Supersize Me?

Supersize Me?

Brian W. Zagol, M.D.Dan Dishmon, M.D.

Department of CardiologyUniversity of Tennessee

The Good, the Fat, and the Ugly

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.

Definition

• Based upon observations by the National Health and Nutrition Examination Survey (NHANES), the National Center for Heath Statistics defines the following:

• Underweight: BMI < 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 > 30 kg/m2

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

Relative Risk of All-cause Mortality and Cardiovascular Mortality Based upon

Weight (Obese = BMI > 25) and Fitness Level

Lee C D, et al. Am J Clin Nutr. 1999; 69:373.

Relative Risk of Certain Conditions in Overweight Individuals (BMI>27.8)

Age 20 to 44 years

Age 45 to 74 years

Age 20 to 74 years

Hypertension

5.6 1.9 2.9

Hypercholesterolemia

2.1 1.1 1.5

Diabetes Mellitus

3.8 2.1 2.9

Van Itallie TB, et al. Ann Int Med. 1985; 103:983.

Relative Risk of Certain Conditions as BMI Increases

Dietz W H, et al. NEJM. 1999; 341:427.

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!!!

The Obesity Paradox

• In the 1980’s, 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. 28:331.

The Obesity Paradox

• However, in the late 1990’s and early 2000’s 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.

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


• 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 Women’s 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; 94:1174.


• Cardiac catheterization was performed using standard methods with site of access determined by operator preference and patient suitability.

• Obesity was defined as a BMI > 30kg/m2

• Vascular complications were defined as need for surgical repair, transfusion, the development of arteriovenous fistula, pseudoaneurism, or large hematoma (>8cm)


Percutaneous Complications – Baseline Demographics


Distribution of Patients Undergoing Catheterization by BMI


Vascular Complication Rate Based Upon BMI


Vascular Complications by Obesity Group


Vascular Complications by BMI Looking at Approach Used


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.


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.

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; 95:709.

Taxus-IV Baseline Characteristics


Taxus-IV Clinical Outcomes at 1 Year


Taxus-IV Freedom from TVR or MACE


Taxus-IV Restenosis Rates


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?

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 (BMI<30), obese (BMI 31-36), and severely obese (BMI>36) and were evaluated for procedural and in-hospital complications.

Birkmeyer N, et al. Circulation. 1998; 97:1689.

CABG – Procedural Results Baseline Characteristics


CABG – Procedural Results


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.

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; 95:439.


• 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.


CABG – Long-term Results Baseline Characteristics


CABG – Long-term Results Kaplan-Meier Curve for Survival without

MACE (Death, CVA, MI, or Repeat Revascularization)

N.S.



• 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.


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!!!

Paradox, SchmaradoxParadox, Schmaradox

Obesity is known to predispose Obesity is known to predispose patients to increased overall morbidity patients to increased overall morbidity and mortalityand mortality

Obesity is associated with Obesity is associated with conventional cardiovascular risk conventional cardiovascular risk factors such as HTN, DM, and HPLfactors such as HTN, DM, and HPL

Furthermore, obesity is associated Furthermore, obesity is associated with endothelial dysfunction, insulin with endothelial dysfunction, insulin resistance, and inflammation that may resistance, and inflammation that may contribute to the increased risk for contribute to the increased risk for adverse clinical outcomesadverse clinical outcomes

Dan Dishmon

Obesity and PCIObesity and PCI Clinical outcome in the 1Clinical outcome in the 1stst year after year after

coronary stenting is determined primarily by coronary stenting is determined primarily by restenosis, manifested clinically as recurrent restenosis, manifested clinically as recurrent ischemia prompting repeat revascularization ischemia prompting repeat revascularization of the original target lesion (target lesion of the original target lesion (target lesion revascularization [TLR])revascularization [TLR])

HTN and DM have been associated with an HTN and DM have been associated with an increased risk for TLR after coronary stent increased risk for TLR after coronary stent placementplacement

Any effect of obesity on TLR may be Any effect of obesity on TLR may be influenced by the increased prevalence of influenced by the increased prevalence of these obesity related diseasesthese obesity related diseases

