Subscribe to RSS
Obesity: risk of venous thrombosis and the interaction with coagulation factor levels and oral contraceptive use
16 October 2002
Accepted after revision 03 January 2003
09 December 2017 (online)
Deep vein thrombosis (DVT) is a common disease with an annual incidence of about 1 in 1000. Many risk factors have already been studied, both genetic and acquired. It is unclear whether obesity affects thrombotic risk in unselected patients. Obesity is common, with a prevalence of 20-25% and may therefore have a considerable impact on the overall incidence of thrombosis. We evaluated the risk of thrombosis due to overweight and obesity using data from a large population based case-control study.
Four hundred and fifty-four consecutive patients with a first episode of objectively diagnosed thrombosis from three Anticoagulation Clinics in the Netherlands were enrolled in a case-control study. Controls were matched on age and sex to patients and were introduced by the patients. All patients completed a standard questionnaire and interview, with weight and height measured under standard conditions. The associations of obesity with clotting factor levels were studied to investigate possible mechanisms.
Obesity (BMI ≥30 kg/m2) increased the risk of thrombosis twofold (CI95: 1.5 to 3.4), adjusted for age and sex. Obese individuals had higher levels of factor VIII and factor IX, but not of fibrinogen. The effect on risk of obesity was not changed after adjustment for coagulation factors levels (fibrinogen, F VIII, F IX, D-dimer). The relative risk estimates were similar in different age groups and in both sexes, indicating a larger absolute effect in older age groups. Evaluation of the combined effect of obesity and oral contraceptive pills among women aged 15-45 revealed that oral contraceptives further increased the effect of obesity on the risk of thrombosis, leading to 10-fold increased risk amongst women with a BMI greater than 25 kg/m2 who used oral contraceptives.
Obesity is a risk factor for deep vein thrombosis. Among women with a BMI greater than 25 kg/m2 the synergistic effect with oral contraceptives should be considered when prescribing these.
- 1 Nordström M, Lindblad B, Bergqvist D, Kjellstrom T. A prospective study of the incidence of deep-vein thrombosis with a defined urban population. J Intern Med 1992; 232: 155-60.
- 2 Rosendaal FR. Thrombosis in the young: epidemiology and risk factors, a focus on venous thrombosis. Thromb Haemost 1997; 78: 1-6.
- 3 Anderson FA, Wheeler HB, Goldberg RJ. et al A population based perspective of the hospital incidence and case-fatality rates of deep vein thrombosis and pulmonary embolism. The Worcester DVT study. Arch Intern Med 1991; 151: 933-8.
- 4 Rosendaal FR. Venous thrombosis: a multi-causal disease. Lancet 1999; 353: 1167-73.
- 5 Samama MM. An epidemiologic study of risk factors for deep vein thrombosis in medical outpatients: the Sirius study. Arch Intern Med 2000; 160: 3415-20.
- 6 White HR, Gettner S, Newman J, Trauner K B, Romano SP. Predictors of rehospitalization for symptomatic venous thromboembolism after total hip arthroplasty. N Engl J Med 2000; 343: 1758-64.
- 7 Avellone G, Di Carbo V, Cordova R. et al Blood coagulation and fibrinolysis in obese NIDDM patients. Diabetes Res 1994; 25: 85-92.
- 8 Avellone G, Di Carbo V, Cardova R. et al Coagulation, fibrinolysis and haemorheology in premenopausal obese women with different body fat distribution. Thromb Res 1994; 79: 223-31.
- 9 Swann KW, Black PM. Deep vein thrombosis and pulmonary emboli in neurosurgical patients: a review. J Neurosurg 1984; 61: 1055-62.
- 10 Spannagel U, Kujath P. Low molecular weight heparin for the prevention of thromboembolism in outpatients immobilized by plaster cast. Semin Thromb Hemost 1993; 19 (Suppll) 131-41.
- 11 Kim YH, Choi IY, Park MR, Park TS, Cho JL. Prophylaxis for deep vein thrombosis with aspirin or low molecular weight dextran in Korean patients undergoing total hip replacement. A randomized controlled trial. Int Orthop 1998; 22: 6-10.
- 12 Shead GV, Natayanan R. Incidence of postoperative venous thromboembolism in South India. Br J Surg 1980; 67: 813-4.
- 13 Gleysteen JJ, Hussey CV, Caya JG. Preoperative coagulation indices in patients with morbid obesity. Int J Obesity 1988; 13: 195-201.
- 14 De Lorenzo F, Mukherjee M, Kadziola Z. et al Association of overall adiposity rather than body mass index with lipids and procoagulant factors. Thromb Haemost 1998; 80: 603-6.
