Polytrauma in Older Adults Leads to Significantly Increased TIMP-1 Levels in the Early Posttraumatic Period

Abstract

Background: Patients after polytrauma regularly suffer from posttraumatic immune system destabilization, which closely influences the further clinical development. Increasing age has recently been identified as an isolated risk factor for an adverse outcome after major trauma. Higher rates and intensity of acute inflammation following severe injury suggest that deregulated inflammation may contribute to these higher rates of posttraumatic morbidity and mortality in older adults. MMP-9 and TIMP-1 have been found to play a major role in posttraumatic immune disorder in a previous genome-wide mRNA analysis.

Objective: The aim of this study was to evaluate the differences in serum protein dynamics in older and younger polytraumatized adults.

Methods: Blood samples were drawn immediately within 90 minutes after trauma and subsequently after 6, 12, 24, 48, and 72 h. Serum levels of TIMP-1 and MMP-9 were quantified using ELISA. Age groups were divided according to a cutoff of 60 years.

Results: 60 polytrauma patients (ISS > 16) were included (<60 years, n = 49; ≥60 years, n = 49; ≥60 years, n = 11). Serum TIMP-1 and MMP-9 levels showed a highly significant serum dynamic in young and old polytrauma patients (p < 0.001). Patients ≥ 60 years showed significantly higher overall TIMP-1 levels (p < 0.001). Patients ≥ 60 years showed significantly higher overall TIMP-1 levels (p = 0.008). TIMP-1 levels showed a significant maximum after 72 h in the older study population. MMP-9 levels were nonsignificantly higher during the whole observational period in older polytrauma patients when compared to younger patients.

Conclusion: The posttraumatic immune response is characterized by significantly higher TIMP-1 levels in older polytrauma patients. This significant association between TIMP-1 levels and patients' age indicates a more extensive immune dysregulation following major trauma in older adults.

Figure 1

Mean ISS of all patients according to age decades (n = 60). The results show higher ISS scores between 20 and 40 years and over the age of 80 years.

Figure 2

Mean NISS of all patients according to age decades (n = 60). The results show higher NISS scores in patients aged between 20 and 40 years and again between the ages of 70 and 90 years.

Figure 3

Outcome according to patient's mean age. Patients who died after the traumatic event were older on average when compared to younger polytrauma patients (nonsurvivors n = 8, mean age 54.9 years; survivors n = 52, mean age 43.4 years).

Figure 4

Mean ISS of all patients correlated to patient's outcome. Patients who died after the traumatic event showed higher mean ISS than those who survived (mean ISS survivors: 35 ± 11.6 SD; mean ISS nonsurvivors: 39.3 ± 12.2 SD).

Figure 5

Mean NISS of all patients according to patient's outcome. Patients who died after the traumatic event showed higher mean NISS than those who survived (mean NISS survivors: 40.2 ± 12.8 SD; mean NISS nonsurvivors: 50.5 ± 12.2 SD).

Figure 6

TIMP-1 serum levels within the first 72 h after trauma correlated to patient's age. Multivariate testing of TIMP-1 serum levels and time after trauma revealed a highly statistical significance (p < 0.001) in both groups. TIMP-1 levels were significantly higher in patients ≥ 60 years when compared to younger polytrauma patients (p = 0.008). Post hoc analysis revealed significantly higher TIMP-1 levels in older patients after 72 h (p = 0.039).

Figure 7

MMP-9 serum levels over the first 72 h after trauma correlated to patient's age. Multivariate analysis of concentration kinetic of MMP-9 and time after trauma revealed a highly statistical significance (p < 0.001) in both groups. General linear regression model (test of between-subject effects) revealed no statistical significance for MMP-9 serum levels and age (p = 0.227).