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

  • Nicola VeroneseEmail author
  • Brendon Stubbs
  • Lee Smith
  • Stefania Maggi
  • Sarah E. Jackson
  • Pinar Soysal
  • Jacopo Demurtas
  • Stefano Celotto
  • Ai Koyanagi
Original Research Article



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.


Compliance with Ethical Standards


This study was funded by five contracts (N01-AR-2-2258; N01-AR-2-2259; N01-AR-2-2260; N01-AR-2-2261; N01-AR-2-2262) from the National Institutes of Health, a branch of the Department of Health and Human Services, and conducted by the OAI Study Investigators. Private funding partners include Merck Research Laboratories; Novartis Pharmaceuticals Corporation, GlaxoSmithKline; and Pfizer, Inc. Private-sector funding for the OAI is managed by the Foundation for the National Institutes of Health. This manuscript was prepared using an OAI public use data set and does not necessarily reflect the opinions or views of the OAI investigators, the NIH, or the private funding partners.

Conflict of interest

Veronese, Stubbs, Smith, Maggi, Jackson, Soysal, Demurtas, Celotto and Koyanagi declare that they have no potential conflicts of interest that might be relevant to the contents of this manuscript.


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Nicola Veronese
    • 1
    Email author
  • Brendon Stubbs
    • 2
    • 3
    • 4
  • Lee Smith
    • 5
  • Stefania Maggi
    • 1
  • Sarah E. Jackson
    • 6
  • Pinar Soysal
    • 7
  • Jacopo Demurtas
    • 8
  • Stefano Celotto
    • 9
  • Ai Koyanagi
    • 10
    • 11
  1. 1.National Research Council, Neuroscience Institute, Aging BranchPaduaItaly
  2. 2.Physiotherapy DepartmentSouth London and Maudsley NHS Foundation TrustLondonUK
  3. 3.Health Service and Population Research Department, Institute of Psychiatry, Psychology and NeuroscienceKing’s College LondonLondonUK
  4. 4.Faculty of Health, Social Care and EducationAnglia Ruskin UniversityChelmsfordUK
  5. 5.The Cambridge Centre for Sport and Exercise SciencesAnglia Ruskin UniversityCambridgeUK
  6. 6.Department of Behavioural Science and HealthUniversity College LondonLondonUK
  7. 7.Department of Geriatric Medicine, Faculty of MedicineBezmialem Vakif UniversityIstanbulTurkey
  8. 8.Primary Care DepartmentAzienda USL Toscana Sud EstGrossetoItaly
  9. 9.Primary Care DepartmentAziendale AAS3 Alto Friuli, Collinare, Medio FriuliUdineItaly
  10. 10.Research and Development Unit, Parc Sanitari Sant Joan de DéuUniversitat de Barcelona, Fundació Sant Joan de DéuBarcelonaSpain
  11. 11.Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAMMadridSpain

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