Small, dense low-density lipoprotein and C-reactive protein in obese subjects with and without other criteria for the metabolic syndrome Gianluca Iacobellis, MD, PhD*, Maria Cristina Ribaudo, MD, PhD, Alessandra Zappaterreno, MD, Concetta Valeria Iannucci, MD, Frida Leonetti, MD, PhD Center for Human Nutrition, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA (Dr. Iacobellis); Endocrinology, Department of Clinical Sciences, La Sapienza University, Rome, Italy (Drs. Ribaudo, Zappaterreno, Iannucci, and Leonetti) BACKGROUND: Although obesity is an important cardiovascular risk factor, growing evidence shows that a substantial portion of obese subjects can be considered metabolically healthy but obese (MHO). However the extent to which obese subjects manifest small, dense low-density lipoprotein (LDL) particles without other characteristics of the metabolic syndrome (MS) remains unknown. OBJECTIVE: The purpose of this study was to determine the difference between MHO (only meeting the obesity criteria) and obese subjects meeting all the criteria for the MS with regard to LDL size and high-sensitivity C-reactive protein (hs-CRP), as a biomarker of inflammation. METHODS: Two hundred obese subjects (168 women, mean age 36.5  5 years [range, 20 – 60]; mean body mass index [BMI; calculated as kg/m 2 ] 39  5 [range, 30 – 80.4] ) were studied for LDL particles size and hs-CRP levels. RESULTS: Of 200 enrolled obese subjects, 55 were defined MHO subjects meeting only obesity criteria. The other 145 met all five criteria and were defined as having MS. Although MHO and MS subjects had similar BMI, MHO subjects had a lower percentage of small LDL particles (8% vs 29%, P  0.001), higher average LDL diameter (274  5 vs 270  7 Å, P  0.001), and lower hs-CRP levels (P  0.05) than MS patients. CONCLUSION: The major finding of this study is that MHO subjects compared to equally obese subjects meeting the criteria of the MS have statistically significant differences in size of LDL and concentration of hs-CRP. However, the absolute differences are very small and of uncertain clinical significance. © 2007 National Lipid Association. All rights reserved. KEYWORDS: Atherosclerosis; LDL size; Metabolic syndrome; Metabolically healthy obese; Uncomplicated obesity It is commonly assumed that obesity is associated with risks that predispose to cardiovascular disease. Obesity is believed to confer this risk through other definable charac- teristics, such as insulin resistance, high blood pressure, low high-density lipoprotein (HDL), and high blood triglycer- ides. The metabolic syndrome (MS) has been defined by setting criteria for such clinical measures. 1 Nevertheless, presence of obese subjects that do not meet these criteria appears to be reasonably common with a prevalence of 8% to 28%. 2–10 Absence of these risk factors is considered to * Corresponding author. Present address: Department of Medicine, McMaster University St. Joseph’s Healthcare, Fontbonne Building 5th Floor, 50 Charlton Avenue E, Hamilton, ON, L8 4A6 Canada. E-mail address: gianluca@ccc.mcmaster.ca or gianluca.iaco@tin.it Submitted June 26, 2007. Accepted for publication October 12, 2007. 1933-2874/$ -see front matter © 2007 National Lipid Association. All rights reserved. doi:10.1016/j.jacl.2007.10.006 Journal of Clinical Lipidology (2007) 1, 599 – 604