Hemostatic risk factors in ischemic stroke

Franziska Demarmels Biasiutti; Daniela Berger; Heinrich P. Mattle; Bernhard Lämmle; Walter A. Wuillemin

doi:10.1160/TH03-03-0134

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2003; 90(06): 1094-1099
DOI: 10.1160/TH03-03-0134

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Hemostatic risk factors in ischemic stroke

Franziska Demarmels Biasiutti

¹Central Hematology Laboratory, Inselspital, University of Bern, Switzerland

,

Daniela Berger

¹Central Hematology Laboratory, Inselspital, University of Bern, Switzerland

,

Heinrich P. Mattle

²Department of Neurology, Inselspital, University of Bern, Switzerland

,

Bernhard Lämmle

¹Central Hematology Laboratory, Inselspital, University of Bern, Switzerland

,

Walter A. Wuillemin

¹Central Hematology Laboratory, Inselspital, University of Bern, Switzerland

³Division of Hematology, Department of Internal Medicine, Kantonsspital Lucerne, Switzerland

› Author Affiliations

Abstract

Summary

The role played by hemostasis in the pathogenesis of ischemic stroke is still controversial. In the present study, we looked for a possible association of ischemic stroke and high clotting activity of factor II (FII:C), factor V (FV:C), factor VII (FVII:C), factor X (FX:C) and fibrinogen. We investigated 157 non-anti-coagulated patients (86 males, 71 females; median age 41 y, range 16-73 ), who had survived ischemic stroke for at least 2 months, and 193 healthy controls with similar age and sex distribution (104 males, 89 females; median age 39 y, range 19-74). Patients showed significantly higher body mass index, as well as significantly higher prevalence of arterial hypertension, smoking and hyperlipidemia. FV:C (p = 0.05), FX:C (p = 0.04) and fibrinogen (p = 0.05) were higher in patients as compared to controls. In a univariate risk analysis FX:C and FV:C were associated with the relative risk for ischemic stroke showing an odds ratio (OR) of up to 2.8 (95% CI: 1.05-7.6) and 3.4 (95%CI: 1.4-7.9), respectively, for levels above 130%. In a multivariate analysis using a logistic regression model including age, sex, arterial hypertension, smoking habit, diabetes, hyperlipidemia, BMI and the coagulation factors, FV:C was still found to significantly (p=0.03) add to the risk of ischemic stroke. An increase of factor FV:C by 10% was associated with an increase in the relative risk of 19% (95% CI.: 2%-38%). In conclusion, we found a high plasma level of FV:C to be a prevalent (FV:C > 130% in 20/157 patients) and independent risk factor for ischemic stroke.

