Abstract
Hemostatic factors associated with the development of cardiovascular disease (CVD) include fibrinogen, von Willebrand factor, tissue plasminogen activator (tPA) antigen, plasminogen activator inhibitor-1 (PAI-1), and factor VII. Each SD increment of these increases the association by 24–30%. Most hemostatic factors are intercorrelated with inflammatory markers [e.g., C-reactive protein (CRP)] and LDL cholesterol. Fibrinogen seems the most fundamental hemostatic risk factor for CVD. The Framingham Study reaffirms the significant linear risk factor trends across fibrinogen tertiles (P<0.001) for age, body mass index, smoking, diabetes mellitus, total cholesterol, HDL cholesterol, and TG in both sexes. Fibrinogen may also directly increase CVD risk because of its role in platelet aggregation, plasma viscosity, and fibrin formation. Fibrinogen is also an acute-phase reactant that is elevated in inflammatory states. Fibrinogen mediates the thrombogenic effect of other risk factors. Fibrinogen levels increase with the number of cigarettes smoked and quickly fall after smoking cessation. This rapid fibrinogen decline may be a mechanism for CVD risk reduction after smoking cessation. Weight loss is accompanied by reduced fibrinogen. The correlation between fibrinogen and LDL cholesterol suggests that lipidimposed CVD risk is mediated partly through fibrinogen. Hyperreactive platelets of diabetics may result in part from their increased fibrinogen. Elevated fibrinogen and CRP of unstable angina suggest an acute-phase reaction. Prevalence, case-control, angiographic, and echocardiogram investigations incriminate hemostatic and inflammatory markers as strong independent risk factors for initial and recurrent CVD. Framingham Study data indicate that each SD increase in fibrinogen imposes a 20% independent increment in risk. It may be concluded that fibrinogen and CRP determination may be useful screening tools to identify individuals at added risk for thrombotic complications of CVD.
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Abbreviations
- BMI:
-
body mass index
- CHD:
-
coronary heart disease
- CI:
-
confidence interval
- CRP:
-
C-reactive protein
- CVD:
-
cardiovascular disease
- HDL-C:
-
HDL cholesterol
- LDL-C:
-
LDL cholesterol
- PAI-1:
-
plasminogen activator inhibitor-1
- RR:
-
relative risk, risk ratio
- tPA:
-
tissue plasminogen activator
References
Fuster, V., Badimon, L., and Chesebro, J.H. (1992) The Pathogenesis of Coronary Artery Disease and the Acute Coronary Syndromes, N. Engl. J. Med. 326, 242–250.
Wilson, P.W.F. (2004) CDC/AHA Workshop on Markers of Inflammation and Cardiovascular Disease. Application to Clinical and Public Health Practice in Asymptomatic Patients: A Back-ground Paper, Circulation 110, e568-e571.
Ernst, E., Hammerschmidt, D.E., Bagge, U., Matrai, A., and Dormandy, J.A. (1987) Leukocytes and the Risk of Ischemic Diseases, J. Am/Med. Assoc. 257, 2318–2324.
Danesh, J., Collins, R., Appleby, P., and Peto, R. (1998) Association of Fibrinogen, C-Reactive Protein, Albumin or Leukocyte Count with Coronary Heart Disease; Meta-analyses of Prospective Studies, J. Am. Med. Assoc. 279, 1477–1482.
Scarabin, P.Y., Aillaud, M.F., Amouyel, P., Evans, A., Luc, G., Ferrieres, J., Arveiler, D., and Juhan-Vague, I. (1998) Association of Fibrinogen, Factor VII and PAI-1 with Baseline Findings Among 10,500 Male Participants in a Prospective Study of Myocardial Infarction—The PRIME Study. Prospective Epidemiological Study of Myocardial Infarction, Thromb. Haemost. 80, 749–756.
Stec, J.J., Silbershatz, H., Tofler, G.H., Matheney, T.H., Sutherland, P., Lipinska, I., Massaro, J.M., Wilson, P.W.F., Muller, J.E., and D’Agostino, R.B. (2000) Association of Fibrinogen with Cardiovascular Risk Factors in the Framingham Offspring Population, Circulation 102, 1634–1638.
Ernst, E., and Resch, K.L. (1993) Fibrinogen as a Cardiovascular Risk Factor: A Meta-analysis and Review of the Literature, Ann. Intern. Med. 118, 956–963.
