Semin Vasc Med 2002; 02(4): 429-440
DOI: 10.1055/s-2002-36771
Copyright © 2002 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Hemostatic and Rheological Variables and Risk of Cardiovascular Disease

Gordon D.O. Lowe1 , Ann Rumley1 , Peter H. Whincup2 , John Danesh3
  • 1University Department of Medicine, Royal Infirmary, Glasgow, United Kingdom
  • 2Department of Public Health Sciences, St. George's Hospital Medical School, London, United Kingdom
  • 3Department of Public Health and Primary Care, University of Cambridge, United Kingdom
Further Information

Publication History

Publication Date:
22 January 2003 (online)

ABSTRACT

Increasing blood levels of hemostatic variables may increase the risk of thrombosis, while increasing levels of rheological variables which reduce blood flow may increase the risk of ischemic events. Systematic reviews of prospective cohort studies of hemostatic and rheological variables suggest that increasing blood levels of fibrinogen, von Willebrand factor, tissue plasminogen activator antigen, fibrin D-dimer, hematocrit, viscosity, and erythrocyte sedimentation rate may be predictors of risk of coronary heart disease (CHD), but their causal relevance is unknown. At present, data for the associations of other hemostatic variables with CHD, and for the associations of hemostatic variables with stroke, venous thromboembolism, and mortality, is relatively sparse and inconclusive. More detailed syntheses of existing prospective data (such as the Fibrinogen Studies Collaboration), observational studies of CHD and the genetic determinants of these plasma components, as well as large-scale randomized trials should help to determine whether or not these associations are (1) useful in prediction of cardiovascular risk and/or (2) of causal significance.

