Semin Thromb Hemost 2011; 37(8): 885-896
DOI: 10.1055/s-0031-1297367
© Thieme Medical Publishers

Relationship between Venous and Arterial Thrombosis: A Review of the Literature from a Causal Perspective

Willem M. Lijfering1 , Linda E. Flinterman1 , Jan P. Vandenbroucke1 , Frits R. Rosendaal1 , 2 , Suzanne C. Cannegieter1
  • 1Department of Clinical Epidemiology, Leiden University Medical Center, The Netherlands
  • 2Department of Thrombosis and Hemostasis, Leiden University Medical Center, The Netherlands
Further Information

Publication History

Publication Date:
23 December 2011 (online)


Venous thrombosis and arterial thrombosis are traditionally regarded as two different diseases with respect to pathophysiology, epidemiology, and treatment strategies. Research findings of the past few years suggest that this categorical distinction may be too strict. However, whether the described relationship between venous and arterial thrombosis is real or a result of other factors such as confounding, chance, or bias is still unclear. In this review, we discuss the current literature while using causal diagrams to better understand possible causal relations between cardiovascular risk factors, atherosclerosis, arterial thrombosis, and venous thrombosis. Furthermore, we propose study designs to investigate the causal link between venous and arterial thrombosis. In addition, we comment on the effect of statin use on the occurrence of both arterial and venous thrombosis. The possible clinical implications of these findings are discussed.


  • 1 Fauci A S, Braunwald E, Kasper D L et al.. Harrison's Principles of Internal Medicine. 17th ed. New York, NY: McGraw-Hill; 2008
  • 2 Squizzato A, Galli M, Romualdi E et al.. Statins, fibrates, and venous thromboembolism: a meta-analysis.  Eur Heart J. 2010;  31 (10) 1248-1256
  • 3 Ageno W, Becattini C, Brighton T, Selby R, Kamphuisen P W. Cardiovascular risk factors and venous thromboembolism: a meta-analysis.  Circulation. 2008;  117 (1) 93-102
  • 4 Sørensen H T, Horvath-Puho E, Søgaard K K et al.. Arterial cardiovascular events, statins, low-dose aspirin and subsequent risk of venous thromboembolism: a population-based case–control study.  J Thromb Haemost. 2009;  7 (4) 521-528
  • 5 Sørensen H T, Horvath-Puho E, Pedersen L, Baron J A, Prandoni P. Venous thromboembolism and subsequent hospitalisation due to acute arterial cardiovascular events: a 20-year cohort study.  Lancet. 2007;  370 (9601) 1773-1779
  • 6 Becattini C, Agnelli G, Prandoni P et al.. A prospective study on cardiovascular events after acute pulmonary embolism.  Eur Heart J. 2005;  26 (1) 77-83
  • 7 Klok F A, Mos I C, Broek L et al.. Risk of arterial cardiovascular events in patients after pulmonary embolism.  Blood. 2009;  114 (8) 1484-1488
  • 8 Prandoni P, Bilora F, Marchiori A et al.. An association between atherosclerosis and venous thrombosis.  N Engl J Med. 2003;  348 (15) 1435-1441
  • 9 van der Hagen P B, Folsom A R, Jenny N S et al.. Subclinical atherosclerosis and the risk of future venous thrombosis in the Cardiovascular Health Study.  J Thromb Haemost. 2006;  4 (9) 1903-1908
  • 10 Reich L M, Folsom A R, Key N S et al.. Prospective study of subclinical atherosclerosis as a risk factor for venous thromboembolism.  J Thromb Haemost. 2006;  4 (9) 1909-1913
  • 11 Lijfering W M, Rosendaal F R, Cannegieter S C. Risk factors for venous thrombosis - current understanding from an epidemiological point of view.  Br J Haematol. 2010;  149 (6) 824-833
  • 12 Collins R, MacMahon S, Flather M et al.. Clinical effects of anticoagulant therapy in suspected acute myocardial infarction: systematic overview of randomised trials.  BMJ. 1996;  313 (7058) 652-659
