Boosting muscle health with ACEIs: A Muscle-Saving Treatment for Hypertension in Older Adults
Discover how ACEI medications can help improve muscle health and physical performance in older adults with hypertension. Learn about the benefits of ACEIs and the potential mechanisms underlying their positive effects.
DR T S DIDWAL MD
10/14/20248 min read
The research published in The Journal of Frailty and Aging examined the relationship between hypertension, physical performance, and Angiotensin-Converting Enzyme Inhibitor (ACEI ) use in very old adults. The study found that ACEI use, particularly peripherally acting agents, may positively influence physical performance in older adults with hypertension. This is possibly due to their impact on the IGF-1 pathway, which is crucial for muscle protein synthesis. However, the study has limitations and further research is needed to confirm these findings and understand the underlying mechanisms.
Key points
Hypertension and Physical Performance: The study found that the association between high blood pressure and poor physical performance in older adults may be mediated by the use of ACEI medications.
ACEI Use and Muscle Power: Older adults taking ACEIs were more likely to have greater specific muscle power compared to those not taking ACEIs.
ACEI Subtypes and IGF-1: Peripherally acting ACEIs (ACEI-p) were associated with higher blood levels of IGF-1, a crucial regulator of muscle protein synthesis.
Potential Mechanisms: The researchers proposed that ACEIs may improve muscle function by counteracting the negative effects of angiotensin II, a hormone that can promote muscle wasting.
Study Limitations: The study was cross-sectional, limiting the ability to infer causal relationships. Other limitations included the use of calf circumference to estimate muscle mass and the lack of detailed information on ACEI treatment regimens.
Future Research: Future studies should investigate the temporal relationships between ACEI use, hypertension, and physical performance, examine the effects of different ACEI subtypes on muscle function, and explore the underlying mechanisms.
Clinical Implications: The findings suggest that ACEI use, particularly peripherally acting agents, may be beneficial for maintaining muscle function in older adults with hypertension. However, further research is needed to confirm these findings and guide clinical practice.
This research examines the complex relationships between hypertension, physical performance, and the use of angiotensin-converting enzyme inhibitors (ACEIs) in very old adults. The study was conducted as part of the ilSIRENTE project, focusing on a population of adults aged 80 and older living in a mountainous region of central Italy.
Background and Rationale:
The aging process is associated with various physiological changes that can lead to chronic conditions. Hypertension is particularly prevalent in older adults, affecting over 70% of those 65 and older. Simultaneously, physical performance tends to decline with age, starting around the third decade of life and accelerating in advanced age. Both hypertension and poor physical function are associated with negative health outcomes in older adults.
Previous studies have found conflicting results regarding the relationship between hypertension and physical performance in older adults. Some studies have reported positive associations, others inverse associations, and some no significant relationship at all. The researchers hypothesized that these inconsistent findings might be due to the failure to account for the use of ACEIs, a common class of antihypertensive medications.
ACEIs are widely prescribed for hypertension and have been shown to reduce the risk of cardiovascular events and mortality. Additionally, some research suggests that ACEIs may help counteract age-related decline in neuromuscular function. This potential benefit is thought to be related to the inhibition of angiotensin II (ANGII), which has negative effects on skeletal muscle mass and function. The use of ACEIs may increase the expression of insulin-like growth factor 1 (IGF-1) and related proteins, which play a crucial role in muscle protein synthesis.
However, not all studies have found significant associations between ACEI use and improved neuromuscular performance in older adults. The researchers proposed that this inconsistency might be due to the failure to distinguish between centrally acting (ACEI-c) and peripherally acting (ACEI-p) agents.
Study Design and Methods:
The ilSIRENTE study was a cross-sectional investigation involving 364 adults with a mean age of 85.8 years. The study collected detailed clinical and biological information to characterize the health and functional status of this very old population.
