PS-BPP01-3: DIFFERENTIAL ASSOCIATION OF CIRCULATING PROPROTEIN CONVERTASE SUBTILISIN/KEXIN TYPE 9 WITH THE SUBCLINICAL CEREBRAL SMALL VESSEL DISEASE AND INTRACRANIAL ARTERY STENOSIS

Abstract

Background and aims: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a new target for reducing low density lipoprotein cholesterol (LDL C) and incident cardiovascular disease, including stroke. However, how PCSK9 work on developing stroke is not fully elucidated. In this study we assessed the association of circulating PCSK9 levels with subclinical cerebrovascular disease, including cerebral small vessel diseases (CSVD) and intracranial artery stenosis (ICAS), in a general population. Methods: In community dwelling Japanese men (n = 526) aged 46–82 years, without a history of lipid lowering medications or cardiovascular disease, we assessed the associations of serum PCSK9 levels with CSVD and ICAS using magnetic resonance imaging. CSVD included lacunar infarction, deep and subcortical white matter hyperintensity, periventricular hyperintensity, cerebral microbleeds. Multivariable Poisson regression with robust error variance was performed to estimate the relative risk (RR) and 95% confidence interval (CI) of the serum PCSK9 levels for the presence of CSVD and ICAS. Additionally, ordinal logistic regression was performed to estimate odds ratio (OR) and 95% CI for ICAS, with graded detectable stenosis, mild (1%-50%) and severe (> 50%). Results: The average (standard deviation: SD) age at baseline and median (interquartile range) PCSK9 were 68 (9) years and 240 (205 - 291) ng/mL, respectively. After multivariable adjustment including traditional cardiovascular risk factors (e.g., LDL C), a 1- SD increase of PCSK9 levels was associated with ICAS (adjusted RR 1.18, 95% CI 1.02 - 1.37), and the ordinal logistic regression model also showed a similar association (adjusted OR 1.31, 95% CI 1.04 - 1.64). However, there was no significant association between serum PCSK9 levels and CSVD. Conclusions: Higher circulating PCSK9 level was associated with the higher prevalence of ICAS but not with CSVD, and the association was independent of traditional cardiovascular risk factors including LDL-C. The results of this study imply the direct and independent association of PCSK9 with cerebral atherosclerotic plaque formation.