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Updated: Jun 1, 2025
Author Spotlight: Advancing the Analysis of Plasma Extracellular Vesicle Proteome for Cardiovascular Biomarker Studies
Published on: January 31, 2025
Plasma SVEP1 Levels Predict Cardiovascular Events in Hypertrophic Cardiomyopathy Beyond Conventional Clinical Risk
Itsuki Osawa1,2, Keitaro Akita1,2, Kohei Hasegawa3
1Division of Cardiology, Department of Medicine, New York, NY (I.O., K.A., M.P.R., M.S.M., Y.J.S.).
Insights
Plasma SVEP1 levels improve prognostication for major adverse cardiovascular events (MACE) in hypertrophic cardiomyopathy patients. Adding SVEP1 to clinical predictors enhances risk prediction beyond NT-proBNP alone.
Area of Science:
- Cardiology
- Genetics
- Biomarkers
Background:
- Hypertrophic cardiomyopathy (HCM) is a primary genetic heart condition linked to major adverse cardiovascular events (MACE).
- SVEP1 (Sushi, von Willebrand factor type A, epidermal growth factor, and pentraxin domain containing 1) is a plasma-detectable extracellular matrix protein.
- The prognostic value of plasma SVEP1 in HCM, particularly when combined with NT-proBNP (N-terminal pro-B-type natriuretic peptide), remains unclear.
Purpose of the Study:
- To investigate whether plasma SVEP1 levels improve risk prediction for MACE in patients with HCM.
- To evaluate the added predictive value of SVEP1 to established clinical predictors and NT-proBNP.
Main Methods:
- A multicenter prospective cohort study included 610 HCM patients.
- MACE was defined as heart failure hospitalization or cardiac death.
- Cox proportional hazards models and Lasso-regularized Cox models were used to assess MACE risk and predictive performance, with SVEP1 and NT-proBNP as key variables.
Main Results:
- High SVEP1 levels were associated with increased MACE risk, even in patients with low NT-proBNP.
- The addition of SVEP1 significantly improved the predictive accuracy (C statistics) of models incorporating clinical factors and NT-proBNP.
- The model with clinical factors plus SVEP1 outperformed the model with clinical factors plus NT-proBNP.
Conclusions:
- Plasma SVEP1 is a valuable prognostic biomarker in HCM.
- SVEP1 enhances the predictive capability of current risk stratification models for MACE in HCM patients.
- Incorporating SVEP1 levels can refine prognostication for adverse cardiovascular outcomes in HCM.
Background:
Hypertrophic cardiomyopathy is the most common genetic cardiomyopathy and causes major adverse cardiovascular events (MACE). SVEP1 (Sushi, von Willebrand factor type A, epidermal growth factor, and pentraxin domain containing 1) is a large extracellular matrix protein that is detectable in the plasma. However, it is unknown whether adding plasma SVEP1 levels to clinical predictors including NT-proBNP (N-terminal pro-B-type natriuretic peptide) improves the prognostication in patients with hypertrophic cardiomyopathy.
Methods:
We performed a multicenter prospective cohort study of 610 patients with hypertrophic cardiomyopathy. The outcome was MACE defined as heart failure hospitalization or cardiac death. In 4 groups stratified by the median levels of SVEP1 and NT-proBNP, we compared the risk of MACE using the Cox proportional hazards model adjusting for 15 clinical predictors. We also developed a Lasso-regularized Cox proportional hazards model to predict time to first MACE by adding SVEP1 to the 15 clinical predictors with or without NT-proBNP and compared the predictive performance based on C statistics using 10-fold cross-validation.
Results:
Even in the low NT-proBNP groups, the high SVEP1 group had higher risks of MACE compared with the low SVEP1 group (adjusted hazard ratio, 4.52 [95% CI, 1.05-19.4]; P=0.042). In predicting time to first MACE, the addition of SVEP1 improved the C statistics of the clinical plus NT-proBNP model (0.87 [0.83-0.91] versus 0.82 [0.78-0.86]; P=0.01). The clinical plus SVEP1 model also outperformed the clinical plus NT-proBNP model (0.86 [0.82-0.91] versus 0.82 [0.78-0.86]; P=0.04).
Conclusions:
SVEP1 improved the predictive performance of conventional models, including known clinical parameters with or without NT-proBNP, to predict future MACE in patients with hypertrophic cardiomyopathy.
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