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LipidManagement is certified for CME credit
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Antonio
M. Gotto, Jr, MD, DPhil
Joan and Sanford I. Weill Medical
College of Cornell University |
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Elizabeth
Barrett-Connor, MD
University of California, San Diego,
School of Medicine
Peter Ganz, MD
Harvard Medical School
Brigham and Women's Hospital
Scott
M. Grundy, MD, PhD
University of Texas Southwestern
Medical Center at Dallas
Steven
M. Haffner, MD
University of Texas Health Science Center
Donald B. Hunninghake, MD
University of Minnesota Medical School

Ronald M. Krauss, MD
Lawrence Berkeley National Laboratory
University of California, Berkeley
John C. LaRosa, MD
SUNY Downstate Medical Center
Peter Libby, MD
Harvard Medical School
Brigham and Women's Hospital
Harry L. Metcalf, MD
SUNY/Buffalo School of Medicine and
Biomedical Sciences
Copyright © 2002 Thomson Professional Postgraduate Services®
(PPS), 150 Meadowlands Parkway, Secaucus, NJ 07094-2304
USA. All rights reserved.
This
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permission of PPS. LipidManagement is an
educational initiative of the National Lipid Education
Council™. NLEC, National Lipid Education Council and
LipidManagement are trademarks used herein under
license.
Supported by an unrestricted educational
grant from Pfizer Inc
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| Related
information on this website: |
In
the Slide Library section:
ATP
III: Nutritional Components of the TLC Diet
ATP
III: The Metabolic Syndrome
In
the Current Literature section:
Mediterranean
Diet, Traditional Risk Factors, and the Rate of Cardiovascular
Complications After Myocardial Infarction: Final Report
of the Lyon Diet Heart Study
de Lorgeril M, Salen P, Martin J-L, Monjaud I, Delaye
J, Mamelle N.
Circulation. 1999;99:779-785.
AHA Dietary
Guidelines; Revision 2000: A Statement for Healthcare
Professionals From the Nutrition Committee of the American
Heart Association
Krauss RM, Eckel RH, Howard B, et al.
Circulation. 2000;102:2296-2311. |
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Obesity and
Cardiovascular Disease
Excess
weight has serious repercussions on a person's healthbesides
compromising his or her cardiovascular health, this excess weight
increases the individual's risk for developing hypertension, type
2 diabetes, and several forms of cancer, among other disorders.
Today, more than half (55%61%) of the adults in the United
States are overweight or obese.1,2
By helping these patients to lose weight and improve their overall
conditioning, physicians can promote a reduction in their risk for
cardiovascular disease (CVD).
As defined by the National Institute of Diabetes and Digestive and
Kidney Diseases (NIDDK) of the National Institutes of Health (NIH),
overweight is excess body weight from muscle, bone, fat,
and/or body water, compared with set standards. Obesity refers
to an abnormally high proportion of body fat.2
The relation between obesity and CVD is complex.
Some studies indicate that it is an independent risk factor. However,
other studies have found that the association is weakened by multivariate
adjustment for the established risk factors of blood pressure (BP),
TC, HDL-C, and diabetes. In either caseindependent risk factor
or a cause of abnormalities directly linked to CVDobesity
contributes to cardiovascular morbidity and mortality.3
Syndrome Increases CHD Risk
Abdominal obesity is an underlying cause of the metabolic syndrome,
a cluster of disorders that work not merely additively, but synergistically,
to increase the risk of developing CVD (see "The
Metabolic Syndrome").4
This syndrome, which increases the risk for coronary heart disease
(CHD) at any LDL-C level, is also associated with "emerging risk
factors" (eg, prothrombotic/proinflammatory states) that are common
in obese persons but are not usually detected in a routine clinical
workup.3,5 The Third Report of
the Expert Panel on Detection, Evaluation, and Treatment of High
Blood Cholesterol in Adults (ATP III) identifies the metabolic syndrome
as a potential secondary target of risk-reduction therapy. Patients
with this syndrome require intensified treatment to reduce obesity,
increase physical activity, and correct associated lipid and nonlipid
risk factors.5
Definitions of Obesity, Overweight
Body mass index, or BMI, represents body weight relative to height,
and correlates strongly with total body fat content in adults. It
has become the new standard for defining overweight and obesity.
