Physiologic frailty progression following severe infections in US Veterans ≥65 years

Abstract Background Frailty is a state of increased vulnerability that may worsen after severe infections. We aimed to determine whether physiologic frailty progression worsens following severe infections in individuals aged ≥65 years. Methods We did a matched cohort study using electronic health records from the US Department of Veterans Affairs (VA), 2008-2019. We matched individuals with a severe (hospitalised) infection after age 65 years to those without by age, sex, race, ethnicity and VA site in calendar time order. We used Veterans Aging Cohort Study (VACS) Index 2.0 to measure physiologic frailty, calculated from routinely available clinical biomarkers. Scores typically range between 0 and 100 with each 5-point increment corresponding to a 6.5% increase in mortality risk. Using linear regression, we estimated the conditional mean difference in frailty in each follow-up year 1-5 between individuals with and without a severe infection, adjusting for baseline frailty, age, sex, race, ethnicity, deprivation, smoking, alcohol use, and comorbidity. We explored effect modification by baseline age, dementia, diabetes mellitus and HIV. Results We included 1,066,301 individuals (median age 74, IQR [70-81] years), of whom were 98% male. After adjustment, VACS Index scores increased by 2.0 points more in individuals with a severe infection compared to those without in year 1 (2.0, 95% CI 1.9-2.1) with the size of the difference declining in subsequent years; year 2 (0.40, 95% CI 0.34-0.46), year 3 (0.32, 95% CI 0.25-0.39), year 4 (0.30, 95% CI 0.22-0.38), and year 5 (0.41, 95% CI 0.31-0.50). In stratified analyses, the difference in VACS Index scores at follow-up was higher in older individuals and those with dementia, with no differences by diabetes mellitus and HIV status. Conclusions Among individuals aged ≥65 years, physiologic frailty increased more among individuals with severe infections after age 65 years than those without, especially in the first year after infection. Key messages • We have shown that severe (hospitalised) infections can worsen physiologic frailty progression. • This presents an opportunity for interventions aiming to prevent worsening frailty progression in old age.