REFERENCES

  • 1 Bloom A L, Forbes C D, Thomas D P, Tuddenham E GD. Haemostasis and Thrombosis, 3rd ed. Edinburgh: Churchill Livingstone 1994
  • 2 Emmerich J, Rosendaal F R, Cattaneo M. Combined effect of factor V Leiden and prothrombin 20210A on the risk of venous thromboembolism-pooled analysis of 8 case-control studies including 2310 cases and 3204 controls.  Thromb Haemost . 2001;  86 809-816
  • 3 Castaman G, Tosetto A, Simioni M. Phenotypic APC resistance in carriers of the A20210 prothrombin mutation is associated with an increased risk of venous thrombosis.  Thromb Haemost . 2001;  86 804-808
  • 4 Rosendaal F R. High levels of factor VIII and venous thrombosis.  Thromb Haemost . 2000;  83 1-2
  • 5 Lowe G DO, Rumley A, Woodward M. Epidemiology of coagulation factors, inhibitors and activation markers: the Third Glasgow MONICA Survey. I. Illustrative reference ranges by age, sex and hormone use.  Br J Haematol . 1997;  97 775-784
  • 6 Lowe G DO, Rumley A, Woodward M, Reid E, Rumley J. Activated protein C resistance and the FV: R506Q mutation in a random population sample: associations with cardiovascular risk factors and coagulation variables.  Thromb Haemost . 1999;  81 918-924
  • 7 Gaffney P J, Brasher M. Subunit structure of the plasmin-induced degradation products of cross-linked fibrin.  Biochem Biophys Acta . 1973;  295 308-313
  • 8 Lip G YH, Lowe G DO. Fibrin D-dimer: a useful clinical marker of thrombogenesis?.  Clin Sci . 1995;  89 205-214
  • 9 Al-Mohana J MA, Lowe G DO, Murray G D, Burns H G. Association of fibrinolytic tests with outcome of acute upper-gastrointestinal-tract bleeding.  Lancet . 1993;  341 518-521
  • 10 Lowe G DO. Clinical Blood Rheology Boca Raton, FL: CRC Press 1988: 1-10
  • 11 McCallum P K, Meade T W. Haemostatic function, arterial disease and the prevention of arterial thrombosis.  Bailliere's Clin Haematol . 1999;  12 577-599
  • 12 Lowe G DO. Haemostatic risk factors for arterial and venous thrombosis. In: Poller L, Ludlam CA, eds. Recent Advances in Blood Coagulation, 7 Edinburgh: Churchill Livingstone 1997: 69-96
  • 13 Reiner A P, Siscovick D S, Rosendaal F R. Hemostatic risk factors and arterial thrombotic disease.  Thromb Haemost . 2001;  85 584-595
  • 14 Verstraete M, Fuster V, Topol E J. Cardiovascular Thrombosis 2nd ed. New York: Lippincott-Raven 1998: 23-45
  • 15 Davies M J, Thomas A C. Plaque fissuring-one cause of acute myocardial infarction, sudden ischaemic death and crescendo angina.  Br Heart J . 1985;  53 363-373
  • 16 Antithrombotic Trialists' Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high-risk patients.  BMJ . 2002;  324 71-86
  • 17 Meade T W, North W RS, Chakrabarti R. Haemostatic function and cardiovascular death; early results of a prospective study.  Lancet . 1980;  1 1050-1054
  • 18 Lowe G DO, Drummond M M, Lorimer A R. Relationship between extent of coronary artery disease and blood viscosity.  Br Med J . 1980;  1 673-674
  • 19 Danesh J, Collins R, Appleby P, Peto R. Association of fibrinogen, C-reactive protein, albumin, or leukocyte count with coronary heart disease. Meta-analyses of prospective studies.  JAMA . 1998;  279 1477-1482
  • 20 Danesh J, Whincup P, Walker M. Low-grade inflammation and coronary heart disease: prospective study and updated meta-analyses.  Br Med J . 2000;  321 199-204
  • 21 Danesh J, Collins R, Peto R, Lowe G DO. Haematocrit, viscosity, erthryocyte sedimentation rate: meta-analyses of prospective studies of coronary heart disease.  Eur Heart J . 2000;  21 515-520
  • 22 Danesh J, Whincup P, Walker M. Fibrin D-dimer and coronary heart disease: prospective study and meta-analysis.  Circulation . 2001;  103 2323-2327
  • 23 Whincup P, Danesh J, Walker M. Von Willebrand factor and coronary heart disease: new prospective study and meta-analysis.  Eur Heart J . 2002;  23 1766-1770
  • 24 Lowe G DO, Danesh J, Rumley A. Tissue plasminogen activator antigen and coronary heart disease: new prospective study and meta-analysis.  Blood Coagul Fibrinolysis. 12 A1-A2
  • 25 Lewis M R, Callas P W, Jenny N S, Tracy R P. Longitudinal stability of coagulation, fibrinolysis, and inflammation factors in stored plasma samples.  Thromb Haemost . 2001;  86 1495-1500
  • 26 Lowe G DO, Smith W CS, Tunstall-Pedoe H D. Cardiovascular risk and haemorheology-results from the Scottish Heart Health Study and the MONICA Project, Glasgow.  Clin Hemorheol . 1988;  8 518-524
  • 27 Rumley A. Fibrinolytic and endothelial markers in cardiovascular disease and diabetes mellitus [Ph.D  thesis]. Glasgow: University of Glasgow 1996
