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Poor response to activated protein C as a prominent risk predictor of advanced atherosclerosis and arterial disease
1Department of Neurology, Innsbruck University Clinic, Innsbruck, Austria. stefan.kiechl@uibk.ac.at
Insights
Low activated protein C (APC) resistance is linked to increased risk of arterial stenosis and cardiovascular disease. This association exists independently of the factor V Leiden mutation, highlighting broader implications for vascular health.
Area of Science:
- Vascular Biology
- Thrombosis Research
- Epidemiology
Background:
- The role of activated protein C (APC) resistance in arterial thrombosis remains controversial.
- Understanding APC resistance is crucial for assessing arterial disease risk.
Purpose of the Study:
- To investigate the association between APC resistance and atherosclerotic vascular disease.
- To determine if APC resistance independently predicts arterial stenosis and cardiovascular disease.
Main Methods:
- A population-based survey of 826 individuals.
- High-resolution duplex ultrasound of carotid and femoral arteries.
- Assessment of APC response (APC ratios) and factor V Leiden mutation status.
Main Results:
- Decreased APC response correlated with increased risk of carotid and femoral artery stenosis.
- Lower APC ratios were associated with prevalent cardiovascular disease, irrespective of factor V Leiden mutation.
- Nongenetic factors significantly influence APC response in the general population.
Conclusions:
- A clear, independent association exists between low APC response and advanced atherosclerosis.
- Factor V Leiden mutation is only one aspect of APC resistance's link to vascular disease.
Background:
The potential role of activated protein C (APC) resistance in arterial thrombosis and disease is a matter of ongoing controversy.
Methods And Results:
In the present population-based survey, a random sample of 826 men and women underwent high-resolution duplex ultrasound scanning of the carotid and femoral arteries. Response to APC was expressed in APC ratios. Subjects were tested for the factor V Leiden mutation. The risk of carotid stenosis increased gradually with decreasing response to APC (adjusted OR [95% CI] for a 1-U decrease of response to APC, 1.6 [1. 2 to 2.2]), as did the risk of femoral artery stenosis (1.7 [1.3 to 2.3]) and prevalent cardiovascular disease (1.4 [1.1 to 2.0]). The association between low APC ratio and atherosclerotic vascular disease applied equally to subjects with the factor V Leiden mutation and those without. Our study identified various nongenetic determinants of poor response to APC in the general population, including behavioral, hormonal, and environmental factors.
Conclusions:
The present study revealed an independent and gradual association between low response to APC and both advanced atherosclerosis (stenosis) and arterial disease. Resistance to APC due to factor V Leiden mutation was only one facet of this relationship.