SEVERE OBESITY ASSOCIATED WITH CARDIOVASCULAR

DECONDITIONING, HIGH PREVALENCE OF CARDIOVASCULAR

RISK FACTORS, DIABETES MELLITUS/HYPERINSULINEMIA,

AND RESPIRATORY COMPROMISE

SAMUEL S. GIDDING, MD, RODRIGO NEHGME, MD, CHARLES HEISE, AS, CAROL MUSCAR, BS,ANNIE LINTON, MS, AND SANDRA HASSINK, MD

Objective To determine the extent and severity of obesity-related cardiorespiratory morbidity in children with body mass

index (BMI) $40 kg/m2.

Study design Cross-sectional analysis of a cohort comprised of 48 boys and girls aged 8 to 17 years with BMI $40 kg/m2.

Cardiorespiratory fitness (graded cycle exercise test), left ventricular (LV) mass (echocardiography), blood pressure, fasting

lipid profile, fasting insulin, fasting glucose, HbA1c, and pulmonary function (spirometry and sleep studies) were measured.

Results The cohort averaged 14.2 ± 2 years of age with mean BMI of 45.5 kg/m2. Only 2 patients had normal fitness; 37 of 48

had peak oxygen consumption <20 mL O2/minute. Hypertension was present in 10 of 48 patients. Mean lipid values were:

triglycerides 103 ± 48 mg/dL, HDL cholesterol 41 ± 10 mg/dL, and LDL cholesterol 108 ± 26 mg/dL. Type II diabetes mellitus

was diagnosed in 6 patients. Mean fasting insulin was 31 ± 19 mU/mL. Asthma treatment, small airways disease by pulmonary

function testing, or both were present in 35 of 48 patients; upper airway obstruction was present in 7 patients. LV hypertrophy

was present in 8 patients, with a mean LV mass of 43 ± 11 g/m2.7.

Conclusions Children and adolescents with BMI $40 kg/m2 have substantial cardiorespiratory morbidity including severe

physical deconditioning. (J Pediatr 2004;144:766-9)

The obesity epidemic is associated with an increased prevalence of children and adolescents with a body mass index (BMI)$40 kg/m2. The association of poor physical fitness, cardiovascular risk factors, diabetes mellitus/insulin resistance, andrespiratory abnormalities with obesity is well recognized; however, the frequency and severity of cardiorespiratory

morbidity in the severely obese patient has not been assessed.1,2 Recent studies have suggested that adults with this degree ofobesity may have substantially reduced life expectancy, by as much as 15 to 20 years.3,4 A small but significant proportion ofmorbidly obese adults die of sudden cardiac death/congestive heart failure related tocardiomyopathy of obesity.5

The purpose of this study was to identify the prevalence of cardiorespiratorymorbidity in severely overweight children and adolescents by performing a completecardiac and respiratory evaluation in children and adolescents with BMI $40 kg/m2 whopresented to a specialized obesity management program. Evaluation included a gradedmaximal exercise stress test, pulmonary function and spirometry testing, echocardiography,sleep study, lipid profile, and assessment of hyperinsulinemia/diabetes mellitus. Prevalenceof cardiac, respiratory, and metabolic comorbidities was documented. There are few dataavailable to understand the extent of comorbidities and the medical care needs in youngerage groups presenting with this level of obesity.

From Nemours Cardiac Center andthe A. I. duPont Hospital for Children,Wilmington, Delaware; and theDepartment of Pediatrics, ThomasJefferson University, Philadelphia,Pennsylvania.Submitted for publication Dec 30, 2003;last revision received Feb 10, 2004;accepted Mar 17, 2004.

Reprint requests: Samuel S. Gidding,MD, Nemours Cardiac Center, 1600Rockland Rd, Wilmington, DE 19899.E-mail: sgidding@nemours.org.0022-3476/$ - see front matter

Copyrightª 2004 Elsevier Inc. All rightsreserved.

10.1016/j.jpeds.2004.03.043

BIPAP Biphasic positive airway pressureBMI Body mass indexLV Left ventricleLVIDd LV internal diameter, diastole

PWTd Posterior wall thickness, diastoleVO2 O2 consumptionVSTd Ventricular septal thickness, diastole

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METHODSForty eight children and adolescents from a specialized

center for the management of obesity were studied. The studyentry criterion was the presence of BMI $40 kg/m2. Thecohort represents approximately 80% of patients with BMI$40 kg/m2 currently being followed. All study childrenunderwent a complete laboratory evaluation of the cardiac andrespiratory systems. Review of medical records for this reportwas approved by the Institutional Review Board of the A. I.duPont Hospital for Children.

