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Link between venous and arterial thrombosis

An article from the e-journal of the ESC Council for Cardiology Practice

In the last decade, studies have shown that there is an association between atherothrombotic disease and idiopathic venous thrombosis. This presumption is supported by common risk factors for both diseases, by similar or identical pathogenetic mechanisms and by the associated appearance of atherosclerosis and venous thrombosis. Therefore, it seems that venous and arterial thromboses represent a continuous spectrum of the same disease.

Peripheral Artery Disease
Diseases of the Aorta, Peripheral Vascular Disease, Stroke

1 - Common risk factors

Table 1
Risk factors  involved in pathogenesis of both - arterial and venous  thrombosis.

risk factor

pathogenetic  mechanism   reference
older age    increased  oxidative  stress    Prandoni et al – 8
increased BMI   

metabolic deterioration


Nurses Health Study – 9

haemodynamic stress    

metabolic deterioration

Nurses Health Study – 9

damage of vessel wall   

oxidative  stress

Nurses Health Study – 9
hypercholesterolemia  impairment of  regulation of coagulation  

increased  viscosity and erythrocyte aggregation  
Voya et al – 10
Spbieszcyk  at el - 4
Libby  and Simon - 5

In line with these arguments, is also recognition that some other nonclasical risk factors like: hyperhomocysteinemia, factor V Leiden, and lupus anticoagulants represent potential risk for both atherosclerosis and venous thrombosis.

2 - Similar or identical pathogenetic mecanism

The relationship between arterial and venous thrombosis process is also supported by the effects of measures used in prevention of atherosclerotic cardiovascular events on the prevention of venous thrombosis. For statins that are effective in the prevention of cardiovascular disease among individuals with normal or elevated levels of cholesterol, it was shown that these drugs also have antithrombotic properties (11).

In a retrospective subgroup analysis of the Heart and Estrogen Replacement Study (HERS) the use of statins was associated with a 50% risk reduction of venous thrombembolism (12). This beneficial effect of statins may be due to decreased thrombus formation mediated by their anti-inflammatory activity, suppression of the prothrombotic and endothelial-altering properties of circulating lipids and improvement of the rheological properties of the blood. Statins also seem to alter elements of the coagulation cascade consistent with an antithrombotic effect. In this study it was also first shown that long-term aspirin therapy decreased the risk of venous thrombembolism in women with established coronary artery disease (12).

3 - Associated appearance of atherosclerosis and venous thrombosis

A relation was also found between subjects with preclinical or clinical atherosclerotic disease and venous thrombembolism. Prandoni and co-workers showed that the prevalence of carotid plaques was significantly higher in patients with unexplained (primary) thrombotic events than in those with secondary ones or in age- and sex- matched subjects without thrombosis (3). This association was still present after adjustment for risk factors of atherosclerosis and thrombophilic conditions. In elderly patients, the association became even stronger. In addition, other features of atherosclerosis (such as intima-media thickness of the carotid arteries, the degree of carotid stenosis and the number of carotid segments involved) were far more frequent among subjects with spontaneous venous thrombosis. This study suggests either that atherosclerosis can induce venous thrombosis or that the two conditions share common risk factors.

In one of our studies we investigated the relation of endothelial function to VTE. Endothelial dysfunction  known as one of the earliest measurable  functional  disturbance  in atherogenesis was also detected in patients with idiopathic venous thrombosis.  Patients with thrombosis had significantly  lower endothelium – dependent vasodilating capability  of brachial artery than heatly subjects (14).
A relationship was also found between manifested atherosclerotic disease and venous thrombembolism. In the study of Grady and co-workers, women who had myocardial infarction had a 2.1-fold higher risk of venous thrombembolism over the entire course of follow-up, but during the first 90 days after infarction, the risk was increased more than by 5-fold (12). Further, in a case-control study an association between venous thrombembolic disorders and arterial disease of the lower limbs was found (15).

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.


There is evidence of an association between atherosclerotic disease and venous thrombosis. This thesis is supported by common risk factors for both diseases: older age, hyperlipidemia, hypertension, hyperhomocysteinemia, factor V Leiden, and lupus anticoagulants, by similar or identical pathogenetic mechanisms and by the association of the appearance of both diseases. 

The existence of the link between arterial and venous disorders opens important new avenues for further research, including the potential role of certain drugs like statins - presently mainly used in the prevention of arterial cardiovascular disease also in management of venous thrombembolic disorders.


1. Prandoni P, Bilora F, Marchiori A et al. An association between atherosclerosis and venous thrombosis. N Engl J Med 2003; 348: 1435-41.
2. Jerjes-Sanchez C. Venous and arterial thrombosis: a continuous spectrum of the same disease? Europ Heart J 2005; 26: 3-4.
3. Viles-Gonzalez J, Fuster V, Badimon JJ. Thrombin/inflammation paradigms: A closer look at arterial and venous thrombosis.  Am Heart J 2005; 49: 519-31.
4. Spbieszcyk P, Fishbein MC, Goldhaber SZ. Acute pulmonary embolism. Don?t ignore the platelet. Circulation 2002; 106: 1748-9.
5. Libby P, Simon DI. Thrombosis and atherosclerosis. In: Colman RW, Hirsh J, Marer VJ, Clowes AW, George JN, eds. Hemostasis and Thrombosis: Basic Principles & Clinical Practice. 4th ed. Philadelphia: Lippincott William & Wilkins, 2000: 743-52.
6. Levi M, van der Poll T, Buller HR. Bidirectional relation between inflammation and coagulation. Circulation 2004; 109: 2698-704.
7. Prandoni P, Bilora F, Marchiori A et al. An association between atherosclerosis and venous thrombosis. N Engl J Med 2004; 346: 1435-41.
8. Heit JA. Venous thromboembolism epidemiology: implications for prevention and management. Semin Thromb Hemost 2002; 28 (Suppl. 2): 3-13.
9. Goldhaber SZ, Grodstein F, Stampfer MJ, Marison JAE, Colditz GA, Speizer FE et al. A prospective study of risk factors.for pulmonary embolism in women. JAMA 1997; 277: 642-5.
10. VayaA, Mira Y, Ferrando F,Contreras MT,  Estelles A, Espara F et al. Hyperlipidemia and venous thromboembolism in patients lacking thrombophilic risk factors.  Brit J Hematol 2002; 118: 255-9.
11. Ray JG, Mamdoni M, Tsuyuki RT et al. Use of statins and the subsequent development of deep vein thrombosis. Arch Intern Med 2001; 161: 1405-10.
12. Grady D, Wenger NK, Herrington D, Khan S,  Furberg C, Hunninghake D et al. Postmenopausal hormone therapy increases risk for venous thromboembolic disease. Ann Intern Med 2000; 132: 689-6.
13. Prandoni P, Bilora F, Marchiori A, Bernardi E, Petrobelli F,  Lensing AWA et al. An association between atherosclerosis and venous thrombosis. N Engl J Med  2003;  348: 12435-41.
14. Štalc M, Poredoš P, Peternel P, Tomšic M, Šebeštjen M, Kveder T. Endothelial function is impaired in patients with primary antiphospholipid syndrome.  Thromb Res 2006 (in press).
15. Libertiny G, Hands L. Deep venous thrombosis in peripheral vascular disease. Br J Surg 1999; 86: 907-10.



Vol5 N°02

Notes to editor

Prof. P. Poredos
Ljubljana, Slovenia
Past Chairperson of the ESC Working Group on Peripheral Circulation

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.