Postgraduate Medicine

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Sarcopenic obesity as a determinant of

cardiovascular disease risk in older people: a
systematic review

Katherine Evans, Dima Abdelhafiz & Ahmed H Abdelhafiz

To cite this article: Katherine Evans, Dima Abdelhafiz & Ahmed H Abdelhafiz (2021): Sarcopenic
obesity as a determinant of cardiovascular disease risk in older people: a systematic review,
Postgraduate Medicine, DOI: 10.1080/00325481.2021.1942934

To link to this article: https://doi.org/10.1080/00325481.2021.1942934

Published online: 12 Jul 2021.

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POSTGRADUATE MEDICINE
https://doi.org/10.1080/00325481.2021.1942934

CLINICAL FOCUS: CARDIOMETABOLIC CONDITIONS

REVIEW

Sarcopenic obesity as a determinant of cardiovascular disease risk in older people:

a systematic review
Katherine Evansa, Dima Abdelhafizb and Ahmed H Abdelhafiza
a
Department of Geriatric Medicine, Rotherham General Hospital, Rotherham UK; bLancaster Medical School, Lancaster, UK

Abstract ARTICLE HISTORY

Background: Aging is associated with body composition changes that include a reduction of muscle Received 24 February 2021
mass or sarcopenia and an increase in visceral obesity. Thus, aging involves a muscle-fat imbalance with Accepted 10 June 2021
a shift toward more fat and less muscle. Therefore, sarcopenic obesity, defined as a combination of
KEYWORDS
sarcopenia and obesity, is a global health phenomenon due to the increased aging of the population
Aging; sarcopenia; obesity;
combined with the increased epidemic of obesity. Previous studies have shown inconsistent association sarcopenic obesity;
between sarcopenic obesity and the risk of cardiovascular disease (CVD). cardiovascular risk
Aims: To systematically review the recent literature on the CVD risks associated with sarcopenic obesity
and summarizes ways of diagnosis and prevention.
Methods: A systematic review of studies that reported the association between sarcopenic obesity and
CVD risk in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses
(PRISMA) recommendations.
Results: Risk factors of sarcopenic obesity included genetic factors, aging, malnutrition, sedentary
lifestyle, hormonal deficiencies and other molecular changes. The muscle-fat imbalance with increasing
age results in an increase in the pro-inflammatory adipokines secreted by adipocytes and a decline in
the anti-inflammatory myokines secreted by myocytes. This imbalance promotes and perpetuates
a chronic low-grade inflammatory state that is characteristic of sarcopenic obesity. After application
of exclusion criteria, only 12 recent studies were included in this review. The recent studies have shown
a consistent association between sarcopenic obesity and cardiovascular disease risk although most of
the studies are of cross-sectional design that does not confirm a causal relationship. In addition, most of
the population studied were of Asian origin which may limit the generalizability of the results. Non-
pharmacological interventions by exercise training and adequate nutrition appear to be useful in
maintenance of muscle strength and muscle mass in combination with a reduction of adiposity to
promote healthy aging.
Conclusions: Sarcopenic obesity appears to increase the risk of CVD in older people; however, future
prospective studies of diverse population are still required. Although non-pharmacologic interventions
are useful in reducing the risk of sarcopenic obesity, novel specific pharmacologic agents are lacking.

Introduction
Aging of population or the demographic shift toward older
age is a global phenomenon. For example, in 2015, there was
900 million people aged ≥60 years and by 2050 this is
expected to increase to 2 billion. [1] Aging of the population
affects both high-income countries such as Japan, with around
30% of the population above the age of 60 years, as well as
low- and middle-income countries. By the year 2050, about
80% of all older populations will be living in the low- and
middle-income countries. [1] The prevalence of cardiovascular
disease (CVD) increases proportionally with increasing age,
from 54% in individuals aged 40–59 years and 78% in the
age group of 60–79 years to 90% in those who are above
the age of 80 years. [2] CVD-age linked association is related to
cardiac degeneration, increased inflammation, oxidative stress
and apoptosis. [3] Aging is also associated with body compo­
sition changes such as a reduction in the muscle mass and an
increase in visceral fat that shift the metabolism to an unfa­
vorable state which increases the risk of CVD. Other age-
related conditions such as sedentary lifestyle and malnutrition
may further exaggerate the age-related body composition
changes leading to a state of sarcopenic obesity which
appears to emerge as a new determinant of CVD risk in old
age. Although there is a wealth of literature on the relation­
ship between sarcopenic obesity and cardiovascular risk fac­
tors, so far there is paucity of studies that examined the
associations between sarcopenic obesity and the risk of CVD
in old age. [4,5] This manuscript explores age-related body
composition changes, muscle-adipose tissue interaction, risk
factors and prevalence of sarcopenic obesity, systematically
reviews the recent literature on the CVD risks associated with
sarcopenic obesity and summarizes ways of diagnosis and
prevention.

CONTACT Ahmed H Abdelhafiz ahmedhafiz@hotmail.com Department of Geriatric Medicine, Rotherham General Hospital, Rotherham S60 2UD, UK
© 2021 Informa UK Limited, trading as Taylor & Francis Group
2 K. EVANS ET AL.
Methods
We undertook a detailed literature search for studies that
reported the association of sarcopenic obesity with CVD risk
in accordance with the Preferred Reporting Items for
Systematic Reviews and Meta-Analyses (PRISMA) recommen­
dations. Full assessment of relevant articles was conducted by
searching the following databases: Google Scholar, Medline
and Embase. We used Medical Subject Heading (MeSH) terms:
aging, older people, old age, elderly, composition, body,
changes, cardiac, vascular, risk, factor, complications, sarcope­
nia, sarcopenic obesity, obesity, muscle mass, muscle strength,
outcome, diagnosis, screening, prevention. These MeSH were
searched for in a combined or in an individual format. We
reviewed all the articles initially by abstract alone. Then we
performed a manual search of the citations in the relevant
articles to retrieve further related studies. Search was limited
to the studies on humans published only in English language
over the last five years from 1/04/2016 to 31/03/2021. We
defined old age as ≥55 years old. The inclusion criteria of the
study were as follows: (1) studies reported an outcome of the
association between sarcopenic obesity and CVD risk and (2)
studies evaluating individuals aged ≥55 years. The exclusion
criteria of the study were as follows: 1. Studies evaluating the
association between sarcopenic obesity and only CV risk fac­
tors rather than CVD risk, 2. Studies reporting relationship of
sarcopenic obesity with metabolic or other outcomes, 3.
Studies on younger age groups (<55 years old), 4. Case
reports, review articles, editorials, conference proceedings or
expert opinions. Data were extracted from each study in
a predesigned standardized information table that included
author, study design, year of publication, country of origin,
participants studied, aim of the study and the main findings.
We have compared recent studies with the previous literature
to draw valid conclusions. Any disagreement between authors
was resolved by consensus.
Age-related body composition changes
Aging is associated with body composition changes that pre­
dispose older people to unfavorable metabolism such as
increased insulin resistance and glucose intolerance making
them more susceptible to develop CVD. [6] By increasing age,
body fat increases and muscle mass declines, such that
weight is mostly gained as fat rather than as lean muscle
mass. [7,8] Age-related progressive muscle loss may reach
about 6% per decade after mid-life. [9] This age-related reduc­
tion in the lean muscle mass contributes to a reduction in the
basal metabolic rate. [10] Adaptation to the low resting meta­
bolic rate increases thermogenesis that further perpetuates
muscle mass loss and increases body fat. [11] Other contribut­
ing factors to the reduced basal metabolic rate are reduced
physical activity, reduced mitochondrial volume and reduced
oxidative capacity. [12,13] Reduction in energy expenditure
due to age-related inactivity is associated with a gradual
increase in body fat, positive energy balance and weight
gain. [14] As the muscle is the main site of glucose consump­
tion, the loss of muscle mass and the accumulation of fat
within the muscles reduces insulin sensitivity. Moreover,
aging is associated with changes in body fat distribution
that includes a loss of subcutaneous fat, accumulation of
visceral fat and deposition of ectopic fat. [15] Insulin resis­
tance, as a result, increases due to the increased level of free
fatty acids resulting from increased lipolysis of visceral fat.
[16] Muscle strength, independent of muscle mass, is also
reduced with increasing aging as well as reduction in muscle
quality due to a decline in muscle fiber size and number and
reduced synthesis of muscle protein. [17–19] There is
a reduction in pancreatic β-cell number and function with
increasing age leading to reduced insulin secretion further
increasing glucose intolerance. [20] Sex-specific hormonal
changes are also an important factor contributing to the
development of sarcopenic obesity. For example, reduced
estrogen levels in women after menopause results in
increased body weight and fat mass and a shift in the accu­
mulation of fat from subcutaneous to visceral sites. [21,22]
Testosterone levels decline in men by about 1% per year
which contributes to a reduction in muscle mass, muscle
strength and muscle function. [23,24] Other skeletal changes
such as vertebral body compressions result in a reduction in
height which may affects anthropometric measurements such
as the body mass index (BMI). [25]
Muscle-adipose tissue interaction
Skeletal muscle cells secret endocrine, autocrine and paracrine
mediators collectively known as myokines. These myokines
have a positive metabolic effects such as increasing muscular
glucose uptake by enhancing insulin sensitivity, increasing
oxidation of free fatty acids, stimulating hepatic gluconeogen­
esis, inducing lipolysis and regulation of energy expenditure.
[26,27] The balance between catabolic and anabolic pathways
determines muscle metabolic efficiency. This balance however,
is disturbed with increasing age that leads to a shift toward
increasing catabolism and subsequently to a loss of muscle
mass. Age-related sedentary lifestyle and the reduction in
physical activity lead to an increase in visceral fat deposition
and adipose tissue mass. The production of adipokines
increases due to increased hyperplasia and hypertrophy of
adipocytes with increasing age. In addition, the production
of pro-inflammatory cytokines, interleukins and tumor necrosis
factor alpha (TNF-α) increases due to the increased accumula­
tion of immune cells and secretion of leptin in the adipose
tissue. [28,29] Therefore, the balance between the harmful
pro-inflammatory adipokines secreted by adipocytes such as
leptin, IL-6, IL-12, IL-18 and TNFα and the beneficial anti-
inflammatory myokines such as IL-8, IL-10, IL-13, IL-15 and
apelin secreted by myocytes is disturbed by increasing age.
[30] The pro-inflammatory cytokines reduce the anabolic
effects of insulin-like growth factor-1 (IGF-1) which results in
a reduction of muscle mass. The negative metabolic effects of
adipokines create a state of chronic low-grade inflammation
which may be the main factor behind the increased risk of
CVD with sarcopenic obesity. The low-grade chronic inflam­
mation may be also due to the increased infiltration of mus­
cles by adipose tissue. Therefore, the loss of muscle mass
combined with the increase in adipose tissue leads to
a vicious circle that promotes an unfavorable metabolic state

