OBESITY AND CARDIOVASCULAR DISEASE - ACP: Oklahoma Chapter Scientific Meeting 2017 - American College of ...
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OBESITY AND CARDIOVASCULAR
DISEASE
ACP: Oklahoma Chapter Scientific Meeting 2017
Nicole Tintera Tran, M.D.
Assistant Professor of Medicine
Department of Cardiology
Relevant Disclosure
Under Accreditation Council for Continuing Medical Education
guidelines disclosure must be made regarding relevant financial
relationships with commercial interests within the last 12 months.
Nicole Tintera Tran, M.D.
I have no relevant financial relationships or affiliations with
commercial interests to disclose.
Learning Objectives
• Upon completion of this session, participants will be able to:
– Understand the data supporting obesity as an independent risk factor for
cardiovascular disease.
– Identify the direct physiologic effects of obesity on the cardiovascular
system.
– Understand the contribution of obesity to hypertension and identify
which pharmacologic therapies might be most effective in this
population.
– Recognize the concept of the “obesity paradox” in patients with existing
cardiovascular disease, and identify a potential mechanism for this
paradox as well as confounding factors.Background OBESITY AND CARDIOVASCULAR DISEASE
Epidemiology
• The prevalence of obesity in the USA has doubled since 1980
• CDC estimates that obesity cost the USA > $147 billion in 2008
• 68% of adults in the USA are either overweight or obese
• Childhood obesity often translates to obesity in adulthood
– 80% of obese children become obese adults
Ogden CL, National Center for Health Statistics; 2010.
Kotchen TA, Am J Hypertens 2010;23(11):1170. Baker JC,
N Engl J Med. 2007;357(23):2329.WHO Classification
• BMI = weight (kg)/(height (m)2)
Class BMI (kg/m2)
Underweight < 18.5
Normal weight 18.5 – 24.9
Overweight 25 – 29.9
Class I obesity 30 – 34.9
Class II obesity 35 – 39.9
Class III obesity (severe, morbid) ≥ 40
WHO Guidelines on Obesity. 2009;9Limitations of BMI
• At lower BMIs does not distinguish well between lean body mass
and adipose tissue
• Better predictive of amount of adipose tissue at higher BMIs
• Centripetal obesity (waist to hip ratio) may be more predictive of
cardiovascular outcomes
Kotchen TA, Am J Hypertens 2010;23(11):1170.Obesity as a Cardiovascular Risk Factory
• 27th Bethesda conference
– Category I: risk factors for which interventions have been proved to
reduce the incidence of coronary artery disease (CAD) events
Obesity is a category II risk factor
– Category II: a risk factor for which intervention is likely to lead to
decreased likelihood of CAD events
for coronary artery disease.
– Category III: risk factors clearly associated with increase risk of CAD
which if modified might decrease risk of CAD events
– Category IV: risk factors associated with increased risk which cannot be
modified
Pasternak RC, Task force 3. J Am Coll Cardiol
1996;27(5):978.Obesity as a Cardiovascular Risk Factory
• Obesity isAll of which
associated are risk factors for
with:
– Insulin resistance/hyperinsulinemia
cardiovascular disease…
– Diabetes type II
– Dyslipidemia
– Hypertension Is obesity an independent risk factor for
– Left ventricular hypertrophy
–
cardiovascular disease or is it associated
Sympathetic nervous system (SNS) dysfunction
– with cardiovascular disease due to the
Endothelial dysfunction
– Obstructive sleep apnea above?
Kotchen TA, Am J Hypertens 2010;23(11):1170.Obesity as an independent risk factor OBESITY AND CARDIOVASCULAR DISEASE
Nurses Health Study
• 119,195 women in the BMI (kg/m2) Mortality (HR)
USA between 30-55 yo
19 – 24.9 1.2
• Free of cardiovascular
disease in 1976 25 – 26.9 1.3
• Among non-smokers, risk
of death increased directly 27 – 28.9 1.6
and significantly with
> 29 2.1-2.2
increasing BMI
Mansen JE. N Engl J Med. 1995;333(8):677.Framingham Heart Study
• 30 years of follow-up
• Strong positive and significant correlation between baseline
weight and mortality
• Overweight, non-smoking men had 3.9 fold increase in mortality
when compared to normal weight men
What about cardiovascular disease
and cardiovascular mortality?