  • 13 Bath P M, Iddenden R, Bath F J. Low-molecular-weight heparins and heparinoids in acute ischemic stroke : a meta-analysis of randomized controlled trials.  Stroke. 2000;  31 (7) 1770-1778
  • 14 Prandoni P. Venous thromboembolism and atherosclerosis: is there a link?.  J Thromb Haemost. 2007;  5 (Suppl 1) 270-275
  • 15 Meade T W, Mellows S, Brozovic M et al.. Haemostatic function and ischaemic heart disease: principal results of the Northwick Park Heart Study.  Lancet. 1986;  2 (8506) 533-537
  • 16 Folsom A R, Rosamond W D, Shahar E The Atherosclerosis Risk in Communities (ARIC) Study Investigators et al. Prospective study of markers of hemostatic function with risk of ischemic stroke.  Circulation. 1999;  100 (7) 736-742
  • 17 De Buyzere M, Philippé J, Duprez D, Baele G, Clement D L. Coagulation system activation and increase of D-dimer levels in peripheral arterial occlusive disease.  Am J Hematol. 1993;  43 (2) 91-94
  • 18 Becattini C, Vedovati M C, Ageno W, Dentali F, Agnelli G. Incidence of arterial cardiovascular events after venous thromboembolism: a systematic review and a meta-analysis.  J Thromb Haemost. 2010;  8 (5) 891-897
  • 19 Hansson G K. Inflammatory mechanisms in atherosclerosis.  J Thromb Haemost. 2009;  7 (Suppl 1) 328-331
  • 20 Borissoff J I, Heeneman S, Kilinç E et al.. Early atherosclerosis exhibits an enhanced procoagulant state.  Circulation. 2010;  122 (8) 821-830
  • 21 Roumen-Klappe E M, den Heijer M, van Uum S H, van der Ven-Jongekrijg J, van der Graaf F, Wollersheim H. Inflammatory response in the acute phase of deep vein thrombosis.  J Vasc Surg. 2002;  35 (4) 701-706
  • 22 Roumen-Klappe E M, Janssen M C, Van Rossum J et al.. Inflammation in deep vein thrombosis and the development of post-thrombotic syndrome: a prospective study.  J Thromb Haemost. 2009;  7 (4) 582-587
  • 23 Price P A, Faus S A, Williamson M K. Warfarin causes rapid calcification of the elastic lamellae in rat arteries and heart valves.  Arterioscler Thromb Vasc Biol. 1998;  18 (9) 1400-1407
  • 24 Rennenberg R J, van Varik B J, Schurgers L J et al.. Chronic coumarin treatment is associated with increased extracoronary arterial calcification in humans.  Blood. 2010;  115 (24) 5121-5123
  • 25 Handke M, Harloff A, Bode C, Geibel A. Patent foramen ovale and cryptogenic stroke: a matter of age?.  Semin Thromb Hemost. 2009;  35 (5) 505-514
  • 26 Bova C, Marchiori A, Noto A et al.. Incidence of arterial cardiovascular events in patients with idiopathic venous thromboembolism. A retrospective cohort study.  Thromb Haemost. 2006;  96 (2) 132-136
  • 27 Abdollahi M, Cushman M, Rosendaal F R. Obesity: risk of venous thrombosis and the interaction with coagulation factor levels and oral contraceptive use.  Thromb Haemost. 2003;  89 (3) 493-498
  • 28 Pomp E R, le Cessie S, Rosendaal F R, Doggen C J. Risk of venous thrombosis: obesity and its joint effect with oral contraceptive use and prothrombotic mutations.  Br J Haematol. 2007;  139 (2) 289-296
  • 29 Lijfering W M, Christiansen S C, Naess I A et al.. The risk of venous thrombosis related to increase in body mass index is mediated by factor VIII induced APC-resistance.  Blood. 2009;  114 453 (ASH Annual Meeting Abstracts)
  • 30 Bank I, Libourel E J, Middeldorp S et al.. Elevated levels of FVIII:C within families are associated with an increased risk for venous and arterial thrombosis.  J Thromb Haemost. 2005;  3 (1) 79-84
  • 31 Faber D R, de Groot P G, Visseren F L. Role of adipose tissue in haemostasis, coagulation and fibrinolysis.  Obes Rev. 2009;  10 (5) 554-563
