obesity and cv disease 1.ppt

Obesity and Cardiovascular

DiseaseDionisio B. Yorro, Jr., M.D., FACC

16th USTMAAA Convention

Caesar’s Palace, LV, NV

May 22-26, 2008

Learning Objectives

Describe the epidemiology of obesity in the US and the increasing prevalence in the world.

Explain the relationships between obesity, insulin resistance, metabolic syndrome, cardiovascular disease, and other co-morbid conditions.

Emphasize the impact of obesity on mortality and morbidity.

Touch on the approach in the management of obesity.

Epidemiology of Obesity

The WHO and NHLBI have classified obesity as an epidemic.

In 2002, about 64% of Americans are overweight, while 32% are obese.

16% or 9 million kids are overweight.

There is a continuing trend towards an ever-fatter America.

By 2009, almost 70% of the population will be overweight or obese

Obesity is responsible for more than 300,000 deaths a year

From a global perspective, the increase in the prevalence of obesity is also alarming.

No Data <10% 10%–14%

Obesity Trends Among U.S. Adults1985


No Data <10% 10%–14%


No Data <10% 10%-14%


No Data <10% 10%–14%


No Data <10% 10%–14% 15%–19%


No Data <10% 10%–14% 15%–19% ≥20


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

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

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



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

Obesity Rates Are Projected to Double Over the Next 30 Years

50

40

30

20

10

01960 1970 1980 1990 2000 2010 2020 2030

USEnglandAustraliaBrazil

Year

BM

I

30

(%)

(Sichieri R, et al. Am J Public Health. 1994) (Bennett SA, Magnus P. Med J Aust. 1994) (Prentice AM, Jebb SA. BMJ. 1995) (Mokdad AH, et al. JAMA. 1999) (Flegal KM, et al. Int J Obes Relat Metab Disord. 1998) (NIH. Obes Res. 1998)

OBESITY, why?OBESITY, why?

140 calories 3-inch diameter

Calorie Difference: 210 calories

350 calories 6-inch diameter

Bagel

20 Years Ago Today


590 calories

Cheeseburger

20 Years Ago Today

333 calories


1,025 calories 2 cups of pasta with sauce and 3 large meatballs

20 Years Ago Today

500 calories1 cup spaghetti with sauce and 3 small meatballs

Spaghetti and Meatballs

610 Calories6.9 ounces

Calorie Difference: 400 Calories

French Fries

20 Years Ago Today

210 Calories

2.4 ounces

Calorie Difference: 165 Calories

250 Calories 20 ounces

85 Calories 6.5 ounces

Soda20 Years Ago Today


820 calories 320 calories

Turkey Sandwich

20 Years Ago Today

Coffee 20 Years Ago

Coffee(with whole milk and sugar)

Today

Mocha Coffee(with steamed whole milk and

mocha syrup)

45 calories 8 ounces

350 calories16 ounces


Pepperoni Pizza

20 Years Ago Today

500 calories 850 calories


Chicken Caesar Salad

20 Years Ago Today

390 calories 1 ½ cups

790 calories

3 ½ cups


Causes of Overweight & Obesity Science shows that genetics does play a role in obesity

– However in most cases, both genes and behavior are necessary for

a person to be overweight

Body weight is the result of a combination of influences:

– genetic, metabolic, behavioral, environmental, cultural, and

socioeconomic influences

Therefore behavioral and environmental factors provide the

greatest “opportunity” for action and intervention

Assessing Obesity

Measurement of body fat by: – hydrodensitometry – x-ray absorptiometry – bioelectrical impedance analysis (BIA) – skinfold thickness measurement

Assessing Obesity

Waist circumference at level of iliac crest– Above 40 inches for men and 35 inches for women are

indicative of health risk.

