Obesity and CV Disease 1.PPTPresentation Transcript
Obesity and Cardiovascular Disease Dionisio B. Yorro, Jr., M.D., FACC 16 th USTMAAA Convention Caesar’s Palace, LV, NV May 22-26, 2008
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.
Prevalence of Obesity Among US Adults From Years 1991, 1993, 1995, and 1998 (Reprinted with permission from Mokdad AH, et al. JAMA . 1999) < 10% 10% to 15% > 15% 1991 1993 1995 1998
Obesity Trends Among U.S. Adults 1985 No Data <10% 10%–14%
Obesity Trends Among U.S. Adults 1986 No Data <10% 10%–14%
Obesity Trends Among U.S. Adults 1987 No Data <10% 10%-14%
Obesity Trends Among U.S. Adults 1988 No Data <10% 10%–14%
Obesity Trends Among U.S. Adults 1990 No Data <10% 10%–14%
Obesity Trends Among U.S. Adults 1991 No Data <10% 10%–14% 15%–19%
Obesity Trends Among U.S. Adults 1992 No Data <10% 10%–14% 15%–19%
Obesity Trends Among U.S. Adults 1993 No Data <10% 10%–14% 15%–19%
Obesity Trends Among U.S. Adults 1994 No Data <10% 10%–14% 15%–19%
Obesity Trends Among U.S. Adults 1995 No Data <10% 10%–14% 15%–19%
Obesity Trends Among U.S. Adults 1996 No Data <10% 10%–14% 15%–19%
Obesity Trends Among U.S. Adults 1997 No Data <10% 10%–14% 15%–19% ≥20
Obesity Trends Among U.S. Adults 1998 No Data <10% 10%–14% 15%–19% ≥20
Obesity Trends Among U.S. Adults 1999 No Data <10% 10%–14% 15%–19% ≥20
Obesity Trends Among U.S. Adults 2000 No Data <10% 10%–14% 15%–19% ≥20
Obesity Trends Among U.S. Adults 2001 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% Obesity Trends Among U.S. Adults 2002
Obesity Trends Among U.S. Adults 2003 No Data <10% 10%–14% 15%–19% 20%–24% ≥25%
Obesity Trends Among U.S. Adults 2004 No Data <10% 10%–14% 15%–19% 20%–24% ≥25%
Obesity Rates Are Projected to Double Over the Next 30 Years (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) 50 40 30 20 10 0 1960 1970 1980 1990 2000 2010 2020 2030 US England Australia Brazil Year BMI 30 (%)
Bagel 140 calories 3-inch diameter Calorie Difference: 210 calories 350 calories 6-inch diameter 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 calories 1 cup spaghetti with sauce and 3 small meatballs Spaghetti and Meatballs
610 Calories 6.9 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 Soda 20 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 calories 16 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
Obesity Statistics: Prevalence in 2000 < 10% (1) > 15% (49) BMI > 30 kg/m 2 , or ~ 30 lb overweight for 5’4” person. Adapted from: Mokdad AH, et al. JAMA. 2001;286:1195-1200. Centers for Disease Control and Prevention. US Obesity Trends in Adults.
Measurement of body fat by:
bioelectrical impedance analysis (BIA)
skinfold thickness measurement
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 Underweight Normal 18.5 – 24.9 Normal range Overweight 25.0 – 29.9 Preobese Obesity class 1 30.0 – 34.9 Obese class 1 Obesity class 2 35.0 – 39.9 Obese class 2 Obesity class 3 ≥ 40.0 Obese class 3 NHLBI = National Heart, Lung, and Blood Institute; WHO = World Health Organization. NHLBI Terminology BMI, kg/m 2 , 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:
Diabetes mellitus, Type 2
Cancer – endometrium, breast, prostate, and colon.
