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By Jean-Pierre Després, PhD, FAHA, Scientific Director, International Chair on Cardiometabolic Risk, Professor, Division of Kinesiology, Université Laval, Centre de recherche de l’Institut universitaire de cardiologie et de pneumologie de Québec, Québec, QC, Canada.
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Source: International Chair on Cardiometabolic Riskwww.cardiometabolic-risk.org
Abdominal Obesity, Intra-abdominal Adiposity and Related Cardiometabolic
Risk: Part I
Jean-Pierre Després, PhD, FAHADirector of Research, Cardiology
Centre de recherche de l’Institut universitaire de cardiologie et de pneumologie de Québec
Scientific Director, International Chair on Cardiometabolic Risk
Québec, Canada
Source: International Chair on Cardiometabolic Riskwww.cardiometabolic-risk.org
<21.0 29.0
BMI (kg/m2)<22.0 35.0
BMI (kg/m2)<19.0 32.0
BMI (kg/m2)
Relative Risk of Mortality, Coronary Heart Disease (CHD), and Type 2 Diabetes According to Body Mass Index (BMI)
Mortality
Adapted from Manson JE et al. N Engl J Med 1995; 333: 677–85 | Willett WC et al. JAMA 1995; 273: 461–5 | Colditz GA et al. Ann Intern Med 1995; 122: 481-6
CHD Diabetes
Relative risk of:
2.0
1.5
1.0
0.5
0.0
4.0
3.0
2.0
1.0
0.0
8.0
6.0
4.0
2.0
0.0
Source: International Chair on Cardiometabolic Riskwww.cardiometabolic-risk.org
Is waist circumference better than body mass index to predict
cardiometabolic risk?
Source: International Chair on Cardiometabolic Riskwww.cardiometabolic-risk.org
Saving and Overconsuming Energy
Source: International Chair on Cardiometabolic Riskwww.cardiometabolic-risk.org
Obesity: Body Mass Index (BMI)
BMI (kg/m2)Risk of
Comorbidities
Healthy weight 18.5 – 24.9 Normal
Overweight 25.0 – 29.9 Increased
Obese Class I 30.0 – 34.9 High
Obese Class II 35.0 – 39.9 Very High
Obese Class III > 40.0 Extremely High
BMI =
Adapted from the World Health Organization. Obesity: Preventing and Managing the Global Epidemic. Geneva: WHO, 2000
Weight (kg)
Height (m2)
Source: International Chair on Cardiometabolic Riskwww.cardiometabolic-risk.org
Cholesterol Diabetes Smoking
The “Heavyweights” of Modifiable Cardiovascular Disease (CVD) Risk Factors
Hypertension
Global CVD RiskGlobal CVD Risk
LDL HDL
Source: International Chair on Cardiometabolic Riskwww.cardiometabolic-risk.org
Obesity: An Ill-defined Modifiable Cardiovascular Disease (CVD) Risk Factor
ObesityBMI
Others
?
