MicroRNA 150-5p Improves Risk Classification for Mortality within 90 Days after Acute Ischemic Stroke

Abstract

Background and purpose: Micro ribonucleic acid-150-5p (miR-150-5p) regulates proinflammatory cytokines as well as vessel integrity. We evaluated the incremental prognostic value of logarithm (log) of miR-150-5p plasma levels after ischemic stroke.

Methods: In a prospective cohort study, levels of miR-150-5p were measured within 72 hours of symptom onset in 329 ischemic stroke patients. The outcome measures were unfavorable functional outcome (assessed by the modified Rankin Scale score >2) and mortality within 90 days. Logistic regression and Cox proportional hazards models were fitted to estimate odds ratio (OR), respectively hazard ratio (HR) and 95% confidence interval (CI) for the association between log-miR-150-5p and the outcome measures. The discriminatory accuracy was assessed with the area under the receiver-operating-characteristic curve (AUC) and the incremental prognostic value was estimated with the net reclassification index.

Results: After adjusting for demographic and vascular risk factors, lower log-miR-150-5p levels were independently associated with mortality (HR 0.21 [95% CI, 0.08-0.51], P=0.001) but not functional outcome (OR 1.10 [95% CI, 0.54-2.25], P=0.79). Adding log-miR-150-5p improved the discriminatory accuracy of the best multivariate model to predict mortality from an AUC of 0.91 (95% CI, 0.88-0.95) to 0.92 (95% CI, 0.88-0.96 Likelihood-ratio test-P<0.001), and resulted in a net reclassification index of 37.3% (95% CI, 0.28-0.52).

Conclusions: In patients with ischemic stroke, log-miR-150-5p is a novel prognostic biomarker, highly associated with mortality within 90 days, improving risk classification beyond traditional risk factors.

Keywords: Biomarkers; Ischemic stroke; MicroRNAs; Mortality; Prognosis; Stroke.

Figure 1.

Flowchart of patient’s enrollment and follow up. From 605 screened patients, ischemic stroke was diagnosed in 362 patients. 359 patients completed follow-up and were finally included in the analysis. Of these, 30 patients were excluded from the analysis because of missing plasma samples for miR-150-5p determination.

Figure 2.

Kaplan-Meier survival estimates for patients stratified by log-miR-150-5p quartiles. The numbers of patients at risk are indicated at multiples of 20 days. Overall, Kaplan–Meier survival curves of patients stratified per log-miR-150-5p quartiles differed (P<0.001, log-rank test). Q means quartiles of log10-transformed values of miR-150-5p were used in these analyses. The x-axis is abridged and shows only the results of the 90 days after event.