- 15 Shippinger G, Wirnsberger GH, Obernesterer A, Babinski K. Thrombeembolic complications after arthroscopic knee surgery. Incidence and risk factors in 101 patients. Acta Orthop Scand 1998; 69: 144-6.
- 16 Serrano Rios M. Relationship between obesity and the increased risk of major complications in non-insulin-dependent diabetes mellitus. Eur J Clin Invest 1998; 28 (Suppl. 02) 14-17.
- 17 Hubert HB, Feinleib M, McNamara PM, Castelli WP. Obesity as an independent risk factor for cardiovascular disease: a 26-year follow-up of participants in the Framingham heart study. Circulation 1983; 67: 968-77.
- 18 Lundgren CH, Brown SL, Nordt TK. et al Elaboration of type 1 plasminogen activator inhibitor from adipocytes. A potential pathogenic link between obesity and cardiovascular disease. Circulation 1996; 93: 106-10.
- 19 Lee I. et al Body weight and mortality: A 27-year follow up of middle-aged men. JAMA 1993; 270: 2823-9.
- 20 World Health Organization Obesity: Preventing and managing the global epidemic. WHO technical report series; 894. Geneva 2000.
- 21 National Institutes of Health, Lung, and Blood Institute Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults-the evidence report. Obes Res 1998; 6 (Suppl. 02) 512
- 22 Van der Meer FJM, Koster T, Vandenbroucke JP. et al The Leiden Thrombophilia Study (LETS). Thromb Haemost 1997; 78: 631-5.
- 23 Koster T, Blann AD, Briët E, Vandenbroucke JP, Rosendaal FR. Role of clotting factor VIII in effect of von Willebrand factor on occurrence of deep-vein thrombosis. Lancet 1995; 345: 152-5.
- 24 Van Hylckama Vlieg A, van der Linden IK, Bertina RM, Rosendaal FR. High levels of factor IX increase the risk of venous thrombosis. Blood 2000; 95: 3678-82.
- 25 Koster T, Rosendaal FR, Van der Velden PA, Briët E, Vandenbroucke JP. Factor VII and fibrinogen levels as risk factors for venous thrombosis: a case-control study of plasma levels and DNA polymorphisms: the Leiden Thrombophilia Study (LETS). Thromb Haemost 1994; 71: 719-22.
- 26 Kamphuisen PW, Eikenboom JCJ, Vos HL, Pablo R, Sturk A, Bertina RM. et al Increased levels of factor VIII and fibrinogen in patients with venous thrombosis are not caused by acute phase reactions. Thromb Haemost 1999; 81: 680-3.
- 27 Andreescu ACM, Cushman M, Rosendaal FR. D-Dimer as a risk factor for venous thrombosis: the Leiden Thrombophilia Study. Thromb Haemost 2002; 87: 47-51.
- 28 Hansson PO, Eriksson H, Welin L. et al Smoking and abdominal obesity: Risk factors for venous thromboembolism among middle-aged men: “The study of men bon in 1913”. Arch Intern Med 1999; 159: 1886-90.
- 29 Tsai AW, Cushman M, Rosamond WD, Heckbert SR, Polak JF, Folsom AR. Cardiovascular risk factors and venous thrombo-embolism incidence: The Longitudinal Investigation of Thromboembolism Etiology (LITE) Study. Arch Intern Med 2002; 162: 1182-9.
- 30 Vague P, Juhan-Vague I, Aillaud MF. et al Correlation between blood fibrinolytic activity, plasminogen activator inhibitor level, plasma insulin level, and relative body weight in normal and obese subjects. Metabolism 1986; 35: 250-3.
- 31 Quattrone A, Gambardella A, Carbone AM. et al A hypofibrinolytic state in overweight patients with cerebral venous thrombosis and isolated intracranial hypertension. J Neurol 1999; 246: 1086-9.
- 32 Cushman M, Yanez D, Psaty BM. et al Association of fibrinogen and coagulation factors VII and VIII with cardiovascular risk factors in elderly. Am J Epidemiol 1996; 143: 6665-76.
- 33 Nightingale AL, Lawrenson RA, Simpson EL, Williams TJ, MacRae KD, Farmer RDT. The effects of age, body mass index, smoking and general health on the risk of venous thromboembolism in users of combined oral contraceptives. Eur J Contrac Repr H Care 2000; 5: 265-74.
- 34 De Pergola G, De Mitrio V, Giorgino F. et al Increase in both pro-thrombotic and anti-thrombotic factors in obese premenopausal women: relationship with body fat distribution. Int Obes Relat Metab Disord 1997; 21: 527-35.