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. What is new? What are the clinical implications? ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study is supported by grants from the National Natural Science Foundation of China (81870905, U20A20358, 82111530203), Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (2019-I2M-5-029), and the Capital's Funds for Health Improvement and Research (2020-1-2041), National Key R&D Program of China (2022YFC2502403) ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: the ethics committee of Beijing Tiantan Hospital and other participating hospitals I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Contact the corresponding author via email