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Can haemostatic factors predict atherothrombosis?

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Abstract

Thrombosis is “haemostasis in the wrong place”, and there is increasing evidence that haemostatic factors are associated with increased risk of atherothrombotic events. Increasing plasma levels of fibrinogen are associated with increased risks of coronary heart disease, stroke and peripheral arterial disease, and with vascular and nonvascular mortality. However, as with other markers of haemostasis (and of inflammation), their additional predictive value to conventional risk factors is small. Ongoing studies of activation markers of coagulation (e.g. fibrin D-dimer), endothelium (e.g. von Willebrand factor, tissue plasminogen activator antigen) and platelets (mean platelet volume) may provide additional predictive value for atherothrombotic events. However, at present there is no sufficient evidence base for their routine measurement in prediction.

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References

  1. Macfarlane RG (1977) Introduction. Br Med Bull 33:183–185

    Google Scholar 

  2. Vasan RS (2006) Biomarkers of cardiovascular disease: molecular basis and practical considerations. Circulation 113:2335–2362

    Article  PubMed  Google Scholar 

  3. Lowe GDO (2006) Can haematological tests predict cardiovascular risk? The 2005 Kettle Lecture. Br J Haematol 133:232–250

    Article  PubMed  CAS  Google Scholar 

  4. Lowe GDO (2008) Common risk factors for both arterial and venous thrombosis. Br J Haematol 140:488–495

    Article  PubMed  Google Scholar 

  5. Jefferis BJ, Lowe GDO, Welsh P, Rumley A, Lawlor DA, Ebrahim S, Carson C, Doig M, Feyerabend C, McMeekin L, Wannamethee SG, Cook DG, Whincup PH (2010) Secondhand smoke (SHS) exposure is associated with circulating markers of inflammation and endothelial function in adult men and women. Atherosclerosis 208:550–556

    Article  PubMed  CAS  Google Scholar 

  6. Ramsay S, Lowe GDO, Rumley A, Whincup PH, Morris RW, Wannamethee SG (2008) Relationships of inflammatory and haemostatic markers with social class: results from a population-based study of older men. Atherosclerosis 197:654–661

    Article  PubMed  CAS  Google Scholar 

  7. Woodward M, Rumley A, Welsh P, MacMahon S, Lowe G (2007) A comparison of the associations between seven haemostatic or inflammatory variables and coronary heart disease. J Thromb Haemost 5:1795–1800

    Article  PubMed  CAS  Google Scholar 

  8. Libby P, Ridker PM, Maseri A (2002) Inflammation and atherosclerosis. Circulation 105:1135–1143

    Article  PubMed  CAS  Google Scholar 

  9. Danesh J, Wheeler JG, Hirshfield GM, Eda S, Eiriksdottir G, Rumley A, Lowe GDO, Pepys MB, Gudnason V (2004) C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease. N Engl J Med 350:1387–1397

    Article  PubMed  CAS  Google Scholar 

  10. Danesh J, Kaptoge S, Mann AG, Sarwar N, Wood A, Angleman SB, Wensley F, Higgins JPT, Lennon L, Eiriksdottir G, Rumley A, Whincup PH, Lowe GDO, Gudnason V (2008) Long-term interleukin-6 levels and subsequent risk of coronary heart disease: two new prospective studies and a systematic review. PLoS Med 5:e78

    Article  PubMed  Google Scholar 

  11. Woodward M, Rumley A, Tunstall-Pedoe H, Lowe GDO (1999) Associations of blood rheology and interleukin-6 with cardiovascular risk factors and prevalent cardiovascular disease. Br J Haematol 104:246–257

    Article  PubMed  CAS  Google Scholar 

  12. Wannamethee SG, Whincup PH, Rumley A, Lowe GDO (2007) Interrelationships of interleukin-6, cardiovascular risk factors and the metabolic syndrome among older men. J Thromb Haemost 5:1637–1643

