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.