Advocate Heart InstituteOBESITY, DYSLIPIDEMIA AND THE METABOLIC SYNDROME

Vincent Bufalino, MDSenior Vice President – Advocate Heart Institute

Senior Medical Director of Cardiology - AMG

Evolution

2

Age-adjusted prevalence of obesity in adults 20–74 years of age, by sex and survey year (NAHES: 1960–1962; NHANES: 1971–

1975, 1976–1980, 1988–1994, 1999-2002 and 2003-2006)

.

Men Women0

5

10

15

20

25

30

35

40

10.7

15.7

12.2

16.8

12.8

17.1

20.6

26.028.1

34.033.1

35.2

1960-62 1971-75 1976-80 1988-94 1999-2002 2003-06

Per

cen

t o

f P

op

ula

tio

n

Obesity is defined as a BMI of ≥30.0. Source: Health, United States, 2009 (NCHS).

Roger VL et al. Circulation 2011. Circulation. 2011;123(4):e18-e209.

The Obesity Epidemic

3

Obesity Trends* Among U.S. AdultsBRFSS, 1990, 1999, 2008

(*BMI 30, or about 30 lbs. overweight for 5’4” person)

www.cdc.gov/obesity/data/trends.htm . Accessed Feb 3, 2010.

4

1999

2008

1990

No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30%

BMI and Prevalence of Metabolic Disease NHANES 1999-2002

Body Mass Index (BMI)

Bays HE, et al. Int J Clin Pract. 2007;61:737-747.Bays HE. Am J Med. 2009;122(1 suppl):S26-37.

18.5-24.9 25-26.9 27-29.9 30-34.9 35-39.9 400

10

20

30

40

50

60

70 Diabetes MellitusHypertensionDyslipidemia

OVERALL<18.5

1.7

22.324

4.2

17.6

38.2

5.7

25.3

53.1

10.1

30.8

62.2

12.2

39.3

68

16.4

44

67.5

27.3

51.3

62.5

9

28.9

52.9

Body Mass Index (BMI)

% o

f P

atie

nts

Lean Normal Overweight Obese

5

6

Obesity-related Hypertension: Pathogenesis, Cardiovascular Risk,

and Treatment -- A Position Paper of The Obesity Society and The American Society of Hypertension

Landsberg L, Aronne LJ, Beilin LJ, Burke V, Igel LI, et al. Obesity (Silver Spring, Md). 2013;21:8-24. 7

Clinical Practice Guidelines for Healthy Eating for the Prevention and Treatment of Metabolic and Endocrine

Diseases in Adults: Cosponsored by American Association of Clinical Endocrinologists and The

Obesity Society

Gonzalez-Campoy JM, et a. Endocr Pract. 2013. Vol 19 (Suppl 3).

• “Primary disturbances in adipose tissue anatomy and function, adiposopathy, are etiologic in the development of . . . metabolic derangements”

• “Thus, . . . a major focus of nutrition counseling for overweight or obesity is to correct adiposopathy”

• “Nutrition counseling for overweight and obesity should be aimed to decrease fat mass and also to correct adipose tissue dysfunction (adiposopathy)”

8

Definition

9

Risk Factor Defining Level

Abdominal obesity Men Women

Waist circumference>102 cm (>40 in)>88 cm (>35 in)

Triglycerides ≥150 mg/dL (1.7 mmol/L)

HDL cholesterol Men Women

<40 mg/dL (1.04 mmol/L)<50 mg/dL (1.30 mmol/L)

Blood pressure ≥130/ ≥85 mmHg

Fasting glucose ≥100 mg/dL (5.6 mmol/L)

Three or more of the following five risk factors:

Metabolic syndrome: The NCEP ATP III definition*

*2001, updated 2005

Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Final Report. Circulation. 2002;106;3143.

10

IDF Worldwide Definition of the Metabolic Syndrome. www.idf.org/metabolic_syndrome

11

Adapter from Grundy SM. J Clin Endocrinol Metab. Jun 2004;89(6):2595-2600.Slide Source: Obesityonline.org

Obesity and Metabolic Syndrome: A Cluster of Coronary Heart Disease Risk

Factors

12

Bays HE. JACC 2011;57:2461-73.

Contribution of Adipose Tissue to Metabolic Syndrome and CVD Risk

13

Bays H, Ballantyne C. Future Lipidology. 2006;1:389-420.Kalant D, et al. Can J Diabetes. 2003;27:154-171.Pausova Z. Curr Opin Nephrol Hypertens. 2006;15:173-178.Landsberg L. Cell Mol Neurobiol. 2006;26:497-508.Yu YH, Ginsberg HN; Circ Res. 2005;96:1042-1052.

Metabolic Syndrome: Mechanisms

14

Bays HE, et al. Int J Clin Pract. 2007;61:737-747.Bays HE. Am J Med. 2009;122(1 suppl):S26-37.