  • 32 Darvall K A, Sam R C, Silverman S H, Bradbury A W, Adam D J. Obesity and thrombosis.  Eur J Vasc Endovasc Surg. 2007;  33 (2) 223-233
  • 33 Hautanen A. Synthesis and regulation of sex hormone-binding globulin in obesity.  Int J Obes Relat Metab Disord. 2000;  24 (Suppl 2) S64-S70
  • 34 Middeldorp S, Meijers J C, van den Ende A E et al.. Effects on coagulation of levonorgestrel- and desogestrel-containing low dose oral contraceptives: a cross-over study.  Thromb Haemost. 2000;  84 (1) 4-8
  • 35 Naess I A, Christiansen S C, Romundstad P, Cannegieter S C, Rosendaal F R, Hammerstrøm J. Incidence and mortality of venous thrombosis: a population-based study.  J Thromb Haemost. 2007;  5 (4) 692-699
  • 36 Mahmoodi B K, Gansevoort R T, Veeger N J Prevention of Renal and Vascular End-stage Disease (PREVEND) Study Group et al. Microalbuminuria and risk of venous thromboembolism.  JAMA. 2009;  301 (17) 1790-1797
  • 37 Tsai A W, Cushman M, Rosamond W D, Heckbert S R, Polak J F, Folsom A R. Cardiovascular risk factors and venous thromboembolism incidence: the longitudinal investigation of thromboembolism etiology.  Arch Intern Med. 2002;  162 (10) 1182-1189
  • 38 Holst A G, Jensen G, Prescott E. Risk factors for venous thromboembolism: results from the Copenhagen City Heart Study.  Circulation. 2010;  121 (17) 1896-1903
  • 39 Heit J A, Leibson C L, Ashrani A A, Petterson T M, Bailey K R, Melton III L J. Is diabetes mellitus an independent risk factor for venous thromboembolism?: a population-based case–control study.  Arterioscler Thromb Vasc Biol. 2009;  29 (9) 1399-1405
  • 40 Petrauskiene V, Falk M, Waernbaum I, Norberg M, Eriksson J W. The risk of venous thromboembolism is markedly elevated in patients with diabetes.  Diabetologia. 2005;  48 (5) 1017-1021
  • 41 Ageno W, Prandoni P, Romualdi E et al.. The metabolic syndrome and the risk of venous thrombosis: a case–control study.  J Thromb Haemost. 2006;  4 (9) 1914-1918
  • 42 Dentali F, Squizzato A, Ageno W. The metabolic syndrome as a risk factor for venous and arterial thrombosis.  Semin Thromb Hemost. 2009;  35 (5) 451-457
  • 43 Steffen L M, Cushman M, Peacock J M et al.. Metabolic syndrome and risk of venous thromboembolism: Longitudinal Investigation of Thromboembolism Etiology.  J Thromb Haemost. 2009;  7 (5) 746-751
  • 44 Borch K H, Braekkan S K, Mathiesen E B et al.. Abdominal obesity is essential for the risk of venous thromboembolism in the metabolic syndrome: the Tromsø study.  J Thromb Haemost. 2009;  7 (5) 739-745
  • 45 Chamberlain A M, Folsom A R, Heckbert S R, Rosamond W D, Cushman M. High-density lipoprotein cholesterol and venous thromboembolism in the Longitudinal Investigation of Thromboembolism Etiology (LITE).  Blood. 2008;  112 (7) 2675-2680
  • 46 Glynn R J, Rosner B. Comparison of risk factors for the competing risks of coronary heart disease, stroke, and venous thromboembolism.  Am J Epidemiol. 2005;  162 (10) 975-982
  • 47 Doll R, Peto R, Wheatley K, Gray R, Sutherland I. Mortality in relation to smoking: 40 years' observations on male British doctors.  BMJ. 1994;  309 (6959) 901-911
  • 48 Wannamethee S G, Lowe G D, Shaper A G, Rumley A, Lennon L, Whincup P H. Associations between cigarette smoking, pipe/cigar smoking, and smoking cessation, and haemostatic and inflammatory markers for cardiovascular disease.  Eur Heart J. 2005;  26 (17) 1765-1773
  • 49 Pomp E R, Rosendaal F R, Doggen C J. Smoking increases the risk of venous thrombosis and acts synergistically with oral contraceptive use.  Am J Hematol. 2008;  83 (2) 97-102