Cholesterol Diabetes SmokingHypertension
LDL HDL
Global CVD RiskGlobal CVD Risk
BMI: body mass index
Source: International Chair on Cardiometabolic Riskwww.cardiometabolic-risk.org
Android (Apple) vs. Gynoid (Pear) Obesity
AATributeTribute
to a to a PioneerPioneer
Jean Vague (1947)
Adapted from Vague J. Presse Med 1947; 30: 339–40
Source: International Chair on Cardiometabolic Riskwww.cardiometabolic-risk.org
Obesity as a Risk Factor for Type 2 Diabetes:Importance of Abdominal Fat Accumulation
9.1
0
5
10
15
20
9.1 9.1
2.9
9.1
15.2
2.9
0.5 0.5 0.5
Another Pioneer…the Late
III II II
II
III
13.5-year incidence of
type 2 diabetes (%)
(Overweight) (Lean)Body mass index tertiles
Waist-to-hipratio tertiles
Per Björntorp
Adapted from Ohlson LO et al. Diabetes 1985; 34: 1055-8
Source: International Chair on Cardiometabolic Riskwww.cardiometabolic-risk.org
Risk of Myocardial Infarction Across Quintiles of BMI and WHR: INTERHEART
4.0
3.0
2.5
2.0
1.5
Od
ds
rat
io (
95%
CI)
1.25
1.00.90.8
<20 20–23 23.1–25 25.1–27 27.1–29 >30
BMI (kg/m2)
Adapted from Yusuf S et al. Lancet 2005; 366: 1640-9Copyright 2005, with permission from Elsevier
BMI: body mass indexWHR: waist-to-hip ratio
3.5
Source: International Chair on Cardiometabolic Riskwww.cardiometabolic-risk.org
77
4655
106
8997
128
110
83
Abdominal Obesity and Coronary Heart Disease in Women: The Nurses’ Health Study
LowMiddleHigh
High (81.8 - <139.7)
Middle (73.7 - <81.8)
Low (38.1 - <73.7)
(25.2 - <48.8) (22.2 - <25.2) (12.2 - <22.2)
Waist girthtertiles (cm)
Inci
den
ce r
ate
per
100
,000
p
erso
n-y
ears
Body mass index tertiles (kg/m2)
Adapted from Rexrode KM et al. JAMA 1998; 280: 1843-8
Follow-up of 8 years
140
120
100
80
60
40
20
0
Source: International Chair on Cardiometabolic Riskwww.cardiometabolic-risk.org
Is total adiposity (body mass index, body fat mass) or subcutaneous fat better than intra-abdominal (visceral) fat to predict cardiometabolic risk?
Source: International Chair on Cardiometabolic Riskwww.cardiometabolic-risk.org
Intra-abdominal (Visceral) Fat: The Dangerous Inner Fat
Intra-abdominal adipose tissue
Subcutaneous adipose tissue
Front
Adapted from Lemieux I et al. Ann Endocrinol 2001; 62: 255-61
Back
Source: International Chair on Cardiometabolic Riskwww.cardiometabolic-risk.org
Association Between Fat Mass and Intra-abdominal (Visceral) Adipose Tissue in Men and Premenopausal Women
Adapted from Lemieux S et al. Am J Clin Nutr 1993; 58: 463-7
Intr
a-ab
do
min
al
ad
ipo
se
tiss
ue
(c
m2)
0 10 20 30 40 50 60 70
Fat mass (kg)
300
250
200
150
100
50
0
Women: r=0.85Men: r=0.69
Source: International Chair on Cardiometabolic Riskwww.cardiometabolic-risk.org
Intra-abdominal (Visceral) Fat Accumulation in Equally Overweight Men
Fat mass: 19.8 kg
Intra-abdominal fat: 155 cm2
Fat mass: 19.8 kg
Intra-abdominal fat: 96 cm2
Adapted from Després JP et al. In: AF Roche, SB Heymsfield, TG Lohman (eds.), Human Body Composition, Human Kinetics,149-66,1996
Source: International Chair on Cardiometabolic Riskwww.cardiometabolic-risk.org
Individual Variation in Subcutaneous / Intra-abdominal (Visceral) Fat Accumulation in Obese Women
Adapted from Després JP Nutrition 1993; 9: 452-9
Source: International Chair on Cardiometabolic Riskwww.cardiometabolic-risk.org
Intra-abdominal (Visceral) Fat Increases the Risk of Type 2 Diabetes in Premenopausal Women
Time (min.)