  • 28 Bashir S A, Duffy S W, Qizilbash N. Repeat measurement of case-control data: corrections for measurement error in a study of ischaemic stroke and haemostatic factors.  Int J Epidemiol . 1997;  26 64-70
  • 29 Sakkinen P A, Macy E M, Callas P W. Analytic and biologic variability in measures of hemostasis, fibrinolysis and inflammation: assessment and implications for epidemiology.  Am J Epidemiol . 1999;  149 261-267
  • 30 Emberson J R, Whincup P H, Morris R W. Regression dilution of established and novel coronary risk factors: results from the British Regional Heart Study. Submitted for publication. 
  • 31 Lowe G DO. Fibrinogen-A Cardiovascular Risk Factor.  Mannheim, Germany: Boehringer Mannheim 1997: 1-63
  • 32 Lowe G DO. Fibrinogen: an independent coronary heart disease risk factor. In: Betteridge DJ, ed. Lipids and Vascular Disease London: Dunitz 2000: 77-84
  • 33 Maresca G, Di Blasio A, Marchioli R, Di Minno G. Measuring plasma fibrinogen to predict stroke and myocardial infarction: an update.  Arterioscler Thromb Vasc Biol . 1999;  19 1368-1377
  • 34 Lowe G DO, Fowkes F GR, Dawes J. Blood viscosity, fibrinogen and activation of coagulation and leukocytes in peripheral arterial disease and the normal population in the Edinburgh Artery Study.  Circulation . 1993;  87 1915-1920
  • 35 Lee A J, Mowbray P I, Lowe G DO. Blood viscosity and elevated carotid intima-media thickness in men and women: the Edinburgh Artery Study.  Circulation . 1998;  97 1467-1473
  • 36 Wilhelmsen L, Svardsudd K, Korsan-Bengsten K. Fibrinogen as a risk factor for stroke and myocardial infarction.  N Engl J Med . 1984;  311 501-505
  • 37 Lowe G DO, Lee A J, Rumley A. Blood viscosity and risk of cardiovascular events: the Edinburgh Artery Study.  Br J Haematol . 1997;  96 168-173
  • 38 Bainton D, Sweetnam P, Baker I. Peripheral vascular disease. Consequence for survival and association with risk factors in the Speedwell Prospective Heart Disease Study.  Br Heart J . 1994;  72 128-132
  • 39 Smith F B, Lee A J, Hau C. Plasma fibrinogen, haemostatic factors and prediction of peripheral arterial disease in the Edinburgh Artery Study.  Blood Coagul Fibrinol . 2000;  11 43-50
  • 40 Koster T, Rosendaal F R, Reitsma P H. Factor VII and fibrinogen levels as risk factors for venous thrombosis. A case-control study of plasma levels and DNA polymorphisms. Leiden Thrombophilia Study (LETS).  Thromb Haemost . 1994;  71 719-722
  • 41 Kannel W B. Influence of fibrinogen on cardiovascular disease.  Drugs . 1997;  54 S32-S40
  • 42 Woodward M, Lowe G DO, Rumley A, Tunstall-Pedoe H. Fibrinogen as a risk factor for coronary heart disease and mortality in middle-aged men and women-the Scottish Heart Health Study.  Eur Heart J . 1998;  19 55-62
  • 43 Sweetnam P M, Yarnell J WG, Lowe G DO. The relative power of heat-precipitation nephelometric and clottable (Clauss) fibrinogen in the prediction of ischaemic heart disease: the Caerphilly and Speedwell studies.  Br J Haematol . 1998;  100 582-588
  • 44 Lowe G DO, Rumley A, Mackie I J. Analytical review: plasma fibrinogen (in press).  Ann Biochem.
  • 45 Lee A J, Smith W CS, Lowe G DO, Tunstall-Pedoe H. Plasma fibrinogen and coronary risk factors: the Scottish Heart Health Study.  J Clin Epidemiol . 1990;  43 913-919
  • 46 Simmonds R E, Hermida J, Rezende S M, Lane D A. Haemostatic genetic risk factors in arterial thrombosis.  Thromb Haemost . 2001;  86 374-385
  • 47 Lane D A, Grant P J. Role of hemostatic gene polymorphisms in venous and arterial thrombosis.  Blood . 2000;  95 1517-1532
  • 48 Lowe G DO. Ancrod in treatment of acute ischaemic stroke.  Proc R Coll Phys Edin . 2001;  31(Suppl 8) 20-24
  • 49 Lowe G DO. Rheological influences on thrombosis.  Bailliere's Clin Haematol . 1994;  7 573-589
  • 50 Sweetnam P M, Thomas H F, Yarnell J WG. Fibrinogen, viscosity and the 10-year incidence of ischaemic heart disease. The Caerphilly and Speedwell studies.  Eur Heart J . 1996;  17 1814-1820
  • 51 Lowe G DO, Rumley A, Norrie J, on behalf of the West of Scotland Coronary Prevention Group. Blood rheology, cardiovascular risk factors, and cardiovascular disease: the West of Scotland Coronary Prevention Study.  Thromb Haemost . 2000;  84 553-558
  • 52 Rumley A, Lowe G DO, Sweetnam P M, Yarnell J WG, Ford R P. Factor VIII, von Willebrand factor and the risk of major ischaemic heart disease in the Caerphilly Study.  Br J Haematol . 1999;  105 110-116
  • 53 Brinkhous K M, Reddick R L, Read M S. Von Willebrand's factor and animal models: contributions to gene therapy, thrombotic thrombocytopenic purpura, and coronary artery thrombosis.  Mayo Clin Proc . 1991;  66 733-742
  • 54 Meade T W, Cooper J C, Stirling Y. Factor VIII, ABO blood group and the incidence of ischaemic heart disease.  Br J Haematol . 1994;  88 601-607
