Atherosclerosis 206 (2009) 239–244 Contents lists available at ScienceDirect Atherosclerosis journal homepage: www.elsevier.com/locate/atherosclerosis Circulating retinol-binding protein 4, cardiovascular risk factors and prevalent cardiovascular disease in elderly Erik Ingelsson a,b,∗ , Johan Sundström c , Håkan Melhus c , Karl Michaëlsson d , Christian Berne c , Ramachandran S. Vasan e , Ulf Risérus b , Rune Blomhoff f , Lars Lind c , Johan Ärnlöv b,g a Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden b Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden c Department of Medical Sciences, Uppsala University, Uppsala, Sweden d Department of Surgical Sciences, Uppsala University, Uppsala, Sweden e The Framingham Heart Study, Boston University School of Medicine, Framingham, MA, USA f Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway g Department of Health and Social Sciences, Högskolan Dalarna, Falun, Sweden article info Article history: Received 11 August 2008 Received in revised form 9 January 2009 Accepted 16 February 2009 Available online 11 March 2009 Keywords: Adipokines Obesity Cardiovascular disease Atherosclerosis Metabolic syndrome abstract Objective: Our aim was to examine relations of serum retinol-binding protein 4 (RBP4) to cardiovascu- lar risk factors, and prevalent metabolic syndrome (MetS) and cardiovascular disease (CVD) in a large community-based sample of elderly. Methods: We evaluated cross-sectional relations of serum RBP4 to cardiovascular risk factors including anthropometrical measures, blood pressure, lipid measures, fasting glucose and insulin, body fat distri- bution including truncal fat by dual-energy x-ray absorptiometry (DXA), homeostasis model assessment insulin resistance (HOMA-IR) and prevalent MetS in one thousand eight 70-year old participants (50% women) of the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS), and in five hun- dred seven 82-year old men from Uppsala Longitudinal Study of Adult Men (ULSAM). In ULSAM, we also examined associations with prevalent CVD. Results: RBP4 concentrations were positively correlated with serum triglycerides (r = 0.30; P < 0.0001 in both samples), whereas correlations with body mass index (BMI), waist circumference, sagittal abdom- inal diameter, total and truncal fat mass, total cholesterol, fasting glucose and HOMA-IR were weak. In multivariable-adjusted models, RBP-4 was associated with MetS (odds ratio (OR), 1.16 and 1.33; 95% con- fidence interval (CI), 0.99–1.37 and 1.05–1.67 per 1-standard deviation (SD) increase in PIVUS and ULSAM, respectively), and prior cerebrovascular disease (OR, 1.37; 95% CI, 1.00-1.88 per 1-SD increase in ULSAM), but not with prior myocardial infarction. Conclusion: In elderly, RBP4 concentrations were associated with MetS and its components in both sexes, and prior cerebrovascular disease in men. These findings are consistent with the hypothesis that circu- lating RBP4 could be a marker of metabolic complications and possibly also atherosclerosis and overt CVD. © 2009 Elsevier Ireland Ltd. All rights reserved. 1. Introduction The prevalence of obesity is rising rapidly worldwide [1,2]. This mounting epidemic of obesity has major clinical and public health implications, since overweight and obesity are associated with increased risk of several disease conditions, most prominently type 2 diabetes and cardiovascular disease (CVD) [1–3]. Recent advances have shown that the adipose tissue is involved actively in many ∗ Corresponding author. Tel.: +46 8 52482334; fax: +46 8 314975. E-mail address: erik.ingelsson@ki.se (E. Ingelsson). physiological processes; one of the more important ones being the production of adipokines. Adipokines, such as retinol-binding pro- tein 4 (RBP4), provide an important link between obesity, insulin resistance, and inflammation, and there is emerging evidence that they also are closely involved in the development of CVD [4]. GLUT4 is the major glucose transporter protein that mediates glucose uptake in adipose tissue and skeletal muscle, and it is thus a key regulator of glucose homeostasis [5]. The expression of RBP4 is elevated in adipose tissue of adipose-GLUT4-/- mice, [6] and cir- culating levels of RBP4 are elevated in insulin resistant mice, [6] and in humans with obesity and type 2 diabetes [6,7]. Also, RBP4 homozygous knockout (RBP4-/-) mice demonstrate lower free fatty acid levels, and enhanced insulin sensitivity as compared to control 0021-9150/$ – see front matter © 2009 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.atherosclerosis.2009.02.029