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Obesity and Cardiovascular Disease
Paul Poirier, MD, PhD, FRCPC, and Robert H. Eckel, MD
Address
Institut Universitaire de Cardiologie et de Pneumologie, Hôspital Laval,
2725 Chemin Sainte-Foy, Sainte-Foy, Québec G1V 4G5, Canada.
Current Atherosclerosis Reports 2002, 4:448–453
Current Science Inc. ISSN 1523–3804
Copyright © 2002 by Current Science Inc.
Introduction
Calorie imbalance, in part due to excess calorie con-
sumption, is related to a rising prevalence of obesity. Popu-
lations of industrialized countries are becoming more
overweight as a result of changes in lifestyle, and obesity
may well become the most common health problem of the
21st century [1,2,3•]. Obesity is a major contributor to
the prevalence of cardiovascular disease (CVD) in the
developed world, and yet has only recently been afforded
the same level of attention as other risk factors of coronary
artery disease (CAD).
It was recently stated by the Public Health Approaches
to the Prevention of Obesity (PHAPO) working group
of the International Obesity Task Force (IOTF) that "In
every country in the world today, depending on its stage of
epidemiologic transition, chronic non-communicable
diseases such as CVD, cancer, diabetes, and osteoporosis
are either newly appearing, rapidly rising, or already estab-
lished at high levels" [3•]. Thus, obesity is a major con-
tributor to the global burden of disease and disability
because it is a risk factor for numerous medical conditions
such as heart disease, diabetes, hypertension, stroke, pul-
monary emboli, certain cancers, osteoarthritis, gallbladder
disease, and respiratory abnormalities [1]. Indeed, deaths
from noncommunicable diseases are expected to rise from
28.1 million to 49.7 million a year, an increase in absolute
numbers of 77% [3•], and ischemic heart disease is pre-
dicted to become the leading worldwide cause of disease
burden in 2020 (Table 1).
The Metabolic Syndrome
A high body mass index (BMI) is significantly associated
with myocardial infarction, coronary insufficiency, and
sudden death; the association seems strongest with sudden
death [4]. Although, obesity per se is considered a major
modifiable risk factor for ischemic heart disease [2], it is of
importance to remember that a remarkable heterogeneity
exists among obese subjects, and the presence of visceral obe-
sity generally worsens the metabolic portrait that is assoc-
iated with a cluster of traditional and nontraditional risk
factors, which are all potentially synergistic and deleterious
(Table 2). Because not all obese individuals are at increased
risk of CVD, the challenge for the clinician is to screen the
obese patients who are at risk (ie, the obese state associated
with the metabolic syndrome). Using the criteria established
by the National Cholesterol Education Panel (NCEP) [5••],
the metabolic syndrome is defined as three or more of the
following: 1) waist circumference for men greater than
102 cm and for women greater than 88 cm; 2) fasting tri-
glycerides of 150 mg/dL or greater (≥1.7 mmol/L); 3) high-
density lipoprotein (HDL) cholesterol less than 40 mg/dL
(<1.0 mmol/L) for men and less than 50 mg/dL (<1.3
mmol/L) for women; 4) blood pressure greater than 130/85
mm Hg; and 5) fasting plasma glucose of 110 mg/dL or more
(≥6.1 mmol/L). Presently, the "metabolic syndrome" is a
working definition only, and it remains unclear as to whether
the five components provide equal risk to the development
of cardiovascular disease events.
Obesity is a major contributor to the prevalence of
cardiovascular disease in the developed world, and yet has
only recently been afforded the same level of
attention as other risk factors of coronary artery disease.
Obesity is a chronic metabolic disorder associated with
cardiovascular disease and increased morbidity and mortal-
ity. It is apparent that a variety of adaptations/alterations in
cardiac structure and function occur as excessive adipose
tissue accumulates, even in the absence of comorbidities.
