Chapter 4
Does Obesity Paradox Exist?
PREM RATAN DEGAWAT • RAJEEV GUPTA
INTRODUCTION
The worldwide prevalence of obesity and over-
weight has increased dramatically in the last few
decades1. Currently obesity is defined as body mass
index (BMI; weight in kg/height in m2) of ⱖ30.0
units and is a risk factor for cardiovascular disease,
diabetes mellitus, chronic kidney disease and many
cancers2,3. In this chapter, we review that epidemi-
ology of obesity and association of increasing (or
decreasing) BMI with all-cause and cardiovascular
mortality, the pathophysiology or obesity and
a critical review of the so-called obesity paradox:
increasing obesity is associated with lower cardio-
vascular mortality in patients with pre-existing
cardiovascular disease.
EPIDEMIOLOGY
De Gonzalez et al.4 examined the relationship be-
tween BMI and all-cause mortality in a pooled
analysis of 19 prospective studies in White adults.
The age-standardized rate of death from any cause
was lowest among patients with BMI of 22.5–24.9.
The hazard ratios increased with progressively
higher and lower levels of BMI. In this study, the
sequential exclusion of current and former smokers,
patients reporting cancer or heart disease at base-
line changed the shape of the relationship between
BMI and the hazard ratio for death. The hazard
ratio increased for a BMI of 25.0 or higher and
decreased for a BMI of less than 22.5, with each
exclusion.
Zheng et al.5 examined association between BMI
and the risk of death among more than 1.1 million
persons of 19 cohorts in Asia (mainly China, Korea,
Japan and India). The lowest risk of death was
seen among persons with a BMI in the range of
22.6–27.5. Among persons with BMI either higher
or lower than this range, the risk was elevated. An
increase by a factor of up to 1.5 was seen among
those with a BMI ⬎ 35.0 and by a factor of 2.8
among those with a BMI ⱕ 15.0. A U-shaped asso-
ciation was also seen between BMI and the risk of
death from cancer, CVD and some of the other
causes as studied. The risks of death were increased
among persons with a BMI ⱕ 20.0, as compared
with those with a BMI of 22.6–25.0, from any cause
in the cohorts comprising Indians and Bangla-
deshis. Whereas no excess risk of either death from
any cause or cause-specific death was seen to be as-
sociated with a higher BMI. Underweight group of
patients were associated with a substantially in-
creased risk of death in all Asian populations. Among
East Asians, an excess risk of death associated with a
high BMI; however, this was not noted among Indi-
ans and Bangladeshis (Fig. 4-1).
Regarding cardiovascular mortality, most of the
data of BMI are from developed countries and show
U-shaped associations similar to all-cause mortality
trends. Yusuf et al. studied correlation of BMI and
other measures of obesity (waist circumference and
waist-to-hip ratio [WHR]) with incidence of acute
myocardial infarction in a large case–control IN-
TERHEART study6. This study was a standardized
case–control study of first myocardial infarction in
262 centres in 52 countries in Asia including India,
Europe, Middle East, Africa, and North and South
America. The study reported that WHR had a
graded and highly significant association with myo-
cardial infarction risk worldwide. Fig. 4-2 shows the
age-adjusted percentage of cases and controls with
abdominal obesity (WHR) and by region. BMI,
however, was only modestly associated with risk of
myocardial infarction. The risk was further dra-
matically reduced when adjusted for WHR and
31
32 SECTION II — Preventive Cardiology

Death from CVD Death from cancer Death from other causes

A East Asians B Indians and Bangladeshis

3.0 3.0
Hazard Ratio

Hazard Ratio
2.0 2.0

1.0 1.0

0.0 0.0
.1 0

.6 5

.1 0

.6 5

.1 0

5
5

.1 0

.6 5

.1 0

.6 5

.1 0

5
5

6
0.

22 22.

25 25.

27 27.

30 30.

2.
7.

2.

2 0 0.

2 2 22.

25 25.

27 27.

30 30.

2.
7.

