Clinical Implications of Obesity With Specific Focus on
A Statement for Professionals From the American Heart Association
Council on Nutrition, Physical Activity, and Metabolism
Endorsed by the American College of Cardiology Foundation
Samuel Klein, MD; Lora E. Burke, RN, MPH, PhD; George A. Bray, MD; Steven Blair, PED;
David B. Allison, PhD; Xavier Pi-Sunyer, MD; Yuling Hong, MD, PhD; Robert H. Eckel, MD
Abstract—Obesity adversely affects cardiac function, increases the risk factors for coronary heart disease, and is an
independent risk factor for cardiovascular disease. The risk of developing coronary heart disease is directly related to
the concomitant burden of obesity-related risk factors. Modest weight loss can improve diastolic function and affect the
entire cluster of coronary heart disease risk factors simultaneously. This statement from the American Heart Association
Council on Nutrition, Physical Activity, and Metabolism reviews the relationship between obesity and the cardiovas-
cular system, evaluates the effect of weight loss on coronary heart disease risk factors and coronary heart disease, and
provides practical weight management treatment guidelines for cardiovascular healthcare professionals. The data
demonstrate that weight loss and physical activity can prevent and treat obesity-related coronary heart disease risk
factors and should be considered a primary therapy for obese patients with cardiovascular disease. (Circulation. 2004;
Key Words: AHA Scientific Statements ? obesity ? cardiovascular diseases ? exercise ? diet
heart failure, stroke, and cardiac arrhythmias. Weight loss in
obese patients can improve or prevent many of the obesity-
related risk factors for CHD (ie, insulin resistance and type 2
diabetes mellitus, dyslipidemia, hypertension, and inflamma-
tion)1,2and can improve diastolic function.3Therefore, it is
important for cardiovascular healthcare professionals to un-
derstand the clinical effects of weight loss and be able to
implement appropriate weight-management strategies in
obese patients. The purpose of this statement is to review the
physiological and cardiovascular effects of weight loss and
provide clinicians with appropriate treatment guidelines for
weight management in patients with obesity and cardiovas-
besity is an important risk factor for coronary heart
disease (CHD), ventricular dysfunction, congestive
Clinical Effects of Weight Loss
The increase in body fat mass in most obese persons
represents primarily an increase in the size of fat cells,
although the number of fat cells may also be increased,
particularly in people with childhood-onset obesity.4In addi-
tion, the specific distribution of excess fat can influence the
relationship between obesity and cardiac disease. Excess
abdominal adipose tissue, particularly visceral fat, and excess
triglyceride content in liver, skeletal muscle, and heart tissues
are associated with hepatic and skeletal muscle insulin
resistance, impaired ventricular function, and increased
Although an energy deficit of ?3500 kcal is needed to
oxidize 1 lb of adipose tissue, a 3500-kcal energy deficit will
cause a ?1-lb loss in body weight because of the oxidation of
lean tissue and associated water losses. Approximately 75%
of weight lost by dieting is composed of fat and 25% is
fat-free mass (FFM).10The addition of exercise training to a
diet program can decrease the percentage of weight lost as
FFM by half.10,11Most, if not all, of the loss of fat results
from a decrease in the size (triglyceride content) of existing
fat cells,12not a decrease in the number of fat cells.13The
distribution of fat loss is heterogeneous, with greater relative
The American Heart Association makes every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside
relationship or a personal, professional, or business interest of a member of the writing panel. Specifically, all members of the writing group are required
to complete and submit a Disclosure Questionnaire showing all such relationships that might be perceived as real or potential conflicts of interest.
This statement was approved by the American Heart Association Science Advisory and Coordinating Committee on August 18, 2004. A single reprint
is available by calling 800-242-8721 (US only) or writing the American Heart Association, Public Information, 7272 Greenville Ave, Dallas, TX
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© 2004 American Heart Association, Inc.
Circulation is available at http://www.circulationaha.orgDOI: 10.1161/01.CIR.0000145546.97738.1E
AHA Scientific Statement
losses of intraabdominal fat than total body fat mass, partic-
ularly in men and women with increased initial intraabdomi-
nal fat mass.14In addition, diet-induced weight loss decreases
Intentional weight loss can improve or prevent many of the
obesity-related risk factors for CHD (ie, insulin resistance and
type 2 diabetes mellitus, dyslipidemia, hypertension, and
inflammation). Moreover, these metabolic benefits are often
found after only modest weight loss (?5% of initial weight)
and continue to improve in a monotonic fashion with increas-
ing weight loss.17
The metabolic syndrome represents a constellation of physi-
cal and metabolic abnormalities that are risk factors for
cardiovascular disease. The characteristics of this syndrome,
as defined by the National Cholesterol Education Program
(NCEP) Expert Panel on Detection, Evaluation, and Treat-
ment of High Blood Cholesterol in Adults (Adult Treatment
Panel III [ATP III]), include large waist circumference,
insulin-resistant glucose metabolism (impaired fasting glu-
cose, impaired glucose tolerance, and type 2 diabetes melli-
tus), dyslipidemia (high triglyceride and low serum HDL-C
[cholesterol] concentrations), and increased blood pressure.18
Patients who have the metabolic syndrome have a 1.5- to
3-fold increase in the risk of CHD and stroke.19–21Weight
loss can improve all features of the metabolic syndrome.17
Insulin Resistance and Type 2 Diabetes Mellitus
Insulin sensitivity, with regard to glucose metabolism, im-
proves rapidly after beginning an energy-deficit diet before
much weight loss occurs and continues to improve with
continued weight loss.22In patients with obesity and type 2
diabetes mellitus, a 5% weight loss at the end of 1 year of
dietary therapy can decrease fasting blood glucose, insulin,
hemoglobin A1cconcentrations, and the dose of oral hypo-
glycemic therapy,23whereas an average weight loss of ?30%
in extremely obese patients with diabetes after gastric bypass
surgery resulted in normalization of blood glucose and
glycosylated hemoglobin concentrations in 83% of patients.24
Weight loss can also prevent the development of new
diabetes in high-risk persons who are overweight or obese.25–28
Lifestyle dietary and activity modifications, which resulted in
modest (?5%) weight loss, decreased the 4- to 6-year
cumulative incidence of diabetes by ?50% in men and
women who were overweight or obese and had impaired
glucose tolerance.25,26The Swedish Obese Subjects (SOS)
Study demonstrated that greater weight losses (?16% of
body weight) induced by gastric surgery in patients who are
extremely obese (initial body mass index [BMI; weight in
kilograms divided by height in square meters] of 41 kg/m2)
were associated with a 5-fold decrease in the cumulative
incidence of diabetes for 8 years.27
Weight loss decreases serum LDL-C and triglyceride concen-
trations, whereas increases in serum HDL-C typically are
seen when weight loss is sustained.1,29,30The greatest relative
improvements in serum triglyceride and LDL-C usually occur
within the first 2 months of weight loss.31The beneficial
effects on serum lipids are related to the percentage of weight
lost, and regaining the lost weight leads to a relapse in serum
concentrations. A sustained weight loss of ?5% is needed to
maintain a decrease in serum triglyceride concentrations,
whereas serum total and LDL-C revert toward baseline if a
?10% diet-induced weight loss is not maintained.31,32In
contrast, data from the SOS study showed that an average
weight loss of 33% at 2 years after bariatric surgery decreased
serum triglyceride concentrations and increased serum
HDL-C concentrations, but it did not affect serum total
Weight loss decreases both systolic and diastolic blood
pressure in a dose-dependent fashion; therefore, greater
weight loss is generally associated with greater improvement
in blood pressure.33,34Weight regain results in a steady
increase in blood pressure toward baseline. The results of
retrospective analyses of large surgical group experiences
showed that marked weight loss induced by gastric surgery
improved or completely resolved hypertension in ?67% of
patients.35,36In contrast, data from the SOS study revealed
that on average blood pressure began to progressively in-
crease 2 years after surgery.27Most subjects enrolled in the
SOS study underwent vertical banded gastroplasty or gastric
banding procedures and lost less weight than those who
underwent gastric bypass. Subjects who had gastric bypass
surgery maintained a decrease in both systolic and diastolic
blood pressure for 5 years after surgery.37
Diet-induced weight loss can prevent the development of
hypertension in persons who are obese. The results from large
epidemiological studies and intervention trials suggest that
the risk of developing hypertension in normotensive women
is inversely correlated with changes in body weight.33,38Data
from the SOS study showed, however, that the beneficial
effect of gastric surgery-induced weight loss in preventing
new cases of hypertension disappeared 3 years after surgery,
despite persistent weight loss.27
Obesity is associated with altered pulmonary function. A
marked excess in abdominal fat mass can mechanically
interfere with lung function because of the increased weight
on the chest wall and thoracic cage. In addition, obesity is
associated with serious pulmonary diseases, obstructive sleep
apnea (OSA), and obesity hypoventilation syndrome (OHS).
OSA is characterized by multiple episodes of apnea and
hypopnea during sleep caused by partial or complete upper
airway obstruction. The interruption in nighttime sleep and
hypoxemia causes daytime sleepiness and cardiopulmonary
dysfunction. Episodes of oxygen desaturation during apnea
and hypopnea cause transient increases in pulmonary artery
and pulmonary wedge pressures, and myocardial perfusion
defects.39Over time, electrocardiographic abnormalities and
cardiac rhythm alterations, permanent pulmonary hyperten-
sion, right ventricle hypertrophy, and bilateral leg edema can
Klein et alClinical Implications of Obesity
OHS is caused by a decreased ventilatory response to
hypercapnia, hypoxia, or hypercapnia and hypoxia and inad-
equate respiratory muscle strength to meet the increased
ventilatory demand caused by the mechanical effects of
obesity. Patients with OHS have shallow and inefficient
breathing, and a pCO2?50 mm Hg. Patients may become
more symptomatic when lying down because abdominal
pressure pushes up the diaphragm, which increases intratho-
racic pressure and reduces respiratory capacity. Pickwickian
syndrome is a severe form of OHS and is associated with
extreme obesity, irregular breathing, cyanosis, somnolence,
and right ventricular dysfunction.
Obesity is associated with an increase in circulating inflam-
matory markers, including C-reactive protein (CRP)43–45and
cytokines (ie, interleukin-6 [IL-6], IL-18, and P-selec-
tin).46–49Adipose tissue itself is a likely source of these
excess cytokines,46,50and IL-6 stimulates the production of
CRP by the liver.51The increase in inflammatory markers is
associated with insulin resistance52–56and is an important
predictor of atherosclerotic events.57–61
Data from studies that have ranged in duration from 3
months to 2 years have revealed that weight reduction
decreases plasma CRP concentration.49,52,62–67The decrease
in CRP is directly related to the amount of weight loss, fat
mass, and change in waist circumference. In one study, only
subjects who were insulin resistant experienced a weight
loss–induced decrease in CRP, an effect that paralleled
changes in insulin sensitivity.52Plasma CRP concentrations
did not decrease and insulin sensitivity did not increase in
subjects who were insulin sensitive before weight reduction.
Decreases in plasma IL-6,48,49,65,67–69IL-18,49,67P-selectin,48
and tumor necrosis factor-?48concentrations have also been
reported66,68,69after weight loss in subjects who are obese.
