Tumor Necrosis Factor Receptor 1 and 2 Are Associated With Risk of Intracerebral Hemorrhage

Raised plasma concentrations of tumor necrosis factor receptors (TNFR) have been linked to arterial stiffness, cerebral microbleeds, and vascular events. The aim of this study was to investigate the association of circulating levels of TNFR1 and TNFR2 with risk for future intracerebral hemorrhage (ICH).

The population-based MDCS cohort (Malmö Diet and Cancer Study; n=28 449) was conducted in 1991 to 1996. A nested case-control study was performed in the MDCS, including 220 cases who experienced ICH during the follow-up period (mean age at inclusion 62 years, 48% men) and 244 matched controls. Of the 220 ICH cases, 68 died within 28 days. Conditional logistic regression was used to study the association between plasma levels of TNFR1 and TNFR2 and incident ICH, adjusting for known ICH risk factors.

Concentrations of both TNFR1 and TNFR2 were significantly higher in subjects who developed ICH during the follow-up. The associations remained after adjustment for ICH risk factors (TNFR1: odds ratio [OR], 2.28; 95% confidence interval [CI], 1.26-4.11; P=0.006; TNFR2: OR, 1.77; CI, 1.16-2.70; P=0.008). ORs were somewhat higher for nonlobar ICH (3.04; CI, 1.29-7.14 and 2.39; CI, 1.32-4.32, respectively) than for lobar ICH (2.03; CI, 0.93-4.41 and 1.35; CI, 0.78-2.37, respectively). TNFR1 and TNFR2 were also associated with increased risk of fatal ICH (TNFR1: OR, 4.42; CI, 1.67-11.6; TNFR2: OR, 2.90; CI, 1.50-5.58) and with poor functional outcome according to the modified Rankin Scale.

High plasma levels of TNFR1 and TNFR2 were associated with incident ICH, most clearly with ICH of nonlobar location. The results suggest that tumor necrosis factor-mediated inflammation could be associated with vascular changes preceding ICH.