Journal
AMERICAN JOURNAL OF CARDIOLOGY
Volume 105, Issue 1, Pages 17-24Publisher
EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
DOI: 10.1016/j.amjcard.2009.08.643
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Funding
- National Institutes of Health, Bethesda, Maryland [R01 HL6 744 BARI 2D]
- National Institutes of Health [U01HL63804, R01 HL71306]
- National Heart, Lung, and Blood Institute, Bethesda, Maryland [U01 HL061744, U01 HL061746, U01 HL061748, U01 HL063804]
- National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland
- GlaxoSmithKline
- Collegeville, Pennsylvania
- Bristol-Myers Squibb Medical Imaging, Inc., North-Billerica, Massachusetts
- Astellas Pharma US, Inc.
- Deerfield
- Illinois
- Merck & Co., Inc., Whitehouse Station, New Jersey
- Abbott Laboratories, Inc.
- Abbott Park
- Pfizer, Inc., New York
- MediSense Products, Mississauga, Ontario, Canada
- Bayer Diagnostics, Tanytown, New York
- Becton-Dickinson and Company, Franklin Lakes, New Jersey
- JR Carlson Laboratories
- Arlington Heights
- Centocor, Inc.
- Malvern, Pennsylvania
- Eli Lilly and Company, Indianapolis, Indiana
- LipoScience, Inc.
- Raleigh, North Carolina
- Merck
- Sante, Lyon, France
- Novartis Pharmaceuticals Corporation, East Hanover, New Jersey
- Novo Nordisk, Inc., Princeton, New Jersey
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL071306, U01HL061746, U01HL061744, U01HL061748, U01HL063804] Funding Source: NIH RePORTER
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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 BAR! 2D trial were grouped by age (<50, 50 to 59, 60 to 69, and >= 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. (C) 2010 Elsevier Inc. All rights reserved. (Am J Cardiol 2010;105:17-24)
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