Overview of Epidemiology and Contribution of Obesity to Cardiovascular Disease

Overview of Epidemiology and Contribution of Obesity to
Cardiovascular Disease
Marjorie Bastiena, b , Paul Poiriera, b,⁎, Isabelle Lemieuxa, c, d , Jean-Pierre Desprésa, c, d
aInstitut Universitaire de Cardiologie et de Pneumologie de Québec, Québec, QC, Canada
bFaculté de Pharmacie, Université Laval, Québec, QC, Canada
cFaculté de Médecine, Université Laval, Québec, QC, Canada
dChaire Internationale sur le Risque Cardiométabolique, Université Laval, Québec, QC, Canada
A R T I C L E I N F O A B S T R A C T
The prevalence of obesity has increased worldwide and is a source of concern since the
negative consequences of obesity start as early as in childhood. The most commonly used
anthropometric tool to assess relative weight and classify obesity is the body mass index
(BMI); BMI alone shows a U- or a J-shaped association with clinical outcomes and mortality.
Such an inverse relationship fuels a controversy in the literature, named the ‘obesity
paradox', which associates better survival and fewer cardiovascular (CV) events in patients
with elevated BMI afflicted with chronic diseases compared to non-obese patients.
However, BMI cannot make the distinction between an elevated body weight due to high
levels of lean vs. fat body mass. Generally, an excess of body fat (BF) is more frequently
associated with metabolic abnormalities than a high level of lean body mass. Another
explanation for the paradox is the absence of control for major individual differences in
regional BF distribution. Adipose tissue is now considered as a key organ regarding the fate
of excess dietary lipids, which may determine whether or not body homeostasis will be
maintained (metabolically healthy obesity) or a state of inflammation/insulin resistance
will be produced, with deleterious CV consequences. Obesity, particularly visceral obesity,
also induces a variety of structural adaptations/alterations in CV structure/function.
Adipose tissue can now be considered as an endocrine organ orchestrating crucial
interactions with vital organs and tissues such as the brain, the liver, the skeletal muscle,
the heart and blood vessels themselves. Thus, the evidence reviewed in this paper suggests
that adipose tissue quality/function is as important, if not more so, than its amount in
determining the overall health and CV risks of overweight/obesity.
© 2014 Elsevier Inc. All rights reserved.
Keywords:
Cardiovascular disease
Obesity
CV risks
Ectopic fat
Epidemiology
The prevalence of obesity has increased dramatically world-
wide over the last decades and has now reached epidemic
proportions. For instance, the global prevalence of obesity has
nearly doubled between 1980 and 2008. According to the
World Health Organization, 35% of adults worldwide aged > 20
years were overweight (34% men and 35% women) in 2008
P R O G R E S S I N C A R D I O V A S C U L A R D I S E A S E S 5 6 ( 2 0 1 4 ) 3 6 9 – 3 8 1
Statement of Conflict of Interest: see page 377.
⁎ Address reprint requests to Paul Poirier, Institut universitaire de cardiologie et pneumologie de Québec, 2725 Chemin Ste-Foy, Québec,
Québec, Canada, G1V 4G5.
E-mail address: [e-mail] (P. Poirier).
0033-0620/$ – see front matter © 2014 Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.pcad.2013.10.016
A v a i l a b l e o n l i n e a t w w w . s c i e n c e d i r e c t . c o m
ScienceDirect
w w w . o n l i n e p c d . c o m

including10%menand
14% women being con-
sidered as obese. Prev-
alence is particularly
high in America with
a high proportion of
overweightandobesity
(62% and 26% respec-
tively in both sexes)
while South East Asia
shows the lowest pre-
valence (14% over-
weight in both sexes
and 3% for obesity). 1
IntheUnitedStates,
the prevalence of obe-
sity has increased
by 8% between 1976
and 1980, by another
8% between 1988 and
1994 with similar in-
creases between 1988–
1994 and 1999–2000.
