Association of PCSK9 levels and genetic polymorphisms with stroke recurrence and functional outcome after acute ischemic stroke

Background: Protein convertase subtilisin/kexin type 9 (PCSK9) is a hepatic protein that participated in the lipid homeostasis.Its high levels and polymorphisms are associated with high low-density lipoprotein cholesterol, increasing the vascular risk potentially.However, the association between PCSK9 levels, genetic polymorphisms, and ischemic stroke remains unclear.We aimed to study the relationship between PCSK9 levels, genetic polymorphisms, and stroke outcomes in patients with ischemic stroke.Methods: A total of 9,782 acute ischemic stroke patients registered in the China National Stroke Registry-III were included in this prospective study.Circulating PCSK9 concentrations and 11 key single-nucleotide polymorphisms (SNPs) were examined.The clinical outcomes included stroke recurrence, death, and poor functional outcome at 12 months. Results:The median PCSK9 level was 361.28 ng/mL.After adjusting for confounders, patients in the highest quartile of circulating PCSK9 had a relatively lower risk of 12-month stroke recurrence (HR 0.80, 95% CI: 0.67-0.96).No significant relationship between PCSK9 level and death or poor functional outcome was found.No significant relationship between SNPs and stroke outcomes at 12 months was found.Conclusions: The high level of PCSK9 was associated with decreased stroke recurrence at 12 months in ischemic stroke patients.There was no significant association between PCSK9 polymorphisms and acute ischemic stroke based on a Chinese registry.