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