Relationship between De Ritis and clinical outcomes in patients with aneurysmal subarachnoid hemorrhage: Insights from the LongTEAM registry

Abstract

Elevated aspartate aminotransferase-to-alanine aminotransferase ratio (De Ritis) has been associated with cardiovascular diseases and mortality. The clinical significance of De Ritis in the prognosis of hemorrhagic stroke has yet to be established. We aimed to investigate the associations between De Ritis levels and clinical outcomes in aneurysmal subarachnoid hemorrhage (aSAH). We retrospectively reviewed all aSAH patients admitted to their institution between January 2015 and September 2022 in the LongTEAM registry. Patients with aSAH were divided into four groups by quartiles of De Ritis, and two groups according to De Ritis < 1 and De Ritis ≥ 1. The functional outcomes at discharge and 90 days after discharge were assessed using the modified Rankin Scale (mRS). Multivariable logistic regression for poor functional outcome (mRS 3-6 and mRS 4-6) and in-hospital complications were adopted to explore the associations between De Ritis and clinical outcomes. Furthermore, restricted cubic spline models were used to assess the dose-response relationships between De Ritis and clinical outcomes. A total of 1,098 aSAH patients were included. The median De Ritis was 1.20 (interquartile range [IQR], 0.98-1.58). After adjusting for all the potential covariates and compared with those in the reference quartile, patients in the Q2 (0.89 to < 1.20) had a lower risk of unfavorable functional outcome (both mRS 3-6 and mRS 4-6) at discharge assessment (OR 0.623, 95% CI 0.408-0.951; OR 0.547, 95% CI 0.318-0.943 respectively), patients in the Q2 had a higher risk of MACE (OR 1.550, 95% CI 1.039-2.312), Q3 (1.20 to < 1.58) a higher risk of DCI (OR 1.569, 95%CI 1.047-2.353), and Q4 (≥ 1.58) with a higher risk of anemia (OR 1.662, 95%CI 1.092-2.530). Furthermore, patients with higher levels of De Ritis had lower risk of hepatic function (Q2, Q3, and Q4) and disorder of lipoprotein metabolism (Q3 and Q4) in fully-adjusted models. Restricted cubic spline models showed a non-linear associations between De Ritis levels and risk of mRS 4-6 at discharge assessment, MACE, abnormal hepatic function, anemia and disorders of lipoprotein metabolism. There was no significant difference between the TAPS model (AUC: 0.801) and the TAPS plus De Ritis index model (AUC: 0.801) (P = 0.345). No improvement was observed (net reclassification improvement [NRI]: 0.0022 [-0.0409-0.0384], P = 0.9457; integrated discrimination improvement [IDI]: 0.0183 [-0.0008-0.0007], P = 0.8522). Similar associations were also observed when De Ritis ≥ 1 compared with De Ritis < 1. Similar findings were robust after excluding participants with De Ritis > 2. We speculated that elevated De Ritis was associated with higher risk of unfavorable functional outcome at discharge, MACE, DCI and anemia. Given that postoperative De Ritis levels could help to identify high-risk patients with aSAH, these findings are of clinical relevance.

Keywords: Alanine aminotransferase; Aneurysmal subarachnoid hemorrhage; Aspartate aminotransferase; Complications; Outcomes.

Fig. 1

Non-linear associations between De Ritis ratio and clinical outcomes in patients with aneurysmal subarachnoid hemorrhage (aSAH). Restricted cubic spline regression models with fully adjusted covariates were used to explore the dose–response relationship between postoperative De Ritis levels and the risks of (A) unfavorable outcome (modified Rankin Scale score 4–6) at discharge, (B) death at discharge, (C) major adverse cardiac events (MACE), (D) abnormal hepatic function, (E) anemia, and (F) disorders of lipoprotein metabolism. Solid lines represent adjusted odds ratios (ORs) and shaded areas indicate 95% confidence intervals. Models were adjusted for age, sex, BMI, smoking, alcohol drinking, medical history, WFNS grade, modified Fisher score, aneurysm location, treatment modality, and laboratory variables including WBC, TC, TG, HDL, and LDL.