THE OBESITY PARADOX: IS IT ALL ABOUT CARDIOVASCULAR FITNESS?

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1 PCNA LIVE WEBINAR SERIES THE OBESITY PARADOX: IS IT ALL ABOUT CARDIOVASCULAR FITNESS? Moderator Kathy Berra, MSN, ANP, FAHA, FPCNA, FAAN Stanford Prevention Research Center, Stanford, CA This course is being presented by PCNA through an educational grant from The Coca-Cola Company and co-sponsored by The Coca-Cola Company Beverage Institute for Health & Wellness. THANK YOU TO OUR SUPPORTER This activity is presented by the Preventive Cardiovascular Nurses Association (PCNA) and is supported by The Coca-Cola Company Beverage Institute for Health & Wellness. 1

2 JOIN PCNA: PCNA MEMBERS MAKE A DIFFERENCE Join PCNA to expand your knowledge and network! Some of our Membership Benefits include: Bi-monthly journal subscription to the Journal of Cardiovascular Nursing Free evidence-based clinical tools for professionals and patients Over 30 free online CE courses Membership in a local chapter Reduced rates to the PCNA Annual Symposium To see a complete listing of membership benefits, visit ACCREDITATION RN, NP Accreditation: The Preventive Cardiovascular Nurses Association is accredited by the American Association of Nurse Practitioners as an approved provider of nurse practitioner continuing education. Provider number: This program was planned in accordance with AANP CE Standards and Policies and AANP Commercial Support Standards. RD, DTR Accreditation: The Coca-Cola Company Beverage Institute For Health & Wellness is a Continuing Professional Education (CPE) Accredited Provider with the Commission on Dietetic Registration (CDR). Provider number: BF001. 2

3 PROGRAM NAVIGATION Use the MESSAGE box on the left of your screen to submit a question for the Q&A Session Click on this icon for technical assistance: Click on this icon to enlarge slides: Click on this icon for program handouts: Click on the Get Your CE Credit icon before exiting this program today to access the Course Evaluation and Obtain a CPE/CE Certificate.* The CPE/CE LINK will also be provided in a follow-up to all preregistered participants. *This program is pre-approved for CE & CPE for nursing and dietetic professionals. - Other professionals may obtain a Certificate of Attendance by ing pcna@commpartners.com or calling FACULTY DISCLOSURES Ms. Berra: no relationships to disclose Dr. Lavie: no relationships to disclose Ms. Fletcher: serves on the Coca Cola Company s Health and Wellness Advisory Board 3

LEARNING OBJECTIVES List the adverse effects of overweight and obesity on cardiovascular risk and cardiac structure/function Summarize the evidence that relative to normal weight, overweight is

maintenance, based on frequency, intensity, type and duration PCNA LIVE WEBINAR SERIES THE OBESITY PARADOX: IS IT ALL ABOUT CARDIOVASCULAR FITNESS? Presenters Carl (Chip) Lavie, Jr., M.D., FACC, FACP, FCCP Barbara J.

4 LEARNING OBJECTIVES List the adverse effects of overweight and obesity on cardiovascular risk and cardiac structure/function Summarize the evidence that relative to normal weight, overweight is associated with lower all-cause mortality Review the evidence for the benefit of exercise on cardiovascular health independent of weight loss Identify the impact of exercise on weight loss and weight maintenance, based on frequency, intensity, type and duration PCNA LIVE WEBINAR SERIES THE OBESITY PARADOX: IS IT ALL ABOUT CARDIOVASCULAR FITNESS? Presenters Carl (Chip) Lavie, Jr., M.D., FACC, FACP, FCCP Barbara J. Fletcher, RN, MN, FAHA, FPCNA, FAAN This course is being presented by PCNA through an educational grant from The Coca- Cola Company and co-sponsored by The Coca-Cola Company Beverage Institute for Health & Wellness. 4

5 The Obesity Paradox : Is It All About Cardiovascular Fitness? Carl J. Lavie, MD, FACC, FACP, FCCP Professor of Medicine Medical Director, Cardiac Rehabilitation and Preventive Cardiology Director, Exercise Laboratories John Ochsner Heart and Vascular Institute Ochsner Clinical School-The UQ School of Medicine New Orleans, Louisiana LavieCL et al. J Am CollCardiol2009; 53:

6 Obesity and Cardiovascular Diseases Obesity increasing in epidemic proportions Body mass index (BMI) is primarily used Body fatness, waist circumference (WC), waist to hip ratio (WHR), and waist to height ratio may be superior Lavie CJ et al. JACC 2009;53: Obesity and Cardiovascular Diseases 70% of adults in US are overweight or obese Morbid obesity especially increased Obesity is second to only tobacco abuse as the #1 cause of preventable death in US Due to obesity, we may soon see a reversal in the steady increase in life expectancy Lavie CJ et al. JACC 2009;53:

7 Adverse Effects of Obesity Increases in insulin resistance - Glucose intolerance - Metabolic Syndrome - Type 2 Diabetes Mellitus Hypertension Abnormal LV Geometry - Concentric Remodeling - LVH Lavie CJ et al. JACC 2009;53: Adverse Effects of Obesity DYSLIPIDEMIA Elevated total cholesterol Elevated VLDL and triglycerides Elevated LDL and small, dense particles Elevated non-hdl Elevated apolipoprotein B Reduced HDL and apolipoprotein A-1 Lavie CJ et al. JACC 2009;53:

8 Adverse Effects of Obesity Abnormal endothelial function Abnormal systolic and diastolic LV function Increased systemic inflammation (eg CRP) Increased Pro-thrombotic state Albuminuria Obstructive sleep apnea / sleep disordered breathing Lavie CJ et al. JACC 2009;53: Cardiovascular Diseases Associated With Obesity Hypertension Heart Failure Coronary Heart Disease Atrial Fibrillation Complex Ventricular Dysrhythmias Stroke Venous Thromboembolism OSA / SDB Lavie CJ et al. JACC 2009;53:

Obesity and CV Disease Alpert MA, Am J Med Sci 2001;321:225-230 Higher BMI Risk of Development of Mortality in the General Population BMI Associated Death

9 Obesity and CV Disease Alpert MA, Am J Med Sci 2001;321: Higher BMI Risk of Development of Mortality in the General Population BMI Associated Death Risk: General Population Relative Risk of Death General Population Calle et al, N EnglJ Med 341: BMI, kg/m 2 9

10 Meta-Analysis of BMI and Survival 97 studies,2.88 million individuals >270,000 deaths Relative to normal weight, obesity (all grades combined) and grades 2 and 3 obesity were associated with higher all-cause mortality Grade 1 obesity was associated with a trend for lower mortality(hr 0.95; CI ), and overweight had significantly lower mortality (HR 0.94;CI ) Flegal KM et al.jama 2013;309(1):71-82 Obesity Paradox and Cardiovascular Diseases Although obesity has been implicated as one of the major risk factors for most CV diseases, including HTN, HF, and CHD, evidence from clinical cohorts of patients with established CV diseases indicates an obesity paradox because overweight and obese with these diseases tend to have a more favorable short- and long-term prognosis. Lavie CJ et al. JACC 2009;53:

11 Obesity and Hypertension Obesity increases levels of BP Obesity increases CR and LVH, independent of BP Obesity increases metabolic abnormalities in HTN Despite the increased prevalence, obese hypertensives have a favorable prognosis Lavie CJ et al. JACC 2009;53: BMI and HTN Prognosis Patients (%) Primary outcome Nonfatal MI Death (all cause) Nonfatal stroke CV related death Patients (%) Male Female 0 n <25 20 to <25 25 to <30 30 to < <25 20 to <25 25 to <30 BMI (kg/m 2 ) BMI (kg/m 2 ) Male, n Female, n ,158 2,368 4,730 4, to <35 2,692 2, ,079 1,890 Uretsky S et al. Am J Med 2007;120:

Obesity Paradox and Hypertension In aggregate, although obesity is a powerful risk factor for hypertension and LVH, obese hypertensive patients may

