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Tissue-plasminogen activator, plasminogen activator inhibitor and risk of peripheral arterial disease
1Wolfson Unit for Prevention of Peripheral Vascular Diseases, Department of Public Health Sciences, University of Edinburgh Medical School, UK.
Insights
Elevated levels of tissue-plasminogen activator (t-PA) antigen and plasminogen activator inhibitor (PAI) activity are linked to peripheral arterial disease. This association is influenced by lipids and smoking.
Area of Science:
- Cardiovascular Research
- Hematology
- Epidemiology
Background:
- Peripheral arterial disease (PAD) is a significant manifestation of atherosclerosis.
- Fibrinolytic system components, including tissue-plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI), play a role in vascular health.
- Understanding the interplay between fibrinolysis and PAD risk factors is crucial for prevention.
Purpose of the Study:
- To investigate the association between fibrinolytic variables (t-PA antigen, PAI activity) and peripheral arterial disease.
- To explore the mediating role of cardiovascular risk factors (lipids, smoking) in this relationship.
Main Methods:
- Population-based case-control study design.
- Selection of cases and controls from the Edinburgh Artery Study (men and women aged 55-74).
- Measurement of t-PA antigen and PAI activity, alongside assessment of cardiovascular risk factors.
Main Results:
- Significantly elevated mean levels of t-PA antigen and PAI activity observed in PAD cases compared to controls.
- Increased risk of PAD associated with higher PAI activity and t-PA antigen levels.
- Risk reduction observed upon adjustment for serum triglycerides, HDL cholesterol, and smoking, indicating partial mediation.
Conclusions:
- Impaired fibrinolytic potential, characterized by raised PAI activity and t-PA antigen, is associated with peripheral atherosclerosis.
- Lipid profiles and cigarette smoking significantly influence the relationship between fibrinolytic markers and PAD.
- These findings highlight potential therapeutic targets for PAD prevention and management.
Abstract:
In this population-based case-control study, we examined the relationship between the fibrinolytic variables tissue-plasminogen activator (t-PA) antigen and plasminogen activator inhibitor (PAI) activity, cardiovascular risk factors and peripheral arterial disease. Cases and controls were selected from the Edinburgh Artery Study, a random sample survey of men and women, aged 55-74 years. Mean levels of t-PA antigen and PAI activity were significantly elevated in 121 cases compared to 126 controls. The increased risks of peripheral arterial disease with increasing PAI activity and t-PA antigen levels were partly mediated by interactions with serum triglycerides, high density lipoprotein (HDL) cholesterol and cigarette smoking. For example, adjustment for triglycerides significantly reduced the odds of disease for PAI activity from 1.41 (95% confidence intervals 1.08, 1.86) to 1.24 (0.93, 1.65) and from 1.47 (1.09, 1.98) to 1.34 (0.99, 1.82) for t-PA antigen. We conclude that impaired fibrinolytic potential (raised PAI activity and t-PA antigen) is associated with peripheral atherosclerosis and that this relationship is partly influenced by lipids and cigarette smoking.