| Summary: | (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.
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