Autonomic Nervous System Dysfunction
Overweight and obesity are associated with cardiac auto-
nomic neuropathy. For example, a 10% increase in body
weight is associated with a decline in parasympathetic tone
and an increase in heart rate.70Alterations in autonomic
nervous system function might be an important cause of
cardiovascular disease events and mortality, as suggested by
the relationship between heart rate and cardiovascular disease
mortality.71,72Marked weight loss induced by bariatric sur-
gery increases vagal activity.73In addition, weight loss
achieved by dieting also increases cardiac parasympathetic
activity,74–77but this increase is not maintained in the absence
of sustained weight loss.77
Although weight loss modifies many cardiovascular disease
(CVD) risk factors, it is not known whether weight reduction
decreases CVD events or CVD mortality in obese per-
sons.78–80This important question has not yet been answered
because it is difficult to achieve prolonged periods of sus-
tained weight reduction (eg, ?5 years) with nonsurgical
therapy81and to perform prospective randomized controlled
trials (RCTs) involving bariatric surgery. Data from the SOS
study showed that despite a greater reduction in weight and
CVD risk factors after surgical than medical therapy for
obesity, no difference in cardiovascular disease events or
mortality was found at 10 years.82
Data from large population studies have revealed that
obesity is associated with increased CVD mortality.83–87
Moreover, CVD death rates are directly related to BMI in
both men and women. The risk of CVD mortality in obese
persons who have a BMI ?35 kg/m2was 2 to 3 times the risk
among lean persons (BMI 18.5 to 24.9 kg/m2),88and a 30%
higher CHD mortality rate occurs for every 5-unit increment
of BMI.89In addition, overweight in adolescence is associ-
ated with a 130% increased risk of CHD mortality in
In general, data from large epidemiological studies have
shown that weight variability is associated with an increased
rate of CVD mortality.91The interpretation of the results from
these studies is complicated because many studies assessed
weight variability rather than weight loss, included large
numbers of lean and mildly overweight subjects, and included
subjects who experienced “unintentional” weight loss, which
may have been caused by diseases that influence mortality.
Therefore, the available data are not adequate to reliably
determine whether intentional weight loss affects CVD mor-
tality, and carefully designed RCTs are needed to address this
Cardiovascular Structure and Function
Obesity, particularly severe obesity, is associated with abnor-
malities in cardiac structure and function.8,92The severity of
these defects is associated with both the degree and duration
of obesity.93Obesity is associated with an increase in total
blood volume and cardiac output and a decrease in peripheral
vascular resistance.8,94In this setting, ventricular filling
pressures are elevated,95which eventually results in increased
wall stress, diastolic dysfunction, and left ventricular hyper-
trophy.93,96,98Abnormalities of the right heart can also occur
and may represent a combination of left heart disease,
recurrent pulmonary thromboemboli, and OSA or hypoven-
tilation or both.99Finally, lipomatous deposition in the
interatrial septum has also been described100; however, this
anatomic alteration is unlikely to contribute to cardiac
Weight loss, particularly in persons who are severely
obese, can improve cardiac structure and function.3,101Im-
provements in fractional shortening are associated with de-
creases in hypertension and left ventricular internal dimen-
sion with reduced atrial and left ventricular free and septal
wall thickness. Moreover, improvements in left ventricular
diastolic filling and ejection fraction also occur.102Improve-
ments in left ventricular mass occur in both normotensive and
hypertensive patients and are independent of the reduction in
blood pressure.103,104In addition, adding exercise to a low-
calorie diet (LCD) may produce greater benefits in cardiac
structure105,106; however, these benefits are not consistent
across all studies.107,108For example, substantial weight loss
(?15% of baseline)108and modest weight loss plus physical
training109did not have beneficial cardiac effects in obese
adolescents. At present, the potential benefits of weight loss
November 2, 2004
on cardiac function are not completely clear and require
Clinical Efficacy of Obesity Therapies
The goals of obesity therapy include decreasing body fat to
improve appearance, physical function, quality of life, and
medical health. Although surgical removal of large amounts
of subcutaneous adipose tissue (?20% of total body fat mass)
can improve a person’s appearance, ability to ambulate, and
quality of life, it does not improve the metabolic CHD risk
factors associated with obesity110; it seems that fat loss
induced by negative energy balance is necessary to achieve
metabolic benefits. Current therapies available for weight
management that cause weight loss by inducing a negative
energy balance include dietary intervention, physical activity,
pharmacotherapy, and surgery. Behavior modification to
enhance dietary and activity compliance is an important
component of all of these treatments.
Many different diets have been proposed for the treatment of
obesity. These dietary approaches vary in their total energy
prescription, macronutrient (fat, carbohydrate, and protein)
content, energy density, glycemic index, and portion control.
The energy content of a diet is the primary determinant of
weight loss. Very-low-calorie diets (VLCDs) provide ?800
kcal/d, LCDs usually contain 800 to 1500 kcal/d, and a
balanced-deficit diet usually provides ?1500 kcal/d. An LCD
usually causes an ?8% loss of body weight at ?6 months of
treatment. The results from clinical trials may not reflect the
experience in clinical practice because these trials involved
subjects who volunteered for a weight loss study and often
included formal behavior modification as part of the study
protocol. The use of a VLCD usually produces a weight loss
of ?15% to 20% within 4 months111–113; however, VLCDs
are associated with poorer weight loss maintenance and a
greater weight regain than are LCDs, so weight loss at 1 year
after treatment with a VLCD does not differ from treatment
with an LCD.113In addition, treatment with a VLCD may be
particularly problematic for patients with CHD because of the
risk of diet-induced hypokalemia, dehydration, and
The macronutrient composition of a diet does not affect the
rate of weight loss unless macronutrient manipulation influ-
ences total energy intake or expenditure. The Expert Panel on
the Identification, Evaluation, and Treatment of Overweight
and Obesity in Adults convened by the National Institutes of
Health/National Heart, Lung, and Blood Institute recom-
mended a 500- to 1000-kcal/d deficit diet for obese persons,
which will initially result in a weekly weight loss of 1 to 2 lb
(0.45 to 0.9 kg). It is often difficult, however, to accurately
determine a patient’s daily energy requirements. Therefore,
calorie-intake guidelines for a weight-loss diet have been
suggested based on a patient’s initial body weight (Table
1).114The calorie content of any prescribed diet must be
adjusted regularly, based on the patient’s weight-loss re-
sponse and treatment goals.
A low-fat diet is considered the standard approach for the
treatment of obesity.1Data from diet intervention studies
support the notion that decreasing fat intake, even while
allowing ad libitum intake of carbohydrates and proteins,
causes a spontaneous decrease in total energy intake and
weight loss.115In addition, a survey of obese persons who
were successful at maintaining long-term weight loss found
that they consumed ?25% of calories from fats.116However,
a recent systematic review of randomized controlled studies
that were specifically conducted to evaluate dietary therapy
for obesity found that weight loss induced by low-fat diets
and other weight-reducing diets were similar.117The compos-
ite of these data suggests that low-fat diets can enhance
weight loss and may be particularly useful in selected
persons, but they are not necessarily more effective than
The use of low-carbohydrate diets has become increasingly
popular. Several RCTs compared the effect of low-
carbohydrate, high-protein, high-fat diets (eg, the Atkins diet)
with a conventional low-fat diet (?30% energy from fats) in
adults118–123or a very-low-fat diet (?12% energy from fats)
in adolescents.124In all studies, weight loss at 3 and 6 months
in subjects randomized to the low-carbohydrate diet was ?2
times as great (?4- to 5-kg greater weight loss) as those
randomized to the low-fat group. In 2 studies that observed
patients for 1 year, weight loss at 1 year was not significantly
different between groups, however.121,122In general, these
studies also found the low-carbohydrate diet was more
beneficial in serum triglyceride and HDL-C concentrations as
compared with the low-fat diet, but the low-fat diet was more
beneficial in serum LDL-C concentration. Although these
changes in triglycerides and HDL-C after weight reduction on
low-carbohydrate diets appear favorable, it is not known
whether these alterations are associated with long-term ben-
eficial effects on CHD.125
The type of carbohydrate consumed also may be involved
in regulating energy intake, and a low glycemic index diet has
been proposed as a treatment for obesity. The glycemic index
refers to the increase in blood glucose that occurs after
consuming a fixed amount (usually 50 g) of available
carbohydrate from a test food relative to the increase in blood
glucose that occurs after consuming the same amount of
bread.126,127Most refined grain products and potatoes have a
high glycemic index, whereas most fruits, legumes, and
nonstarchy vegetables have a low glycemic index. The
glycemic response to a specific food that is ingested as part of
a meal can be altered by many factors, such as the method of
preparation and the effect of concomitantly ingested foods on
either glucose orwhite
Initial Reduced-Calorie Diet
Suggested Energy and Macronutrient Composition of
Body Weight, lb
Klein et al Clinical Implications of Obesity
intestinal motility. Data from a small (n?14) randomized
controlled 1-year trial conducted in overweight adolescents
revealed that a reduced glycemic index diet resulted in a
greater decrease in body weight and BMI than did a reduced-
fat diet.128The writing group is unaware of any RCTs
evaluating the effect of a low glycemic index diet on body
weight in adults.
The use of low-energy-density foods may be another
effective approach for treating obesity. The energy density of
a diet is defined as the calories present in a given weight of
food. A food’s energy density is directly correlated with its
fat content and inversely correlated with its water content.
Energy intake during a meal is partially regulated by the
weight of ingested food and is inversely correlated with
energy density.129Moreover, the results of a 6-month RCT
demonstrated that providing subjects with ad libitum low-fat
and low-energy-density foods causes modest (1% to 2%)
Portion control is an important aspect of reducing energy
intake. During ad libitum feeding, a direct relationship is
found between portion size served and intake; therefore,
increasing the size of the portion served increases the amount
of food consumed.131
Providing prepackaged prepared meals, either as frozen
entrees of mixed foods or liquid-formula meal replacements
improves portion control and can enhance weight loss. Data
from RCTs have shown that obese persons who were given
prepackaged prepared meals or liquid-formula meal replace-
ments lost several kilograms more weight than did those who
were randomized to a standard diet.132–134Educating patients
about food labels, recipe modification, restaurant ordering,
social eating, and healthy cooking methods are also important
to help patients understand portion size and energy intake
during meals and snacks.
In summary, the data from RCTs demonstrate that different
dietary interventions can cause short-term weight loss. At the
present time, we suggest that patients who are overweight or
obese and trying to lose weight consume a diet that induces an
energy deficit of 500 to 1000 kcal/d and has a macronutrient
composition that is known to reduce the risk of CVD. This
diet involves (1) consuming a variety of fruits, vegetables,
grains, low-fat or nonfat dairy products, fish, legumes,
poultry, and lean meats; (2) limiting intake of foods that are
high in saturated fat, trans-fatty acids, and cholesterol; and
(3) following the current dietary guidelines of the American
Heart Association135and the NCEP ATP III18(Table 2).
These recommendations may require modification, based on
the results of ongoing and future dietary therapy studies. The
key to successful weight management is to provide patients
with a dietary regimen that results in long-term compliance.
The available data suggest that it is unlikely that one
approach is appropriate for all patients.
Regular physical activity has important health benefits. A
consensus public health recommendation for physical activity
developed in the mid-1990s proposed that sedentary adults
should accumulate ?30 minutes of at least moderate-
intensity physical activity (eg, brisk walking) on most but
preferably all days of the week.136–138The health benefits of
30 minutes of daily moderate-intensity physical activity apply
to all persons. Data from several studies show that persons
who are overweight or obese and physically active (ie,
participate in ?30 minutes of moderate-intensity physical
activity most days of the week) or who have moderate to high
levels of cardiorespiratory fitness (ie, in the upper four fifths
of the age and sex fitness distributions) have much lower
death rates from cardiovascular disease and all-cause mortal-
ity than people who are sedentary and unfit.87,139–143There-
fore, regular physical activity may improve survival in
persons who are overweight or obese, independent of weight
Weight loss results from a negative energy balance, which
can be achieved by decreasing energy intake, increasing
energy expenditure, or both. It is usually much easier to
induce a daily energy deficit by restricting energy intake than
by increasing energy expenditure. The calories consumed
during physical activity can be estimated as a function of a
metabolic equivalent task (MET) score. One MET is the
energy consumed during resting conditions, such as television
viewing, and is equal to ?1 kcal/kg of body weight per hour.