Waist-to-hip ratio: Circumference of the waist at the level of L3 divided by the circumference of the hip at the largest area of the gluteal region. (Helps to identify central or android obesity.) – For men waist-to-hip ratio > 1 – For women waist-to-hip ratio > 0.85

Assessing Obesity: BMI

Body mass index (BMI)

– calculated as weight in kilos divided by height in meters squared.

– evaluates weight relative to height

– replaced % ideal body weight as the primary criterion for assessing obesity

– correlates significantly with body fat, morbidity, and mortality

– used most by researchers and health organizations in measuring and defining overweight and obesity.

(Willett WC, et al. N Engl J Med. 1999) (NIH. Obes Res. 1998)

Weight Classification by BMI

Underweight < 18.5 UnderweightNormal 18.5 – 24.9 Normal rangeOverweight 25.0 – 29.9 PreobeseObesity class 1 30.0 – 34.9 Obese class 1Obesity class 2 35.0 – 39.9 Obese class 2Obesity class 3 ≥ 40.0 Obese class 3

NHLBI = National Heart, Lung, and Blood Institute; WHO = World Health Organization.

NHLBI Terminology

BMI, kg/m2, Range

WHO Classification

(Reprinted with permission from Must A, et al. JAMA. 1999) (NIH. Obes Res. 1998) (World Health Organization. Obesity: preventing and managing the global epidemic. Report of a WHO Consultation presented at: the World Health Organization; June 3-5, 1997; Geneva, Switzerland. Publication WHO/NUT/NCD/98.1)

Classic Risk Factors in CAD

Diabetes

Nicotine

Obesity and lack of exercise

Dyslipidemia

Hypertension

(JNC VI. Arch Intern Med. 1997)

CAD

Obesity and Overweight Increase the Risk of: Hypertension

Stroke

Diabetes mellitus, Type 2

Metabolic syndrome

CV mortality

Cancer – endometrium, breast, prostate, and colon.

Gallbladder disease

Osteoarthritis

Respiratory diseases and sleep-apnea

Relationship Between BMI and the Relative Risk of Comorbid Conditions

21 22 23 24 25 26 27 28 29 30

7

6

4

3

2

1

0

5

Type 2 diabetesHypertensionCholelithiasisCHD

Rel

ativ

e R

isk

BMI(Reprinted with permission from Willett WC, et al. N Engl J Med. 1999. Copyright © 1999 Massachusetts Medical Society. All rights reserved)

Obesity and Mortality Risk, 1989

MenWomen

Digestive Disease Pulmonary Disease

Cardiovascular Disease

Gallbladder Disease Diabetes Mellitus

Moderate Risk

Very Low Risk

Low Risk

Moderate Risk

High Risk

Very High Risk

2.5

2.0

1.5

1.0

020 25 30 35 40

BMI (kg/m2)

(Reprinted with permission from Gray DS. Med Clin North Am. 1989)

Mor

talit

y R

atio

Obesity and Cardiovascular Disease

0

1

2

3

4

Rel

ativ

e R

isk

Relative Risk of Nonfatal MI and Fatal CHD (Combined) Based on BMI (Women)

< 21 21 – 22.9 23 – 24.9 25 – 28.9 29

BMI (kg/m2)MI = myocardial infarction.

(Adapted with permission from Willett WC, et al. JAMA. 1995)

How does obesity cause cardiovascular disease?

Patterns of Body Fat Distribution

Intrabdominal orVisceral type

(android or “apple shaped”)

Lower body or external type

(gynoid or“pear shaped”)

Normal Visceral obesity

Courtesy of Wilfred Y. Fujimoto, MD.

