Sex Differences in Coagulation and Fibrinolysis in Subjects with Coronary Artery Disease

Summary

Women with coronary artery disease (CAD) have a prognosis at least as bad and possibly worse than men. Differences in classical risk factors do not fully account for these findings and there is evidence that circulating levels of haemostatic factors may predict CAD risk. In this study sex differences in haemostatic risk factors were examined in relation to coronary stenosis.

609 (420 men, 69%) subjects admitted for coronary angiography for suspected CAD were recruited. Levels of Factor VII:C (FVII:C), fibrinogen, plasminogen activator inhibitor-1 (PAI-1) and von Willebrand factor (vWF) were estimated in 296 subjects from one centre. Of these, women (n = 107) had higher levels of FVII:C (134% vs 117%, p <0.0005), and fibrinogen (3.4 g/l vs 3.2 g/l p = 0.01) than men (n = 189) and these differences remained after adjusting for other covariates. In subjects with angiographically significant atheroma these differences in haemostatic factors (n = 50 for women vs n = 147 for men) were exaggerated, (FVII:C 139% vs 117, p <0.0001, fibrinogen 3.7 g/l vs 3.3 g/l p = 0.003), PAI-1 (26.2 ng/ml vs 19.7 ng/ml, p = 0.02) with a trend towards higher levels of vWF in the women. Women with significant atheroma at angiography (n = 50) had higher levels of PAI-1 (25.0 ng/ml vs 13.4 ng/ml p <0.0001) and vWF (1.25 IU/ml vs 1.06 IU/ml, p = 0.02) and a trend towards higher levels of both fibrinogen and FVII:C than women with normal or in significant coronary vessel disease (n = 57).

Elevated circulating levels of PAI-1, vWF, fibrinogen and FVII:C in women with angiographically proven CAD may contribute to an adverse cardiovascular risk factor profile and the poorer prognosis in females than male patients with proven coronary artery disease.

