PCSK9 LEVELS ARE ASSOCIATED WITH CENTRAL HEMODYNAMICS AND SUBCLINICAL ATHEROSCLEROSIS

Abstract

Objective: Proprotein convertase subtilisin/kexin type 9 (PCSK9) levels are related with cardiovascular risk. The aim of the present study was 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 dyslipidaemias. Design and method: Thirty three asymptomatic subjects (mean age = 45.4 ± 12.3, 21 men) with either familial combined hyperlipidemia or heterozygous familial hypercholesterolemia, free of hypolipidemic therapy, underwent evaluation of aortic augmentation index ([email protected]) and augmented pressure, 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), [email protected] (r = 0.463, P = 0.007), augmented pressure (r = 0.442, P = 0.011) and cIMT (r = 0.559, P = 0.001). In multivariable analysis, a significant positive association of [email protected], augmented pressure and cIMT with PCSK9 levels was observed after adjusting for relevant confounders (P < 0.05 for all). Patients with both high cIMT (>0.81 mm) and high [email protected] (>20%) had significantly increased PCSK9 levels compared with subjects presented with both low cIMT and low [email protected] (316 ng/ml vs 155 ng/ml, p = 0.037). (Figure)Conclusions: In patients with familial dyslipidemia PCSK9 levels were positively associated with central hemodynamics and cIMT. These relationships may imply that part of the effect of PSCK9 in cardiovascular risk is mediated by abnormal central hemodynamics and cIMT in patients with familial dyslipidemias, and may permit identification of a high risk subgroup of patients within these entities.