To study the predictive value of serum PCSK9 on cardiovascular complications in patients with systemic lupus erythematosus (SLE).
Consecutive patients who fulfilled ≥4 ACR criteria for SLE and consented for a biomarker study in 2009-2012 were included. Stored serum samples were assayed for PCSK9. New ischemic vascular events over time were evaluated. Patients were stratified into high/low PCSK9 groups based on the best cut-off by ROC analysis in predicting vascular events. Cox regression was performed to study the effect of the PCSK9 subgroups on vascular events adjusted for confounders.
539 SLE patients were studied (93% women, age 41.9±14.0 years). A PCSK9 level of 243.25ng/ml best predicted a new vascular event (sensitivity 69%; specificity 61%). The high PCSK9 group (n=220) did not differ from the low PCSK9 group (n=319) in SLE manifestations except for more frequent renal disease. Over 91.3±18.6 months, 29 patients developed 31 vascular events and 40 patients succumbed (25% for vascular events). The cumulative incidence of a first vascular event at 5 years was 7.8% in the high PCSK9 and 1.9% in the low PCSK9 group (p=0.003). Patients with high PCSK9 had a significantly higher risk of all-cause mortality (HR2.68[1.39-5.14]; p=0.003) and vascular mortality (HR12.4[1.56-98.4]; p=0.02). Cox regression showed high PCSK9 was significantly associated with new vascular events (HR2.56[1.10-5.99]; p=0.03) independent of age, sex, SLE duration, traditional risk factors, antiphospholipid antibody and the use of statins, aspirin and immunosuppressive drugs.
Serum PCSK9 is a promising biomarker for ischemic vascular events in patients with SLE.