Garrison RJ, Ann Intern Med. 1985;103(6 (Pt 2)):1006.• Prospective study of over 1 million USA adults
– 457,785 males
– 588,369 females
• Obesity significantly associated with increased all cause mortality
and increased cardiovascular (CVS) mortality in men and women
- High BMI most strongly predicted CVS death in
who were non-smokers
males
with no baseline CAD
- Risk greatest in both men and women with BMI ≥ 40
kg/m2
Calle EE, N Engl J Med. 1999;341(15):1097.What about “metabolically healthy” obesity?
• In Class I-III obese patients without evidence of any of the
components of the metabolic syndrome
– Impaired vasoreactivity
– More echolucent carotid plaque
– Increased left ventricular mass
– Impaired coagulation/fibrinolytic systems
Lind L, Thromb Vasc Biol. 2011;31(6):327Obesity and Cardiovascular disease • Conclusion: obesity is both an independent risk factor for cardiovascular disease as well as a facilitating causal agent through various associated co-morbidities
Direct cardiovascular effects of obesity OBESITY AND CARDIOVASCULAR DISEASE
Physiologic Effects of Obesity
↑ total blood volume and ↓ systemic vascular
central blood volume resistance*
↑ cardiac output
↑ left ventricular end-
diastolic dimension
↑ wall stress
Eccentric
hypertrophy
*normotensive obesity
Alpert M, J Cardiopulm Rehab Prev. 2016;36:1.Physiologic Effects of Obesity
↑ total blood volume and ↑ systemic vascular
central blood volume resistance*
↑ cardiac output
↑ left ventricular end-
diastolic dimension
↑ wall stress ↑ afterload
Concentric hypertrophy
*hypertensive obesity
Alpert M, J Cardiopulm Rehab Prev. 2016;36:1.Physiologic Effects of Obesity
• Class III obesity (morbid, severe)
– Left ventricular end-diastolic pressure (LVEDP) and pulmonary capillary
wedge pressure (PCWP) are increased
– Increased left-heart filling pressures along with obstructive sleep apnea
(OSH) and obesity hypoventilation syndrome → increased right-heart
filling pressures
– Exaggerated increased of LVEDP/PCWP with exercise
– Pulmonary edema threshold can be exceeded
Alpert M, J Cardiopulm Rehab Prev. 2016;36:1.Obesity Cardiomyopathy
• Heart failure due predominantly
or entirely to severe obesity
• Common in class III obesity,
related to duration obesity
– 70% at 20 years
– 90% at 30 years
• Incidence diastolic dysfunction
increases with obesity class
• Severe systolic dysfunction rare
in uncomplicated obesity
Alpert M, J Cardiopulm Rehab Prev. 2016;36:1.Obesity-related hypertension OBESITY AND CARDIOVASCULAR DISEASE
The Problem
• 60-70% of hypertension in adults attributable to obesity
• Obese individuals are 3.5 x more likely than normal weight
individuals to develop hypertension
• Central obesity more strongly associated with hypertension than
peripheral obesity in both men and women
Kotchen TA, Am J Hypertens. 2010;23(11):1170.Pathophysiology • Through what mechanisms does obesity contribute to hypertension? – Insulin-resistance – Sodium retention – Altered vascular function – Increased sympathetic nervous system (SNS) activity – Increased renin-angiotensin-aldosterone (RAA) activity
Pathophysiology
Increased SNS activity Renal factors
• Baseline SNS activity • Increased Na retention
increased in obesity • Impaired pressure natriuresis
• Most prominent in the
kidney and skeletal muscle • Increased intrarenal pressure
due to abdominal obesity
• Increased renal SNS →
sodium retention and may also impair natriuresis
activation of the renin-
angiotensin-aldosterone
(RAA) system
Kotchen TA, Am J Hypertens. 2010;23(11):1170.Pathophysiology
• Impaired endothelial function
– Insulin resistance and central obesity are both associated with impaired