    Article  PubMed  CAS  Google Scholar 

  13. Patterson CC, Smith AE, Yarnell JWG, Rumley A, Ben-Shlomo Y, Lowe GDO (2009) The associations of interleukin-6 (IL-6) and downstream inflammatory markers with risk of cardiovascular disease: the Caerphilly Study. Atherosclerosis (Epub ahead of print). PMID: 19836021 [PubMed: as supplied by publisher]

  14. Empana JP, Canoui-Poitrine F, Luc G, Juhan-Vague I, Morange P, Arveiler D, Ferrieres J, Amoyel P, Bingham A, Montaye M, Ruidavets JB, Haas B, Evans A, Ducimetiere P, PRIME Study Group (2008) Contribution of novel biomarkers to incident stable angina and acute coronary syndrome: the PRIME Study. Eur Heart J 29:1966–1974

    Article  PubMed  CAS  Google Scholar 

  15. Wannamethee SG, Whincup PH, Shaper AG, Rumley A, Lennon L, Lowe GDO (2009) Circulating inflammatory and hemostatic biomarkers are associated with risk of myocardial infarction and coronary death, but not angina pectoris, in older men. J Thromb Haemost 7:1605–1611

    Article  PubMed  CAS  Google Scholar 

  16. Rumley A, Emberson JR, Wannamethee SG, Lennon L, Whincup PH, Lowe GDO (2006) Effects of older age on fibrin D-dimer, C-reactive protein and other hemostatic and inflammatory variables in men aged 60–79 years. J Thromb Haemost 4:982–987

    Article  PubMed  CAS  Google Scholar 

  17. Fibrinogen Studies Collaboration (2004) Collaborative meta-analysis of prospective studies of plasma fibrinogen and cardiovascular disease. Eur J Cardiovas Prev Rehabil 11:9–17

    Google Scholar 

  18. The Emerging Risk Factors Collaboration (2007) Analysis of individual data on lipid, inflammatory and other markers in over 1.1 million participants in 104 prospective studies of cardiovascular disease. Eur J Epidemiol 22:839–869

    Google Scholar 

  19. Woodward M, Tunstall-Pedoe H, Rumley A, Lowe GDO (2009) Does fibrinogen add to prediction of cardiovascular disease? Results from the Scottish Heart Health Extended Cohort Study. Br J Haematol 146:442–446

    Article  PubMed  CAS  Google Scholar 

  20. Shah T, Casas JP, Cooper JA, Tzoulaki I, Sofat R, McCormack V, Smeeth L, Deanfield JE, Lowe GD, Rumley A, Fowkes FGR, Humphries SE, Hingorani AD (2008) Critical appraisal of CRP measurement for the prediction of coronary heart disease events: new data and systematic review of 31 prospective cohorts. Int J Epidemiol 38:217–231

    Google Scholar 

  21. Wu O, Robertson L, Twaddle S, Lowe GD, Clark P, Greaves M, Walker ID, Langhorne P, Brenkel I, Regan L, Greer I (2006) Screening for thrombophilia in high-risk situations: systematic review and cost-effectiveness analysis. The thrombosis: risk and economic assessement of thrombophilia screening (TREATS) study. Health Technol Assess 10:1–110

    PubMed  CAS  Google Scholar 

  22. Tuinenburg A, Mauser-Bunschoten EP, Verhaar MC, Biesma DH, Schutgens REG (2009) Cardiovascular disease in patients with hemophilia. J Thromb Haemost 7:247–254

    Article  PubMed  CAS  Google Scholar 

  23. Wu O, Bayoumi N, Vickers MA, Clark P (2008) ABO(H) blood groups and vascular disease: a systematic review and meta-analysis. J Thromb Haemost 6:62–69

    Article  PubMed  CAS  Google Scholar 

  24. Kim RJ, Becker RC (2003) Association between factor V Leiden, prothrombin G20210A, and methylenetetrahydrofolatereductase C677T mutations and events of the arterial circulatory system: a meta-analysis of published studies. Am Heart J 146:948–957

    Article  PubMed  CAS  Google Scholar 

  25. Ye Z, Liu EHC, Higgins JPT, Keavney BD, Lowe GDO, Collins R, Danesh J (2006) Seven haemostatic gene polymorphisms in coronary disease: meta-analysis of 66,155 cases and 91,307 controls. Lancet 367:651–658