Glu
co
se (
mm
ol/l
)
0
1,2
1,2
1,2
1,2 1,2
1,2
1
30 60 90 120 150 180
10.0
9.0
8.0
7.0
6.0
5.0
4.0
Nonobese controls (1)Obese low intra-abdominal fat (2)Obese high intra-abdominal fat
1000
800
600
400
200
0
Time (min.)0 30 60 90 120 150 180
Ins
ulin
(p
mo
l/l)
1,2
1
1,21,2
1,2
11
1
111
From Després JP. In: H Rifkin, JA Colwell, SI Taylor (eds.), Diabetes 1991, Elsevier Science Publishers BV Amsterdam, The Netherlands, 95-9, 1991Reproduced with permission
1,2: significantly different from the corresponding subgroups
11
Source: International Chair on Cardiometabolic Riskwww.cardiometabolic-risk.org
Intra-abdominal (Visceral) Fat Increases Cardiovascular Risk in Premenopausal Women
HD
L c
ho
lest
ero
l (m
mo
l/l)
Tri
gly
cer
ide
s (m
mo
l/l)
1,2
1
Adapted from Després JP et al. Arteriosclerosis 1990; 10: 497-511
1,2
Nonobese controls (1)Obese low intra-abdominal fat (2)Obese high intra-abdominal fat
1.5
1.4
1.3
1.2
1.1
1.0
0.9
0.8
3.0
2.5
2.0
1.5
1.0
0.5
0.0
1,2: significantly different from the corresponding subgroup
Source: International Chair on Cardiometabolic Riskwww.cardiometabolic-risk.org
Features of the Metabolic Syndrome Commonly Found Among Intra-abdominally (Viscerally) Obese Patients
• Hypertriglyceridemia • Insulin resistance
• Low HDL cholesterol • Hyperinsulinemia
• Elevated apolipoprotein B • Glucose intolerance
• Small, dense LDL particles • Impaired fibrinolysis
• Inflammatory profile• Endothelial
dysfunction
Genetic susceptibility to hypertension, type 2 diabetes, and coronary heart disease ultimately affects the clinical features of the metabolic syndrome
Adapted from Lemieux I and Després JP. In: PG Kopelman (ed.), Management of Obesity and Related Disorders, Martin Dunitz, 45-63, 2001
Source: International Chair on Cardiometabolic Riskwww.cardiometabolic-risk.org
The Atherogenic Metabolic Triad of Intra-abdominal (Visceral) Obesity
Hyperinsulinemia
Small, denseLDL particles
Elevated apo Bconcentrations
Beyond LDL cholesterol, blood pressure, type 2 diabetes…
The atherogenic metabolic
triad
Source: International Chair on Cardiometabolic Riskwww.cardiometabolic-risk.org
Risk of Ischemic Heart Disease (IHD) According to the Cumulative Number of “Traditional” and “Nontraditional” Risk Factors: The Québec Cardiovascular Study
Adapted from Lamarche B et al. JAMA 1998; 279: 1955-61
Od
ds
rati
o*
Traditional risk factors: LDL cholesterol, triglycerides and HDL cholesterol
Nontraditional risk factors: Insulin, apolipoprotein B and small, dense LDL particles
* Odds ratios are adjusted for systolic blood pressure, family history of IHD, and medication use
25
20
15
10
5
00 1 2 3
1.0 1.01.8
4.7
2.8
9.1 (p=0.01)
4.4(p=0.01)
20.8(p<0.001)
Source: International Chair on Cardiometabolic Riskwww.cardiometabolic-risk.org
The Prevalent Form of the Metabolic Syndrome as Defined by NCEP-ATP III and IDF
Pro-inflammatory state
Elevated blood pressure
Insulin resistance
Atherogenic dyslipidemia
NCEP-ATP III: National Cholesterol Education Program – Adult Treatment Panel III
IDF: International Diabetes Federation
Abdominal obesity
Pro-thrombotic state
Source: International Chair on Cardiometabolic Riskwww.cardiometabolic-risk.org
100
120
140
160
180
200
220
Intra-abdominal (Visceral) Adipose Tissue Area and Waist Girth According to C-Reactive Protein (CRP) Quintiles
Intr
a-ab
do
min
al a
dip
ose
ti
ssu
e (c
m2 )
CRP quintiles(1) (2) (3) (4) (5)
1
1
1 1,3
Wai
st c
ircu
mfe
ren
ce (
cm)
90
94
98
102
106
110
CRP quintiles
(1) (2) (3) (4) (5)
11
1,21,2,3
Adapted from Lemieux I et al. Arterioscler Thromb Vasc Biol 2001; 21: 961-7
Legend:1,2,3: significantly different from the corresponding quintiles
Source: International Chair on Cardiometabolic Riskwww.cardiometabolic-risk.org
Inflammation and Cardiovascular Disease: Is Abdominal Obesity the Missing Link?
