Serum Concentrations of Losartan Metabolites Correlate With Improved Physical Function in a Pilot Study of Prefrail Older Adults
© The Author(s) 2022. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissionsoup.com..
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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2022 |
|---|---|
| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:77 |
|---|---|
| Enthalten in: |
The journals of gerontology. Series A, Biological sciences and medical sciences - 77(2022), 12 vom: 29. Dez., Seite 2356-2366 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Lee, Jessica L [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 02.01.2023 Date Revised 26.02.2024 published: Print ClinicalTrials.gov: NCT01989793 Citation Status MEDLINE |
|---|
| doi: |
10.1093/gerona/glac102 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM340405287 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM340405287 | ||
| 003 | DE-627 | ||
| 005 | 20240229163256.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2022 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1093/gerona/glac102 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1308.xml |
| 035 | |a (DE-627)NLM340405287 | ||
| 035 | |a (NLM)35511890 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Lee, Jessica L |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Serum Concentrations of Losartan Metabolites Correlate With Improved Physical Function in a Pilot Study of Prefrail Older Adults |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 02.01.2023 | ||
| 500 | |a Date Revised 26.02.2024 | ||
| 500 | |a published: Print | ||
| 500 | |a ClinicalTrials.gov: NCT01989793 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © The Author(s) 2022. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissionsoup.com. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, N.I.H., Intramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Citric acid cycle | |
| 650 | 4 | |a EXP3174 | |
| 650 | 4 | |a EXP3179 | |
| 650 | 4 | |a Frailty, Losartan | |
| 650 | 7 | |a 2-butyl-4-chloro-1-((2'-(1H-tetrazol-5-yl)(1,1'-biphenyl)-4-yl)methyl)-1H-imidazole-5-carboxaldehyde |2 NLM | |
| 650 | 7 | |a 140868-18-4 |2 NLM | |
| 650 | 7 | |a Angiotensin Receptor Antagonists |2 NLM | |
| 650 | 7 | |a Antihypertensive Agents |2 NLM | |
| 650 | 7 | |a Imidazoles |2 NLM | |
| 650 | 7 | |a Losartan |2 NLM | |
| 650 | 7 | |a JMS50MPO89 |2 NLM | |
| 650 | 7 | |a losartan carboxylic acid |2 NLM | |
| 650 | 7 | |a GD76OCH73X |2 NLM | |
| 650 | 7 | |a Tetrazoles |2 NLM | |
| 700 | 1 | |a Zhang, Cissy |e verfasserin |4 aut | |
| 700 | 1 | |a Westbrook, Reyhan |e verfasserin |4 aut | |
| 700 | 1 | |a Gabrawy, Mariann M |e verfasserin |4 aut | |
| 700 | 1 | |a Nidadavolu, Lolita |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Huanle |e verfasserin |4 aut | |
| 700 | 1 | |a Marx, Ruth |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Yuqiong |e verfasserin |4 aut | |
| 700 | 1 | |a Anders, Nicole M |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Lina |e verfasserin |4 aut | |
| 700 | 1 | |a Bichara, Marcela-Dávalos |e verfasserin |4 aut | |
| 700 | 1 | |a Kwak, Min-Ji |e verfasserin |4 aut | |
| 700 | 1 | |a Buta, Brian |e verfasserin |4 aut | |
| 700 | 1 | |a Khadeer, Mohammed |e verfasserin |4 aut | |
| 700 | 1 | |a Yenokyan, Gayane |e verfasserin |4 aut | |
| 700 | 1 | |a Tian, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Xue, Qian-Li |e verfasserin |4 aut | |
| 700 | 1 | |a Siragy, Helmy M |e verfasserin |4 aut | |
| 700 | 1 | |a Carey, Robert M |e verfasserin |4 aut | |
| 700 | 1 | |a de Cabo, Rafael |e verfasserin |4 aut | |
| 700 | 1 | |a Ferrucci, Luigi |e verfasserin |4 aut | |
| 700 | 1 | |a Moaddel, Ruin |e verfasserin |4 aut | |
| 700 | 1 | |a Rudek, Michelle A |e verfasserin |4 aut | |
| 700 | 1 | |a Le, Anne |e verfasserin |4 aut | |
| 700 | 1 | |a Walston, Jeremy D |e verfasserin |4 aut | |
| 700 | 1 | |a Abadir, Peter M |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t The journals of gerontology. Series A, Biological sciences and medical sciences |d 1997 |g 77(2022), 12 vom: 29. Dez., Seite 2356-2366 |w (DE-627)NLM074698443 |x 1758-535X |7 nnns |
| 773 | 1 | 8 | |g volume:77 |g year:2022 |g number:12 |g day:29 |g month:12 |g pages:2356-2366 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1093/gerona/glac102 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 77 |j 2022 |e 12 |b 29 |c 12 |h 2356-2366 | ||