Association of Serum PCSK9 with Near-Infrared Spectroscopy Derived Lipid Core Burden Index and Long-Term Cardiac Outcome

Background: We aimed to study the association between serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels, and near-infrared spectroscopy (NIRS)-derived lipid core burden index (LCBI) and the occurrence of major adverse cardiac events (MACE) in patients with coronary artery disease (CAD).Methods: Serum PCSK9 levels were measured in 576 CAD patients who underwent diagnostic coronary angiography (CAG). NIRS imaging was performed in a subset of 203 patients, in a non-culprit coronary artery segment of at least 40 mm in length. LCBI was assessed in a core laboratory. Data on all-cause mortality, nonfatal ACS or unplanned coronary revascularization was collected during a median follow-up of 4·7 years.Findings: In multivariable analysis, after adjustment for cardiac risk factors, statin use at time of hospital admission and serum LDL cholesterol levels, serum PCSK9 was positively associated with LCBI (mean increase of 0·390 (95% CI [0·011-0·769] ZlnLCBI per unit increase in lnPCSK9 level p =0·044)). During a median follow-up of 4·7 years, 155 patients (27%) had MACE. After multivariable adjustment, serum PCSK9 levels showed a tendency towards an association with MACE (HR [95%CI]: 1·64[0·99-2·71], p=0·055) and a positive association with the composite of death or ACS (HR [95%CI]: 1·88[1·01-3·51], p=0·047). Patients admitted with serum PCSK9 levels above the median of 270 μg/L had 53% higher risk of MACE and 67% higher risk of death or ACS than those with levels below the median.Interpretation: CAD patients with elevated serum PCSK9 levels had a higher NIRS-derived LCBI and higher incidence of adverse cardiac outcome than those with lower levels.Funding Statement: This ATHEROREMO-IVUS study was supported by the European Commission, Seventh Framework Programme (theme FP7-HEALTH-2007-2.4.2-1). The current study was also funded by BBMRI-NL (a research infrastructure financed by the Dutch government, NWO 184.021.007) and the Netherlands Heart Foundation (NHS2007B012 to R.M.O.). The funders had no role in study design, data collection, data analysis, interpretation, and/or writing of the report.Declaration of Interests:The authors report no relationships that could be construed as a conflict of interest.Ethics Approval Statement: The medical ethics committee of Erasmus MC approved the ATHEROREMO-IVUS study and its NIRS sub-study and written informed consent was obtained from all patients. The ATHEROREMO-IVUS study and its NIRS sub-study were performed in accordance with the declaration of Helsinki.