Abstract 16101: Serum Proprotein Convertase Substilisin/Kexin Type 9 Level is Associated With Coronary Plaque Inflammation and Cardiovascular Outcome Independent From Serum LDL Level
Introduction: Experimental studies have suggested that proprotein convertase substilisin/kexin type 9 (PCSK9) might directly promote inflammatory processes contributing to atherosclerosis by mechanisms independent from low-density lipoprotein (LDL) cholesterol level. This study aims to investigate the association between serum PCSK9 level and the amount of necrotic core tissue in coronary atherosclerotic plaque, 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. None of the patients received PCSK9 inhibitors.
Results: Median serum PCSK9 level was 270 μg/L and ranged from 91 to 804 μg/L. After adjustment for established cardiac risk factors, statin use and serum LDL, serum PCSK9 level was linearly associated with the fraction of plaque consisting of necrotic core tissue (β=1.24 percent increase per 100 μg/L increase in PCKS9, 95%CI 0.55-1.94, p=0.001) (Figure) and with the absolute volume of necrotic core tissue (β=0.09, 95%CI 0.01-0.18, p=0.033), but was 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). High PCSK9 levels were associated with the composite endpoint of death or ACS (definite culprit lesion-related events not included as endpoints) during 1 year of follow-up (HR 1.42 per 100 μg/L increase, 95%CI 1.02-1.99, p=0.040) (Figure).
Conclusion: The natural variation in serum PCSK9 level is linearly associated with the fraction and amount of necrotic core tissue in coronary atherosclerosis and with 1-year clinical outcome after coronary angiography, independent from serum LDL level. Therefore, PCSK9 may be an interesting therapeutic target for the treatment of atherosclerotic disease beyond LDL regulation.
Author Disclosures: J.M. Cheng: None. R. Oemrawsingh: None. H. Garcia-Gracia: None. E. Boersma: None. R. van Geuns: None. P. Serruys: None. I. Kardys: None. M. Akkerhuis: None.
- © 2014 by American Heart Association, Inc.