Contemporary Management of Cardiometabolic Risk

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Contemporary Management of Cardiometabolic Risk
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A continuing epidemic 2 of 3 US adults are
overweight or obese
National Health and Nutrition Examination Surveys
1999-2004US adults 20 years of age
Year of survey
Overweight BMI 25-29.9 kg/m2Obesity BMI 30
kg/m2
Ogden CL et al. JAMA. 20062951549-55.
3
Parallel epidemics of diabetes and obesity
2004
1994
Diabetes
lt4
4-4.9
5-5.9
6
Obesity (BMI 30 kg/m2)
10-14
15-19
20-24
25
CDC. www.cdc.gov.
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Defining cardiometabolic risk

Risk factors linked to cardiovascular disease
(CVD)and diabetes
Adiposity
Dysglycemia
Hypertension
Dyslipidemia
Cardiometabolic risk factors
Eckel RH et al. Circulation. 20061132943-6.
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Associations of adiposity with CVD
Insulin resistance
Dysglycemia
Left ventricular dysfunction
Dyslipidemia
Hypertension
CAD
Sleep apnea syndrome
White visceral fat area (VFA) Black
subcutaneous (sc) fat
Matsuzawa Y. Nat Clin Pract Cardiovasc Med.
2006335-42.
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Adiposity predicts mortality
3.0
2.5
2.0
Relative
risk of
1.5
death
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. 2006355763-78.
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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 with AMI (years)
65
62.3
60
55
lt25(n 306)
25-30(n 362)
gt30(n 238)
BMI (kg/m2)
Suwaidi JA et al. Clin Cardiol. 200124542-7.
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Majority of patients undergoing PCI are
overweight or obese
N 9633
BMI lt25 kg/m2(n 1923)
BMI 25 kg/m2(n 7710)
Gruberg L et al. J Am Coll Cardiol.
200239578-84.
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Adverse consequences of chronic adiposity and
ectopic fat
Lipid overflow ectopic fat
?Muscle fat(?Intracellular lipid)
?Cardiac function?Insulin sensitivityDyslipidemi
a?ß-cell functionAtherosclerosisNASH
Altered FFA metabolism Altered release of
adipokines
?Epicardial fat
?Liver fat andaltered function
FFA free fatty acidsNASH nonalcoholic
steatohepatitis
Adapted from Després J-P, Lemieux I. Nature.
2006444881-7.Molavi B et al. Curr Opin
Cardiol. 200621479-85.
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Epicardial adipose tissue may be increased in
visceral obesity
Patient withvisceral obesity
Patient withperipheral obesity

• Hypertension
• Diabetes
• Dyslipidemia

No metabolic complications
Iacobellis G et al. Clin Cardiol. 200326237.
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Adiposity in the development of NASH
Adipose
Insulin
Leptin
Adiponectin
Fatty acids
Liver
Normal
Steatosis(fatty liver)
Steatohepatitis(steatosis and inflammation)
Fibrosis(collagen deposition)
Adapted from Ahima RS. Gastroenterology.
2007132444-6. Angulo P. N Engl J Med.
20023461221-31.

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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. 20068(suppl
B)B4-12.
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Neutral effect of liposuction on cardiometabolic
risk factors
Magnetic resonance images

• No significant change at 10-12 weeks
• BP
• Plasma glucose
• Plasma insulin
• Total-C, LDL-C, HDL-C, TG
• Adiponectin
• TNF-a
• IL-6
• CRP

Pre-liposuction
sc fat
Post-liposuction

Klein S et al. N Engl J Med. 20043502549-57.
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Central adiposity Better marker of CVD than BMI
N 8802 HOPE Study participants
1.5
P 0.14
P 0.003
P 0.0127
BMI, WHR, WC tertiles
1
Adjusted RR of CVD death
First
Second
Third
0.5
0
BMI(kg/m2)
WHR
WC(cm)
WC waist circumferenceWHR waist/hip ratio
Dagenais GR et al. Am Heart J. 200514954-60.
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A new vital sign Waist circumference
Abdominal adiposity
Coronaryheart disease
Dyslipidemia
Hypertension
RISK
Dysglycemia
Adapted from Després J-P et al. BMJ.
2001322716-20.
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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