Highlights
- •Serum PCSK9 levels are associated with necrotic core on IVUS-VH of coronary plaque.
- •This association is independent of serum LDL and applies for all patient subgroups.
- •High serum PCSK9 levels are associated with 1-year death and ACS after angiography.
Abstract
Background and aims
Experimental studies have suggested that proprotein convertase substilisin/kexin type
9 (PCSK9) might directly promote inflammatory processes contributing to atherosclerosis
by mechanisms independent of low-density lipoprotein (LDL) cholesterol levels. This
study aims to investigate the association between serum PCSK9 levels and the fraction
and amount of necrotic core tissue in coronary atherosclerotic plaque, as assessed
by intravascular ultrasound virtual histology (IVUS-VH) imaging.
Methods
Between 2008 and 2011, IVUS-VH imaging of a non-culprit coronary artery was performed
in 581 patients who underwent coronary angiography for acute coronary syndrome (ACS)
or stable angina. PCSK9 concentrations were measured in serum samples that were drawn
prior to coronary angiography. None of the patients received PCSK9 inhibitors.
Results
After adjustment for established cardiac risk factors, statin use and serum LDL cholesterol,
serum PCSK9 levels were linearly associated with the fraction of plaque consisting
of necrotic core tissue (β = 1.24% increase per 100 μg/L increase in PCKS9, 95%CI
0.55–1.94, p = 0.001) and with the absolute volume of necrotic core tissue (β = 0.09,
95%CI 0.01–0.18, p = 0.033), but were not significantly associated with plaque burden
(p = 0.11), plaque volume (p = 0.22) or the presence of IVUS-VH-derived thin-cap fibroatheroma
lesions (p = 1.0).
Conclusion
Serum PCSK9 levels were linearly associated with the fraction and amount of necrotic
core tissue in coronary atherosclerosis, independently of serum LDL cholesterol levels
and statin use. Therefore, PCSK9 may be an interesting therapeutic target for the
treatment of atherosclerotic disease beyond LDL cholesterol regulation.
Keywords
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Article info
Publication history
Published online: March 11, 2016
Accepted:
March 8,
2016
Received in revised form:
March 5,
2016
Received:
December 1,
2015
Identification
Copyright
© 2016 Elsevier Ireland Ltd. All rights reserved.