Figure 1. Muscle-fat interaction of sarcopenic obesity leading to a vicious circle that promotes unfavorable metabolism and increased risk of CVD.
CVD = Cardiovascular disease.
such as increased insulin resistance, pro-inflammatory cyto­
kines, increased dietary energy, reduced physical activity,
increased oxidative stress and mitochondrial dysfunction
which in turn increases the risk of atherosclerosis and CVD.
[31,32] (Figure 1)
Risks factors for sarcopenic obesity
The risk factors for developing sarcopenic obesity appear to
be multifactorial. Genetic ACTN3 R577X polymorphism has
been shown to be associated with sarcopenia in older
women >75 years of age. [33] Advanced age which is asso­
ciated with loss of motor neuron units, malnutrition such as
low protein and vitamin D intake and sedentary lifestyle are
other contributing factors. In addition, other cellular and
POSTGRADUATE MEDICINE 3
molecular mechanisms are involved such as inflammation,
insulin resistance, oxidative stress and low gonadal and
growth hormone levels. Testosterone is an anabolic hormone
that stimulates protein synthesis by increasing amino acid
utilization and androgen receptor expression in skeletal mus­
cle cells that increase muscle mass. Therefore, reduction of
testosterone with increasing age contributes to reduced mus­
cle mass. [34] Similarly, in menopausal women, decreased
levels of estrogen results in increased deposition of visceral
adipose tissues and decreased fat-free mass. [35] Growth hor­
mone is another anabolic hormone that deceases with increas­
ing age leading to decreased muscle mass. These changes
lead to an increase in muscle protein breakdown,
a reduction in muscle protein synthesis and an increase in
muscle fat infiltration. [36,37] Therefore, the risk of sarcopenia
4 K. EVANS ET AL.
is related to age, gender and nutritional status. In a cross-
sectional Brazilian study of 148 patients with coronary artery
disease, mean (SD) age 73.9 (7.4) years, the prevalence of
sarcopenia was 62.8%. The variables associated with sarcope­
nia were age >80 years (p = 0.005), male gender (p = 0.014)
and malnutrition according to BMI (p < 0.001), arm circumfer­
ence (p = 0.006) and calf circumference (p = 0.045). [38] Also
increased number of comorbidities appears to increase the
risk of sarcopenic obesity. It has been reported that the odds
ratio (OR) of sarcopenic obesity among individuals with >3
comorbidities was 2.71 {95% confidence interval (CI) 1.62 to
4.54} among males and 1.14 (0.79 to 1.65) among females
compared to those with no morbidities, independent of
other determinants. [39] Risk factors of sarcopenic obesity
are summarized in Box 1.
Prevalence of sarcopenic obesity
The prevalence of sarcopenic obesity may vary due to the
inconsistency in its definition. The US National Health and
Nutrition Examination Survey (NHANES) which included 4,984
subjects aged ≥60 years, reported a prevalence of 12.6% in
men and 33.5% in women. The prevalence increased with age,
reaching up to 48.0% and 27.5% in females and males respec­
tively, in those >80 years old. [40] In a Brazilian study of 270
non-institutionalized older people, mean (SD) age 77.5 (5.92)
years, the prevalence of sarcopenic obesity was 29.3% but
contrary to the US study, the prevalence was higher among
men (65.3%) than among women (34.6%). This could be due
to the difference in the evaluation methods, criteria or ethnic
differences of the participants. [41] Data from the Korea
NHANES reported a prevalence of 7.8% for men and 9.6% for
women among 1,583 older people, average age 72.8 years.
[42] Recently 119,494 participants, aged 18–90 years were
included in the Dutch Lifelines cohort study which showed
an overall prevalence of 0.9% for men and 1.4% for women.
Age was a significant determinant of sarcopenic obesity with
a prevalence of 0.4% for those aged 20–29.9 years, 2.6% in
those aged 60–69.9 years, 4.2% in those aged 70–79.9 years
and 12.2% in those aged 80–89.9 years. Females had a higher
prevalence than men in all age groups especially in those
aged 80–89 (16.7% vs 6.3%). Overall, an inverse association
was found between sarcopenic obesity and physical activity
and macronutrient intake. [39]
Box1: Risks factors for sarcopenic obesity.
● Genetic.
● Aging.
● Malnutrition.
● Inadequate protein intake.
● Vitamin D deficiency.
● Sedentary lifestyle.
● Insulin resistance.
● Reduced growth and sex hormones.
● Oxidative stress.
● Low grade chronic inflammation.
● Mitochondrial dysfunction.
● Loss of motor neurone units.
● Peripheral neuropathy.
● Multiple comorbidities.
Sarcopenic obesity and cardiovascular risk
Several cross-sectional earlier studies have confirmed the asso­
ciation between sarcopenic obesity and increased risk of car­
diovascular risk factors such as insulin resistance, adverse
glucose metabolism, dyslipidaemia, hypertension and meta­
bolic syndrome compared to sarcopenia or obesity alone. [43–
46] The association, however, was not always consistent as
demonstrated by recent meta-analyses that showed that sar­
copenic obesity significantly increased the risk of type 2 dia­
betes (OR 1.38, 95% CI 1.27 to 1.50) but not metabolic
syndrome (risk ratio 1.08, 95% CI 0.99 to 1.17). [47,48] The
results of these meta-analyses should be interpreted with
caution as most of the studies included were cross-sectional
and examined an association rather than a causal relationship.
On the other hand, the association between sarcopenic obe­
sity and CVD risk, rather than CV risk factors, is not well
established. The following summarizes the earlier studies
that examined this association followed by a systematic search
of the recently published studies over the last 5 years.
A. Previous evidence
Previous observational studies have examined the association
between sarcopenic obesity and CVD but results were not
consistent. The cross-sectional New Mexico Ageing Process
Study which compared the prevalence of CVD in older people
≥ 60 years old has demonstrated similarities in the prevalence
of CVD in sarcopenic obese individuals and non-sarcopenic,
non-obese individuals (11.5% vs 13.7%, respectively,). [49]
However, the Korea NHANES of people ≥ 60 years old has
found that the sarcopenic obese individuals had higher but
non-significant prevalence of CVD compared to non-
sarcopenic obese ones (12.3 vs 10.0%). [50] Similarly, the risk
of CVD events were found to be comparable among sarcope­
nic obese participants and those with normal body composi­
tion as prospectively demonstrated in the cardiovascular
health study that included 3,366 community-dwelling older
people (aged ≥ 65 years) followed up for 8 years. [51] Data
from the prospective British regional heart study, which
included 4,111 men, aged 60–79 years and followed up for
11 years, showed no association between sarcopenic obesity
and CVD or cardiovascular events. [52] The inconsistencies
between these studies could be related to the variations in
the definition of sarcopenic obesity. [53]
B. Results of Recent research
Initial literature search has yielded a total of 788 studies. After
application of exclusion criteria, only 12 studies were
included. (Figure 2). Several recent studies have demonstrated
that sarcopenic obesity is associated with an increased CVD
risk. [54–65] (Table 1) A large cross sectional Korean study of
1,282 Korean subjects reported a significant association of
sarcopenic obesity with arterial atherosclerosis measured by
coronary artery calcification compared to those without sar­
copenia or obesity independent of age, sex, hypertension,
diabetes, dyslipidaemia or serum creatinine level. [54] This
study, however, included subjects who voluntarily underwent

