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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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. 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.[1]


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