Homocitrulline and 3-year mortality in older hospitalised adults: an exploratory study

Reliable biomarkers may allow early risk stratification for mortality in older adults. Post-translational modification-derived products (PTMDPs), such as homocitrulline, and the tissue accumulation of advanced glycation end products (AGEs), measured by skin autofluorescence, have been suggested as potential biomarkers of adverse outcomes in older and frail individuals. The aim of this study was to assess their association with 3-year mortality following hospitalisation.

We followed a cohort of 250 hospitalised patients over 3 years. Serum PTMDPs (homocitrulline, carboxymethyllysine, pentosidine, and MG-H1) were measured using liquid chromatography coupled with tandem mass spectrometry, and AGEs were quantified by skin autofluorescence. We examined associations with mortality using bivariable analyses and a multivariable Cox regression model. An exploratory cut-off for homocitrulline was established at the third quartile of its distribution within the study population.

During follow-up, 92 deaths occurred. In bivariable analyses, all biomarkers were associated with mortality. In the multivariable model, homocitrulline levels of >400 μmol/mol Lys were significantly associated with mortality (hazard ratio 1.73, 95 % confidence interval 1.06-2.82), after adjustment for age, frailty, and comorbidities. The model's predictive performance, with an area under the curve (AUC) of 0.76, was only slightly affected by the exclusion of homocitrulline (AUC=0.755).

These results indicate that although elevated homocitrulline was independently associated with mortality, its incremental value for risk prediction was modest. Larger studies are needed to further evaluate the clinical utility of PTMDPs, especially homocitrulline, for risk prediction and clinical decision-making.