Figure 2. PRISMA flow diagram.
health evaluation therefore, they may not represent the gen­
eral Korean population. A Chinese cross-sectional analysis
from Shanghai Changfeng study, which included 2,432
Chinese subjects, has shown an independent association of
sarcopenia with myocardial infarction risk in all participants
and atrial fibrillation risk in those who are either overweight or
obese. [55] This study was limited by using indirect evidence
of ischemia such as history and symptoms rather than the
gold standard of coronary angiography. In a Japanese cross-
sectional study, which included 321 Japanese subjects, para­
meters reflecting lower limb muscle function such as gait
speed and quadriceps isometric strength were associated
with atherosclerosis in older patients with ischemic heart dis­
ease. [56] However, potential confounding factors for athero­
sclerosis such as lifestyle, physical activity and socioeconomic
status were not adjusted for in this study. In comparison with
non-obese, non-sarcopenic subjects the risk of diastolic dys­
function was found to be much higher in sarcopenic obesity,
followed by obesity alone as demonstrated in a Korean cross-
sectional study which included a large sample size of 31,258
Korean subjects. [57] The association between sarcopenic
obese status and diastolic dysfunction remained significant
after adjustment for diabetes, hypertension and regular exer­
cise however, due to the cross sectional design of the study,
a causal relation cannot be drawn. Low skeletal muscle mass,
diagnosed by CT scan, was found to be an independent
predictor of major adverse cardiovascular events (MACE) and
all-cause mortality in patients with known coronary artery
disease (CAD) undergoing per-cutaneous coronary interven­
tion in another prospective Korean study of 475 Korean
POSTGRADUATE MEDICINE 5
subjects[58]. Minor differences between the excluded (mostly
due to absence of CT data) and included participants may
have affected the outcome of this study. In addition the
sample size of 475 was not large enough to draw a solid
conclusion. A Chinse prospective study has demonstrated
that the cerebrovascular and MACE-free survival time to be
significantly shorter in 345 CAD Chinese patients with com­
pared to those without sarcopenia. [59] However, there were
no significant differences in the rates of MACE and all-cause
mortality between sarcopenic and non-sarcopenic patients
with CAD likely due to the small sample size and the short
duration of follow-up (median 351 days). In a large British
cohort study and analysis of 452,931 subjects (94% white,
2.5% South Asians, 2.0% African Caribbean and 1.5% other
ethnic groups) using UK Biobank, low hand grip strength was
associated with all-cause and cardiovascular mortality and
obesity was associated with adverse outcomes. There was no
evidence to suggest that good muscle quality would reduce
the negative effects of obesity on outcomes. [60] In a small
Brazilian retrospective study which included 99 older patients
(31.3% white and 68.7% nonwhite) hospitalized for acute
myocardial infarction, the risk of thrombolysis was increased
by the presence of sarcopenia but other prognostic markers
such as type of myocardial infarction or cardiac enzymes were
not associated with sarcopenia. [61] However, the analysis of
this study is limited by the retrospective design, which may
have incomplete or missing medical records data and the
small sample size, which may have an impact on the statistical
power of the study. In a Japanese retrospective study, which
included 716 Japanese patients, sarcopenic obesity,
6 K. EVANS ET AL.

Table 1 : Recent studies on sarcopenia/sarcopenic obesity and cardiovascular disease risk in older people.
Study Patients Aim to Main findings
Chung GE, et al, 1,282 subjects, mean (SD) age 58.1 (9.3) Investigate association of sarcopenic obesity A. Prevalence of high CAC score was higher in
2021, cross Y. and atherosclerosis. sarcopenic obese subjects (40.7%, p < 0.001).
sectional, B. After adjusting for confounding factors, subjects
54]
Korea.[ with sarcopenic obesity had higher odds of high
CAC score (OR 1.92, 95% CI 1.16 to 3.18, p-0.011).
Xia MF, et al, 2,432 participants, mean (SD) age 62.2 Investigate associations of sarcopenia, Compared with non-sarcopenic participants:
2021, cross (8.4) Y. sarcopenic overweight/obesity with A. Sarcopenia associated with high prevalence of
sectional, carotid atherosclerosis, CVD and CA (26.4% vs 20.4%, p = 0.027), MI (4.0% vs 1.1%,
China[55] arrhythmia. p = 0.001), and PVC (4.0% vs 2.0%, p = 0.034) in
normal body weight subjects.
B. Sarcopenia associated with high prevalence of
CA (45.0% vs 31.2%, p = 0.016), MI (10.0% vs
4.3%, p = 0.020) and AF (7.5% vs 1.3%, p < 0.001)
in overweight/obese subjects.
C. Sarcopenia associated with MI in whole
population and AF in overweight/obese subjects
p < 0.05).
D. Risk of MI increased in sarcopenic lean (OR 3.08,
95% CI 1.28 to 7.45, p = 0.012).
E. Concomitant sarcopenia and overweight/
obesity associated with 5-fold risk of AF (57.5, 1.34
to 24.12, p = 0.019).
Uchida S, et al, 321 patients with IHD, mean (SD) age Investigate link between sarcopenia and A. IMT significantly lower in patients with high
2020, cross 74.1 (6.0) Y. atherosclerosis. muscle strength compared to medium and low
sectional, strength (p < 0.05).
Japan.[56] B. Gait speed and quadriceps isometric strength
associated with IMT (p < 0.05).
Yoo JH, et al, 31,258 subjects, mean (SD) 55.0 (9.9) Y. Investigate relationship of low skeletal A. OR of diastolic dysfunction 1.56, 95% CI 1.31 to
2020, cross muscle mass, sarcopenic obesity, and 1.85, p < 0.001 for lowest SMI tertile relative to
sectional, diastolic dysfunction. highest SMI tertile.
Korea.[57] B. Compared to non-obese, non-sarcopenic: risk of
diastolic dysfunction higher in sarcopenic obese
(1.70, 1.44 to 1.99), followed by obese only (1.40,
1.21 to 1.62), and sarcopenic-only (1.32, 1.08
to1.61), results remained consistent in those ≥ 65
Y.
Kang DO, et al, 475 patients (141 with low SMI, mean Investigate prognostic impact of sarcopenia A. Low SMI was present in 141 (29.7%) of patients.
2019, (SD) age 70.4 (11.0) Y, 334 with high on CAD in patients with CAD and B. Incidence of all-cause mortality (23.7% vs. 5.9%,
prospective, SMI, mean (SD) age 64.0 (9.2) Y. successful PCI. p < 0.001) and MACE (39.6% vs. 11.8%, p < 0.001)
58]
Korea.[ was significantly higher in patients with low SMI
than in those with high SMI.
C. Low SMI was independent predictor of higher
risk of all-cause mortality (HR 4.07, 95% CI 1.95 to
8.45, p < 0.001) and MACE (3.76, 2.27 to 6.23,
p < 0.001).
Zhang N, et al, 345 patients with CAD, median (IQR) age Investigate prevalence of sarcopenia and its A. 78 (22.6%) patients were diagnosed with
2019, 74 (69, 79) Y. effect on short term prognosis of sarcopenia.
prospective, hospitalized patients with CAD. B. Significantly more unscheduled return visits in
China.[59] sarcopenic than in non-sarcopenic patients (34.2%
vs. 21.8%, p = 0.036).
C. MACCE-free survival time of sarcopenic was
significantly shorter than non-sarcopenic patients
(p = 0.043).
D. After adjustment for confounders, sarcopenia
was not an independent risk factor of unscheduled
return visits.
Farmer RE, et al, Using UK Biobank of 452,931 patients, Test associations of sarcopenic obesity and A. Obesity was associated with increased risk of all
2019, cohort, mean age range 56.2 to 59.5 Y. CVD risk and mortality. outcomes (fatal and non-fatal CVD and mortality),
UK[60] HR range 1.10–1.82.
B. Low HGS associated with increased risks of CV
and all-cause mortality (HR range 1.39–1.72) and
CVD events (HR range 1.05–1.09).
Santana ND, et al, 99 patients, mean (SD) age 71.6 (7.4) Y. Investigate sarcopenia and sarcopenic A. Prevalence of sarcopenia 64.6%, higher in older
2019, obesity as predictors in hospitalized age >80 Y (p = 0.008) and in males (p = 0.017)
retrospective, elderly with acute MI. and prevalence of sarcopenic obesity 34.5%.
Brazil.[61] B. Thrombolysis in MI was the only marker of CV
risk significantly associated with sarcopenia
(p = 0.002).
C. Sarcopenic obesity was not associated with
prognostic predictors.
(Continued )
 POSTGRADUATE MEDICINE 7

