title: Markers of fibrinolysis may predict development of lower extremity arterial disease in patients with diabetes: A longitudinal prospective cohort study with 10 years of follow-up.
abstract: A previous cross-sectional study suggested that tissue plasminogen activator-activity might be an early marker of asymptomatic lower extremity arterial disease, but the long-term relationship is unknown.
  
  
  
  This study included 96 diabetic (48 type 1/48 type 2) and 62 non-diabetic subjects aged 30-70 years without previously known lower extremity arterial disease (age: 50.3 ± 9.3 years, gender: M/W 47.5/52.5% and body mass index: 26.6 ± 4.5 kg/m(2)). The relationships between asymptomatic lower extremity arterial disease and fibrinolytic markers (tissue plasminogen activator-activity, tissue plasminogen activator-mass, plasminogen activator inhibitor-1 activity) at baseline and after 10 years were assessed by logistic regression analysis adjusting for age, hypertension, statin treatment, HbA1c, triglycerides and low-density lipoprotein cholesterol as fixed covariates.
  
  
  
  The tissue plasminogen activator-activity at baseline and at the 10-year follow-up significantly predicted the presence of sign(s) of lower extremity arterial disease (odds ratio = 1.78, 95% confidence interval: 1.02-3.10, p = 0.043 and odds ratio = 1.78, 95% confidence interval: 1.12-2.23, p = 0.014, respectively). In addition, tissue plasminogen activator-mass at the 10-year follow-up was associated with signs of lower extremity arterial disease (odds ratio = 1.07, 95% confidence interval: 1.00-1.15, p = 0.046). Baseline age, hypertension and HbA1c were independently associated with sign(s) of lower extremity arterial disease at 10 years (odds ratio = 1.09, 95% confidence interval: 1.04-1.14, p = < 0.001; odds ratio = 3.68, 95% confidence interval: 1.67-8.12, p = 0.001 and odds ratio = 1.54, 95% confidence interval: 1.21-1.95, p = < 0.001, respectively).
  
  
  
  This long-term study supports previous findings of a significant association between asymptomatic lower extremity arterial disease and tissue plasminogen activator-activity. Thus, tissue plasminogen activator-activity may be an early marker of lower extremity arterial disease although the mechanism of this relationship remains unclear.
authors.affiliation: Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden Department of Medicine, Sunderby Hospital, Luleå, Sweden aslak.rautio@gmail.com.
authors.forename: Aslak
authors.initials: A
authors.lastname: Rautio
authors.affiliation: Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden Research Unit, Skellefteå Hospital, Skellefteå, Sweden.
authors.forename: Kurt
authors.initials: K
authors.lastname: Boman
authors.affiliation: Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Jan W
authors.initials: JW
authors.lastname: Eriksson
authors.affiliation: Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Maria K
authors.initials: MK
authors.lastname: Svensson
mesh_terms: D000328:Adult; D000368:Aged; D058070:Asymptomatic Diseases; D015415:Biomarkers / Q000097:blood; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000150:complications* / Q000175:diagnosis; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications* / Q000175:diagnosis; D003925:Diabetic Angiopathies / Q000097:blood / Q000175:diagnosis / Q000209:etiology*; D042241:Early Diagnosis; D005260:Female; D005342:Fibrinolysis; D006801:Humans; D016015:Logistic Models; D008137:Longitudinal Studies; D035002:Lower Extremity / Q000098:blood supply*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D058729:Peripheral Arterial Disease / Q000097:blood / Q000175:diagnosis / Q000209:etiology*; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000097:blood
chemical_list: D015415:Biomarkers; D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; D010959:Tissue Plasminogen Activator
keywords: Fibrinolysis; diabetes mellitus; lower extremity arterial disease