    Article  PubMed  CAS  Google Scholar 

  26. Fibrinogen Studies Collaboration (2005) Plasma fibrinogen level and the risk of major cardiovascular diseases and non-vascular mortality: an individual participant meta-analysis. JAMA 294:1799–1809

    Google Scholar 

  27. Fibrinogen Studies Collaboration (2007) Associations of plasma fibrinogen levels with established cardiovascular risk factors, inflammatory markers and other characteristics; individual participant meta-analysis of 154,211 adults in 31 prospective studies. Am J Epidemiol 166:867–879

    Google Scholar 

  28. Ridker PM, Stampfer MJ, Rifai N (2001) Novel risk factors for systemic atherosclerosis: a comparison of C-reactive protein, fibrinogen, homocysteine, lipoprotein (a), and standard cholesterol screening as predictors of peripheral arterial disease. JAMA 285:2481–2485

    Article  PubMed  CAS  Google Scholar 

  29. Tzoulaki I, Murray GD, Lee AJ, Rumley A, Lowe GDO, Fowkes FGR (2007) Inflammatory, haemostatic and rheological markers for incident peripheral arterial disease: Edinburgh Artery Study. Eur Heart J 28:354–362

    Article  PubMed  CAS  Google Scholar 

  30. Emerging Risk Factors Collaboration (2010) C-reactive protein concentration and the risk of coronary heart disease, stroke and mortality. Lancet 375:132–140

    Article  Google Scholar 

  31. Davey Smith G, Harbord R, Milton J, Ebrahim S, Sterne JAC (2005) Does elevated plasma fibrinogen increase the risk of coronary heart disease? Evidence from a meta-analysis of genetic association studies. Arterioscler Thromb Vasc Biol 25:2228–2233

    Article  Google Scholar 

  32. Keavney B, Danesh J, Parish S, Palmer A, Clark S, Youngman L, Delepine M, Lathrop M, Peto R, Collins R for the International Studies of Infarct Survival (ISIS) Collaborators (2006) Fibrinogen and coronary heart disease: test of causality by ‘Mendelian randomization’. Int J Epidemiol 35:935–943

    Google Scholar 

  33. Freeman MS, Mansfield MW, Barrett JH, Grant PJ (2002) Genetic contribution to circulating levels of hemostatic factors in healthy families with effects of known genetic polymorphisms on heritability. Arterioscler Thromb Vasc Biol 22:506–510

    Article  PubMed  CAS  Google Scholar 

  34. Meade TW, Cooper JC, Stirling Y, Howarth DJ, Factor RuddockV, II VI (1994) ABO blood group and the incidence of ischaemic heart disease. Br J Haematol 88:601–607

    Article  PubMed  CAS  Google Scholar 

  35. Rumley A, Lowe GDO, Sweetnam PM, Yarnell JWG, Ford RP (1999) Factor VIII, von Willebrand factor and the risk of major ischaemic heart disease in the Caerphilly Study. Br J Haematol 105:110–116

    Google Scholar 

  36. Whincup P, Danesh J, Walker M, Lennon L, Thomson A, Appleby P, Rumley A, Lowe GDO (2002) Von Willebrand factor and coronary heart disease: prospective study and meta-analysis. Eur Heart J 23:1764–1770

    Article  PubMed  CAS  Google Scholar 

  37. Sramek A, Kriek MD, Rosendaal MD (2003) Decreased mortality of ischaemic heart disease among carriers of haemophilia. Lancet 362:351–354

    Article  PubMed  CAS  Google Scholar 

  38. Juul K, Tybjaerg-Hansen A, Schnohr P, Nordestgaard BG (2004) Factor V Leiden and the risk for venous thromboembolism in the adult Danish population. Ann Intern Med 140:330–347

    PubMed  CAS  Google Scholar 

  39. Weischer M, Juul K, Zacho J, Jensen GB, Steffensen R, Schroeder TV, Tybjarg-Hansen A, Nordestgaard BG (2010) Prothrombin and risk of venous thromboembolism, ischemic heart disease and ischemic cerebrovascular disease in the general population. Atherosclerosis 208(2):480–483

