Abstract 14979: Proprotein Convertase Subtilisin / Kexin Type 9 (PCSK9) is a Novel Risk Predictor in Statin-Treated Coronary Artery Disease Patients
Objective: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an essential regulator of hepatic LDL receptor turnover and serum LDL-C concentrations. PCSK9 inhibitors currently emerge as a new option to lower LDL-C and as therapeutic tools in the prevention of cardiovascular (CV) disease. The association of PCSK9 and event-free survival has not been clarified prospectively in high-risk patients. This prospective cohort study analyzes risk prediction with PCSK9 serum concentrations in patients with stable coronary artery disease (CAD) on statin treatment.
Methods & Results: PCSK9 concentrations were measured by ELISA in 504 consecutive patients with clinically stable CAD confirmed by angiography (median age 68 years, 83% male, 95% treated with statins, median LDL-C 100mg/dl). PCSK9 correlated strongly with fasting triglycerides (R=0.33, p<0.0001) and were associated with statin treatment, age, hypertension, hyperlipidemia, C-reactive protein, hemoglobin A1c, fasting insulin and total cholesterol. No association was observed with obesity, LDL- or HDL-cholesterol (linear regression analyses and Spearman’s rank correlation).
The primary outcome was the composite endpoint of cardiovascular death and cardiovascular hospitalization for acute coronary syndrome or hospitalization for unplanned, symptom-induced coronary angiography and revascularization (including bypass surgery) within 48 months follow-up. Comparison of event-free-survival between PCSK9 tertiles showed that serum concentrations of PCSK9 predicted CV outcomes (PCSK9 >622ng/ml vs. <471ng/ml: univariate HR 1.55, 95%-CI 1.11-2.16, p=0.009). In multivariate analyses (Cox proportional hazards regression), PCSK9 remained predictive after adjustment for age, gender, risk factors, medication, glucose metabolism and cholesterol (multivariate HR 1.44, 95%-CI 1.02-2.44, p=0.04). The association of PCSK9 levels with CV events was reduced to non-significance after adjustment for fasting TG.
Summary & Conclusion: PCSK9 serum concentrations predict cardiovascular events in patients with stable coronary artery disease on statin treatment. Fasting triglycerides, but not LDL-cholesterol, are correlated with PCSK9 and modify risk prediction by PCSK9.
Author Disclosures: C. Werner: None. M.M. Hoffmann: None. M. Böhm: None. U. Laufs: None.
- © 2014 by American Heart Association, Inc.