Introduction: Epigenetic changes, such as DNA methylation and demethylation, offer a measure of ‘phenotypic age’ distinct from chronological age. In the general population, epigenetic age is related to morbidity and mortality. More accurate risk stratification methods are needed for adult spinal deformity (ASD) surgeries.
Methods: A multicenter ASD registry of patients undergoing complex reconstructions was queried. Adverse events (AE) were captured prospectively and adjudicated by a surgeon panel. Phenotypic age was calculated per Levine et al. using albumin, creatinine, glucose, CRP, lymphocyte count, mean cell volume, red cell distribution width, alkaline phosphatase, white blood cell count, and chronological age. Correlation between phenotypic and chronological age was examined. Logistic regression examined the relationship between phenotypic and chronological age and risk of AE, including those requiring major intervention and neurologic complications. Age was modeled nonlinearly. The C-statistic and r2 were computed for each model.
Results: Lab data were available for 200 patients. Mean phenotypic age was lower than chronological age (Phenotypic: 53.7±18.1, chronological: 61.1±15.4, p<.001, 95% CI: 6.3-8.5). Chronological age was associated with phenotypic age (r2=.79). Phenotypic age outperformed chronological age for several important complication categories, including any complication (C =.66 vs .60), AE requiring moderate intervention (.7 vs .69), AE requiring severe intervention (.73 vs .69) and new motor deficit (.64 vs .61).
Conclusion : Phenotypic age measured risk of a number of ASD surgery-related complications differently than chronological age, sometimes outperforming chronological age. Phenotypic age may offer an opportunity for more precise risk estimation in ASD surgery. While chronological age is unidirectional, phenotypic age may be modifiable, offering an opportunity for risk modification prior to surgical intervention.
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