Risk prediction with proprotein convertase subtilisin/kexin type 9 (PCSK9) in patients with stable coronary disease on statin treatment

BackgroundProprotein convertase subtilisin/kexin type 9 (PCSK9) is a regulator of LDL-cholesterol receptor homeostasis and emerges as a therapeutic target in the prevention of cardiovascular (CV) disease. This prospective cohort study analyzes risk prediction with PCSK9 serum concentrations in patients with stable coronary artery disease (CAD) on statin treatment.Methods and resultsFasting PCSK9 concentrations were measured in 504 consecutive patients with stable CAD confirmed by angiography. Oral glucose tolerance tests were performed in all patients without known diabetes. Patients were followed up for 48 months. The primary outcome was the composite of cardiovascular death and unplanned cardiovascular hospitalization. Serum concentrations of PCSK9 predicted CV outcomes (PCSK9 > 622 ng/ml vs. < 471 ng/ml: HR 1.55, 95%-CI 1.11–2.16, p = 0.009). Higher PCSK9 concentrations were associated with female gender, hypertension, statin treatment, C-reactive protein, HbA1c, insulin, total cholesterol and fasting triglycerides, but not with LDL- or HDL-cholesterol. The association of PCSK9 levels with CV events was reduced after adjustment for fasting TG.ConclusionPCSK9 concentrations predict cardiovascular events in patients with coronary artery disease on statin treatment. Serum triglycerides are correlated with PCSK9 and modify risk prediction by PCSK9.

PCSK9 concentrations were measured in 504 patients with stable coronary artery disease. 95% were on statin therapy and median LDL-C was 100 mg/dl. The primary outcome was the composite of cardiovascular death and unplanned cardiovascular hospitalization. Serum concentrations of PCSK9 predicted cardiovascular outcomes within a 4-year follow-up. The association of PCSK9 levels with CV events was reduced after adjustment for fasting triglycerides (TG). The forest plot depicts the association of PCSK9 with cardiovascular outcomes. Cox proportional hazards regression analyses were used to calculate hazard ratios (HR) and 95%-confidence intervals (95%-CI); p-values are for the comparison of the upper vs. the lower PCSK9 tertile.Figure optionsDownload high-quality image (155 K)Download as PowerPoint slide