12 Obesity Paradox and Hypertension In aggregate, although obesity is a powerful risk factor for hypertension and LVH, obese hypertensive patients may paradoxically have a better prognosis, possibly due to low SVR and PRA Lavie CJ et al. JACC 2009;53: Lavie CL et al. JACC, HF 2013:1:

13 BMI and HF Prevalence KenchaiahS et al. N EnglJ Med 2002;347: BMI and HF Prognosis Horwich TB et al. J Am Coll Cardiol 2001:38;

14 Obesity Status and Heart Failure Mortality Meta-Analysis of 9 Observational Studies Oreopoulos et al. Am Heart J The message from >28,000 CHF patients: Once you have heart failure, bigger = live longer BMI and HF Hospital Mortality 108,927 decompensated HF patients Higher BMI associated with lower mortality For every 5-unit increase in BMI, HF mortality was 10 % lower (p < 0.001) Fonarow GC et al. Am Heart J 2007;153:

15 Body Composition and HF Prognosis Lavie et al. Am J Cardiol 2003;91: Possible Reasons for Obesity Paradox in Heart Failure Advanced HF is catabolic state; obese may have more metabolic reserve Adipose tissue produces TNF-α receptors that may neutralize TNF-α Obese have lower ANP and PRA Obese have higher BP, so may tolerate more meds Higher circulating lipoproteins may detoxify lipopolysaccharides that effect inflammatory cytokines Lavie CJ et al. JACC 2009;53:

16 Obesity and CHD Obesity adversely effects most major CV risk factors (HTN, dyslipidemia, MetS/T2DM) Obesity probably an independent CHD risk factor Obesity strongly related with 1 st premature MI at young age (Mandala MC et al. JACC 2008;52: ) Lavie CJ et al. JACC 2009;53: Obesity Paradox and CHD 40 cohort studies of over 250,000 CHD patients followed for 3.8 years Overweight and obese had lower risk of total and CV mortality compared with underweight and normal weight patients Similar in stable CHD, PCI and CABG In BMI 35 kg/m 2, there was excess risk of CV mortality without an increase on total mortality Romero-Corral A, et al. Lancet 2006; 368:

Obesity Paradox and CHD 529 consecutive CHD patients post events Overweight and obese (n = 393) had more adverse CHD risk profiles than leaner patients (n = 136) During 3-year

17 Obesity Paradox and CHD 529 consecutive CHD patients post events Overweight and obese (n = 393) had more adverse CHD risk profiles than leaner patients (n = 136) During 3-year follow-up, overweight/obese had significantly lower mortality Lavie CJ, et al. Am J Med 2009;122: Obesity Paradox and CHD Lavie CJ et al. Am J Med 2009;122:

Obesity Paradox and CHD A. Low BMI B..20.20 Low Fat.15.15 Cumulative Hazard.10.05 p<0.

18 Obesity Paradox and CHD A. Low BMI B Low Fat Cumulative Hazard p<0.001 High BMI Cumulative Hazard p<0.01 High Fat Time (Days) Time (Days) 2000 Lavie CJ et al. Am J Med 2009;122: Obesity Paradox and CHD Lavie CJ et al. Am J Med 2009;122:

LavieCJ et al. Mayo Clinic Proc 2011;86(9):857-864.

19 LavieCJ et al. Mayo Clinic Proc 2011;86(9): The "Obesity Paradox" in CHD Lavie CJ et al. Mayo Clinic Proc 2011;86(9):

Mayo Clinic Proc 2011;86(9): 857-864 Body Composition

20 The "Obesity Paradox" in CHD *p< compared to other group Lavie CJ et al. Mayo Clinic Proc 2011;86(9): Body Composition and CHD Mortality De SchutterA, LavieCJ et al. Am J Cardiol, online December,

21 LavieCJ et al. JACC 2012;60: Lean Mass Index and CHD Mortality Lavie CJ et al. JACC 2012;60:

22 Body Fat, Lean Mass Index and CHD Mortality LavieCJ et al. JACC 2012; 60: Obesity Paradox and CHD Mechanisms None of the studies accounted for non-purposeful weight loss Lower renin and ANP in obese Confounders COPD Impact of Fitness Baseline genetic differences Lavie CJ, et al. Mayo Clin Proc 2011;86(9):