In contrast, data from
the last decade
(1999–2010) suggest that
theprevalenceofobesity
may have plateaued
in the USA.2–4 Accord-
ing to the latest National
Health and Nutrition
Examination Survey
(NHANES), the age-
adjusted obesity pre-
valence was 35.7%
in the United States
in 2010 with no sex
differences. Extreme
obesity has more
than doubled since
1988–1994 NHANES,
shifting from 2.9 to
6.3% in 2010 for grade 3 (severe) obesity while reaching
15.2% for grade 2 obesity (Table 1). 4,5 The age-adjusted
prevalence of overweight and obesity combined (body mass
index; BMI ≥ 25 kg/m 2
) was 68.8% in 2010 with a mean BMI of
28.7 kg/m 2 in the US population. 5 In Canada, the prevalence of
obesity is lower than in the United States reaching 27 and 25%
of Canadian men and women, respectively. It is also relevant
to mention that in Canada, 29% of men and 41% of women
reach cut off values for waist circumference (WC; above 102
cm in men and 88 cm in women) suggesting the presence of
abdominal obesity, with mean WC values of 95.1 cm for men
and 87.3 cm for women. 6
Such growing numbers are a source of concern since the
negative consequences of obesity start as early as in
childhood. Some experts predict a decrease life expectancy
at birth in the US during the first half of the 21st century. 7
Each year, 28 million individuals are dying from the
consequences of overweight or obesity worldwide. 1 High BMI
is associated with the development of cardiovascular (CV) risk
factors such as hypertension (HTN), dyslipidemia, insulin
resistance, and diabetes mellitus (DM) leading to CV diseases
(CVD), such as coronary heart disease (CHD) and ischemic
stroke. 8–10 The development of these comorbidities is propor-
tionate to the BMI and obesity is considered as an indepen-
dent risk factor for CVD. 11,12 Several studies have documented
that a high BMI is significantly associated, in both men and
women, with manifestations of CVD such as angina, myocar-
dial infarction (MI), heart failure (HF) and sudden death. 13,14
The higher incidence of CVD events in obese patients seems
to be related to endothelial dysfunction and subclinical
inflammation in addition to the worsening of CVD risk
factors. 15 Overall, obesity is associated with an increased
mortality rate, 16 but obesity grades must be considered in risk
stratification. In a recent meta-analysis including 2.88 mil-
lions of individuals, all obesity grades combined were
associated with an increase in mortality rate, with a hazard
ratio of 1.18 (95% CI, 1.12–1.25). However, when analyzed
separately, obesity grade 1 (Table 1) was not associated with
an increased mortality risk, with a hazard ratio of 0.97 (95% CI,
0.90–1.04), compared to normal weight. In contrast, severe
obesity (grades 2 and 3) was associated with an increased
mortality risk (hazard ratio of 1.34 – 95% CI, 1.21–1.47). 17
Childhood obesity also seems to impact mortality rate in early
adulthood. Increased BMI in children has been positively
associated with the risk of premature death in a population of
American Indians born between 1945 and 1984 and followed
between February 1966 and December 2003. 18 According to
the authors, this association could be partly mediated by the
development of glucose intolerance and hypertension, but
not hypercholesterolemia. 18 Another study performed in
older children also found a close relationship between BMI
at adolescence and all-cause mortality rate assessed during
adulthood. Indeed, after a follow-up of 31.5 years, it was
reported that a BMI above the 95th percentile assessed during
adolescence predicted increased adult mortality rates in both
men (80% increase) and women (~100% increase) when
compared to those who had a BMI between the 25th and
75th percentiles during their teenage years. Even among
adolescents who had less severe obesity (between the 85th
and 95th percentiles), such moderate obesity was associated
with a 30% increase in all-cause mortality assessed during
adulthood. 16 Such an increased mortality rate observed in
adults who were obese at childhood appears to be largely
independent from adult BMI. 19
Obesity assessment
The most commonly used anthropometric tool to assess
relative weight and classify obesity is the BMI, which is
expressed as the ratio of total body weight over height
squared (kg/m 2
). Individuals with a BMI < 18.5 kg/m 2 are
considered as being underweight, whereas those with a BMI
between 18.5 and 24.9 kg/m 2 are classified as having normal
or acceptable weight. Individuals with a BMI ranging from 25
to 29.9 kg/m 2 are classified as overweight while obesity is
Abbreviations and Acronyms
BF = Body fat
BMI = Body mass index
CHD = Coronary heart disease
CRP = C-reactive protein
CV = Cardiovascular
CVD = Cardiovascular disease
DM = Diabetes mellitus
FFAs = Free fatty acids
HDL = High-density lipoprotein