  • 50 Severinsen M T, Kristensen S R, Johnsen S P, Dethlefsen C, Tjønneland A, Overvad K. Smoking and venous thromboembolism: a Danish follow-up study.  J Thromb Haemost. 2009;  7 (8) 1297-1303
  • 51 Mulder R, van Schouwenburg I M, Mahmoodi B K et al.. Associations between high factor VIII and low free protein S levels with traditional arterial thrombotic risk factors and their risk on arterial thrombosis: results from a retrospective family cohort study.  Thromb Res. 2010;  126 (4) e249-e254
  • 52 Doggen C J, Rosendaal F R, Meijers J C. Levels of intrinsic coagulation factors and the risk of myocardial infarction among men: opposite and synergistic effects of factors XI and XII.  Blood. 2006;  108 (13) 4045-4051
  • 53 Folsom A R, Wu K K, Shahar E, Davis C E. The Atherosclerosis Risk in Communities (ARIC) Study Investigators . Association of hemostatic variables with prevalent cardiovascular disease and asymptomatic carotid artery atherosclerosis.  Arterioscler Thromb. 1993;  13 (12) 1829-1836
  • 54 Ye Z, Liu E H, Higgins J P et al.. Seven haemostatic gene polymorphisms in coronary disease: meta-analysis of 66,155 cases and 91,307 controls.  Lancet. 2006;  367 (9511) 651-658
  • 55 Mahmoodi B K, Brouwer J L, Veeger N J, van der Meer J. Hereditary deficiency of protein C or protein S confers increased risk of arterial thromboembolic events at a young age: results from a large family cohort study.  Circulation. 2008;  118 (16) 1659-1667
  • 56 Rosendaal F R. Clotting and myocardial infarction: a cycle of insights.  J Thromb Haemost. 2003;  1 (4) 640-642
  • 57 Rosendaal F R, Varekamp I, Smit C et al.. Mortality and causes of death in Dutch haemophiliacs, 1973-86.  Br J Haematol. 1989;  71 (1) 71-76
  • 58 Triemstra M, Rosendaal F R, Smit C, Van der Ploeg H M, Briët E. Mortality in patients with hemophilia. Changes in a Dutch population from 1986 to 1992 and 1973 to 1986.  Ann Intern Med. 1995;  123 (11) 823-827
  • 59 Srámek A, Kriek M, Rosendaal F R. Decreased mortality of ischaemic heart disease among carriers of haemophilia.  Lancet. 2003;  362 (9381) 351-354
  • 60 Smith P, Arnesen H, Holme I. The effect of warfarin on mortality and reinfarction after myocardial infarction.  N Engl J Med. 1990;  323 (3) 147-152
  • 61 The Lipid Research Clinics Coronary Primary Prevention Trial results. I. Reduction in incidence of coronary heart disease.  JAMA. 1984;  251 (3) 351-364
  • 62 Baigent C, Keech A, Kearney P M Cholesterol Treatment Trialists' (CTT) Collaborators et al. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins.  Lancet. 2005;  366 (9493) 1267-1278
  • 63 Ramcharan A S, Van Stralen K J, Snoep J D, Mantel-Teeuwisse A K, Rosendaal F R, Doggen C J. HMG-CoA reductase inhibitors, other lipid-lowering medication, antiplatelet therapy, and the risk of venous thrombosis.  J Thromb Haemost. 2009;  7 (4) 514-520
  • 64 Glynn R J, Danielson E, Fonseca F A et al.. A randomized trial of rosuvastatin in the prevention of venous thromboembolism.  N Engl J Med. 2009;  360 (18) 1851-1861
  • 65 Cushman M. A new indication for statins to prevent venous thromboembolism? Not yet.  J Thromb Haemost. 2009;  7 (4) 511-513
  • 66 Morishita E, Asakura H, Saito M et al.. Elevated plasma levels of free-form of TFPI antigen in hypercholesterolemic patients.  Atherosclerosis. 2001;  154 (1) 203-212
  • 67 Musiał J, Undas A, Undas R, Brozek J, Szczeklik A. Treatment with simvastatin and low-dose aspirin depresses thrombin generation in patients with coronary heart disease and borderline-high cholesterol levels.  Thromb Haemost. 2001;  85 (2) 221-225
