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

家族性血脂异常患者PCSK9水平与血管功能指标及亚临床动脉粥样硬化的关系

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作者:Charalambos Vlachopoulos, Iosif Koutagiar, Dimitrios Terentes-Printzios, Ioannis Skoumas, Angeliki Rigatou, Antigoni Miliou, Alexandros-Nikitas Skliros, Stavroula Pantou, Kostantinos Filis, Dimitrios Tousoulis

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.

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.

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.

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.

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