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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
31
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
35
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
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