• References

• 1 Ayanian JZ, Epstein AM. Differences in the use of procedures between women and men hospitalized for coronary heart disease. N Engl J Med 1991; 325: 221-5.
• 2 Healy B. The Yentl Syndrome. N Engl J Med 1991; 325: 274-6.
• 3 Kannel WB, Feinleib M. Natural history of angina pectoris in the Framingham study. Am J Cardiol 1972; 29: 154-63.
• 4 Lerner DJ, Kannel WB. Patterns of coronary heart disease morbidity and mortality in the sexes; a 26 year follow up of the Framingham population. Am Heart J 1986; 111: 383-90.
• 5 Murabito JM, Evans JC, Larson MG, Levy D. Prognosis after the onset of coronary heart disease. An investigation of differences in outcome between the sexes according to initial coronary disease presentation. Circulation 1993; 88: 2548-55.
• 6 Orencia A, Bailey K, Yawn BP, Kottke TE. Effect of gender on long term outcome of angina pectoris and myocardial infarction/sudden unexpected death. JAMA 1993; 269: 2392-7.
• 7 Bemiller CR, Pepine C, Rogers AK. Long term observations in patients with angina and normal coronary arteriograms. Circulation 1973; 47: 36-43.
• 8 Kemp HG, Kronmal RA, Vliestra RE, Frye RL. Seven year survival of patients with normal or near normal coronary arteriograms; a CASS registry study. J Am Coll Cardiol 1986; 7: 479-83.
• 9 Kannel WB, McGee DL. Diabetes and cardiovascular disease, the Framingham study. JAMA 1979; 241: 2035-8.
• 10 Mansfield MW, Heywood DM, Grant PJ. Sex differences in coagulation and fibrinolysis in white subjects with non-insulin dependent diabetes mellitus. Arterioscler Thromb Vasc Biol. 1996; 16: 160-4.
• 11 Kannel WB, Wolf PA, Castelli WP, D’Agostino RB. Fibrinogen and risk of cardiovascular disease; the Framingham Study. JAMA 1987; 258: 1183-6.
• 12 Meade TW, Mellows S, Brozovic M, Miller GJ, Chakrabarti RR, North W, Haines AP, Sterling Y, Imeson JD, Thompson SG. Haemostatic function and ischaemic heart disease: principal results of the Northwick Park Heart Study. Lancet 1986; 2: 533-7.
• 13 Heinrich J, Balleisen L, Schulte H, Assmann G, van de Loo J. Fibrinogen and factor VII in the prediction of coronary risk: results from the PROCAM Study in healthy men. Arterioscler Thromb 1994; 14: 54-9.
• 14 Yarnell J, Baker IA, Sweetnam PM, Bainton D, O’Brien R, Whitehead PJ, Elwood PC. Fibrinogen, viscosity, and white blood cell count are major risk factors for ischaemic heart disease: the Caerphilly and Speedwell Collaborative Heart Disease Studies. Circulation 1991; 83: 836-44.
• 15 Thompson SG, Kienast J, Pyke S, Haverkate F, van de Loo J. Haemostatic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. N Engl J Med 1995; 332: 625-41.
• 16 ECAT Angina Pectoris Study Group.. ECAT angina pectoris study: baseline associations of haemostatic factors with extent of coronary arteriosclerosis and other coronary risk factors in 3000 patients with angina pectoris undergoing coronary angiography. Eur Heart J 1993; 14: 8-17.
• 17 Hamsten A, de Faire U, Walldius G, Dahlen G, Szamosi A, Landou C, Blomback M, Wiman B. Plasminogen activator inhibitor in plasma; risk for recurrent myocardial infarction. Lancet 1987; 2: 3-9.
• 18 Marbet GA, Duckert F. Fibrinogen. In: Jespersen J, Bertina RM, Haverkate F. eds. ECAT Assay Procedures. A Manual of Laboratory Results. Dordrecht, Netherlands: Kluwer; 1992: 47-55.
• 19 Carlson LA, Bottiger LE. Risk factors of ischaemic heart disease in men and women: Results of the 19 year follow-up of the Stockholm prospective study. Acta Med Scand 1985; 207-11.
• 20 Lee AJ, Smith WCS, Lowe GDO, Tunstall-Pedoe H. Plasma fibrinogen and coronary risk factors: The Scottish Health Study. J Clin Epidemiol 1990; 43: 913-9.
• 21 Thompson SG, Duckert F. Haemostasis factors in angina pectoris; relation to gender, age and acute-phase reaction: results of the ECAT angina pectoris study group. Thromb Haemost 1995; 73: 561-7.
• 22 Kennedy JW, Killip T, Fisher LD, Alderman EL, Fillespie MJ, Monk MB. The clinical spectrum of coronary artery disease and its surgical and medical management, 1974-1979. The coronary artery surgery study. Circulation 1982; 66 (Suppl. 03) 16-23.
• 23 Eliasson M, Evrin PE, Lundblad D, Asplund K, Ranby M. Influence of gender, age and sampling time on plasma fibrinolytic variables and fibrinogen. Fibrinolysis 1993; 7: 316-23.
• 24 Ranby M, Sundell IB, Johnson O, Ledin M-C, Dahlen G. Activity of plasminogen activator inhibitor-1 (PAI-1) in a population in Northern Sweden. Fibrinolysis 1990; 4 (Suppl. 02) 54-5.
• 25 Gebara OC, Mittleman MA, Sunderland P, Lipinska I, Matheney T, Xu P, Welty FW, Wilson PW, Levy D, Muller JE, Tofler GH. Association between increased oestrogen status and increased fibrinolytic potential in the Framingham Offspring Study. Circulation 1995; 91: 1952-8.
• 26 Potter van Loon BJ, Kluft K, Radder JK, Blankenstein MA, Meinders AE. The cardiovascular risk factor plasminogen activator inhibitor type 1 is related to insulin resistance. Metabolism 1993; 42: 945-9.
• 27 Conlan MG, Folsom AR, Finch A, Davis CE, Sorlie P, Marcucci G, Wu KK. Associations of factor VIII and von Willebrand factor with age, race, sex, and risk factors for arteriosclerosis: the Arteriosclerosis Risk in Communities (ARIC) study. Thromb Haemost 1993; 70: 380-5.
• 28 Balliesen L, Bailey J, Epping PH, Schulte H, van de Loo J. Epidemiological study on factor VII, factor VIII and fibrinogen in an industrial population, 1: baseline data on the relation to age, gender, body-weight, smoking, alcohol, pill-using and menopause. Thromb Haemost 1985; 54: 475-9.
• 29 Benamer H, de Prost D, Bridey F, Boccara A, Brochet E, Himbert D, Sustendal L, Steg P, Assayag P. Gender difference in factor VII and in activated factor VII levels in unstable angina. Thromb Haemost 1996; 75: 981-2.
• 30 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.