Association between proprotein convertase subtilisin/kexin type 9 and subclinical cerebrovascular disease in the community

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a new target for reducing low-density lipoprotein cholesterol and incident cardiovascular disease, including stroke. However, the clinical relevance of circulating PCSK9 levels has been poorly elucidated in the general population, particularly in association with subclinical cerebrovascular disease including cerebral small vessel disease (CSVD) and intracranial artery stenosis (ICAS).In community-dwelling Japanese men (n = 526) aged 46-82 years without a history of cardiovascular disease, the associations of serum PCSK9 levels with the prevalence of CSVD and ICAS were assessed using magnetic resonance imaging. CSVD included lacunar infarction, deep and subcortical white matter hyperintensity, periventricular hyperintensity and cerebral microbleeds.The median (interquartile range) age at baseline and serum PCSK9 levels were 69 (63-74) years and 240 (205-291) ng/ml, respectively. After adjusting for traditional cardiovascular risk factors including low-density lipoprotein cholesterol, multivariable Poisson regression with robust error variance revealed a significant association between PCSK9 levels (per 1 SD) and ICAS (relative risks 1.18, 95% confidence interval 1.02-1.37). Multivariable ordinal logistic regression for ICAS, with stenosis graded as mild (<50%) or moderate-severe (≥50%), revealed a similar association (common odds ratio 1.31, 95% confidence interval 1.04-1.64). However, no significant association was observed between serum PCSK9 levels and CSVD.Higher circulating PCSK9 levels were independently associated with an ICAS prevalence but not with CSVD prevalence. The quantification of circulating PCSK9 levels may help to identify individuals at high risk for cerebrovascular disease in the general population.