Background/Purpose: To study the predictive value of serum PCSK9 level on cardiovascular complications in Chinese patients with systemic lupus erythematosus (SLE).

Methods: Consecutive patients who fulfilled ≥4 1997 ACR criteria for SLE and consented for a biomarker study between 2009 and 2012 were included. Stored serum samples from these patients were assayed for PCSK9 using a commercial ELISA kit. New ischemic vascular events in these patients during follow-up were evaluated. ROC analysis was performed to adopt the best cut-off value of PCSK9 for the prediction of a new vascular event. Patients were divided into two groups according to this cut-off value. The cumulative incidence of new vascular event and mortality over time was studied by Kaplan-Meier’s analysis and compared between the high and low PCSK9 subgroups. Cox regression was performed to study the effect of the PCSK9 subgroups on new vascular events and mortality, adjusted for other confounding factors.

Results: 539 SLE patients were studied (93% women, age 41.9±14.0 years; disease duration 106±90.4 months at entry). The mean PCSK level at baseline was 265±158ng/ml and a cut-off of 243.25ng/ml best predicted a new vascular event by the maximum Youden’s index (ROC analysis: AUC 0.63[0.51-0.74]; sensitivity 69%; specificity 61%). 220 SLE patients had baseline PCSK9 level of ≥243.25ng/ml (high PCSK9) and 319 patients had level below 243.25ng/ml (low PCSK9). No significant difference in SLE manifestations and autoantibody profile was observed between the high and low PCSK9 groups except the former had a significantly higher prevalence of lupus nephritis. 31 new vascular events (13 ischemic stroke, 13 acute coronary syndrome and 5 peripheral vascular disease) developed in 29 patients over a mean follow-up of 91.3±18.6 months. Patients with a new vascular event had a significantly higher baseline PCSK9 level than those without (350±225 vs 260±153ng.ml; p=0.02). The cumulative incidence of a first vascular event at 5 years from study entry was 7.8% in the high PCSK9 group and 1.9% in the low PCSK9 group (log rank test; p=0.003, univariate hazard ratio [HR] 3.08[1.39-6.80]). At last follow-up, 40 patients succumbed (10 due to vascular event [vascular death]). Kaplan-Meier’s analysis showed that the high PCSK9 group had a significant higher cumulative risk of all-cause mortality (log rank test p=0.003; HR2.68[1.39-5.14]) and vascular mortality (log rank test p=0.002; HR12.4[1.56-98.4]) over time than the low PCSK9 group. Cox regression analyses showed that high PCSK9 was significantly associated with new vascular events (HR2.56[1.10-5.99]; p=0.03) independent of age, sex, SLE duration, diabetes mellitus, hypertension, body mass index, atherogenic index, smoking, antiphospholipid antibody, past history of vascular events, and the use of statins, aspirin, hydroxychloroquine, prednisolone, mycophenolate mofetil, azathioprine and the calcineurin inhibitors at study entry.

Conclusion: A higher serum PCSK9 level is a strong risk factor for ischemic vascular events in patients with SLE, which is independent of age, sex, traditional atherosclerotic risk factors, antiphospholipid antibody and the use of statins and immunosuppressive medications.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/serum-proprotein-convertase-subtilisin-kexin-type-9-pcsk9-and-cardiovascular-risk-in-systemic-lupus-erythematosus-a-longitudinal-cohort-study/