Other activities such as carrying packages, doing housework
or gardening (2 to 5 METs), walking at a pace of 3 to 4 mph
(3 to 4 METs), and jogging (8 to 10 METs) consume greater
amounts of energy. A person weighing 90 kg would need to
walk briskly for 4 to 5 h/d to increase his or her energy
expenditure above resting metabolic rate by an amount that is
equivalent to reducing energy intake by 750 to 1000 kcal/d.
Therefore, it is difficult to lose a substantial amount of weight
through physical activity. A review of 19 studies with
randomized designs showed that exercise plus diet caused a
0.1-kg/wk greater weight loss than did diet alone.144Weight
loss induced by combining physical activity with diet de-
creases the loss of FFM that occurs when weight loss is
induced by diet alone.145
Data from observational studies strongly support the notion
that physical activity is critical for preventing weight re-
gain.145,146Moreover, the available evidence suggests that a
high volume of physical activity, 80 to 90 minutes of
moderate-intensity activity such as walking or 35 minutes of
vigorous activity such as jogging, is necessary to maintain
weight loss.145The interpretation of the results from these
Patients Who Are Overweight or Obese
Suggested Dietary Nutrient Composition for
Nutrient Recommended Intake
Monounsaturated fat ?20% of total calories
?10% of total calories
Total fat 25% to 35% or less of total calories
50% to 60% or more of total calories (complex
carbohydrates from a variety of vegetables, fruits,
?15% of total calories
?7% of total calories
November 2, 2004
studies is complicated because subjects who achieved suc-
cessful long-term weight loss had chosen to be physically
active and had not been randomized a priori to a high-volume
physical activity program. Data from a recent prospective
RCT revealed that high-volume physical activity did not
completely prevent weight regain.147Nonetheless, weight
regain after 6 months was smaller and total weight loss was
greater at 12 and 18 months in obese subjects who were
randomized to dietary and behavior therapy plus high-volume
physical activity (2500 kcal of energy expenditure per week)
than they were in persons randomized to dietary and behavior
therapy plus conventional physical activity (1000 kcal of
energy expenditure per week). Although it is in general
difficult to achieve long-term adherence to an exercise
program, several approaches have been used to enhance
adoption and maintenance of physical activity. Behavior-
intervention strategies originally developed for smoking ces-
sation or dietary programs have been used to increase
physical activity. One study showed comparable improve-
ments over 24 months in activity, fitness, and CHD risk
factors for participants who were randomly assigned to a
traditionally structured gymnasium-based program or to a
behaviorally based intervention.148Increased contact by mail
or telephone also helps maintain long-term adherence to
exercise.149Total exercise time during the course of a study is
greater when daily exercise is divided into multiple short
bouts (eg, 10-minute bouts 3 to 4 times per day) than one long
bout (eg, 30- to 40-minute bout once per day)150; ie, multiple
short bouts of exercise result in greater adherence to an
exercise program. In addition, many patients may be more
compliant with an exercise program conducted at home than
at a health club because fewer barriers are found with
home-based exercise, including costs and travel time. Devel-
oping a home-based walking program and using home exer-
cise equipment such as a treadmill has been shown to
improve exercise adherence and long-term weight loss.151,152
Finally, exercise does not need to be a structured activity.
Altering daily lifestyle activities (eg, walking instead of
riding, using stairs instead of escalators/elevators) may make
it easier to increase overall physical activity than would
participation in programmed exercise. In one study, weight
loss was similar after dietary therapy plus either lifestyle
activity or programmed exercise, but a trend toward better
maintenance of weight loss 1 year after treatment was
observed in individuals randomized to lifestyle activity than
to programmed exercise.153Although these strategies are a
welcome improvement, all studies still report a decline in
exercise adherence over time.148,149,151,154
In summary, physical activity is not an effective approach
for achieving initial weight loss, but it does have beneficial
effects on fitness and obesity-related complications such as
CHD and diabetes. In addition, a high level of regular
physical activity is important for preventing and attenuating
weight regain after diet-induced weight loss. Most data
suggest that it is the total volume of physical activity that is
important to weight management and that it does not matter
whether the activity is of moderate or vigorous intensity, a
lifestyle or structured program, or taken in a single bout each
day or in several intermittent bouts.
Behavior therapy focuses on analyzing and modifying eating
and activity behaviors that increase body weight and provides
techniques to help patients change their lifestyle habits and
overcome barriers to compliance. A summary of behavioral
strategies for treating obesity is shown in Table 3. The most
important principles of behavioral treatment are that it (1) is
goal-oriented and specifies goals that can be easily attained
and measured, (2) is process-oriented and helps patients
develop realistic goals and a reasonable plan for reaching
those goals, and (3) involves making small rather than large
changes so that incremental steps are taken to achieve larger
and more distant goals.155,156
Self-monitoring, the systematic observation and recording
of target behaviors, is the cornerstone of behavioral treat-
ment.156Self-monitoring tools include (1) food diaries in
which to record food intake, including types, amounts, energy
contents, and times, places, and feelings associated with
eating (usually in paper-and-pencil format but also available
on the Internet or in commercially available programs for use
on a personal digital assistant), (2) physical activity logs in
which to record the frequency, duration, and intensity of
exercise or step counters on which to monitor the daily steps
TABLE 3. Behavioral Strategies to Improve Weight Management
Self-monitoring Record “what, where, and when” of eating and
physical activity to increase patients’
awareness of their own behavior.
Set specific short-term targets in eating and
exercise habits to achieve incremental
Identify triggers associated with poor eating
and physical activity behaviors, and design
strategies to break link.
Change perceptions, thoughts, or beliefs
undermining weight control efforts, and help
patients develop realistic expectations about
Analyze situations preventing maintenance of a
healthier lifestyle and identify possible solutions
to problems; maintain philosophy that planning,
not willpower, is key to weight management.
Develop skills based on premise that lapses in
weight control behavior can be anticipated in
certain situations (eg, travel, celebrations, bad
Decrease psychological stress to prevent
Use rewards (tangible or verbal) to increase
performance of specific behaviors or when
specified goals reached.
Use assistance from family members and
friends in modifying lifestyle behaviors.
Maintain visits, telephone calls, or Internet
communication with physician and office staff
or other healthcare professionals to promote
adherence with recommended lifestyle
Klein et al Clinical Implications of Obesity
taken, and (3) weight scales on which to measure changes in
body weight. Self-monitoring increases patients’ awareness
of their behaviors, generates records that can be reviewed by
healthcare professionals, and provides targets for
In clinical practice, formal behavior therapy can be pro-
vided through group sessions or individual meetings with a
healthcare professional who is skilled in the delivery of
behavioral techniques used to modify lifestyle habits.155,157If
possible, contact should be regular, preferably once every 1 to
2 weeks, during the initial 6-month phase of a treatment
program.155Comprehensive group behavior therapy, in con-
junction with diet and physical activity, usually results in an
?9% body weight loss within 26 weeks of treatment (?0.5
kg/week).157Patients usually regain ?33% of their lost
weight in the year after ending behavior therapy, but most
still maintain a weight loss of ?5% at the end of 1 year.
Providing ongoing contact by scheduled visits, telephone
calls, food evaluation and exercise diaries, and Internet
communication can enhance long-term adherence and helps
prevent weight regain.158,159In addition, Internet-based treat-
ment programs for weight loss160,161and structured commer-
cial programs such as Weight Watchers162can augment the
professional guidance provided by the physician.
Pharmacotherapy can help selected patients lose weight. The
approved indications for drug therapy for obesity are a BMI
?30 kg/m2or a BMI between 27 and 29.9 kg/m2in conjunc-
tion with an obesity-related medical complication in patients
with no contraindications for therapy. Effective pharmaco-
therapy for obesity is likely to require long-term, if not
lifelong, treatment because patients who respond to drug
therapy usually regain weight when the therapy is stopped.
The expected length of drug treatment of obese patients who
respond to therapy makes it important to carefully consider
the long-term risks of being obese, the beneficial effects of
pharmacotherapy on body weight and obesity-associated
diseases, and the side effects and costs of treatment before
beginning therapy. In addition, pharmacotherapy alone is not
as effective as pharmacotherapy given in conjunction with a
comprehensive weight-management program.163Therefore,
patients given drug treatment without the other standard
approaches to weight management, including behavior mod-
ification, diet education, and activity counseling, are exposed
to all of the risks of drug treatment without all of the medical
Drug therapy adds a level of complexity to the treatment of
obesity. The patient with medication prescribed for obesity
may have comorbidities that already require pharmacother-
apy, thereby increasing the likelihood of nonadherence.164
Strategies to enhance medication compliance include regu-
larly assessing adherence and response to therapy, counseling
about and reinforcing the importance of adherence, simplify-
ing the treatment regimen, assisting the patient in reducing
barriers to adherence, providing reminders and cues to
facilitate improved adherence, and enlisting support when
needed.159,164–166In addition, weight loss drugs usually are
not covered by health insurance or health care plans, so a
considerable economic incentive exists for the obese
patient to discontinue taking these medications.
Medications for the treatment of obesity available in the
United States are listed in Table 4. Effective therapy for
obesity usually requires chronic intervention; however, only 2
drugs, sibutramine and orlistat, are approved for long-term
Sibutramine is a ?-phenethylamine derivative that blocks
the reuptake of norepinephrine, sibutramine, and, to a lesser
degree, dopamine. Sibutramine decreases food intake by
producing early satiety during feeding and by delaying
initiation of the next meal. Although sibutramine has no
potential for abuse, it is classified as a Schedule IV drug.
Sibutramine is available in 5-, 10-, and 15-mg doses; 10 mg/d
as a single daily dose is the recommended starting level, with
titration up or down based on response. Doses ?15 mg/d are
In a 1-year RCT, subjects treated with sibutramine lost 7%
of their initial body weight and those treated with placebo lost
2%. Of the subjects treated with sibutramine or placebo, 57%
and 20%, respectively, lost ?5% of their initial body weight;
34% and 7%, respectively, lost ?10% of their initial body
weight.167Weight loss with intermittent sibutramine therapy
(15 mg/d given during weeks 1 through 12, 19 through 30,
and 37 through 48, and placebo given during the two 6-week
periods when sibutramine was withdrawn) was equivalent to
weight loss with continuous sibutramine therapy (15 mg/
d).168Sibutramine therapy also has been shown to maintain
weight loss for 12 to 18 months in subjects who initially lost
weight by eating a VLCD163or who successfully lost weight
after 6 months of sibutramine treatment.170The use of
sibutramine in obese patients with either medication-
controlled hypertension171or type 2 diabetes mellitus172
causes greater weight loss than with placebo therapy, but the
overall weight loss is less than that observed in studies
conducted in subjects who do not have comorbid disease.
Weight loss with sibutramine therapy is more effective
when combined with behavior and dietary therapies. In a
1-year RCT, weight loss with sibutramine therapy alone was
?5 kg, with sibutramine therapy plus behavior modification
was ?10 kg, and with sibutramine therapy plus behavior
modification and a structured meal plan was ?15 kg.173
Side Effects and Safety
The most common side effects of sibutramine are dry
mouth, constipation, and insomnia. Sibutramine increases
TABLE 4. Drugs Approved by FDA for Treating Obesity
DEA indicates Drug Enforcement Agency.
November 2, 2004
heart rate (a dose of 10 to 15 mg/d causes an increase in heart
rate of 4 to 6 bpm) usually in the first few weeks of treatment
and lasts as long as the drug is taken. Sibutramine also causes
a dose-related increase in blood pressure (a dose of 10 to 15
mg/d causes an average increase in systolic and diastolic
blood pressure of 2 to 4 mm Hg) and can prevent weight
loss–induced decrease in blood pressure.155Therefore, careful
monitoring is needed when combining sibutramine with other
drugs that can increase blood pressure. Sibutramine should
not be used in patients who have uncontrolled hypertension,
a history of coronary artery disease, congestive heart failure,
cardiac arrhythmias, or stroke, or who are being treated with
monoamine oxidase inhibitors or selective serotonin reuptake
CVD Risk Factors
The composite data from RCTs demonstrate that sibutra-
mine causes improvements in serum triglyceride, total cho-
lesterol, LDL-C, and HDL-C concentrations that are directly
related to the magnitude of the weight loss. However,
sibutramine therapy decreases or eliminates weight loss–
induced benefits on blood pressure.
