Skip to main content
Log in

Beyond Coagulation: Fibrinogen as a Cause of Cardiovascular Surgical Disease

  • Published:
Cardiovascular Drugs and Therapy Aims and scope Submit manuscript

Abstract

Fibrinogen is generally considered to be an important mediator of clot formation. However, its effects on clots and perhaps other more direct effects may also make it a powerful mediator in the genesis and progression of atheromatous disease. Indeed, raised fibrinogen levels may pose as great a cardiovascular risk as classical risk factors such as elevated blood pressure or cholesterol levels. The plasma fibrinogen level of any given individual, and its associated cardiovascular risk, is dependent upon an interaction between environmental and intrinsic (genetic) factors. Most environmental factors associated with elevated fibrinogen levels are also potent cardiovascular risk factors (e.g., cigarette smoking). Less is known of the role played by genetic factors. However, as research into the genotypic influences on both basal and “stimulated” fibrinogen production continues, high-risk groups may be identified that may benefit from therapeutic intervention aimed at lowering plasma fibrinogen.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Lowe G, Reavy M, Johnston R, Forbes C, Prentice C. Increased platelet aggregates in vascular and non-vascular illness: Correlation with plasma fibrinogen and effects of ancrod. Thromb Res 1979;14:377-386.

    Google Scholar 

  2. Group EAPS. 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.

    Google Scholar 

  3. Smith EB. Fibrinogen, fibrin and fibrin degradation products in relation to atherosclerosis. Clins Haematol 1986;15: 355-370.

    Google Scholar 

  4. Fatah K, Hamsten A, Blomback B, Blomback M. Fibrin gel network characteristics and coronary heart disease: Relations to plasma fibrinogen concentration, acute phase protein, serum lipoproteins and coronary atherosclerosis. Thromb Haemost 1992;68.

  5. Velican D, Velican C. Study of fibrous plaques occuring in the coronary arteries of children. Atherosclerosis 1979;33: 201-215.

    Google Scholar 

  6. Thompson W, Sabally K, Smith E, Benjamin N. Stimulation of proliferation of smooth muscle cell and fibroblasts in culture by fibrin degradation products and human atherosclerotic plaque extracts. Blood Coagul Fibrinol 1994; 5(Suppl. 2):P-43.

    Google Scholar 

  7. Smith E, Thompson W. Fibrin as a factor in atherogenesis. Thromb Res 1994;73:1-19.

    Google Scholar 

  8. Lowe G. Blood viscosity and cardiovascular disease. Thromb Haemos 1992;67:494-498.

    Google Scholar 

  9. Yarnell JW, Baker IA, Sweetnam PM, et al. Fibrinogen, viscocity, and white blood cell count are major risk factors for ischaemic heart disease. Circulation 1991;83:836-844.

    Google Scholar 

  10. Stout RW, Crawford V. Seasonal variations in fibrinogen concentrations among elderly people. Lancet 1991;338:9-13.

    Google Scholar 

  11. Lassila R, Pltonen S, Lepantalo M, Saarinen O, Kauhanen P, Manninen V. Severity of peripheral atherosclerosis is associated with fibrinogen and degradation of cross-linked fibrin. Arterioscler Thromb 1993;13:1738-1742.

    Google Scholar 

  12. Resch K, Ernst E, Matrai A, Paulsen H. Fibrinogen and viscocity as risk factors for subsequent cardiovascular events in stroke survivors. Ann Intern Med 1992;117: 371-375.

    Google Scholar 

  13. Shah P, Chander R, Daly K. Plasma fibrinogen level and other risk factor profile; association with coronary artery disease. Br Heart J 1995;71:P25.

    Google Scholar 

  14. Qizilbash N, Jones L, Warlow C, Mann J. Fibrinogen and lipid concentrations as risk factors for transient ischaemic attacks and minor ischaemic strokes. Br Med J 1991; 303:605-609.

    Google Scholar 

  15. Kannel WB, Wolf PA, Catelli WP, D'Agostino RB. Fibrinogen and risk of cardiovascular disease. The Framingham Study. JAMA 1987;258:1183-1186.

    Google Scholar 

  16. Stone MC, Thorp JM. Plasma fibrinogen-a major coronary risk factor. J R Coll Gen Pract 1985;35:565-569.

    Google Scholar 

  17. Meade TW, North WR, Chakrabarti R, Tirling Y, Haines AP, Thompson SG. Haemostatic function and cardiovascular death: Early results of the Northwick Park Heart Study. Lancet 1980;1980:1050-1054.

