Supersize Me

1
Supersize Me?
Brian W. Zagol, M.D. Dan Dishmon, M.D. Department
of Cardiology University of Tennessee
2
The Good, the Fat, and the Ugly
3
Introduction

• We have all been taught that obesity is bad.
• Movies, television, and magazines all preach that
  obesity in this country is an epidemic and that
  there are many health problems associated with
  its condition.
• The medical literature also supports that obesity
  is a problem.

4
Definition

• Based upon observations by the National Health
  and Nutrition Examination Survey (NHANES), the
  National Center for Heath Statistics defines the
  following
• Underweight BMI lt 18.5 kg/m2
• Normal weight BMI 18.6 kg/m2 to 24.9 kg/m2
• Overweight BMI 25 kg/m2 to 29.9 kg/m2
• Obese BMI gt 30 kg/m2

5
Introduction

• Obesity has been implicated as a risk factor for
  the following medical conditions
• - Decreased life expectancy
• - Hypertension
• - Hypercholesterolemia
• - Diabetes Mellitus
• - Gout
• - Coronary disease
• - Heart Failure
• - Atrial fibrillation
• - Stroke

• Hepatobiliary Disease
• - Osteoarthritis
• Cancer (esophogus, colon,
• rectum, liver, gallbladder,
• pancreas, kidney,
• non-Hodgkins lymphoma,
• multiple myeloma, stomach,
• prostate, endometrial, breast
• - Kidney Stones
• - Psychosocial disorders
• i.e. Lonely Saturday nights

6
Relative Risk of All-cause Mortality and
Cardiovascular Mortality Based upon Weight
(Obese BMI gt 25) and Fitness Level
Lee C D, et al. Am J Clin Nutr. 1999 69373.
7
Relative Risk of Certain Conditions in Overweight
Individuals (BMIgt27.8)
Van Itallie TB, et al. Ann Int Med. 1985
103983.
8
Relative Risk of Certain Conditions as BMI
Increases
Dietz W H, et al. NEJM. 1999 341427.
9
The Advantage of Obesity?

• It is evident by large, observational studies
  that obesity contributes to a number of
  conditions which are known to lead to
  atherosclerotic disease and also to the
  development of coronary artery disease itself.
• However once CAD has developed and these patients
  require revascularization, the picture is not as
  clear cut. In fact, FAT PEOPLE DO BETTER!!!

10
The Obesity Paradox

• In the 1980s, the bias of both cardiologists and
  cardiothoracic surgeons persisted and overweight
  and obese patients were believed to carry a
  higher risk to revascularization than their
  non-overweight counterparts.
• This bias persisted despite conflicting data on
  the subject.
• The bias was so evident that an editorial in the
  Canadian Journal of Surgery, published in 1985
  questioned whether obese patients should receive
  CABG surgery at all!

Koshal A, et al. Can J Surg. 1985. 28331.
11
The Obesity Paradox

• However, in the late 1990s and early 2000s
  retrospective analysis of large revascularization
  studies were finding surprising results in
  overweight and obese patients they had fewer
  complications.
• These results applied to both percutaneously
  revascularized patients and to those surgically
  revascularized.

12
Percutaneous Complications

• Obese patients undergoing coronary angiography
  would seemingly have higher procedural
  complication rates
• Difficulty gaining femoral arterial access
• Difficulty achieving post-procedural hemostasis
• Delayed recognition of vascular complications

13
Percutaneous Complications

• In an article by Nicholas Cox, et al. published
  in the American Journal of Cardiology in 2004,
  the group collected data on 5234 consecutive
  patients undergoing cardiac catheterization at
  the Brigham and Womens Hospital in Boston,
  Massacusetts as well as the Western Hospital in
  Fottscray, Victoria, Australia between January
  2002 and July 2003.
• They retrospectively looked at complication rates
  of those patients in comparison to their body
  mass indices.