Orlistat blocks the digestion and absorption of dietary fat
by binding to intestinal lipases.174The percentage of fat that
is malabsorbed is related to drug dose in a curvilinear
fashion.175Near-maximal fat malabsorption occurs at a dose
of 120 mg when given with a meal, which causes malabsorp-
tion of ?30% of fat ingested from a meal that contains ?30%
of energy as fat. Less than 1% of ingested orlistat is absorbed;
therefore, it has no effect on systemic lipases.176
The effects of orlistat on body weight and CHD risk factors
have been evaluated in a large number of RCTs. The data
from most studies demonstrate that at 1 year, subjects who
were randomized to orlistat therapy (120 mg tid) lost ?8% to
10% of their initial body weight and those randomized to
placebo therapy lost ?4% to 6%.177–181Approximately 33%
more patients treated with orlistat lost ?5% of their body
weight than did those treated with placebo; ?2 times as many
patients treated with orlistat lost ?10% of their body weight
as did those treated with placebo. Ending orlistat therapy
results in weight regain,177,180and starting orlistat therapy
after successful diet-induced weight loss helps maintain body
weight.182In subjects with obesity and type 2 diabetes
mellitus who are treated with sulfonylureas,183metformin,184
or insulin,185the percentage who achieve a ?5% or ?10%
reduction in body weight is 2 to 3 times higher in those
receiving orlistat plus dietary therapy than it is in those
receiving dietary therapy alone. The overall weight loss effect
of orlistat therapy in patients with diabetes is less than that
reported in previous studies of obese patients who did not
have diabetes, however.
Recently, the results of a 4-year RCT were reported.28The
lowest body weight was achieved during the first year and
was greater in the orlistat-treated group (11% weight loss)
than in the placebo-treated group (6% weight loss). Subjects
regained weight during the remainder of the trial; orlistat-
treated subjects had lost 6.9% of their initial body weight and
placebo-treated subjects had lost 4.1% at the end of 4 years.
Orlistat therapy also decreased the cumulative 4-year inci-
dence of type 2 diabetes mellitus by 37%.
Side Effects and Safety
About 70% to 80% of subjects treated with orlistat
experienced ?1 gastrointestinal event as compared with
?50% to 60% of those treated with placebo. Gastrointes-
tinal events usually occurred early (within the first 4
weeks), were of mild or moderate intensity, were usually
limited to 1 or 2 episodes, and resolved despite continued
orlistat treatment. Approximately 4% of subjects treated
with orlistat and 1% of subjects treated with placebo
withdrew from the studies because of gastrointestinal
complaints. During treatment, small decreases in plasma
fat-soluble vitamins, particularly vitamins A, D, and E, can
occur, although plasma concentrations almost always re-
main within the reference range. A few patients, however,
may experience decreases in plasma vitamin concentra-
tions to below the reference range. Because it is impossible
to determine a priori which patients will need vitamin
supplements, it is recommended that all patients who are
treated with orlistat be given a daily multivitamin supple-
ment that is taken at a time when orlistat is not being
Orlistat can have medically significant effects on the
absorption of lipophilic medications if both drugs are taken
simultaneously. Subtherapeutic plasma cyclosporin levels
that occurred in organ transplant recipients after they began
orlistat therapy for obesity have been reported.186–189There-
fore, orlistat should not be taken for ?2 hours before or after
the ingestion of lipophilic drugs, and plasma drug concentra-
tions should be followed to ensure appropriate dosing. Or-
listat does not affect the absorption of selected drugs with a
narrow therapeutic index (warfarin, digoxin, phenytoin) and
selected drugs that are likely to be taken concomitantly with
orlistat (glyburide, oral contraceptives, furosemide, captopril,
nifedipine, and atenolol).189
CVD Risk Factors
Because of its weight loss effects, orlistat therapy
improves all major cardiovascular disease risk factors such
as blood pressure and insulin sensitivity. Moreover, data
from several RCTs suggest that orlistat has a beneficial
effect on serum cholesterol concentrations that is indepen-
dent of weight loss alone. Subjects given orlistat had a
greater reduction in serum LDL-C concentrations than
those given placebo, even after adjusting for percentage of
weight loss.178,179The mechanism responsible for this
additional lipid-lowering effect may be related to the effect
of orlistat in blocking both dietary cholesterol and triglyc-
eride absorption.190In contrast, orlistat is not as effective
in lowering serum triglyceride concentrations, presumably
because it increases the proportion of absorbed energy
derived from carbohydrate, which tends to increase serum
Phentermine is a ?-phenethylamine derivative that stimu-
lates the release of norepinephrine and dopamine from
nerve terminals. Although phentermine is not approved by
the Food and Drug Administration (FDA) for long-term
use, it is the most commonly prescribed anorexiant medi-
cation in the United States,192presumably because it is less
expensive than sibutramine. Phentermine was approved by
the FDA ?30 years ago, when the criteria needed for
approval were less rigorous than they are currently. There-
fore, fewer studies have evaluated the efficacy and safety
Klein et al Clinical Implications of Obesity
of phentermine therapy than have evaluated sibutramine
and orlistat. Only one long-term (36 weeks) RCT evaluated
the effect of phentermine therapy on body weight.193In
that study, obese women were randomized to dietary
therapy and treatment with daily phentermine, daily phen-
termine every other month alternating with daily placebo
every other month, or daily placebo. Of the 108 enrolled
subjects, approximately two thirds completed the study;
among those who completed the study, the groups that
received either continuous or intermittent phentermine
therapy lost ?13% of their initial weight as compared with
a 5% weight loss in the placebo group.
Side Effects and Safety
The most common side effects of phentermine are dry
mouth, insomnia, and constipation. Although all sympatho-
mimetic agents can increase blood pressure and heart rate,
these side effects are uncommon when weight loss is
Several different dietary supplements and herbal preparations
have been used to treat obesity, including chromium picoli-
nate, garcinia cambogia as a source of hydroxycitrate, chi-
tosan that is claimed to reduce fat absorption, phenylephrine
from Citrus aurantium (bitter orange), and ma huang as a
source of ephedra alkaloids with or without guarana as a
source of caffeine. In general, few RCTs have evaluated the
clinical efficacy of these agents, and most of the RCTs that
have been done were of substandard quality194–196; however,
data from several RCTs demonstrated greater weight loss in
subjects given herbal products that contain ephedra than in
those given placebo.197,198Nonetheless, the sale of ephedra in
over-the-counter products was recently banned by the FDA
because of concerns about serious adverse cardiovascular
Bariatric surgery is the most effective therapy available for
people who are extremely obese. The current indications for
surgical therapy were established at a consensus conference
held at the National Institutes of Health in 1991.199The panel
recommended that bariatric surgery be considered for obese
persons who have a BMI of 35.0 to 39.9 kg/m2plus ?1
severe obesity-related medical complication such as hyper-
tension, type 2 diabetes mellitus, heart failure, or OSA and
persons with a BMI ?40 kg/m2. At present, ?109 000
bariatric surgery procedures are performed each year in the
Five surgical procedures are most commonly used to
treat obesity: (1) gastric bypass (Roux-en-Y anastomosis),
(2) gastroplasty (gastric stapling, vertical banded gastro-
plasty, silastic ring gastroplasty), (3) gastric banding
(LAP-BAND), (4) biliopancreatic diversion (partial bilio-
pancreatic bypass), and (5) biliopancreatic diversion with
duodenal switch (partial biliopancreatic bypass with duo-
denal switch). Gastric bypass accounts for ?70% of the
bariatric operations performed in the United States. This
procedure involves the construction of a small (?20 mL)
proximal gastric pouch, which empties into a segment of
jejunum that is anastomosed to the pouch as a Roux-en-Y
limb. Gastroplasty involves the formation of a small pouch
along the lesser curvature near the gastroesophageal junc-
tion, which empties into the rest of the stomach through a
1-cm outlet stoma. Gastric banding involves the placement
of a band around the upper stomach. The band circumfer-
ence size can be changed by percutaneously inflating or
deflating a balloon in the band that is connected to a
subcutaneous port and is commonly adjusted after surgery
based on weight loss response and gastrointestinal symp-
toms. Biliopancreatic diversion involves the creation of a
200- to 500-mL proximal gastric pouch and transsection of
the small intestine 250 cm from the ileocecal valve; the distal
end of the small intestine is anastomosed to the gastric pouch
and the proximal limb anastomosed to the ileum 50 cm from the
ileocecal valve. These anastomoses create a 200-cm “alimentary
tract,” a variable length (300 to 500 cm) “biliary tract,” and a
50-cm “common tract” in which digestion and absorption of
ingested food occur. The biliopancreatic diversion with duode-
nal switch procedure involves the removal of ?60% of the
greater curvature of the stomach and transection of the proximal
duodenum. The proximal portion of the duodenum is anasto-
mosed end-to-end to the distal small intestine 250 cm proximal
to the ileocecal valve. The distal end of the resected proximal
intestine, which receives secreted pancreatic enzymes, is anas-
bariatric surgical procedures have been performed as open and
The approximate weight loss reported after each procedure
is shown in Table 5.114It is difficult to determine the relative
weight loss effectiveness of each procedure because only
vertical banded gastroplasty and gastric bypass have been
compared directly in RCTs.200–203The data from these RCTs
consistently revealed that weight loss was greater with the
gastric bypass procedure than with vertical banded gastro-
plasty. Fewer studies have evaluated the long-term effects of
gastric banding, biliopancreatic diversion, and biliopancreatic
diversion with duodenal switch than gastric bypass or gastro-
plasty because the procedure has been more recently devel-
oped or has been performed less often.
The perioperative mortality rate within 30 days after
open bariatric surgery is ?1%23,200,204,205but can vary
depending on the experience of the surgeon.206Approxi-
mately 75% of deaths are caused by anastomotic leaks and
peritonitis and 25% by pulmonary embolism. Laparoscopic
gastric bypass is associated with fewer wound complica-
Long-Term (>2 y) Body Weight
Effect of Different Bariatric Surgical Procedures on
Loss of Initial
Loss of Excess
Biliopancreatic diversion ?
November 2, 2004
tions, less postoperative pain, less blood loss, and shorter
hospital stays and convalescence periods than does the
open procedure207; however, late anastomotic strictures
occur more frequently after the laparoscopic than after the
The goal of weight loss therapy for patients with CVD is to
reduce or eliminate CHD risk factors and improve cardiac
function. Aggressive weight loss therapy could be harmful in
selected patients, such as those who have had a recent
myocardial infarction or stroke or who have unstable angina,
and attempts at weight loss should be delayed until these
patients are medically stable.
The physician’s office should be an environment that is
sensitive to the needs of obese patients. The waiting room
should contain chairs without arms, large gowns and large
blood pressure cuffs should be available, and a scale that can
weigh patients who weigh ?300 lb should be available and
located in a private area. The initial assessment should
include an appropriate history, physical examination, and
In addition to a standard medical interview, a patient’s
history should include an assessment of (1) weight history
(highest and lowest adult body weight, previous weight
loss attempts, weight pattern, and potential triggers and
social and environmental factors that contributed to weight
gain), (2) dietary history, including an assessment of types
and timing of meals and snacks and an attempt to identify
possible triggers that result in excessive energy intake, (3)
physical activity and function (daily and exercise activi-
ties, physical limitations, effect of obesity on physical
lifestyle), (4) obesity-related health risk (age of onset and
duration of obesity, family history of obesity and obesity-
related medical complications, current obesity-related dis-
ease), (5) possible psychiatric illnesses, such as binge
eating disorder and depression, that may require therapy
before a weight loss program is initiated, and (6) ability to
lose weight (desire to lose weight, weight loss goals and
expectations, limitations for achieving weight loss, includ-
ing medications and illnesses, lifestyle and work patterns,
financial resources, and special needs).
