Serum albumin and risk of venous thromboembolism

Summary

The incidence of venous thromboembolism (VTE) is increased in patients with albuminuria. However, whether a low serum albumin concentration is associated with increased risk of VTE has been a matter of controversy. We determined the association of serum albumin with VTE incidence in two large, prospective, population-based cohorts: the Atherosclerosis Risk in Communities (ARIC) Study (n = 15,300) and the Cardiovascular Health Study (CHS) (n = 5,400). Validated VTE occurrence (n = 462 in ARIC and n = 174 in CHS) was ascertained during follow-up. In both studies, after adjustment for age, sex, race, use of hormone replacement therapy, estimated glomerular filtration rate, history of cancer, and diabetes, serum albumin tended to be associated inversely with VTE. The adjusted hazard ratio per standard deviation lower albumin was 1.18 (95% confidence interval [CI] = 1.08, 1.31) in ARIC and 1.10 (95% CI = 0.94, 1.29) in CHS. The hazard ratio for albumin below (vs. above) the fifth percentile was 1.28 (95% CI = 0.90, 1.84) in ARIC and 1.80 (95% CI = 1.11, 2.93) in CHS. In conclusion, low serum albumin was a modest marker of increased VTE risk. The observed association likely does not reflect cause and effect, but rather that low serum albumin reflects a hyperinflammatory or hypercoagulable state. Whether this association has clinical relevance warrants further study.

Keywords

Albumin - prospective study - pulmonary embolism - venous thrombosis

• References

• 1 Llach F, Papper S, Massry SG. The clinical spectrum of renal vein thrombosis: acute and chronic. Am J Med 1980; 69: 819-827.
• 2 Llach F. Hypercoagulability, renal vein thrombosis, and other thrombotic complications of nephrotic syndrome. Kidney Int 1985; 28: 429-439.
• 3 Velasquez Forero F, Garcia Prugue N, Ruiz Morales N. Idiopathic nephrotic syndrome of the adult with asymptomatic thrombosis of the renal vein. Am J Nephrol 1988; 08: 457-462.
• 4 Lilova I M, Velkovski IG, Topalov IB. Thromboembolic complications in children with nephrotic syndrome in Bulgaria (1974–1996). Pediatr Nephrol 2000; 15: 74-78.
• 5 Singhal R, Brimble KS. Thromboembolic complications in the nephrotic syndrome: pathophysiology and clinical management. Thromb Res 2006; 118: 397-407.
• 6 Kayali F, Najjar R, Aswad F, Matta F, Stein PD. Venous thromboembolism in patients hospitalized with nephrotic syndrome. Am J Med 2008; 121: 226-230.
• 7 Mahmoodi BK, ten Kate MK, 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: 224-230.
• 8 Mahmoodi BK, Gansevoort RT, Veeger NJ. et al Microalbuminuria and risk of venous thromboembolism. J Am Med Assoc 2009; 301: 1790-1797.
• 9 Wattanakit K, Cushman M. Chronic kidney disease and venous thromboembolism: epidemiology and mechanisms. Curr Opin Pulm Med 2009; 15: 408-412.
• 10 Bellomo R, Wood C, Wagner I. et al Idiopathic membranous nephropathy in an Australian population: the incidence of thromboembolism and its impact on the natural history. Nephron 1993; 63: 240-241.
• 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 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.
• 13 The Atherosclerosis Risk in Communities (ARIC) Study Investigators. The Atherosclerosis Risk in Communities (ARIC) Study: design and objectives. The ARIC investigators. Am J Epidemiol 1989; 129: 687-702.
• 14 Fried LP, Borhani NO, Enright P. et al The Cardiovascular Health Study: design and rationale. Ann Epidemiol 1991; 01: 263-276.
• 15 Tell GS, Fried LP, Hermanson B. et al Recruitment of adults 65 years and older as participants in the Cardiovascular Health Study. Ann Epidemiol 1993; 03: 358-366.
• 16 Doumas BT, Watson WA, Biggs HG. Albumin standards and the measurement of serum albumin with bromcresol green. Clin Chim Acta 1971; 31: 87-96.
• 17 Eckfeldt JH, Chambless LE, Shen YL. Short-term, within-person variability in clinical chemistry test results. Experience from the Atherosclerosis Risk in Communities Study. Arch Pathol Lab Med 1994; 118: 496-500.
• 18 Cushman M, Cornell ES, Howard PR. et al Laboratory methods and quality assurance in the Cardiovascular Health Study. Clin Chem 1995; 41: 264-270.
• 19 Levey AS, Stevens LA, Schmid CH. et al A new equation to estimate glomerular filtration rate. Ann Intern Med 2009; 150: 604-612.
• 20 Tsai AW, Cushman M, Rosamond WD. et al Cardiovascular risk factors and venous thromboembolism incidence: the longitudinal investigation of thromboembolism etiology. Arch Intern Med 2002; 162: 1182-1189.
• 21 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.
• 22 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.
• 23 National Kidney Foundation K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 2002; 39 (02) (Suppl. 01) S1-266.
• 24 Northup PG, McMahon MM, Ruhl AP. et al Coagulopathy does not fully protect hospitalized cirrhosis patients from peripheral venous thromboembolism. Am J Gastroenterol 2006; 101: 1524-1528 quiz 680.