Relationship between Circulating PCSK9 and Markers of Subclinical Atherosclerosis—The IMPROVE Study

• Main Authors: Daniela Coggi, Beatrice Frigerio, Alice Bonomi, Massimiliano Ruscica, Nicola Ferri, Daniela Sansaro, Alessio Ravani, Palma Ferrante, Manuela Damigella, Fabrizio Veglia, Nicolò Capra, Maria Giovanna Lupo, Chiara Macchi, Kai Savonen, Angela Silveira, Sudhir Kurl, Philippe Giral, Matteo Pirro, Rona Juliette Strawbridge, Bruna Gigante, Andries Jan Smit, Elena Tremoli, Mauro Amato, Damiano Baldassarre, on behalf of the IMPROVE Study Group
• Format: Article
• Language: English
• Published: MDPI AG 2021-07-01
• Series: Biomedicines
• Subjects: PCSK9; subclinical atherosclerosis; carotid artery; intima-media thickness; echolucency
• Online Access: https://www.mdpi.com/2227-9059/9/7/841

(1) Background and purpose: circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) is one of the key regulators of cholesterol metabolism. Despite this, its role as a player in atherosclerosis development is still matter of debate. Here, we investigated the relationships between this protein and several markers of subclinical atherosclerosis. (2) Methods: the IMPROVE study enrolled 3703 European subjects (54–79 years; 48% men; with ≥3 vascular risk factors), asymptomatic for cardiovascular diseases. PCSK9 levels were measured by ELISA. B-mode ultrasound was used to measure markers of carotid subclinical atherosclerosis. (3) Results: in the crude analysis, PCSK9 levels were associated with several baseline measures of carotid intima-media thickness (cIMT) (all <i>p</i> < 0.0001); with cIMT change over time (Fastest-IMTmax-progr) (<i>p</i> = 0.01); with inter-adventitia common carotid artery diameter (ICCAD) (<i>p</i> < 0.0001); and with the echolucency (Grey Scale Median; GSM) of both carotid plaque and plaque-free common carotid IMT (both <i>p</i> < 0.0001). However, after adjustment for age, sex, latitude, and pharmacological treatment, all the afore-mentioned correlations were no longer statistically significant. The lack of correlation was also observed after stratification for sex, latitude, and pharmacological treatments. (4) Conclusions: in subjects who are asymptomatic for cardiovascular diseases, PCSK9 plasma levels do not correlate with vascular damage and/or subclinical atherosclerosis of extracranial carotid arteries.