endothelial function
– Nitric oxide (NO) dependent vasodilation is impaired
– This correlates most strongly with waist-hip ratio
– Weight loss has been shown to improve endothelial function
Kotchen TA, Am J Hypertens. 2010;23(11):1170.Treatment: Lifestyle Modifications
INTERVENTION DESCRIPTION ANTICIPATED DECREASE IN
• x SBP
Dietary Sodium Restriction < 2.4 grams/day 4.8 mm Hg
Weight Loss BMI 18.5-24.9 1 mm Hg per pound lost
DASH Diet High in vegetables, fruit, low 6 mm Hg
fat dairy, whole grains,
poultry, fish, nuts
Aerobic Exercise 40 minutes of moderate 4-6 mm Hg
intensity exercise 3-4x a
week
Limit Alcohol Intake ≤ 1 beverages/day women, ≤ 2-4 mm Hg
2 beverages/day men
JNC-7, Hypertension. 2003;42:1206-1252. Kotchen TA,
Am J Hypertens. 2010;23(11):1170.Treatment: Anti-Hypertensive Therapy
• Obesity is not a specific population in JNC-8
• ACE inhibitors and angiotensin receptor blockers (ARBs) are
associated with increased insulin sensitization and decreased
diabetic risk
• Adverse metabolic effects of diuretics are dose dependent
• Beta blockers may be more effective in treating hypertension in
obesity due to SNS over activity but are still not first line agents
in the treatment of hypertension
JNC-8, JAMA 2014;311(5):507. Kotchen TA, Am J
Hypertens. 2010;23(11):1170.The obesity paradox OBESITY AND CARDIOVASCULAR DISEASE
The Obesity Paradox and Heart Failure
• Meta-analysis of 9 observational studies of patients with heart
failure where BMI and mortality reported
• 28,209 patients, mean follow-up 2.7 years
• Overweight and Class I-II obesity were associated with a
reduction in mortality
• Overweight (BMI 25 – 29.9): all-cause
• This remainedmortality
true whenRR
adjusted
0.84 for baseline
(0.79 risk
– 0.90)
• There was a very high mortality
• Obese in the underweight
(BMI 30-39.9): all-causegroup
mortality
RR 0.67 (0.62 – 0.77)
Oreopoulos A, Am Heart J 2008;156:13.The Obesity Paradox and Heart Failure:
Discussion
• Selection bias:
– Obese patients may be identified earlier in the disease due to
comorbidities
– Only the “healthiest” obese may be surviving long enough to get heart
failure
– Obese patients were younger, less likely to smoke, had a lower incidence
of previous MI, had higher EF, higher systolic BP and higher rate of beta
blocker use
• Chronic heart failure is a catabolic state
Oreopoulus A, Am Heart J. 2008;156:13.The Obesity Paradox and Coronary Disease
• Meta-analysis of 40 studies of patients with CAD which
reported BMI and all-cause mortality
• 250,152 patients with mean follow-up of 3.8 years
• Underweight (BMI ≤ 20): RR all-cause mortality 1.37
(1.32 - 1.43), CVS mortality 1.45 (1.16 – 1.81)
• Overweight (BMI 25 – 29.9): RR all-cause mortality 0.87
(0.81-0.94), no significant reduction CVS mortality
• Class III obesity (BMI ≥ 40): RR CVS mortality 1.88
(1.85 – 3.34)
Kotchen TA, Am J Hypertens. 2010;23(11):1170.The Obesity Paradox and Coronary Disease:
Discussion
• BMI not optimal for distinguishing between lean mass and
adipose tissue in the overweight category
• Fewer cardiovascular risk factors in lower BMI groups
• Risk factors potentially identified earlier in obese
• Underweight have decreased muscle mass which is associated
with decreased exercise capacity
Romero-Corral A, Lancet. 2006;368:666.The Obesity Paradox and Cardiorespiratory
Fitness
• Poor cardiorespiratory fitness (CRF) measured in METs may be
the strongest cardiovascular risk factor
• 1 MET increase in CRF is associated with a 13% reduction in
CVS mortality and 15% reduction in all-cause mortality (2)
• 1 MET increase in CRF is associated with a 17% reduction in
heart failure hospitalization (2)