Obesity and Mortality Risk, 1989 Men Women 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 0 20 25 30 35 40 BMI (kg/m 2 ) (Reprinted with permission from Gray DS. Med Clin North Am . 1989) Mortality Ratio
Obesity and Cardiovascular Disease 0 1 2 3 4 Relative Risk 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/m 2 ) 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 or Visceral type (android or “ apple shaped”) Lower body or external type (gynoid or “ pear shaped”)
Visceral Fat Distribution Normal vs Obesity Normal Visceral obesity Courtesy of Wilfred Y. Fujimoto, MD.
All Fat Cells Are Not Created Equal
Large Insulin-Resistant Adipocytes
Small Insulin-Sensitive Adipocytes
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?
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 5000 Visceral adipose tissue volume per unit surface area (mL/m 2 ) Glucose disposal (mg/kg LBM/min) Women Men
Obesity and Insulin Resistance Hyperinsulinemia + Hyperglycemia Activation of the sympathetic nervous system Increase of arterial tone Na+ reabsorption Hypertension Overstimulation of pancreatic -cell function Reduction of insulin secretion Type 2 Diabetes
Worldwide Diabetes Prevalence Africa Americas Eastern Mediterranean Europe Southeast Asia 1995 2000 2025 (projected) 80 0 10 20 30 40 50 Estimated Prevalence (millions) 60 70 Western Pacific World Health Organization; 2001.
What is the Metabolic Syndrome? Syndrome X Dysmetabolic Syndrome Insulin Resistance Syndrome
The Metabolic Syndrome The Insulin Resistance Syndrome The Dysmetabolic Syndrome
The Insulin Resistance Syndrome A syndrome in which the physiologic response is inadequate for the amount of insulin secreted Reaven, Olefsky
The Metabolic Syndrome Associated With Insulin Resistance Insulin Resistance Hypertension Type 2 Diabetes Disordered Fibrinolysis Complex Dyslipidemia TG, sdLDL, HDL Endothelial Dysfunction Systemic Inflammation Athero - sclerosis Visceral Obesity Adapted from ADA. Diabetes Care. 1998;21:310-314. Pradhan et al. JAMA. 2001;286:327-334.
Risk Factor Defining Level Abdominal obesity Waist Circumference Men >102 cm (>40 in) Women >88cm (>35 in) Triglycerides 150 mg/dL HDL-C Men <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 Syndrome NCEP ATP III Criteria NCEP ATP III. JAMA. 2001;285:2486–2497.
Risk Factor Defining Level
Abdominal Obesity (waist circumference)
Men >40 inches
Women >35 inches
Triglycerides > 150 mg/dL
Men <40 mg/dL
Women <50 mg/dL
Blood Pressure > 130/ > 85 mm Hg
Fasting Glucose > 110 mg/dL
3 of the following
Prevalence of the Metabolic Syndrome Among US Adults Prevalence (%) 0 5 10 15 20 25 30 35 40 45 20-29 30-39 40-49 50-59 60-69 >70 Men Women Age (years) Ford E et al. JAMA . 2002; 287: 356
Insulin Resistance and Heart Disease
Increased number of small, dense LDL particles
LVH (left ventricular hypertrophy)
Increased C-reactive protein
Twin Epidemics: Parallels in Prevalence ~61% of US Adults Are Overweight or Obese 1 1. Available at: http://www.cdc.gov/nchs/products/pubs/pubd/hestats/obese/obse99.htm 2. Available at: http://www.cdc.gov/nchs/about/major/nhanes/overweight.pdf 3. Ford ES, et al. JAMA. 2002;287:356-359. 0 10 20 30 40 50 60 70 80 20-29 30-39 40-49 50-59 60-69 ≥ 70 Age, yr Prevalence, % Women Men Women Men Overweight/Obesity 2 Metabolic Syndrome 3
Prevalence of the Metabolic Syndrome by ATP III Criteria — NHANES III Population Overall 22% for age 20 and older Age (yr) Prevalence (%) Adapted from: Ford ES et al. JAMA. 2002;287:356–359.