According to the NIH and the Centers for Disease Control and Prevention
(CDC), overweight is defined as a BMI of 25 to 29.9 kg/m2,
and obesity as a BMI of 30 kg/m2
or greater.6,7 BMI can be calculated
by dividing weight in pounds by height in inches squared, and then
multiplying the quotient by 703.7
According to a new analysis of the National Health and Nutrition
Examination Surveys (NHANES) III, BMI correlates positively with
BP and TC values, and inversely with HDL-C.8
Compared with their normal-weight counterparts, men in the highest
obesity category have more than twice the risk of hypertension,
hypercholesterolemia, or both, and women in the highest obesity
category have four times the risk.8
One study showed that, in young men (aged 15 to 34 years) who had
died of nonCVD-related causes, BMI was positively associated
with fatty streaks and raised atherosclerotic lesions in the right
coronary artery (RCA) and with microscopic lesion-grade atherosclerosis
and stenosis in the left anterior descending artery. The association
between BMI and raised lesions in the RCA was greater in young men
with central obesitya finding consistent with most other reports.9
Childhood and Adolescent Obesity
Perhaps one of the most alarming facets of the condition is the
toll obesity is taking on children. According to the NIDDK, the
proportion of overweight US children and adolescents has more than
doubled from the 1960s and 1970s to the period of 1988 to 1994:
from 5% to 11%.2,10 The CDC, using
data from NHANES II (19761980), III (19881994), and
as well as 1999 NHANES data, found similarly disturbing trends1:
The prevalence of overweight in both groups nearly doubled between
NHANES II (5%7%) and NHANES III (11%). By 1999, 13% of children
aged 6 to 11 years and 14% of those aged 12 to 19 years were overweight.
Children and adolescents of African-American or Latino background
have relatively greater rates of obesity.11
All of these overweight/obese youngsters are at increased risk for
developing heart disease in adulthood unless early intervention
is undertaken.
Diagnosis
The NIH Clinical Guidelines on the Identification, Evaluation, and
Treatment of Overweight and Obesity in Adults recommend that physicians
use BMI to assess overweight and obesity and to monitor body-weight
changes.7 Because some very muscular
individuals may meet criteria for being overweight without being
obese,2 physicians are advised
to check for another indicator of overweight or obesity: waist circumference
or waist-to-hip ratio (WHR; waist circumference divided by hip circumference).7
This is because excess abdominal fat, as opposed to excess fat deposited
on the hips and/or thighs, is an independent predictor of risk factors
and disorders associated with obesity.6
One study showed that, in middle-aged men, abdominal obesitymore
than overall obesitywas an independent risk factor for the
development of CHD.12
For persons with a BMI of 25 to 34.9 kg/m2,
a waist circumference of greater than 40 inches in men or greater
than 35 inches in women is considered to increase the relative risk
of developing obesity-related risk factors.7
(These values should be decreased in persons who are under 5 feet
tall.13) A WHR of 1.0 or higher
signifies added risk.13
Obese individuals' CVD risk is exacerbated by
presence of the following7:
 |
established CHD, other atherosclerotic disease, type 2 diabetes,
sleep apnea |
 |
cigarette smoking, hypertension, high LDL-C (>160
mg/dL), low HDL-C (<35 mg/dL), impaired fasting glucose (110125
mg/dL), family history of premature CHD |
 |
sedentary lifestyle |
 |
serum TG exceeding 200 mg/dL |
Management
According to the NIH guidelines, the initial goal of weight-loss therapy
is to reduce body weight by about 10% over a 6-month period.7
Lifestyle modifications. To achieve this
goal, persons with a BMI of 27 to 35 kg/m2
should reduce caloric intake by 300 to 500 kilocalories (kcal) per
day, and those with a BMI above 35 kg/m2,
by 500 to 1,000 kcal.7 Once a 10%
weight reduction is attained, further weight loss can be attempted
if needed. Weight loss and weight maintenance are best accomplished
by a program incorporating dietary therapy, exercise, and behavior
therapy, all of which must be continued indefinitely.
