© 2006 Schattauer GmbH, Stuttgart 991 Increased cardiovascular risk markers in obesity are associated with body adiposity: Role of leptin Javier Gómez-Ambrosi 1 , Javier Salvador 2 , Camilo Silva 2 , Carlos Pastor 3 , Fernando Rotellar 3 , María J. Gil 4 , Javier A. Cienfuegos 3 , Gema Frühbeck 1,2 1 Metabolic Research Laboratory, 2 Department of Endocrinology, 3 Department of Surgery and 4 Department of Biochemistry; Clínica Universitaria de Navarra, University of Navarra, Pamplona, Spain Summary Epidemiological studies have shown that obesity is associated with increased blood concentrations of proinflammatory fac- tors and markers of endothelial dysfunction such as fibrinogen, C-reactive protein (CRP), and vonWillebrand factor (vWF).We analyzed the association of these markers with percentage of body fat (BF), and the influence of leptin in a cross-sectional study of 1,089 subjects (366 men) aged 44 (34–53) [median (in- terquartile range)] years, who were classified as obese or non- obese according to BF estimated by whole-body air displace- ment plethysmography.Obesity was defined as BF ≥ 25% in men and ≥ 35% in women.Compared with non-obese subjects (mean ± SD), obese patients had higher concentrations of fibrinogen (312 ± 78 vs. 342 ± 81 mg/dl, P < 0.001), CRP (0.41 ± 0.75 vs. 0.75 Keywords Obesity, adipose tissue, inflammation, leptin, insulin resistance ± 1.04 mg/l, P = 0.014), vWF (107 ± 29 vs. 123 ± 55%, P < 0.001), and leptin (10.4 ± 6.5 vs. 37.5 ± 26.1 ng/ml, P < 0.0001). A posi- tive correlation was observed between BF and fibrinogen (r = 0.266; P < 0.0001), logCRP (r = 0.409; P < 0.0001), and vWF (r = 206; P < 0.0001). Leptin was correlated with fibrinogen (r = 0.219, P < 0.0001), logCRP (r = 0.339, P < 0.0001), and vWF (r = 0.124, P = 0.002), but the statistical significance was lost after including BF in adjusted-correlation and multivariate analysis, suggesting that they are not regulated by leptin per se. In conclu- sion, the obesity-associated increase in the circulating concen- trations of fibrinogen, CRP, and vWF is highly associated to BF and apparently not determined by leptin. Thromb Haemost 2006; 95: 991– 6 Cardiovascular Biology and Cell Signalling Correspondence to: Gema Frühbeck, RNutr, MD, PhD Department of Endocrinology Clínica Universitaria de Navarra Avda. Pío XII 36, 31008-Pamplona, Spain Tel.: +34 948 25 54 00 Ext. 4484, Fax: +34 948 29 65 00 E-mail: gfruhbeck@unav.es Financial support: This study was funded by Instituto de Salud Carlos III, FIS RGTO G03/028 from the Ministerio de Sanidad y Consumo, Spain and by the Department of Health of the Gobierno de Navarra (48/2003 and 20/2005), Spain. Received February 9, 2006 Accepted after resubmission April 28, 2006 Prepublished online May 11, 2006 doi:10.1160/TH06–02–0079 Introduction The prevalence of obesity is increasing dramatically worldwide (1, 2). Obesity is an independent risk factor for cardiovascular disease (CVD) development being associated with increased morbidity and mortality. Obesity is defined medically as a state of increased adipose tissue mass of sufficient magnitude to pro- duce adverse health consequences. A great effort has been made during the last years to elucidate how excess adiposity leads to CVD (1, 2). In the past decade, it has become increasingly evident that adipose tissue represents an important determinant of a chronic, low-grade inflammatory state. In this sense, obesity is associated with an increase in circulating inflammatory markers, including fibrinogen, C-reactive protein (CRP), and von Willebrand factor (vWF), among others (1, 3–5). In addition, excess adiposity is accompanied by a clustering of metabolic alterations that can lead to CVD. The pathophysiological relevance of adipocyte- derived factors resides in the participation of these molecules beyond body weight balance in vascular homeostasis through ef- fects on blood pressure, fibrinolysis, coagulation, angiogenesis, and immunity, among others.Adipokines have been shown to be implicated either directly or indirectly in the regulation of several processes that regulate the development of inflammation, athe- rogenesis, hypertension, insulin resistance and vascular remod- elling (5). In this sense, leptin has been shown to play a role in in- flammation (6) and has been suggested to be involved in CVD (7). However, it is difficult to discriminate whether the involve- For personal or educational use only. No other uses without permission. All rights reserved. Downloaded from www.thrombosis-online.com on 2012-05-02 | ID: 1000323023 | IP: 159.237.12.82