Methods of determining whether a subject is at risk of developing arterial plaques

Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds low-density lipoprotein receptor (LDLR), preventing its recycling. PCSK9 is a risk predictor and a biotarget in atherosclerosis progression. The aim of the inventors was to determine whether the PCSK9-LDLR axis can predict carotid artery plaques between two visits separated by almost 20 years in a longitudinal population cohort (i.e. STANISLAS cohort), and whether underlying genetic polymorphisms could be identified. Participants attending two visits (visit 1 and visit 4) separated by 18.5 years (mean) were included (n=997). The independent clinical predictors of arterial plaques were age, smoking and LDLc. Higher PCSK9 levels predicted arterial plaques on top of the clinical model, OR (95%CI) =2.14 (1.28-3.58); the missense mutation coding the single-nucleotide polymorphism (SNP) rs562556 is associated with both higher PCSK9 concentration and arterial plaques. In conclusion higher PCSK9 concentration predicted the development of arterial plaques almost 20 years in advance in a healthy middle-aged population. Mutations of the SNP rs562556 associated with both PCSK9 levels and arterial plaques reinforce the potential causality of the findings. Finally PCSK9 inhibitors would be useful for cardiovascular prevention in patients considering having risk of developing arterial plaques.

Keywords: ELISA, Sequencing, Immunoassay, Risk Prediction in Atherosclerotic cardiovascular disease
Patent Application number: EP19 306 180.1 on 2019/09/24
PCT/EP2020/076617 on 23/09/2020

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