Table 1 (Continued).
Fukuda T, et al, 716 patients, mean (SD) age 65.0 (13) Y. Investigate impact of sarcopenic obesity on Over a median follow up of 2.6 years, sarcopenic
2018, incident CVD in patients with type 2 obesity was independently associated with
retrospective, diabetes. incident CVD when using A/G ratio (HR 2.63, 95%
Japan.[62] CI 1.10 to 6.28, p = 0.030) and android fat mass
(2.57, 1.01 to 6.54, p = 0.048) to define obesity,
but not %BF (1.67, 0.69 to 4.02, p = 0.252) or BMI
(1.55, 0.44 to 5.49, p = 0.496).
Bellanti F, et al, 115 patients, mean (SD) age 76.5 (7.0) Define if circulating markers of oxidative A. Oxidative stress markers were significantly higher
2018, cross for non-sarcopenic and 78.0 (6.2) for stress correlate with sarcopenia and CVD in sarcopenic than in non-sarcopenic patients (OR
sectional, Italy. sarcopenic patients. 1.13, 95% CI 1.06 to 1.22 and 1.59, 1.02 to 1.99).
[63] B. Strong associations between oxidative stress
biomarkers and carotid IMT or Framingham CVD
risk in sarcopenic obesity group (p < 0.0001).
Kamiya K, et al, 1,603 patients with CVD, mean (SD) age Investigate prevalence and prognostic value A. Sarcopenia total prevalence 29.7% (19.6% men,
2017, 74.4 (6.2) Y. of sarcopenia in older patients with CVD. 48.7% women), 17.8% in ACS, 31.8% in post-
retrospective, cardiac surgery and 35.2% in HF.
64]
Japan.[ B. Sarcopenia increased risk of all-cause mortality
(HR 1.44, 95% CI 1.01 to 2.05, p = 0.044).
Campos AM, 208 patients, mean (SD) age 83.0 (6.0) Y. Investigate if sarcopenia, excess weight or A. Muscle mass inversely associated with CCS
et al, 2017, both are associated with CCS and/or categories (OR 2.54, 95% CI 1.06 to 6.06,
cross sectional, endothelial dysfunction. p = 0.018).
65]
Brazil.[ B. Low gait speed negatively related to CCS>100
(2.36, 1.10 to 5.06, p = 0.028).
C. Skeletal muscle index directly associated with
FMD (5.44, 1.22 to 24.24, p = 0.026).
SD = Standard deviation, Y = Year, CAC = Coronary artery calcification, OR = Odds ratio, CI = Confidence interval, CVD = Cardiovascular disease, CA = Carotid
atherosclerosis, PVC = Premature ventricular contractions, AF = Atrial fibrillation, MI = Myocardial infarction, IHD = Ischemic heart disease, IMT = intima-media
thickness, SMI = Skeletal muscle mass index, CAD = Coronary artery disease, PCI = Percutaneous coronary intervention, MACE = Major adverse cardiovascular
events, IQR = Inter quartile range, MACCE = Major adverse cardiovascular and cerebral events, HR = Hazard ratio, HGS = Handgrip strength, A/G = Android to
gynoid, BF = Body fat, BMI = Body mass index, ACS = Acute coronary syndrome, HF = Heart failure, CCS = coronary calcium score, FMD = flow-mediated dilation.

