Nicola Veronese1, Brendon Stubbs2, Marianna Noale3, Marco Solmi4, Alberto Pilotto5, Alberto Vaona6, Jacopo Demurtas7, Christoph Mueller8, Jonathan Huntley8, Gaetano Crepaldi3, Stefania Maggi3. 1. National Research Council, Neuroscience Institute, Aging Branch, Padua, Italy; Institute for clinical Research and Education in Medicine, IREM, Padua, Italy; Department of Geriatric Care, OrthoGeriatrics and Rehabilitation, E.O. Galliera Hospital, Genova, Italy. Electronic address: ilmannato@gmail.com. 2. South London and Maudsley NHS Foundation Trust, Denmark Hill, London, United Kingdom; Faculty of Health, Social care and Education, Anglia Ruskin University, Chelmsford, United Kingdom; Institute of Psychiatry, Psychology and Neuroscience (IoPPN) King's College London, London, United Kingdom. 3. National Research Council, Neuroscience Institute, Aging Branch, Padua, Italy. 4. Institute for clinical Research and Education in Medicine, IREM, Padua, Italy; Department of Neurosciences, University of Padova, Padova, Italy. 5. Department of Geriatric Care, OrthoGeriatrics and Rehabilitation, E.O. Galliera Hospital, Genova, Italy. 6. Primary Care Department, Azienda ULSS20 Verona, Verona, Italy. 7. Primary Care Department, Azienda USL Toscana Sud Est, Grosseto, Italy. 8. South London and Maudsley NHS Foundation Trust, Denmark Hill, London, United Kingdom; Institute of Psychiatry, Psychology and Neuroscience (IoPPN) King's College London, London, United Kingdom.
Abstract
OBJECTIVE: To investigate whether polypharmacy is associated with a higher incidence of frailty in a large cohort of North Americans during 8 years of follow-up. DESIGN: Longitudinal study, follow-up of 8 years. PARTICIPANTS: A total of 4402 individuals at high risk or having knee osteoarthritis free from frailty at baseline. MEASUREMENTS: Details regarding medication prescription were captured and categorized as 0-3, 4-6, and ≥7. Frailty was defined using the Study of Osteoporotic Fracture index as the presence of ≥2 out of (1) weight loss ≥5% between baseline and the subsequent follow-up visit; (2) inability to do 5 chair stands; and (3) low energy level according to the Study of Osteoporotic Fracture definition. Cox's regression models calculating a hazard ratio (HR) with 95% confidence intervals (CIs), adjusted for potential confounders, were undertaken. RESULTS: During the 8-year follow-up, from 4402 participants at baseline, 361 became frail. Compared with participants taking 0-3 medications, the incidence of frailty was approximately double in those taking 4-6 medications and 6 times higher in people taking ≥7 medications. After adjusting for 11 potential baseline confounders, participants using 4-6 medications had a higher risk of frailty of 55% (HR = 1.55; 95% CI 1.22-1.96; P < .0001), whereas those using more than 7 drugs were at approximately 147% (HR = 2.47; 95% CI 1.78-3.43; P < .0001). Each additional drug used at the baseline increased the risk of frailty at the follow-up of 11% (HR = 1.11; 95% CI 1.07-1.15; P < .0001). CONCLUSIONS: Polypharmacy is associated with a higher incidence of frailty over 8-year follow-up period. Our data suggest evidence of a dose response relationship. Future research is required to confirm our findings and explore underlying mechanisms.
OBJECTIVE: To investigate whether polypharmacy is associated with a higher incidence of frailty in a large cohort of North Americans during 8 years of follow-up. DESIGN: Longitudinal study, follow-up of 8 years. PARTICIPANTS: A total of 4402 individuals at high risk or having knee osteoarthritis free from frailty at baseline. MEASUREMENTS: Details regarding medication prescription were captured and categorized as 0-3, 4-6, and ≥7. Frailty was defined using the Study of Osteoporotic Fracture index as the presence of ≥2 out of (1) weight loss ≥5% between baseline and the subsequent follow-up visit; (2) inability to do 5 chair stands; and (3) low energy level according to the Study of Osteoporotic Fracture definition. Cox's regression models calculating a hazard ratio (HR) with 95% confidence intervals (CIs), adjusted for potential confounders, were undertaken. RESULTS: During the 8-year follow-up, from 4402 participants at baseline, 361 became frail. Compared with participants taking 0-3 medications, the incidence of frailty was approximately double in those taking 4-6 medications and 6 times higher in people taking ≥7 medications. After adjusting for 11 potential baseline confounders, participants using 4-6 medications had a higher risk of frailty of 55% (HR = 1.55; 95% CI 1.22-1.96; P < .0001), whereas those using more than 7 drugs were at approximately 147% (HR = 2.47; 95% CI 1.78-3.43; P < .0001). Each additional drug used at the baseline increased the risk of frailty at the follow-up of 11% (HR = 1.11; 95% CI 1.07-1.15; P < .0001). CONCLUSIONS: Polypharmacy is associated with a higher incidence of frailty over 8-year follow-up period. Our data suggest evidence of a dose response relationship. Future research is required to confirm our findings and explore underlying mechanisms.
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