23 Obesity Paradox and CHD Impact of Central Obesity and Fitness Mayo Clinic Studies with No Obesity Paradox in CHD with Central Obesity:1) Goel K et al.am Heart J 2011;16(3): and 2)Coutinho T et al. JACC 2011;57(19): UCLA HF Studies with Strong Obesity Paradox with Central Obesity:1) Clark AL et al. J Cardiac Failure 2011;17: and 2) Clark AL et al. Am J Cardiol 2012;110:77-82 Obesity Paradox in Central Obesity only with Low Fitness: McAuley PA et al. Mayo Clin Proc 2012;87(5): McAuley PA et al. Mayo Clin Proc 2012;87(5):

24 BMI Impact of Fitness on All-Cause Mortality in CHD % Body Fat Waist Circumference McAuley PA et al.mayo Clin Proc 2012;87(5): BMI Impact of Fitness on CVD Mortality in CHD % Body Fat Waist Circumference McAuley PA et al. Mayo Clin Proc 2012;87(5):

LavieCL et al. Mayo ClinProc 2013; 88(3):251-258.

25 LavieCL et al. Mayo ClinProc 2013; 88(3): Fitness, Mortality, Obesity Paradox in Heart Failure Low Fitness Higher Fitness Lavie CJ et al. Mayo Clin Proc 2013;88(3): Lavie CJ et al. Am Heart J

26 Obesity Paradox and CVD Impact of Cardiorespiratory Fitness Goel K et al. Am Heart J 2011;16(3): McAuley PA et al.mayo Clin Proc 2010;85(2): McAuley PA et al. Mayo Clin Proc 2012;87(5): Lavie CJ et al. Circulation 2012;Nov, in press Weight Loss in CV Diseases Obesity increases most CV risk factors and CV diseases However, an obesity paradox is present Weight loss improves risk factors Impact of weight loss on CV events remains controversial ArthamSM, LavieCJ et al. Curr Treatment Options in CV Med 2010;12:

27 Potential Adverse Effects of Weight Loss Obesity Paradox Prolonged QTc and increased ventricular dysrhythmias (starvation, very low calorie, liquid protein diets, and obesity surgeries) Pharmacologic agents have limited efficacy and considerable toxicity Lavie CJ et al. JACC 2009;53: Weight Loss and Lifestyle Modifications Calorie restriction and exercise training is safe and is associated with 60% reduction in development of T2DM Knowler WL et al. NEJM 2002;346: Tuomilehto J, et al. NEJM 2001;344: CRET reduces MS by 37% Milani RV, Lavie CJ. AJC 2003;92:50-54 In 1,500 CHD patients, 6 month weight loss programs associated with lower CHD events in 4 years Eilat-Adar S, et al. Am J Epidemiology 2005;161: In 377 patients at Mayo Clinic, weight loss, even in those with BMI < 25 kg/m 2, was associated with reduced mortality/cv events Sierra-Johnson J et al. EurCV PrevRehabil2008;15:

28 Weight Loss in CV Diseases In HTN, weight loss reduces BP and LVH In HF, weight loss improves LVM, systolic and diastolic LV function, and functional class Obesity surgery improves CHD risk factors, T2DM, and short- and long-term mortality Obesity surgery in small studies is safe in CHD and HF Lavie CJ et al. JACC 2009;53: Obesity, HF and Weight Loss Guideline Statements American Heart Association 40 kg/m 2 Heart Failure Society of America 35 kg/m 2 European Society of Cardiology 30 kg/m 2 Canadian Cardiovascular Society 30 kg/m 2 Vastly different cut-points due to minimal data by which to base these exact recommendations Clearly further research is needed to determine ideal BMI and body composition in CVD, including systolic and diastolic HF 28

29 Archer E et al. PLOS ONE 2013;8(2): e Household Management Energy Expenditure in Women over 5 Decades Archer E et al. PLOS ONE 2013;8(2): e

30 Church TS et al. PLOS ONE 2011;6(5): e19657 Occupational METs over 5 Decades Figure3. Church Occupational TS et al. METsand PLOS ONE energy2011;6(5): expendituresince1960. e19657theupper panel of Figure3p 30

