Abstract
(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 p < 0.0001); with cIMT change over time (Fastest-IMTmax-progr) (p = 0.01); with inter-adventitia common carotid artery diameter (ICCAD) (p < 0.0001); and with the echolucency (Grey Scale Median; GSM) of both carotid plaque and plaque-free common carotid IMT (both p < 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.
Highlights
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a circulating enzyme involved in cholesterol homeostasis
Plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) levels were successfully measured in 3673 (52.1% women and 47.9% men) out of the 3703 participants included in the IMPROVE study [32]
The baseline characteristics of the study population are reported according to PCSK9 quintiles (Table 1)
Summary
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a circulating enzyme involved in cholesterol homeostasis. This, combined with the fact that (a) carriers of loss of function variants for PCSK9 show low levels of LDL-cholesterol with a reduction in the risk of coronary events [7], and (b) PCSK9 is expressed in endothelial cells, vascular smooth muscle cells and macrophages [6] suggests that PCSK9 may play a role in plaque development. Despite this evidence, conflicting results emerge when the association is investigated on the basis of relationships between circulating levels of this proprotein and the incidence of cardiovascular events. Regarding traditional indices of subclinical atherosclerosis, such as carotid intima-media thickness (cIMT) and plaque-size, both positive [15,16,17,18,19] and null associations [9,20,21,22] were observed
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