Nontraditional Risk Factors for Residual Recurrence Risk in Patients with Ischemic Stroke of Different Etiologies

Background and objective: With the popularization of guideline-based secondary prevention based on traditional risk factors, rates of stroke recurrence reduced greatly after ischemic stroke (IS) or transient ischemic attack (TIA), but the residual risk still exists. We aim to evaluate which IS subtype benefits the most from the current secondary prevention and to evaluate nontraditional risk factors for residual recurrence risk of different IS etiologies.

Methods: The study included IS/TIA patients who participated in both biomarker substudy and imaging substudy of the Third China National Stroke Registry. We used 5 guideline-recommended interventions (antiplatelet, statins, anticoagulant, antihypertensive, and antidiabetic therapies) to document the performance of secondary prevention care. Residual risk was defined as the risk of stroke recurrence despite adherence to these 5 guideline-based secondary prevention strategies. Risk factors associated with stroke recurrence were analyzed by using Cox regression models.

Results: In total, 9,733 patients were included in this study. At 3 months, 4,186 (43.0%) patients adhered to 5 secondary prevention strategies, and the residual risk of recurrence was 5.1%. According to Trial of Org 10172 in Acute Stroke Treatment subtypes, cardioembolism benefited the most from current secondary prevention (relative risk reduction: 65.2%), followed by large-artery atherosclerosis (LAA) (29.0%) and small-artery occlusion (SAO) (20.0%). Despite adhering to secondary prevention strategies, high sensitivity C-reactive protein, interleukin-6 (IL-6) levels, and impaired renal function were independent risk factors for the residual recurrence risk of LAA subtype, while IL-6 and trimethylamine N-oxide significantly contributed to the residual risk of SAO subtype.

Conclusions: LAA and SAO subtypes own the specific nontraditional risk factors while inflammation is a common risk factor for residual recurrence risk of both.