title: Venous thromboembolism and cardiovascular risk: results from the NAVIGATOR trial.
abstract: BACKGROUND
  Contemporary studies suggest an association between venous thromboembolism and a higher incidence of major cardiovascular events, mostly attributed to arterial atherothrombosis. Using data from the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial, we assessed the association of venous thromboembolism with major cardiovascular events.
  
  
  METHODS
  In NAVIGATOR, patients with impaired glucose tolerance were randomly allocated to receive valsartan or placebo and nateglinide or placebo in addition to lifestyle modification. Baseline characteristics and prior history of venous thromboembolism were assessed. After adjusting for important baseline covariates, Cox proportional hazards regression models were used to assess the association between venous thromboembolism and major cardiovascular outcomes.
  
  
  RESULTS
  Of the 9306 patients enrolled, 129 (1.4%) had a history of venous thromboembolism. Patients with venous thromboembolism were older, more frequently white and female, and had a higher body mass index. Patients with venous thromboembolism had higher 5-year event rates for the composite of death, myocardial infarction, and stroke, as compared with patients without venous thromboembolism (10.7% vs 5.9%; P < .001; adjusted hazard ratio 2.12; 95% confidence interval, 1.36-3.31; P = .001).
  
  
  CONCLUSIONS
  In patients with impaired glucose tolerance at high risk for cardiovascular events, the prevalence of venous thromboembolism was rare but associated with worse long-term cardiovascular outcomes, including arterial events. Venous thromboembolism is a marker of risk, and attention should be paid to this high-risk group of patients.
authors.affiliation: Brazilian Clinical Research Institute, Sao Paulo, Brazil; Hospital Israelita Albert Einstein, Sao Paulo, Brazil.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Katz
authors.affiliation: Duke Translational Medicine Institute, Duke University Medical Center, Durham, NC.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Califf
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC.
authors.forename: Jie-Lena
authors.initials: JL
authors.lastname: Sun
authors.affiliation: BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, UK.
authors.forename: John J V
authors.initials: JJ
authors.lastname: McMurray
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC.
authors.forename: Laine
authors.initials: L
authors.lastname: Thomas
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC. Electronic address: renato.lopes@duke.edu.
authors.forename: Renato D
authors.initials: RD
authors.lastname: Lopes
mesh_terms: D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage*; D002318:Cardiovascular Diseases / Q000453:epidemiology*; D016001:Confidence Intervals; D003510:Cyclohexanes / Q000008:administration & dosage*; D005260:Female; D018149:Glucose Intolerance / Q000097:blood / Q000188:drug therapy*; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D000077715:Nateglinide; D017063:Outcome Assessment, Health Care; D010649:Phenylalanine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D015995:Prevalence; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D013777:Tetrazoles / Q000008:administration & dosage*; D013997:Time Factors; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000068756:Valsartan; D054556:Venous Thromboembolism / Q000453:epidemiology*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D003510:Cyclohexanes; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000077715:Nateglinide; D010649:Phenylalanine; D013777:Tetrazoles; D014633:Valine; D000068756:Valsartan
keywords: Cardiovascular; Outcomes; Venous thrombosis