Factor V Leiden Is not a Risk Factor for Arterial Vascular Disease in the Elderly: Results from the Cardiovascular Health Study

Summary

Coagulation factor V Leiden is a risk marker for venous thrombosis. For arterial thrombosis no large study to date has included population-based elderly patients. The Cardiovascular Health Study is a longitudinal study of 5,201 men and women over age 65. With 3.4-year follow-up, we studied 373 incident cases of myocardial infarction (MI), angina, stroke, or transient ischemic attack (TIA), and 482 controls. The odds ratios for each event with heterozygous factor V Leiden were: MI, 0.46 (95% CI 0.17 to 1.25); angina, 1.0 (95% CI 0.45 to 2.23); stroke, 0.77 (95% CI 0.35 to 1.70); TIA, 1.33 (95% CI 0.5 to 3.55); any outcome, 0.83 (95% CI 0.48 to 1.44). Adjustment for cardiovascular risk factors did not change relationships. In older adults factor V Leiden is not a risk factor for future arterial thrombosis.

• References

• 1 Koster T, Rosendaal FR, de Ronde H, Briët E, Vandenbroucke JP, Bertina RM. Venous thrombosis due to poor anticoagulant response to activated protein C: Leiden Thrombophilia Study. Lancet 1993; 342: 1503-6.
• 2 Griffin JH, Evatt B, Wideman C, Fernandez JA. Anticoagulant protein C pathway defective in majority of thrombophilic patients. Blood 1993; 82: 1989-93.
• 3 Svensson PJ, Dahlbäck B. Resistance to activated protein C as a basis for venous thrombosis. N Engl J Med 1994; 330: 517-22.
• 4 Bertina RM, Koeleman BP, Koster T, Rosendaal FR, Dirven RJ, de Ronde H, van der Velden PA, Reitsma PH. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994; 369: 64-7.
• 5 Kalafatis M, Bertina RM, Rand MD, Mann KG. Characterization of the molecular defect in factor V- R506Q. J Biol Chem 1995; 270: 4053-7.
• 6 Ridker PM, Hennekens CH, Lindpaintner K, Stampfer MJ, Eisenberg PR, Miletich JP. Mutation in the gene encoding for coagulation factor V and the risk of myocardial infarction, stroke, and venous thrombosis in apparently healthy men. N Engl J Med 1995; 332: 912-17.
• 7 Tracy PB, Eide LL, Bowie EJW, Mann KG. Radioimmunoassay of factor V in plasma and platelets. Blood 1982; 60: 59-67.
• 8 Camire RM, Kalafatis M, Cushman M, Tracy RP, Mann KG, Tracy PB. The mechanism of inactivation of human platelet factor Va from normal and APC-resistant individuals. J Biol Chem 1995; 270: 20794-800.
• 9 Price D, Ridker P. Factor V Leiden mutation and the risks for thromboembolic disease: a clinical perspective. Ann Intern Med 1997; 127: 895-903.
• 10 Rosendaal FR, Siscovick DS, Schwartz SM, Beverly RK, Psaty BM, Longstreth Jr WT, Raghunathan TE, Koepsell TD, Reitsma PH. Factor V Leiden (resistance to activated protein C) increases the risk of myocardial infarction in young women. Blood 1997; 89: 2817-21.
• 11 National Center for Health Statistics.. Advance report of final mortality statistics. 1987. Public Health Service; Hyattsville, MD: 1989
• 12 Bauer KA, Weiss LM, Sparrow D, Vokonas PS, Rosenberg RD. Aging-associated changes in indices of thrombin generation and protein C activation in humans. J Clin Invest 1987; 80: 1527-34.
• 13 Kuller LH, Shemanski L, Psaty BM, Borhani NO, Gardin J, Haan MN, O’Leary DH, Savage PJ, Tell GS, Tracy R. Subclinical disease as an independent risk factor for cardiovascular disease. Circulation 1995; 92: 720-6.
• 14 Fried LP, Borhani NO, Enright P, Furberg CD, Gardin JM, Kronmal RA, Kuller LH, Manolio TA, Mittelmark MB, Newman A, O’Leary DH, Psaty B, Rautaharju P, Tracy RP, Weiler PG. CHS Research Group.. The Cardiovascular Health Study: design and rationale. Ann Epidemiol 1991; 1: 263-76.
• 15 Cushman M, Cornell ES, Howard PR, Bovill EG, Tracy RP. Laboratory methods and quality assurance in the Cardiovascular Health Study. Clin Chem 1995; 42: 264-70.
• 16 Ives DG, Fitzpatrick AL, Bild DE, Psaty BM, Kuller LH, Crowley PM, Cruise RG, Theroux S. Surveillance and ascertainment of cardiovascular events: the Cardiovascular Health Study. Ann Epidemiol 1995; 5: 278-85.
• 17 O’Leary DH, Polak JF, Wolfson SK, Bond MG, Bommer W, Sheth S, Psaty BM, Sharrett AR, Manolio TA. for CHS Investigators. Use of sonography to evaluate carotid atherosclerosis in the elderly: the Cardiovascular Health Study. Stroke 1991; 22: 1155-63.
• 18 Furberg CD, Manolio TA, Psaty BM, Bild DE, Borhani NO, Newman A, Tabatznik B, Rautaharju PM. for the Cardiovascular Health Study Research Group. Major electrocardiographic abnormalities in persons aged 65 years and older (the Cardiovascular Health Study). Am J Cardiol 1992; 69: 1329-35.
• 19 Gardin JM, Wong JD, Bommer W, Klopfenstein HS, Smith VE, Tabatznik G, Siscovick D, Lobodzinski S, Anton-Culver H, Manolio TA. Echo-cardiographic design of a multi-center investigation of free living elderly subjects. J Am Soc Echocard 1992; 5: 63-72.
• 20 Miller S, Dykes D, Polesky H. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988; 16: 1215.
• 21 Rees DC, Cox M, Clegg JB. World distribution of factor V Leiden. Lancet 1995; 346: 1133-4.
• 22 De Lucia D, Cerbone AM, Belli A, Di Mauro C, Renis V, Conte M, Rocino A, Papa ML, de Basi R. Resistance to activated protein C in adults with a history of juvenile transient ischemic attacks. Thromb Haemost 1996; 76: 627-31.
• 23 Fisher M, Fernandez JA, Ameriso SF, Xie D, Gruber A, Paganini-Hill A, Griffin JH. Activated protein C resistance in ischemic stroke not due to factor V arginine506 --> glutamine mutation. Stroke 1996; 27: 1163-6.
• 24 van der Bom JG, Bots ML, Haverkate F, Slagboom E, Meijer P, de Jong TVM, Hofman A, Grobbee DE, Kluft C. Reduced response to activated protein C is associated with increased risk for cerebrovascular disease. Ann Intern Med 1996; 125: 265-9.
• 25 Esmon CT. Defects in natural anticoagulant pathways as potential risk factors for myocardial infarction. Circulation 1997; 96: 9-11.