Decreased Glycocalyx Shedding on Presentation in Hemorrhaging Geriatric Trauma Patients

Plasma levels of syndecan-1 (Sdc-1), a biomarker of endothelial glycocalyx (EG) damage, correlate with worse outcomes in trauma patients. However, EG injury is not well characterized in injured older adults (OA). The aims of this study were to characterize Sdc-1 shedding in OA trauma patients relative to younger adults (YA) and determine associations with putative regulators of EG sheddases.

We performed a secondary analysis of data from the Pragmatic, Randomized Optimal Platelet, and Plasma Ratios (PROPPR) trial, stratifying bluntly injured subjects into OA and YA groups based on upper age quartile (57 y). Plasma Sdc-1 levels were compared in OA and YA at hospital arrival through postinjury day 3, and the independent association between age and Sdc-1 level at arrival was determined after adjusting for differences in gender, shock index (SI), and pre-existing comorbidities. In a follow-up analysis, case-control matching was used to create populations of OA and YA with equivalent SI and injury severity score. Levels of Sdc-1 were compared between these matched groups, and the relationships with candidate regulators of EG shedding were assessed.

Of 680 subjects in the Pragmatic, Randomized Optimal Platelet, and Plasma Ratios trial, 350 (51%) had blunt injuries, and 92 (26.3%) of these were OA. Plasma Sdc-1 levels at arrival, 2 h, and 6 h were significantly lower in OA compared to YA (all P < 0.05). After adjusting for sex, pre-existing morbidities and SI, age was associated with decreased Sdc-1 levels at arrival. In the matched analyses, Sdc-1, high-mobility group box 1 and tissue inhibitor of metalloproteinase-2 levels were lower in OA compared to YA. Both high-mobility group box-1 and tissue inhibitor of metalloproteinase-2 significantly correlated with arrival Sdc-1 and were inversely associated with age.

This study indicates that increased age is independently associated with decreased Sdc-1 levels among patients with blunt injuries. Suppressed plasma levels of sheddases in relation to diminished Sdc-1 shedding suggest that mechanisms regulating EG cleavage may be impaired in injured older adults. These findings provide novel insight into the age-dependent impact of injury on the vascular endothelium, which could have important implications for the clinical management of older adults following trauma.