Abstract 3968: The Metabolic Syndrome Is Associated with Hyperaggregable Platelets
Background: The metabolic syndrome (MetSyn) is a conglomerate of insulin resistance and obesity-related factors that together create a proatherosclerotic, proinflammatory, and prothrombotic milieu in which coronary artery disease (CAD) events are expressed. Although platelets have been shown to have higher reactive P-selectin expression in diabetics, little is known about platelet aggregation in the presence of MetSyn. We thus tested platelet aggregation both in vitro and ex vivo in relation to the presence or absence of MetSyn in families with a history of premature coronary disease.
Methods: We recruited 722 male and 965 female 20–79 year old nondiabetic relatives of a proband with CAD at a young age (< 60 years); 38% Black, 26% current smokers, all not currently taking antiplatelet agents. We examined ex-vivo whole blood agonist-induced platelet activation representing multiple pathways, and determined urinary excretion of 11-dehydro-thromboxane B2 (uTxM) by ELISA as a measure of in vivo platelet activation. Components of MetSyn (waist circumference, blood pressure, fasting plasma glucose, HDL-cholesterol, triglycerides) were measured and MetSyn was defined according to the Adult Treatment Panel III (ATP III) Guidelines.
Results: MetSyn was present in 339 (20%) of the sample. The table⇓ demonstrates that multivariable-adjusted aggregation to all agonists and uTxM was consistently significantly higher in persons with MetSyn. The associations were preserved when further adjusted for LDL-cholesterol. In models where the MetSyn components were tested for independent effects, low HDL-cholesterol was associated with all aggregation measures.
Conclusion: The findings indicate that the presence of MetSyn markedly increased platelet activation in all pathways, both in vivo and ex vivo. Thus, hyperaggregability may be one mechanism by which MetSyn is causally related to excess risk for cardiovascular events.