HF = Heart failure
HTN = Hypertension
Il = Interleukin
LDL = Low-density lipoprotein
LV = Left ventricular
LVH = Left ventricular
hypertrophy
LVM = Left ventricular mass
MI = Myocardial infarction
NHANES = National Health and
Nutrition Examination Survey
NSTEMI = Non-ST segment
elevation myocardial infarction
TGs = Triglycerides
TNF = Tumor necrosis factor
VLDL = Very low-density
lipoprotein
WC = Waist circumference
WHR = Waist-to-hip ratio
370 P R O G R E S S I N C A R D I O V A S C U L A R D I S E A S E S 5 6 ( 2 0 1 4 ) 3 6 9 – 3 8 1

present when BMI reaches ≥30 kg/m 2
. Beyond that point,
obesity is graded into 3 categories: grade 1 (BMI ranging from
30 to 34.9 kg/m 2
), grade 2 (BMI ranging from 35.0 to 39.9 kg/
m 2
), and grade 3 (BMI ≥ 40 kg/m 2
). 11 The American Heart
Association has proposed additional obesity subgroups to
take into consideration the rapidly expanding subgroup of
patients with massive obesity and introduced grade 4 obesity
corresponding to a BMI ≥50 kg/m 2 and grade 5 as a BMI ≥ 60 kg/
m 2 20,21 (Table 1). It has also been recently pointed out that
BMI was not very discriminant in order to distinguish lean
from fat body mass particularly among patients with a BMI
≥ 30 kg/m 2
. 22 Generally, an excess of body fat (BF) is more
frequently associated with metabolic abnormalities than a
high level of lean body mass. 10 BMI alone seems to present a
U- or a J-shaped association with clinical outcomes and
mortality. 23 Such an inverse relationship fuels a controversy
in the literature, named the ‘obesity paradox’, which associ-
ates better survival and fewer CVD events in patients with
mildly elevated BMI afflicted with chronic diseases. 22,24,25
Although obesity as defined by the BMI influences CV risk,
one may argue that other adiposity indices should be taken
into consideration by the clinician in the risk stratification of
a given patient (Fig 1). Obesity assessed with the BMI presents
some limitation in the prediction of CV mortality. Among
patients who have CVD, it has been reported that overweight
or mildly obese patients show better outcomes in terms of CV
and total mortality, with a paradoxical association between
BMI and survival. 22 However, reasons for this “obesity
paradox” remain unclear and some of them including the
issue of selection bias are illustrated in Fig 2. Even with a
worse perceived health, poorer adherence to lifestyle behav-
iour, more co-morbidities and risk factors, overweight and
obese cardiac patients appear to nevertheless present a better
prognosis than normal weight individuals. 26 One explanation
for this paradox could be found in BF distribution. For
instance, markers of absolute and relative accumulation of
abdominal fat accumulation, such as elevated WC and waist-
to-hip ratio (WHR) have been associated with an increased
risk of MI, HF and total mortality in patients with CVD. 27 In
the Trandolapril Cardiac Evaluation register, increased mor-
tality (23%) was observed among patients with an antecedent
of CVD presenting abdominal obesity. This relationship
remained after exclusion of DM and HTN from the multivar-
iate analyses, underlining the importance of abdominal
obesity as an independent factor of all-cause mortality in
patients with CVD. 28 An increase in both WC and WHR
predicted an increased risk of CVD in men and women; a 1 cm
increase in WC and a 0.01 unit increase in WHR were
respectively associated with a 2% increase and 5% increase
in risk of future CVD events. 29 Of importance, a lower lean
body mass also appeared to partially explain this obesity
paradox, 30 underlining the importance of going beyond the
measurement of relative weight in risk assessment (Fig 2).
Indeed, overweight and obese individuals may show
strikingly different CVD risk factor profiles on the basis of
their BF distribution (Fig 2). Excess abdominal visceral adipose
tissue, irrespective of the BMI, has been associated with a
constellation of diabetogenic and atherogenic abnormalities
such as insulin resistance, increased triglycerides and apoli-
poprotein B levels, low high-density lipoprotein cholesterol
and an increased proportion of small dense low-density
lipoprotein (LDL) and high-density lipoprotein (HDL) particles,
the latter lipid abnormalities being generally described as the
atherogenic dyslipidemia (Fig 3). On the contrary, low levels of
visceral adipose tissue and subcutaneous obesity are associ-
ated with a low risk metabolic risk profile. 31 There is now
Table 1 – Classification of body weight.
Underweight BMI <18.5 kg/m2
Normal or acceptable weight BMI 18.5–24.9 kg/m2
Overweight BMI 25–29.9 kg/m2
Obese BMI ≥30 kg/m2
Grade 1 BMI 30–34.9 kg/m2
Grade 2 BMI 35.0–39.9 kg/m2
Grade 3 BMI ≥40 kg/m2 (severe, extreme,
or morbid obesity)
Grade 4 BMI ≥50 kg/m2
Grade 5 BMI ≥60 kg/m2
Abbreviations: BMI: body mass index.
