Table 4.
Associations between Endothelial Dysfunction and Acute Brain Dysfunction by Blood-Brain Barrier Injury
| Percentile | Without S100B | With S100B | ||||
|---|---|---|---|---|---|---|
| Variable | 25th | 75th | Adj Difference* | P value | Adj Difference* | P value |
| Associations with delirium/coma-free days among all patients (N=134) | ||||||
| PAI-1(ng/mL) | 74.3 | 171.5 | −1.72 (−2.65, −0.79)† | 0.002 | −1.54 (−2.46, −0.61)† | 0.005 |
| E-selectin(ng/mL) | 9.8 | 29.8 | 0.24 (−0.62, 1.10)† | 0.02 | 0.41 (−0.49, 1.31)† | 0.07 |
| Ang-2(pg/mL) | 9639 | 26369 | −0.25 (−1.32, 0.82) | 0.64 | Did not perform | |
| RHI | 1.21 | 1.76 | 1.09 (0.50, 1.68) | <0.001 | 0.97 (0.38, 1.56) | 0.001 |
| Associations with delirium days among survivors (N=113) | ||||||
| PAI-1(ng/mL) | 74.3 | 171.5 | 0.83 (0.25, 1.40)† | 0.007 | 0.74 (0.18, 1.31)† | 0.01 |
| E-selectin(ng/mL) | 9.8 | 29.8 | 0.28 (−0.26, 0.83)† | 0.12 | Did not perform | |
| Ang-2(pg/mL) | 9639 | 26369 | 0.22 (−0.54, 0.99) | 0.57 | Did not perform | |
| RHI | 1.21 | 1.76 | −0.63 (−1.15, −0.12) | 0.02 | −0.61 (−1.11, −0.11) | 0.02 |
Results, which were determined using multiple linear regression, show the adjusted difference (and 95% confidence intervals) in delirium/coma-free days or delirium days when the variable increased from the 25th percentile value to the 75th percentile value. In the delirium/coma-free days models, a negative adjusted difference indicates that higher biomarker concentrations were associated with worse cognitive outcomes, i.e., fewer days without brain dysfunction. Alternatively, in the delirium duration model, a positive adjusted difference indicates that higher biomarker concentrations were associated with worse cognitive outcomes, i.e., more days of delirium.
Indicates the association was nonlinear.
Abbreviations: Adj, adjusted; Ang-2, angiopoietin-2; PAI-1, plasminogen activator inhibitor-1; RHI, reactive hyperemia index
We included S100B as a covariate in linear regression models to assess whether BBB/neurological injury mediated any significant associations observed between markers of endothelial activation or vascular reactivity and delirium/coma-free days. Higher PAI-1 plasma concentrations at enrollment remained significantly associated with fewer delirium/coma-free days among all patients and with longer delirium duration among survivors. The association between E-selectin at enrollment and delirium/coma-free days, while no longer statistically significant, was very similar in size and direction to the association without adjustment for S100B; therefore, the nonsignificance was likely due to having more terms and less power in the model. Improved vascular reactivity (higher RHI) remained significantly associated with increased delirium/coma-free days among all patients and with shorter delirium duration among survivors.