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How Do Common Comorbidities Modify the Association of Frailty With Survival After Elective Noncardiac Surgery? A Population-Based Cohort Study

Hui, Yin MD*; van Walraven, Carl MD, FRCPC, MSc†,‡,§; McIsaac, Daniel I. MD, MPH, FRCPC*,‡,§

doi: 10.1213/ANE.0000000000004387
Geriatric Anesthesia: Original Clinical Research Report

BACKGROUND: Older people with frailty have decreased postoperative survival. Understanding how comorbidities modify the association between frailty and survival could improve risk stratification and guide development of interventions. Therefore, we evaluated whether the concurrent presence of common and high-risk comorbidities (dementia, chronic obstructive pulmonary disease [COPD], coronary artery disease [CAD], diabetes mellitus, heart failure [HF]) in conjunction with frailty might be associated with a larger decrease in postoperative survival after major elective surgery than would be expected based on the presence of the comorbidity and frailty on their own.

METHODS: This cohort study used linked administrative data from Ontario, Canada to identify adults >65 years having elective noncardiac surgery from 2010 to 2015. Frailty was identified using a validated index; comorbidities were identified with validated codes. We evaluated the presence of effect modification (also called interaction) between frailty and each comorbidity on (1) the relative (or multiplicative) scale by assessing whether the risk of mortality when both frailty and the comorbidity were present was different than the product of the risks associated with each condition; and (2) the absolute risk difference (or additive) scale by assessing whether the risk of mortality when both frailty and the comorbidity were present was greater than the sum of the risks associated with each condition.

RESULTS: 11,150 (9.7%) people with frailty died versus 7826 (2.8%) without frailty. After adjustment, frailty was associated with decreased survival (adjusted hazard ratio [HR] = 2.42; 95% confidence interval [CI], 2.31–2.54). On the relative (multiplicative) scale, only diabetes mellitus demonstrated significant effect modification (P value for interaction .03; reduced risk together). On the absolute risk difference (additive) scale, all comorbidities except for coronary disease demonstrated effect modification of the association of frailty with survival. Co-occurrence of dementia with frailty carried the greatest excess risk (Synergy Index [S; the excess risk from exposure to both risk factors compared to the sum of the risks from each factor in isolation] = 2.29; 95% CI, 1.32–10.80, the excess risk from exposure to both risk factors compared to the sum of the risks from each factor in isolation).

CONCLUSIONS: Common comorbidities modify the association of frailty with postoperative survival; however, this effect was only apparent when analyses accounted for effect modification on the absolute risk difference, as opposed to relative scale. While the relative scale is more commonly used in biomedical research, smaller effects may be easier to detect on the risk difference scale. The concurrent presence of dementia, COPD, and HF with frailty were all associated with excess mortality on the absolute risk difference scale.

From the Departments of *Anesthesiology & Pain Medicine, and †Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada

Institute for Clinical Evaluative Sciences, Ottawa, Ontario, Canada

§Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.

Published ahead of print 22 August 2019.

Accepted for publication July 16, 2019.

Funding: This study was supported by the Institute for Clinical Evaluative Sciences (ICES), which is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care (MOHLTC). The opinions, results, and conclusions reported in this paper are those of the authors and are independent from the funding sources. No endorsement by ICES or the Ontario MOHLTC is intended or should be inferred. These data sets were held securely in a linked, deidentified form and analyzed at the Institute for Clinical Evaluative Sciences. This study used the Johns Hopkins ACG System v10.

Conflicts of Interest: See Disclosures at the end of the article.

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Reprints will not be available from the authors.

Address correspondence to Daniel I. McIsaac, MD, MPH, FRCPC, Department of Anesthesiology, The Ottawa Hospital, Room B311, Civic Campus, 1053 Carling Ave, Ottawa, ON K1Y 4E9, Canada. Address e-mail to

Copyright © 2019 International Anesthesia Research Society
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