1. 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
J Am Coll Cardiol 2007;50:752-9
Raphael See, Shuaib Abdullah, Darren K. McGuire, Amit Khera, Mahesh J. Patel, Jason B. Lindsey, Scott M. Grundy, James A. de Lemos

2. Background
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
Obesity has been shown to be associated with an increase in CV mortality in the general population.
The majority of prior investigations examining the link between obesity and CV risk have used BMI as the measure of obesity over other measures, such as WC or WHR
However, BMI poorly characterizes central or abdominal obesity in comparison to waist circumference and WHR.
In addition, WC and WHR have recently been found to more strongly correlate with CV event rates.
However, it remains unclear if this association is due to an increase in atherosclerotic burden or due to other associated conditions, such as CHF, arrhythmias, or inflammation
Rimm EB, et al., Am J Epidemiol 1995;141: ; Dagenais GR, et al., Am Heart J 2005;149:54-60.; Yusuf S, et al., Lancet 2005;366:

3. Obesity & CV Events
Yusuf S, et al. Lancet 2005;366:1640-9

4. Obesity & Coronary Artery Calcification
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
CAC is tightly associated with atherosclerosis and can be utilized as a measure of atherosclerotic burden.
Studies examining the association between obesity and CAC have shown differing results.
In a study of 443 non-diabetic asymptomatic white men, BMI, WC, and WHR were all shown to have an independent association with CAC, but only in subjects with low estimated 10-year. No association was observed in higher-risk individuals.
In a study by Snell-Bergeon of 383 aSx men and 379 aSx women, BMI and WC was independently associated with CAC in both men and women; however, only among men was whr shown to be independently associated with CAC
These studies however were limited by the fact that the study populations were homogenous and were selected, relatively healthy populations. (incident CAD excluded, DM excluded, any other comorbids excluded)
Cassidy AE, et al., Circulation 2005;111: ; Snell-Bergeon JK, et al. Int J Obes Relat Metab Disord 2004;28:

5. Objective
Determine the association between differing measures of obesity and atherosclerosis
The objective of our study is to ….

6. Methods Dallas Heart Study: Measures of body composition:
Population-based probability sample of 6,101 subjects
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 with interpretable scan data
1) Our study was performed in a cohort from the Dallas Heart Study.
2) The DHS is a- population-based probability sample of 6101 subjects in Dallas County. The African american population was deliberately oversampled to represent 50% of the study cohort.
Detailed phenotyping of these subjects ocurred over 3 visits
3) Our study is limited to 2744 subjects ages who had datasets complete with anthropometrics and atherosclerosis imaging data.
4) The presence of subclinical atherosclerosis was defined by the presence of CAC > 10 Agatston units or by the presence of detectable abdominal aortic plaque assessed by magnetic resonance imaging
CAC score >10 was utilized as it was a cutpoint at which the signal-noise ratio was maximized in obese subjects
Measures of body composition:
Body mass index Waist circumference
Waist-to-hip ratio Hip circumference

7. Measures of Atherosclerosis
Coronary Artery Calcification by CT
Abdominal Aortic Plaque by MRI
1) 3 Measures of obesity evaluated in this study were BMI, HR, WC, and WHR
2) The presence of atherosclerosis was defined by the presence of > 10 Agatston units of CAC or by the presence of detectable abdominal aortic plaque assessed by magnetic resonance imaging
CAC score >10 was utilized as it was a cutpoint at which the signal-noise ratio was maximized in obese subjects

8. 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
Independent variables: obesity measures in quintiles + traditional CV risk factors
C-statistic comparisons for above models
Univariable and multivariable logistic regression models were perfomed, using prevalent atherosclerosis as the outcome and quintiles of differing measures of obesity as the predictor
Odds ratio point estimates were obtained for each quintile of obesity
MV models were performed to adjust for the traditional CV risk factors
Area under the receiver operating charateristics curves were compared for each of these models

9. Quintile Cut-points Quintile BMI (kg/m2) WC (cm) WHR WOMEN (n=1511)
1st
< 24.6
< 81.8
< 0.80
2nd
24.6 – 28.5
81.9 – 91.6
0.80 – 0.84
3rd
28.5 – 32.7
91.7 – 100.5
0.84 – 0.88
4th
32.7 – 38.4
100.6 – 113.0
0.88 – 0.92
5th
> 38.4
> 113.0
> 0.92
MEN (n=1233)
< 24.4
< 88.4
< 0.91
24.4 – 27.2
88.5 – 96.0
0.91 – 0.94
27.2 – 29.8
96.1 – 102.5
0.94 – 0.97
29.8 – 33.4
102.6 – 111.6
0.97 – 1.01
> 33.4
> 111.6
> 1.01

10. Association Between Obesity & CAC
Here we have a chart evaluating the association between CAC and differing obesity measures. On the x-axis, are differing measures of obesity: BMI, HC, WC, and WHR. Within each measure of obesity, subjects were stratified into sex-specific quintiles where men in q1 were combined with women in q1, etc. On the y-axis, you see the unadjusted odds ratios for the prevalence of detectable CAC for each quintile of obesity measurement.
For BMI on the left here, a J-shaped relationship was observed between the odds of having CAC as you move from quintile 1 to quintile 5 of BMI.
No appreciable association was demonstrated between hip circumference and CAC
For WC and WHR on the here, a stepwise increase was observed in the odds of CAC across increasing quintiles of WC and WHR.

11. Association Between Obesity & Aortic Plaque
In this plot we examine the association between obesity and aortic plaque, instead of CAC as in the last slide.
No association was noted between bmi or hip circumference, or WC and aortic plaque.
However, a stepwise association was observed between whr and aortic plaque.

12. Association Between Obesity & CAC after MV adjustment
Adjusted for: age, smoking, DM, dyslipidemia, low HDL, high TG
In this plot, we examine the association between CAC and differing obesity measures after multivariable adjustment. Covariates adjusted for included age, smoking, diabetes, dyslipidemia, low HDL, and Hypertriglyceridemia.
After adjustment. the J-shaped relationship between BMI and CAC was accentuated. No association was observed between HC and WC and CAC after MV adjustment
And, WHR remained independently associated with detectable CAC after MV-adjustment.

13. Association Between Obesity & Aortic Plaque after MV Adjustment
Adjusted for: age, smoking, DM, dyslipidemia, low HDL, high TG
Similarly with aortic plaque, after MV-adjusted, only WHR was independently associated with aortic model for AP.
Summarizing these analyses, WHR was positively and independently associated with atherosclerosis, and the patterns of association (i.e. J-shaped curve with BMI; linear trends with WC and WHR) resemble those seen before with obesity and events.

14. C-statistics from Univariable Models
Predictors
Outcomes
CAC
Aortic Plaque
Women
BMI
0.55
0.52 WC
0.61*
0.53*
WHR
0.66*±
0.62*±
Men
0.54
0.53
0.59*
0.49*
0.64*±
0.58±
* P < 0.01 vs BMI
± p < 0.01 vs WC

15. C-statistics from MV Models
Predictors
Outcomes
CAC
Aortic Plaque
Women
CV RF
0.86
0.72
+ BMI
0.73
+ WC
0.87
+ WHR
Men
0.83
0.76

16. Waist & Hip Circumference Analyses
Women
“large” waist
“normal” waist
Men
p-values for WCxHC interaction: Women < 0.01
Men = 0.07

17. 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