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Preliminary Communication
JAMA. 2009;301(17):1790-1797. doi: 10.1001/jama.2009.565

Microalbuminuria and Risk of Venous Thromboembolism

  1. Bakhtawar K. Mahmoodi, BSc;
  2. Ron T. Gansevoort, MD, PhD;
  3. Nic J. G. M. Veeger, MSc;
  4. Abigail G. Matthews, PhD;
  5. Gerjan Navis, MD, PhD;
  6. Hans L. Hillege, MD, PhD;
  7. Jan van der Meer, MD, PhD
  8. for the Prevention of Renal and Vascular End-stage Disease (PREVEND) Study Group
  1. Author Affiliations: Division of Hemostasis, Thrombosis and Rheology, Department of Hematology (Messrs Mahmoodi and Veeger and Dr van der Meer), Department of Nephrology (Drs Gansevoort and Navis), and Trial Coordination Center, Department of Epidemiology (Mr Veeger and Dr Hillege), University Medical Center Groningen, Groningen, the Netherlands; and Laboratory of Statistical Genetics, Rockefeller University, New York, New York (Dr Matthews). †Deceased.

Abstract

Context Microalbuminuria (albuminuria 30-300 mg per 24-hour urine collection) is a well-known risk marker for arterial thromboembolism. It is assumed that microalbuminuria reflects generalized endothelial dysfunction. Hence, microalbuminuria may also predispose for venous thromboembolism (VTE).

Objective To assess whether microalbuminuria is associated with VTE.

Design, Setting, and Participants Prevention of Renal and Vascular End-stage Disease (PREVEND) study, an ongoing community-based prospective cohort study initiated in 1997. All inhabitants of Groningen, the Netherlands, aged 28 through 75 years (n = 85 421) were sent a postal questionnaire and a vial to collect a first morning urine sample for measurement of urinary albumin concentration. Of those who responded (40 856), a cohort (8592 participants) including more participants with higher levels of urinary albumin concentration completed screening at an outpatient clinic. Screening data were collected on urinary albumin excretion (UAE) and risk factors for cardiovascular and renal disease.

Main Outcome Measure Symptomatic and objectively verified VTE (ie, deep vein thrombosis, pulmonary embolism, or both) between study initiation and June 1, 2007.

Results Of 8574 evaluable participants (mean [SD] age, 49 [13] years; 50% men), 129 experienced VTE during a mean (SD) follow-up period of 8.6 (1.8) years, corresponding to overall annual incidence of 0.14% (95% confidence interval [CI], 0.11%-0.19%). Annual incidences were 0.12%, 0.20%, 0.40%, and 0.56% in participants with UAE of less than 15 (n = 6013), 15-29 (n = 1283), 30-300 (n = 1144), and greater than 300 (n = 134) mg per 24-hour urine collection, respectively (P for trend <.001). When adjusted for age, cancer, use of oral contraceptives, and atherosclerosis risk factors, hazard ratios associated with UAE levels of 15-29, 30-300, and greater than 300 mg/24 h were 1.40 (95% CI, 0.86-2.35), 2.20 (95% CI, 1.44-3.36), and 2.82 (95% CI, 1.21-6.61), respectively, compared with participants with UAE of less than 15 mg/24 h (global P = .001). Adjusted hazard ratio for microalbuminuria vs normoalbuminuria (UAE <30 mg/24 h) was 2.00 (95% CI, 1.34-2.98; P < .001). Microalbuminuria-related number needed to harm was 388 per year.

Conclusion Microalbuminuria is independently associated with an increased risk for VTE.

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