Relationship of PCSK9 levels with indices of vascular function and subclinical atherosclerosis in patients with familial dyslipidemias

Abstract

Objective: Proprotein convertase subtilisin/kexin type 9 (PCSK9) levels predict cardiovascular risk. We aimed to determine the correlation of PCSK9 levels with predictors of cardiovascular risk, such as central hemodynamics and carotid intima-media thickness (cIMT), in subjects with familial dyslipidemias. Methods: Thirty-three asymptomatic subjects (age: 45.4 ± 12.3 years, 21 men) with either familial combined hyperlipidemia or heterozygous familial hypercholesterolemia, free from hypolipidemic therapy, underwent evaluation for central hemodynamics (aortic augmentation index [AIx@75] and augmented pressure [AP]) and cIMT. PCSK9 levels were measured by ELISA. Results: In the univariate model, circulating PCSK9 levels were related to age (r = 0.351, P = 0.045), AP (r = 0.442, P = 0.011), AIx@75 (r = 0.463, P = 0.007), and cIMT (r = 0.559, P = 0.011). In multivariate analysis, significant positive associations of AP, AIx@75, and cIMT with PCSK9 levels were observed after adjusting for relevant confounders (P = 0.018, P = 0.002, and P = 0.011, respectively). Patients with both high cIMT (>0.81 mm) and high AIx@75 (>20%) had significantly increased PCSK9 levels compared with subjects with both low cIMT and low AIx@75 (316 ng/ml vs. 155 ng/ml, P = 0.037). Conclusions: In familial dyslipidemias, PCSK9 levels are positively associated with predictors of cardiovascular risk, such as central hemodynamics and cIMT. These relationships may aid in the stratification of cardiovascular risk by identifying a high-risk subgroup within these entities. Keywords: Biomarkers, Central hemodynamics, Carotid Intima-Media Thickness (cIMT), Hyperlipidemias