31 Occupational EE and Obesity Church TS et al. PLOS ONE 2011;6(5): e19657 Obesity and CV Diseases Summary and Conclusions Overwhelming evidence supports the importance of obesity in the pathogenesis and progression of most CV diseases An Obesity Paradox exists At present, evidence supports purposeful weight reduction If the current obesity epidemic continues, we may soon witness and unfortunate end to the steady increase in life expectancy Lavie CJ et al. JACC 2009;53:

Laboratories John Ochsner Heart and Vascular Institute Ochsner Clinical School-The UQ School of Medicine New Orleans, Louisiana

32 The Obesity Paradox : Is It All About Cardiovascular Fitness? Carl J. Lavie, MD, FACC, FACP, FCCP Professor of Medicine Medical Director, Cardiac Rehabilitation and Preventive Cardiology Director, Exercise Laboratories John Ochsner Heart and Vascular Institute Ochsner Clinical School-The UQ School of Medicine New Orleans, Louisiana Cardiovascular Benefits of Exercise Independent of Weight Loss Barbara J. Fletcher, RN, MN, FAHA, FAACVPR, FPCNA, FAAN Clinical Associate Professor School of Nursing, Brooks College of Health Jacksonville, FL 32

33 Exercise Standards for Testing and Training Fletcher GF, Balady GJ, Amsterdam EA, Chaitman B, Eckel R, Fleg J, Froelicher VF, Leon AS, Pina IL, Rodney R, Simons-Morton DA, Williams MA, Bazzarre T. Exercise standards for testing and training: A Statement for Healthcare Professionals from the American Heart Association. Circulation. 2001;104: Fletcher G, Ades P, Kligfield P, et al. Exercise Standards for Testing and Training: A Scientific Statement From the American Heart Association Circulation: In Press, August 2013 Circulation is available at Objectives Review the evidence for the benefit of exercise on cardiovascular health independent of weight loss Review necessary amount of exercise needed to impact weight loss 33

34 Biological Mechanisms Effects that Lead to Prevention of CAD Antiatherogenic Effects Antithrombotic Effects Endothelial Function Alteration Autonomic Functional Changes Anti-Ischemic Effects Antiarrhythmic Effects Antiatherogenic Effects Regular Exercise has direct & indirect beneficial effects on coronary atherosclerosis Less severe CAD Larger coronary luminal diameters Reduced progression of atherosclerosis 34

35 Antiatherogenic Effects Antiatherogenic Effects of Exercise occur through Effects of Exercise Training on Cardiovascular Risk Factors Blood Lipid Profiles Hypertension Obesity Insulin Sensitivity Antiatherogenic Effects Blood Lipid Profiles Cross-sectional studies show greater physical activity & fitness correlate with Lower Total, LDL Cholesterol and Triglycerides (especially in patients with elevated Triglycerides) Higher HDL Cholesterol Longitudinal changes are more difficult to demonstrate due to variation in weight & diet 35

36 Antiatherogenic Effects Hypertension Aerobic Exercise training lowers resting blood pressure in normotensive & hypertensive individuals Randomized controlled trials show regular exercise lowers systolic & diastolic BP Average reduction in BP is 10 mmhg for systolic BP & 7.5 mmhg for diastolic BP Antiatherogenic Effects Obesity Exercise training is an important contributor to weight loss Body composition & fat distribution are improved with exercise Goal is caloric expenditure Best achieved with moderate intensity / low impact (brisk walking or cycling) with a longer duration & frequency Involves a long term commitment 36

37 Antiatherogenic Effects Insulin Sensitivity Exercise has favorable effects of both glucose metabolism & insulin sensitivity Increase sensitivity to insulin Decreased production of glucose by liver More muscle cells using glucose as oppose to adipose tissue Reduced obesity Improvement in insulin sensitivity & glucose use and reduction in type 2 diabetes Antithrombic Effects Exercise training favorably affects the fibrinolytic system in plasma fibrinogen levels in tissue plasminogen activator in plasminogen activator inhibitor Beneficial effects seen in platelet activation 37