  • 68 Dangas G, Badimon J J, Smith D A et al.. Pravastatin therapy in hyperlipidemia: effects on thrombus formation and the systemic hemostatic profile.  J Am Coll Cardiol. 1999;  33 (5) 1294-1304
  • 69 Ridker P M, Danielson E, Fonseca F A JUPITER Study Group et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein.  N Engl J Med. 2008;  359 (21) 2195-2207
  • 70 Piazza G, Goldhaber S Z. Venous thromboembolism and atherothrombosis: an integrated approach.  Circulation. 2010;  121 (19) 2146-2150
  • 71 Heit J A, Silverstein M D, Mohr D N, Petterson T M, O'Fallon W M, Melton III L J. Risk factors for deep vein thrombosis and pulmonary embolism: a population-based case–control study.  Arch Intern Med. 2000;  160 (6) 809-815
  • 72 Heit J A, Kobbervig C E, James A H, Petterson T M, Bailey K R, Melton III L J. Trends in the incidence of venous thromboembolism during pregnancy or postpartum: a 30-year population-based study.  Ann Intern Med. 2005;  143 (10) 697-706
  • 73 van Hylckama Vlieg A, Helmerhorst F M, Vandenbroucke J P, Doggen C J, Rosendaal F R. The venous thrombotic risk of oral contraceptives, effects of oestrogen dose and progestogen type: results of the MEGA case–control study.  BMJ. 2009;  339 b2921
  • 74 Lidegaard Ø, Løkkegaard E, Svendsen A L, Agger C. Hormonal contraception and risk of venous thromboembolism: national follow-up study.  BMJ. 2009;  339 b2890
  • 75 Blom J W, Doggen C J, Osanto S, Rosendaal F R. Malignancies, prothrombotic mutations, and the risk of venous thrombosis.  JAMA. 2005;  293 (6) 715-722
  • 76 Ginsberg J S, Wells P S, Brill-Edwards P et al.. Antiphospholipid antibodies and venous thromboembolism.  Blood. 1995;  86 (10) 3685-3691
  • 77 Matta F, Singala R, Yaekoub A Y, Najjar R, Stein P D. Risk of venous thromboembolism with rheumatoid arthritis.  Thromb Haemost. 2009;  101 (1) 134-138
  • 78 Brouwer J L, Bijl M, Veeger N J, Kluin-Nelemans H C, van der Meer J. The contribution of inherited and acquired thrombophilic defects, alone or combined with antiphospholipid antibodies, to venous and arterial thromboembolism in patients with systemic lupus erythematosus.  Blood. 2004;  104 (1) 143-148
  • 79 Grainge M J, West J, Card T R. Venous thromboembolism during active disease and remission in inflammatory bowel disease: a cohort study.  Lancet. 2010;  375 (9715) 657-663
  • 80 van Zaane B, Squizzato A, Huijgen R et al.. Increasing levels of free thyroxine as a risk factor for a first venous thrombosis: a case–control study.  Blood. 2010;  115 (22) 4344-4349
  • 81 Lijfering W M, Ten Kate M K, Sprenger H G, van der Meer J. Absolute risk of venous and arterial thrombosis in HIV-infected patients and effects of combination antiretroviral therapy.  J Thromb Haemost. 2006;  4 (9) 1928-1930
  • 82 Mahmoodi B K, ten Kate M K, Waanders F et al.. High absolute risks and predictors of venous and arterial thromboembolic events in patients with nephrotic syndrome: results from a large retrospective cohort study.  Circulation. 2008;  117 (2) 224-230
  • 83 Wattanakit K, Cushman M, Stehman-Breen C, Heckbert S R, Folsom A R. Chronic kidney disease increases risk for venous thromboembolism.  J Am Soc Nephrol. 2008;  19 (1) 135-140
  • 84 Ocak G, Verduijn M, Vossen C Y et al.. Chronic kidney disease stages 1-3 increase the risk of venous thrombosis.  J Thromb Haemost. 2010;  8 (11) 2428-2435
  • 85 Cannegieter S C, Doggen C J, van Houwelingen H C, Rosendaal F R. Travel-related venous thrombosis: results from a large population-based case control study (MEGA study).  PLoS Med. 2006;  3 (8) e307
  • 86 Smeeth L, Cook C, Thomas S, Hall A J, Hubbard R, Vallance P. Risk of deep vein thrombosis and pulmonary embolism after acute infection in a community setting.  Lancet. 2006;  367 (9516) 1075-1079