    Article  PubMed  CAS  Google Scholar 

  40. Emmerich J, Rosendaal FR, Cattaneo M, Margaglione M, De Stefano V, Cumming T, Arruda V, Hillop A, Reny J-L (2001) Combined effect of factor V Leiden and prothrombin 20210A on the risk of venous thromboembolism. Thromb Haemost 86:809–816

    PubMed  CAS  Google Scholar 

  41. Castaman G, Tosetto A, Simioni M, Ruggeri M, Madeo D, Rodeghiero F (2001) Phenotypic APC resistance in carriers of the A20210 prothrombin mutation is associated with an increased risk of venous thrombosis. Thromb Haemost 86:804–808

    PubMed  CAS  Google Scholar 

  42. Smith A, Patterson C, Yarnell J, Rumley A, Ben-Shlomo Y, Lowe G (2005) Which hemostatic markers add to the predictive value of conventional risk factors for coronary heart disease and ischemic stroke? The Caerphilly Study. Circulation 112:3080–3087

    Article  PubMed  Google Scholar 

  43. van der Bom JG, Bots ML, Haverkate F, ElineSlagboom P, Meijer P, de long Paulus TVM, Hofman A, GrobbeeDE KluftC (1996) Reduced response to activated protein C is associated with increased risk for cerebrovascular disease. Ann Intern Med 125:265–269

    PubMed  Google Scholar 

  44. Meade TW, De Stavola B (2007) Long-term effects of haemostatic variables on fatal coronary heart disease: 30 year results from the first prospective Northwick Park Heart Study (NPHS-1). J Thromb Haemost 5:461–471

    Article  PubMed  Google Scholar 

  45. Rumley A, Lowe G, Stott D, Welsh P, Robertson M, Murray H, Ford I, Sattar N, Westendorp R, de Craen T (2009) Coagulation activation markers are associated with cardiovascular events and death in the elderly at risk: PROSPER study cohort. J Thromb Haemost 7:Suppl 2 (abstract OC-WE-033)

  46. Danesh J, Whincup P, Walker M, Lennon L, Thomson A, Appleby P, Rumley A, Lowe GDO (2001) Fibrin D-dimer and coronary heart disease: prospective study and meta-analysis. Circulation 103:2323–2327

    PubMed  CAS  Google Scholar 

  47. Tzoulaki I, Murray GD, Lee AJ, Rumley A, Lowe GDO, Fowkes GR (2007) Relative value of inflammatory, hemostatic and rheological factors for incident myocardial infarction and stroke: the Edinburgh Artery Study. Circulation 115:2119–2127

    Article  PubMed  Google Scholar 

  48. Lowe GDO, Danesh J, Lewington S, Walker M, Lennon L, Thomson A, Rumley A, Whincup PH (2004) Tissue plasminogen activator antigen and coronary heart disease: prospective study and meta-analysis. Eur Heart J 25:252–259

    Article  PubMed  CAS  Google Scholar 

  49. van der Bom JG, Heckbert SR, Lumley T, Holmes CE, Cushman M, Folsom AR, Rosendaal FR, Psaty BM (2009) Platelet count and the risk for thrombosis and death in the elderly. J Thromb Haemost 7:399–405

    Article  PubMed  Google Scholar 

  50. Chu SG, Becker RC, Berger PB, Bhatt DL, Eikelboom JW, Konkle B, Mohler ER, Berger JS (2007) Mean platelet volume as a predictor of cardiovascular risk: a meta-analysis. J Thromb Haemost 5:Suppl 2 (abstract number AS-TH-033)

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  1. Emeritus Professor of Vascular Medicine, Institute of Cardiovascular and Medical Sciences, University of Glasgow, BHF GCRC, 126 University Place, Glasgow, G12 8TA, UK

    Gordon Lowe

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Correspondence to Gordon Lowe.

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Lowe, G. Can haemostatic factors predict atherothrombosis?. Intern Emerg Med 6, 497–501 (2011). https://doi.org/10.1007/s11739-011-0536-4

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