Cox N, et al. Am J Card. 2004 941174.
14
Percutaneous Complications

• Cardiac catheterization was performed using
  standard methods with site of access determined
  by operator preference and patient suitability.
• Obesity was defined as a BMI gt 30kg/m2
• Vascular complications were defined as need for
  surgical repair, transfusion, the development of
  arteriovenous fistula, pseudoaneurism, or large
  hematoma (gt8cm)

Cox N, et al. Am J Card. 2004 941174.
15
Percutaneous Complications Baseline Demographics
Cox N, et al. Am J Card. 2004 941174.
16
Distribution of Patients Undergoing
Catheterization by BMI
Cox N, et al. Am J Card. 2004 941174.
17
Vascular Complication Rate Based Upon BMI
Cox N, et al. Am J Card. 2004 941174.
18
Vascular Complications by Obesity Group
Cox N, et al. Am J Card. 2004 941174.
19
Vascular Complications by BMI Looking at Approach
Used
Cox N, et al. Am J Card. 2004 941174.
20
Discussion

• The authors of this study speculated that the
  lower rate of vascular complications seen in
  obese people may be accounted for by the
  following variables
• Obese patients have larger arterial size sheath
  size ratio
• Obese patients, at least in this study, more
  frequently received device closure.
• The perceived increased risk of vascular
  complications in obese people may lead to
  increased diligence in vascular access and in
  obtaining hemostasis at the end of the procedure.
  

Cox N, et al. Am J Card. 2004 941174.
21
Percutaneous Results

• It is clear that overweight and obese patients
  have fewer complications from percutaneous
  cardiac interventions during the actual
  procedure, but how do they do long-term?
• My colleague, I am sure, will point out that
  there are multiple studies associating increased
  restenosis rates in obese patients.
• The medical literature documents that obesity,
  independent of blood pressure and diabetes
  status, is a risk factor for repeat target lesion
  revascularization, that some speculate is due to
  increased inflammation and insulin resistance.

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Percutaneous Results

• However it appears with drug-eluting stents, the
  increased risk of restenosis may also no longer
  be a problem.
• In a review of the data from the Taxus-IV trial,
  Eugenia Nikolsky, et al. published a study in the
  American Journal of Cardiology in March, 2005
  looking at the impact of obesity on restenosis
  rates in the era of drug-eluting stents versus
  bare metal stents.

Nikolsky E, et al. Am J Card. 2005 95709.
23
Taxus-IV Baseline Characteristics
Nikolsky E, et al. Am J Card. 2005 95709.
24
Taxus-IV Clinical Outcomes at 1 Year
Nikolsky E, et al. Am J Card. 2005 95709.
25
Taxus-IV Freedom from TVR or MACE
Nikolsky E, et al. Am J Card. 2005 95709.
26
Taxus-IV Restenosis Rates
Nikolsky E, et al. Am J Card. 2005 95709.
27
CABG and Obesity

• It is clear that obese patients undergoing
  percutaneous interventions have fewer
  peri-procedural complications AND with the advent
  of drug-eluting stents increased restenosis rates
  no longer seem to be a problem.
• But what about obese patients who require
  surgical revascularization?

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CABG Procedural Results

• Obesity is frequently cited as a risk factor for
  adverse outcomes with CABG surgery.
• Nancy Birkmeyer, et al. in a study published in
  Circulation in 1998 prospectively looked at
  11,101 consecutive patients undergoing CABG
  between 1992 and 1996 at medical centers in
  Maine, New Hampshire, and Vermont.
• Patients were categorized into the following
  groups non-obese (BMIlt30), obese (BMI 31-36),
  and severely obese (BMIgt36) and were evaluated
  for procedural and in-hospital complications.

Birkmeyer N, et al. Circulation. 1998 971689.
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CABG Procedural Results Baseline Characteristics
Birkmeyer N, et al. Circulation. 1998 971689.
30
CABG Procedural Results
Birkmeyer N, et al. Circulation. 1998 971689.
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CABG Procedural Results Conclusions

• With the exception of sternal wound infections,
  the perception among clinicians that obesity
  predisposes to various post-operative
  complications is not supported by the data.
• Furthermore, there is no difference in mortality
  among these patients and obesity seems to be
  protective on the risk of postoperative bleeding.
  

