Inflammatory resilience index combining hsCRP, albumin, and appendicular lean mass predicts functional limitations and mortality in U.S. adults: derivation and external validation study.
V Jaiswal, A Bouras, V Thaker, A Jaiswal, S P Ang, R Yadav, M Hanif, A Qamar, A Bielecka-Dabrowa, M BanachAbstract
Background
Inflammation, nutritional status, and muscle mass independently predict adverse health outcomes including mortality and functional decline. An integrated index combining these domains may better capture overall physiologic resilience than individual biomarkers.
Purpose
To develop an Inflammatory Resilience Index (IRI) combining high-sensitivity C-reactive protein (hsCRP), serum albumin, and appendicular lean mass index (ALMI), and evaluate its association with functional outcomes and mortality in U.S. adults.
Methods
We analyzed data from 11,854 adults aged 30–79 years without baseline atherosclerotic cardiovascular disease from the National Health and Nutrition Examination Survey (NHANES) 2003–2006 and 2015–2016, with mortality follow-up through December 2019 (median 13.8 years). The IRI was computed as the mean of sex-specific z-scores for serum albumin, ALMI, and the inverse of log-transformed hsCRP: IRI = (Albumin_z + ALMI_z – log[hsCRP]_z) / 3, where higher values indicate greater physiologic resilience. Self-reported general health status was assessed using the standardized NHANES question "Would you say your health in general is excellent, very good, good, fair, or poor?"; fair/poor health was defined as a response of "fair" or "poor". Cross-sectional associations with functional outcomes were evaluated using survey-weighted logistic regression. Prospective associations with mortality were assessed using survey-weighted Cox proportional hazards models. Discrimination was compared using Harrell’s C-statistic.
Results
The IRI was approximately normally distributed (mean 0.00, SD 0.54) with an interquartile reference range of –0.36 to 0.36 and a 10th–90th percentile range of –0.67 to 0.68. In cross-sectional analyses (n=10,875), each 1-SD increase in IRI was associated with 21% lower odds of fair/poor self-reported health (OR: 0.79; 95% CI: 0.74–0.85; P<0.001) and 31% lower odds of walking difficulty (OR: 0.69; 95% CI: 0.61–0.78; P<0.001). Over a median follow-up of 13.8 years (806 all-cause deaths; 221 cardiovascular deaths), each 1-SD increase in IRI was associated with 29% lower all-cause mortality (HR: 0.71; 95% CI: 0.64–0.79; P<0.001), 35% lower cardiovascular mortality (HR: 0.65; 95% CI: 0.54–0.78; P<0.001), and 34% lower heart disease–specific mortality (HR: 0.66; 95% CI: 0.53–0.82; P<0.001). Adding IRI to the base model improved discrimination for all-cause mortality (ΔC-statistic +0.002) and outperformed the addition of hsCRP alone (ΔC +0.000) or ALMI alone (ΔC +0.000).
Conclusions
The Inflammatory Resilience Index integrating inflammation, nutritional reserve, and muscle mass independently predicts functional limitations and mortality in U.S. adults after adjustment for demographic, clinical, and socioeconomic factors, and provides incremental discrimination over individual components. IRI may serve as a composite marker of physiologic reserve for clinical risk stratification.Figure 1Figure 2.