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Overview of hemostatic factors involved in atherosclerotic cardiovascular disease

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Lipids

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

  1. 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.

    Article  PubMed  CAS  Google Scholar 

  2. 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.

    Article  PubMed  CAS  Google Scholar 

  3. 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.

    Article  CAS  Google Scholar 

  4. 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.

    Article  CAS  Google Scholar 

  5. 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.

    PubMed  CAS  Google Scholar 

  6. 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.

    PubMed  CAS  Google Scholar 

  7. 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.

    PubMed  CAS  Google Scholar 

  8. 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.

    Article  CAS  Google Scholar 

  9. Kannel, W.B. (1997) Influence of Fibrinogen on Cardiovascular Disease, Drugs 54, 32–40.

    Article  PubMed  CAS  Google Scholar 

  10. 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.

    PubMed  CAS  Google Scholar 

  11. Catanzaro, J.A., and Suen, R. (1996) Clinical Laboratory Indicators of Cardiovascular Disease Risk, Alt. Med. Rev. 1, 185–194.

    Google Scholar 

  12. Athukorala, T.M., and Ranjini, L.P. (1991) Lipid Patterns and Fibrinogen Levels of Smokers and Non-smokers, Ceylon Med. J. 36, 98–101.

    PubMed  CAS  Google Scholar 

  13. 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.

    Article  PubMed  CAS  Google Scholar 

  14. Ditschuneit, H.H., Flechtner-Mors, M., and Adler, G. (1995) Fibrinogen in Obesity Before and After Weight Reduction, Obesity Res. 3, 43–48.

    CAS  Google Scholar 

  15. 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.

    PubMed  CAS  Google Scholar 

  16. Vanninen, E., Laitinen, J., and Uusitupa, M. (1994) Physical Activity and Fibrinogen Concentration in Newly Diagnosed NIDDM, Diabetes Care 17, 1031–1038.

    PubMed  CAS  Google Scholar 

  17. 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.

    Article  Google Scholar 

  18. 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.

    Article  PubMed  CAS  Google Scholar 

  19. 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.

    PubMed  Google Scholar 

  20. Ridker, P. (2003) Clinical Application of C-Reactive Protein for Cardiovascular Disease Detection and Prevention, Circulation 107, 363–369.

    Article  PubMed  Google Scholar 

  21. 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.

    Article  PubMed  CAS  Google Scholar 

  22. Koenig, W. (1998) Haemostatic Risk Factors for Cardiovascular Diseases, Eur. Heart J. 19 (Suppl. C), C39-C43.

    PubMed  Google Scholar 

  23. 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.

    PubMed  CAS  Google Scholar 

  24. 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.

    PubMed  CAS  Google Scholar 

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Correspondence to William B. Kannel.

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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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