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Correlates of antithrombin, protein C, protein S, and TFPI in a healthy elderly cohort
P A Sakkinen1, M Cushman, B M Psaty
1Dept of Pathology, University of Vermont, Colchester 05446, USA.
Insights
Anticoagulant proteins like Antithrombin, Protein C, Protein S, and Tissue Factor Pathway Inhibitor (TFPI) were studied in older adults. These proteins were linked to inflammation and lipids, not directly to age, suggesting a potential age-related hemostatic imbalance.
Area of Science:
- Gerontology
- Cardiovascular Medicine
- Hematology
Background:
- Acute myocardial infarctions are predominantly thrombotic events, often fatal in the elderly.
- Understanding the role of anticoagulant proteins in aging cardiovascular health is crucial.
- Previous research has not fully elucidated the age-related associations of key anticoagulant proteins.
Purpose of the Study:
- To investigate the cross-sectional associations of Antithrombin, Protein C, Protein S, and Tissue Factor Pathway Inhibitor (TFPI) in elderly individuals.
- To determine relationships between these anticoagulant proteins, age, inflammation, lipids, coagulation factors, and subclinical cardiovascular disease (CVD).
Main Methods:
- Cross-sectional study of 400 healthy participants (≥65 years) from the Cardiovascular Health Study, free of clinical CVD.
- Assessed levels of Antithrombin, Protein C, Protein S, and TFPI.
- Analyzed associations with age, inflammation markers (e.g., fibrinogen), lipids (e.g., LDL-cholesterol), coagulation factors, and subclinical atherosclerosis markers (e.g., ankle-arm index, carotid artery measures).
Main Results:
- No strong age-associated trends were observed for most inhibitors, though Protein C was lower in older women and TFPI higher in older men.
- Inhibitors were highly intercorrelated and associated with inflammation markers, lipids, and certain coagulation factors.
- Only TFPI showed associations with subclinical atherosclerosis (ankle-arm index, carotid artery stenosis, and carotid wall thickness).
Conclusions:
- Anticoagulant protein levels did not significantly increase with age but were linked to inflammation and lipids.
- The study hypothesizes an age-related hemostatic imbalance due to increased thrombin production, potentially raising thrombotic risk.
- TFPI's association with subclinical CVD suggests it may be a marker of endothelial damage.
Abstract:
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 Antithrombin, 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 > or = 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 < or = 0.001), and TFPI was higher in older men (p < or = 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 < or = 0.01; and carotid wall thickness, p trend < or = 0.05. In multivariate analysis the independent predictors of TFPI were levels of fibrinogen; the fibrinolytic marker plasmin-antiplasmin 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.