2.
–2

–3
≤1

≥3

–2

–3
≤1

≥3
–

–
.6

.6
17

20

17
BMI BMI

C East Asians D Indians and Bangladeshis

3.0 3.0
Hazard Ratio

Hazard Ratio

2.0 2.0

1.0 1.0

0.0 0.0
20 0.0

22 22.5

25 25.0

27 27.5

30 30.0

20 0.0

22 22.5

25 25.0

27 27.5

30 30.0

6
.6 5

.6 5
2.

2.

2.
7.

2.

7.
–2

–3

–2

–3

≥3
≤1

≥3

≤1
–

–
.1

.6

.1

.6

.1

.1

.6

.1

.6

.1
17

17

BMI BMI

Figure 4-1. Association of BMI with all-cause mortality in Asian cohorts5. The associations are U-shaped among East Asian co-
horts and Reverse J-shaped in South Asian cohorts. (Source: From The New England Journal of Medicine, Zheng et al., Association
between Body-Mass Index and Risk of Death in More Than 1 Million Asians, 364, 719-29. Copyright © (2017) Massachusetts Medical
Society. Reprinted with permission from Massachusetts Medical Society.)

became nonsignificant with adjustment of other OBESITY PATHOPHYSIOLOGY

risk factors. In contrast to BMI, for WHR, the odds
ratios for every successive quintile were signifi-
cantly greater than that of previous one even after
multiple adjustments. WHR and waist circumfer-
ences were closely associated with risk of myocar-
dial infarction even after adjustment for other risk
factors (P ⬍ .0001). It was suggested that obesity
should be redefined according to WHR instead of
BMI to estimate of myocardial infarction risk in
most ethnic groups.
Obesity typically evolves slowly over time and is a
result of long-term positive energy balance. Accu-
mulation of lipids, mainly triglycerides, in the adi-
pose tissue occurs in conjunction with volume
excess in skeletal muscle, liver, and other organs
and tissues7. Subcutaneous adipose tissue holds
most of the stored lipid at a variety of anatomical
sites that differ in metabolic and physiological
characteristics8.
 Chapter 4 — Does Obesity Paradox Exist? 33

Adjusted for age, sex, smoking, and region Adjusted for age, sex, smoking, and region
Adjusted for age, sex, smoking, region, and WHR Adjusted for age, sex, smoking, region, and BMI
Adjusted for all other INTERHEART risk factors Adjusted for all other INTERHEART risk factors
3·0

2·5

2·0
OR (95% CI)

1·5

1·0

0·75
Q1 Q2 Q3 Q4 Q5 Q1 Q2 Q3 Q4 Q5

Controls 2860 2936 2906 2890 2906 2866 2870 2865 2862 2869
Cases 2122 2235 2568 2480 2651 1629 1816 2105 2750 3507

BMI quintiles WHR quintile

Figure 4-2. Association of BMI and WHR with risk of acute myocardial infarction in the INTERHEART study6. The risk of increas-
ing BMI quintiles declines with adjustments for various risk factors while increased risk of greater WHR remains after multiple
adjustments. (Source: Reprinted from The Lancet, 366, Yusuf et al., Obesity and the risk of myocardial infarction in 27000 participants
from 52 countries: a case-control study, 1640-49., Copyright (2005), with permission from Elsevier.)

