1. Raphael See, Shuaib Abdullah, Darren K. McGuire, Amit Khera, Mahesh J. Patel, Jason B. Lindsey, Scott M. Grundy, James A. de Lemos J Am Coll Cardiol 2007;50:752-9 Waist-to-Hip Ratio is a Superior Predictor of Atherosclerosis Compared with Body Mass Index in a Population-Based Sample: Observations from the Dallas Heart Study

2. Copyright ©2007 American College of Cardiology Foundation. Restrictions may apply. J Am Coll Cardiol 2007;50:752-9 Obesity is associated with an increased risk of CV mortality Most prior studies examining CV risk have used BMI as the measure of obesity BMI poorly characterizes central obesity Waist circumference (WC) and waist-to-hip ratio (WHR) more strongly correlate with CV event rates Rimm EB, et al., Am J Epidemiol 1995;141:1117-27; Dagenais GR, et al., Am Heart J 2005;149:54-60.; Yusuf S, et al., Lancet 2005;366:1640-9. Background

3. Copyright ©2007 American College of Cardiology Foundation. Restrictions may apply. J Am Coll Cardiol 2007;50:752-9 Obesity & CV Events Yusuf S, et al. Lancet 2005;366:1640-9

4. Copyright ©2007 American College of Cardiology Foundation. Restrictions may apply. J Am Coll Cardiol 2007;50:752-9 Cassidy et al: 443 non-diabetic, aSx white men BMI, WC, & WHR independently associated with CAC in low risk men Snell-Bergeon et al: 762 aSx subjects BMI & WC independently associated with CAC in men & women WHR associated with CAC only in men Study populations were small, homogeneous, and selected Cassidy AE, et al., Circulation 2005;111:1877-82; Snell-Bergeon JK, et al. Int J Obes Relat Metab Disord 2004;28:1594-9. Obesity & Coronary Artery Calcification

5. Copyright ©2007 American College of Cardiology Foundation. Restrictions may apply. J Am Coll Cardiol 2007;50:752-9 Determine the association between differing measures of obesity and atherosclerosis Objective

6. Copyright ©2007 American College of Cardiology Foundation. Restrictions may apply. J Am Coll Cardiol 2007;50:752-9 Methods Dallas Heart Study: Population-based probability sample of 6,101 subjects Measures of body composition: Body mass indexWaist circumference Waist-to-hip ratioHip circumference Visit 1 Detailed health survey n=6,101 Visit 2 Blood / urine collection n=3,398 Visit 3 Anthropometrics EBCT/MRI n=2,971 2,744 subjects ages 30-65 with interpretable scan data

7. Copyright ©2007 American College of Cardiology Foundation. Restrictions may apply. J Am Coll Cardiol 2007;50:752-9 Measures of Atherosclerosis Coronary Artery Calcification by CT Abdominal Aortic Plaque by MRI

8. Copyright ©2007 American College of Cardiology Foundation. Restrictions may apply. J Am Coll Cardiol 2007;50:752-9 Statistical Analysis Sex-specific quintiles for each obesity measurement BMI, WC, and WHR Logistic regression analyses Univariable models Dependent variable: CAC or aortic plaque Independent variables: obesity measures in quintiles Multivariable models Dependent variable: CAC or aortic plaque Independent variables: obesity measures in quintiles + traditional CV risk factors C-statistic comparisons for above models

9. Copyright ©2007 American College of Cardiology Foundation. Restrictions may apply. J Am Coll Cardiol 2007;50:752-9 Quintile BMI (kg/m 2 ) WC (cm)WHR WOMEN (n=1511) 1 st < 24.6< 81.8< 0.80 2 nd 24.6 – 28.581.9 – 91.60.80 – 0.84 3 rd 28.5 – 32.791.7 – 100.50.84 – 0.88 4 th 32.7 – 38.4100.6 – 113.00.88 – 0.92 5 th > 38.4> 113.0> 0.92 MEN (n=1233) 1 st < 24.4< 88.4< 0.91 2 nd 24.4 – 27.288.5 – 96.00.91 – 0.94 3 rd 27.2 – 29.896.1 – 102.50.94 – 0.97 4 th 29.8 – 33.4102.6 – 111.60.97 – 1.01 5 th > 33.4> 111.6> 1.01 Quintile Cut-points

10. Copyright ©2007 American College of Cardiology Foundation. Restrictions may apply. J Am Coll Cardiol 2007;50:752-9 Association Between Obesity & CAC

11. Copyright ©2007 American College of Cardiology Foundation. Restrictions may apply. J Am Coll Cardiol 2007;50:752-9 Association Between Obesity & Aortic Plaque

12. Copyright ©2007 American College of Cardiology Foundation. Restrictions may apply. J Am Coll Cardiol 2007;50:752-9 Association Between Obesity & CAC after MV adjustment Adjusted for: age, smoking, DM, dyslipidemia, low HDL, high TG

13. Copyright ©2007 American College of Cardiology Foundation. Restrictions may apply. J Am Coll Cardiol 2007;50:752-9 Association Between Obesity & Aortic Plaque after MV Adjustment Adjusted for: age, smoking, DM, dyslipidemia, low HDL, high TG

14. Copyright ©2007 American College of Cardiology Foundation. Restrictions may apply. J Am Coll Cardiol 2007;50:752-9 C-statistics from Univariable Models PredictorsOutcomes CAC Aortic Plaque Women BMI 0.550.52 WC 0.61 * 0.53 * WHR 0.66 *± 0.62 *± Men BMI 0.540.53 WC 0.59 * 0.49 * WHR 0.64 *± 0.58 ± * P < 0.01 vs BMI ± p < 0.01 vs WC

15. Copyright ©2007 American College of Cardiology Foundation. Restrictions may apply. J Am Coll Cardiol 2007;50:752-9 C-statistics from MV Models PredictorsOutcomes CAC Aortic Plaque Women CV RF 0.860.72 + BMI 0.860.73 + WC 0.870.72 + WHR 0.860.73 Men CV RF 0.830.76 + BMI 0.830.76 + WC 0.830.76 + WHR 0.830.76

16. Copyright ©2007 American College of Cardiology Foundation. Restrictions may apply. J Am Coll Cardiol 2007;50:752-9 “large” waist “normal” waist Men Women Waist & Hip Circumference Analyses p-values for WCxHC interaction: Women < 0.01 Men = 0.07

17. Copyright ©2007 American College of Cardiology Foundation. Restrictions may apply. J Am Coll Cardiol 2007;50:752-9 Conclusions WHR is more closely associated with atherosclerosis than other measures of obesity Independent of traditional risk factors Did not increment the c-statistic over CV risk factor model Superiority of WHR may be due to an interaction between WC & HC Associations between differing measures of obesity and atherosclerosis resemble those with CV events Suggest atherosclerosis may be a link between obesity and events