C-reactive protein and venous thromboembolism

Aaron R. Folsom; Pamela L. Lutsey; Brad C. Astor; Mary Cushman

doi:10.1160/TH09-04-0274

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2009; 102(04): 615-619
DOI: 10.1160/TH09-04-0274

Rapid and Short Communication

Schattauer GmbH

C-reactive protein and venous thromboembolism

A prospective investigation in the ARIC cohort

Authors

Aaron R. Folsom

¹Division of Epidemiology & Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA
Pamela L. Lutsey

¹Division of Epidemiology & Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA
Brad C. Astor

²Department of Epidemiology, The Johns Hopkins Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, Maryland, USA; 3Department of Medicine, University of Vermont, Burlington, Vermont, USA
Mary Cushman

³Department of Pathology, University of Vermont, Burlington, Vermont, USA

Abstract

PDF Download

Summary

The role of inflammation in the causation of venous thromboembolism (VTE) is uncertain. In 10,505 participants of the Atherosclerosis Risk in Communities (ARIC) Study, we assessed the association of the systemic inflammation marker, elevated C-reactive protein (CRP), with incidence of VTE (n=221) over a median of 8.3 years of follow-up. Adjusted for age, race, and sex, the hazard ratios of VTE across quintiles of CRP were 1.0, 1.61, 1.16, 1.56, and 2.31 (p for trend p<0.0007). For CRP above the upper 10 percentile (≥8.55 mg/L), compared with the lowest 90% of CRP values, the hazard ratio of VTE was 2.07 (95% CI 1.47, 2.94). Further adjustment for baseline hormone replacement therapy, diabetes, and body mass index attenuated the hazard ratios only slightly. For example, the adjusted hazard ratio of VTE was 1.76 (95% CI 1.23, 2.52) for CRP above versus below the 90th percentile. In conclusion, this prospective, populationbased study suggests elevated CRP is independently associated with increased risk of VTE.

Keywords

C-reactive protein - prospective study - pulmonary embolus - venous thrombosis

PDF (86 kb)

References

References
1 Casas JP, Shah T, Hingorani AD. et al. C-reactive protein and coronary heart disease: a critical review. J Intern Med 2008; 264: 295-314.
2 Ridker PM, Cushman M, Stampfer MJ. et al. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med 1997; 336: 973-979.
3 Tsai AW, Cushman M, Rosamond WD. et al. Coagulation factors, inflammation markers, and venous thromboembolism: the Longitudinal Investigation of Thromboembolism Etiology (LITE). Am J Med 2002; 113: 636-642.
4 Mahmoodi BK, Gansevoort RT, Veeger NJGM. et al. Microalbuminuria and risk of venous thromboembolism. JAMA 2009; 301: 1790-1797.
5 Kamphuisen PW, Eikenboom JCJ, Vos HL. 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: 680-683.
6 Vormittag R, Vukovich T, Schönauer V. et al. Basal high-sensitivity-C-reactive protein levels in patients with spontaneous venous thromboembolism. Thromb Haemost 2005; 93: 488-493.
7 Zee RYL, Hegener HH, Cook NR. et al. C-reactive protein gene polymorphisms and the risk of venous thromboembolism: a haplotype-based analysis. J Thromb Haemost 2004; 02: 1240-1243.
8 Vormittag R, Funk M, Mannhalter C. et al. C-reactive protein 3’ UTR + 1444C>T polymorphism in patients with spontaneous venous thromboembolism. Atherosclerosis 2006; 188: 406-411.
9 van Aken BE, Reitsma PH, Rosendaal FR. Interleukin 8 and venous thrombosis: evidence for a role of inflammation in thrombosis. Br J Haematol 2002; 116: 173-177.
10 Reitsma PH, Rosendaal FR. Activation of innate immunity in patients with venous thrombosis: the Leiden Thrombophilia Study. J Thromb Haemost 2004; 02: 619-622.
11 Fox EA, Kahn SR. The relationship between inflammation and venous thrombosis. A systematic review of clinical studies. Thromb Haemost 2005; 94: 362-365.
12 The ARIC Investigators. The Atherosclerosis Risk in Communities (ARIC) Study: Design and objectives. Am J Epidemiol 1989; 129: 687-702.
13 Zakai NA, Ohira T, White R. et al. Activated partial thromboplastin time and risk of future venous thromboembolism. Am J Med 2008; 121: 231-238.
14 Cushman M, Tsai AW, White RH. et al. Deep vein thrombosis and pulmonary embolism in two cohorts: The Longitudinal Investigation of Thromboembolism Etiology. Am J Med 2004; 117: 19-25.
15 Macy E, Hayes T, Tracy R. Variability in the measurement of C-reactive protein in healthy subjects: implications for reference intervals and epidemiological applications. Clin Chem 1997; 43: 52-58.
16 Glynn RJ, Danielson E, Fonseca FA. et al. A randomized trial of rosuvastatin in the prevention of venous thromboembolism. N Engl J Med 2009; 360: 1851-1861.
17 Cermak J, Key NS, Bach RR, Balla J, Jacob HS, Vercellotti GM. C-reactive protein induces human peripheral blood monocytes to synthesize tissue factor. Blood 1993; 82: 513-520.
18 Chooi CC, Gallus AS. Acute phase reaction, fibrinogen level and thrombus size. Thromb Res 1989; 53: 493-501.
19 Prandoni P, Bilori F, Marchiori A. et al. An association between atherosclerosis and venous thrombosis. N Engl J Med 2003; 348: 1435-1441.
20 Reich LM, Folsom AR, Key NS. et al. Prospective study of subclinical atherosclerosis as a risk factor for venous thromboembolism. J Thromb Haemost 2006; 04: 1909-1913.
21 Sørensen HT, Horvath-Puho E, Pedersen L. et al. Venous thromboembolism and subsequent hospitalisation due to acute arterial cardiovascular events: a 20-year cohort study. Lancet 2007; 370: 1773-1779.
22 Lowe GDO. Is venous thrombosis a risk factor for arterial thrombosis?. Lancet 2007; 370: 1742-1743.
23 Cushman M. Epidemiology and risk factors for venous thrombosis. Semin Hematol 2007; 44: 62-69.
24 Ageno W, Becattini C, Brighton T. et al. Cardiovascular risk factors and venous thromboembolism: a meta-analysis. Circulation 2008; 117: 93-102.
25 Fibrinogen Studies Collaboration. Danesh J, Lewington S, Thompson SG. et al. Plasma fibrinogen level and the risk of major cardiovascular diseases and nonvascular mortality: an individual participant metaanalysis. JAMA 2005; 294: 1799-1809.
26 Koster T, Rosendaal FR, Reitsma PH. et al. 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: 719-722.