  • 55 Smith F B, Lee A J, Fowkes F GR. Hemostatic factors as predictors of ischaemic heart disease and stroke in the Edinburgh Artery Study.  Arterioscler Thromb Vasc Biol . 1997;  17 3321-3325
  • 56 Folsom A R, Wu K K, Rosamond W D, Sharrett A R, Chabless L E. Prospective study of hemostatic factors and incidence of coronary heart disease. The Atherosclerosis Risk in Communities (ARIC) study.  Circulation . 1997;  96 1102-1108
  • 57 Stephoe A, Kunz-Ebrecht S, Rumley A, Lowe G DO. Prolonged elevations in haemostatic and rheological responses following psychological forces in low socioeconomic status men and women (in press).  Thromb Haemost.
  • 58 Wannamethee S G, Lowe G DO, Whincup P H. Physical activity and hemostatic and inflammatory variables in elderly men.  Circulation . 2002;  105 1785-1790
  • 59 Rosendaal F R, Briet E, Stibbe J. Haemophilia protects against ischaemic heart disease: a study of risk factors.  Br J Haematol . 1990;  75 525-530
  • 60 Lowe G DO. Factor IX and thrombosis.  Br J Haematol . 2001;  115 507-513
  • 61 Meade T W, Ruddock V, Stirling Y, Chakrabati R, Miller G J. Fibrinolytic activity, clotting factors, and long-term incidence of ischaemic heart disease in the Northwick Park Heart Study.  Lancet . 1993;  342 1076-1079
  • 62 Junker R, Heinrich J, Schulte H, van de Loo J, Assmann G. Coagulation factor VII and the risk of coronary heart disease in healthy men.  Arterioscler Thromb Vasc Biol . 1997;  17 1539-1544
  • 63 Lowe G DO, Rumley A, Sweetnam P, Yarnell J WG, RumleyJ. Fibrin D-dimer, markers of coagulation activation, and the risk of major ischaemic heart disease in the Caerphilly Study.  Thromb Haemost . 2001;  86 822-827
  • 64 Cooper J A, Miller G J, Bauer K A. Comparison of novel haemostatic factors and conventional risk factors for prediction of coronary heart disease.  Circulation . 2000;  102 2816-2822
  • 65 The Medical Research Council's General Practice Research Framework. Thrombosis Prevention Trial.  Lancet . 1998;  351 233-241
  • 66 Meade T W, Cooper J A, Miller G J. Platelet counts and aggregation measures in the incidence of ischaemic heart disease (IHD).  Thromb Haemost . 1997;  78 926-929
  • 67 Elwood P C, Beswick A, Pickering J. Platelet tests in the prediction of myocardial infarction and ischaemic stroke: evidence from the Caerphilly Prospective Study.  Br J Haematol . 2001;  113 514-520
  • 68 Martin J F, Bath P MW, Burr M L. Influence of platelet size on outcome after myocardial infarction.  Lancet . 1991;  338 1409-1411
  • 69 Trip M D, Cats V M, van Capelle J L F, Breeken J. Platelet hyper-reactivity and prognosis in survivors of myocardial infarction.  N Engl J Med . 1990;  322 1549-1554
  • 70 Booth N A. Fibrinolysis and thrombosis.  Bailliere's Clin Haematol . 1999;  12 423-433
  • 71 De Bono D. Significance of raised plasma concentrations of tissue-type plasminogen activator and plasminogen activator inhibitor in patients at risk from ischaemic heart disease.  Br Heart J . 1994;  71 504-507
  • 72 Smith F B, Fowkes F GR, Hau C M. Tissue plasminogen activator and leucocyte elastase as predictors of cardiovascular events in subjects with angina pectoris: Edinburgh artery study.  Eur Heart J . 2000;  21 1607-1613
  • 73 Lowe G DO, Woodward M, Vessey M P. Thrombotic variables and risk of idiopathic venous thromboembolism in women aged 45-64 years: relationships to hormone replacement therapy.  Thromb Haemost . 2000;  83 530-535
  • 74 Lowe G DO, Haverkate F, Thompson S G, on behalf of the ECAT DVT Study Group. Prediction of deep vein thrombosis after elective hip replacement surgery by preoperative clinical and haemostatic variables: the ECAT DVT Study.  Thromb Haemost . 1999;  81 879-886
  • 75 McMahon A J, O'Dwyer P J, Cruickshank A M. Comparison of metabolic responses to laparoscopic and minilaparotomy cholecystectomy.  Br J Surg . 1993;  80 1255-1258
  • 76 Lowe G DO, Yarnell J WG, Rumley A, Bainton D, Sweetnam P M. C-reactive protein, fibrin D-dimer, and incident ischemic heart disease in the Speedwell Study. Are inflammation and fibrin turnover linked in pathogenesis?.  Arterioscler Thromb Vasc Biol . 2001;  21 603-610
  • 77 Lip G YH, Lowe G DO, Rumley A, Dunn F G. Increased markers of thrombogenesis in chronic atrial fibrillation: effects of warfarin treatment.  Br Heart J . 1995;  73 527-533
  • 78 Lip G YH, Zafiris J, Watson R DS. Fibrin D-dimer and β-thromboglobulin as markers of thrombogenesis and platelet activation in atrial fibrillation. Effects of introducing ultra-low-dose warfarin and aspirin.  Circulation . 1996;  94 425-431
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