An obese person with stable weight, as compared
with a person without overweight or obesity, thus
has larger fat and lean mass, along with higher rest-
ing energy expenditure, cardiac output, and blood
pressure and greater pancreatic ␤-cell mass8–12. With
weight gain over time, excess lipids are distributed
to many body compartments. Obesity is accompa-
nied by increases in macrophages and other im-
mune cells in adipose tissue, in part because of tissue
remodelling in response to adipocyte apoptosis13.
These immune cells secrete proinflammatory cyto-
kines, which contribute to the insulin resistance in
patients with obesity. Visceral adipose tissue is a
smaller storage compartment for lipids than is sub-
cutaneous adipose tissue, with omental and mesen-
teric fat mechanistically linked to many of the
metabolic disturbances and adverse outcomes asso-
ciated with obesity12. Adipose tissue surrounds the
kidney, and the blood pressure increase with renal
compression may contribute to the hypertension
frequently observed in patients who are obese10.
Obesity is often accompanied by an increase in pha-
ryngeal soft tissues, which can block airways during
sleep and lead to obstructive sleep apnoea14. Excess
adiposity also imposes a mechanical load on joints,
making obesity a risk factor for the development of
osteoarthritis15. An increase in intra-abdominal
pressure purportedly accounts for the elevated risks
of gastroesophageal reflux disease, Barrett oesopha-
gus and oesophageal adenocarcinoma among per-
sons who are overweight or obese16.
Adipocytes synthesize adipokines (cell-signalling
proteins) and hormones, the secretion rates and ef-
fects of which depend on the distribution and
amount of adipose tissue present. Excessive secre-
tion of proinflammatory adipokines by adipocytes
and macrophages within adipose tissue leads to a
low-grade systemic inflammatory state in some
34 SECTION II — Preventive Cardiology
persons with obesity. Hydrolysis of triglycerides
within adipocytes releases free fatty acids, which
are then transported in plasma to sites where they
can be useful metabolically. Plasma free fatty acid
levels are often high in patients with obesity, re-
flecting several sources that include the enlarged
adipose tissue mass12.
In addition to being found in adipose tissue, lip-
ids are also found in liposomes, with excess adipos-
ity, liposomes in hepatocytes can increase in size
(steatosis), forming large vacuoles that are accom-
panied by a series of pathological states, including
nonalcoholic fatty liver disease, steatohepatitis and
cirrhosis. Accumulation of excess lipid intermedi-
ates (e.g. ceramides) in some nonadipose tissues can
lead to lipotoxicity with cellular dysfunction and
apoptosis12. Elevated levels of free fatty acids, in-
flammatory cytokines, and lipid intermediates in
nonadipose tissues contribute to impaired insulin
signalling and the insulin-resistant state that is
present in many patients who are overweight or
obese12,17. Insulin resistance is also strongly associ-
ated with excess intra-abdominal adipose tissue12,17.
These metabolic and anatomical findings are one
of several pathophysiological mechanisms underly-
ing the dyslipidaemia of obesity (elevated fasting
plasma triglyceride and low-density lipoprotein cho-
lesterol levels and low levels of high-density lipopro-
tein cholesterol), type 2 diabetes, obesity-related liver
disease and osteoarthritis. Elevated bioavailable levels
of insulin-like growth factor 1 and other tumour-
promoting molecules have been implicated in the
development of some cancers18. Chronic overactivity
of the sympathetic nervous system is present in some
patients with obesity and may account in part for
multiple pathophysiological processes, including
high blood pressure9. Heart diseases, stroke and
chronic kidney diseases all have as their main patho-
physiological mechanisms high blood pressure and
the cluster of findings associated with insulin resis-
tance, obesity-associated dyslipidaemia and type 2
diabetes. Fig. 4-3 (see ref 19) shows some of the path-
ways by which the mechanical, metabolic and physi-
ological effects of excess adiposity lead to coexisting
chronic diseases. Obesity is also associated with an
increased prevalence of mood, anxiety and other psy-
chiatric disorders, particularly among persons with
severe obesity and those seeking bariatric surgery20,21.
OBESITY PARADOX
Overweight and obesity are associated with adverse
cardiovascular outcome. Despite this, some studies
in past few decades demonstrate an obesity paradox,
where overweight and obese patients with cardiovas-
cular disease show a better outcome than do their
leaner counterparts22. Lavie et al.23 reported in an-
other review that mechanism/s of this paradox are
difficult to understand but few possible explanations
that need to be considered include a younger age of
presentation in this group with greater metabolic
reserves and greater muscle mass and muscular
strength. The prevalence of smoking and cachexia
may also be lower. Lower atrial natriuretic peptides
and attenuated response to renin–angiotensin–
aldosterone system are also contributing factors.
Higher blood pressure, greater intake of cardiac
medications and differing aetiologies may be associ-
ated with better prognosis.
Uretsky et al.24 investigated the effects of obesity
on outcomes in 22,576 patients with treated hyper-
tension. The all-cause mortality was 30% lower in
overweight and obese and hypertensive patients
compared with their leaner counterparts. Similarly, a
meta-analysis of 40 cohort studies with more than
250,000 patients with coronary heart disease (CHD)
performed by Romero-Corral et al.25 reported a lower
risk of total and cardiovascular mortality in over-
weight and obese patients as compared with under-
weight and normal-weight CHD. It appears that
there is a strong obesity paradox with the best prog-
nosis noted in overweight CHD patients, as opposed
to those with more severe obesity26.
In a study of 550 nondiabetic subjects, increased
BMI on its own was not seen to be associated with
an increased risk of heart failure; however, meta-
bolic syndrome showed a 2.5-fold increased risk of
heart failure27. In this study, metabolically healthy
obese subjects had a decreased heart failure risk
when compared with normal weight metabolic syn-
drome patients in a 6-year follow-up. Oreopoulous
et al.28 reported reductions in cardiovascular risk in
overweight and obese heart failure patients (–19%
and –40%, respectively) when compared with pa-
tients with normal BMI. In a follow-up of 2.7 years,
total mortality was also reduced in overweight and
obese heart failure patients (–16% and –33%, re-
spectively).
Wanahita et al.29 conducted a meta-analysis of 16
studies with more than 120,000 patients. Obese pa-
tients reported a 50% increased risk of developing
atrial fibrillation. However, these overweight and
obese patients with atrial fibrillation as in patients
with hypertension, CHD and heart failure, had a con-
siderably better prognosis than those patients with
normal BMI.
On the other hand, multiple pathophysiological
and clinical studies have reported direct association
 Chapter 4 — Does Obesity Paradox Exist? 35

