Correlates of Antithrombin, Protein C, Protein S, and TFPI in a Healthy Elderly Cohort

Pamela A. Sakkinen; Mary Cushman; Bruce M. Psaty; Lewis H. Kuller; S. Paul Bajaj; Arun K. Sabharwal; Robin Boineau; Elizabeth Macy; Russell P. Tracy

doi:10.1055/s-0037-1615152

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 1998; 80(01): 134-139
DOI: 10.1055/s-0037-1615152

Rapid Communication

Schattauer GmbH

Correlates of Antithrombin, Protein C, Protein S, and TFPI in a Healthy Elderly Cohort

Pamela A. Sakkinen

¹Depts of Pathology and Biochemistry

,

Mary Cushman

²Depts of Medicine and Pathology, University of Vermont

,

Bruce M. Psaty

³Depts of Medicine, Epidemilogy and Health Services, University of Washington, Seattle, Washington

,

Lewis H. Kuller

⁴Dept of Epidemiology, University of Pittsburgh

,

S. Paul Bajaj

⁵Depts of Medicine and Biochemistry

,

Arun K. Sabharwal

⁶Dept of Biochemistry, St. Louis University

,

Robin Boineau

⁷Division of Epidemiology and Clinical Applications, NHLBI, NIH, Bethesda, MD

,

Elizabeth Macy

⁸Dept of Pathology, University of Vermont, USA

,

Russell P. Tracy

¹Depts of Pathology and Biochemistry

› Institutsangaben

Abstract

Summary

The majority of fatal acute myocardial infarctions occur in the elderly. Since these events are predominantly thrombotic, we studied the cross-sectional associations of the anticoagulant proteins Anti-thrombin, Protein C, Protein S, and Tissue Factor Pathway Inhibitor (TFPI) in a subgroup (n = 400) of the Cardiovascular Health Study (a study of healthy men and women ≥65 years) free of clinical cardiovascular disease (CVD).

We did not observe any strong age-associated trends, although Protein C was lower in older women (p ≤0.001), and TFPI was higher in older men (p ≤0.01). The inhibitors were highly intercorrelated, and were associated with increased levels of inflammation-sensitive proteins (e.g., fibrinogen, plasminogen), lipids (especially total and LDL-cholesterol), and coagulation factors, such as Factors VIIc, IXc, and Xc. None was associated with the procoagulant markers Prothrombin Fragment F1-2 or Fibrinopeptide A. Only TFPI was associated with subclinical atherosclerosis: ankle-arm index and internal carotid artery stenosis, p trend ≤0.01; and carotid wall thickness, p trend ≤0.05. In multivariate analysis the independent predictors of TFPI were levels of fibrinogen; the fibrinolytic marker plasminantiplasmin complex; LDL-cholesterol; and carotid wall thickness (R² for the model = 0.35).

In summary, the inhibitors did not appear to increase with age, and were predominantly associated with inflammation markers and lipids. Since markers of thrombin production do increase with age, we hypothesize that an age-related hemostatic imbalance may ensue, with associated increased thrombotic risk. Only TFPI was associated with subclinical CVD, suggesting that it may more closely reflect endothelial damage. (250)

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