Visceral Fat DistributionNormal vs Obesity

All Fat Cells Are Not Created Equal

• Large Insulin-Large Insulin-ResistantResistantAdipocytes Adipocytes

• Adrenergic Adrenergic Receptors Receptors

• Insulin-MediatedInsulin-MediatedAntilypolysisAntilypolysis

• Catecholamine-Catecholamine-Mediated Mediated Lipolysis Lipolysis

• Small Insulin-SensitiveSmall Insulin-SensitiveAdipocytes Adipocytes

• Adrenergic Receptors Adrenergic Receptors

Fatty Acids Fatty Acids

BODY FAT DISTRBUTION

Men are apt to develop visceral type obesity while women develop the peripheral type

Androgens appear to influence this distribution

PCO with androgenemia predisposes to visceral type adiposity

Corticosteroids and growth hormone also tend to develop visceral obesity

How does obesity cause cardiovascular disease?

M u sc le & P an c reasIn su lin res is tan ceH yp erin su lin em iaM et. S yn ., D M T2

L ive rG lu con eog en es is

In c . Trig s an d L D LD ec . H D L

B lood V esse lsH yp erten s ion

H yp ercoag u lab le s ta teE n d oth e lia l d ys fu n c tion

C ard iovascu la r d isease

F F A

L ip o lys is(in sen s it ive to in su lin )

A b d om in a l O b es ity(d eep viscera l fa t)

Cytokines: TNF-alpha Interleukin 6

‘Adipokines:’ Resistin Adiponectin

Pro-thrombotic mediators: PAI-1

Adipose Tissue

Relationship Between Visceral Adipose Tissue and Insulin Action

Banerji M et al. Am J Physiol 1997;273(2 pt 1):E425–E432.

18

16

14

12

10

8

6

4

2

0 1000 2000 3000 4000 5000Visceral adipose tissue volume per unit surface area (mL/m2)

Glu

cose

dis

posa

l (m

g/kg

LB

M/m

in)

Women Men

Obesity and Insulin Resistance

Hyperinsulinemia Hyperinsulinemia + +

HyperglycemiaHyperglycemia

Activation of the sympathetic nervous

systemIncrease of arterial tone

Na+ reabsorption

Hypertension

Overstimulation of pancreatic -cell

functionReduction of insulin

secretion

Type 2 Diabetes

The Metabolic Syndrome

The Insulin Resistance Syndrome

The Dysmetabolic Syndrome

A syndrome in which the physiologic response is

inadequate for the amount of insulin secreted

Reaven, Olefsky


InsulinResistance

Hypertension

Type 2 Diabetes

DisorderedFibrinolysis

ComplexDyslipidemia TG, sdLDL, HDL

EndothelialDysfunction Systemic

Inflammation

Athero -sclerosis

VisceralObesity

Adapted from ADA. Diabetes Care. 1998;21:310-314.Pradhan et al. JAMA. 2001;286:327-334.

The Metabolic Syndrome Associated With Insulin Resistance

Central obesityGlucose intolerance

AtherosclerosisHypertension

Polycystic ovary syndrome

Clinical Manifestations

Lipid:Carbohydrate:

Biochemical Abnormalities

Fibrinolysis:Insulin resistanceHyperinsulinemia

High TGLow HDL-C

Small, dense LDL

Increased PAI-1


Risk Factor Defining LevelAbdominal obesity Waist Circumference

Men >102 cm (>40 in)Women >88cm (>35 in)

Triglycerides 150 mg/dL

HDL-CMen <40 mg/dL

Women <50 mg/dL

Blood Pressure 130/85 mmHg

Fasting Glucose 110 mg/dL

Risk Factor Defining LevelAbdominal obesity Waist Circumference

Men >102 cm (>40 in)Women >88cm (>35 in)

Triglycerides 150 mg/dL

HDL-CMen <40 mg/dL

Women <50 mg/dL

Blood Pressure 130/85 mmHg

Fasting Glucose 110 mg/dL

NCEP ATPIII. JAMA 2001;285:2486-2497

Risk Factors of the Metabolic Syndrome: ATPIII Definitions

Metabolic syndrome: 3 or more

Metabolic SyndromeNCEP ATP III Criteria

NCEP ATP III. JAMA. 2001;285:2486–2497.