↑ Adiposity

↑ Adipokine synthesis ↑ Lipid production ↑ Activity of ↑ Activity of the Mechanical stress

the sympathetic renin–angiotensin–
nervous system aldosterone system

↑ Adipose tissue
macrophages and other Hydrolysis of
inflammatory cells triglycerides

↑ Proinflammatory Release of
cytokines free fatty acids

Renal ↑ Pharyngeal ↑ Mechanical ↑ Intraabdominal

compression soft tissue load on joints pressure
Impaired insulin
signaling and
↑ insulin resistance Lipotoxicity Dyslipidemia

↑ Insulin Systemic and

pulmonary
hypertension

Nonalcoholic
fatty liver disease

Steatohepatitis Coronary Obstructive

Type 2 diabetes Osteoarthritis Gastroesophageal
artery disease sleep apnea reflux disease
Cirrhosis
Barrett’s esophagus

Esophageal
adenocarcinoma

Congestive heart failure

Stroke

Chronic kidney disease

Figure 4-3. Effects of excessive obesity (adiposity) on multiple cellular pathways19. (Source: From The New England Journal
of Medicine, Steven B. Heymsfield, Thomas A. Wadden, Mechanisms, Pathophysiology, and Management of Obesity, 376, 254-66.
Copyright © (2017) Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society.)

of increasing obesity (BMI or WHR) with various
biological pathways linking obesity with abnormal
adipokine alterations, insulin resistance, sympa-
thetic nervous system and renin–angiotensin–
aldosterone system activation, OSA, renal abnor-
malities, maladaptive immunity and abnormal gut
microbiome. This is also associated with incidence
CHD and mortality (Fig. 4-4)30.
In a meta-analysis, Oga et al.31 reviewed the evi-
dence of the relationship between heart failure sur-
vival and mortality against the weight status of an
individual. In the initial search, 10 studies met the
36 SECTION II — Preventive Cardiology

Figure 4-4. Pathophysiological pathways of obesity with cardiovascular risk30. (Source: Reprinted from Nature Reviews Endocrinology,
Vincent G. DeMarco, Annayya R. Aroor, James R. Sowers, The pathophysiology of hypertension in patients with obesity, (2014);10(6):364-376.)