    Google Scholar 

  18. Ernst E, Resch KL. Fibrinogen as a cardiovascular risk factor: A meta-analysis and review of the literature. Ann Intern Med 1993;118:956-963.

    Google Scholar 

  19. Ernst E, Schmid M. Regular aerobic exercise lowers fibrinogen levels: Results of a pilot study. Arch Phys Med Rehab 1993;3:196-198.

    Google Scholar 

  20. Ernst E. Plasma fibrinogen-an independent cardiovascular risk factor. J Intern Med 1990;227:365-372.

    Google Scholar 

  21. Balleisen L, Bailey J, Epping P, Schulte H, van de Loo J. Epidemiological study of factor VII, factor VIII and fibrinogen in an industrial population. I. Baseline data on the relation to age, gender, body weight, smoking, alcohol, pill-using, and menopause. Thromb Haemost 1985;54:475-479.

    Google Scholar 

  22. Meade T. Stirling Y, Thompson S, et al. An international and interregional comparison of haemostatic variables in the study of ischaemic heart disease. Report of a working group. Int J Epidemiol 1986;15:331-336.

    Google Scholar 

  23. Letcher RL, Chien S, Pickering TG, Sealey JE, Laragh JH. Direct relationship between blood pressure and blood viscosity in normal and hypertensive subjects. Role of fibrinogen concentration. Am J Med 1981;70:1195-1202.

    Google Scholar 

  24. Haught WH, Mansour M, Rothlein R, et al. Alterations in circulating intercellular adhesion molecule-1 and L-selectin: Further evidence for chronic inflammation in ischaemic heart disease. Am Heart J 1996;132:1-8.

    Google Scholar 

  25. Kohchi K, Takebayashi S, Hiroki T, Nobuyoshi M. Significance of adventitial inflammation of the coronary artery in patients with unstable angina: Results of autopsy. Circulation 1985;71:709-716.

    Google Scholar 

  26. Haverkate F, Thompson SG, Pyke SD, Gallimore JR, Pepys MB. Production of C-reactive protein and risk of coronary events in stable and unstable angina. European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group. Lancet 1997;349:462-466.

    Google Scholar 

  27. Montgomery H, Clarkson P, Nwose O, et al. The acute rise in plasma fibrinogen concentration with exercise is influenced by the G-453-A polymorphism of the beta-fibrinogen gene. Arterioscler Thromb Vase Biol 1996;16: 386-391.

    Google Scholar 

  28. Miche E. Baller D, Gleichmann U, Mannebach H, Schmidt H, Prohaska W. Fibrinogen and leukocyte number in coronary heart disease. Correlation with angiography and clinical degree. Z Kardiol 1995;84:92-97.

    Google Scholar 

  29. Mendall MA, Patel P, Ballam L, Strachan D, Northfield TC. C reactive protein and its relation to cardiovascular risk factors: A population based cross sectional study. B. Med J 1996;312:1049-1050.

    Google Scholar 

  30. Hamsten A, Iselius L, de Faire U, Blomback M. Genetic and cultural inheritance of plasma fibrinogen concentration. Lancet 1987;2:988-990.

    Google Scholar 

  31. Hoffman C, Burns P, Lawson W, Katz J, Miller R, Hultin M. Plasma fibrinogen level is not elevated in young adults from families with premature ischaemic heart disease. Arterioscler Thromb 1993;13:800-803.

    Google Scholar 

  32. Roy S, Mukhopadhyay G, Redman C. Regulation of fibrinogen assembly: Transfection of hep G2 cells with Bbeta cDNA specifically enhances synthesis of the three component chains of fibrinogen. J. Biol Chem 1990;265:6389-6393.

    Google Scholar 

  33. Thomas AE, Green FR, Kelleher CH, et al. Variation in the promotor region of the b fibrinogen gene is associated with plasma fibrinogen levels in smokers and non-smokers. Thromb Haemost 1991;65:487-490.

    Google Scholar 

  34. Scarabin P-Y, Bara L, Ricard S, et al. Genetic variation at the b-fibrinogen locus in relation to plasma fibrinogen concentrations and risk of myocardial infarction. The ECTIM study. Arterioscl Thromb 1993;13:886-891.

