Natural history of MRI-defined intraplaque hemorrhage-positive asymptomatic carotid stenosis in the contemporary medical era: a prospective multicenter cohort study.

The optimal management of asymptomatic carotid stenosis remains controversial despite advances in medical therapy. Although intraplaque hemorrhage (IPH) is an established marker of plaque vulnerability, the prospective natural history of magnetic resonance imaging (MRI)-defined IPH-positive asymptomatic carotid stenosis remains incompletely characterized. We investigated the clinical course of this population. The Stratification by Multidimensional Approach for Rational Treatment of Asymptomatic Carotid Stenosis (SMART-K) study is a prospective multicenter cohort of patients with asymptomatic carotid stenosis and MRI-confirmed IPH. Patients were followed for up to 36 months under medical management according to contemporary clinical practice. Baseline assessments included plaque-to-muscle (PM) ratio and soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1). The primary endpoint was ipsilateral ischemic events, including ischemic stroke, transient ischemic attack (TIA), and amaurosis fugax. Kaplan-Meier and exploratory Cox proportional hazards analyses were performed. Among 76 patients included in the final analysis, 11 (14.5%) developed primary endpoint events: ischemic stroke in 8, TIA in 2, and amaurosis fugax in 1. The 3-year cumulative incidence was 14.8%. Stenosis severity showed a trend toward association with ischemic events (hazard ratio per 10% increase, 1.46; 95% confidence interval, 0.92-2.31; P = 0.11), whereas PM ratio and sLOX-1 were not associated with events. Patients with MRI-defined IPH-positive asymptomatic carotid stenosis remained at clinically meaningful risk of ipsilateral ischemic events under contemporary clinical management. These findings provide prospective natural history data for this specifically defined population and support further evaluation of MRI-defined IPH in individualized risk-stratification strategies.