Levels of intrinsic coagulation factors and the risk of myocardial infarction among men: Opposite and synergistic effects of factors XI and XII.

The role of the intrinsic coagulation system on the risk of myocardial infarction is unclear. In the Study of Myocardial Infarctions Leiden (SMILE) that included 560 men younger than age 70 with a first myocardial infarction and 646 control subjects, we investigated the risk of myocardial infarction for levels of factor XI (factor XIc) and factor XII (factor XIIc). Furthermore, the risks for factor VIII activity (factor VIIIc) and factor IX activity (factor IXc) were assessed. Factor XIc was 113.0% in patients compared with 109.8% in control subjects (difference, 3.2%; 95% CI, 1.1%-5.4%). The risk of myocardial infarction adjusted for age for men in the highest quintile compared with those in the lowest quintile was 1.8-fold increased (ORadj, 1.8; 95% CI, 1.2-2.7). In contrast, factor XIIc among patients with myocardial infarction was lower than in control subjects, respectively, 93.0% and 98.6% (difference, 5.6%; 95% CI, 3.3%-7.9%). The odds ratio of myocardial infarction for men in the highest quintile versus those in the lowest quintile was 0.4 (ORadj, 0.4; 95% CI, 0.2-0.5). The highest risk was found among men with both high factor XIc and low factor XIIc (analyses in tertiles: ORadj, 6.4; 95% CI, 2.2-18.0). Factor VIIIc increased the risk of myocardial infarction although not dose dependently. Factor IXc increased the risk; odds ratio of myocardial infarction for men in the highest quintile versus those in the lowest quintile was 3.2 (ORadj, 3.2; 95% CI, 2.0-5.1). Thus, factors XIc and XIIc have opposite and synergistic effects on the risk of myocardial infarction in men; factor VIIIc and factor IXc increase the risk.

[1]  J. Cooper,et al.  Factor VIII, ABO blood group and the incidence of ischaemic heart disease , 1994, British journal of haematology.

[2]  M. Silverberg,et al.  Activation of the classical pathway of complement by Hageman factor fragment , 1981, The Journal of experimental medicine.

[3]  Jacqueline P Mitchell,et al.  Comparison of Novel Hemostatic Factors and Conventional Risk Factors for Prediction of Coronary Heart Disease , 2000, Circulation.

[4]  M. Balbi,et al.  Acute coronary syndromes do not promote prolonged in vivo FXII-dependent prothrombotic activity. , 2005, Thrombosis research.

[5]  A. Algra,et al.  Procoagulant factors and the risk of myocardial infarction in young women , 2006, European journal of haematology.

[6]  K Fujikawa,et al.  The coagulation cascade: initiation, maintenance, and regulation. , 1991, Biochemistry.

[7]  W. Halbmayer,et al.  Prevalence of factor XII (Hageman factor) deficiency among 426 patients with coronary heart disease awaiting cardiac surgery , 1994, Coronary artery disease.

[8]  T. Renné,et al.  Defective thrombus formation in mice lacking coagulation factor XII , 2005, The Journal of experimental medicine.

[9]  P. A. von dem Borne,et al.  Feedback activation of factor XI by thrombin in plasma results in additional formation of thrombin that protects fibrin clots from fibrinolysis. , 1995, Blood.

[10]  G. Lowe,et al.  Interleukin-6, Fibrin D-Dimer, and Coagulation Factors VII and XIIa in Prediction of Coronary Heart Disease , 2004, Arteriosclerosis, thrombosis, and vascular biology.

[11]  B. Freedman,et al.  Factors influencing the time from onset of chest pain to arrival at hospital , 1989, The Medical journal of Australia.

[12]  C. Hack,et al.  Enhancement of rabbit jugular vein thrombolysis by neutralization of factor XI. In vivo evidence for a role of factor XI as an anti-fibrinolytic factor. , 1998, The Journal of clinical investigation.

[13]  T. Meade,et al.  Hageman factor and risk of myocardial infarction in middle-aged men. , 1992, Atherosclerosis.

[14]  J. Meijers,et al.  Fibrinolysis and the Contact System: A Role for Factor XI in the Down-Regulation of Fibrinolysis , 1999, Thrombosis and Haemostasis.

[15]  A. Gruber,et al.  Factor XI-dependence of surface- and tissue factor-initiated thrombus propagation in primates. , 2003, Blood.

[16]  M S Golden,et al.  Prevalence of total coronary occlusion during the early hours of transmural myocardial infarction. , 1980, The New England journal of medicine.

[17]  G. Feuerstein,et al.  Effects of factor IX or factor XI deficiency on ferric chloride‐induced carotid artery occlusion in mice , 2005, Journal of thrombosis and haemostasis : JTH.

[18]  N. Brooks,et al.  Myocardial infarction with normal coronary arteries and factor XII deficiency. , 1985, British heart journal.

[19]  L. Björck,et al.  Activation of the contact-phase system on bacterial surfaces—a clue to serious complications in infectious diseases , 1998, Nature Medicine.

[20]  J Col,et al.  Predictors of 30-day mortality in the era of reperfusion for acute myocardial infarction. Results from an international trial of 41,021 patients. GUSTO-I Investigators. , 1995, Circulation.

[21]  G. Miller,et al.  Epidemiological and Genetic Associations of Activated Factor XII Concentration With Factor VII Activity, Fibrinopeptide A Concentration, and Risk of Coronary Heart Disease in Men , 2000, Circulation.

[22]  J. Vandenbroucke,et al.  John Hageman's factor and deep‐vein thrombosis: Leiden Thrombophilia Study , 1994, British journal of haematology.

[23]  B. Lämmle,et al.  Elevated levels of plasma prekallikrein, high molecular weight kininogen and factor XI in coronary heart disease. , 2002, Atherosclerosis.

[24]  F. Rosendaal,et al.  High levels of coagulation factor XI as a risk factor for venous thrombosis. , 2000, The New England journal of medicine.

[25]  D. Steinberg,et al.  Inherited factor XI deficiency confers no protection against acute myocardial infarction , 2003, Journal of thrombosis and haemostasis : JTH.

[26]  F R Rosendaal,et al.  Risk of Myocardial Infarction Associated With Factor V Leiden or Prothrombin Interaction of Coagulation Defects and Cardiovascular Risk Factors : Increased , 1998 .

[27]  G. Lowe,et al.  Factor VIII, von Willebrand factor and the risk of major ischaemic heart disease in the Caerphilly Heart Study , 1999, British journal of haematology.

[28]  P. A. von dem Borne,et al.  Thrombin-mediated activation of factor XI results in a thrombin-activatable fibrinolysis inhibitor-dependent inhibition of fibrinolysis. , 1997, The Journal of clinical investigation.

[29]  J. Cooper,et al.  Risk of coronary heart disease and activation of factor XII in middle-aged men. , 1997, Arteriosclerosis, thrombosis, and vascular biology.

[30]  A. Folsom,et al.  Prospective study of hemostatic factors and incidence of coronary heart disease: the Atherosclerosis Risk in Communities (ARIC) Study. , 1997, Circulation.

[31]  A. Scalvini,et al.  Defective intrinsic fibrinolytic activity in a patient with severe factor XII-deficiency and myocardial infarction. , 2009, Scandinavian journal of haematology.

[32]  K. Fujikawa,et al.  Mechanism of activation of bovine factor XI by factor XII and factor XIIa. , 1980, Biochemistry.

[33]  M. Winter,et al.  Plasma levels of factor XII, prekallikrein and high molecular weight kininogen in normal blood donors and patients having suffered venous thrombosis. , 2004, Thrombosis research.