Keywords

Ischemic stroke - risk factors - coagulation - factor V

Full Text

References

References
1 WHO. Report of the WHO Task Force on Stroke and other Cerebrovascular Disorders. Stroke-1989: Recommendations on stroke prevention, diagnosis, and therapy. Stroke 1989; 20: 1407-31.
2 Sacco RL, Benjamin EJ, Broderick JP. et al. AHA Conference Proceedings: Risk Factors. Stroke 1997; 28: 1507-17.
3 Wolf PA. Prevention of stroke. Lancet 1998; III suppl 15-18.
4 Shinton R, Beevers G. Meta-analysis of relation between smoking and stroke. Br Med J 1989; 25: 789-94.
5 Wannamethee SG, Perry IJ, Shaper G. Nonfasting serum glucose and insulin concentrations and the risk of stroke. Stroke 1999; 30: 1780-6.
6 Iso H, Jacobs Jr DR, Wentworth D. et al. Serum cholesterol levels and six-year mortality from stroke in 350’977 men screened for the multiple risk factor intervention trial. N Engl J Med 1989; 320: 904-10.
7 Tegos TJ, Kalodiki E, Daskalopoulou SS. et al. Stroke: Epidemiology, clinical picture, and risk factors. Angiology 2000; 51: 793-808.
8 Catto AJ, Grant PJ. Risk factors for cerebro-vascular disease and the role of coagulation and fibrinolysis. Blood Coagul Fibrinolysis 1995; 6: 497-510.
9 Wilhelmsen L, Svardsudd K, Korsan-Bengtsen K. et al. Fibrinogen as a risk factor for stroke and myocardial infarction. N Engl J Med 1984; 23: 501-5.
10 Kannel WB, Wolf PA, Castelli WP. et al. Fibrinogen and risk of cardiovascular disease: the Framingham Study. JAMA 1987; 258: 1183-6.
11 Ernst E, Resch KL. Fibrinogen as a cardiovascular risk factor: a meta-analysis and review of the literature. Ann Int Med 1993; 118: 956-63.
12 Kario K, Matsuo M, Miyata T. Are there any associations among coagulation factor VII gene polymorphism, plasma activated factor VII levels, and cerebrovascular disease ?. Circulation 2000; 101: E48
13 Folsom AR, Rosamond WD, Shahar E. et al. for the ARIC Study investigators. Prospective study of markers of hemostatic function with risk of ischemic stroke. Circulation 1999; 100: 736-42.
14 Qizilbash N, Duffy S, Prentice CR. et al. Von Willebrand factor and risk of ischemic stroke. Neurology 1997; 49: 1552-56.
15 Smith FB, Lee AJ, Fowkes FGR. et al. Hemostatic factors as predictors of ischemic heart disease and stroke in the Edinburgh Artery Study. Arterioscler Thromb Vasc Biol 1997; 17: 3321-5.
16 Macko RF, Kittner SJ, Epstein A. et al. Elevated tissue plasminogen activator antigen and stroke risk. The stroke prevention in young women study. Stroke 1999; 30: 7-11.
17 De Stefano V, Chiusolo P, Paciaroni K. et al. Prothrombin G20210A mutant genotype is a risk factor for cerebrovascular ischemic disease in young patients. Blood 1998; 91: 3562-5.
18 Ridker PM, Hennekens CH, Miletich JP. G20210A mutation in prothrombin gene and risk of myocardial infarction, stroke, and venous thrombosis in a large cohort of US men. Circulation 1999; 99: 999-1004.
19 Szolnoki Z, Somogyvári F, Szabó M. et al. A clustering of unfavourable commmon genetic mutations in stroke cases. Acta Neurol Scand 2000; 102: 124-8.
20 Wu AH, Tsongalis GJ. Correlation of polymorphisms to coagulation and biochemical risk factors for cardiovascular diseases. Am J Cardiol 2001; 87: 1361-6.
21 Catto A, Carter A, Ireland H. et al. Factor V Leiden gene mutation and thrombin generation in relation to the development of acute stroke. Arterioscler Thromb Vasc Biol 1995; 15: 783-5.
22 Ridker PM, Hennekens CH, Lindpaintner K. et al. Mutation in the 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.
23 Voetsch B, Damasceno BP, Camargo ECS. et al. Inherited thrombophilia as a risk factor for the development of ischemic stroke in young adults. Thromb Haemost 2000; 83: 229-33.
24 Sacco RL, Owen J, Mohr JP. et al. Free protein S deficiency: a possible association with cerebrovascular occlusion. Stroke 1989; 20: 1657-61.
25 D’Amico D, Moschiano F, Leone M. et al. Genetic abnormalities of the protein C system: shared risk factors in young adults with migraine with aura and with ischemic stroke. Cephalgia 1998; 18: 618-21.
26 Boushey CJ, Beresford SA, Omenn GS. et al. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease: probable benefits of increasing folic acid intakes. JAMA 1995; 274: 1049-57.
27 Madonna P, de Stefano V, Coppola A. et al. Hyperhomocysteinemia and other inherited prothrombotic conditions in young adults with a history of ischemic stroke. Stroke 2002; 33: 51-56.
28 Vasse M, Guegan-Massardier E, Borg JY. et al. Frequency of protein Z deficiency in patients with ischemic stroke. Lancet 2001; 357: 933-4.
29 Kobelt K, Demarmels Biasiutti F, Mattle HP. et al. Protein Z in ischemic stroke. Br J Haematol 2001; 114: 169-73.
30 Tuhrim S, Rand JH, Wu X. et al. Antiphosphatidyl serine antibodies are independently associated with ischemic stroke. Neurology 1999; 53: 1523-7.
31 Brey RL, Hart RG, Sherman DG. et al. Antiphospholipid antibodies and cerebral ischemia in young people. Neurology 1990; 40: 1190-6.
32 Adams HP, Bendixen BH, Kappelle LJ. et al. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter trial. TOAST. Trial of Org 10172 in acute stroke treatment. Stroke 1993; 24: 35-41.
33 Clauss A. Gerinnungsphysiologische Schnellmethode zur Bestimmung des Fibrinogens. Acta Haematol 1957; 17: 237-46.
34 Bland JM, Altman DG. Multiple significance tests: the Bonferroni method. Br Med J 1995; 310: 170
35 Hankey GJ, Eikelboom JW, van Bockxmeer FM. et al. Inherited thrombophilia in ischemic stroke and its pathogenic subtypes. Stroke 2001; 32: 1793-9.
36 Redondo M, Watzke HH, Stucki B. et al. Coagulation factors II, V, VII, and X, pro-thrombin 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 1999; 19: 1020-5.