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This study aims to determine whether frailty increases mortality compared to pre-frailty and to identify variables associated with a higher risk of mortality. Materials: Two cohorts, frail and pre-frail subjects, are evaluated according to the Fried phenotype. A complete examination of frailty, cognitive status, comorbidities and pharmacology was carried out at hospital admission and was extracted through electronic health record (EHR). Mortality was evaluated from the EHR. Methods: Kaplan\u2013Meier estimates of survival probability functions were calculated at two years censoring time for frail and pre-frail cohorts. The log-rank test assessed significant differences between survival probability functions. Significant variables for frailty (p &lt; 0\u201305) were extracted by independent sample t-test. Further selection was based on variable significance found in multivariate logistic regression discrimination between frail and pre-frail subjects. Cox regression over univariate t-test-selected variables was calculated to identify variables associated with higher proportional hazard risks (HR) at two years. Results: Frailty is associated with greater mortality at two years censoring time than pre-frailty (log-rank test, p &lt; 0.0001). Variables with significant (p &lt; 0.05) association with mortality identified in both cohorts (HR 95% (CI in the frail cohort) are male sex (0.44 (0.29\u20130.66)), age (1.05 (1.01\u20131.09)), weight (0.98 (0.96\u20131.00)), and use of proton-pump inhibitors (PPIs) (0.60 (0.41\u20130.87)). Specific high-risk factors in the frail cohort are readmission at 30 days (0.50 (0.33\u20130.74)), SPPB sit and stand (0.62 (0.45\u20130.85)), heart failure (0.67 (0.46\u20130.98)), use of antiplatelets (1.80 (1.19\u20132.71)), and quetiapine (0.31 (0.12\u20130.81)). Specific high-risk factors in the pre-frail cohort are Barthel\u2019s score (120 (7.7\u20131700)), Pfeiffer test (8.4; (2.3\u201331)), Mini Nutritional Assessment (MNA) (1200 (18\u201388,000)), constipation (0.025 (0.0027\u20130.24)), falls (18,000 (150\u20132,200,000)), deep venous thrombosis (8400 (19\u20133,700,000)), cerebrovascular disease (0.01 (0.00064\u20130.16)), diabetes (360 (3.4\u201339,000)), thyroid disease (0.00099 (0.000012\u20130.085)), and the use of PPIs (0.062 (0.0072\u20130.54)), Zolpidem (0.000014 (0.0000000021\u20130.092)), antidiabetics (0.00015 (0.00000042\u20130.051)), diuretics (0.0003 (0.000004\u20130.022)), and opiates (0.000069 (0.00000035\u20130.013)). Conclusions: Frailty is associated with higher mortality at two years than pre-frailty. Frailty is recognized as a systemic syndrome with many links to older-age comorbidities, which are also found in our study. Polypharmacy is strongly associated with frailty, and several commonly prescribed drugs are strongly associated with increased mortality. It must be considered that frail patients need coordinated attention where the diverse specialist taking care of them jointly examines the interactions between the diversity of treatments prescribed.<\/jats:p>","DOI":"10.3390\/jcm12093103","type":"journal-article","created":{"date-parts":[[2023,4,25]],"date-time":"2023-04-25T01:37:01Z","timestamp":1682386621000},"page":"3103","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Mortality Risks after Two Years in Frail and Pre-Frail Older Adults Admitted to Hospital"],"prefix":"10.3390","volume":"12","author":[{"given":"Guillermo","family":"Cano-Escalera","sequence":"first","affiliation":[{"name":"Department of Computer Science and Artificial Intelligence, University of the Basque Country (UPV\/EHU), 20018 Donostia-San Sebastian, Spain"},{"name":"Computational Intelligence Group, University of the Basque Country (UPV\/EHU), 20018 Donostia-San Sebastian, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7373-4097","authenticated-orcid":false,"given":"Manuel","family":"Gra\u00f1a","sequence":"additional","affiliation":[{"name":"Department of Computer Science and Artificial Intelligence, University of the Basque Country (UPV\/EHU), 20018 Donostia-San Sebastian, Spain"},{"name":"Computational Intelligence Group, University of the Basque Country (UPV\/EHU), 20018 Donostia-San Sebastian, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6763-8602","authenticated-orcid":false,"given":"Jon","family":"Irazusta","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine and Nursing, University of the Basque Country (UPV\/EHU), 48940 Bilbao, Spain"},{"name":"BioCruces Health Research Institute, 48903 Barakaldo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4334-3287","authenticated-orcid":false,"given":"Idoia","family":"Labayen","sequence":"additional","affiliation":[{"name":"Institute for Innovation & Sustainable Development in Food Chain (IS-FOOD), Public University of Navarra, 31006 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Gonzalez-Pinto","sequence":"additional","affiliation":[{"name":"BioAraba, Health Research Institute, Department of Medicine, Hospital Universitario de Araba, 01004 Vitoria, Spain"},{"name":"Biomedical Research Centre in Mental Health Network (CIBERSAM), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariadna","family":"Besga","sequence":"additional","affiliation":[{"name":"BioAraba, Health Research Institute, Department of Medicine, Hospital Universitario de Araba, 01004 Vitoria, Spain"},{"name":"Biomedical Research Centre in Mental Health Network (CIBERSAM), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1016\/S0140-6736(19)31786-6","article-title":"Frailty: Implications for clinical practice and public health","volume":"394","author":"Hoogendijk","year":"2019","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1016\/S0140-6736(19)31785-4","article-title":"Management of frailty: Opportunities, challenges, and future directions","volume":"394","author":"Dent","year":"2019","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1111\/jgs.16976","article-title":"Progression of Physical Frailty and the Risk of All-Cause Mortality: Is There a Point of No Return?","volume":"69","author":"Xue","year":"2021","journal-title":"J. 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