diagnosed using dual energy X-ray absorptiometry (DEXA)
scan, was significantly associated with incident CVD events
in patients with type 2 diabetes. [62] In a small cross sectional
Italian study which included 115 older Italian subjects, there
was a significant association of markers of oxidative stress,
indicating an increased CVD risk, and sarcopenic obesity. [63]
Sarcopenia was also found to be highly prevalent among
older patients with CVD and a significant predictor of all-
cause mortality in a retrospective Japanese study of 1,603
Japanese subjects, however, other factors associated with
mortality such as physical activity, socioeconomic status and
dementia were not taken into account. [64] In the cross-
sectional Brazilian study of 208 Brazilian subjects, sarcopenia
was associated with subclinical atherosclerosis and endothe­
lial dysfunction however, increased fat mass was not asso­
ciated with atherosclerosis in the very elderly (≥80 years
old). [65] Summary of recent studies is detailed in Table 1.
Management
Although a causal relationship between sarcopenic obesity and
CVD outcomes is not yet established, improving muscle mass
and power could be a potential therapeutic target for
a possible reduction of adverse CVD events. Recently, increased
genetically predicted muscle strength, but not muscle mass, has
been shown to be causally associated with decreased risk of
CVD. This suggests that in sarcopenic obesity the reduction in
muscle power, not only the muscle mass is responsible for the
increased risk of CVD. [66] In addition to CVD adverse out­
comes, sarcopenic obesity is also associated with increased
risk of frailty, disability, poor quality of life and all-cause mor­
tality. [67] The effects of sarcopenic obesity on all-cause mor­
tality appears to be more than that of sarcopenia alone or
obesity alone suggesting a synergistic effect. [68] Since sarco­
penia is affected by multifactorial etiologies, a comprehensive
multidisciplinary approach including both non-pharmacologic
and pharmacologic interventions should be considered.
Screening and diagnosis
The diagnosis of sarcopenic obesity is not straightforward as
so far there is no clear agreement on its definition. From its
name, sarcopenic obesity is a combination of sarcopenia and
obesity. SARC-F is a screening tool for sarcopenia consisting of
a questionnaire including five self-reported symptoms and
BMI can be used to screen for obesity. [69] (Box 2) The
diagnosis of sarcopenic obesity should include the diagnosis
of the combined sarcopenia and obesity. The diagnosis of
sarcopenia is based on the presence of low muscle mass,
low muscle strength and low muscle function. Diagnostic
methods in clinical practice include ways of measuring these
parameters such as DEXA scan, handgrip strength, gait speed
and short physical performance battery. Based on these para­
meters, the revised European Working Group on Sarcopenia in
Older People (EWGSOP2) has emphasized that sarcopenia is
a muscle disease or a muscle failure with low muscle strength
overtaking the role of low muscle mass as a principal determi­
nant. Therefore, the diagnosis of sarcopenia should include
the reduction of muscle mass associated with reduced
strength or function and the evaluation of muscle mass
alone would be insufficient and of a limited clinical value.
[70] The definition of obesity includes the measurement of
body fat that is over a cutoff level compared to a reference
population of the same age and gender. DEXA scan is more
accurate and superior to BMI for the diagnosis of obesity. BMI
fails to account for the age-related body composition changes
8 K. EVANS ET AL.
Box2: Screening and diagnosis of sarcopenic obesity.
Screening for sarcopenic obesity
69*
Sarcopenia: SARC-F Scale
(1) Strength (difficulty lifting a weight of 10 pounds).
(2)Assistance in walking (difficulty walking across a room).
(3)Rise from a chair (difficulty to transfer from chair to bed).
(4)Climbing stairs (difficulty to climb a flight of stairs).
(5)Falls (number of falls in the last year).
Obesity: BMI
≥30 Kg/m2
Diagnosis of sarcopenic obesity
A. Decreased muscle mass and decreased muscle strength or performance.
B. Increased body fat.
Muscle mass measurement
ASM <20.0 kg (men), <15.0 kg (women).
SMI <7.0 kg/m2 (men), <6.0 kg/m2 (women).
Muscle strength measurement
Hand grip strength <27.0 kg (men), <16.0 kg (women).
Chair stand >15.0 s for five rises.
Muscle performance measurement
Gait speed ≤0.8 m/s.
SPPB ≤8.
TUG ≥20s.
400 meter walk test, non-completion or ≥6 min for completion.
Body fat measurement
Body fat >27% (men), >38% (women).
*Scores: answer none = 0, some difficulty = 1, unable = 2, no falls = 0, 1–3
falls = 1, ≥4 falls = 2.
Score≥4 indicates high risk of adverse outcomes from sarcopenia.
ASM = Appendicular skeletal muscle mass, M = Men, W = Women,
SPPB = Short physical performance battery, TUG = Timed-Up and Go test,
SMI = Skeletal muscle mass index (ASM/height in m2).
while DEXA scan can measure both fat and muscle
masses. [62]
Non-pharmacologic intervention
Non-pharmacologic interventions in patients with sarcopenic
obesity mainly include adequate nutrition to reach ideal body
weight and reducing obesity, exercise training to restore mus­
cle mass and strength or a combination of both. In addition,
such multidisciplinary programs that focus on nutrition and
resistance exercise training may also improve overall func­
tional capacity in older people. [71] Protective myokines are
released by muscle contractions which may inhibit the activity
of the pro-inflammatory adipokines. Therefore, an increase in
muscle activity may have a protective effect that may reduce
the chronic low-grade inflammation associated with sarcope­
nic obesity. [72] Both resistance and aerobic exercise are use­
ful although a combination of both has been shown to be
superior to either of them alone in older people with sarco­
penic obesity. [71] Resistance exercise may improve sarcope­
nia while aerobic exercise improves obesity. Resistance
exercise training may result in improvements in physical capa­
city, muscle quality, fat-free mass and gait speed in a short
period of time. [73] Aquatic exercise may be a useful exercise
modality in older people to help compliance and adherence
and is also suitable for patients with arthritis. [74] Other exer­
cise modalities which may be suitable in disabled older people
with sarcopenic obesity such as whole-body
electromyostimulation, vibration, yoga and tai-chi may have
some benefits and can be considered as an alternative in
these patients. [75,76] Whole body electromyostimulation
application has shown a favorable effect on the metabolic
profile in community-dwelling women aged ≥70 years with
sarcopenic obesity which may be considered an effective and
safe novel technology to prevent cardiometabolic risk in those
who are unable or unwilling to exercise conventionally. [75]
Nutritional management of sarcopenic obesity is mainly based
on weight reduction to reduce obesity and adequate nutri­
tional intake to reduce muscle mass loss. Diet with sufficient
protein is important in the management of sarcopenic obesity.
A daily protein intake of 1–1.2 g/kg may enhance muscle mass
and function. [77] Little data is available on the quality of
protein supplements although the inclusion of the essential
amino acids in the diet seems reasonable, especially leucine
enriched essential amino acids (whey protein). [78] Weight loss
via energy restriction alone should be avoided because it may
cause simultaneous loss of muscle mass. Diet combined with
exercise appears to be the best strategy for improving meta­
bolic profile and preservation of lean muscle mass. [79] The
combination of resistance training and protein supplementa­
tion has been shown to reduce fat mass and to improve lean
muscle mass and strength in sarcopenic older people than
exercise alone. [80] High protein intake (35 g) after resistance
training 3 days per week for a total of 12 weeks was associated
with significant improvement in parameters of cardiometa­
bolic profile compared to low protein intake (35 g placebo)
in preconditioned older women. [81]
Pharmacologic intervention
So far, there is no specific pharmacologic agents for sarcopenic
obesity. However, the molecular changes involved in the patho­
genesis of sarcopenic obesity can be the targets for potential
therapeutic interventions. Therefore, identification of the aber­
rant molecular pathways and the possible hormone causing this
imbalance could lead to novel agents that target this abnorm­
ality. For example, drugs that may have a potential therapeutic
effect include myostatin antibodies and hormonal therapy. [26]
Myostatin antibodies may decrease body fat, increase muscle
mass and improve physical function in older people with sarco­
penic obesity although this still needs to be confirmed. [82]
Hormonal therapies such as growth hormone, growth hormone
releasing hormone analogues, hormone replacement in post-
menopausal women and androgen receptor agonists in men are
still experimental. [83–85] There is also some evidence that
metformin, as an insulin sensitizer, may improve mobility in
people with diabetes mellitus. [86] Vitamin D supplementation
may increase muscle strength and reduce the frequency of falls
especially in older people with low vitamin D levels. [87,88] The
new hypoglycemic therapies, glucagon like peptide-1 receptor
agonist (GLP-1RA) and sodium glucose cotransporter-2 (SGLT-2)
inhibitors have shown the potential to reduce weight and to
significantly reduce cardiovascular events and mortality and
may be useful in reducing obesity. [89–91] The GLP-1RA liraglu­
tide is now approved for the treatment of obesity in the absence
of diabetes and also has been shown to reduce visceral fat such
as liver fat content and induce histological resolution of biopsy-

