Abdominal obesity, intra-abdominal adiposity and related cardiometabolic risk: part I
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Transcript of Abdominal obesity, intra-abdominal adiposity and related cardiometabolic risk: part I
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