The patient’s BMI and waist circumference should be
determined. BMI is generally correlated with percentage of
body fat in a curvilinear fashion.208Some people with an
“obese” BMI, who have a normal amount of body fat and
a large muscle mass, are not at increased risk for CHD,
whereas people with a “normal” BMI, who have excessive
body fat and small muscle mass, are at increased risk.
Waist circumference, measured halfway between the last
rib and the iliac crest, correlates with abdominal fat mass.5
Table 6 provides a classification of risk based on BMI. A
waist circumference of ?88 cm (35 in) for women and
?102 cm (40 in) for men is associated with an increased
risk of metabolic diseases and CHD.1Additional assess-
ments should include measuring blood pressure with a
large cuff and searching for physical signs of right or left
ventricular dysfunction, congestive heart failure, and pul-
monary disease. An electronic stethoscope can increase a
physician’s ability to detect cardiac abnormalities in pa-
tients who are extremely obese.
An ECG is needed to check for evidence of CHD and to
obtain a baseline tracing for future comparisons. Standard
blood tests should be performed to search for CHD risk
factors, including prediabetes (impaired fasting blood
glucose or impaired glucose tolerance), dyslipidemia (in-
creased triglycerides, low HDL-C, and increased LDL-C),
and the metabolic syndrome. Additional studies may be
needed to further evaluate specific clinical suspicions
based on the history and physical examination, such as
TABLE 6. Weight Classification by BMI*
Obesity ClassBMI, kg/m2
III Extreme Obesity
*Data from Obes Res.1
Additional adiposity-related risk factors: waist circumference ?40 (in men)
and ?35 (in women); weight gain of ?5 kg since age 18–20 y.
TABLE 7. Weight Loss Treatment Guidelines*
BMI Category, kg/m2
Treatment 25.0–26.927.0–29.930.0–34.9 35.0–39.9
Diet, physical activity, behavior therapy, or all 3
With obesity-related disease
With obesity-related disease
*Data from Obes Res.1
†Pharmacotherapy should be considered only in patients who are not able to achieve adequate weight loss by available conventional lifestyle modifications and
who have no absolute contraindications for drug therapy.
‡Bariatric surgery should be considered only in patients who are unable to lose weight with available conventional therapy and who have no absolute
contraindications for surgery.
Klein et al Clinical Implications of Obesity
sleep studies to diagnose OHS or OSA and an exercise
treadmill test or electron beam computerized tomography
scanning or both to evaluate CHD risk. The comparative
value of exercise tolerance testing and electron beam
computerized tomography in obese subjects has not been
determined. Exercise treadmill testing is not recommended
for patients without cardiac symptoms, and neither exer-
cise treadmill testing nor electron beam computerized
tomography scanning should be performed in patients who
are at low risk for CHD, based on clinical judgment or
Framingham risk score.209–211
Appropriate management requires identifying patients who
need treatment, developing a realistic treatment plan, and
implementing a defined treatment strategy that can be
modified as needed during long-term surveillance. The
Practical Guide to the Identification, Evaluation, and
Treatment of Overweight and Obesity in Adults was
developed by the North American Association for the
Study of Obesity in conjunction with the National Heart,
Lung, and Blood Institute.212Suggested guidelines from
the guide for selecting among different weight loss treat-
ment options, based on disease risk, are shown in Table 7.
A typical clinical consultation involves a physician’s
giving advice without adequate consideration of the pa-
tient’s priorities, motivation, or confidence in undertaking
change.213In contrast, obesity therapy should involve
“patient-centered counseling,” which encourages patients
to set goals and express their own ideas for therapy, with
input from the healthcare professional. The treatment plan
also must take into account the patient’s readiness for
therapy and the patient’s ability to comply with the
proposed treatment plan. Realistic goals should be estab-
lished and frequent follow-up visits should be scheduled to
monitor progress, modify the treatment plan as needed, and
provide encouragement. Effective therapy requires a long-
term structured approach with continued support from the
physician and other caregivers, particularly during periods
of patient recidivism and weight regain.
Reducing energy intake is the cornerstone of weight
management therapy. Providing appropriate nutrition
counseling and the behavior modification therapy needed
to implement dietary changes within the setting of a busy
outpatient practice is difficult if not impossible for most
physicians because they do not have the time or expertise
to provide this kind of care. Therefore, referral to a
reputable weight loss program or experienced dietitian
should be considered, if these resources are available.
Additional therapy with weight loss medications or bari-
atric surgery can be useful in properly selected patients.
Member NameResearch Grant
Dr Samuel KleinTransneuronixMerckNoneObesity and Diabetes Educational Council
Takeda Pharmaceutical; Johnson&Johnson
Life Fitness International; Jenny Craig;
Bally Total Fitness Sports Medicine;
Sherbrooke Capital; Miavita; International
Life Sciences Institute Center for Health
Promotion; Healthetech; Westport Realty;
Air Canada; Archer Daniels Midland;
Coca-Cola; Cytodyne Technologies Inc;
Entelos; FTC; Fertin Pharma A/S; FDA;
Genome Explorations; Gibson, Dunn
&Crutcher LLP; International Food
Information Council; Kraft Foods; Ligand
Pharmaceuticals; Lilly Research Labs;
Lockheed Martin; Maynard, Cooper &
Gale, LLP; McKenna & Duneo, LLP;
Nutricia; NutriPharma; Parenti, Falk, Waas,
Hernandez & Cortina; Paterson,
MacDougall; Pinnacle; Rand Corporation;
Research Testing Laboratories; Rexall; RW
Johnson Pharmaceutical Research
Institute; United Soybean Board; United
States Postal Service; Veterans
Administration; Wilentz, Goldman &
Sanofi Synthelabo; Transneuronix; McNeil
Specialty Products; Roche; Lilly
Dr Lora E. Burke
Dr George Bray
Dr Steven N. Blair
Abbott Laboratories; Human
Kinetics; McNeil Consumer &
Specialty Pharmaceuticals, Inc;
Masterfoods; The Sugar
Dr David B. Allison Alabama Agricultural Land Grant
Alliance; Coca-Cola; General Mills;
Gerber Foundation; International
Life Sciences Institute;
M&M Mars; Merck; National
Alliance for Research on
Schizophrenia and Affective
Disorders; NIH; NSF; Ortho-McNeil
Pharmaceuticals; Pfizer Central
Research; Proctor & Gamble;
SlimFast Foods Company
American Oil Chemists
Society; Bristol Myers
Federation of American
Societies of Experimental
Biology; Health Learning
Systems; Institute for the
Dr Pi-Sunyer Novartis; Merck;
Dr Yuling Hong
Dr Robert Eckel
This table represents the relationships of writing group members that may be perceived as actual or reasonably perceived conflicts of interest as reported on the
Disclosure Questionnaire, which all members of the writing group are required to complete and submit.
November 2, 2004
1. Clinical Guidelines on the Identification, Evaluation, and Treatment of
Overweight and Obesity in Adults—The Evidence Report. National
Institutes of Health. Obes Res. 1998;6:51S–209S.
2. Sjostrom CD, Lissner L, Wedel H, Sjostrom L. Reduction in incidence
of diabetes, hypertension and lipid disturbances after intentional weight
loss induced by bariatric surgery: the SOS Intervention Study. Obes Res.
3. Alpert MA, Terry BE, Kelly DL. Effect of weight loss on cardiac
chamber size, wall thickness and left ventricular function in morbid
obesity. Am J Cardiol. 1985;55:783–786.
4. Salans LB, Cushman SW, Weismann RE. Studies of human adipose
tissue. Adipose cell size and number in nonobese and obese patients.
J Clin Invest. 1973;52:929–941.
5. Pouliot MC, Despres JP, Lemieux S, Moorjani S, Bouchard C, Tremblay
A, Nadeau A, Lupien PJ. Waist circumference and abdominal sagittal
diameter: best simple anthropometric indices of abdominal visceral
adipose tissue accumulation and related cardiovascular risk in men and
women. Am J Cardiol. 1994;73:460–468.
6. Krssak M, Falk Petersen K, Dresner A, DiPietro L, Vogel SM, Rothman
DL, Roden M, Shulman GI. Intramyocellular lipid concentrations are
correlated with insulin sensitivity in humans: a 1H NMR spectroscopy
study. Diabetologia. 1999;42:113–116.
7. Seppala-Lindroos A, Vehkavaara S, Hakkinen AM, Goto T,
Westerbacka J, Sovijarvi A, Halavaara J, Yki-Jarvinen H. Fat accumu-
lation in the liver is associated with defects in insulin suppression of
glucose production and serum free fatty acids independent of obesity in
normal men. J Clin Endocrinol Metab. 2002;87:3023–3028.
8. Alpert MA. Obesity cardiomyopathy: pathophysiology and evolution of
the clinical syndrome. Am J Med Sci. 2001;321:225–236.
9. Peterson LR, Waggoner AD, Schechtman KB, Meyer T, Gropler RJ,
Barzilai B, Davila-Roman VG. Alterations in left ventricular structure
and function in young healthy obese women: assessment by echocardi-
ography and tissue Doppler imaging. J Am Coll Cardiol. 2004;43:
10. Ballor DL, Poehlman ET. Exercise-training enhances fat-free mass pres-
ervation during diet-induced weight loss: a meta-analytical finding. Int
J Obes Relat Metab Disord. 1994;18:35–40.
11. Garrow JS, Summerbell CD. Meta-analysis: effect of exercise, with or
without dieting, on the body composition of overweight subjects. Eur
J Clin Nutr. 1995;49:1–10.
12. Knittle JL, Ginsberg-Fellner F. Effect of weight reduction on in vitro
adipose tissue lipolysis and cellularity in obese adolescents and adults.
13. Naslund I, Hallgren P, Sjostrom L. Fat cell weight and number before
and after gastric surgery for morbid obesity in women. Int J Obes.
14. Ross R, Rissanen J, Pedwell H, Clifford J, Shragge P. Influence of diet
and exercise on skeletal muscle and visceral adipose tissue in men.
J Appl Physiol. 1996;81:2445–2455.
15. Goodpaster BH, Theriault R, Watkins SC, et al. Intramuscular lipid
content is increased in obesity and decreased by weight loss. Metabo-
16. Tiikkainen M, Bergholm R, Vehkavaara S, Rissanen A, Hakkinen AM,
Tamminen M, Teramo K, Yki-Jarvinen H. Effects of identical weight
loss on body composition and features of insulin resistance in obese
women with high and low liver fat content. Diabetes. 2003;52:701–707.
17. Goldstein DJ. Beneficial health effects of modest weight loss. Int J Obes
Relat Metab Disord. 1992;16:397–415.
18. National Cholesterol Education Program (NCEP) Expert Panel on
Detection, Evaluation, and Treatment of High Blood Cholesterol in
Adults (Adult Treatment Panel III). Third Report of the National Cho-
lesterol Education Program (NCEP) Expert Panel on Detection, Eval-
uation, And Treatment of High Blood Cholesterol in Adults (Adult
Treatment Panel III) final report. Circulation. 2002;106:3143–3421.
19. Isomaa B, Almgren P, Tuomi T, Forsen B, Lahti K, Nissen M, Taskinen
MR, Groop L. Cardiovascular morbidity and mortality associated with
the metabolic syndrome. Diabetes Care. 2001;24:683–689.