Regular physical activity not only enhances the
weight-loss process but also helps to prevent weight regain. It also
helps to reduce CVD risk beyond the reduction produced by weight loss
alone.7 Most obese patients should
initiate exercise programs slowly (walking or swimming at a slow pace
for about 30 minutes 3 times per week) and gradually increase the
intensity, duration, and frequency of the activity (to about 45 minutes
of faster walking at least 5 days per week). A maintenance goal would
be 30 minutes of moderate-intensity exercise nearly every day of the
week.
Pharmacotherapy. Candidates for adjunctive
use of antiobesity drugs include patients with a BMI of 30 kg/m2
or greater and no concomitant diseases, or those with a BMI of 27
to 29.9 kg/m2 who have concomitant
hypertension, dyslipidemia, CHD, type 2 diabetes, and/or sleep apnea.7
Two drugs, orlistat and sibutramine, are approved
for long-term treatment of obesity.4
Three large, randomized, double-blind trials showed that orlistat,
a lipase inhibitor, was significantly superior to placebo in effecting
weight loss (9% mean loss after 1 year vs 5% with placebo) and in
preventing weight regain.14 In addition,
orlistat users experienced significant reductions in five obesity-related
risk factors: hypertension, hyperglycemia, hypercholesterolemia, hyperinsulinemia,
and larger-than-normal waist circumference. Of interest, in these
three trials and in a similar, more recent investigation, TC and LDL-C
reductions in orlistat users were independent of weight loss.14,15
Sibutramine inhibits reuptake of norepinephrine, serotonin, and, to
a lesser extent, dopamine, in the central nervous system. Clinical
trials have shown that sibutramine use produces a dose-dependent 5%
to 10% decrease in body weight.4
Sibutramine use has also been associated with favorable changes in
CVD risk factors, including plasma lipids, uric acid, and glucose.4
However, it also exerts hypertensive and tachycardic effects, and
should not be used in patients with hypertension, CHD, heart failure,
arrhythmia, or stroke.14
Sympathomimetics such as phentermine suppress the
appetite by stimulating release of norepinephrine and dopamine. Phentermine
is indicated only for short-term treatment of obesity and should not
be prescribed for patients with hypertension or CVD because it may
raise BP. With a chemical structure related to that of amphetamines,
phentermine may also be addictive.14
In some patients, weight loss may not be sufficient
to modify their CVD risk profiles substantially, or they may have
multiple risk factors (eg, the metabolic syndrome), requiring a multifaceted
approach. Thus, physicians will need to determine on a case-by-case
basis whether treatment with lipid-lowering, antihypertensive, and/or
hypoglycemic drugs may be indicated. One recent study conducted in
52 viscerally obese men with dyslipidemia and insulin resistance showed
that those who received atorvastatin for 6 weeks experienced significant
reductions in TG, TC, LDL-C, remnant-like particle-cholesterol, apolipoprotein
B, and apolipoprotein C-III, as well as a significant increase in
HDL-C.16
Conclusion
Strong evidence from randomized controlled trials suggests that weight
loss produced by lifestyle modifications in overweight/obese individuals
reduces BP, improves lipid profiles (ie, reduces serum TG and increases
HDL-C levels, with some reductions in TC and LDL-C levels), and improves
blood glucose levels (ie, in persons without diabetes and in some
with type 2 diabetes). Pharmacologic intervention should be considered
for those who do not show adequate responses to nondrug therapies,
although medicine-induced weight loss may be less effective than diet-related
weight reduction in modifying lipid levels.7
References
| 1. |
Centers for Disease Control and
Prevention. National Health and Nutrition Examination Survey.
