PCSK9 Plasma Levels Are Associated with Mechanical Vascular Impairment in Familial Hypercholesterolemia Subjects without a History of Atherosclerotic Cardiovascular Disease: Results of Six-Month Add-On PCSK9 Inhibitor Therapy

• Main Authors: Cinquegrani, M. (Author), Di Pino, A. (Author), Ferrara, V. (Author), Gullo, A.L (Author), Imbalzano, E. (Author), Mandraffino, G. (Author), Morace, C. (Author), Piro, S. (Author), Purrello, F. (Author), Scicali, R. (Author), Scuruchi, M. (Author), Squadrito, G. (Author), Toscano, A. (Author)
• Format: Article
• Language: English
• Published: MDPI 2022
• Subjects: acetylsalicylic acid; adult; alirocumab; apolipoprotein B; arterial stiffness; Article; atherosclerosis; atherosclerotic injury; atorvastatin; biochemical analysis; body mass; breathing pattern; clopidogrel; cohort analysis; common carotid artery; controlled study; coronary artery atherosclerosis; diabetes mellitus; diastolic blood pressure; dyslipidemia; electrocardiogram; enzyme linked immunosorbent assay; evolocumab; ezetimibe; familial hypercholesterolemia; female; gene expression; genetic analysis; glucose blood level; heart infarction; hemoglobin A1c; heterozygosity; high density lipoprotein cholesterol; human; hypertension; hypertransaminasemia; low density lipoprotein cholesterol; low density lipoprotein receptor; major clinical study; male; mechanical vascular impairment; metformin; non insulin dependent diabetes mellitus; PCSK9; PCSK9 inhibitor; proprotein convertase 9; protein blood level; protein function; pulse wave velocity; risk factor; rosuvastatin; single nucleotide polymorphism; sulfonylurea; systolic blood pressure; triacylglycerol
• Online Access: View Fulltext in Publisher

 Proprotein convertase subtilisin/kexin type-9 (PCSK9) is a key regulator of low-density lipoprotein (LDL) metabolism involved in the degradation of the low-density lipoprotein receptor (LDLR) through complex mechanisms. The PCSK9 plasma levels change according to lipid lowering therapy (LLT). Few data exist regarding the role of PCSK9 in vascular damage. We aimed to evaluate the impact of PCSK9 plasma levels on pulse wave velocity (PWV) and the effect of PCSK9 inhibitors (PCSK9-i) on circulating PCSK9 and PWV in a cohort of heterozygous familial hypercho-lesterolemia (HeFH) subjects. In a previous step, HeFH patients were enrolled and LLT was pre-scribed according to guidelines. Biochemical analyses and PWV assessment were performed at baseline (T0), after 6 months of high-efficacy statin plus ezetimibe (T1) and after 6 months of PCSK9-i (T2). The PCSK9 levels were evaluated in 26 selected HeFH subjects at the three time points and 26 healthy subjects served as controls for the reference value for PCSK9 plasma levels. The PWV values decreased at each time point in HeFH subjects after LLT starting (8.61 ± 2.4 m/s, −8.7%; p < 0.001 vs. baseline at T1, and 7.9 ± 2.1 m/s, −9.3%; p < 0.001 vs. both T1 and baseline) and it was correlated to PCSK9 (r = 0.411, p = 0.03). The PCSK9 levels increased on statin/EZE therapy (+42.8% at T1) while it decreased after PCSK9-i was started (−34.4% at T2). We noted a significant relationship between PCSK9 levels and PWV changes at T1 and T2. In conclusion, PCSK9 levels were associated with baseline PWV values in HeFH subjects; moreover, we found that PCSK9 level variations seemed to be correlated with PWV changes on LLT. A longer observation time and wider sample size are needed to assess the potential role of PCSK9 plasma levels on the vascular function and remodelling, and to clarify the effects of PCSK9-i in these pathways. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.