Shifts toward a less physically demanding lifestyle are
observed today throughout different populations, and this
scourge associated with obesity implicates a corresponding
increase in the number of individuals afflicted with the met-
abolic syndrome, which defines the obese patient as being
"at risk." Adipose tissue is not simply a passive storehouse
for fat, but an endocrine organ that is capable of
synthesizing and releasing into the bloodstream a variety
of molecules that may impact unfavorably the risk
factor profile of a patient. Indeed, obesity may affect
atherosclerosis through unrecognized variables and risk
factors for coronary artery disease such as dyslipidemia,
hypertension, glucose intolerance, inflammatory markers,
and the prothrombotic state. By favorably modifying
lipids, decreasing blood pressure, and decreasing levels
of glycemia, proinflammatory cytokines, and adhesion
molecules, weight loss may prevent the progression of
atherosclerosis or the occurrence of acute coronary
syndrome events in the obese high-risk population.
Obesity and Cardiovascular Disease • Poirier and Eckel 449
There is ample evidence suggesting that the presence of
excess fat in the abdomen in proportion to total body fat is
an independent predictor of CVD [6–8], and the features of
the metabolic syndrome are most often the consequence of
an excessive accumulation of abdominal fat (especially when
accompanied by a high accumulation of visceral adipose
tissue) [9–13]. For instance, among equally overweight and
obese individuals, patients with a high accumulation of
visceral adipose tissue are characterized by disturbances in
plasma glucose/insulin homeostasis; elevated triglycerides
(TG) and apolipoprotein B concentrations; low HDL choles-
terol levels; an increased proportion of small dense low-
density lipoprotein (LDL) and small dense HDL particles;
and by postprandial hyperlipidemia, reflecting a more
saturated system for the clearance of TG-rich lipoproteins
either of exogenous or endogenous origin [9-13]. This profile
is also accompanied by a prothrombotic, inflammatory state
[14–18]. Abdominal distribution of body fat is associated
with increased plasma levels of fibrinogen, factor VII and
factor VIIIc coagulant activities, and tissue plasminogen acti-
vator (tPA) antigen and plasminogen activator inhibitor I
(PAI-I) antigen and activity [19–22]. This hypercoagulable
state, which accompanies excessive central fat deposition,
may also be associated with impaired endothelial function
[23,24]. Therefore, the abdominally obese patient with the
features of the metabolic syndrome is characterized by an
atherogenic, prothrombotic, and inflammatory profile,
which probably substantially increases the risk of an acute
coronary syndrome [25].
From a pathophysiologic viewpoint, it is important to
keep in mind that adipose tissue is not simply a passive
storehouse for fat, but an endocrine organ that is capable
of synthesizing and releasing into the bloodstream a vari-
ety of molecules [1]. Of clinical consideration, circulating
concentrations of PAI-1, angiotensin II, C-reactive protein
(CRP), fibrinogen, and tumor necrosis factor α (TNF-α)
are all related to BMI [15,20]. It has been estimated that
in vivo, approximately 30% of the total circulating con-
centrations of interleukin 6 (IL-6) originate from adipose
tissue [15,26]. This is of importance because IL-6 modu-
lates CRP production in the liver, and CRP may be a
marker of a chronic inflammatory state that predisposes to
acute coronary syndromes [27–30].
Thus, when obesity is associated with the metabolic
syndrome, attention from the clinician is needed; this is
not an uncommon relationship [31]. The metabolic syn-
drome was encountered in approximately 10% of subjects
with normal glucose tolerance, approximately 50% of the
subjects with impaired fasting glucose/impaired glucose
tolerance, and approximately 80% of those with type 2
diabetes [32]. From an epidemiologic perspective, a recent
report indicated that 20% to 25% of the adult US
population has the metabolic syndrome [33••]. This is
of concern because the magnitude of risk associated with
insulin resistance (ie, the metabolic syndrome) may be of
the same magnitude as that of hypercholesterolemia [34].