  • 87 Lijfering W M, Brouwer J L, Veeger N J et al.. Selective testing for thrombophilia in patients with first venous thrombosis: results from a retrospective family cohort study on absolute thrombotic risk for currently known thrombophilic defects in 2479 relatives.  Blood. 2009;  113 (21) 5314-5322
  • 88 Rosendaal F R, Koster T, Vandenbroucke J P, Reitsma P H. High risk of thrombosis in patients homozygous for factor V Leiden (activated protein C resistance).  Blood. 1995;  85 (6) 1504-1508
  • 89 Poort S R, Rosendaal F R, Reitsma P H, Bertina R M. A common genetic variation in the 3′-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis.  Blood. 1996;  88 (10) 3698-3703
  • 90 Jick H, Slone D, Westerholm B et al.. Venous thromboembolic disease and ABO blood type. A cooperative study.  Lancet. 1969;  1 (7594) 539-542
  • 91 Lijfering W M, Mulder R, ten Kate M K, Veeger N J, Mulder A B, van der Meer J. Clinical relevance of decreased free protein S levels: results from a retrospective family cohort study involving 1143 relatives.  Blood. 2009;  113 (6) 1225-1230
  • 92 Koster T, Blann A D, Briët E, Vandenbroucke J P, Rosendaal F R. Role of clotting factor VIII in effect of von Willebrand factor on occurrence of deep-vein thrombosis.  Lancet. 1995;  345 (8943) 152-155
  • 93 den Heijer M, Koster T, Blom H J et al.. Hyperhomocysteinemia as a risk factor for deep-vein thrombosis.  N Engl J Med. 1996;  334 (12) 759-762
  • 94 Meltzer M E, Lisman T, Doggen C J, de Groot P G, Rosendaal F R. Synergistic effects of hypofibrinolysis and genetic and acquired risk factors on the risk of a first venous thrombosis.  PLoS Med. 2008;  5 (5) e97
  • 95 Folsom A R, Lutsey P L, Astor B C, Cushman M. C-reactive protein and venous thromboembolism. A prospective investigation in the ARIC cohort.  Thromb Haemost. 2009;  102 (4) 615-619
  • 96 Quist-Paulsen P, Naess I A, Cannegieter S C et al.. Arterial cardiovascular risk factors and venous thrombosis: results from a population-based, prospective study (the HUNT 2).  Haematologica. 2010;  95 (1) 119-125
  • 97 Bots M L, Hoes A W, Koudstaal P J, Hofman A, Grobbee D E. Common carotid intima-media thickness and risk of stroke and myocardial infarction: the Rotterdam Study.  Circulation. 1997;  96 (5) 1432-1437
  • 98 James A H, Jamison M G, Biswas M S, Brancazio L R, Swamy G K, Myers E R. Acute myocardial infarction in pregnancy: a United States population-based study.  Circulation. 2006;  113 (12) 1564-1571
  • 99 Van Den Bosch M A, Kemmeren J M, Tanis B C et al.. The RATIO study: oral contraceptives and the risk of peripheral arterial disease in young women.  J Thromb Haemost. 2003;  1 (3) 439-444
  • 100 Tanis B C, van den Bosch M A, Kemmeren J M et al.. Oral contraceptives and the risk of myocardial infarction.  N Engl J Med. 2001;  345 (25) 1787-1793
  • 101 Yusuf S, Hawken S, Ounpuu S INTERHEART Study Investigators et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case–control study.  Lancet. 2004;  364 (9438) 937-952
  • 102 Sytkowski P A, D'Agostino R B, Belanger A, Kannel W B. Sex and time trends in cardiovascular disease incidence and mortality: the Framingham Heart Study, 1950-1989.  Am J Epidemiol. 1996;  143 (4) 338-350
  • 103 Teo K K, Ounpuu S, Hawken S INTERHEART Study Investigators et al. Tobacco use and risk of myocardial infarction in 52 countries in the INTERHEART study: a case–control study.  Lancet. 2006;  368 (9536) 647-658
  • 104 Kannel W B. Range of serum cholesterol values in the population developing coronary artery disease.  Am J Cardiol. 1995;  76 (9) 69C-77C