All study participants underwent a graded bicyclemaximal exercise test using a stationary ergometer (cycle)with increasing effort. The cycle allowed for adjustment of seatand handlebar for patient comfort. A study goal was to havethe knee at 5% flexion at full extension. Ramps were usually 20watts/minute; however, some children underwent 15- or 25-watt/minute protocols based on age and perceived level offitness before the start of the study (based on questionnaireadministered before the study). Height and weight weremeasured before the test. Blood pressure was measured by anautomated device, with the patient at rest, every 3 minutesduring exercise, at peak exercise, 1 minute into recovery, and at3-minute intervals thereafter. The arm-cuff size was selectedbased on patient arm size; most required a large adult or thighcuff. An electrocardiogram was continuously recorded, andheart rate was calculated from the tracings. Arrhythmias andthe presence of ST segment changes were noted. Continuousanalysis of expiratory gases was performed for assessment ofO2 consumption (VO2) and CO2 production. Values wereadjusted for body weight (kg). The respiratory quotient (Rvalue), used to assess achievement of a maximal effort definedas passing the metabolic (anaerobic) threshold and peak VO2,was measured. Values for critical measures were visualized onthe screen on a breath-by-breath basis and also were plottedfor review at the end of the study. Total work in watts wascalculated. Complete assessment for a full effort includedobservation of slopes of CO2 and O2 and heart rate at peakexercise, but only the R value was used in analyses. Pulmonaryfunction testing and spirometry were performed before andafter exercise. Albuterol was administered by nebulizer tothose whose tests, after exercise, suggested the presence ofsmall airways obstruction. Small airways disease was diagnosedif forced expiratory flow 25% to 75% values were < 85% ofpredicted. Sleep apnea (upper airway obstruction) was di-agnosed if a sleep study/polysomnogram demonstrated apneaof >20 seconds duration accompanied by chest wall movementconsistent with airway obstruction and an airway obstructionindex $1.0. Presence of hypoxemia and hypercarbia werenoted. Treatment with bronchodilators was consideredevidence of a prior diagnosis of asthma, and biphasic positiveairway pressure (BIPAP) treatment was considered equivalentto a positive sleep study.

Standard 2-D echocardiograms were performed ac-cording to American Society of Echocardiography protocols.Of particular interest was the calculation of left ventricular(LV) mass indexed for height ðLVmass½g� ¼ 0:80 3 1:04

Severe Obesity Associated with Cardiovascular Deconditioning,High Prevalence of Cardiovascular Risk factors, Diabetes Mellitus/Hyperinsulinemia, and Respiratory Compromise

½ðVSTdþ LVIDdþ PWTdÞ3 � ðLVIDdÞ3Þ þ 0:6�Þ and es-timation of right ventricular systolic pressure from tricuspidregurgitation velocity (VSTd = ventricular septal thickness indiastole, LVIDd = left ventricular diameter in diastole, andPWTd = posterior wall thickness in diastole).6 Left ventric-ular hypertrophy was diagnosed when LV mass exceeded51 g/m2.7. Elevated right ventricular pressure was diagnosed ifestimated pressure was >30 mm Hg. Technically inadequatestudies were present in 6 cases. Echocardiography datapresented are from 42 participants.

Fasting lipid profiles were obtained with measurementof total cholesterol, HDL cholesterol, and triglycerides ac-cording to the Centers for Disease Control and Preventionstandardized laboratory practices. Fasting insulin, glucose, andHbA1c were obtained in all patients, with a glucose tolerancetest performed in some when diabetes mellitus was suspected.All laboratory studies were obtained generally within 3months of the exercise test.

Cardiovascular risk abnormalities were consideredpresent if: (1) blood pressure exceeded the 95th percentilefor age/gender/height or antihypertensive treatment wasprescribed; (2) LDL cholesterol was $130 mg/dL; (3) HDLcholesterol was < 40 mg/dL; (4) triglycerides were$100mg/dL (those >200 mg/dL were assessed also); (5)American Diabetes Association criteria for diabetes mellituswere met; and (6) fasting insulin was $20 mg/dL in theabsence of diabetes mellitus.7-10

The medical chart was reviewed to identify noncardio-respiratory morbidities. Elevated liver enzymes with fat in-filtrates in the absence of other liver disease were presumednonalcoholic steatohepatitis.

Data Analysis

Descriptive statistics were calculated for all variables ofinterest. The prevalence of specific comorbidities was tabu-lated. Subgroup analyses, comparing by unpaired t test thosewho completed a maximal exercise test (R value $1.05) withthose who did not, were performed.

