Usefulness of Visceral Obesity (Waist/ Hip Ratio) in Predicting Vascular Endothelial Function in Healthy Overweight Adults Robert D. Brook, MD, Robert L. Bard, MA, Melvyn Rubenfire, MD, Paul M. Ridker, MD, and Sanjay Rajagopalan, MD Vascular endothelial dysfunction (VED) is associated with obesity; however, its etiology remains controver- sial. By determining the predictors of fasting and post- prandial endothelial function in overweight adults with- out other cardiovascular risk factors, we were able to investigate novel mechanisms directly linking obesity to VED. Thirty-two healthy adults (body mass index [BMI] >27 kg/m 2 ) underwent determination of fasting low- density lipoprotein (LDL) particle size, high sensitivity C-reactive protein levels, anthropometric measurements, and endothelial function by flow-mediated dilation (FMD) of the brachial artery. Postprandial lipemia and FMD were measured 4 hours after ingestion of a high-fat meal. Blood pressures and fasting levels of lipoproteins, glucose, insulin, and fatty acids were within normal limits in all subjects. An abdominal fat pattern, as de- termined by an increased waist/hip ratio (WHR), was the sole significant predictor of FMD (r 0.58, p  0.001), despite no significant correlation between whole body obesity (BMI) and FMD. At comparable levels of BMI, obese subjects with a WHR >0.85 had a signifi- cantly blunted FMD compared with those with a WHR <0.85 (3.93  2.85% vs 8.34  5.47%, p  0.016). Traditional coronary risk factors, C-reactive protein, postprandial lipemia, and LDL particle size did not pre- dict FMD. We found no appreciable alteration in the postprandial state from fasting FMD (6.31  4.62% vs 6.25  5.47%, p  0.95). The same results were found when women were analyzed alone. Increased abdomi- nal adiposity determined by a simple WHR is a strong independent predictor of VED even in healthy over- weight adults; this is a finding unexplained by alter- ations in conventional risk factors, systemic inflamma- tion, or the atherogenic lipoprotein pattern. 2001 by Excerpta Medica, Inc. (Am J Cardiol 2001;88:1264 –1269) O besity is associated with increased cardiovascu- lar morbidity and mortality 1,2 and is now con- sidered a major independent risk factor. 3 In addition to whole body obesity, the degree of abdominal adipos- ity conveys an independent prediction of risk beyond body mass index (BMI). 2,4–6 Vascular endothelial dysfunction (VED) plays a pivotal role in the pathogenesis of atherosclerosis 7 and enhances the risk of future cardiovascular events. 8,9 The presence of VED has been demonstrated in over- weight patients with insulin resistance 10 and with vis- ceral obesity. 11,12 Therefore, VED may be an impor- tant link between obesity per se and heightened car- diovascular risk. To provide insight into the mechanisms by which obesity itself may directly lead to VED, we deter- mined the predictors of fasting and postprandial vas- cular reactivity in otherwise healthy overweight adults. To minimize the confounding effects of other cardiovascular risk factors often associated with obe- sity, we studied young overweight adults without ad- ditional conventional risk factors (uncomplicated obe- sity). In this manner we were able to directly investi- gate chronic systemic inflammation, 13,14 atherogenic lipoprotein alterations, 15–20 and body fat distribution as potential underlying mechanisms linking uncompli- cated obesity to VED. METHODS Study subjects: Potential subjects were recruited by local advertisements. Study subjects met the following inclusion and exclusion criteria during an initial screening visit: (1) inclusion criteria: overweight (BMI 27 kg/m 2 ); male or female between 18 and 50 years old; and (2) exclusion criteria: current tobacco use; any established cardiovascular disease; medica- tions for hypertension, hyperlipidemia, birth control, and hormone replacement; and those taking antioxi- dants (vitamin E, vitamin C) or folate. Subjects all had blood pressures of 140/90 mm Hg, fasting total cholesterol 200 mg/dl, fasting glucose 126 mg/dl, and no family history of premature cardiovascular disease. Study protocol: The study was approved by the Institutional Review Board and was performed in the From the Divisions of Hypertension and Cardiology, University of Michigan, Ann Arbor, Michigan and Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts. This study was supported by General Clinical Re- search Center Grant MO1-RR00042 from the University of Michigan, Ann Arbor, Michigan; and by investigator initiated Grant XEN086 from Roche Laboratories, Inc., Nutley, New Jersey. Manuscript re- ceived May 21, 2001; revised manuscript received and accepted July 26, 2001. Address for reprints: Robert D. Brook, MD, 3918 Taubman Cen- ter,1500 East Medical Center Dr., Ann Arbor, Michigan 48104. E-mail: Robdbrok@groupwise.umich.edu 1264 ©2001 by Excerpta Medica, Inc. All rights reserved. 0002-9149/01/$–see front matter The American Journal of Cardiology Vol. 88 December 1, 2001 PII S0002-9149(01)02088-4