BMI Among Patients With Metabolic Disease NHANES 1999-2002

18.5

0.4%

17.1%

9.9%

21.7%

23.2%

13.9%

13.8%

Diabetes Mellitus

1.7%

21.9%

13.4%20.7%

23.0%

11.7%

7.6%

Hypertension

0.9%

25.5%

15.1%

22.3%

21.5%

9.5%

5.1%

Dyslipidemia

Body Mass Index (BMI)18.5-24.9 25-26.9 30-34.9 35-39.9 4027-29.9

Lean Normal Overweight Obese

15

Age-Specific Prevalence of the Metabolic Syndrome

Ford E et al. JAMA 2002;287:356-359.

• 8814 US adults from NHANES III Survey, 1988-94

16

20-29 30-39 40-49 50-59 60-69 700

5

10

15

20

25

30

35

40

45

Men

Women

Age, y

Perc

en

tag

e,

%

Data are presented as percentage (SE)

Prevalence of the NCEP Metabolic Syndrome: NHANES III by Sex and Race/Ethnicity

Ford ES et al. JAMA 2002;287:356-359.

Series10%

10%

20%

30%

40%

Pre

vale

nce,

%

Men

Ford ES et al. JAMA 2002;287:356-359.

Women

WhiteAfrican AmericanMexican AmericanOther

25%

16%

28%

21%23%

26%

36%

20%

17

Prevalence of CHD by the Metabolic Syndrome & Diabetes in the NHANES

Population Age 50+

Alexander CM et al. Diabetes 2003;52:1210-1214.

Series10%

5%

10%

15%

20%

25%

8.7%

13.9%

7.5%

19.2%

Chart Title

CH

D P

revale

nce

% of Population =

No MS/No DM54.2%

MS/No DM28.7%

DM/No MS2.3%

DM/MS14.8%

18

Cardiometabolic Risk:Metabolic Syndrome Associated With Increased

CV Morbidity and Mortality

Isomaa B, Almgren P, Tuomi T, et al. Diabetes Care. Apr 2001;24(4):683-689.

* Cardiovascular mortality was defined using ICD-9 (codes 390-459) before 1997 and ICD-10 (codes 100-199) thereafter,

19

Courtesy of Prof. Yuji Matsuzawa, Osaka, Japan

20

• Small insulin-sensitive adipocytes

• Adrenergic receptors

Fatty Acids

• Large insulin- resistant adipocyte

• Adrenergic receptors • Insulin-

mediated antilypolysis

• Catecholamine-

mediated lipolysis

All Fat Cells Are Not Created Equal

21

DietPhysical activity/

FitnessSocioeconomic

statusBirth size,

childhood growthGenes

Hypertension

METABOLIC

SYNDROME

Hypercoagulability,impaired fibrinolysis

Hypoandrogenism (men),Hyperandrogenism (women)

Endothelial dysfunction

Hyperuricemia

Adipose hormones

Inflammation

Abdominal obesity/Ectopic fat deposition

Insulin resistance/Hyperinsulinemia

Overweight

Diabetes CVD

Dyslipidemia• Low HDL, high TG• High ApoB, low Apo A• Small dense LDL

Elevated fasting or2-h post-load glycemia

22

Dagenais GR, Yi Q, Mann JF, et al. Am Heart J. Jan 2005;149(1):54-60.

Cardiometabolic Risk:Abdominal Adiposity Is Associated With Increased

Risk of CV Events

23

Risk of Major CHD Event Associated with High Insulin Levels in Non-diabetic Men

Pyörälä M, et al. Circulation. 1998;98:398–404.

Q1 to Q5=quintiles of area under the curve (AUC) insulin (Q1=lowest quintile; Q5=highest quintile).

Pro

po

rtio

n w

itho

ut

ma

jor

CH

D e

ven

t

Years0

0

5

0.75

0.80

0.85

0.90

0.95

1.00

10 15 20 25

Log rank:Overall P = 0.001Q5 vs Q1 P <0.001

Q1

Q2

Q3

Q4

Q5

Kaplan-Meier Survival Curve

24

Coronary HeartDisease Mortality

0 2 4 6 8 10 12

0

5

10

15

20

RR (95% CI),3.77 (1.74-8.17)

Follow-up, Y

Cu

mu

lati

ve H

azar

d (

%)

YesNo

866288

852279

834234

292100

Unadjusted Kaplan-Meier Curve

No. at Risk Metabolic Syndrome

0 2 4 6 8 10 12

RR (95% CI),3.55 (1.96-6.43)

Follow-up, Y

866288

852279

834234

292100

0 2 4 6 8 10 12

RR (95% CI),2.43 (1.64-3.61)

Follow-up, Y

866288

852279

834234

292100

CardiovascularDisease Mortality

All-causeMortality

YesMetabolic Syndrome: No

Lakka H-M, et al. JAMA. 2002;288:2709-2716.

25

Treatment

26

© 2010, American Heart Association. All rights reserved.

“Aggressive comprehensive risk factor management improves

survival, reduces recurrent events and the need for interventional

procedures, and improves quality of life for these patients.”

Smith (2006). AHA/ACC Guidelines for Secondary Prevention for Patients With Coronary and Other Atherosclerotic Vascular Disease: 2006 Update. Circulation

© 2006 American Heart Association, Inc.