RESULTSThe cohort was comprised of 48 children and

adolescents with a mean age of 14.2 years (range, 8-17.6years); there were 26 girls and 22 boys. Average BMI was45.5 ± 4.3 kg/m2. Results of the graded exercise test arepresented in Table I, stratified by the presence of a maximal orsubmaximal effort. The rate of those achieving the anaerobicthreshold (26/48 [54%]) is well below that of leaner patientswho exercised for other indications in our laboratory, about80%. Those with a submaximal effort were younger, hada lower peak systolic blood pressure, a lower maximal VO2,and did substantially less work. Only 2 participants had a peakVO2 greater than 30 mLO2/minute; the remainder had valuesbelow the predicted average for age and gender and below thelower limit of normal, 25 mL O2/minute. Clinical historywas roughly consistent with exercise performance. The fewchildren engaging in regular exercise performed best, whereas

767

those who reported inability to walk more than a few blockswithout having to rest had the worst exercise tolerance. Therewere 2 patients who demonstrated T-wave inversion onelectrocardiogram; these patients had subsequent normalradionuclide perfusion scans.

Most patients had a respiratory abnormality. Upperairway obstruction/sleep apnea was diagnosed in 7 patients,with 1 receiving BIPAP. Asthma treatment was present in 27patients, small airways disease was present by pulmonary func-tion testing in 26 patients, and bothwere present in 18 patients.

Cardiovascular risk data are presented in Table II. Themean value for LV mass is just above the 80th percentile; 8participants had LV hypertrophy. Right ventricular pressure>30 mm Hg was present in 2 patients. Mean systolic bloodpressure was well above that expected for this age group; 10patients had elevated blood pressure or were taking antihy-pertensive medication. Dyslipidemia, particularly low HDLcholesterol, was common: 18 had HDL cholesterol < 40, 6had LDL cholesterol $130 mg/dL, and 22 had triglycerides$100 mg/dL, with 2 $200 mg/dL.

Insulin metabolism data also are presented in Table II.Mean fasting insulin concentration was abnormal for theentire cohort, with only 13 patients in the normal range. MeanHbA1c was at the upper limit of normal. There were 6 patientswith diabetes mellitus. Additional noncardiac or respiratorydiagnoses were frequent and included dysmenorrhea/poly-cystic ovary syndrome in 14 patients, behavior disorder/depression in 19 patients, nonalcoholic steatohepatitis in 5patients, and hypothyroidism in 2 patients.

DISCUSSIONObese children with BMI $40 presenting to a referral

center for clinical management have substantial cardiovascularand respiratory morbidity. Severe physical deconditioning,hyperinsulinemia, dyslipidemia, and respiratory abnormalitieswere present in the majority of patients. Hypertension, LVhypertrophy, and diabetes mellitus were present in 15% to20%. The average value for LV mass in this cohort is higherthan the value obtained in a recent series of children with

Table I. Results of graded exercise testing

R $1.05(n = 26)

R <1.05(n = 22)

Age (y)* 15.1 (1.3) 13.1 (2.1)BMI (kg/m2) 45.3 (4.5) 45.7 (4.2)Resting HR (beats/min) 88 (13) 88 (13)Resting SBP (mm Hg) 117 (12) 115 (11)Work (watts)* 163 (41) 112 (34)Peak VO2 (mL/kg/min)

* 19.2 (5.0) 14.9 (3.0)Peak HR (beats/min) 177 (13) 170 (14)Peak SBP (mm Hg)* 168 (27) 153 (20)

R, Respiratory quotient; HR, heart rate; SBP, systolic blood pressure.Data are given as mean (SD).*P < .05.

768 Gidding et al

chronic hypertension.11 Blood pressure and LV mass weredistributed at the upper limits of the normal range. These datasuggest that children and adolescents with BMI $40 kg/m2

require a complete cardiac, respiratory, and metabolicevaluation to identify comorbidities that may require phar-macologic as well as nonpharmacologic treatment.

The association of physical deconditioning with obesityis well known.4,12 However, children with BMI$40 kg/m2 inthis study had a level of deconditioning that is commonly seenin patients with congestive heart failure or other severeconditions that limit exercise performance. Although a pro-portion of our patients did not attain a maximal effort, it isunlikely that their value would have been normal witha maximal effort.

