MiR-34c Is Predictive of Delayed Cerebral Ischemia After Subarachnoid Hemorrhage

TL;DR

This study finds that higher levels of miR-34c in the blood predict delayed cerebral ischemia in patients with subarachnoid hemorrhage.

Contribution

The study identifies miR-34c as a novel predictor of delayed cerebral ischemia after subarachnoid hemorrhage.

Findings

Higher miR-34c levels were significantly associated with delayed cerebral ischemia (DCI) in SAH patients.

Adjusting for clinical factors, higher miR-34c levels increased the odds of DCI by 5.7-fold.

Survival analysis showed a 5.4-fold higher hazard of DCI for patients with elevated miR-34c.

Abstract

Introduction
Delayed cerebral ischemia (DCI) is a potentially preventable complication from an aneurysmal subarachnoid hemorrhage (SAH). The micro-RNAs (miR) 34 family has shown its ability to disrupt the blood-brain barrier and redox metabolism and might contribute to the complex pathophysiology of DCI. This study aimsto evaluate the association between the serum levels of miR-34c and the occurrence of DCI.
Methods
This retrospective observational study is based on 72 subjects with acute aneurysmal SAH who were admitted to a single tertiary center between December 2017 and July 2021. Subjects were prospectively adjudicated for clinical outcomes, including delayed cerebral ischemia.Levels of miR-34c were measured in plasma collected within 48 hours of ictus. Patients were median-dichotomized into having a higher or lower plasma level of miR-34c. miR34c levels were compared between DCI and no DCI groups using the Wilcoxon rank sum tests. A multivariable logistic regression model and the Cox proportional hazard model were used to evaluate the effect of higher miR-34c levels.
Results
The median age was 54 years, 76% were females, and 21% developed DCI. Early miR-34c levels were significantly higher in SAH subjects who progressed to have DCI with Cohen’s
d
of 0.75 (p<0.05). Even after adjusting for age, sex, histories of diabetes, hypertension, Hunt-Hess grade, and modified Graeb scores, a higher miR-34c level was associated with 5.7-fold increased odds of DCI (p<0.05; 95% CI: 1.35-32.22). Survival analysis adjusting for the known predictors also revealeda 5.4-fold higher hazard of DCI for the patients with a higher miR-34c level (p < 0.05; 95% CI 1.22-25.43).
Conclusion
The present study demonstrates the potential importance of circulating miR-34c in predicting DCI in SAH patients. Given the known importance of the miR-34 family in vascular physiology, it may be an important target for future studies.