Fibrinolytic risk factor clustering and insulin resistance in healthy male relatives of men with intermittent claudication
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Published on: April 1, 2015
D J Parry1, P J Grant, D J A Scott
1Department of Vascular Surgery, St James's Hospital, Leeds, UK.
Insights
Healthy male relatives of men with intermittent claudication show higher levels of fibrinolytic factors, including plasminogen activator inhibitor 1 (PAI-1) and tissue plasminogen activator (tPA), and increased insulin resistance, indicating a potential genetic predisposition to cardiovascular disease.
Area of Science:
- Cardiovascular Research
- Hematology
- Metabolic Syndrome
Background:
- Elevated fibrinolytic factors are linked to cardiovascular risk in healthy individuals.
- Intermittent claudication (IC) in men under 65 suggests potential inherited cardiovascular risk factors.
Purpose of the Study:
- To assess fibrinolytic factors and insulin resistance in healthy male first-degree relatives of men with premature IC.
- To investigate fibrinolytic risk factor clustering in a high-risk population.
Main Methods:
- Comparison of 165 healthy first-degree relatives with 165 matched controls.
- Measurement of plasminogen activator inhibitor 1 (PAI-1), tissue plasminogen activator (tPA), and D-dimer levels.
- Estimation of insulin resistance using Homeostasis Model Assessment (HOMA) and genotyping for PAI-1 4G/5G polymorphism.
Main Results:
- Relatives exhibited significantly higher PAI-1, tPA, and D-dimer levels compared to controls.
- Increased insulin resistance and clustering of atherogenic risk factors were observed in relatives.
- The association of tPA and D-dimer with relative status was independent of other variables on multivariate analysis.
Conclusions:
- Healthy male first-degree relatives of men with IC display elevated PAI-1, tPA, D-dimer, and insulin resistance.
- These findings support the hypothesis of fibrinolytic risk factor clustering in this genetically predisposed population.
- This suggests a potential inherited component for cardiovascular disease risk.
Background:
Raised fibrinolytic factors predict cardiovascular risk in healthy subjects. The aim of this study was to measure fibrinolytic factors and insulin resistance in healthy male first-degree relatives of men with intermittent claudication younger than 65 years.
Methods:
The study compared 165 healthy first-degree relatives with 165 age-, sex- and race-matched control subjects free from a personal or family history of premature cardiovascular disease. Primary outcome measures were plasminogen activator inhibitor 1 (PAI-1), tissue plasminogen activator (tPA) and D-dimer levels. Insulin resistance was estimated by Homeostasis Model Assessment. Clinical and biochemical risk factors were measured and subjects genotyped for the PAI-1 4G/5G polymorphism.
Results:
First-degree relatives had significantly higher mean PAI-1 (10.23 versus 7.85 ng/ml; P = 0.024), tPA (9.98 versus 8.29 ng/ml; P < 0.001) and D-dimer levels (56.6 versus 46.1 ng/ml; P = 0.004). They also had significantly higher insulin resistance (1.85 versus 1.53; P < 0.001) and clustered multiple atherogenic risk factors. On multivariate analysis the association between both tPA and D-dimer levels and relative status was independent of other variables.
Conclusion:
Raised levels of PAI-1, tPA, D-dimer and estimated insulin resistance were present in the healthy male first-degree relatives of men with intermittent claudication. These data support the hypothesis of fibrinolytic risk factor clustering in this high-risk population.
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