 185.
15 Ardissino D, Peyvandi F, Merlini P, Colombi E, Mannucci P. Factor V(Arg506 - Gln) mutation in young survivors of myocardial infarction. Thromb Haemost 1996; 75: 701-2.
16 Cushman M, Rosendaal FR, Psaty BM. et al Factor V Leiden is not a risk factor for arterial vascular disease in the elderly: Results from the cardiovascular health study. Thromb Haemost 1998; 79: 912-5.
17 Rosendaal FR, Siscovick DS, Schwartz SM. et al Factor V Leiden (Resistance to activated protein C) increases risk of myocardial infarction in young women. Blood 1997; 89 (08) 2817-21.
18 Holm J, Zöller B, Svensson PJ, Berntorp E, Erhardt L, Dahlbäck B. Myocardial infarction associated with homozygous resistance to activated protein C. Lancet 1994; 344: 952-3.
19 Ridker PM, Hennekens CH, Lindpainter K, Stampfer MJ, Eisenberg PR, Miletich JP. Mutation in gene coding for coagulation factor V and the risk of myocardial infarction, stroke and venous thrombosis in apparently healthy men. N Engl J Med 1995; 332: 912-7.
20 Hille ETM, Westendorp RGJ, Vandenbroucke JP, Rosendaal RR. Mortality and causes of death in families with the factor V Leiden mutation (resistance to activated protein C). Blood 1997; 89 (06) 1963-7.
21 Fuster V, Fallon JT, Nemerson Y. Coronary thrombosis. Lancet 1996; 348 (Suppl I) s7-s10.
22 Botker HE, Ravkilde J, Sogaard P, Jorgensen PJ, Horder M, Thygesen K. Graduation of unstable angina based on a sensitive immunoassay for serum creatine kinase MB. Br Heart J 1991; 65: 72-6.
23 Yang Q, Khoury MJ. Evolving methods in genetic epidemiology. III. Gene-environment interaction in epidemiologic research. Epidemiol Rev 1997; 19 (Suppl. 01) 33-43.
24 Scott BD, Esmon CT, Comp PC. The natural anticoagulant protein S is decreased in male smokers. Am Heart J 1991; 122: 76-80.
25 Zöller B, Berntsdotter A, Garcia de Frutos P, Dahlbäck B. Resistance to activated protein C as an additional genetic risk factor in hereditary deficiency of protein S. Blood 1995; 85 (12) 3518-23.
26 Barbash I G, Reiner J, White HD. et al Evaluation of paradoxic beneficial effects of smoking in patients receiving thrombolytic therapy for acute myocardial infarction; mechanism of the “smokers parado” from the GUSTO-I trial, with angiographic insights. J Am Coll Cardiol 1995; 26 (05) 1222-9.