    Google Scholar 

  35. Winocour P, Durrington P, Bhatnagar D, et al. Double blind placebo controlled study of the effect of bezafibrate on blood lipids, lipoproteins and fibrinogen in hyperlipidaemic diabetes mellitus. Diabet Med 1990;7:736-743.

    Google Scholar 

  36. Heinrich J, Balleisen L, Schulte H, van de Loo J, Assmann G. Fibrinogen adds to the predictive power of LDL cholesterol in healthy individuals. Results from the PROCAM study. Blood Coagul Fibrinolys 1994;5(Suppl. 2):P-33.

    Google Scholar 

  37. Wilhelmsen L, Svardsudd K, Korsan-Bengtsen K, Larsson B, Welin L, Tibblin G. Fibrinogen as a risk factor for stroke and myocardial infarction. N Eng J Med 1984;311:501-505.

    Google Scholar 

  38. Meade TW, Mellows S, Brozovic M, et al. Hemostatic function and ischaemic heart disease: Principal results of the Northwick Park Heart Study. Lancet 1986;2:533-537.

    Google Scholar 

  39. Folsom AR, Wu KK, Davis CE, Conlan MG, Sorlie PD, Szklo M. Population correlates of plasma fibrinogen and factor VII, putative cardiovascular risk factors. Atherosclerosis 1991;91:191-205.

    Google Scholar 

  40. Folsom AR, Qamhieh HT, Flack JMea. Plasma fibrinogen: Levels and correlates in young adults. Am J Epidemiol 1993;138:1023-1036.

    Google Scholar 

  41. Folsom AR, Johnson KM, Lando EA, McGovern PG, Solberg LI, Ekstrum JK. Plasma fibrinogen and other cardiovascular risk factors in urban American Indian smokers. Ethnicity Dis 1993;3:344-350.

    Google Scholar 

  42. Lee AJ, Smith WCS, Lowe GDO, Tunstall-Pedoe H. Plasma fibrinogen and coronary risk factors: The Scottish Heart Health Study. J Clin Epidemiol 1990;9:913-919.

    Google Scholar 

  43. Krobot K, Hense HW, Cremer P, Eberle E, Keil U. Determinants of plasma fibrinogen: Relation to body weight, waisttohip ratio, smoking, alcohol, age, and sex: Results from the Second MONICA Augsberg Survey 1989-90. Arterioscler Thromb 1992;12:780-788.

    Google Scholar 

  44. Meade TW, Chakrabati R, Haines AP, NorthWRS, Y S. Characteristics affecting fibrinolytic activity and plasma fibrinogen concentrations. Br Med J 1979;1:153-156.

    Google Scholar 

  45. Yarnell JW, Sweetnam PM, Rogers S, et al. Some long-term effects of smoking on the haemostatic system: A report from the Caerphilly and Speedwell Collaborative Surveys. J Clin Pathol 1987;40:909-913.

    Google Scholar 

  46. Kannel WB, D'Agostino RB, Belanger AJ. Fibrinogen, cigarette smoking, and risk of cardiovascular disease: Insights from the Framingham Study. Am Heart J 1987;113: 1006-1010.

    Google Scholar 

  47. Meade TW, Imeson J, Stirling Y. Effects of changes in smoking and other characteristics on clotting factors and the risk of ischaemic heart disease. Lancet 1987;2:986-988.

    Google Scholar 

  48. Feher MD, Rampling MW, Brown JEA. Acute changes in atherogenic and thrombogenic factors with cessation of smoking. J R Soc Med 1990;83:146-148.

    Google Scholar 

  49. Moller L, Kristensen TS. Plasma fibrinogen and ischaemic heart disease risk factors. Arterioscler Thromb 1991;11: 344-350.

    Google Scholar 

  50. Yarnell JWG, Fehily AM, Milbank J, Kubicki AJ, Eastham R, Hayes TM. Determinants of plasma lipoproteins and coagulation factorsin men from Caerphilly, South Wales. J Epidemiol Commun Health 1983;37:137-140.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sumeray, M.S., Montgomery, H.E. & Humphries, S.E. Beyond Coagulation: Fibrinogen as a Cause of Cardiovascular Surgical Disease. Cardiovasc Drugs Ther 12, 261–265 (1998). https://doi.org/10.1023/A:1007713715744

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1007713715744

Navigation