Predictive Value of Lipoprotein(a) for Stroke Recurrence Risk in Embolic Stroke Patients with Different Pathogenesis

Background Acute embolic stroke has a high risk of recurrence, including artery-to-artery embolic, cardioembolism, and embolic stroke of undetermined source. Whether lipoprotein(a) contributes to stroke recurrence risk in embolic stroke patients remains unknown. Methods This prospective cohort biomarker sub-study included 8,076 patients with ischemic stroke or transient ischemic attack from the Third China National Stroke Registry who had measurements of plasma Lp(a) and magnetic resonance imaging sequences and were followed up for 1 year. Cutoffs were set at the 50 mg/dL for Lp(a). Acute embolic stroke was caused by brain embolism from potential embolic sources, which show multiple acute infarctions rather than lacunar infarct by magnetic resonance imaging. Multivariable-adjusted hazard ratio (HR) were calculated using Cox proportional-hazards models for each category to investigate the associations of Lp(a) with stroke recurrence within 1 year. Results Among the 8,076 patients, the median (interquartile range) age was 63 (55–70) years; 5,627 males (69.7%). In the multiple acute infarctions group, patients with elevated lipoprotein(a) levels had a higher risk of ischemic stroke recurrence than those with non-elevated lipoprotein(a) levels (13.7% vs. 10.5%, hazard ratio, 1.30; 95% confidence interval, 1.02–1.66)after adjustment for potential confounders at one-year follow-up. This association was not observed in the single acute infarction group (8.9% vs. 7.2%, hazard ratio, 1.25; 95% confidence interval, 0.91–1.70). Based on the embolism mechanism in patients with multiple acute infarctions, the stroke recurrence risk significantly increased in patients with elevated lipoprotein(a) levels (14.0% vs. 8.9%; hazard ratio, 1.75; 95% confidence interval, 1.23–2.48) compared with those with non-elevated lipoprotein(a) levels in the embolic stroke of undetermined source group, but not in the artery-to-artery embolism group (13.7% vs. 12.6%; hazard ratio, 0.98; 95% confidence interval, 0.68–1.41) and cardioembolism group (13.5% vs. 9.7%; hazard ratio, 1.50; 95% confidence interval, 0.57–3.97). Conclusions Elevated lipoprotein(a) levels were significantly associated with ischemic stroke recurrence risk in patients with multiple acute infarctions, especially in patients with embolic stroke of undetermined source. Lipoprotein(a) may be a new therapeutic target for these patients in the future. Clinical Perspective What is new? Elevated lipoprotein(a) levels were associated with risk of stroke recurrence in patients with multiple acute infarctions, especially in patients with embolic stroke of undetermined source. What are the clinical implications? With the coming era of drugs specifically designed to lower lipoprotein(a) levels, these results indicate that lipoprotein(a) may be a new therapeutic target for embolic stroke of undetermined source patients in the future. Further study is needed to confirm an association of elevated lipoprotein(a) levels and stroke recurrence risk in Embolic Stroke Patients.