proven nonalcoholic steatohepatitis (NASH). [92] The SGLT-2
inhibitors may reduce muscle mass by increasing proteolysis as
they activate gluconeogenesis but studies have shown that the
effect of such therapy is overall beneficial on body composition.
[93–94]
Future perspectives
Although recent studies have consistently shown that sarcope­
nic obesity is associated with increased risk of CVD, most of the
studies were cross-sectional that could not confirm a causal
relationship. In addition, most of the population included in
these studies were of Asian origin which may limit the general­
izability of the findings. Therefore, future prospective cohort
studies that include diverse participants are still required to
confirm the causal relationship between sarcopenic obesity
and CVD risk. Due to the inconsistencies in the definition of
sarcopenic obesity, prevalence is very variable that ranged from
4.4 to 84.0% and 3.6 to 94% in older (≥ 60 years) men and
women respectively in one study. [95] Therefore, there is still
a need for an agreed definition of sarcopenic obesity which
would help to have accurate estimation of the prevalence of
sarcopenic obesity and would also facilitate inclusion of correct
cases in future studies. Diagnosis of sarcopenic obesity needs to
be simplified. A new formula based on sex, body weight and calf
circumference for the diagnosis of sarcopenia is introduced with
a sensitivity and specificity of 80.8% and 95.6%, respectively and
may have a future use in sarcopenic obesity screening. [96] So
far, sarcopenic obesity is not routinely assessed in clinical prac­
tice and introduction of new formulae of this kind may help
identification of high-risk groups of older people who may
benefit from early intervention. A Body Shape Index (ABSI) that
reflects the body shape using waist circumference, weight and
height might be another useful tool in the assessment of sarco­
penic obesity. [97] The relationship between sarcopenic obesity
and CVD risk may be reciprocal. For example, CV risk factors,
particularly diabetes mellitus, were found to be significantly
associated with increased risk of sarcopenia in older people.
[98] Whether treatment of CV risk factors would prevent the
development of sarcopenia will need exploration. So far, no
pharmacologic agent is available to target sarcopenic obesity.
Novel agents to target the pathological pathways of sarcopenic
obesity such as increased oxidative stress are required. Redox
balance analysis is a novel way to detect oxidative stress.
Interventional studies aiming at the correction of redox imbal­
ance, or to define redox-dependent molecular mechanisms
underlying sarcopenic obesity may be a useful develop­
ment. [63]
Conclusion
Current evidence suggests that sarcopenic obesity is associated
with an increased risk of CVD. However, the causal relationship
between sarcopenic obesity and CVD still needs confirmation by
future prospective studies. Although non-pharmacologic inter­
vention appears effective in improving sarcopenic obesity, there
is still a need to develop novel pharmacologic therapy for the
treatment of sarcopenic obesity.
POSTGRADUATE MEDICINE 9
Key points
● Aging is associated with body composition changes that
increase the risk of sarcopenic obesity.
● Sarcopenic obesity is associated with unfavorable meta­
bolic profile that increases the risk of CVD.
● Previous studies showed inconsistent association of sar­
copenic obesity and the risk of CVD.
● Recent evidence suggests that sarcopenic obesity is
associated with CVD although a causal relationship still
needs further exploration.
● Novel specific pharmacologic therapies of sarcopenic
obesity are still required.
Transparency
Declaration of funding
The authors have no funding to declare.
Declaration of financial/other relationships
The authors have no relevant financial or other relationships to declare.
Peer reviewers on this manuscript have no relevant financial or other
relationships to disclose.
Declaration of interest
No potential conflict of interest was reported by the author(s).
References
1. Ageing and health. world health organisation. Accessed September
2020.
2. Benjamin EJ, Muntner P, Alonso A, et al. Heart disease and stroke
statistics-2019 update: a report from the american heart
association. Circulation. 2019;139:e56–e528.
3. Curtis AB, Karki R, Hattoum A, et al. Arrhythmias in patients ≥80
years of agePathophysiology, management and outcomes. J Am
Coll Cardiol. 2018;71(18):2041–2057. .
4. Atkins JL, Wannamathee SG. Sarcopenic obesity in ageing: cardio­
vascular outcomes and mortality. Br J Nutr. 2020;124
(10):1102–1113.
5. Hong SH, Choi KM. Sarcopenic obesity, insulin resistance, their
implications in cardiovascular and metabolic consequences.
Int J Mol Sci. 2020;21(2):494.
6. Evans WJ. Skeletal muscle loss: cachexia, sarcopenia, and inactivity.
Am J Clin Nutr. 2010;91(4):1123S–7S.
7. Heo M, Faith MS, Pietrobelli A, et al. Percentage of body fat cut offs
by sex, age, and race ethnicity in the US adult population from
NHANES 1999–2004. Am J Clin Nutr. 2012;95(3):594–602.
8. Sayer AA, Syddall H, Martin H, et al. The developmental origins of
sarcopenia. J Nutr Health Aging. 2008;12(7):427–432.
9. Choi KM. Sarcopenia and sarcopenic obesity. Korean J Intern Med.
2016;31(6):1054–1060.
10. Abizanda P, Romero L, Sanchez-Jurado PM, et al. Energetics of
aging and frailty: the FRADEA study. J Gerontol A Biol Sci Med
Sci. 2016;71(6):787–796. .
11. Tremblay A, Royer MM, Chaput JP, et al. Adaptive thermogenesis
can make a difference in the ability of obese individuals to lose
body weight. Int J Obes (Lond). 2013;37(6):759–764.
10 K. EVANS ET AL.
12. Conley KE, Esselman PC, Jubrias SA, et al. Ageing, muscle properties
and maximal O2 uptake rate in humans. J Physiol 2000; 526:
211–217.
13. Conley KE, Jubrias SA, Esselman PC. Oxidative capacity and ageing
in human muscle. J Physiol. 2000;526(1):203–210.
14. Doucet E, St PS, Almeras N, et al. Changes in energy expenditure
and substrate oxidation resulting from weight loss in obese men
and women: is there an important contribution of leptin? J Clin
Endocrinol Metab. 2000;85(4):1550–1556.
15. Cartwright MJ, Tchkonia T, Kirkland JL. Aging in adipocytes: poten­
tial impact of inherent, depot-specific mechanisms. Exp Gerontol.
2007;42(6):463–471.
16. Guilherme A, Virbasius JV, Puri V, et al. Adipocyte dysfunctions
linking obesity to insulin resistance and type 2 diabetes. Nat Rev
Mol Cell Biol. 2008;9(5):367–377.
17. Vandervoort AA. Aging of the human neuromuscular system.
