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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


<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


Is waist circumference better than body mass index to predict

cardiometabolic risk?


Saving and Overconsuming Energy


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)


Cholesterol Diabetes Smoking

The “Heavyweights” of Modifiable Cardiovascular Disease (CVD) Risk Factors

Hypertension

Global CVD RiskGlobal CVD Risk

LDL HDL


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


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


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


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


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


Is total adiposity (body mass index, body fat mass) or subcutaneous fat better than intra-abdominal (visceral) fat to predict cardiometabolic risk?


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


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


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


Individual Variation in Subcutaneous / Intra-abdominal (Visceral) Fat Accumulation in Obese Women

Adapted from Després JP Nutrition 1993; 9: 452-9


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


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


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


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


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)


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


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


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-


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


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


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


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)


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


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