Faculty, Staff and Student Publications
Publication Date
12-29-2022
Journal
The Journals of Gerontology: Series A
Abstract
Losartan is an oral antihypertensive agent that is rapidly metabolized to EXP3174 (angiotensin-subtype-1-receptor blocker) and EXP3179 (peroxisome proliferator-activated receptor gamma [PPARγ] agonist), which was shown in animal studies to reduce inflammation, enhance mitochondrial energetics, and improve muscle repair and physical performance. We conducted an exploratory pilot study evaluating losartan treatment in prefrail older adults (age 70-90 years, N = 25). Participants were randomized to control (placebo) or treatment (daily oral losartan beginning at 25 mg per day and increasing every 8 weeks) for a total of 6 months. Fatigue, hyperkalemia, and hypotension were the most observed side effects of losartan treatment. Participants in the losartan group had an estimated 89% lower odds of frailty (95% confidence interval [CI]: 18% to 99% lower odds, p = .03), with a 0.3-point lower frailty score than the placebo group (95% CI: 0.01-0.5 lower odds, p = .04). Frailty score was also negatively associated with serum losartan and EXP3179 concentrations. For every one standard deviation increase in EXP3179 (ie, 0.0011 ng/μL, based on sample values above detection limit) and EXP3174 (ie, 0.27 ng/μL, based on sample values above detection limit), there was a 0.0035 N (95% CI: 0.0019-0.0051, p < .001) and a 0.0027 N (95% CI: 0.00054-0.0043, p = .007) increase in average knee strength, respectively.
Trial registration: ClinicalTrials.gov NCT01989793.
Keywords
Angiotensin Receptor Antagonists, Antihypertensive Agents, Frailty, Imidazoles, Losartan, Pilot Projects, Tetrazoles, Humans, Aged, Physical Fitness, Citric acid cycle; EXP3174; EXP3179; Frailty, Losartan
DOI
10.1093/gerona/glac102
PMID
35511890
PMCID
PMC9799219
PubMedCentral® Posted Date
5-4-2022
PubMedCentral® Full Text Version
Post-print
Graphical Abstract
Published Open-Access
yes