Muscle Nerve. 2002;25(1):17e25.
18. Nair KS. Aging muscle. Am J Clin Nutr. 2005;81(5):953e63.
19. Marcell TJ. Sarcopenia: causes, consequences and preventions.
J Gerontol Med Sci. 2003;58A:M 911e6.
20. Szoke E, Shrayyef MZ, Messing S, Szoke E, Shrayyef MZ, Messing S,
et al.. Effect of aging on glucose homeostasis: accelerated dete­
rioration of β-cell function in individuals with impaired glucose
tolerance. Diabetes Care. 2008;31(3):539–543.
21. Lovejoy JC, Champagne CM, de Jonge L, et al. Increased visceral fat
and decreased energy expenditure during the menopausal
transition. Int J Obes. 2008;32(6):949–958.
22. Sowers M, Zheng H, Tomey K, et al. Changes in body composition
in women over six years at midlife: ovarian and chronological
aging. J Clin Endocrinol Metab. 2007;92(3):895–901.
23. Schaap LA, Pluijm SM, Smit JH, et al. The association of sex hor­
mone levels with poor mobility, low muscle strength and incidence
of falls among older men and women. Clin Endocrinol. 2005;63
(2):152–160.
24. O’Donnell AB, Travison TG, Harris SS, et al. Testosterone, dehydroe­
piandrosterone, and physical performance in older men: results
from the massachusetts male aging study. J Clin Endocrinol
Metab. 2006;91(2):425–431.
25. Xu WW, Perera S, Medich D, et al. Height loss, vertebral fractures,
and the misclassification of osteoporosis. Bone. 2011;48
(2):307–311.
26. Batsis JA, Villareal DT. Sarcopenic obesity in older adults: aetiology,
epidemiology and treatment strategies. Nat Rev Endocrinol.
2018;14:513–537.
27. El Bizri I, Batsis JA. Linking epidemiology and molecular mechan­
isms in sarcopenic obesity in populations. Proc Nutr Soc.
2020;14:1–9.
28. Kalinkovich A, Livshits G. Sarcopenic obesity or obese sarcopenia:
a cross talk between age-associated adipose tissue and skeletal
muscle inflammation as a main mechanism of the pathogenesis.
Ageing Res Rev. 2017;35:200–221.
29. Sente T, van Berendoncks AM, Fransen E, et al. Tumor necrosis
factor-alpha impairs adiponectin signalling, mitochondrial biogen­
esis, and myogenesis in primary human myotubes cultures. Am
J Physiol Heart Circ Physiol. 2016;310(9):H1164–75. .
30. Targeting Age-Dependent CC. Functional and metabolic decline of
human skeletal muscle: the geroprotective role of exercise, myo­
kine IL-6, and vitamin D. Int J Mol Sci. 2020;21(3):1010.
31. Kim G, Kim JH. Impact of skeletal muscle mass on metabolic health.
Endocrinol Metab. 2020;35(1):1–6.
32. Petermann-Rocha F, Chen M, Gray SR, et al. Factors associated with
sarcopenia: a cross-sectional analysis using UK Biobank. Maturitas.
2020;133:60–67.
33. Romero-Blanco C, Artiga González MJ, Gómez-Cabello A, et al.
ACTN3 R577X polymorphism related to sarcopenia and physical
fitness in active older women. Climacteric. 2021;24(1):89–94.
34. Kalyani RR, Corriere M, Ferrucci L. Age-related and disease-related
muscle loss: the effect of diabetes, obesity, and other diseases.
Lancet Diabetes Endocrinol. 2014;2(10):819–829.
35. Abdulnour J, Doucet E, Brochu M, et al. The effect of the meno­
pausal transition on body composition and cardiometabolic risk
factors: a montreal-ottawa new emerging team group study.
Menopause. 2012;19(7):760–767.
36. Amato MC, Guarnotta V, Giordano C. Body composition assessment
for the definition of cardiometabolic risk. J Endocrinol Invest.
2013;36(7):537–543.
37. Ochi M, Kohara K, Tabara Y, et al. Arterial stiffness is associated with
low thigh muscle mass in middle-aged to elderly men.
Atherosclerosis. 2010;212(1):327–332.
38. Mendes RML, Pinho CPS, Santana NDM, et al. Sarcopenia in elderly
hospitalized coronary patients. Rev Chil Nutr. 2019;46(1):12–20.
39. Wagenaar CA, Dekker LH, Navis GJ. Prevalence of sarcopenic obe­
sity and sarcopenic overweight in the general population: the life­
lines cohort study. Clin Nutr. 2021. S0261-5614(21)00012-1.
10.1016/j.clnu.2021.01.005
40. Batsis JA, Mackenzie TA, Emeny RT, et al. Low lean mass with and
without obesity, and mortality: results from the 1999–2004 national
health and nutrition examination survey. J Gerontol A Biol Sci Med
Sci. 2017;72(10):1445–1451.
41. de Campos GC, Lourenço RA, Lopes CS. Prevalence of sarcopenic
obesity and its association with functionality, lifestyle, biomarkers
and morbidities in older adults: the fibra-rj study of frailty in older
brazilian adults. Clinics (Sao Paulo). 2020;75:e1814.
42. Moon JH, Kong MH, Kim HJ. Implication of sarcopenia and sarco­
penic obesity on lung function in healthy elderly: using korean
national health and nutrition examination survey. J Korean Med
Sci. 2015;30(11):1682–1688.
43. Kim TN, Park MS, Lim KI, et al. Relationships between sarcopenic
obesity and insulin resistance, inflammation, and vitamin D status:
the korean sarcopenic obesity study. Clin Endocrinol (Oxf). 2013;78
(4):525–532. .
44. Baek SJ, Nam GE, Han KD, et al. Sarcopenia and sarcopenic obesity
and their association with dyslipidemia in Korean elderly men: the
2008–2010 Korea national health and nutrition examination survey.
J Endocrinol Invest. 2014;37(3):247–260.
45. Park SH, Park JH, Song PS, et al. Sarcopenic obesity as an indepen­
dent risk factor of hypertension. J Am Soc Hypertens. 2013;7
(6):420–425.
46. Chung JY, Kang HT, Lee DC, et al. Body composition and its
association with cardiometabolic risk factors in the elderly:
a focus on sarcopenic obesity. Arch Gerontol Geriatr. 2013;56
(1):270–278.
47. Khadra D, Itani L, Tannir H, et al. Association between sarco­
penic obesity and higher risk of type 2 diabetes in adults:
a systematic review and meta-analysis. World J Diabetes.
2019;10(5):311–323.
48. Khadra D, Itani L, Chebaro Y, et al. Association between sarcopenic
obesity and metabolic syndrome in adults: a systematic review and
meta-analysis. Curr Cardiol Rev. 2020;16(2):153–162.
49. Baumgartner RN, Wayne SJ, Waters DL, et al. Sarcopenic obesity
predicts instrumental activities of daily living disability in the
elderly. Obes Res. 2004;12(12):1995–2004.
50. Chin SO, Rhee SY, Chon S, et al. Sarcopenia is independently
associated with cardiovascular disease in older Korean adults: the
Korea National Health and Nutrition Examination Survey
(KNHANES) from 2009. PLoS One. 2013;8(3):e60119.
51. Stephen WC, Janssen I. Sarcopenic-obesity and cardiovascular dis­
ease risk in the elderly. J Nutr Heal Aging. 2009;13(5):460–466.
52. Atkins JL, Whincup PH, Morris RW, et al. Sarcopenic obesity and
risk of cardiovascular disease and mortality: a population-based
cohort study of older men. J Am Geriatr Soc. 2014;62
(2):253–260.