Cardiovascular Mortality Associated With Metabolic Syndrome (MS) Diabetes Care 2001;24:683 p < 0.001
Incidence of CHD Events in Patients With and Without Diabetes Incidence During Follow-up (%) (n=69) Nondiabetics with no prior MI Nondiabetics with prior MI Diabetics with no prior MI Diabetics with with prior MI 18.8 Haffner SM et al. N Engl J Med. 1998;339:229–234. (n=1304) (n=169) (n=890) 3.0 0.5 7.8 3.2 3.5 45.0 20.2 Events per 100 person-yr: P <.001* P <0.001 † * Non diabetics with vs without prior MI. † Diabetics with vs without prior MI.
Goals for Managing the Metabolic Syndrome
An opportunity to prevent predictable complications:
Type 2 diabetes
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
Elevated uric acid
Nonalcoholic hepatic steatosis and NASH
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/m 2 BMI 25 – 26 kg/m 2 BMI 27 – 29 kg/m 2 BMI 30 kg/m 2 18.2 22.5 25.2 38.4 16.5 21.9 24 32.2 0 10 20 30 40 Men Women Hypertension (%) BMI Levels (NIH. Obes Res . 1998)
Obesity and Hypertension Insulin Resistance + Hyperinsulinemia 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 Hypertension Cardiac Output Visceral Obesity Atherosclerosis Arterial Resistance Concentric Hypertrophy Congestive Heart Failure (CHF), Coronary Artery Disease (CAD), Sudden Death (Adapted with permission from Zhang R, Reisin E. Am J Hypertens . 2000)
Issues in Choice of Antihypertensive Therapy for the Obese Hypertensive
Reduction in pre- and afterload
No neuroendocrine activation
Favorable metabolic effects
No weight gain
Reduction in renal hyperfiltration and microalbuminuria
Reduction in mortality
(Sharma AM, et al. J Hyptertens . 2001)
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 diabetes Verapamil heart rate peripheral resistance No excess risk of diabetes No dyslipidemic effects Regression of LVH Effects similar to those of ACEIs Possible improvement in insulin sensitivity Improvement in metabolic profile SNS activity SNS and RAS activity Possible dose-related worsening of insulin resistance and dyslipidemia risk of both weight gain and diabetes Possible 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)
Pharmacologic Treatment of Obesity Hypertension
Low-dose diuretic +++
Beta blocker +
Treatment threshold: 135/85 mmHg!
Potential Benefits From ACE Inhibition
Inhibition of the formation of angiotensin II by ACE
Enhancement of the effects of prostaglandin and nitric oxide
Inhibition of sympathetic activation
Regression of ventricular and vascular smooth muscle hypertrophy
Improvement of endothelial function
Reduction of proteinuria
(Bakris GL, et al. Kidney Int . 1998) (Brown NJ, et al. Thromb Haemost . 1997) (Dzau VJ. Eur Heart J . 1998) (Emeis JJ, Tranquille N. Agents Actions . 1992) (Feener EP, et al. J Clin Invest . 1995) (Greenwald L, Becker RC. Am Heart J. 1994) (The Heart Outcomes Prevention Evaluation Study Investigators. New Engl J Med . 2000) (Kober L, et al. N Engl J Med . 1995) (Ridker PM, et al. Circulation . 1993)
Obesity Assessment: Risk Factors Existing Disease Conditions* Other Obesity- associated Diseases Cardiovascular 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
improves serum lipids
Improves prognosis in type 2 diabetic patients
Can significantly reduce sleep apnea
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/m 2 , or with BMI 27 kg/m 2 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 leakage Decrease 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)
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
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
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
(cont’d) (Eckel RH, Krauss RM, for the AHA Nutrition Committee. Circulation . 1998)
Key Factors for Development of Insulin Resistance
Excess peritoneal fat
Excess inflammatory adipocytokines produced by peritoneal adipocytes