20. Alexander CM, Landsman PB, Teutsch SM, Haffner SM; Third National
Health and Nutrition Examination Survey (NHANES III); National
Cholesterol Education Program (NCEP). NCEP-defined metabolic
syndrome, diabetes, and prevalence of coronary heart disease among
NHANES III participants age 50 years and older. Diabetes. 2003;52:
21. Lakka HM, Laaksonen DE, Lakka TA, Niskanen LK, Kumpusalo E,
Tuomilehto J, Salonen JT. The metabolic syndrome and total and car-
diovascular disease mortality in middle-aged men. JAMA. 2002;288:
22. Kelley DE, Wing R, Buonocore C, Sturis J, Polonsky K, Fitzsimmons
M. Relative effects of calorie restriction and weight loss in noninsulin-
dependent diabetes mellitus. J Clin Endocrinol Metab. 1993;77:
23. Wing RR, Koeske R, Epstein LH, Nowalk MP, Gooding W, Becker D.
Long-term effects of modest weight loss in type II diabetic patients.
Arch Intern Med. 1987;147:1749–1753.
24. Pories WJ, Swanson MS, MacDonald KG, Long SB, Morris PG, Brown
BM, Barakat HA, deRamon RA, Israel G, Dolezal JM, et al. Who would
have thought it? An operation proves to be the most effective therapy for
adult-onset diabetes mellitus. Ann Surg. 1995;222:339–350.
25. Tuomilehto J, Lindstrom J, Eriksson JG, Valle TT, Hamalainen H,
Ilanne-Parikka P, Keinanen-Kiukaanniemi S, Laakso M, Louheranta A,
Rastas M, et al. Finnish Diabetes Prevention Study Group. Prevention of
type 2 diabetes mellitus by changes in lifestyle among subjects with
impaired glucose tolerance. N Engl J Med. 2001;344:1343–1350.
26. Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM,
Walker EA, Nathan DM; Diabetes Prevention Program Research Group.
Reduction in the incidence of type 2 diabetes with lifestyle intervention
or metformin. N Engl J Med. 2002;346:393–403.
27. Sjostrom CD, Peltonen M, Wedel H, Sjostrom L. Differentiated
long-term effects of intentional weight loss on diabetes and hyper-
tension. Hypertension. 2000;36:20–25.
28. Torgerson JS, Hauptman J, Boldrin MN, Sjostrom L. XENical in the
prevention of diabetes in obese subjects (XENDOS) study: a ran-
domized study of orlistat as an adjunct to lifestyle changes for the
prevention of type 2 diabetes in obese patients. Diabetes Care. 2004;
29. Dattilo AM, Kris-Etherton PM. Effects of weight reduction on blood
lipids and lipoproteins: a meta-analysis. Am J Clin Nutr. 1992;56:
30. Eckel RH, Yost TJ. HDL subfractions and adipose tissue metabolism in
the reduced-obese state. Am J Physiol. 1989;256:E740–E746.
31. Wadden TA, Anderson DA, Foster GD. Two-year changes in lipids and
lipoproteins associated with the maintenance of a 5% to 10% reduction
in initial weight: some findings and some questions. Obes Res. 1999;7:
32. Rossner S, Bjorvell H. Early and late effects of weight loss on
lipoprotein metabolism in severe obesity. Atherosclerosis. 1987;64:
33. Effects of weight loss and sodium reduction intervention on blood
pressure and hypertension incidence in overweight people with high-
normal blood pressure. The Trials of Hypertension Prevention, phase II.
The Trials of Hypertension Prevention Collaborative Research Group.
Arch Intern Med. 1997;157:657–667.
34. Stevens VJ, Obarzanek E, Cook NR, Lee IM, Appel LJ, Smith West D,
Milas NC, Mattfeldt-Beman M, Belden L, Bragg C, et al. Long-term
weight loss and changes in blood pressure: results of the Trials of
Hypertension Prevention, phase II. Ann Intern Med. 2001;134:1–11.
35. Foley EF, Benotti PN, Borlase BC, Hollingshead J, Blackburn GL.
Impact of gastric restrictive surgery on hypertension in the morbidly
obese. Am J Surg. 1992;163:294–297.
36. Carson JL, Ruddy ME, Duff AE, Holmes NJ, Cody RP, Brolin RE. The
effect of gastric bypass surgery on hypertension in morbidly obese
patients. Arch Intern Med. 1994;154:193–200.
37. Sjostrom CD, Peltonen M, Sjostrom L. Blood pressure and pulse
pressure during long-term weight loss in the obese: the Swedish Obese
Subjects (SOS) Intervention Study. Obes Res. 2001;9:188–195.
38. Huang Z, Willett WC, Manson JE, Rosner B, Stampfer MJ, Speizer FE,
Colditz GA. Body weight, weight change, and risk for hypertension in
women. Ann Intern Med. 1998;128:81–88.
39. Orea-Tejeda A, Valencia-Flores M, Castillo-Martinez L, Rebollar-
Gonzalez V, Gonzalez-Barranco J, Castano A, Asensio E, Dorantes-
Garcia J, Sepulveda-Mendez J, Oseguera-Moguel J, et al. Abnormal
SPECT myocardial perfusion imaging during periods of obstructive
sleep apnea in morbid obese patients without known heart disease. Rev
Invest Clin. 2003;55:18–25.
40. Blankfield RP, Hudgel DW, Tapolyai AA, Zyzanski SJ. Bilateral leg
edema, obesity, pulmonary hypertension, and obstructive sleep apnea.
Arch Intern Med. 2000;160:2357–2362.
Klein et al Clinical Implications of Obesity
41. Valencia-Flores M, Orea A, Castano VA, Resendiz M, Rosales M,
Rebollar V, Santiago V, Gallegos J, Campos RM, Gonzalez J, et al.
Prevalence of sleep apnea and electrocardiographic disturbances in
morbidly obese patients. Obes Res. 2000;8:262–269.
42. Marrone O, Bonsignore MR. Pulmonary haemodynamics in obstructive
sleep apnoea. Sleep Med Rev. 2002;6:175–193.
43. Liuzzo G, Biasucci LM, Gallimore JR, Grillo RL, Rebuzzi AG, Pepys
MB, Maseri A. The prognostic value of C-reactive protein and serum
amyloid a protein in severe unstable angina. N Engl J Med. 1994;331:
44. Thompson G, Kienast J, Pyke SD, Haverkate F, van de Loo JC. Hemo-
static factors and the risk of myocardial infarction or sudden death in
patients with angina pectoris, European Concerted Action on
Thrombosis and Disabilities Angina Pectoris Study Group. N Engl
J Med. 1995;332:635–641.
45. Danesh J, Collins R, Appleby P, Peto R. Association of fibrinogen,
C-reactive protein, albumin, or leukocyte count with coronary heart
disease: meta-analyses of prospective studies. JAMA. 1998;279:
46. Mohamed-Ali V, Goodrick S, Rawesh A, Katz DR, Miles JM, Yudkin
JS, Klein S, Coppack SW. Subcutaneous adipose tissue releases
interleukin-6, but not tumor necrosis factor-alpha, in vivo. J Clin Endo-
crinol Metab. 1997;82:4196–4200.
47. Bastard JP, Jardel C, Bruckert E, Blondy P, Capeau J, Laville M, Vidal
H, Hainque B. Elevated levels of interleukin 6 are reduced in serum and
subcutaneous adipose tissue of obese women after weight loss. J Clin
Endocrinol Metab. 2000;85:3338–3342.
48. Ziccardi P, Nappo F, Giugliano G, Esposito K, Marfella R, Cioffi M,
D’Andrea F, Molinari AM, Giugliano D. Reduction of inflammatory
cytokine concentrations and improvement of endothelial functions in
obese women after weight loss over one year. Circulation. 2002;105:
49. Esposito K, Pontillo A, Ciotola M, Di Palo C, Grella E, Nicoletti G,
Giugliano D. Weight loss reduces interleukin-18 levels in obese women.
J Clin Endocrinol Metab. 2002;87:3864–3866.
50. Kern PA, Saghizadeh M, Ong JM, Bosch RJ, Deem R, Simsolo RB. The
expression of tumor necrosis factor in human adipose tissue. Regulation
by obesity, weight loss, and relationship to lipoprotein lipase. J Clin
51. Heinrich PC, Castell JV, Andus T. Interleukin-6 and the acute phase
response. Biochem J. 1990;265:621–636.
52. McLaughlin T, Abbasi F, Lamendola C, Liang L, Reaven G, Schaaf P,
Reaven P. Differentiation between obesity and insulin resistance in the
association with C-reactive protein. Circulation. 2002;106:2908–2912.
53. Hak AE, Stehouwer CD, Bots ML, Polderman KH, Schalkwijk CG,
Westendorp IC, Hofman A, Witteman JC. Associations of C-reactive
protein with measures of obesity, insulin resistance and subclinical
atherosclerosis in healthy, middle-aged women. Arterioscler Thromb
Vasc Biol. 1999;19:1986–1991.
54. Yudkin JS, Stehouwer CD, Emeis JJ, Coppack SW. C-reactive protein in
healthy subjects: associations with obesity, insulin resistance, and en-
dothelial dysfunction: a potential role for cytokines originating from
adipose tissue? Arterioscler Thromb Vasc Biol. 1999;19:972–978.
55. Lemieux I, Pascot A, Prud’homme D, Almeras N, Bogaty P, Nadeau A,
Bergeron J, Despres JP. Elevated C-reactive protein: another component
of the atherothrombotic profile of abdominal obesity. Arterioscler
Thromb Vasc Biol. 2001;21:961–967.
56. Festa A, D’Agostino R Jr, Howard G, Mykkanen L, Tracy RP, Haffner
SM. Chronic subclinical inflammation as part of the insulin resistance
syndrome: the Insulin Resistance Atherosclerosis Study (IRAS). Circu-
57. Kuller LH, Tracy RP, Shaten J, Meilahn EN. Relation of C-reactive
protein and coronary heart disease in the MRFIT nested case-control
study. Multiple Risk Factor Intervention Trial. Am J Epidemiol. 1996;
58. Ridker PM, Cushman M, Stampfer MJ, Tracy RP, Hennekens CH.
Inflammation, aspirin, and the risk of cardiovascular disease in
apparently healthy men. N Engl J Med. 1997;336:973–979.
59. Harris TB, Ferrucci L, Tracy RP, Corti MC, Wacholder S, Ettinger WH
Jr, Heimovitz H, Cohen HJ, Wallace R. Associations of elevated
interleukin-6 and C-reactive protein levels with mortality in the elderly.
Am J Med. 1999;106:506–512.
60. Ridker PM. High-sensitivity C-reactive protein: potential adjunct for
global risk assessment in the primary prevention of cardiovascular
disease. Circulation. 2001;103:1813–1818.
61. Ridker PM, Hennekens CH, Buring JE, Rifai N. C-reactive protein and
other markers of inflammation in the prediction of cardiovascular
disease in women. N Engl J Med. 2000;342:836–843.
62. Heilbronn LK, Noakes M, Clifton PM. Energy restriction and weight
loss on very low-fat diets reduce C-reactive protein concentrations in
obese, healthy women. Arterioscler Thromb Vasc Biol. 2001;21:
63. Tchernof A, Nolan A, Sites CK, Ades PA, Poehlman ET. Weight loss
reduces C-reactive protein levels in obese postmenopausal women. Cir-
64. Hanusch-Enserer U, Cauza E, Spak M, Dunky A, Rosen HR, Wolf H,
Prager R, Eibl MM. Acute-phase response and immunological markers
in morbid obese patients and patients following adjustable gastric
banding. Int J Obes Relat Metab Disord. 2003;27:355–361.