From Poirier P, Alpert MA, Fleisher LA, Thompson PD, Sugerman HJ,
Burke LE, Marceau P and Franklin BA: Cardiovascular evaluation
and management of severely obese patients undergoing surgery. A
science advisory from the American Heart Association. Circulation
2009;120: 86–95.INTERMEDIATERISK FACTORS- Blood pressure- Glucose (diabetes)- Dyslipidemia- Insulin resistance- Inflammation- Etc.ANTHROPOMETRICADIPOSITY MARKERS- BMI- Waist- WHRCardiovascular(+) (+)Xevents
Fig 1 – Relationships between adiposity indices, intermediate risk factors and cardiovascular events in the general population.
Under this model, most of the association between adiposity indices and cardiovascular disease is explained by altered levels
of intermediate risk factors. However, increased adiposity indices are the main drivers behind the altered levels of
intermediate risk factors. Abbreviations: BMI: Body mass index; WHR: waist-to-hip ratio.
371P R O G R E S S I N C A R D I O V A S C U L A R D I S E A S E S 5 6 ( 2 0 1 4 ) 3 6 9 – 3 8 1

considerable evidence to support the notion that regional fat
accumulation is much more important in CVD risk stratifica-
tion than excess total adiposity per se. On that basis, a simple
anthropometric index of total adiposity such as the BMI
should be refined by measuring additional indices of fat
distribution namely WC, WHR or waist-to height ratio to
discriminate higher-risk individuals. 32,33 Visceral adiposity
can be measured accurately by computed tomography,
magnetic resonance imaging, and with less precision by dual
energy x-ray absorptiometry. Imaging cardiometabolic stud-
ies recently conducted in large cohort studies (Framingham
Heart Study and the Jackson Heart Study) have shown that
excess visceral adiposity accompanied by excess ectopic fat
deposition such as excess heart, liver, and intrathoracic fat
was significantly associated with cardiac and metabolic
abnormalities, and that such relationship was independent
from the amount of total or subcutaneous adipose tissue. 34–36
Unfortunately, these imaging techniques are not available for
large scale use to physicians. Since abdominal obesity is of
importance in CVD risk stratification, measuring WC in
addition to the BMI may represent the best alternative
measurement for the health care professional. It is low cost,
easy to perform and shows a reasonable association with
visceral adiposity for a given BMI unit (Fig 2). 25,37,38 Based on
experts consensus, the World Health Organization has
proposed sex-specific cut-off values associated with in-
creased CVD risk: 94 cm in men and 80 cm in women for
increased risk, and 102 cm in men and 88 cm in women for
substantially increased risk. 39 Many other techniques (air
displacement plethysmography, bioelectrical impedance,ENTIRE POPULATION OF ASYMPTOMATIC YOUNG ADULTSLean Overweight ObeseFOLLOW-UP(decades)CVD (-) CVD (+)Less of:- Smoking- Hypertension- Dyslipidemia- Diabetes- Abdominal obesity and metabolic syndrome- Visceral obesity/ectopic fat- Physical inactivity- Poor cardiorespiratory fitness- Poor nutritional quality- Etc.FOLLOW-UPMore of:- Smoking- Hypertension- Dyslipidemia- Diabetes- Abdominal obesity and metabolic syndrome- Visceral obesity/ectopic fat- Physical inactivity- Poor cardiorespiratory fitness- Poor nutritional quality- Etc.- BMI- Waist for a given BMI- Visceral/ectopic fat?- Cardiorespiratory fitness- Lean body mass- Etc.- BMI- Waist for a given BMI- Visceral/ectopic fat?- Cardiorespiratory fitness- Lean body mass- Etc.NO RECURRENT CVD RECURRENT CVD
Fig 2 – Contribution of the selection bias in the obesity paradox in patients with cardiovascular disease (CVD). Under this
model, patients with CVD* are no longer characterized by the distribution of CVD risk factors/behaviors observed in the entire
population. It is proposed that nonobese individuals who developed CVD in the absence of overall obesity may have been
exquisitely more prone to CVD due to factors other than obesity. This could partly explain why, among individuals with CVD,
obesity is associated with lower mortality. Other important confounding factors for the body mass index (BMI)/obesity paradox
include: lack of control for individual variation in body fat distribution (visceral adiposity/ectopic fat), cardiorespiratory fitness,
muscle mass/cachexia, frailty, physical activity/inactivity level, nutritional quality and intake, markers of adipose tissue
function/quality, underlying diseases, etc.
372 P R O G R E S S I N C A R D I O V A S C U L A R D I S E A S E S 5 6 ( 2 0 1 4 ) 3 6 9 – 3 8 1