38 Effects on Vascular Endothelial Function Vascular Endothelium helps regulate arterial tone & local platelet aggregation Through release of endothelium-derived relaxing factors such as nitric oxide This release is stimulated by rise in shear stress associated with short & long term increases in blood flow More evidence suggesting exercise improves endothelial function Autonomic Functional Changes Balance between sympathetic & parasympathetic activity modulates cardiovascular activity Improved measures of Heart Rate Variability (HRV) is seen in CVD patients HRV in physically trained 38

39 Anti-Ischemic Effects Exercise training improves the balance between myocardial oxygen supply & demand resulting in an anti-ischemic effect metabolic capacity & improved mechanical performance of myocardium HR slowing with training allows more time during diastole for coronary arteries to fill HR SBP at fixed submaximal work loads oxygen demand & coronary blood flow needs Antiarrhythmic Effects Risk of Ventricular Fibrillation (VF) or sudden cardiac death during strenuous exercise is documented Long term exercise training is thought to risk of VF induced improvements in Myocardial oxygen supply-demand balance in sympathetic tone & catecholamine release 39

40 Biological Mechanisms Effects that Lead to Prevention of CAD Antiatherogenic Effects Antithrombotic Effects Endothelial Function Alteration Autonomic Functional Changes Anti-Ischemic Effects Antiarrhythmic Effects How Much Exercise is Needed to Impact Weight Meeting in Bangkok, May 2002, with experts in Exercise, Energy Expenditure, & Body Weight Regulation Focused on emerging problem of Obesity Worldwide Unanimous Consensus Saris WH, Blair SN, et al. Obes Rev May; 4 (2):

41 Consensus Meeting; Bangkok, 2002; Conclusions min/day ( min/week) of mod intensity for prevention of weight re-gain (lesser amounts of vigorous intensity) min/day ( min/week) to prevent transition of overweight to obesity Reduce Sedentary Activity with Leisure Time Physical Activity Impact of Exercise on Weight Loss Prevent Weight Gain / minutes/week of moderate-intensity activity Weight Loss & Prevention of Weight Re-gain/ 250 minutes/week of moderate-intensity ACSM Position Stand

42 Exercise Intensity/Equivalents Levels %VO 2 R METs Min/mile MPH Low <40 <3 >20 <3 Moderate < High (vigorous) >60 6 <15 >4 Garber CE, et al. Med Sci Sports Exerc; 2011; 43 (7) Ainsworth BE, et al. Med Sci Sports Exerc; 1993: 25(1) QUESTIONS & ANSWERS Use the chat box located on the left side of your screen to ask a question 42

THANK YOU TO OUR SUPPORTERS This activity is presented by the Preventive

Beverage Institute for Health & Wellness.

Throughout the Lifespan Wednesday, August 14, 2013 1:00 pm - 2:00 pm EDT 12:00 pm

43 THANK YOU TO OUR SUPPORTERS This activity is presented by the Preventive Cardiovascular Nurses Association (PCNA) and is supported by The Coca-Cola Company Beverage Institute for Health & Wellness. UPCOMING WEBINAR Never Too Early, Never Too Late: Cardiovascular Health for Women Throughout the Lifespan Wednesday, August 14, :00 pm - 2:00 pm EDT 12:00 pm 1:00 pm CDT 11:00 am 12:00 pm MDT 10:00 am 11:00 am PDT More Information & Registration: 43

44 CONTINUING EDUCATION CERTIFICATE To Access to the Course Evaluation and Obtain a CE Certificate or a Certificate of Attendance: Click on the link Get your Certificate on the left side of your screen before exiting this program to access the Course Evaluation and Obtain a CE Certificate or Certificate of Attendance. This link will also be provided in a follow-up to all participants. Website Link: 44

Carl J. Lavie, MD, FACC, FACP, FCCP

Untangling the Heavy Cardiovascular Burden of Obesity and the Obesity Paradox Carl J. Lavie, MD, FACC, FACP, FCCP Professor of Medicine Medical Director, Cardiac Rehabilitation and Preventive Cardiology