Risk Factor Defining LevelAbdominal Obesity (waist circumference)

Men >40 inchesWomen >35 inches

Triglycerides >150 mg/dLHDL Cholesterol

Men <40 mg/dLWomen <50 mg/dL

Blood Pressure >130/>85 mm HgFasting Glucose >110 mg/dL

3 of the following3 of the following

Prevalence of the Metabolic Syndrome Among US AdultsPrevalence of the Metabolic Syndrome Among US Adults

Prevalence

(%)

Prevalence

(%)

0

5

10

15

20

25

30

35

40

45

20-29 30-39 40-49 50-59 60-69 >70

MenMenWomenWomen

Age (years)Age (years)Ford E et al. JAMA. 2002; 287: 356Ford E et al. JAMA. 2002; 287: 356

Insulin Resistance and Heart Disease Diabetes

Hypertension

Low HDL

High triglycerides

Increased number of small, dense LDL particles

Endothelial dysfunction

LVH (left ventricular hypertrophy)

Increased PAI-1

Increased C-reactive protein

Twin Epidemics: Parallels in Prevalence

~61% of US Adults Are Overweight or Obese~61% of US Adults Are Overweight or Obese11

0

10

20

30

40

50

60

70

80

20-29 30-39 40-49 50-59 60-69 ≥70Age, yr

Pre

vale

nce

, %

Women

Men

Women

Men

Overweight/ObesityOverweight/Obesity22

Metabolic SyndromeMetabolic Syndrome33

1. Available at: http://www.cdc.gov/nchs/products/pubs/pubd/hestats/obese/obse99.htm2. Available at: http://www.cdc.gov/nchs/about/major/nhanes/overweight.pdf3. Ford ES, et al. JAMA. 2002;287:356-359.

Prevalence of the Metabolic Syndrome by ATP III Criteria — NHANES III Population

Overall 22% for age 20 and older

0

5

10

15

20

25

30

35

40

45

30-39 40-49 50-59 60-69 >70

Men

Women

Age (yr)

Pre

vale

nce

(%

)

Adapted from: Ford ES et al. JAMA. 2002;287:356–359.

Cardiovascular Mortality AssociatedWith Metabolic Syndrome (MS)

2.2

12

0

2

4

6

8

10

12

14

No MS MS

Inci

den

ce o

f C

V M

ort

alit

y

Diabetes Care 2001;24:683 Diabetes Care 2001;24:683

p < 0.001p < 0.001

Goals for Managingthe Metabolic Syndrome

An opportunity to prevent predictable complications:

» Type 2 diabetes

» Cardiovascular events

Management of Metabolic Syndrome

While we are aware of the magnitude of this problem, we are still trying to figure out how to best manage this.

Weight loss, proper diet and exercise are the obvious recommendations.

There are a lot of questions that are unanswered. Is drug therapy helpful? Insulin sensitizers? Statins?

Diseases Associated With Insulin Resistance

PCO

Elevated uric acid

Albuminuria

Nonalcoholic hepatic steatosis and NASH

Acanthosis nigricans

Metabolic syndrome

Obesity Hypertension ?

HYPERTENSION & OBESITY

Epidemiological studies have shown a correlation between body weight and

blood pressure—70% of hypertension in men and

60% in women are associated with excess adiposity

(Sharma AM, et al. J Hyptertens. 2001)

Increased Prevalence of Hypertension* as a Correlate of BMI

*Defined as mean SBP ≥ 140 mmHg or DBP ≥ 90 mmHg, or currently taking antihypertensive medication.