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CABG Long-term Results

• It appears safe to perform CABGs on obese
  patients, but how do they do in the long-term?
• Luis Gruberg, et al. in The American Journal of
  Cardiology in February, 2005 analyzed the
  outcomes of coronary artery revascularization for
  patients with multi-vessel CAD based upon the
  data collected in the large ARTS trial (Arterial
  Revascularization Therapies Study).

Gruberg L, et al. American Journal of
Cardiology. 2005 95439.
33
CABG Long-term Results

• The ARTS trial was a multicenter, randomized
  trial that compared PCI plus stenting with CABG
  in patients who had multi-vessel CAD.
• A total of 1205 patients from 67 participating
  centers worldwide were enrolled between April
  1997 and June 1998.
• The obesity analysis was based upon the 3-year
  outcomes from this trial.

Gruberg L, et al. American Journal of
Cardiology. 2005 95439.
34
CABG Long-term Results Baseline Characteristics
Gruberg L, et al. American Journal of
Cardiology. 2005 95439.
35
CABG Long-term Results
Gruberg L, et al. American Journal of
Cardiology. 2005 95439.
36
CABG Long-term Results Kaplan-Meier Curve for
Survival without MACE (Death, CVA, MI, or Repeat
Revascularization)
N.S.
Gruberg L, et al. American Journal of
Cardiology. 2005 95439.
37
CABG Long-term Results

• In the ARTS registry, BMI had no effect on 3 year
  outcome of those who underwent stenting.
• Conversely, among those who underwent CABG, those
  who were overweight or obese had significantly
  better outcomes than did those who had a normal
  BMI with regard to survival without MACE, mainly
  driven by decreased need for revascularization.

Gruberg L, et al. American Journal of
Cardiology. 2005 95439.
38
Summary for the Obesity Paradox

• Obese patients requiring revascularization
  procedures compared to their non-obese
  counterparts
• Have a lower procedural risk at cardiac
  catheterization.
• Do not have increased rates of restenosis, since
  the advent of drug-eluting stents.
• Have overall equal risk of undergoing surgical
  revascularization, with decreased periprocedural
  bleeding.
• Have better long-term outcomes after undergoing
  CABG in regard to survival, free of major adverse
  cardiac events.
• Bring on the Bacon!!!

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Paradox, Schmaradox

• Obesity is known to predispose patients to
  increased overall morbidity and mortality
• Obesity is associated with conventional
  cardiovascular risk factors such as HTN, DM, and
  HPL
• Furthermore, obesity is associated with
  endothelial dysfunction, insulin resistance, and
  inflammation that may contribute to the increased
  risk for adverse clinical outcomes

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Obesity and PCI

• Clinical outcome in the 1st year after coronary
  stenting is determined primarily by restenosis,
  manifested clinically as recurrent ischemia
  prompting repeat revascularization of the
  original target lesion (target lesion
  revascularization TLR)
• HTN and DM have been associated with an increased
  risk for TLR after coronary stent placement
• Any effect of obesity on TLR may be influenced by
  the increased prevalence of these obesity related
  diseases

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No Paradox Here
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Fat Needs No Friends

• These findings are consistent with an obesity
  effect that is not mediated by DM or HTN
• Insulin resistance and endothelial dysfunction
  are independent predictors of early restenosis
  after coronary stenting
• Neointimal proliferation after stent implantation
  in patients with IGT has been shown to be greater
  than in patients with normal glucose tolerance

44

• Products of adipocytes include IL-6, TNF-a, and
  CRP
• Inflammation has been implicated to play a
  central role in neointimal hyperplasia

45

• Correlation between levels of inflammatory
  markers and propensity for restenosis has also
  been demonstrated
• Previous reports of an obesity paradox after PCI
  are possibly explained by inadequate adjustment
  for high-risk patients at lower extremes of BMI
  and focus on mortality outcomes