  • 105 Booth G L, Kapral M K, Fung K, Tu J V. Relation between age and cardiovascular disease in men and women with diabetes compared with non-diabetic people: a population-based retrospective cohort study.  Lancet. 2006;  368 (9529) 29-36
  • 106 Urbanus R T, Siegerink B, Roest M, Rosendaal F R, de Groot P G, Algra A. Antiphospholipid antibodies and risk of myocardial infarction and ischaemic stroke in young women in the RATIO study: a case–control study.  Lancet Neurol. 2009;  8 (11) 998-1005
  • 107 Peters M J, van Halm V P, Voskuyl A E et al.. Does rheumatoid arthritis equal diabetes mellitus as an independent risk factor for cardiovascular disease? A prospective study.  Arthritis Rheum. 2009;  61 (11) 1571-1579
  • 108 Barcat D, Guérin V, Ryman A et al.. Thrombophilia and thrombosis in systemic lupus erythematosus: a case–control study.  Ann Rheum Dis. 2003;  62 (10) 1016-1017
  • 109 Ha C, Magowan S, Accortt N A, Chen J, Stone C D. Risk of arterial thrombotic events in inflammatory bowel disease.  Am J Gastroenterol. 2009;  104 (6) 1445-1451
  • 110 Flynn R W, Macdonald T M, Jung R T, Morris A D, Leese G P. Mortality and vascular outcomes in patients treated for thyroid dysfunction.  J Clin Endocrinol Metab. 2006;  91 (6) 2159-2164
  • 111 Mann J F, Gerstein H C, Pogue J, Bosch J, Yusuf S. Renal insufficiency as a predictor of cardiovascular outcomes and the impact of ramipril: the HOPE randomized trial.  Ann Intern Med. 2001;  134 (8) 629-636
  • 112 Gerstein H C, Mann J F, Yi Q HOPE Study Investigators et al. Albuminuria and risk of cardiovascular events, death, and heart failure in diabetic and nondiabetic individuals.  JAMA. 2001;  286 (4) 421-426
  • 113 Smeeth L, Thomas S L, Hall A J, Hubbard R, Farrington P, Vallance P. Risk of myocardial infarction and stroke after acute infection or vaccination.  N Engl J Med. 2004;  351 (25) 2611-2618
  • 114 Tanis B, Algra A, van der Graaf Y, Helmerhorst F, Rosendaal F. Procoagulant factors and the risk of myocardial infarction in young women.  Eur J Haematol. 2006;  77 (1) 67-73
  • 115 Folsom A R, Rosamond W D, Shahar E The Atherosclerosis Risk in Communities (ARIC) Study Investigators et al. Prospective study of markers of hemostatic function with risk of ischemic stroke.  Circulation. 1999;  100 (7) 736-742
  • 116 Stampfer M J, Malinow M R, Willett W C et al.. A prospective study of plasma homocyst(e)ine and risk of myocardial infarction in US physicians.  JAMA. 1992;  268 (7) 877-881
  • 117 Loscalzo J. Homocysteine trials—clear outcomes for complex reasons.  N Engl J Med. 2006;  354 (15) 1629-1632
  • 118 Meltzer M E, Doggen C J, de Groot P G, Rosendaal F R, Lisman T. Plasma levels of fibrinolytic proteins and the risk of myocardial infarction in men.  Blood. 2010;  116 (4) 529-536
  • 119 Meltzer M E, Doggen C J, de Groot P G, Rosendaal F R, Lisman T. The impact of the fibrinolytic system on the risk of venous and arterial thrombosis.  Semin Thromb Hemost. 2009;  35 (5) 468-477
  • 120 Snoep J D, Roest M, Barendrecht A D, De Groot P G, Rosendaal F R, Van Der Bom J G. High platelet reactivity is associated with myocardial infarction in premenopausal women: a population-based case–control study.  J Thromb Haemost. 2010;  8 (5) 906-913
  • 121 Kaptoge S, Di Angelantonio E, Lowe G Emerging Risk Factors Collaboration et al. C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis.  Lancet. 2010;  375 (9709) 132-140

Willem M. Lijfering, M.D. , Ph.D. 

Department of Clinical Epidemiology, Leiden University Medical Centre

P.O. Box 9600, 2300 RC Leiden, The Netherlands