inclusion criteria. Of these, one study was a ran-
domized clinical trial while the other nine were
observational cohort studies: six prospective and
three retrospective studies. In all these studies, BMI,
waist circumference or triceps skin fold was used as
a measure of body fatness and New York Heart As-
sociation Classification of Heart Failure. All had a
single outcome, death, as study end point. The
studies were longitudinal studies and all reported
improved outcomes for obese heart failure patients

as compared with their normal weight counter-
parts. However, worse prognosis was demonstrated
for those presenting with extreme obesity (BMI ⬎
40 kg/m2). The findings of this review are of signifi-
cance when recommending weight loss in obese
persons with heart failure. However, any such study
results and recommendation on weight loss can be
made only on better understanding of the mecha-
nisms of the obesity paradox in heart failure pa-
tients and exclusion of collider bias. Clearly more
work is to be done in this area and the last word has
not been said.
Thus, although BMI may not necessarily be the
most accurate measure of adiposity, as it is a height-
normalized sum of fat mass and fat-free mass, it re-
mains the most commonly used metric to delineate
obesity and is a strong predictor of cardiovascular
outcomes. Although several reasons have been sug-
gested to explain the obesity paradox (i.e. marked
weight loss or frailty in those with low or normal
BMI, younger age at presentation among the obese,
less tobacco use, and possibly unmeasured con-
founders and genetic factors), cardiorespiratory
fitness appears to be an important mediator of out-
comes32. Cardiorespiratory or physical fitness appears
to have significant prognostic implications among
the obese and overweight individuals. In fact, there
is evidence that cardiorespiratory fitness modulates
and modifies the relationship between obesity and
CVD outcomes. McAuley et al. investigated the as-
sociations of cardiorespiratory fitness and adiposity
with cardiovascular outcomes in men with known or
suspected CHD and reported that cardiorespiratory
fitness greatly modifies the relation of adiposity to
outcomes with higher risk of all-cause mortality as-
sociated with low physical fitness across the BMI
categories of normal weight and class I, II and III
obese individuals33. Similar findings were reported
by Lavie et al.34, in patients with systolic heart fail-
ure, where no obesity paradox was noted in those
with high cardiorespiratory fitness. A recent prospec-
tive cohort study that included 5344 participants of
55 years of age or older from the population-based
Rotterdam Study examined the association between
overweight and obesity and CVD risk as a function
of physical activity levels and reported that the ben-
eficial impact of physical activity on CVD might
outweigh the negative impact of BMI among middle-
aged and elderly people35,36.
CONCLUSIONS
Obesity is a well-recognized risk factor for CVD.
Although the existence of an obesity paradox
Chapter 4 — Does Obesity Paradox Exist? 37
appears valid there are major concerns with this
concept. These concerns and counterarguments
against the phenomenon are summarized below:
• Obesity paradox has been mostly reported in ret-
rospective studies.
• There is a greater chance of early presentation to
the clinician in case of obese patients with HF,
leading to lag-time bias.
• Use of alternative fat assessment tools such as
dual-energy X-ray absorptiometry have been as-
sociated with conflicting results.
• Obese patients usually have a higher level of arte-
rial blood pressure which may be responsible for
a better tolerance of the guideline-directed medi-
cal therapy.
• An attenuated renin–angiotensin–aldosterone sys-
tem in obese patients may also be responsible for a