46
Obesity and CABG

• Obesity is often thought to be a risk factor for
  perioperative morbidity and mortality with
  cardiac surgery
• Factors predisposing and contributing to severity
  of CAD as well as the technical difficulties in
  surgical and postsurgical care of the obese
  likely contribute to these perceptions

47

• Many previous attempts to study the association
  between obesity and outcomes with cardiac surgery
  have suffered from limitations caused by sample
  size and lack of data about potential confounders
• In most studies, those classified as obese or
  severely obese were on average younger, more
  likely to be female, more likely to have other
  CAD risk factors, had a greater incidence of L
  main disease, and higher LVED pressure

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Patient Characteristics
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Morbidity of Obesity

• It has been demonstrated that obese patients
  undergoing cardiac surgery have a higher
  incidence of peri- and postoperative MIs,
  arrhythmias, respiratory infections, infections
  of the leg donor site, and sternal dehiscence

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Post-CABG Morbidity in the Obese
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Pathophysiology

• Myocardial Infarction, Arrhythmias
• Greater cardiac workload?
• Inadequate myocardial protection of fatty or
  hypertrophied hearts?
• O2 supply/demand mismatch?
• Pneumonia
• Decreased mechanical ventilatory functions
• Longer mechanical ventilation times

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More Pathophysiology

• Wound Infections
• Poor wound healing
• Diabetes
• Excessive adipose tissue with low regional oxygen
  tension
• Inadequate serum levels of prophylactic abx
• Technical difficulties in maintaining sterility
  of tissue folds

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Infectious Implications

• Infection in the setting of cardiac surgery
  increases morbidity and mortality
• In a study by Fowler et al, patients with major
  infection had significantly higher mortality
  (17.3 vs 3.0, plt0.0001) and postoperative
  length of stay gt14 days (47.0 vs 5.9, plt0.0001)
  
• Most common risk factors for infection included
  BMI of 30 to 40 kg/m2, DM, previous MI, and HTN

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Fat and Fib/Flutter

• Obesity is a risk factor for atrial fibrillation
  and atrial flutter in the cardiac surgery setting
• Postoperative atrial dysrhythmias may be
  complicated by significant symptoms, hemodynamic
  instability, and an increased risk of stroke
• Postop fib/flutter is also associated with
  increased length of stay and incurs additional
  costs

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Lose the Weight and Do Great?

• In patients encouraged to undergo preoperative
  weight reduction, there was a trend of better
  postoperative recovery
• They had a shorter time in the ICU (1.5 vs 2.1
  days), a lower incidence of MI (4.7 vs 6.7) and
  arrhythmias (25.7 vs 30.4), and fewer
  respiratory infections (3.8 vs 4.2)

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• Preoperative weight reduction and subsequent
  postoperative weight control should reduce
  perioperative complications and improve patients
  long term results

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References

• Rana, JS, et al. Obesity and Clinical Restenosis
  after Coronary Stent Placement. Am Heart Journal.
  2005 150 821-826.
• Fowler, VG, et al. Clinical Predictors of Major
  Infections After Cardiac Surgery. Circulation.
  112 I 358-365.
• Martinez, EA, et al. ACCP Guidelines for
  Prevention and Management of Postop A-fib After
  Cardiac Surgery. Chest. 2005 128 48-55.

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References Contd

• Fasol, R. et al. The Influence of Obesity on
  Perioperative Morbidity. Thoracic and
  Cardiovascular Surgeon. 1992. 40 126-129.
• Birkmeyer, NJ, et al. Obesity and Risk of Adverse
  Outcomes Associated with CAB Surgery.
  Circulation. 1998 97 1689-1694.
• Gurm, HS, et al. The Impact of BMI on Short- and
  Long-Term Outcomes in Patients Undergoing
  Coronary Revascularization. JACC. 2002 39
  834-840.

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References Contd

• Prasad, US, et al. Influence of Obesity on the
  Early and Long Term Results of Surgery for CAD.
  Eur J Cardiothorac Surg. 1991. 5 67-73.