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Drugs Aging. 2019 Feb 9. doi: 10.1007/s40266-019-00642-3. [Epub ahead of print]

Angiotensin-Converting Enzyme Inhibitor Use and Incident Frailty: A Longitudinal Cohort Study.

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National Research Council, Neuroscience Institute, Aging Branch, Via Giustiniani, 2, 35128, Padua, Italy.
Physiotherapy Department, South London and Maudsley NHS Foundation Trust, Denmark Hill, London, SE5 8AZ, UK.
Health Service and Population Research Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, London, SE5 8AF, UK.
Faculty of Health, Social Care and Education, Anglia Ruskin University, Bishop Hall Lane, Chelmsford, CM1 1SQ, UK.
The Cambridge Centre for Sport and Exercise Sciences, Anglia Ruskin University, Cambridge, UK.
National Research Council, Neuroscience Institute, Aging Branch, Via Giustiniani, 2, 35128, Padua, Italy.
Department of Behavioural Science and Health, University College London, London, UK.
Department of Geriatric Medicine, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkey.
Primary Care Department, Azienda USL Toscana Sud Est, Grosseto, Italy.
Primary Care Department, Aziendale AAS3 Alto Friuli, Collinare, Medio Friuli, Udine, Italy.
Research and Development Unit, Parc Sanitari Sant Joan de Déu, Universitat de Barcelona, Fundació Sant Joan de Déu, Barcelona, Spain.
Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Madrid, Spain.



Angiotensin-converting enzyme inhibitors (ACEI) may have several pleiotropic effects, but the literature regarding a possible relationship between ACEI use and frailty is limited. We investigated whether ACEI use is associated with lower risk of frailty in a cohort of North American individuals.


Data from the Osteoarthritis Initiative, a cohort study with 8 years of follow-up including community-dwelling adults with knee osteoarthritis or at high risk for this condition, were analyzed. ACEI use was defined through self-reported information and confirmed by a trained interviewer. Frailty was defined using the Study of Osteoporotic Fracture (SOF) index as the presence of at least two of the following criteria: (1) weight loss ≥ 5% between baseline and any subsequent follow-up visit; (2) inability to do five chair stands; and (3) low energy level according to the SOF definition. A multivariable Poisson regression analysis was used to assess the association between ACEI use at baseline and incident frailty. The data were reported as relative risks (RRs) with their 95% confidence intervals (CIs).


The final sample consisted of 4295 adults (mean age 61.2 years, females 58.1%). At baseline, 551 participants (12.8%) used ACEI. After adjusting for 15 potential confounders, the use of ACEI was associated with a lower risk of frailty (RR 0.72; 95% CI 0.53-0.99). The adjustment for the propensity score substantially confirmed these findings (RR 0.75; 95% CI 0.54-0.996).


ACEI use may be associated with a reduced risk of frailty in individuals with/at risk of knee osteoarthritis, suggesting a potential role for ACI in the prevention of frailty.


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