Diverse etiologies may account for physical disability in older adults. There is speculation that one common pathway, such as a loss of muscle mass and muscle strength, is frequently associated with the onset and progression of disability. The use of angiotensinconverting enzyme (ACE) inhibitors appears to reduce morbidity, mortality, hospital admission, and decline in physical function and exercise capacity in Congestive Heart Failure (CHF) patients. These therapeutic effects are attributed primarily to beneficial cardiovascular actions, but recent evidence suggests that ACE inhibitors may exert positive metabolic, mechanical and biochemical changes in the muscle and favorably modify markers of inflammation. In addition, genetic studies have suggested that healthy subjects with a reduced expression of ACE secondary to genetic polymorphism present greater muscle mass and strength in response to physical training. We hypothesize that the benefit of ACE inhibition on physical function extends to people without CHF. We propose to conduct an exploratory analysis using 3-year longitudinal data from the Health Aging and Body Composition (HABC) study to assess whether, among older adults without CHF, ACE inhibitors use is associated with a lower decline in muscle strength and muscle mass and, consequently, improved physical performance and decreased disability. In addition, we propose to explore underlying mechanisms responsible for these effects. In particular we aim to explore the interaction of ACE inhibitors with inflammatory markers and physical exercise. The HABC, a prospective cohort study, which enrolled 3,075 well-functioning participants aged 70-79 years, offers unique advantages, including the comprehensive phenotype definition of body composition, muscle performance, disability, the availability of inflammatory markers, and excellent retention of participants in the study. The study may provide evidence suggesting pharmacological benefits in preventing the decline in physical function among older adults as well as preliminary data for planning future studies aimed at preventing physical disability in the elderly. This project complements and extends other ongoing and planned clinical and basic research studies in our OAIC which address the same hypothesis.
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