BMI < 25 kg/m2

BMI 25 – 26 kg/m2

BMI 27 – 29 kg/m2

BMI 30 kg/m2 18.2

22.525.2

38.4

16.5

21.924

32.2

0

10

20

30

40

Men Women

Hyp

erte

nsio

n (%

)

BMI Levels

(NIH. Obes Res. 1998)

Obesity and Hypertension

Insulin ResistanceInsulin Resistance++

HyperinsulinemiaHyperinsulinemia

Activation of the sympathetic nervous system

Vasoconstriction Cardiac output Na+

reabsorption

Blood Pressure(Landsberg L. J Hypertens. 2001)

Mechanisms by Which Obesity May Cause Hypertension and Renal Injury by Activation of the Renin-Angiotensin System and Sympathetic Nervous System, Metabolic Abnormalities

and Compression of the Kidney

Obesity

Renal medullary compression Renin-angiotensin system activity

Sympathetic nervous system activity

Tubular NaCI reabsorption

Renal vasodilation Volume expansion Lipids Glucose intolerance

Glomerular hypertension

Arterial hypertension

Glomerulosclerosis

Glucose

+

(Engeli S, et al. Hypertension. 2000)

Mechanism of Hypertension Associated With Insulin Resistance

Reduced sodium excretion

Stimulation of SNS

Increased Na and Ca content of VSMCs enhancing tone

Proliferation of VSMCs

Upregulation of AT1 receptor

Obesity and Cardiovascular Risk

Eccentric Hypertrophy

Sodium Retention Volume Expansion

Heart Rate Endothelial Dysfunction

Diabetes Mellitus Dyslipidemia

HypertensionHypertension

Cardiac Output

Visceral ObesityVisceral Obesity

Atherosclerosis Arterial Resistance

Concentric Hypertrophy

Congestive Heart Failure (CHF), Congestive Heart Failure (CHF), Coronary Artery Disease (CAD), Sudden DeathCoronary Artery Disease (CAD), Sudden Death

(Adapted with permission from Zhang R, Reisin E. Am J Hypertens. 2000)

Considerations in Selecting Pharmacological Agents For Treating Obesity-related Hypertension

Agent Potential Benefits Potential Drawbacks

Diuretics (low dose)

intravascular volume and cardiac output

May antagonize enhanced SNS activity of obesity-related hypertension

Potential for in peripheral resistance and intravascular volume

No excess risk of diabetesVerapamil heart rate

peripheral resistanceNo excess risk of diabetesNo dyslipidemic effectsRegression of LVH

Effects similar to those of ACEIsPossible improvement in insulin sensitivity

Improvement in metabolic profile

SNS activity

SNS and RAS activityPossible dose-related worsening of insulin resistance and dyslipidemia

risk of both weight gain and diabetesPossible interference with carbohydrate and lipid metabolism

Neuroendocrine activation

None

None

Excess risk of cardiovascular events, particularly CHF?

Possible impairment of glucose tolerance, weight gain

Beta blockers

CCBs

ACEIs

ARBs

Alpha blockers

Centrally-acting agents

(Reprinted with permission from Sharma AM, et al. J Hypertens. 2001)

Obesity Assessment: Risk FactorsExisting Disease

Conditions*Other Obesity-

associated DiseasesCardiovascular Risk Factors†

Other Risk Factors

Established CHD

Other atherosclerotic diseases

Type 2 diabetes

Sleep apnea

OB/GYN abnormalities

Osteoarthritis

Gallstones/gall bladder disease

Stress incontinence

Hypertension (SBP ≥ 140 mmHg or DBP ≥ 90 mmHg, or currently taking antihypertensive medication)

LDL cholesterol ≥ 160 mg/dL

HDL cholesterol < 35 mg/dL

Impaired fasting glucose 110 – 125 mg/dL

Family history of premature CHD‡

Age (men ≥ 45 years; women ≥ 55 years or menopausal)

Serum triglycerides > 200 mg/dL

Physical inactivity

*Patients with these conditions are at very high risk for disease complications and mortality.†Patients with three of these factors are at high absolute risk.‡Definite MI or sudden death at/before 55 years in father or other male first degree relative or at/before 65 years of age in mother or other first degree female relative.