65. Kopp HP, Kopp CW, Festa A, Krzyzanowska K, Kriwanek S, Minar E,
Roka R, Schernthaner G. Impact of weight loss on inflammatory
proteins and their association with the insulin resistance syndrome in
morbidly obese patients. Arterioscler Thromb Vasc Biol. 2003;23:
66. Laimer M, Ebenbichler CF, Kaser S, Sandhofer A, Weiss H, Nehoda H,
Aigner F, Patsch JR. Markers of chronic inflammation and obesity: a
prospective study on the reversibility of this association in middle-aged
women undergoing weight loss by surgical intervention. Int J Obes Relat
Metab Disord. 2002;26:659–662.
67. Marfella R, Esposito K, Siniscalchi M, Cacciapuoti F, Giugliano F,
Labriola D, Ciotola M, Di Palo C, Misso L, Giugliano D. Effect of
weight loss on cardiac synchronization and proinflammatory cytokines
in premenopausal obese women. Diabetes Care. 2004;27:47–52.
68. Monzillo LU, Hamdy O, Horton ES, Ledbury S, Mullooly C, Jarema C,
Porter S, Ovalle K, Moussa A, Mantzoros CS. Effect of lifestyle mod-
ification on adipokine levels in obese subjects with insulin resistance.
Obes Res. 2003;11:1048–1054.
69. Bastard JP, Jardel C, Bruckert E, Vidal H, Hainque B. Variations in
plasma soluble tumour necrosis factor receptors after diet-induced
weight loss in obesity. Diabetes Obes Metab. 2000;2:323–325.
70. Hirsch J, Leibel RL, Mackintosh R, Aguirre A. Heart rate variability as
a measure of autonomic function during weight change in humans. Am J
71. Kannel WB, Kannel C, Paffenbarger RS Jr, Cupples LA. Heart rate and
cardiovascular mortality: the Framingham Study. Am Heart J. 1987;113:
72. Seccareccia F, Pannozzo F, Dima F, Minoprio A, Menditto A, Lo Noce
C, Giampaoli S; Malattie Cardiovascolari Aterosclerotiche Istituto
Superiore di Sanita Project. Heart rate as a predictor of mortality: the
MATISS project. Am J Public Health. 2001;91:1258–1263.
73. Karason K, Molgaard H, Wikstrand J, Sjostrom L. Heart rate variability
in obesity and the effect of weight loss. Am J Cardiol. 1999;83:
74. Arone LJ, Mackintosh R, Rosenbaum M, Leibel RL, Hirsch J.
Autonomic nervous system activity in weight gain and weight loss. Am J
75. Poirier P, Hernandez TL, Weil KM, Shepard TJ, Eckel RH. Impact of
diet-induced weight loss on the cardiac autonomic nervous system in
severe obesity. Obes Res. 2003;11:1040–1046.
76. Laaksonen DE, Laitinen T, Schonberg J, Rissanen A, Niskanen LK.
Weight loss and weight maintenance, ambulatory blood pressure and
cardiac autonomic tone in obese persons with the metabolic syndrome.
J Hypertens. 2003;21:371–378.
77. Rissanen P, Franssila-Kallunki A, Rissanen A. Cardiac parasympathetic
activity is increased by weight loss in healthy obese women. Obes Res.
78. Alexander JK. Obesity and coronary heart disease. Am J Med Sci.
79. Yang D, Fontaine KR, Wang C, Allison DB. Weight loss causes
increased mortality: cons. Obes Rev. 2003;4:9–16.
80. Fontaine KR, Allison DB. Does intentional weight loss affect mortality
rate? Eat Behav. 2001;2:87–95.
81. Miller WC, Koceja DM, Hamilton EJ. A meta-analysis of the past 25
years of weight loss research using diet, exercise or diet plus exercise
intervention. Int J Obes Relat Metab Disord. 1997;21:941–947.
82. Torgerson JS, Sjostrom L. The Swedish Obese Subjects (SOS) study—
rationale and results. Int J Obes Relat Metab Disord. 2001;25:S2–S4.
83. Allison DB, Fontaine KR, Manson JE, Stevens J, VanItallie TB. Annual
deaths attributable to obesity in the United States. JAMA. 1999;282:
November 2, 2004
84. Lee IM, Blair SN, Allison DB, Folsom AR, Harris TB, Manson JE,
Wing RR. Epidemiologic data on the relationships of caloric intake,
energy balance, and weight gain over the life span with longevity and
morbidity. J Gerontol A Biol Sci Med Sci. 2001;56:7–19.
85. Troiano RP, Frongillo EA Jr, Sobal J, Levitsky DA. The relationship
between body weight and mortality: a quantitative analysis of combined
information from existing studies. Int J Obes Relat Metab Disord.
86. Albert CM, Chae CU, Grodstein F, Rose LM, Rexrode KM, Ruskin JN,
Stampfer MJ, Manson JE. Prospective study of sudden cardiac death
among women in the United States. Circulation. 2003;107:2096–2101.
87. Stevens J, Cai J, Evenson KR, Thomas R. Fitness and fatness as
predictors of mortality from all causes and from cardiovascular disease
in men and women in the lipid research clinics study. Am J Epidemiol.
88. Calle EE, Thun MJ, Petrelli JM, Rodriguez C, Heath CW Jr. Body-mass
index and mortality in a prospective cohort of US adults. N Engl J Med.
89. Selmer R, Tverdal A. Body mass index and cardiovascular mortality at
different levels of blood pressure: a prospective study of Norwegian men
and women. J Epidemiol Community Health. 1995;49:265–270.
90. Must A, Jacques PF, Dallal GE, Bajema CJ, Dietz WH. Long-term
morbidity and mortality of overweight adolescents. A follow-up of the
Harvard Growth Study of 1922 to 1935. N Engl J Med. 1992;327:
91. Pamuk ER, Williamson DF, Madans J, Serdula MK, Kleinman JC,
Byers T. Weight loss and mortality in a national cohort of adults,
1971–1987. Am J Epidemiol. 1992;136:686–697.
92. Pascual M, Pascual DA, Soria F, Vicente T, Hernandez AM, Tebar FJ,
Valdes M. Effects of isolated obesity on systolic and diastolic left
ventricular function. Heart. 2003;89:1152–1156.
93. Alpert MA, Lambert CR, Panayiotou H, Terry BE, Cohen MV, Massey
CV, Hashimi MW, Mukerji V. Relation of duration of morbid obesity to
left ventricular mass, systolic function, and diastolic filling, and effect of
weight loss. Am J Cardiol. 1995;76:1194–1197.
94. Kasper EK, Hruban RH, Baughman KL. Cardiomyopathy of obesity: a
clinicopathologic evaluation of 43 obese patients with heart failure. Am J
95. Ku CS, Lin SL, Wang DJ, Chang SK, Lee WJ. Left ventricular filling in
young normotensive obese adults. Am J Cardiol. 1994;73:613–615.
96. Messerli FH. Cardiopathy of obesity—a not-so-Victorian disease.
N Engl J Med. 1986;314:378–380.
97. Deleted in proof.
98. Contaldo F, Pasanisi F, Finelli C, de Simone G. Obesity, heart failure
and sudden death. Nutr Metab Cardiovasc Dis. 2002;12:190–197.
99. Alpert MA, Hashimi MW. Obesity and the heart. Am J Med Sci.
100. Jornet A, Batalla J, Uson M, Mallol A, Reig J, Petit M. Lipomatous
hypertrophy of the interatrial septum: Diagnosis by transesophageal
echocardiography. Echocardiography. 1992;9:501–503.
101. Alaud-din A, Meterissian S, Lisbona R, MacLean LD, Forse RA.
Assessment of cardiac function in patients who were morbidly obese.
102. Karason K, Wallentin I, Larsson B, Sjostrom L. Effects of obesity and
weight loss on cardiac function and valvular performance. Obes Res.
103. MacMahon SW, Wilcken DE, Macdonald GJ. The effect of weight
reduction on left ventricular mass. A randomized, controlled trial in
young, overweight hypertensive patients. N Engl J Med. 1986;314:
104. Himeno E, Nishino K, Nakashima Y, Kuroiwa A, Ikeda M. Weight
reduction regresses left ventricular mass regardless of blood pressure
level in obese subjects. Am Heart J. 1996;131:313–319.
105. Wirth A, Kroger H. Improvement of left ventricular morphology and
function in obese subjects following a diet and exercise program. Int J
Obes Relat Metab Disord. 1995;19:61–66.
106. Hinderliter A, Sherwood A, Gullette EC, Babyak M, Waugh R, Geor-
giades A, Blumenthal JA. Reduction of left ventricular hypertrophy after
exercise and weight loss in overweight patients with mild hypertension.
Arch Intern Med. 2002;162:1333–1339.
107. Reid CM, Dart AM, Dewar EM, Jennings GL. Interactions between the
effects of exercise and weight loss on risk factors, cardiovascular hae-
modynamics and left ventricular structure in overweight subjects.
J Hypertens. 1994;12:291–301.
108. Archibald EH, Stallings VA, Pencharz PB, Duncan WJ, Williams C.
Changes in intraventricular septal thickness, left ventrical wall thickness
and left ventricular volume in obese adolescents on a high protein
weight reducing diet. Int J Obes. 1989;13:265–269.
109. Mitchell BM, Gutin B, Kapuku G, Barbeau P, Humphries MC, Owens
S, Vemulapalli S, Allison J. Left ventricular structure and function in
obese adolescents: relations to cardiovascular fitness, percent body fat,
and visceral adiposity, and effects of physical training. Pediatrics. 2002;
110. Klein S, Fontana L, Young VL, Coggan AR, Kilo C, Patterson BW,
Mohammed BS. Absence of an effect of liposuction on insulin action
and risk factors for coronary heart disease. N Engl J Med. 2004;350:
111. Ryttig KR, Flaten H, Rossner S. Long-term effects of a very low calorie
diet (Nutrilett) in obesity treatment. A prospective, randomized, com-
parison between VLCD and a hypocaloric diet?behavior modification
and their combination. Int J Obes Relat Metab Disord. 1997;21:
112. Wadden TA, Stunkard AJ. Controlled trial of very-low-calorie diet,
behavior therapy, and their combination in the treatment of obesity. J
Consult Clin Psychol. 1986;54:482–488.
113. Wadden TA, Foster GD, Letizia KA. One-year behavioral treatment of
obesity: comparison of moderate and severe caloric restriction and the
effects of weight maintenance therapy. J Consult Clin Psychol. 1994;
114. Klein S, Wadden T, Sugerman HJ. AGA technical review on obesity.
115. Astrup A, Grunwald GK, Melanson EL, Saris WH, Hill JO. The role of
low-fat diets in body weight control: a meta-analysis of ad libitum
dietary intervention studies. Int J Obes Relat Metab Disord. 2000;24:
116. Klem ML, Wing RR, McGuire MT, Seagle HM, Hill JO. A descriptive
study of individuals successful at long-term maintenance of substantial
weight loss. Am J Clin Nutr. 1997;66:239–246.
117. Pirozzo S, Summerbell C, Cameron C, Glasziou P. Advice on low-fat
diets for obesity. Cochrane Database Syst Rev. 2002;2:CD003640.
118. Skov AR, Toubro S, Ronn B, Holm L, Astrup A. Randomized trial on
protein vs carbohydrate in ad libitum fat reduced diet for the treatment
of obesity. Int J Obes Relat Metab Disord. 1999;23:528–536.
119. Brehm BJ, Seeley RJ, Daniels SR, D’Alessio DA. A randomized trial
comparing a very low carbohydrate diet and a calorie-restricted low fat
diet on body weight and cardiovascular risk factors in healthy women.
J Clin Endocrinol Metab. 2003;88:1617–1623.
120. Samaha FF, Iqbal N, Seshadri P, Chicano KL, Daily DA, McGrory J,
Williams T, Williams M, Gracely EJ, Stern L. A low-carbohydrate as
compared with a low-fat diet in severe obesity. N Engl J Med. 2003;
121. Foster GD, Wyatt H, Hill JO, McGuckin BG, Brill C, Mohammed BS,
Szapary PO, Rader DJ, Edman JS, Klein S. A randomized trial of a
low-carbohydrate diet for obesity. N Engl J Med. 2003;348:2082–2090.
