title: Association between inflammation biomarkers, anatomic extent of deep venous thrombosis, and venous symptoms after deep venous thrombosis.
abstract: OBJECTIVE
  Inflammation may play a role in pathogenesis of venous thromboembolism, but the nature of this relationship is not yet understood. The objective of this study was to assess whether inflammation marker levels measured at diagnosis of deep venous thrombosis (DVT) and change in levels during the first month after DVT are associated with anatomic extent of DVT and severity of venous signs and symptoms at baseline and 1 month.
  
  
  METHODS
  The BioSOX study is a biomarker substudy of the Compression Stockings to Prevent the Post-Thrombotic Syndrome (SOX) trial, a multicenter, randomized controlled trial that included patients with a first, acute, symptomatic, proximal DVT. Blood samples were collected from participants at baseline and 1 month, and C-reactive protein (CRP), intercellular adhesion molecule 1, interleukin (IL)-6, and IL-10 were measured by established assays. Linear regression was used to assess the association between continuous log-transformed baseline biomarker levels and anatomic extent of DVT, classified as iliac or common femoral DVT vs femoral or popliteal DVT (reference). Proportional odds ordinal logistic regression models were used to analyze the association between biomarker level and Villalta score (as a measure of severity of venous signs and symptoms) at baseline and 1 month.
  
  
  RESULTS
  Among 717 patients, 60.2% were male, and the mean age was 55.2 years. There was a significant association between more extensive DVT (common femoral or iliac) and levels of CRP and IL-6 at DVT diagnosis. Median (interquartile range) CRP level was 11.6 mg/L (3.84-39.5) in patients with common femoral or iliac DVT vs 6.86 mg/L (3.11-22) in patients with popliteal or femoral DVT, and median IL-6 level was 6.36 pg/mL (1.09-14.37) vs 4.40 pg/mL (2.35-8.27), respectively. These differences were statistically significant in linear regression analyses. In addition, compared with those in the lowest quartile, each higher quartile of baseline CRP concentration was associated with an odds ratio of 2.89 (1.93-4.33) for having a more severe Villalta category at baseline and 1.98 (1.28-3.08) for having a more severe Villalta category 1 month after DVT. Higher baseline levels of IL-6 were associated with Villalta severity category at baseline (odds ratio, 2.40 [1.61-3.59]). Change in biomarker levels during the first month after DVT was not strongly associated with the 1-month Villalta score.
  
  
  CONCLUSIONS
  Levels of CRP and IL-6 at DVT diagnosis were associated with thrombotic disease burden, as measured by DVT extent, and severity of DVT symptoms and signs. Further studies are required to more fully elucidate the role of inflammation in DVT and its clinical course.
authors.affiliation: Center for Clinical Epidemiology, Jewish General Hospital, McGill University, Montreal, Quebec, Canada.
authors.forename: Anat
authors.initials: A
authors.lastname: Rabinovich
authors.affiliation: Center for Clinical Epidemiology, Jewish General Hospital, McGill University, Montreal, Quebec, Canada; Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada.
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Cohen
authors.affiliation: Departments of Medicine and Pathology, Cardiovascular Research Institute, University of Vermont College of Medicine, Burlington, Vt.
authors.forename: Mary
authors.initials: M
authors.lastname: Cushman
authors.affiliation: Center for Clinical Epidemiology, Jewish General Hospital, McGill University, Montreal, Quebec, Canada; Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada; Division of Internal Medicine, Department of Medicine, McGill University, Montreal, Quebec, Canada. Electronic address: susan.kahn@mcgill.ca.
authors.forename: Susan R
authors.initials: SR
authors.lastname: Kahn
mesh_terms: D015415:Biomarkers; D002097:C-Reactive Protein; D006801:Humans; D007249:Inflammation; D015850:Interleukin-6; D008297:Male; D008875:Middle Aged; D054070:Postthrombotic Syndrome / Q000175:diagnosis*; D012307:Risk Factors; D053828:Stockings, Compression / Q000009:adverse effects; D013927:Thrombosis; D020246:Venous Thrombosis / Q000175:diagnosis*
chemical_list: D015415:Biomarkers; D015850:Interleukin-6; D002097:C-Reactive Protein