DISCUSSION
This study showed that both presarcopenia (48.3% vs. 21.1%) and
sarcopenia (33.3% vs. 7.0%) were more prevalent in hypertensive when
compared to normotensive older adults. Of note, among several
parameters, only the presence of hypertension independently increased
(almost 8 times) the risk of sarcopenia in older adults. Interestingly,
it is noteworthy that the use of ACE inhibitors for hypertension
appeared to be preventive against the development of sarcopenia.
A very recent systematic review and meta-analysis investigated the
prevalence of sarcopenia in different comorbid diseases whereby
sarcopenia was found to be highly prevalent in patients with
cardiovascular diseases (31.4%), diabetes mellitus (31.1%), dementia
(26.8%), and respiratory disorders (26.8%).11Unfortunately, the meta-analysis did not include hypertension - which is
actually one of the most frequent problems causing cardiovascular
disease. Another recent study (in 166 older adults with a mean age of
77.2 years) evaluated the prevalence of sarcopenia considering 99
variables by using machine learning techniques (a sub-branch of
artificial intelligence).12 In order of importance;
age, systolic arterial hypertension, mini nutritional assessment, number
of chronic diseases and blood sodium level were reported to be the
determinants for sarcopenia.
In previous studies, the relationship between sarcopenia and
hypertension has been evaluated according to total muscle mass
measurements.13,14 However, as sarcopenia initially
starts at the anterior thigh, it is more reasonable to use those muscle
measurements for the diagnosis of sarcopenia whereby the use of total
muscle mass loss would easily be misleading.5,7,15,16For this reason, we have used anterior thigh (instead of total) muscle
measurements which have higher correlations with knee extensor strength
and performance tests according to the recent
literature.5 Importantly, we have found that
presarcopenia (48.3%) and sarcopenia (33.3%) were highly prevalent in
hypertensive older adults.
One possible mechanism to explain this high prevalence (of sarcopenia in
hypertension) might be the RAS activation which increases the levels of
circulating Ang-II levels - that, in turn, may contribute to the
development of both sarcopenia and hypertension.4 Of
additional note, mineralocorticoid receptor activation also causes a
progressive loss of heart and skeletal muscle myocytes due to apoptosis
in heart failure - called as ‘heart cachexia’ which is a process
resembling sarcopenia.13,17 Further, hypertension has
effects on physical function as well. For instance, like many other
cardiovascular diseases, low gait speed has been associated with
hypertension.18 In a 2-year longitudinal study,
hypertension was found to be related with lower gait speed at baseline
and with higher annual decline in gait speed during follow
up.19 Herein, hypertension can affect the gait speed
not only via white matter abnormalities in the central nervous system
but also due to atherosclerosis in the peripheral
arteries.19 Likewise, higher handgrip strength was
reported to be related with lower risk of hypertension in older
females.20 In our study, while low gait speed was
observed to be more common only in middle-aged hypertensive patients,
low CST was more prevalent in both middle-aged and older hypertensive
patients. However, the frequency of low handgrip strength was not
different in either group. Indeed, CST is a test assessing power which
is more strongly related with functional performance than muscle
strength in the elderly.21,22 Additionally, power
declines at a faster rate than strength by aging.21Therefore, CST can be more useful than muscle strength tests for the
early detection of sarcopenia.
Active classical RAS axis has deleterious effects on the skeletal
muscle; therefore, its inhibition has been important in the treatment of
several pathologies affecting the skeletal muscle (e.g. insulin
resistance, muscle atrophy, fibrosis etc.).4 While
some of the studies have shown favorable effects; others reported no
association in between.23-26 When we focus on their
methodologies, the outcome measures are quite heterogeneous. In this
regard; patient population (functionally impaired elderly, high cardiac
risk, fall history, hearth failure, or hypertension), performance tests,
duration of intervention and follow-up periods, combination of
anti-hypertensive drugs with different exercise protocols, comparison of
ACE inhibitors with ARBs or non-ACE inhibitors instead of placebo would
be some examples. Additionally, the two most commonly used tests (i.e.
grip strength and gait speed) were found to be related with cognition
rather than muscle mass. Yet, it is well-known that possible decline in
these tests requires long years and therefore treatment effect may not
be shown in short periods. Further, high blood pressure can trigger
several changes not only in the skeletal muscle, but also in the
physical function via cognition.27
As mentioned above, the anterior thigh is affected earlier with
aging.16 Therefore, it would be more appropriate to
measure anterior thigh muscle mass and strength (by CST or ideally using
isokinetic muscle strength testing). Likewise, ACE inhibitors was
investigated for the prevention of sarcopenia.28 In a
cohort of the Women’s Health and Aging Study, continuous use of ACE
inhibitors has been found to exert a favorable impact on gait speed and
knee extensor muscle strength after a 3-year
follow-up.23 In the Health, Aging and Body Composition
study, patients using ACE inhibitors had higher lower extremity muscle
mass than those using other antihypertensive drugs.29Similar to these studies, ACE inhibitors appeared to be preventive
against the development of sarcopenia in our study as well; however, we
did not observe a similar (preventive) effect concerning the use of
ARBs. Herein, a possible explanation would be that ACE inhibitors
increase the formation of bradykinin (a potent vasodilator) which
promotes muscle blood flow, glucose uptake and hypertrophy via its type
2 receptor.30,31
In conclusion, sarcopenia is highly prevalent (1 out of 3) in
hypertensive older adults; and among many antihypertensive medications,
ACE inhibitors seem to have favorable effects on both disorders.
Indisputably, further longitudinal studies in larger populations are
awaited also taking into account the contribution of exercise - another
common therapy for the two.
Ethical statement: Authors confirm that their study’s
involvement with human subjects complies with the Declaration of
Helsinki.