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Serial changes in coronary atheroma burden and composition in relation to on-treatment plasma levels of proprotein convertase subtilisin/kexin type 9 (PCSK9) following high-intensity statin therapy
Sub-topic : Cross-Modality and Multi-Modality Imaging Topics
Session type : Poster Session
Authors : KC Koskinas (Bern,CH), S Zaugg (Bern,CH), K Yamaji (Bern,CH), B Gencer (Geneva,CH), A Moschovitis (Bern,CH), M Roffi (Geneva,CH), H Kelbaek (Copenhagen,DK), R Klingenberg (Zurich,CH), TF Luscher (Zurich,CH), F Mach (Geneva,CH), CM Matter (Zurich,CH), S Windecker (Bern,CH), L Raber (Bern,CH)
Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secreted protein implicated in the degradation of the hepatic LDL-receptor. Statins are known to increase plasma PCSK9 levels. While agents that inhibit PCSK9 markedly reduce circulating LDL-cholesterol (LDL-C), the association of plasma PCSK9 levels with changes of coronary plaque burden and composition in patients receiving statin therapy remains unknown.
Objectives: To assess volumetric and compositional changes of coronary atheroma in relation to on-treatment PCSK9 levels in patients with ST-elevation myocardial infarction (STEMI) receiving high-intensity statin therapy.
Methods: In the IBIS-4 study, 82 STEMI patients underwent serial, 2-vessel intravascular ultrasound (IVUS) and radiofrequency (RF)-IVUS of the non-infarct-related arteries at baseline and following 13-month treatment with rosuvastatin 40mg. The present analysis includes 44 patients (80 arteries) with available serial measurements of plasma PCSK9 levels.
Results: The majority of patients (88.6%) were not taking statin at baseline. At 13 months, median LDL-C decreased from 3.27 to 1.99 mmol/L, HDL-C increased from 1.14 to 1.23 mmol/L, and PCSK9 levels increased from 283.1 (235.4 to 362.7) to 388.1 (277.8 to 550.2) ng/ml (p<0.001 vs. baseline for all). Regression of percent atheroma volume (-0.99%, -1.84 to -0.14; p=0.024) did not correlate with baseline (p=0.83) or follow-up levels of PCSK9 (p=0.41). Serial changes of RF-IVUS-defined plaque components consisted of an increase in percent necrotic core volume (p=0.006), increase in dense calcium content (p<0.001) and reduction in percent fibrous (p<0.001) and fibro-fatty tissue content (p=0.04). On-treatment levels of PCSK9 correlated with percent fibrous tissue content (p=0.026) and inversely with necrotic core content at follow-up (p=0.06), but not with serial changes in any of the RF-IVUS tissue components.
Conclusions: In this observations study of STEMI patients treated with high-intensity statin therapy, on-treatment levels of PCSK9 did not correlate with changes in atheroma burden or RF-IVUS-defined plaque composition. Although PCSK9 is an important therapeutic target for reduction of atherogenic lipoprotein concentrations, on-treatment levels of the biomarker do not appear to reflect serial changes in coronary atherosclerosis in statin-treated patients.