122. Stern L, Iqbal N, Seshadri P, Chicano KL, Daily DA, McGrory J,
Williams M, Gracely EJ, Samaha FF. The effects of low-carbohydrate
versus conventional weight loss diets in severely obese adults: one-year
follow up of a randomized trial. Ann Intern Med. 2004;140:778–785.
123. Yancy WS Jr, Olsen MK, Guyton JR, Bakst RP, Westman EC. A
low-carbohydrate, ketogenic diet versus a low-fat diet to treat obesity
and hyperlipidemia: a randomized, controlled trial. Ann Intern Med.
124. Sondike SB, Copperman N, Jacobson MS. Effects of a low-carbohydrate
diet on weight loss and cardiovascular risk factor in overweight ado-
lescents. J Pediatr. 2003;142:253–258.
125. Bonow RO, Eckel RH. Diet, obesity, and cardiovascular risk. N Engl
J Med. 2003;348:2057–2058.
126. Jenkins DJ, Wolever TM, Taylor RH, Barker H, Fielden H, Baldwin JM,
Bowling AC, Newman HC, Jenkins AL, Goff DV. Glycemic index of
foods: a physiological basis for carbohydrate exchange. Am J Clin Nutr.
127. Wolever TM, Nuttall FQ, Lee R, Wong GS, Josse RG, Csima A, Jenkins
DJ. Prediction of the relative blood glucose response of mixed meals
using the white bread glycemic index. Diabetes Care. 1985;8:418–428.
128. Ebbeling CB, Leidig MM, Sinclair KB, Hangen JP, Ludwig DS. A
reduced-glycemic load diet in the treatment of adolescent obesity. Arch
Pediatr Adolesc Med. 2003;157:773–779.
129. Rolls BJ, Bell EA. Dietary approaches to the treatment of obesity. Med
Clin North Am. 2000;84:401–418.
Klein et alClinical Implications of Obesity
130. Saris WH, Astrup A, Prentice AM, Zunft HJ, Formiguera X, Download full-text
Verboeket-van de Venne WP, Raben A, Poppitt SD, Seppelt B, Johnston
S, et al. Randomized controlled trial of changes in dietary carbohy-
drate/fat ratio and simple vs complex carbohydrates on body weight and
blood lipids: the CARMEN study. The Carbohydrate Ratio Management
in European National diets. Int J Obes Relat Metab Disord. 2000;24:
131. Rolls BJ, Morris EL, Roe LS. Portion size of food affects energy intake
in normal-weight and overweight men and women. Am J Clin Nutr.
132. Jeffery RW, Wing RR, Thorson C, Burton LR, Raether C, Harvey J,
Mullen M. Strengthening behavioral interventions for weight loss: a
randomized trial of food provision and monetary incentives. J Consult
Clin Psychol. 1993;61:1038–1045.
133. Ditschuneit HH, Flechtner-Mors M, Johnson TD, Adler G. Metabolic
and weight-loss effects of long-term dietary intervention in obese
subjects. Am J Clin Nutr. 1999;69:198–204.
134. Flechtner-Mors M, Ditschuneit HH, Johnson TD, Suchard MA, Adler G.
Metabolic and weight loss effects of long-term dietary intervention in
obese patients: four-year results. Obes Res. 2000;8:399–402.
135. Krauss RM, Eckel RH, Howard B, Appel LJ, Daniels SR, Deckelbaum
RJ, Erdman JW Jr, Kris-Etherton P, Goldberg IJ, Kotchen TA, et al.
AHA Dietary Guidelines: revision 2000: A statement for healthcare
professionals from the Nutrition Committee of the American Heart
Association. Circulation. 2000;102:2284–2299.
136. Physical activity and cardiovascular health. NIH Consensus Devel-
opment Panel on Physical Activity and Cardiovascular Health. JAMA.
137. Pate RR, Pratt M, Blair SN, Haskell WL, Macera CA, Bouchard C,
Buchner D, Ettinger W, Heath GW, King AC, et al. Physical activity and
public health: a recommendation from the Centers for Disease Control
and Prevention and the American College of Sports Medicine. JAMA.
138. Physical Activity and Health: A Report of the Surgeon General. Atlanta,
Ga: U.S. Department of Health and Human Services, Centers for
Disease Control and Prevention, National Center for Chronic Disease
Prevention and Health Promotion, 1996. S/N 017-023-00196-5.
139. Blair SN, Brodney S. Effects of physical inactivity and obesity on
morbidity and mortality: current evidence and research issues. Med Sci
Sports Exerc. 1999;31:S646–S662.
140. Church TS, Cheng YJ, Earnest CP, Barlow CE, Gibbons LW, Priest EL,
Blair SN. Exercise capacity and body composition as predictors of
mortality among men with diabetes. Diabetes Care. 2004;27:83–88.
141. Lee CD, Jackson AS, Blair SN. US weight guidelines: is it also
important to consider cardiorespiratory fitness? Int J Obes Relat Metab
142. Lee CD, Blair SN, Jackson AS. Cardiorespiratory fitness, body compo-
sition, and all-cause and cardiovascular disease mortality in men. Am J
Clin Nutr. 1999;69:373–380.
143. Wei M, Kampert JB, Barlow CE, Nichaman MZ, Gibbons LW, Paffen-
barger RS Jr, Blair SN. Relationship between low cardiorespiratory
fitness and mortality in normal-weight, overweight, and obese men.
144. Wing RR. Physical activity in the treatment of the adulthood overweight
and obesity: current evidence and research issues. Med Sci Sports Exerc.
145. Saris WH, Blair SN, van Baak MA, Eaton SB, Davies PS, Di Pietro L,
Fogelholm M, Rissanen A, Schoeller D, Swinburn B, et al. How much
physical activity is enough to prevent unhealthy weight gain? Outcome
of the IASO 1st Stock Conference and consensus statement. Obes Rev.
146. Jakicic JM, Clark K, Coleman E, Donnelly JE, Foreyt J, Melanson E,
Volek J, Volpe SL; American College of Sports Medicine. American
College of Sports Medicine position stand. Appropriate intervention
strategies for weight loss and prevention of weight regain for adults.
Med Sci Sports Exerc. 2001;33:2145–2156.
147. Jeffery RW, Wing RR, Sherwood NE, Tate DF. Physical activity and
weight loss: dose prescribing higher physical activity goals improve
outcome? Am J Clin Nutr. 2003;78:684–689.
148. Dunn AL, Marcus BH, Kampert JB Garcia ME, Kohl HW III, Blair SN.
Comparison of lifestyle and structured interventions to increase physical
activity and cardiorespiratory fitness: a randomized trial. JAMA. 1999;
149. Castro CM, King AC, Brassington GS. Telephone versus mail inter-
vention for maintenance of physical activity in older adults. Health
150. Jakicic JM, Wing RR, Butler BA, Robertson RJ. Prescribing exercise in
multiple short bouts versus one continuous bout: effects on adherence,
cardiorespiratory fitness, and weight loss in overweight women. Int J
Obes Relat Metab Disord. 1995;19:893–901.
151. Jakicic JM, Winters C, Lang W, Wing RR. Effects of intermittent
exercise and use of home exercise equipment on adherence, weight loss,
and fitness in overweight women: a randomized trial.. JAMA. 1999;282:
152. Perri MG, Martin AD, Leermakers EA, Sears SF, Notelovitz M. Effects
of group- versus home-based exercise in the treatment of obesity. J
Consult Clin Psychol. 1997;65:278–285.
153. Andersen RE, Wadden TA, Bartlett SJ, Zemel BS, Verde TJ,
Franckowiak SC. Effects of lifestyle activity vs structured aerobic
exercise in obese women: a randomized trial. JAMA. 1999;281:335–340.
154. King AC, Taylor CB, Haskell WL, Debusk RF. Strategies for increasing
early adherence to and long-term maintenance of home-based exercise
training in healthy middle-aged men and women. Am J Cardiol. 1988;
155. Foreyt JP, Poston WS II. The role of the behavioral counselor in obesity
treatment. J Am Diet Assoc. 1998;98:S27–S30.
156. Wing RR. Behavioral approaches to the treatment of obesity. In: Bray
GA, Bouchard C, James WPT, eds. Handbook of Obesity. New York,
NY: Marcel Dekker; 1998:855–877.
157. Wadden TA, Sarwer DB, Berkowitz RI. Behavioural treatment of the
overweight patient. Baillieres Best Pract Res Clin Endocrinol Metab.
158. Perri MG, Nezu AM, Patti ET, McCann KL. Effect of length of
treatment on weight loss. J Consult Clin Psychol. 1989;57:450–452.
159. Perri MG, Shapiro RM, Ludwig WW, Twentyman CT, McAdoo WG.
Maintenance strategies for the treatment of obesity: an evaluation of
relapse prevention training and posttreatment contact by mail and
telephone. J Consult Clin Psychol. 1984;52:404–413.
160. Tate DF, Wing RR, Winett RA. Using Internet technology to deliver a
behavioral weight loss program. JAMA. 2001;285:1172–1177.
161. Tate DF, Jackvony EH, Wing RR. Effects of Internet behavioral coun-
seling on weight loss in adults at risk for type 2 diabetes: a randomized
trial. JAMA. 2003;289:1833–1836.
162. Heshka S, Anderson JW, Atkinson RL, Greenway FL, Hill JO, Phinney
SD, Kolotkin RL, Miller-Kovach K, Pi-Sunyer FX. Weight loss with
self-help compared with a structured commercial program: a ran-
domized trial. JAMA. 2003;289:1792–1798.
163. Wadden TA, Berkowitz RI, Sarwer DB, Prus-Wisniewski R, Steinberg
C. Benefits of lifestyle modification in the pharmacologic treatment of
obesity: a randomized trial. Arch Intern Med. 2001;161:218–227.
164. Haynes RB. Improving patient adherence: state of the art, with a special
focus on medication taking for cardiovascular disorders. In: Burke LE,
Ockene IS, eds. Compliance in Healthcare and Research. Armonk, NY:
Futura Publishing; 2001:3–21.
165. Simkin-Silverman L, Wing RR. Management of obesity in primary care.
Obes Res. 1997;5:603–612.
166. Stephenson BJ, Rowe BH, Haynes RB, Macharia WM, Leon G. The
rational clinical examination. Is this patient taking the treatment as
prescribed? JAMA. 1993;269:2779–2781.
167. Smith IG, Goulder MA; On behalf of the Members of the Sibutramine
Clinical Study 1047 Team. Randomized placebo-controlled trial of
long-term treatment with sibutramine in mild to moderate obesity. J Fam
168. Wirth A, Krause J. Long-term weight loss with sibutramine: a ran-
domized controlled trial. JAMA. 2001;286:1331–1339.
169. Deleted in proof.
170. James WP, Astrup A, Finer N, Hilsted J, Kopelman P, Rossner S, Saris
WH, Van Gaal LF. Effect of sibutramine on weight maintenance after
weight loss: a randomised trial. STORM Study Group. Sibutramine Trial
of Obesity Reduction and Maintenance. Lancet. 2000;356:2119–2125.
171. McMahon FG, Fujioka K, Singh BN, Mendel CM, Rowe E, Rolston K,
Johnson F, Mooradian AD. Efficacy and safety of sibutramine in obese
white and African American patients with hypertension: a 1-year,
double-blind, placebo-controlled, multicenter trial. Arch Intern Med.
172. Fujioka K, Seaton TB, Rowe E, Jelinek CA, Raskin P, Lebovitz HE,
Weinstein SP; Sibutramine/Diabetes Clinical Study Group. Weight loss
with sibutramine improves glycaemic control and other metabolic parame-
November 2, 2004