Controlling Obesity Can Drastically Reduce Medical Costs

Total direct and indirect costs of obesity: United States, estimated to be at least $99.2 billion (1995)– direct costs: 5.7%, National Health Expenditure– costs due obesity-associated diseases

(eg, CHD, diabetes, osteoarthritis)

6% – 10% weight loss reduces treatment costs*– $123 for the insulin-treated diabetic patient– $61 for the hyperlipidemic patient– $43 for the sulfonylurea-treated diabetic patient

(Wolf AM, Colditz GA. Obes Res. 1998) (Greenway FL, et al. Obes Res. 1999)

*Reduction in costs/month/patient.

Health Benefits of Modest Weight Loss*

Possible risk of death CHD risk

MI rate stroke rate– improves serum lipids

Improves prognosis in type 2 diabetic patients glucose, insulin

Can significantly reduce sleep apnea osteoarthritis symptoms Reduces relapse rate of asthma

(Camargo CA, et al. Arch Intern Med. 1999) (Goldstein DJ. Int J Obes. 1992) (Suratt PM, Findley LJ. N Engl J Med. 1999) (Gelber AC. Am J Med. 1999)

*Modest weight loss = minimum of 5 lbs.

Management of Obesity: Treatment Options

Modality Recommendation

Reduced-calorie diet Reduce energy intake by 500 to 1,000 kcal/day to achieve a weight loss of 1 to 2 lbs/week over a 6-month period

Start with 30 to 45 minutes moderate activity 3 to 5 days/week, and work up to at least 30 minutes moderate-intensity physical activity on most or all days/week

Use multiple behavioral strategies (eg, self-monitoring of eating habits and physical activity)

Recommend appropriate pharmacotherapy* for patients with BMI 30 kg/m2, or with BMI 27 kg/m2 with one or more comorbid conditions

Consider for patients with class 3 obesity, or class 2 obesity with comorbid conditions, for whom other treatments have failed

Increased activity

Behavior modification

Pharmacotherapy

Surgery


*In combination with diet, increased activity, and behavior modification.

Actions and Adverse Effects of Weight Loss Agents

Drug Action

Sibutramine

Serotonin-releasing agent

Major Adverse Effects

Possible increase in heart rate and blood pressure

Serotonin-releasing agent

Inhibits pancreatic lipase, decreases fat absorption

Orlistat

Serotonin and norepinephrine reuptake inhibitor

Valvular heart disease

Valvular heart disease

Soft stools and anal leakageDecrease in absorption of fat-soluble vitamins

Dexfenfluramine

Fenfluramine

(Xenical® (orlistat) Capsules. [product information]. Nutley, NJ: Roche Laboratories Inc.; September 1999) (Meridia® (sibutramine hydrochloride monohydrate). [product information]. Mt. Olive, NJ: Knoll Pharmaceutical Company; November 1999) (NIH. Obes Res. 1998)

In light of the emergent evidence about the increasing prevalence of obesity and its link to CHD, we urge healthcare providers, legislators, insurers, and the public to take action on the following points:

(Eckel RH, Krauss RM, for the AHA Nutrition Committee. Circulation. 1998)

AHA Call to Action Statement: Obesity

Support more research into weight regulation, the causes of obesity, and the outcomes of obesity treatment

Recognize that the causes of obesity are complex and that both genetics and behavior are part of the emerging picture

(cont’d)



Nurture efforts that encourage individuals to take small steps toward increasing physical activity

Encourage state and local authorities to provide more opportunities for safe, community-based physical activity programs

Eliminate complacency by healthcare providers and individuals about obesity

(cont’d)



Make the treatment of obesity a shared responsibility between healthcare provider and individual — emphasize the “whole” person

Emphasize the total dietary picture to individuals

Educate the public about the importance of preventing obesity

Develop effective educational programs aimed at preventing the development of obesity in childhood

obesity and cv disease 1.ppt

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