Obesity and CV Disease 1.PPT
Transcript of 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.
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Obesity Trends Among U.S. Adults1985
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Obesity Trends Among U.S. Adults1987
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Obesity Trends Among U.S. Adults1990
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Obesity Trends Among U.S. Adults1991
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Obesity Trends Among U.S. Adults1992
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Obesity Trends Among U.S. Adults1994
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Obesity Trends Among U.S. Adults1996
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Obesity Trends Among U.S. Adults1997
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Obesity Trends Among U.S. Adults1998
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Obesity Trends Among U.S. Adults1999
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Obesity Trends Among U.S. Adults2000
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Obesity Trends Among U.S. Adults2001
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(*BMI 30, or ~ 30 lbs overweight for 5’4” person)
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Obesity Trends Among U.S. Adults2002
Obesity Trends Among U.S. Adults2003
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Obesity Trends Among U.S. Adults2004
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Obesity Rates Are Projected to Double Over the Next 30 Years
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01960 1970 1980 1990 2000 2010 2020 2030
USEnglandAustraliaBrazil
Year
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(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
Calorie Difference: 257 calories
590 calories
Cheeseburger
20 Years Ago Today
333 calories
Calorie Difference: 525 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
Calorie Difference: 500 calories
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
Calorie Difference: 305 calories
Pepperoni Pizza
20 Years Ago Today
500 calories 850 calories
Calorie Difference: 350 calories
Chicken Caesar Salad
20 Years Ago Today
390 calories 1 ½ cups
790 calories
3 ½ cups
Calorie Difference: 400 calories
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
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Type 2 diabetesHypertensionCholelithiasisCHD
Rel
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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
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Obesity and Cardiovascular Disease
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1
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4
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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
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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.
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0 1000 2000 3000 4000 5000Visceral adipose tissue volume per unit surface area (mL/m2)
Glu
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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
The Insulin Resistance Syndrome
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
The Insulin Resistance Syndrome
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
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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
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20-29 30-39 40-49 50-59 60-69 ≥70Age, yr
Pre
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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
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Women
Age (yr)
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Adapted from: Ford ES et al. JAMA. 2002;287:356–359.
Cardiovascular Mortality AssociatedWith Metabolic Syndrome (MS)
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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
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30
40
Men Women
Hyp
erte
nsio
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)
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.
(NIH. Obes Res. 1998)
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
(NIH. Obes Res. 1998)
*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)
(Eckel RH, Krauss RM, for the AHA Nutrition Committee. Circulation. 1998)
AHA Call to Action Statement: Obesity
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)
(Eckel RH, Krauss RM, for the AHA Nutrition Committee. Circulation. 1998)
AHA Call to Action Statement: Obesity
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