Contemporary Management
of Cardiometabolic Risk
A continuing epidemic: 2 of 3 US adults are
overweight or obese
National Health and Nutrition Examination Surveys 1999-2004
US adults ≥20 years of age
70
60
50
Patients 40
(%)
30
Overweight
Obesity
20
10
0
1999-2000
2001-2002
2003-2004
Year of survey
Overweight = BMI 25-29.9 kg/m2
Obesity = BMI ≥30 kg/m2
Ogden CL et al. JAMA. 2006;295:1549-55.
Parallel epidemics of diabetes and obesity
1994
2004
Diabetes
<4%
4%-4.9%
5%-5.9%
≥6%
Obesity
(BMI ≥30 kg/m2)
10%-14%
15%-19%
20%-24%
≥25%
CDC. www.cdc.gov.
Defining cardiometabolic risk
Risk factors linked to cardiovascular disease (CVD)
and diabetes
Adiposity
Hypertension
Dyslipidemia
Dysglycemia
Cardiometabolic risk factors
Eckel RH et al. Circulation. 2006;113:2943-6.
Associations of adiposity with CVD
Insulin resistance
Dysglycemia
Hypertension
White = visceral fat area (VFA)
Black = subcutaneous (sc) fat
Dyslipidemia
CAD
Left ventricular
dysfunction
Sleep apnea
syndrome
Matsuzawa Y. Nat Clin Pract Cardiovasc Med. 2006;3:35-42.
Adiposity predicts mortality
3.0
2.5
2.0
Relative
risk of
death
1.5
1.0
0
0
20
25
30
35
40
45
Current BMI (kg/m2)
All men (n = 313,047; 42,173 deaths)
All women (n = 214,218; 19,144 deaths)
Adams KF et al. New Engl J Med. 2006;355:763-78.
Adiposity associated with premature MI
N = 906 consecutive patients with AMI
75
72.9
10.6 years earlier
occurrence of MI
70
66.9
Age at
presentation
65
with AMI
(years)
62.3
60
55
<25
(n = 306)
25-30
(n = 362)
>30
(n = 238)
BMI (kg/m2)
Suwaidi JA et al. Clin Cardiol. 2001;24:542-7.
Majority of patients undergoing PCI are
overweight or obese
N = 9633
100
80
80
Patients
(%)
60
40
20
20
0
BMI <25 kg/m2
(n = 1923)
BMI ≥25 kg/m2
(n = 7710)
Gruberg L et al. J Am Coll Cardiol. 2002;39:578-84.
Adverse consequences of chronic adiposity and
ectopic fat
Lipid overflow ectopic fat
Muscle fat
(Intracellular lipid)
Altered FFA
metabolism
Altered release
of adipokines
Epicardial fat
Cardiac function
Insulin sensitivity
Dyslipidemia
β-cell function
Atherosclerosis
NASH
Liver fat and
altered function
FFA = free fatty acids
NASH = nonalcoholic steatohepatitis
Adapted from Després J-P, Lemieux I. Nature. 2006;444:881-7.
Molavi B et al. Curr Opin Cardiol. 2006;21:479-85.
Epicardial adipose tissue may be increased
in visceral obesity
Patient with
visceral obesity
Patient with
peripheral obesity
• Hypertension
• Diabetes
• Dyslipidemia
No metabolic complications
Iacobellis G et al. Clin Cardiol. 2003;26:237.
Adiposity in the development of NASH
Adipose
Insulin
Leptin
Adiponectin
Fatty acids
Liver
Normal
Steatosis
Steatohepatitis
Fibrosis
(fatty liver)
(steatosis and
inflammation)
(collagen
deposition)
Adapted from Ahima RS. Gastroenterology. 2007;132:444-6.
Angulo P. N Engl J Med. 2002;346:1221-31.
Visceral vs subcutaneous adiposity
CT scans matched for BMI and total body fat
Visceral obesity
Fat mass: 19.8 kg
VFA: 155 cm2
Subcutaneous (sc)
obesity
Fat mass: 19.8 kg
VFA: 96 cm2
White = VFA
Black = sc fat
Després J-P. Eur Heart J Suppl. 2006;8(suppl B):B4-12.
Neutral effect of liposuction on cardiometabolic
risk factors
Magnetic resonance images
No significant change at 10-12 weeks
Preliposuction
• BP
• Plasma glucose
• Plasma insulin
sc fat
• Total-C, LDL-C, HDL-C, TG
• Adiponectin
Postliposuction
• TNF-α
• IL-6
• CRP
Klein S et al. N Engl J Med. 2004;350:2549-57.
Central adiposity: Better marker of CVD than BMI
N = 8802 HOPE Study participants
1.5
Adjusted
RR of
CVD
death
P = 0.14
P = 0.003
P = 0.0127
BMI, WHR,
WC tertiles
1
First
Second
Third
0.5
0
BMI
(kg/m2)
WC = waist circumference
WHR = waist/hip ratio
WHR
WC
(cm)
Dagenais GR et al. Am Heart J. 2005;149:54-60.
A new vital sign: Waist circumference
Abdominal
adiposity
Coronary
heart disease
Hypertension
Dyslipidemia
RISK
Dysglycemia
Adapted from Després J-P et al. BMJ. 2001;322:716-20.
Continued burden of disease
Central adiposity, hypertension, dyslipidemia, and dysglycemia drive
“cardiometabolic risk”
Cardiometabolic risk is associated with substantial cardiovascular
morbidity and mortality
The ongoing epidemic of adiposity mandates evaluation of new
approaches for managing cardiometabolic risk