Leptin links with plasminogen activator inhibitor–1 in human obesity: the SABPA study
Schutte, Aletta E
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The relationship between obesity and the development of cardiovascular disease is well established. However, the underlying mechanisms contributing to vascular disease and increased cardiovascular risk in the obese remain largely unexplored. Since leptin exerts direct vascular effects, we investigated leptin and the relationship thereof with circulating markers of vascular damage, namely plasminogen activator inhibitor–1 antigen (PAI–1ag), von Willebrand factor antigen (vWFag) and urinary albuminto–creatinine ratio (ACR). The study included a bi–ethnic population of 409 African and Caucasian teachers who were stratified into lean (o0.5) and obese (?0.5) groups according to waist–to–height ratio. We obtained ambulatory blood pressure measurements and determined serum leptin levels, PAI–1ag, vWFag and ACR, as markers of vascular damage. The obese group had higher leptin (Po0.001) and PAI–1ag (Po0.001) levels and a tendency existed for higher vWFag (P=0.068). ACR did not differ between the two groups (P=0.21). In single regression analyses positive associations existed between leptin and all markers of vascular damage (all Po0.001) only in the obese group. After adjusting for covariates and confounders in multiple regression analyses, only the association between leptin and PAI–1ag remained (R2=0.440; ?=0.293; P=0.0021). After adjusting for gender, ethnicity and age, additional analyses indicated that leptin also associated with fibrinogen and clot lysis time in both lean and obese groups, which in turn is associated with 24– h blood pressure and pulse pressure. This result provides evidence that elevated circulating leptin may directly contribute to vascular damage, possibly through mechanism related to thrombotic vascular disease.
- Faculty of Health Sciences