favourable prognosis.
Clearly, there is a need to perform large epide-
miological studies to evaluate the possible existence
of studies on obesity paradox. Large randomized
trials are also needed for identification of strategies
to improve prognosis in this cohort.
REFERENCES
1. Roberto, C. A., Swinburn, B., Hawkes, C., Huang, T. T.,
Costa, S. A., Ashe, M., et al. (2015). Patchy progress on
obesity prevention: Emerging examples, entrenched
barriers, and new thinking. Lancet, 385, 2400–2409.
2. Singh, G. M., Danaei, G., Farzadfar, F., Stevens, G. A.,
Woodward, M., Wormser, D., et al. (2013). The age-spe-
cific quantitative effects of metabolic risk factors on
cardiovascular diseases and diabetes: A pooled analysis.
PLoS One, 8, e65174.
3. Emerging Risk Factors Collaboration, Wormser, D., Kap-
toge, S., Di Angelantonio, E., Wood, A. M., Pennells, L.,
Thompson, A. et al. (2011). Separate and combined as-
sociations of body-mass index and abdominal adiposity
with cardiovascular disease: Collaborative analysis of 58
prospective studies. Lancet, 377, 1085–1099.
4. De Gonzalez, A. B., Hartge, P., Cerhan, J. R., Flint, A. J.,
Hannan, L., MacInnis, R J., et al. (2010). Body-mass in-
dex and mortality among 1.46 million White adults.
New England Journal of Medicine, 363, 2211–2219.
5. Zheng, W., McLerran, D. F., Rolland, B., Zhang, X., In-
oue, M., Matsuo, K., et al. (2011). Association between
body-mass index and risk of death in more than 1 mil-
lion Asians. New England Journal of Medicine, 364, 719–
729.
6. Yusuf, S., Hawken, S., Ounpuu, S., Bautista, L., Franzosi,
M. G., Commerford, P., et al. (2005). Obesity and the
risk of myocardial infarction in 27,000 participants
from 52 countries: A case-control study. Lancet, 366,
1640–1649.
7. Church, T. S., Thomas, D. M., Tudor-Locke, C., Katzmar-
zyk, P. T., Earnest, C. P., Rodarte, R. Q., et al. (2011).
38 SECTION II — Preventive Cardiology
Trends over 5 decades in U.S. occupation-
related physical activity and their associations with
obesity. PLoS One, 6, e19657.
8. Heymsfield, S. B., Gonzalez, M. C., Shen, W., Redman,
L., & Thomas, D. (2014). Weight loss composition is
one-fourth fat-free mass: A critical review and critique
of this widely cited rule. Obesity Reviews, 15, 310–321.
9. Hall, J. E., da Silva, A. A., do Carmo, J. M., Dubinion,
J., Hamza, S., Munusamy, S., et al. (2010). Obesity-
induced hypertension: Role of sympathetic nervous
system, leptin, and melanocortins. Journal of Biological
Chemistry, 285, 17271–17276.
10. Ferrannini, E., Camastra, S., Gastaldelli, A., Maria
Sironi, A., Natali, A., Muscelli, E., et al. (2004). Beta-cell
function in obesity: Effects of weight loss. Diabetes,
53(Suppl 3), S26–S33.
11. Shen, W., Wang, Z., Punyanita, M., Lei, J., Sinav, A.,
Kral, J. G., et al. (2003). Adipose tissue quantification
by imaging methods: A proposed classification.
Obesity Research, 11, 5–16.
12. Tchkonia, T., Thomou, T., Zhu, Y., Karagiannides, I.,
Pothoulakis, C., Jensen, M. D., et al. (2013). Mecha-
nisms and metabolic implications of regional
differences among fat depots. Cell Metabolism, 17,
644–656.
13. Grant, R. W., & Dixit, V. D. (2015). Adipose tissue as an
immunological organ. Obesity, 23, 512–518.
14. Ashrafian, H., Toma, T., Rowland, S. P., Harling, L.,
Tan, A., Efthimiou, E., et al. (2015). Bariatric surgery
or non-surgical weight loss for obstructive sleep ap-
noea? A systematic review and comparison of meta-
analyses. Obesity Surgery, 25, 1239–1250.
15. Goldring, M. B., & Otero, M. (2011). Inflammation
in osteoarthritis. Current Opinion in Rheumatology, 23,
471–478.
16. Hampel, H., Abraham, N. S., & El-Serag, H. B. (2005).
Meta-analysis: Obesity and the risk for gastroesopha-
geal reflux disease and its complications. Annals of
Internal Medicine, 143, 199–211.
17. Kaur, J. (2014). A comprehensive review on metabolic