1. Lavie CJ, Am Heart J. 2014;169:194.
2. Lee DC, J Am Coll Cardiol. 2013;59:665The Obesity Paradox and Cardiorespiratory
Fitness
• In heart failure, the obesity paradox is only present in individuals
with low CRF
• 2066 patients with systolic heart failure (2)
– CRF (peak VO2 max) was ≥ 14 ml/kg/min
• No obesity paradox
• Low mortality
– CRF (peak VO2 max) < 14 ml/kg/min
• Obesity paradox present
• High mortality
1. Lavie CJ, Am Heart J. 2014;169:194.
2. Lavie CJ, Mayo Clin Proc. 2013;88:251.Rapid Weight Fluctuations and Outcomes
• Post hoc analysis of the Treating to New Targets Trial
– Patients with established cardiovascular disease
– Each 1 SD of body weight variability was associated with an
increased risk of any coronary or any cardiovascular event
(HR 1.04)
– Higher body weight variability was associated with higher risk
– Body weight variability also associated with increased risk of
new onset diabetes
Bangalore S, N Engl J Med. 2017;376(14):1335.Conclusions OBESITY AND CARDIOVASCULAR DISEASE
Conclusions • Obesity is an independent risk factor for the development of cardiovascular disease • Obesity is associated with an increased risk of hypertension, congestive heart failure, coronary heart disease, and cardiovascular mortality • Visceral obesity (measured by waist hip ratio) is associated with increased cardiovascular risk at any level of BMI
Conclusions • Purposeful weight loss is associated with: – Decreased total and central blood volume – Decreased oxygen consumption – Decreased stroke volume – Decreased cardiac output – Decreased blood pressure • Improved CRF is associated with decreased cardiovascular and all-cause mortality
ACC/AHA/ACP Guidelines
• Recommend regular assessment of BMI and waist circumference
• Recommend counseling on weight management at each patient
visit with goal BMI 18.5 – 24.9 kg/m2
• Recommend initial goal weight low of 10% of baseline weight
• Recommend lifestyle changes and treatment strategies for
metabolic syndrome in:
– Men with waist ≥ 40”
– Women with waist ≥ 35”
Finn SD, ACCF/AHA Practice Guidelines. Circulation.
2012;126(25):3097Questions? Nicole-Tran@ouhsc.edu
References
• Ogden CL, et al. Prevalence of overweight, obesity and extreme obesity among adults: United States
trends 1960-1962 through 2007-2008. National Center for Health Statistics; 2010.
• Boyers RP, et al. BMI-CHD Collaboration Investigators. Arch Intern Med. 2007;167(16):1720.
• Baker JC, et al. Childhood body-mass index and the risk of coronary heart disease in adulthood.
NEJM. 2007;357(23):2321.
• Schultett, et al. Obesity, mortality and cardiovascular disease in the Munster Heart Study (PROCAM).
Atherosclerosis. 1999;144(1):199.
• Manson JE, et al. Bodyweight and mortality among women. NEJM 1995;333(11):677.
• Zheng W, et al. Association between BMI and risk of death in more than one million Asians. NEJM.
2011;364(8):719.
• Lind L, et al. A detailed cardiovascular characterization of obesity without the metabolic syndrome.
Arterioscler Thromb Vasc Biol. 2011;31(8):e27.
• Garrison RJ, et al. Weight and 30 year mortality of the men in the Framingham Study. Ann Intern
Med. 1985;103(6);1006.
• Alpert MA, et al. Obesity and the Heart. Am J Med Sci. 1993;306(2):117.