No Paradox HereNo Paradox Here

Fat Needs No FriendsFat Needs No Friends These findings are consistent with an These findings are consistent with an

obesity effect that is not mediated by obesity effect that is not mediated by DM or HTNDM or HTN

Insulin resistance and endothelial Insulin resistance and endothelial dysfunction are independent predictors dysfunction are independent predictors of early restenosis after coronary of early restenosis after coronary stentingstenting

Neointimal proliferation after stent Neointimal proliferation after stent implantation in patients with IGT has implantation in patients with IGT has been shown to be greater than in been shown to be greater than in patients with normal glucose tolerancepatients with normal glucose tolerance

Products of Products of adipocytes include adipocytes include IL-6, TNF-a, and IL-6, TNF-a, and CRPCRP

Inflammation has Inflammation has been implicated to been implicated to play a central role play a central role in neointimal in neointimal hyperplasiahyperplasia

Correlation between levels of Correlation between levels of inflammatory markers and propensity inflammatory markers and propensity for restenosis has also been for restenosis has also been demonstrateddemonstrated

Previous reports of an obesity paradox Previous reports of an obesity paradox after PCI are possibly explained by after PCI are possibly explained by inadequate adjustment for high-risk inadequate adjustment for high-risk patients at lower extremes of BMI and patients at lower extremes of BMI and focus on mortality outcomesfocus on mortality outcomes

Obesity and CABGObesity and CABG Obesity is often Obesity is often

thought to be a risk thought to be a risk factor for perioperative factor for perioperative morbidity and mortality morbidity and mortality with cardiac surgerywith cardiac surgery

Factors predisposing Factors predisposing and contributing to and contributing to severity of CAD as well severity of CAD as well as the technical as the technical difficulties in surgical difficulties in surgical and postsurgical care of and postsurgical care of the obese likely the obese likely contribute to these contribute to these perceptionsperceptions

Many previous attempts to study the Many previous attempts to study the association between obesity and association between obesity and outcomes with cardiac surgery have outcomes with cardiac surgery have suffered from limitations caused by suffered from limitations caused by sample size and lack of data about sample size and lack of data about potential confounderspotential confounders

In most studies, those classified as In most studies, those classified as obese or severely obese were on obese or severely obese were on average younger, more likely to be average younger, more likely to be female, more likely to have other CAD female, more likely to have other CAD risk factors, had a greater incidence of risk factors, had a greater incidence of L main disease, and higher LVED L main disease, and higher LVED pressure pressure

Birkmeyer, et al. Obesity and Risk Birkmeyer, et al. Obesity and Risk of Adverse Outcomes Associated wof Adverse Outcomes Associated with CAB Surgery. Circulation.ith CAB Surgery. Circulation.

Patient CharacteristicsPatient Characteristics

Morbidity of ObesityMorbidity of Obesity It has been demonstrated that obese It has been demonstrated that obese

patients undergoing cardiac surgery have patients undergoing cardiac surgery have a higher incidence of peri- and a higher incidence of peri- and postoperative MI’s, arrhythmias, postoperative MI’s, arrhythmias, respiratory infections, infections of the leg respiratory infections, infections of the leg donor site, and sternal dehiscencedonor site, and sternal dehiscence

Post-CABG Morbidity in the Post-CABG Morbidity in the ObeseObese

PathophysiologyPathophysiology

Myocardial Infarction, ArrhythmiasMyocardial Infarction, Arrhythmias– Greater cardiac workload?Greater cardiac workload?– Inadequate myocardial protection of fatty Inadequate myocardial protection of fatty

or hypertrophied hearts?or hypertrophied hearts?– OO22 supply/demand mismatch? supply/demand mismatch?

