Contemporary Management of Cardiometabolic Risk

A continuing epidemic: 2 of 3 US adults are overweight or obese

0

10

20

30

40

50

60

70

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

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

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

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

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

1.0

00 20 25 30 35 40 45

Current BMI (kg/m2)

3.0

2.5

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

55

60

65

70

75

10.6 years earlier occurrence of MI

Majority of patients undergoing PCI are overweight or obese

20

80

0

20

40

60

80

100

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)

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

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.

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)

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

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

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

0

0.5

1

1.5

BMI(kg/m2)

WHR WC(cm)

Adjusted RR of CVD

death

FirstSecondThird

WC = waist circumferenceWHR = waist/hip ratio

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

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