We find graded exercise testing important in individ-ualizing weight management treatment. Only a few personshad levels of exercise performance sufficient to begin a regularexercise program. Instead, most patients required a gradedapproach that began with walking as little as a few hundredyards a day with weekly increases in duration as tolerated.Regular physical activity/exercise is critical in the treatment oftype II diabetes mellitus, insulin resistance, hypertension, anddyslipidemia, as well as obesity.9,13 Completion of a maximalexercise test will allow for the appropriate prescription ofa physical activity program and will demonstrate to familiesthat properly supervised exercise is safe.

Performing exercise stress tests in severely obese patientsis not without limitations. First, overweight patients oftenhave low self-esteem and morale; this may lead to earlytermination of the test before achievement of the anaerobicthreshold and lack of a full effort, particularly in youngerchildren. Next, treadmill testing could not be used in thisgroup of obese patients because of the limitations posed by theweight limits of the equipment, the width of the treadmill belt,and the width of the safety handles. The patient’s weight alsomay restrict gait. A stationary ergometer provides a safealternative when the weight tolerance of this equipment is notexceeded. Adjustment of the apparatus, including seat height,maximizes patient comfort. Finally, in our exercise laboratory,a standard progressive incremental ramp protocol is routinely

Table II. Cardiovascular risk status

ObservedPrevalence of

abnormalities (n)

HR (beats/min) 88 (13) 6 $100 bpmBlood pressure (mm Hg) 116/73 (11/8) 10 hypertensiveTriglycerides (mg/dL) 103 (48) 22 $100 mg/dLHDL-C (mg/dL) 41 (10) 18 <40 mg/dLLDL-C (mg/dL) 108 (26) 6 $130 mg/dLInsulin (uU/mL) 31 (19) 29 $20 lU/mLHemoglobin A1C (%) 5.5 (0.5) 6 type 2 DMGlucose (mg/dL) 91 (13)

HR, Heart rate; HDL-C, high-density lipoprotein cholesterol; LDL-C,low-density lipoprotein cholesterol; DM, diabetes mellitus.

The Journal of Pediatrics � June 2004

based on patient weight but could not be applied in this groupbecause an enormous unrealistic increase in workload wouldhave occurred at each minute of the test. Higher incrementalramps may have led to less compliance with the protocolbecause of rapid leg fatigue. Instead, protocols were based onage with a ramp of 20 watts/minute selected for most patientsand 15 or 25 watts/minute selected occasionally based onpatient questionnaire.

A limitation of this study may be a selection bias towardchildren with increased morbidity as this is a referral pop-ulation.Most of the morbidities presented here are 2 to 6 timesmore common than in a lean cohort. Although the trueprevalence of comorbidities in children with BMI $40 kg/m2

is currently unknown, it is likely that any ‘‘unselected’’ series ofmorbidly obese children from the general population willdemonstrate a high rate of insulin resistance, unrecognizeddiabetes mellitus, treatable chronic lung disease, and a cardio-vascular risk factor distribution (particularly for blood pressure,LV mass, HDL cholesterol, and triglycerides) skewed at least1 standard deviation beyond the general population.

Almost half the children did not reach the metabolicthreshold, the definition used in this study for a completeeffort. For some children, a maximal effort is obtained at Rvalues lower than 1.05, and this may have been true in ourcohort as a few children approached maximal predicted heartrate for age, although for the group, peak heart rate and bloodpressure were significantly lower than for those who gave a fulleffort. Younger age was an important factor in not reachingthis threshold. We believed that, with one possible exception,this group also had severe deconditioning because peak oxygenconsumption at exercise cessation was very low and extrapo-lation of values at test cessation to a theoretical peak would stillproduce values generally < 20 mL/kg/minute.

Complete workup for associated cardiac, respiratory,and metabolic comorbidities is critical as many of these obesechildren and adolescents meet current indications for pharma-cologic management if they fail to respond to weight manage-ment. Types of therapy that may be considered in individualpatients include drugs directed at insulin resistance, antihyper-tensives, bronchodilators, BIPAP, lipid-lowering medica-tions, and, in girls, treatment to regulate the menstrualcycle.7-10,14,15

Children and adolescents with BMI$40 kg/m2 requirea complete cardiac, respiratory, and metabolic workup toidentify treatable comorbidities and to initiate individualizedtreatment programs that include regular exercise and physicalactivity. The majority of these children and adolescents havepoor cardiorespiratory functional capacity, limiting physicalactivity and enhancing risk for future weight gain.4,6,17 Eventhough outcomes from obesitymanagement are currently often

Severe Obesity Associated with Cardiovascular Deconditioning,High Prevalence of Cardiovascular Risk factors, Diabetes Mellitus/Hyperinsulinemia, and Respiratory Compromise

unsatisfactory, the possibility of success with remission ofcomorbidities should encourage physicians to keep trying.18,19

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