PCSK9 Protein and rs562556 Polymorphism Are Associated With Arterial Plaques in Healthy Middle-Aged Population: The STANISLAS Cohort

• Type: Article in International Scientific Journal
• Date: 2020

Authors

Ferreira, JP (Author) Other; Xhaard, C (Author) Other; Lamiral, Z (Author) Other; Borges Canha, M (Author) FMUP; Neves, JS (Author) FMUP; Dandine Roulland, C (Author) Other; LeFloch, E (Author) Other; Deleuze, JF (Author) Other; Bacq Daian, D (Author) Other; Bozec, E (Author) Other; Girerd, N (Author) Other; Boivin, JM (Author) Other; Zannad, F (Author) Other; Rossignol, P (Author) Other

Journal

Title: Journal of the American Heart Association

Vol. 9

ISSN: 2047-9980

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 7 Citations

Scopus - 7 Citations

Other information

Authenticus ID: P-00S-142

DOI: 10.1161/jaha.119.014758

Abstract (EN): Background PCSK9 (Proprotein convertase subtilisin/kexin type 9) binds low-density lipoprotein receptor, preventing its recycling. PCSK9 is a risk predictor and a biotarget in atherosclerosis. The PCSK9-rs562556 variant has been reported as a gain-of-function mutation. The aim of this study was to determine whether the PCSK9-low-density lipoprotein receptor-rs562556 axis is associated with carotid artery plaques between 2 visits separated by almost 20 years in a longitudinal population cohort. Methods and Results The STANISLAS (Suivi Temporaire Annuel Non-Invasif de la Sante des Lorrains Assures Sociaux) cohort is a longitudinal familial cohort from the Lorraine region of France. Participants attending 2 visits (visit 1 and visit 4) separated by 18.5 years (mean) were included (n=997). Carotid artery plaques were determined with standardized vascular echography. The mean age of the adult population at visit 1 was 425 years. At visit 4, 203 (20.4%) participants had arterial plaques. Participants who developed arterial plaques were older (42.7 +/- 5.4 versus 41.7 +/- 4.7 years), more often male (60% versus 49%), smokers (29% versus 18%), with diabetes mellitus (6% versus 3%), and higher cholesterol levels (low-density lipoprotein cholesterol, 1.6 +/- 0.4 versus 1.5 +/- 0.3 g/L) (all P<0.05). The independent factors associated with arterial plaques were age, smoking, and low-density lipoprotein cholesterol. Higher PCSK9 levels were associated with arterial plaques on top of the clinical model (odds ratio, 2.14; 95% CI,= 1.28-3.58); the missense mutation coding the single-nucleotide polymorphism rs562556 was associated with both higher PCSK9 concentration and incident carotid arterial plaques. Conclusions Higher PCSK9 concentration was associated with the development of arterial plaques almost 20 years in advance in a healthy middle-aged population. Mutations of the single-nucleotide polymorphism rs562556 associated with both PCSK9 levels and arterial plaques reinforce the potential causality of our findings. PCSK9 inhibitors could be useful for primary cardiovascular prevention.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 22