27

© 2010, American Heart Association. All rights reserved.

What Is Ideal Cardiovascular Health?

• Absence of disease• Favorable levels of health factors• Favorable health behaviors

© 2010, American Heart Association. All rights reserved.

28

© 2010, American Heart Association. All rights reserved.

Ideal CV Health

Ideal Health Behaviors Metric (ALL)• Nonsmoking• Healthy Weight• Appropriate Levels of Physical Activity• Healthy Eating Pattern

Ideal Health Factors Metric (ALL)• Total cholesterol• Blood pressure• Nondiabetic

© 2010, American Heart Association. All rights reserved.

29

Life’s Simple 71. Never smoked or quit more than one

year ago 2. Body mass index less than 25 kg/m2

3. Physical activity of at least 150 mins (moderate intensity) or 75 mins (vigorous intensity) each week

4. Four to five key components of a healthy diet consistent with current AHA guidelines

5. Total cholesterol of less than 200 mg/dL6. Blood pressure below 120/80 mm Hg7. Fasting blood glucose less than 100 mg/dL

30

Healthy Diet(4-5 Dietary Goals met)

1. Fruits and vegetables: ≥4.5 cups per day2. Fish (preferably oily): ≥2 3.5-oz servings per week3. Fiber-rich whole grains (1.1 grams fiber per 10 grams

carbohydrate): ≥3 1-oz-equivalent servings per day4. Sodium: <1500 mg per day5. Sugar-sweetened beverages: ≤450 kcal (36 oz) /week

Other Dietary Measures1. Saturated fat: < 7% of total energy intake2. Nuts, legumes, and seeds: ≥ 4 servings/week3. Processed meats: ≤ 2 servings/week

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CV Health Metric Definitions*

PoorPoor IntermediateIntermediate IdealIdeal

* The average net percentage of people who move up one level of health

Goal: 20% overall improvementGoal: 20% overall improvement

32

Lifetime Risk: Age 50

Lloyd-Jones, Circulation 2006

2 Major RFs1 Major RF1 Elevated RF1 Not Optimal RFOptimal RFs

Men

Attained Age

Ad

just

ed

Cu

mu

lati

ve I

nci

den

ce

5%

36%

50%

69%

46%

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

50 60 70 80 90

Attained Age

Women

8%

27%

50%

39%39%

Ad

just

ed

Cu

mu

lati

ve I

nci

den

ce

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

50 60 70 80 90

33

© 2010, American Heart Association. All rights reserved.

My Life Check Assessment

34

© 2010, American Heart Association. All rights reserved.

My Life Check Assessment

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Nutritional Therapy• Energy consumption intended to cause

negative caloric balance and fat weight loss

• Low calorie diet is often described as 800 – 1500 kcal/day

• Very low calorie diet is often described as <800 kcal/day

Restricted dietary

carbohydrate Restricted dietary fat

Very low calorie diets

36

37

Physical Activity

• Assist with weight maintenance

• Assist with weight loss• Improve body

composition

• Improve metabolic health• Improve musculoskeletal

health• Improve cardiovascular

health• Improve pulmonary

health• Improve mental health• Improve sexual health

Adiposopathy (Sick Fat Disease)

Non-adipose Health Parameters

38

Physical Activity

• Moderate exercise = 70 minutes per week

• Vigorous exercise = 150 minutes per week

• Percent body fat better assessment of body composition than BMI

• Emphasize “core” muscle exercise

Aerobic Anaerobic

Priority is to increase energy expenditure

39

Exercise and the Heart

LDL Cholesterol

Weight

Hypercoagulability

Atherosclerosis

Preferential loss of abdominal fat

Reduces CRP

Insulin resistance

HDL Cholesterol

Skeletal muscle glycogen transport

Rate & amount fat oxidation at rest

40

41

Behavior Therapy

Frequent encounters with

medical professional or other resources

Education

42

Weight Management Pharmacotherapy

• Facilitate management of eating behavior• Slow progression of weight gain/regain• Improve the health, quality of life, and

body weight of the obese and/or overweight patient

Adjunct to nutritional, physical activity, and behavioral therapies

43

Pharmacotherapy

• Phentermine• Diethylpropion• Phendimetrazine• Benzphetamine• Orlistat

• Lorcaserin• Phentermine

HCI/Topiramate extended-release

Approved < 1999 2012 and Beyond

Weight Loss

44

Glucose Management

45

Blood Pressure Management

46

Lipid Management

47

Comprehensive Management

48

Is Eugastrosis (a Normal Stomach) a Disease?

Gastric Band

Gastric Sleeve

Roux en Y Gastric Bypass

49

Conclusions

• Obesity is increasing worldwide at an alarming rate• Adiposopathy leads to atherogenic dyslipidemia as

well as several other risk factors for CAD• 7%-10% weight loss significantly affects CHD risk• Calorie restriction is the most important criteria for

the diet• Increased physical activity is also critical• Many drugs can contribute to weight gain• Surgical and pharmacologic therapies can be helpful

in selected patients

50

THANK YOU

51