TNF-
IL-6
Atherogenic,insulin resistant“dysmetabolic
milieu”
CRP
?
?
Risk of acute coronary syndrome
?Adipose tissue
Adapted from Després JP Int J Obes 2003; 27: S22-4Reproduced with permission
CRP: C-reactive proteinIL-6: interleukin-6TNF-: tumor necrosis factor-
Source: International Chair on Cardiometabolic Riskwww.cardiometabolic-risk.org
Potential Contribution of Ectopic Fat Deposition to the Cardiometabolic Risk Profile of Intra-abdominally Obese Patients
Altered cardiometabolic risk profile
Systemic free fatty acids
Coronary atherosclerosis unstable plaque
Intra-abdominal (visceral) adipose tissue
Lipoprotein lipase Insulin resistance
Hepatic lipaseLipid deposition
Insulin-resistant subcutaneous adipose tissue
? Portal free fatty acids
Insulin Glucose Triglycerides Apolipoprotein B
Adapted from Després JP. Ann Med 2006; 38: 52-63Reproduced with permission
Plasminogen activator inhibitor-1
Interleukin-6 Tumor necrosis
factor- Adiponectin
Skeletal muscle
Liver
Source: International Chair on Cardiometabolic Riskwww.cardiometabolic-risk.org
Intra-abdominal (Visceral) Fat: The Dangerous Inner Fat
Intra-abdominal adipose tissue
Subcutaneous adipose tissue
Front
Adapted from Lemieux I et al. Ann Endocrinol 2001; 62: 255-61
Back
Source: International Chair on Cardiometabolic Riskwww.cardiometabolic-risk.org
Intra-abdominal (Visceral) Fat is an Independent Predictor of All-cause Mortality in Men
Subject A Subject B
Subject B is at a 2-fold higher risk
for mortalityRis
k o
f d
eath
Intra-abdominal fat (kg)
Intra-abdominal fat is shown in red
0
1
2
3
4
5
6
Adapted from Kuk JL et al. Obesity 2006; 14: 336-41
0 0.5 1.0 1.5
Source: International Chair on Cardiometabolic Riskwww.cardiometabolic-risk.org
Intra-abdominal (Visceral) Fat is an Independent Predictor of All-cause Mortality in Men
* Odds ratios are expressed per standard deviation for each variable
Adapted from Kuk JL et al. Obesity 2006; 14: 336-41
Od
ds
rati
os
for
mo
rtal
ity*
MODEL 1
1.8
1.4 1.4
0.8
1.8
1.0 0.6
1.3
MODEL 2
Control for age + follow-up time Control for age, follow-up time, abdominal subcutaneous fat, intra-
abdominal fat, and liver fat
Intra-abdominal fat Waist circumference
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0O
dd
s ra
tio
s fo
r m
ort
alit
y*
Subcutaneous fat CTL / CTS (index of liver fat)
Source: International Chair on Cardiometabolic Riskwww.cardiometabolic-risk.org
The Prevalent Form of the Metabolic Syndrome as Defined by NCEP-ATP III and IDF
Pro-inflammatory state
Elevated blood pressure
Insulin resistance
Atherogenic dyslipidemia
NCEP-ATP III: National Cholesterol Education Program – Adult Treatment Panel III
IDF: International Diabetes Federation
Abdominal obesity
Pro-thrombotic state
Source: International Chair on Cardiometabolic Riskwww.cardiometabolic-risk.org
www.cardiometabolic-risk.org