From a clinical point of view, abdominal obesity-associ-
ated metabolic syndrome can be assessed easily, at least in
men. It was reported in men with a waist circumference
greater than 90 cm and with triglycerides greater than
2.0 mmol/L that this may identify as many as 80% of the
subjects with the insulin resistance syndrome; this is assoc-
iated with a cluster of risk factors for CVD [9,35]. However,
the waist circumference cutoff may lose predictive power in
patients with a BMI of 35 kg/m
2
or more [36].
Atherosclerosis
An important early event in the development of athero-
sclerosis is endothelial cell dysfunction and inflammation of
the vessel wall [37]. Atherosclerosis begins in childhood with
deposits of cholesterol in macrophages and smooth muscle
cells located in the intima of large muscular arteries to form
fatty streaks [38,39]. As individuals age, fibrous plaques
develop and progress to complicated lesions wherein hemor-
rhage or rupture may lead to acute coronary events [29,30].
In adults, obesity is often associated with advanced
atherosclerosis. Indeed, examination of arteries post-
mortem from young individuals (15 to 34 years of age)
who died from accidental injury, homicide, or suicide
demonstrates that the extent of fatty streaks and raised
lesions (fibrous plaques and plaques with calcification or
ulceration) in the right coronary artery (RCA) and in
the abdominal aorta were associated with obesity and
abdominal panniculus [40–43]. The prevalence of obesity,
defined as the thickness of panniculus adiposus and BMI
Table 1. The five leading causes of disease burden worldwide as measured in disability-adjusted
life years in the 1990s and the 2020s
1990s 2020s (predicted)
1. Lower respiratory infections 1. Ischemic heart disease
2. Diarrheal diseases 2. Unipolar major depression
3. Perinatal conditions 3. Road traffic accidents
4. Unipolar major depression 4. Cerebrovascular disease
5. Ischemic heart disease 5. Chronic obstructive disease
Adapted from Kumanyika et al. [
3•
].
450 Nutrition
of 30 kg/m
2
or more, in the Pathobiological Determinants
of Atherosclerosis in Youth (PDAY) study was 14.3% [44•].
Obesity in young men, as defined by BMI, was associated
with both fatty streaks and raised lesions in the RCA and
with microscopic atherosclerosis and stenosis in the
left anterior descending artery. Black subjects had more
extensive fatty streaks than white subjects in all arterial
segments, and men had more extensive raised lesions in
the RCA than women [44•]. The prevalence of total athero-
sclerosis (fatty streaks and raised lesions) in the RCA
increased from approximately 60% in the youngest age
group (15 to 19 years) to greater than 80% in men and
approximately 70% in women in the oldest age group
(30 to 34 years) [44•]. There was a 5% increase in arterial
surface involved with lesions for each 5-year age increase
[44•]. Importantly, when BMI and panniculus thickness
were used together in males, a BMI of 30 kg/m
2
or more
was associated with RCA raised lesions only within the
higher (≥17 mm) classification of panniculus thickness,
reinforcing that central fat distribution is more important
than total fat as a risk for CVD [44•]. Lesion prevalence was
greatest in the first 2 to 3 cm of the RCA, and in men the
effects of adiposity on raised lesions in this region were
evident even before the age of 25 years [45••]. Moreover
the association between adiposity and RCA lesions after
adjusting for other risk factors, namely non-HDL and HDL
cholesterol concentration, hypertension, smoking, and
glycohemoglobin, was still statistically significant; these
risk factors accounted for only 15% of the effects on
atherosclerosis [45••]. On the other hand, there was little
association of adiposity with coronary atherosclerosis in
young women, with a nonsignificant trend for an assoc-
iation between BMI and fatty streaks in women who
presented a thick panniculus adiposus [45••]. Of note,
however, raised lesions in coronary arteries in young
women lag behind those in young men by about 10 years,
independently of risk factor status [45••]. The same
parallel probably applies to postmenopausal women, who
often present with clinically significant atherosclerosis 10
years later than men. In the proximal left anterior descend-
ing (LAD) artery, obesity and hypertension were associated
with grade 4 and 5 lesions, which were defined as raised
or advanced lesions with necrotic lipid cores that may be
clinically significant [44•,46]. These data provide evidence
that obesity in adolescents and young adults accelerates
the progression of atherosclerosis decades before clinical
manifestations appear. Thus, the control of childhood
obesity is justified for the prevention of CVD as well as
other chronic disease associated with it.