• Koch R, et al. Obesity and Cardiovascular hemodynamic function. Crurr Hypertens Rep.
1999;1(2):127.References
• Kramer CK, et al. Are metabolically healthy overweight and obesity benign conditions? A systematic
review and meta-analysis. Ann Intern Med. 2013;159(11):758.
• Thomsen M, et al. Myocardial infarction and ischemic heart disease in overweight and obesity with and
without metabolic syndrome. JAMA Intern Med. 2014;175(1):15.
• Kenchaiah S, et al. Obesity and the risk of heart failure. NEJM 2002;347(5):305.
• Badheka AO, et al. Influence of obesity on outcomes in atrial fibrillation; yet another obesity paradox.
Am J Med. 2010;123(7):646.
• Carnethon MP, et al. Association of weight status with mortality in adults with incident diabetes.
JAMA 2012;300(6):581.
• Tobias DK, et al. BMI and mortality among adults with incident type II DM. NEJM. 2014;370(3):235.
• Finn SD, et al. 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guidelines for the diagnosis and
management of patients with stable ischemic heart disease: executive summary: a report of the
ACCF/AHA task force on practice guidelines and the ACP, AATS, PCNA, SCAI and STS. Circ.
2012;126(25):3097.
• Bangalore S, et al. Body-weight fluctuations and outcomes in coronary heart disease. NEJM.
2017;376(14):1332.
• Uretsky S, et al. Obesity paradox in patient with hypertension and coronary artery disease. The
INVEST Study. International Verapamil SR-Trandalopril Study. Am J Med. 2007;126:863.References
• Oreopoulos A, et al. BMI and mortality in heart failure: a meta-analysis. Am Heart J. 2008;156:13.
• Fonarow GS, et al. An obesity paradox in acute heart failure: analysis of BMI and in hospital mortality for 108,927
patients in the Acute Decompensated Heart Failure National Registry. Am Heart J. 2007;153:74.
• Romero-Corral A, et al. Association of bodyweight with fatal mortality and with cardiovascular events in CAD: a
systematic review of cohort studies. Lancet. 2006;368:666.
• Lavie CJ, et al. Obesity and the prevalence of cardiovascular disease and prognosis—the obesity paradox updated. Prog
Cardiovasc Dig. 2016;58:537.
• Wang ZJ, et al. Association of BMI with mortality and cardiovascular events for patients with coronary artery disease: a
systematic review and meta-analysis. Heart 2015;101:1631.
• Lavie CJ, et al. Critical impact of fitness in the prevention and treatment of heart failure. Am Heart J. 2014;169:194.
• Alpert M, et al. Cardiac effects of obesity: pathophysiologic, clinical and prognostic consequences—a review. J
Cardiopulm Rehab Prev. 2016;36:1.
• Kotchen T, et al. Obesity-related hypertension. 2010;23(11):1170.
• Lee DC, et al. Changes in fitness and fatness on the development of cardiovascular disease risk factors: hypertension,
metabolic syndrome and hypercholesterolemia. JACC. 2012;59:665.
• Lavie CJ, et al. Impact of cardiorespiratory fitness on the obesity paradox in patients with heart failure. Mayo Clin
Proc. 2013;88:251.The Obesity Paradox and Heart Failure: Possible
Mechanism
• Obesity is associated with increase TNF-α which promotes
cardiac apoptosis, but adipose tissue also produces soluble TNF-
α receptors
• Increased BNP and NT pro-BNP levels are associated with
worse outcomes in heart failure
• Obesity associated with increased systolic blood pressure
• BMI when mildly elevated is not optimal for distinguishing
between adipose tissue and lean body mass
Oreopoulus A, Am Heart J. 2008;156:13.American College of Sports Medicine Guidelines
• Recommendations for physical activity in obese patients
– 5-7 days per week of aerobic physical activity
– 150 minutes/week to maintain weight/improve health
– 150 – 250 minutes/week to prevent weight gain
– 225 – 450 minutes/week to promote weight loss
– 200 – 300 minutes/ week to prevent weight gain after weight
loss
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