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J Gerontol A Biol Sci Med Sci. 2019 Apr 23;74(5):659-666. doi: 10.1093/gerona/gly110.

Frailty and Multimorbidity: A Systematic Review and Meta-analysis.

Author information

Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet and Stockholm University, Sweden.
Department of Geriatrics, Catholic University of Rome, Italy.
San Camillo Hospital IRCCS, Venice, Italy.
Department of Clinical and Experimental Sciences, University of Brescia, Italy.
Scientific Direction, Italian National Research Centre on Aging, Ancona, Italy.
Department of Internal Medicine, Medical University of Graz, Austria.
Andalusian Public Foundation of Progress and Health, Regional Ministry of Health of Andalusia, Spain.
Geriatric Department, Hospital Universitario de Getafe, Madrid, Spain.



Multimorbidity and frailty are complex syndromes characteristics of aging. We reviewed the literature and provided pooled estimations of any evidence regarding (a) the coexistence of frailty and multimorbidity and (b) their association.


We searched PubMed and Web of Science for relevant articles up to September 2017. Pooled estimates were obtained through random effect models and Mantel-Haenszel weighting. Homogeneity (I2), risk of bias, and publication bias were assessed. PROSPERO registration: 57890.


A total of 48 studies involving 78,122 participants were selected, and 25 studies were included in one or more meta-analyses. Forty-five studies were cross-sectional and 3 longitudinal, with the majority of them including community-dwelling participants (n = 35). Forty-three studies presented a moderate risk of bias and five a low risk. Most of the articles defined multimorbidity as having two or more diseases and frailty according to the Cardiovascular Health Study criteria. In meta-analyses, the prevalence of multimorbidity in frail individual was 72% (95% confidence interval = 63%-81%; I2 = 91.3%), and the prevalence of frailty among multimorbid individuals was 16% (95% confidence interval = 12%-21%; I2 = 96.5%). Multimorbidity was associated with frailty in pooled analyses (odds ratio = 2.27; 95% confidence interval = 1.97-2.62; I2 = 47.7%). The three longitudinal studies suggest a bidirectional association between multimorbidity and frailty.


Frailty and multimorbidity are two related conditions in older adults. Most frail individuals are also multimorbid, but fewer multimorbid ones also present frailty. Our findings are not conclusive regarding the causal association between the two conditions. Further longitudinal and well-designed studies may help to untangle the relationship between frailty and multimorbidity.


Chronic diseases; Frailty; Multimorbidity; Older people; Personalized medicine


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