Fibrinolytic risk factor clustering and insulin resistance in healthy male relatives of men with intermittent claudication.
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.


CONCLUSIONS
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.
Parry
D J
DJ
Department of Vascular Surgery, St James's Hospital, Leeds, UK.
Grant
P J
PJ
Scott
D J A
DJ
D002318:Cardiovascular Diseases / Q000097:blood / Q000235:genetics; D003430:Cross-Sectional Studies; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005342:Fibrinolysis; D006801:Humans; D007333:Insulin Resistance; D007383:Intermittent Claudication / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D012307:Risk Factors; D010959:Tissue Plasminogen Activator / Q000097:blood
D005338:Fibrin Fibrinogen Degradation Products; D017395:Plasminogen Activator Inhibitor 1; C036309:fibrin fragment D; D010959:Tissue Plasminogen Activator