PneumoniaPneumonia– Decreased mechanical ventilatory Decreased mechanical ventilatory

functionsfunctions– Longer mechanical ventilation timesLonger mechanical ventilation times

More PathophysiologyMore Pathophysiology

Wound InfectionsWound Infections– Poor wound healingPoor wound healing– DiabetesDiabetes– Excessive adipose tissue with low Excessive adipose tissue with low

regional oxygen tensionregional oxygen tension– Inadequate serum levels of prophylactic Inadequate serum levels of prophylactic

abxabx– Technical difficulties in maintaining Technical difficulties in maintaining

sterility of tissue foldssterility of tissue folds

Infectious ImplicationsInfectious Implications

Infection in the setting of cardiac Infection in the setting of cardiac surgery increases morbidity and surgery increases morbidity and mortalitymortality

In a study by Fowler et al, patients with In a study by Fowler et al, patients with major infection had significantly higher major infection had significantly higher mortality (17.3% vs 3.0%, p<0.0001) mortality (17.3% vs 3.0%, p<0.0001) and postoperative length of stay >14 and postoperative length of stay >14 days (47.0% vs 5.9%, p<0.0001) days (47.0% vs 5.9%, p<0.0001)

Most common risk factors for infection Most common risk factors for infection included BMI of 30 to 40 kg/mincluded BMI of 30 to 40 kg/m22, DM, , DM, previous MI, and HTNprevious MI, and HTN

Fat and Fib/FlutterFat and Fib/Flutter

Obesity is a risk factor for atrial Obesity is a risk factor for atrial fibrillation and atrial flutter in the fibrillation and atrial flutter in the cardiac surgery settingcardiac surgery setting

Postoperative atrial dysrhythmias Postoperative atrial dysrhythmias may be complicated by significant may be complicated by significant symptoms, hemodynamic instability, symptoms, hemodynamic instability, and an increased risk of strokeand an increased risk of stroke

Postop fib/flutter is also associated Postop fib/flutter is also associated with increased length of stay and with increased length of stay and incurs additional costsincurs additional costs

Lose the Weight and Do Lose the Weight and Do Great?Great?

In patients encouraged to undergo In patients encouraged to undergo preoperative weight reduction, there preoperative weight reduction, there was a trend of better postoperative was a trend of better postoperative recoveryrecovery

They had a shorter time in the ICU They had a shorter time in the ICU (1.5 vs 2.1 days), a lower incidence (1.5 vs 2.1 days), a lower incidence of MI (4.7% vs 6.7%) and arrhythmias of MI (4.7% vs 6.7%) and arrhythmias (25.7% vs 30.4%), and fewer (25.7% vs 30.4%), and fewer respiratory infections (3.8% vs 4.2%)respiratory infections (3.8% vs 4.2%)

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

ReferencesReferences

Rana, JS, et al. Obesity and Clinical Rana, JS, et al. Obesity and Clinical Restenosis after Coronary Stent Restenosis after Coronary Stent Placement. Placement. Am Heart JournalAm Heart Journal. 2005; 150: . 2005; 150: 821-826. 821-826.

Fowler, VG, et al. Clinical Predictors of Fowler, VG, et al. Clinical Predictors of Major Infections After Cardiac Surgery. Major Infections After Cardiac Surgery. CirculationCirculation. 112 [I] 358-365. . 112 [I] 358-365.

Martinez, EA, et al. ACCP Guidelines for Martinez, EA, et al. ACCP Guidelines for Prevention and Management of Postop A-Prevention and Management of Postop A-fib After Cardiac Surgery. fib After Cardiac Surgery. ChestChest. 2005; . 2005; 128: 48-55.128: 48-55.

References Cont’dReferences Cont’d Fasol, R. et al. The Influence of Obesity on Fasol, R. et al. The Influence of Obesity on

Perioperative Morbidity. Perioperative Morbidity. Thoracic and Thoracic and Cardiovascular SurgeonCardiovascular Surgeon. 1992. 40: 126-129.. 1992. 40: 126-129.

Birkmeyer, NJ, et al. Obesity and Risk of Birkmeyer, NJ, et al. Obesity and Risk of Adverse Outcomes Associated with CAB Adverse Outcomes Associated with CAB Surgery. Surgery. CirculationCirculation. 1998; 97: 1689-1694.. 1998; 97: 1689-1694.

Gurm, HS, et al. The Impact of BMI on Short- Gurm, HS, et al. The Impact of BMI on Short- and Long-Term Outcomes in Patients and Long-Term Outcomes in Patients Undergoing Coronary Revascularization. Undergoing Coronary Revascularization. JACCJACC. 2002; 39: 834-840. . 2002; 39: 834-840.

References Cont’dReferences Cont’d

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

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