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A High-Throughput Luciferase Assay to Evaluate Proteolysis of the Single-Turnover Protease PCSK9
Published on: August 28, 2018
Plasma proprotein convertase subtilisin/kexin type 9 concentration and recurrent cardiovascular events in patients
Ye-Xuan Cao1, Hui-Hui Liu1, Jing-Lu Jin1
1State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital and National Center for Cardiovascular Diseases, China.
Insights
High proprotein convertase subtilisin/kexin type 9 (PCSK9) levels predict recurrent cardiovascular events in familial hypercholesterolemia patients. This finding improves risk prediction for these high-risk individuals.
Area of Science:
- Cardiovascular Medicine
- Biochemistry
- Genetics
Background:
- Familial hypercholesterolemia (FH) is linked to early atherosclerosis and high cardiovascular event rates.
- Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a known cardiovascular risk predictor in the general population.
- The prognostic value of PCSK9 in FH patients with established cardiovascular disease is not well-defined.
Purpose of the Study:
- To determine the prognostic value of plasma PCSK9 concentrations for recurrent cardiovascular events in FH patients.
- To assess the association between PCSK9 levels and atherosclerosis severity in FH.
- To evaluate if PCSK9 improves existing cardiovascular risk prediction models in FH.
Main Methods:
- 249 FH patients with a prior cardiovascular event were enrolled.
- Plasma PCSK9 levels were measured via ELISA.
- Coronary artery calcification and severity were assessed (Agatston and Gensini scores).
- Patients received standard lipid-lowering therapy and were followed for recurrent events.
Main Results:
- PCSK9 levels positively correlated with coronary artery calcification and Gensini scores.
- During follow-up (43 months), 11.51% of patients experienced recurrent cardiovascular events.
- Higher PCSK9 levels were associated with lower event-free survival.
- Multivariable analysis showed PCSK9 independently predicted recurrent cardiovascular events (HR 1.45).
- Adding PCSK9 to risk models enhanced predictive value.
Conclusions:
- Elevated PCSK9 is a significant risk factor for atherosclerosis in FH.
- PCSK9 independently predicts future cardiovascular events in FH patients on standard therapy.
- PCSK9 measurement can improve cardiovascular risk stratification in FH.
Aims:
Familial hypercholesterolemia patients are characterized by early onset of coronary artery calcification and atherosclerosis, and high incidence of cardiovascular events. Plasma proprotein convertase subtilisin/kexin type 9 was reported to be a predictor for cardiovascular risk in the general population. However, its prognostic value for predicting recurrent cardiovascular events in familial hypercholesterolemia patients remains undetermined.
Methods:
A total of 249 patients with molecularly and/or clinically (Dutch Lipid Clinic Network score > 6) defined familial hypercholesterolemia who had experienced a first cardiovascular event were consecutively included and plasma proprotein convertase subtilisin/kexin type 9 concentrations were measured by enzyme-linked immunosorbent assay. Coronary artery calcification was measured using Agatston method and coronary severity was assessed by Gensini score, respectively. All patients received standard lipid-lowering therapy and were followed-up for recurrent cardiovascular events. Univariate and multivariate regression and Cox analyses was used to calculate hazard ratios with 95% confidence interval.
Results:
Circulating proprotein convertase subtilisin/kexin type 9 concentrations were positively associated with coronary artery calcification scores and Gensini score by both univariate and multivariate analyses. During a mean follow-up of 43 ± 19 months, 29 (11.51%) recurrent cardiovascular events occurred. Kaplan-Meier analysis showed that patients with the highest proprotein convertase subtilisin/kexin type 9 levels had the lowest event-free survival time. Multivariable Cox regression analysis revealed that proprotein convertase subtilisin/kexin type 9 was independently associated with recurrent cardiovascular events (hazard ratio: 1.45, 95% confidence interval: 1.11-1.88). The combination of proprotein convertase subtilisin/kexin type 9 to Cox prediction model led to an enhanced predictive value for recurrent cardiovascular events.
Conclusions:
Increased level of proprotein convertase subtilisin/kexin type 9 was a significant risk factor of atherosclerosis and independently predicted future recurrent cardiovascular events in familial hypercholesterolemia patients receiving standard lipid-lowering treatment.
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