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
Arianna Toscano,
Maria Cinquegrani,
Michele Scuruchi,
Antonino Di Pino,
Salvatore Piro,
Viviana Ferrara,
Carmela Morace,
Alberto Lo Gullo,
Egidio Imbalzano,
Francesco Purrello,
Giovanni Squadrito,
Roberto Scicali,
Giuseppe Mandraffino
Affiliations
Arianna Toscano
Internal Medicine Unit, Department of Clinical and Experimental Medicine Lipid Center, University of Messina, 98122 Messina, Italy
Maria Cinquegrani
Internal Medicine Unit, Department of Clinical and Experimental Medicine Lipid Center, University of Messina, 98122 Messina, Italy
Michele Scuruchi
Internal Medicine Unit, Department of Clinical and Experimental Medicine Lipid Center, University of Messina, 98122 Messina, Italy
Antonino Di Pino
Department of Clinical and Experimental Medicine, University of Catania, 95124 Catania, Italy
Salvatore Piro
Department of Clinical and Experimental Medicine, University of Catania, 95124 Catania, Italy
Viviana Ferrara
Department of Clinical and Experimental Medicine, University of Catania, 95124 Catania, Italy
Carmela Morace
Internal Medicine Unit, Department of Clinical and Experimental Medicine Lipid Center, University of Messina, 98122 Messina, Italy
Alberto Lo Gullo
Unit of Rheumatology, Department of Medicine, ARNAS Garibaldi Hospital, 95122 Catania, Italy
Egidio Imbalzano
Internal Medicine Unit, Department of Clinical and Experimental Medicine Lipid Center, University of Messina, 98122 Messina, Italy
Francesco Purrello
Department of Clinical and Experimental Medicine, University of Catania, 95124 Catania, Italy
Giovanni Squadrito
Internal Medicine Unit, Department of Clinical and Experimental Medicine Lipid Center, University of Messina, 98122 Messina, Italy
Roberto Scicali
Department of Clinical and Experimental Medicine, University of Catania, 95124 Catania, Italy
Giuseppe Mandraffino
Internal Medicine Unit, Department of Clinical and Experimental Medicine Lipid Center, University of Messina, 98122 Messina, Italy
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 hypercholesterolemia (HeFH) subjects. In a previous step, HeFH patients were enrolled and LLT was prescribed 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 p 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.
