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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 Y, van Walraven C, McIsaac DI. Anesth Analg. 2019; Aug 22 [Epub ahead of print]. DOI: 10.1213/ANE.0000000000004387.


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.

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