1999. Available at: www.cdc.gov. Accessed August 8, 2002. |
| 2. |
National Institute of Diabetes
and Digestive and Kidney Diseases. Statistics Related to
Overweight and Obesity. www.niddk.nih.gov. Accessed August
8, 2002. |
| 3. |
Grundy SM. Obesity, metabolic
syndrome, and coronary atherosclerosis. Circulation.
2002;105:2696-2698. |
| 4. |
Giles T. Reducing the risk of
cardiovascular events through weight loss. CME article available
at: www.medscape.com/ viewprogram/1870_pnt. Accessed August
8, 2002. |
| 5. |
Expert Panel on Detection, Evaluation,
and Treatment of High Blood Cholesterol in Adults. Executive
summary of the third report of the National Cholesterol Education
Program (NCEP) expert panel on detection, evaluation and treatment
of high blood cholesterol in adults (Adult Treatment Panel III).
JAMA. 2001;285:2486-2497. |
| 6. |
National Research Council. Diet
and Health: Implications for Reducing Chronic Disease Risk.
Washington, DC: National Academy Press. 1989:114. |
| 7. |
Clinical Guidelines on the
Identification, Evaluation, and Treatment of Overweight and
Obesity in Adults. Bethesda, Md: US Department of Health
and Human Services, Public Health Service, NIH, NHLBI. 1998.
Available at: www.nhlbi.nih.gov. Accessed August 8, 2002. |
| 8. |
National Institutes of Health.
National Heart, Lung, and Blood Institute. First federal obesity
clinical guidelines released. NIH News Release. June
17, 1998. |
| 9. |
McGill HC Jr, McMahan CA, Herderick
EE, et al, for the Pathobiological Determinants of Atherosclerosis
in Youth (PDAY) Research Group. Obesity and atherosclerosis
in youth. Circulation. 2002;105:2712-2718. |
| 10. |
Troiano RP, Flegal KM. Overweight
children and adolescents: description, epidemiology, and demographics.
Pediatrics. 1998;101(3 suppl):497-504. |
| 11. |
Williams CL, Hayman LL, Daniels
SR, et al. Cardiovascular health in childhood: a statement for
health professionals from the Committee on Atherosclerosis,
Hypertension, and Obesity in the Young (AHOY) of the Council
on Cardiovascular Disease in the Young, American Heart Association.
Circulation. 2002;106:143-160. |
| 12. |
Lakka HM, Lakka TA, Tuomilehto
J, Salonen JT. Abdominal obesity is associated with increased
risk of acute coronary events in men. Eur Heart J. 2002;23:706-713. |
| 13. |
Centers for Disease Control and
Prevention. Basics About Overweight and Obesity. Available
at: www.cdc.gov. Accessed August 8, 2002. |
| 14. |
Campbell ML, Mathys ML. Pharmacologic
options for the treatment of obesity. Am J Health-Syst Pharm.
2001;58:1301-1308. Available at: www.medscape.com/ viewarticle/406986_print.
Accessed August 8, 2002. |
| 15. |
Kolanowski ME, Scheen A, Van Gaal
L, for the ObelHyx Study Group. The effects of orlistat on weight
and on serum lipids in obese patients with hypercholesterolemia:
a randomized, double-blind, placebo-controlled, multicentre
study. Int J Obes Relat Metab Disord. 2001;25:1713-1721. |
| 16. |
Chan DC, Watts GF, Mori TA, et
al. Factorial study of the effects of atorvastatin and fish
oil on dyslipidaemia in visceral obesity. Eur J Clin Invest.
2002;32:429-436. |
This article was reviewed for medical accuracy by
Antonio M. Gotto, Jr, MD, DPhil, chairman of the National Lipid Education
Council™. Dr Gotto has indicated a financial interest or affiliation
as noted: retained as a consultant for AstraZeneca, Bayer Corporation,
Bristol-Myers Squibb Company, Merck & Co., Inc., Pfizer Inc, and Reliant
Pharmaceuticals.
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