Although the relationship between obesity and athero-
sclerosis is often dependent on obesity-related comorbidities
(eg, hypertension, glucose intolerance, and dyslipidemia),
after a follow-up of 26 years, the Framingham Heart Study
[47] and the Manitoba Study [4] have both documented
that obesity is an independent predictor of CVD, particularly
among women. This association was more pronounced in
individuals younger than 50 years of age, reinforcing the idea
that obesity leads to premature atherosclerosis. There is
evidence, however, that dyslipidemia, smoking, obesity,
and hyperglycemia are related to fatty streaks in the second
decade of life, and the same risks factors, along with hyper-
tension, are associated with plaques in the third decade
of life [40]. Hence the American Heart Association has
stated that obesity is a major modifiable risk factor, rather
than independent risk factor, for atherosclerotic cardio-
vascular disease [2,48].
Childhood Obesity and the Development
of Cardiovascular Disease
Childhood obesity has reached epidemic proportions.
During the past three decades, the number of overweight
children in the United States has more than doubled.
In 1983, 18.6% of preschool children in the United States
were defined as overweight and 8.5% were defined as
obese, whereas in 2000, 22% of preschool children were
overweight and 10% were obese [49]. Similar increases in
the prevalence of obesity have been observed worldwide
[50]. Obesity has a substantial influence on the cardio-
vascular system [1], and it is of importance to recognize
that childhood obesity is directly linked to abnormalities
in risk profile of both CAD and diabetes [51]. Indeed, over
40 years ago it was suggested that atherosclerosis was at
least in part a pediatric nutrition problem [52]. Because
modification of risk factors should occur before the ages
when the effects of atherosclerosis are observed, simple
risk factor modification (including diet, physical activity,
and weight control) should begin early in life, at least by
the late teens [53]. This has been recently demonstrated by
the observations that the secular trend toward obesity in
children is accompanied by detrimental risk factors for the
eventual development of CVD [54••,55].
Coronary Artery Disease and
Revascularization Therapy
The metabolic syndrome should probably be treated
aggressively following revascularization therapy. Indeed,
abnormal glucose tolerance may be an important determi-
nant for long-term prognosis after coronary angioplasty
[56]. Moreover, following coronary artery bypass graft
(CABG), the components of the metabolic syndrome are
associated with angiographic progression of athero-
sclerosis in nongrafted coronary arteries [57].
The cardiac catheterization laboratory at Duke Univer-
sity has observed an increase in obesity from 20% to 33%
in over 9000 patients studied between 1986 and 1997 [58].
Although obesity was associated with younger age, comor-
bidities, and only single-vessel disease at baseline [58,59],
obesity was associated with more clinical events during
the post–30-day period after cardiac catheterization [58].
In another study [59], obesity was associated with higher
Obesity and Cardiovascular Disease • Poirier and Eckel 451
cumulative in-patient medical costs and significant differ-
ences in unadjusted survival at 10 years [58]. This was not
true in the study of Gruberg et al. [59].
Coronary Artery Bypass Graft
Rightfully, surgeons often quote obesity as a risk factor for
perioperative morbidity and mortality. The presence of
comorbidities like hypertension, CAD, dyslipidemia, and
type 2 diabetes mellitus, as well as the technical difficulties
inherent to the surgical and postsurgical care of obese
patients, likely contribute to this perception. Obese patients
have been shown to have a higher incidence of postoperative
thromboembolic disease in noncardiac surgery, and the
high risk of thromboembolic disease in obese patients may
necessitate an aggressive approach to deep venous thrombo-
sis prophylaxis [60]. In contrast to frequent beliefs, obesity
is not associated with increased mortality or postoperative
cerebrovascular accidents following CABG. There is, however,
an increased risk of sternal and superficial wound infection,
saphenous vein harvest site infection, and atrial dysrhyth-
mias in obese patients undergoing bypass surgery [61,62].
