Longitudinal Change of Serum Inter-α-Trypsin Inhibitor Heavy Chain H4 and its Relation with Inflammation, Disease Recurrence, and Mortality in Acute Ischemic Stroke Patients.

Inter-α-trypsin inhibitor heavy chain H4 (ITIH4) modulates atherosclerosis, lipid, and inflammation, which is involved in the development of acute ischemic stroke. Hence, this study aimed to investigate the longitudinal change and prognostic role of ITIH4 in acute ischemic stroke. In 267 patients with acute ischemic stroke, serum ITIH4 after admission (baseline), the 1st day after admission (D1), D3, D7, and D30, and inflammatory cytokines at baseline were detected by enzyme-linked immunosorbent assay (ELISA). Additionally, serum ITIH4 of 30 controls after enrollment was detected by ELISA. ITIH4 was reduced in acute ischemic stroke patients than controls [median (interquartile range, IQR): 131.0 (95.5-194.3) vs. 418.6 (241.5-506.8) ng/mL] (P < 0.001). Among acute ischemic stroke patients, ITIH4 was negatively associated with tumor necrosis factor-alpha (r = -0.211, P = 0.001), interleukin (IL)-1β (r = -0.164, P = 0.007), IL-6 (r = -0.121, P = 0.049), and IL-17A (r = -0.188, P = 0.002). ITIH4 presented a decreased trend from admission to D3, then increased from D3 to D30 (P < 0.001). The 1-year, 2-year, and 3-year cumulative recurrence rate was 7.5%, 18.0%, and 19.1%, respectively; meanwhile, 1-year, 2-year, and 3-year cumulative death rate was 2.2%, 7.1%, and 7.1%, accordingly. The further analysis presented that ITIH4 at baseline (P = 0.002), D1 (P = 0.049), D3 (P = 0.003), D7 (P < 0.001), and D30 (P < 0.001) was decreased in recurrent patients than non-recurrent patients; besides, ITIH4 at D3 (P = 0.017), D7 (P = 0.004), and D30 (P = 0.002), but not at baseline (P = 0.151) or D1 (P = 0.013), was decreased in deaths than survivors. Serum ITIH4 declines at first and then elevates with time, and its reduction is correlated with higher inflammation, increased risk of recurrence and mortality in acute ischemic stroke patients.