Comparison of plasminogen activator inhibitor-1, tissue type plasminogen activator antigen, fibrinogen, and D-dimer levels in various age decades in patients with type 2 diabetes mellitus and stable coronary artery disease (from the BARI 2D trial)

Am J Cardiol. 2010 Jan 1;105(1):17-24. doi: 10.1016/j.amjcard.2009.08.643. Epub 2009 Nov 14.


Advancing age is associated with downregulation of fibrinolysis in normal subjects. This is reflected by high concentrations of plasminogen activator inhibitor-1 (PAI-1) in the blood, which has been implicated in the increasing cardiovascular morbidity and mortality with age. We sought to delineate the relation of PAI-1 to several factors, including age, gender, and ethnicity in patients with type 2 diabetes mellitus (DM) and stable coronary artery disease enrolled in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial. A total of 2,321 patients with DM and stable coronary artery disease in the BARI 2D trial were grouped by age (<50, 50 to 59, 60 to 69, and > or =70 years). Tissue-type plasminogen activator antigen, PAI-1 antigen and activity, fibrinogen, and D-dimer were quantified at baseline. The PAI-1 antigen (p <0.001) and its activity (p <0.001) and their ratios to tissue-type plasminogen activator (p <0.001) were all paradoxically lower with advancing age. In contrast, D-dimer (p <0.0001) was elevated. The fibrinogen level was greatest in the oldest age group (p = 0.01). The level of tissue-type plasminogen activator antigen did not vary with age. These age-related differences were observed primarily in men and non-Hispanic white and Asian/other participants. In conclusion, PAI-1 is inversely related to age in patients with DM and stable coronary artery disease and is associated with elevation of D-dimer, reflecting augmented fibrinolysis. The unexpected profibrinolytic state seen with advancing age and DM might reflect a protective phenomenon resulting from enhanced survival of some older patients with DM that endowed the older patients with longevity sufficient to enable them to participate in the BARI 2D trial. Targeting the factors that led to the downregulation of PAI-1 in older patients with type 2 DM might offer an attractive strategy for reducing cardiovascular risk.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aged
  • Autoantigens / blood*
  • Coronary Artery Disease / blood*
  • Coronary Artery Disease / complications
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / complications
  • Disease Progression
  • Female
  • Fibrin Fibrinogen Degradation Products / metabolism*
  • Fibrinogen / metabolism*
  • Fibrinolysis / physiology
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Plasminogen Activator Inhibitor 1 / blood*
  • Retrospective Studies
  • Risk Factors
  • Severity of Illness Index
  • Time Factors
  • Tissue Plasminogen Activator / blood
  • Tissue Plasminogen Activator / immunology*


  • Autoantigens
  • Fibrin Fibrinogen Degradation Products
  • Plasminogen Activator Inhibitor 1
  • fibrin fragment D
  • Fibrinogen
  • Tissue Plasminogen Activator