syndrome. Cardiology Research and Practice. doi:
10.1155/2014/943162.
18. Calle, E. E., & Thun, M. J. (2004). Obesity and cancer.
Oncogene, 23, 6365–6378.
19. Heymsfield, S. B., & Wadden, T. A. (2017). Mecha-
nisms, pathophysiology and management of obesity.
New England Journal of Medicine, 376, 254–266.
20. Berkowitz, R. I., Fabricatore, A. N. (2011). Obesity, psy-
chiatric status, and psychiatric medications. Psychiatric
Clinics of North America, 34, 747–764.
21. Wadden, T. A., & Sarwer, D. B. (2006). Behavioral assess-
ment of candidates for bariatric surgery: A patient-
oriented approach. Obesity, 14(Suppl 2), 53S-62S.
22. Lavie, C. J., Milani, R. V., & Ventura, H. O. (2009).
Obesity and cardiovascular disease: Risk factor, para-
dox, and impact of weight loss. Journal of the American
College of Cardiology, 53, 1925–1932.
23. Lavie, C. J., McAuley, P. A., Church, T. S., Milani, R. V.,
& Blair, S. N. (2014). Obesity and cardiovascular
diseases. Journal of the American College of Cardiology,
63, 1345–1354.
24. Uretsky, S., Messerli, F. H., Bangalore, S., Champion,
A., Cooper-Dehoff, R. M., Zhou Q., et al. (2007).
Obesity paradox in patients with hypertension and
coronary artery disease. American Journal of Medicine,
120, 863–870.
25. Romero-Corral, A., Montori, V. M., Somers, V. K., Ko-
rinek, J., Thomas, R. J, Allison, T. G., et al. (2006). As-
sociation of bodyweight with total mortality and with
cardiovascular events in coronary artery disease: A sys-
tematic review of cohort studies. Lancet, 368, 666–678.
26. De Schutter, A., Lavie, C. J., & Milani, R. V. (2014). The
impact of obesity on risk factors and prevalence of coro-
nary heart disease: The obesity paradox. Progress in
Cardiovascular Diseases, 56, 401–408.
27. Voulgari, C., Tentolouris, N., Dilaveris, P., Tousoulis,
D., Katsilambros, N., & Stefanadis, C. (2011). Increased
heart failure risk in normal-weight people with meta-
bolic syndrome compared with metabolically healthy
obese individuals. Journal of the American College of
Cardiology, 58, 1343–1350.
28. Oreopoulos, A., Padwal, R., Kalantar-Zadeh, K., Fon-
arow, G. C., Norris, C. M., & McAlister, F. A. (2008). Body
mass index and mortality in heart failure: A meta-analysis.
American Heart Journal, 156, 13–22.
29. Wanahita, N., Messerli, F. H., Bangalore, S., Gami, A. S.,
Somers, V. K., & Steinberg, J. S. (2008). Atrial fibrillation
and obesity results of a meta-analysis. American Heart
Journal, 155, 310–315.
30. DeMarco, V. G., Aroor, A. R., & Sowers, J. R. (2014). The
pathophysiology of hypertension in patients with obe-
sity. Nature Reviews Endocrinology, 10, 364–376.
31. Oga, E. A., & Esevien, O. R. (2016). The obesity paradox
and heart failure: A systemic review of a decade of
evidence. Journal of Obesity, 2016, 9040248.
32. Mukherjee, D., & Ojha, C. (2017). Obesity paradox in
contemporary cardiology practice. JACC Cardiovascular
Interventions, 10, 1293–1294.
33. McAuley, P. A., Artero, E. G., Sui, X., Lee, D. C.,
Church, T. S., Lavie, C. J. et al. (2012). The obesity
paradox, cardiorespiratory fitness, and coronary heart
disease. Mayo Clinic Proceedings, 87, 443–451.
34. Lavie, C. J., Cahalin, L. P., Chase, P., Myers, J., Bensim-
hon, D., Peberdy, M. A., et al. (2013). Impact of cardio-
respiratory fitness on the obesity paradox in patients
with heart failure. Mayo Clinic Proceedings, 88, 251–258.
35. Dhana, K., Koolhaas, C. M., Schoufour, J. D., Ikram, M. A.,
Kavousi, M., & Franco, O. H. (2017). Impact of physical
activity on the association of overweight and obesity with
cardiovascular disease: The Rotterdam Study. European
Journal of Preventive Cardiology, 24, 934–941.
36. Nagarajan, V., Kohan, L., Holland, E., Keeley, E. C., &
Mazimba, S. (2016). Obesity paradox in heart failure: A
heavy matter. ESC Heart Failure, 3, 227–234.