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

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.

PCSK9 increases vulnerability of carotid plaque by promoting mitochondrial dysfunction and apoptosis of vascular smooth muscle cells

“…In fact, the clinical value of PCSK9 as a potential marker for subclinical carotid atherosclerosis has been investigated in a large cohort. Among 3708 European patients asymptomatic for cardiovascular diseases, PCSK9 plasma levels did not correlate with vascular damage and/or subclinical atherosclerosis of extracranial carotid arteries 23 . Regarding to the progression of carotid atherosclerotic stenosis, plasma PCSK9 levels are associated with 10‐year progression of atherosclerosis as evaluated by total plaque area in 643 Asian patients 24 .…”

Effect of PCSK9 on atherosclerotic cardiovascular diseases and its mechanisms: Focus on immune regulation

“…LRP5 and LRP6, as coreceptors of PCSK9, promote atherosclerosis by activating the Wnt/β-catenin signaling pathway, resulting in significant proliferation of VSMCs and decreased anti-inflammatory macrophages (78,81). However, there may still be lack of correlation between the plasma PCSK9 level and the severity of subclinical atherosclerosis in patients without symptoms of cardiovascular diseases (123).…”

Increased Carotid Intima-Media Thickness in Asymptomatic Individuals Is Associated with the PCSK9 (rs2149041) Gene Polymorphism in the Mexican Mestizo Population: Results of the GEA Cohort

“…Additional studies have informed results with respect to the association between PCSK9 circulating levels and CIMT. Nevertheless, these data have been contradictory, with negative and positive associations, for instance, an association was reported in hypercholesterolemia familiar [ 22 ], subclinical carotid atherosclerosis [ 23 ], also in the progression of carotid atherosclerosis [ 24 ], whereas no association was observed with measures of vascular health [ 25 ], subclinical atherosclerosis of extracranial carotid arteries [ 26 ].…”