Physical performance was assessed using several measures:
Isometric handgrip strength (IHG)
Walking speed (WS) at a normal and fast pace
5-time sit-to-stand test (5STS)
Muscle power measures
Blood pressure was measured after 20–40 minutes of rest, with participants in an upright sitting position. The researchers also collected data on medication use, categorizing ACEIs into centrally and peripherally acting subtypes.
Blood samples were analyzed for inflammatory markers, free insulin-like growth factor 1 (IGF-1), and IGF-binding protein 3 (IGFBP-3).
Key Findings:
1. Association between blood pressure and physical performance
The 5STS test was significantly and negatively associated with diastolic blood pressure values.
However, this association lost statistical significance when the results were adjusted for ACEI use.
2. ACEI use and physical performance:
Participants taking ACEIs were more likely to have greater specific muscle power compared to non-ACEI users.
ACEI users also had higher blood levels of IGFBP-3 than non-users.
3. ACEI subtypes and IGF-1 pathway:
Participants using peripherally acting ACEIs (ACEI-p) had higher blood IGF-1 levels compared to those using centrally acting ACEIs (ACEI-
These findings suggest that ACEI use may influence the relationship between hypertension-related parameters and neuromuscular function in very old adults. The researchers propose that this effect might be linked to the impact of ACEIs, particularly peripherally acting agents, on the IGF-1 pathway.
Discussion of Results:
The study's findings partially align with previous research that found no significant associations between hypertension-related parameters and physical performance in older adults. However, the results also highlight the potential importance of considering ACEI use when examining these relationships.
The loss of significance in the association between diastolic blood pressure and 5STS performance after adjusting for ACEI use suggests that these medications may play a mediating role in the relationship between hypertension and physical function.
The observation that ACEI users had greater specific muscle power is consistent with some previous studies that have reported benefits of ACEI use on neuromuscular function in older adults. However, it's important to note that other studies have found no such associations or even negative relationships between ACEI use and certain aspects of physical performance.
The finding that ACEI-p users had higher IGF-1 levels compared to ACEI-c users is particularly intriguing. This suggests that the subtype of ACEI may be important in determining its effects on muscle function and related biological pathways.
Potential Mechanisms:
The researchers discuss several potential mechanisms that might explain the observed relationships:
1. Angiotensin II and muscle wasting:
ANGII has been shown to promote muscle wasting through various pathways, including
Inhibition of anabolic pathways
Triggering protein degradation
Increasing oxidative stress
Impairing mitochondrial function
Shifting muscle fiber composition
Activating the ubiquitin-proteasome system
2. ACEIs and muscle function:
ACEIs may counteract these negative effects of ANGII by:
Improving exercise capacity
Enhancing mitochondrial respiration efficiency
Decreasing reactive oxygen species (ROS) production
Increasing the proportion of type I muscle fibers
3. IGF-1 pathway:
IGF-1 is a crucial regulator of muscle protein synthesis. ACEIs may influence this pathway by:
Increasing circulating and muscular levels of IGF-1 and IGFBP3
Enhancing the expression of IGF-1 receptors
Increasing the activation of AKT, a key protein in the IGF-1 signaling cascade
The researchers suggest that ACEI use, particularly peripherally acting ACEIs, may help maintain muscle mass and its endocrine function. This could explain the higher IGF-1 levels observed in ACEI-p users and the association with greater specific muscle power.
Limitations and Future Directions:
The study has several limitations that should be considered when interpreting the results:
Appendicular skeletal muscle (ASM) was estimated using calf circumference rather than more precise measurement tools.
Blood concentrations of oxidative stress markers were not measured.
Detailed information on ACEI treatment (dosage, duration, adherence) was not available.
The study lacked a comprehensive description of antihypertensive treatment regimens.
The cross-sectional design limits the ability to infer causal relationships or temporal changes.
Data on specific ACEI subtypes were not available for all participants.
The study population consisted of very old adults from a specific mountainous region, which may limit generalizability to other populations.
Future research directions suggested by this study include:
Conducting longitudinal studies to examine the temporal relationships between ACEI use, hypertension, and physical performance in very old adults.