53. Kwon YN, Yoon SS, Lee KH. Sarcopenic obesity in elderly Korean
women: a nationwide cross-sectional study. J Bone Metab. 2018;25
(1):53–58.
54. Chung GE, Park HE, Lee H, et al. Sarcopenic obesity is significantly
associated with coronary artery calcification. Front Med (Lausanne).
2021;8:651961.
55. Xia MF, Chen LY, Wu L, et al. Sarcopenia, sarcopenic overweight/
obesity and risk of cardiovascular disease and cardiac arrhythmia: a
cross-sectional study. Clin Nutr. 2021;40(2):571–580.
56. Uchida S, Kamiya K, Hamazaki N, et al. Association between sarco­
penia and atherosclerosis in elderly patients with ischemic heart
disease. Heart Vessels. 2020;35(6):769–775. .
57. Yoo JH, Park SW, Jun JE, et al. Relationship between low skeletal
muscle mass, sarcopenic obesity and left ventricular diastolic dys­
function in Korean adults. Diabetes Metab Res Rev. 2020;37(1):
e3363.
58. Kang DO, Park SY, Choi BG, et al. Prognostic impact of low skeletal
muscle mass on major adverse cardiovascular events in coronary
artery disease: a propensity score-matched analysis of a single
center all-comer cohort. J Clin Med. 2019;8(5):712.
59. Zhang N, Zhu WL, Liu XH, et al. Prevalence and prognostic implica­
tions of sarcopenia in older patients with coronary heart disease.
J Geriatr Cardiol. 2019;16(10):756–763. .
60. Farmer RE, Mathur R, Schmidt AF, et al. Associations between
measures of sarcopenic obesity and risk of cardiovascular dis­
ease and mortality: a cohort study and mendelian randomization
analysis using the UK Biobank. J Am Heart Assoc. 2019;8(13):
e011638.
61. Santana NM, Mendes RML, Silva NFD, et al. Sarcopenia and sarco­
penic obesity as prognostic predictors in hospitalized elderly
patients with acute myocardial infarction. Einstein: Sao Paulo,
Brazil 2019; Vol. 17: eAO4632.
62. Fukuda T, Bouchi R, Takeuchi T, et al. Sarcopenic obesity assessed
using dual energy X-ray absorptiometry (DXA) can predict cardio­
vascular disease in patients with type 2 diabetes: a retrospective
observational study. Cardiovasc Diabetol. 2018;17(1):55.
63. Bellanti F, Romano AD, Buglio AL, et al. Oxidative stress is increased
in sarcopenia and associated with cardiovascular disease risk in
sarcopenic obesity. Maturitas. 2018;109:6–12.
64. Kamiya K, Hamazaki N, Matsuzawa R, et al. Sarcopenia: prevalence
and prognostic implications in elderly patients with cardiovascular
disease. J Cachexia Sarco Musc Cli Rep.2017;2:1–13.
65. Campos AM, Moura FA, Santos SN, et al. Sarcopenia, but not excess
weight or increased caloric intake, is associated with coronary
subclinical atherosclerosis in the very elderly. Atherosclerosis.
2017;258:138–144.
66. Liu HM, Zhang O, Shen WD, et al. Sarcopenia-related traits and
coronary artery disease: a bi-directional mendelian randomization
study. Aging (Albany NY). 2020;12(4):3340–3353.
67. Tsekoura M, Kastrinis A, Katsoulaki M, et al. Sarcopenia and its
impact on quality of life. Adv Exp Med Biol. 2017;987:213–218.
68. Tian S, Xu Y. Association of sarcopenic obesity with the risk of
all-cause mortality: a meta-analysis of prospective cohort studies.
Geriatr Gerontol Int. 2016;16(2):155–166.
69. Malmstrom TK, Miller DK, Simonsick EM, et al. SARC-F: a symptom
score to predict persons with sarcopenia at risk for poor functional
outcomes. J Cachexia Sarcopenia Muscle. 2016;7(1):26–28.
70. Cruz-Jentoft AJ, Bahat G, Bauer J, et al. Sarcopenia: revised
European consensus on definition and diagnosis. Age Ageing.
2019;48(1):16–31. .
71. Villareal DT, Aguirre L, Gurney AB, et al. Aerobic or resistance
exercise, or both, in dieting obese older adults. N Engl J Med.
2017;376(20):1943–1955.
72. Asano RY, Sales MM, Coelho JM, et al. Exercise, nitric oxide, and
endothelial dysfunction: a brief review. J Exerc Physiol Online.
2012;15:76–86.
73. Liao CD, Tsauo JY, Lin LF, et al. Effects of elastic resistance exercise
on body composition and physical capacity in older women with
sarcopenic obesity: a CONSORT-compliant prospective randomized
controlled trial. 2017. Medicine (Baltimore). 2017;96(23):e7115.
POSTGRADUATE MEDICINE 11
74. Vasconcelos KSS, Dias JMD, Araújo MC, et al. Land-based versus
aquatic resistance therapeutic exercises for older women with
sarcopenic obesity: study protocol for a randomized controlled
trial. Trials. 2013;14(1):296.
75. Wittmann K, Sieber C, von Stengel S, et al. Impact of whole body
electromyostimulation on cardiometabolic risk factors in older
women with sarcopenic obesity: the randomized controlled
FORMOsA-sarcopenic obesity study. Clin Interv Aging.
2016;11:1697–1706.
76. Kelly OJ, Gilman JC. Can unconventional exercise be help- ful in the
treatment, management and prevention of osteosarcopenic
obesity? Curr Aging Sci. 2017;10(2):106–121.
77. Malafarina V, Uriz-Otano F, Iniesta R, et al. Effectiveness of nutri­
tional supplementation on muscle mass intreatment of sarcopenia
in old age: a systematic review. J Am Med Dir Assoc. 2013;14
(1):10–17.
78. Gryson C, Ratel S, Rance M, et al. Four-month course of soluble mil
proteins interacts with exercise to improve muscle strength and
delay fatigue in elderly participants. J Am Med Dir Assoc 2014; 15:
958.e1-9.
79. Poggiogalle E, Migliaccio S, Lenzi A, et al. Treatment of body
composition changes in obese and overweight older adults: insight
into the phenotype of sarcopenic obesity. Endocrine. 2014;47
(3):699–716.
80. Liao CD, Tsauo JY, Wu YT, et al. Effects of protein supple- mentation
combined with resistance exercise on body composition and phy­
sical function in older adults: a systematic review and metaanalysis.
Am J Clin Nutr. 2017;106(4):1078–1091. .
81. Fernandes RR, Nabuco HCG, Sugihara Junior P, et al. Effect of
protein intake beyond habitual intakes following resisance training
on cardiometabolic risk disease parameters in pre-conditioned
older women. Exp Gerentol. 2018;110:9–14.
82. Becker C, Lord SR, Studenski SA, et al. Myostatin
antibody (LY2495655) in older weak fallers: a proof-of-concept,
randomised, phase 2 trial. Lancet Diabetes Endocrinol. 2015;3
(12):948–957.
83. Blackman MR, Sorkin JD, Munzer T, et al. Growth hormone and sex
steroid administration in healthy aged women and men: a rando­
mised controlled trial. JAMA 2002;288:2282-92..
84. Makimura H, Feldpausch MN, Rope AM, et al. Metabolic effects of
a growth hormone-releasing factor in obese subjects with reduced
growth hormone secretion: a randomized controlled trial. J Clin
Endocrinol Metab. 2012;97(12):4769–4779.
85. Marty E, Liu Y, Samuel A, et al. A review of sarcopenia: enhancing
awareness of an increasingly prevalent disease. Bone.
2017;105:276–286.
86. Bassez G, Audureau E, Hogrel JY, et al. Improved mobility with
metformin in patientswith myotonic dystrophy type 1:
a randomized controlled trial. Brain. 2018;141(10):2855–2865.
87. Beaudart C, Buckinx F, Rabenda V, et al. The effects of vitamin D on
skeletal muscle strength, muscle mass, and muscle power:
a systematic review and meta-analysis of randomized controlled
trials. J Clin Endocrinol Metab. 2014;99(11):4336–4345.
88. Murad MH, Elamin KB, Abu Elnour NO, et al. Clinical review: the
effect of vitamin D on falls: a systematic review and meta-analysis.
J Clin Endocrinol Metab. 2011;96(10):2997–3006.
89. Zinman B, Wanner C, Lachin JM, et al. EMPA-REG OUTCOME inves­
tigators. empagliflozin, cardiovascular outcomes, and mortality in
type 2 diabetes. N Engl J Med. 2015;373(22):2117–2128.
90. Marso SP, Daniels GH, Brown-Frandsen K, et al. LEADER steering
committee; LEADER trial investigators. liraglutide and cardiovascu­
lar outcomes in type 2 diabetes. N Engl J Med. 2016;375
(4):311–322.
91. Neal B, Perkovic V, Mahaffey KW, et al. CANVAS program collabora­
tive group. canagliflozin and cardiovascular and renal events in
type 2 diabetes. N Engl J Med. 2017;377(7):644–657.
92. Armstrong MJ, Gaunt P, Aithal GP, et al. Liraglutide safety and
efficacy in patients with non-alcoholic steatohepatitis (LEAN):
a multicentre, double-blind, randomised, placebo-controlled
phase 2 study. Lancet. 2016;387(10019):679–690.
12 K. EVANS ET AL.
93. Sasaki T, Sugawara M, Fukuda M. Sodium-glucose cotransporter 2
inhibitor-induced changes in body composition and simultaneous
changes in metabolic profile: 52-week prospective LIGHT (luseogli­
flozin: the components of weight loss in japanese patients with
type 2 diabetes mellitus) study. J Diabetes Investig. 2019;10
(1):108–117.
94. Cefalu WT, Leiter LA, Yoon KH, et al. Efficacy and safety of canagli­
flozin versus glimepiride in patients with type 2 diabetes inade­
quately controlled with metformin (CANTATA-SU): 52 week results
from a randomised, double-blind, phase 3 non-inferiority trial.
Lancet. 2013;382(9896):941–950. .
95. Batsis JA, Barre LK, Mackenzie TA, et al. Variation in the preva­
lence of sarcopenia and sarcopenic obesity in older adults asso­
ciated with different research definitions: dual-energy X-ray
absorptiometry data from the national health and nutrition
examination survey 1999–2004. J Am Geriatr Soc. 2013;61
(6):974–980.
96. Sasaki KI, Kakuma T, Sasaki M, et al. The prevalence of sarcopenia
and subtypes in cardiovascular diseases, and a new diagnostic
approach. Cardiol. 2020;76:266–272.
97. Chung W, Park JH, Chung HS, et al. Utility of the Z-score of
log-transformed A Body Shape Index (LBSIZ) in the assessment
for sarcopenic obesity and cardiovascular disease risk in the
United States. Sci Rep. 2019;9(1):9292.
98. Han P, Yu H, Ma Y, et al. The increased risk of sarcopenia in
patients with cardiovascular risk factors in suburb-dwelling
older Chinese using the AWGS definition. Sci Rep.2017; 7
(1):9592.