Clinical Trials and Cardiovascular Disease
Outcome in Patients with Obesity
There is some evidence that patients with obesity and/or
the metabolic syndrome with coronary heart disease (or
with coronary heart disease risk) may respond better to
lipid-modifying interventions in clinical trials. In the
Helsinki Heart Study [63], men with hypercholesterolemia
with a BMI greater than 26 kg/m
2
and either hypertri-
glyceridemia plus low levels of HDL cholesterol and/or three
to four additional risk factors for coronary heart
disease appeared to respond better to the gemfibrozil inter-
vention than patients without obesity. Moreover, in patients
with coronary heart disease and baseline levels of HDL
cholesterol less than 40 mg/dL, the metabolic syndrome
predicted a superior reduction in coronary heart disease
events with gemfibrozil [64]. Whether this relative benefit of
obese patients with or without the metabolic syndrome
extends to other cardiovascular disease risk factors remains
unexamined, but it is clearly worthy of additional attention.
Conclusions
Obesity is a chronic metabolic disorder associated with CVD
and increased morbidity and mortality. It is apparent that a
variety of adaptations/alterations in cardiac structure and
function occur as excessive adipose tissue accumulates, even
in the absence of comorbidities. Large shifts towards a less
physically demanding lifestyle are observed today through-
out different populations, and this scourge associated with
obesity implicates a corresponding increase in the number
of individuals afflicted with the metabolic syndrome. This
deleterious trend endangers the advances made in reducing
morbidity and mortality from CVD over the past two
decades [65]. It also poses a challenge to physicians to mod-
ify their practice to place more emphasis on lifestyle changes
[53]. More prevalent cardiac risk factors in obese and very
obese CAD patients at baseline seemed to counteract poten-
tial survival benefits derived from the younger age and less
extensive CAD of these individuals. Consequently, the long-
term clinical burden of illness is greater [58]. Of note, the
impact of excess body fat on mortality is delayed and may
not be seen in short-term studies [58] compared with other
ones [25,28,45••,47]. Indeed, cardiovascular mortality
assessed in 3606 subjects with a median follow-up of 6.9
years was increased substantially in subjects with the fea-
tures of the metabolic syndrome (12.0% vs 2.2%) [32], and
it was shown recently that abdominal obesity is associated
with increased risk of acute coronary events in men [28].
Obesity may affect atherosclerosis through risk factors
like dyslipidemia, hypertension, glucose intolerance,
inflammatory markers, and the prothrombotic state. Many
of these are components of insulin resistance. Although
there are no prospective studies to date demonstrating that
weight loss increases survival, there is strong evidence that
weight loss in "at risk" overweight and obese individuals
reduces the incidence of diabetes [66,67], and because
diabetes is a CAD equivalent, probably CVD as well. By
favorably modifying lipids and by decreasing blood pres-
sure, levels of glycemia, proinflammatory cytokines (ie,
TNF-α, IL-6, CRP) [68–70], and adhesion molecules (ie, P-
selectin, circulating inter-cellular adhesion molecule-1,
vascular adhesion molecule-1) [68], weight loss may pre-
vent the progression of atherosclerosis or the occurrence of
acute coronary syndrome events. Moreover, weight loss
translates into improvement in endothelial function [68].
If the current worldwide epidemic of childhood obesity
cannot be averted, its full public health impact will be felt
in the contemporary cardiology world as affected children
become adults and the long-term complications of obesity
develop. The best way to treat a disease is to prevent it. For
obesity, this is where the emphasis needs to be placed.
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