Investigating the effects of different ACEI subtypes on muscle function and the IGF-1 pathway in larger, more diverse populations.
Exploring the potential mechanisms underlying the observed relationships using more detailed assessments of muscle mass, oxidative stress markers, and mitochondrial function.
Conclusions:
This study provides evidence that ACEI use may influence the relationship between hypertension-related parameters and physical performance in very old adults. The findings suggest that:
The association between blood pressure and physical performance (specifically the 5STS test) may be mediated by ACEI use.
Older adults taking ACEIs may have greater specific muscle power compared to non-users.
Peripherally acting ACEIs may have specific effects on the IGF-1 pathway, potentially contributing to better muscle function.
These results highlight the importance of considering medication use, particularly ACEIs, when studying the relationships between hypertension and physical function in older adults. They also suggest that the choice of ACEI subtype may have implications for maintaining muscle function in very old individuals.
The study's findings contribute to the growing body of research on the complex interplay between cardiovascular health, physical function, and pharmacological interventions in aging populations. They underscore the need for a nuanced approach to managing hypertension in older adults, taking into account potential effects on muscle function and overall physical performance.
Further research is needed to confirm these findings in larger, more diverse populations and to elucidate the underlying mechanisms. Such investigations could inform clinical practice and potentially lead to more targeted approaches for maintaining physical function in very old adults with hypertension.
FAQs
1. What is hypertension, and why is it a concern for older adults?
Hypertension is a condition where the blood pressure is consistently elevated. It can increase the risk of heart disease, stroke, kidney disease, and other serious health problems. Older adults are particularly susceptible to hypertension due to age-related changes in the cardiovascular system.
2. How does physical performance change with age?
Physical performance generally declines with age, especially after the third decade of life. This decline can affect various aspects of physical function, including strength, endurance, balance, and coordination.
3. What are ACEIs, and how do they work?
ACEIs (angiotensin-converting enzyme inhibitors) are a class of medications used to treat high blood pressure. They work by blocking the production of angiotensin II, a hormone that constricts blood vessels and raises blood pressure.
4. What is the relationship between hypertension and physical performance in older adults?
The relationship between hypertension and physical performance in older adults is complex and can vary. Some studies have found positive associations, others inverse associations, and some no significant relationship at all.
5. How do ACEIs affect physical performance in older adults with hypertension?
ACEIs may have positive effects on physical performance in older adults with hypertension. Research suggests that they can improve muscle function, increase specific muscle power, and enhance overall physical function.
6. Are there different types of ACEIs?
Yes, there are two main types of ACEIs: centrally acting (ACEI-c) and peripherally acting (ACEI-p). Peripherally acting ACEIs may have specific effects on the IGF-1 pathway, which is important for muscle protein synthesis.
7. What are the potential mechanisms by which ACEIs improve physical performance?
ACEIs may improve physical performance by counteracting the negative effects of angiotensin II on muscle function, enhancing mitochondrial respiration efficiency, and increasing the levels of IGF-1.
8. What are the limitations of the research on ACEIs and physical performance in older adults?
The research on ACEIs and physical performance in older adults has some limitations, including the cross-sectional design of many studies, the use of indirect measures of muscle mass, and the lack of detailed information on ACEI treatment regimens.
9. What are the future directions for research in this area?
Future research should focus on conducting longitudinal studies, investigating the effects of different ACEI subtypes, exploring the underlying mechanisms, and examining the impact of ACEIs on muscle endocrine function.
10. What are the clinical implications of the findings from this research?
The findings suggest that ACEI use, particularly peripherally acting agents, may be beneficial for maintaining muscle function in older adults with hypertension. However, more research is needed to confirm these findings and guide clinical practice.
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Journal Reference
Coelho-Junior, H.J., Calvani, R., Tosato, M. et al. Associations Between Hypertension, Angiotensin-Converting Enzyme Inhibitors, and Physical Performance in Very Old Adults: Results from the ilSIRENTE Study. J Frailty Aging 13, 74–81 (2024). https://doi.org/10.14283/jfa.2024.15
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