Kannel, W.B., Wolf, P.A., Castelli, W.P., and D’Agostino, R.B. (1987) Fibrinogen and Risk of Cardiovascular Disease. The Framingham Study, J. Am. Med. Assoc. 258, 1183–1186.
Kannel, W.B. (1997) Influence of Fibrinogen on Cardiovascular Disease, Drugs 54, 32–40.
Smith, F.B., Lee, A.J., Fowkes, F.G.R., Price, J.F., Rumley, A., and Lowe, G.D.O. (1997) Hemostatic Factors as Predictors of Ischemic Heart Disease and Stroke in the Edinburgh Artery Study, Arterioscler. Thromb. Vasc. Biol. 17, 3321–3325.
Catanzaro, J.A., and Suen, R. (1996) Clinical Laboratory Indicators of Cardiovascular Disease Risk, Alt. Med. Rev. 1, 185–194.
Athukorala, T.M., and Ranjini, L.P. (1991) Lipid Patterns and Fibrinogen Levels of Smokers and Non-smokers, Ceylon Med. J. 36, 98–101.
Fogari, R., Zoppi, A., Marasi, G., Vanasia, A., and Villa, G. (1994) Associations Between Plasma Fibrinogen Levels and Cardiovascular Risk Factors in Hypertensive Men, J. Cardiovasc. Risk 1, 341–345.
Ditschuneit, H.H., Flechtner-Mors, M., and Adler, G. (1995) Fibrinogen in Obesity Before and After Weight Reduction, Obesity Res. 3, 43–48.
Heinrich, L., Balleisen, L., Schulte, H., Assmann, G., and van de Loo, J. (1994) Fibrinogen and Factor VII in the Prediction of Coronary Risk: Results of the PROCAM Study in Healthy Men, Arterioscler. Thromb. 14, 54–59.
Vanninen, E., Laitinen, J., and Uusitupa, M. (1994) Physical Activity and Fibrinogen Concentration in Newly Diagnosed NIDDM, Diabetes Care 17, 1031–1038.
Ridker, P.M., Cannon, C.P., Morrow, D., Rifai, N., Rose, L.M., McCabe, C.H., Pfeffer, M.A., and Braunwald, E., Pravastatin Atorvastatin Evaluation and Infection Therapy—Thrombolysis in Myocardial Infarction 22 (PROVE IT—TIMI 22) Investigators (2005) C-Reactive Protein Levels and Outcomes After Statin Therapy, N. Engl. J. Med. 6, 352, 20–28.
Thompson, S.G., Kienast, J., Pyke, S.D., Haverkate, F., and van de Loo, J.C. (1995) Hemostatic Factors and the Risk of Sudden Death in Patients with Angina Pectoris. European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group, N. Engl. J. Med. 332, 635–641.
el Khawand, C., Jamart, J., Donckier, J., Chatelaine, B., Lavenne, E., Moriau, E., and Buysschaert, M. (1993) Hemostasis Variables in Type 1 Diabetic Patients Without Demonstrable Vascular Complications, Diabetes Care 16, 1137–1145.
Ridker, P. (2003) Clinical Application of C-Reactive Protein for Cardiovascular Disease Detection and Prevention, Circulation 107, 363–369.
Ridker, P.M., Vaughan, D.E., Stampfer, M.J., Manson, J.E., and Hennekens, C.H. (1993) Endogenous Tissue-type Plasminogen Activator and Risk of Myocardial Infarction, Lancet 341, 1165–1168.
Koenig, W. (1998) Haemostatic Risk Factors for Cardiovascular Diseases, Eur. Heart J. 19 (Suppl. C), C39-C43.
Tofler, G.H., D’Agostino, R.B., Jacques, P.F., Bostom, A.G., Wilson, P.W., Lipinski, I., Mittleman, M.A., and Selhub, J. (2002) Association Between Increased Homocysteine Levels and Impaired Fibrinolytic Potential: Mechanism for Cardiovascular Risk, Thromb. Haemost. 88, 799–804.
Pearson, T.A., LaCava, J., and Weil, H.F. (1997) Epidemiology of Thrombotic-Hemostatic Factors and Their Association with Cardiovascular Disease, Am. J. Clin. Nutr. 65, 1674S-1682S.
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Kannel, W.B. Overview of hemostatic factors involved in atherosclerotic cardiovascular disease. Lipids 40, 1215–1220 (2005). https://doi.org/10.1007/s11745-005-1488-8
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DOI: https://doi.org/10.1007/s11745-005-1488-8