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Comparative Study
. 2025 Feb;18(2):e012343.
doi: 10.1161/CIRCHEARTFAILURE.124.012343. Epub 2025 Jan 20.

Plasma SVEP1 Levels Predict Cardiovascular Events in Hypertrophic Cardiomyopathy Beyond Conventional Clinical Risk Models Including NT-proBNP

Itsuki Osawa  1   2 , Keitaro Akita  1   2 , Kohei Hasegawa  3 , Michael A Fifer  4 , Albree Tower-Rader  4 , Muredach P Reilly  1   2   5 , Mathew S Maurer  1   2 , Nathan O Stitziel  6 , Ali Javaheri  6   7 , Yuichi J Shimada  1   2
Affiliations
Comparative Study

Plasma SVEP1 Levels Predict Cardiovascular Events in Hypertrophic Cardiomyopathy Beyond Conventional Clinical Risk Models Including NT-proBNP

Itsuki Osawa et al. Circ Heart Fail. 2025 Feb.

Abstract

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.

Keywords: biomarker; cardiomyopathy, hypertrophic; cardiovascular diseases; heart failure; proteomics.

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Conflict of interest statement

Dr Shimada has received funding from Bristol Myers Squibb and consulting income from Bristol Myers Squibb and Moderna Japan. Dr Fifer has received funding from Bristol Myers Squibb and Novartis and consulting income from Bristol Myers Squibb, Cytokinetics, Edgewise Therapeutics, and Viz.ai. Dr Tower-Rader has received funding from Bristol Myers Squibb and Cytokinetics. Dr Maurer has received consulting income from Akcea, Alnylam, Eidos Therapeutics, Pfizer, Prothena, Novo Nordisk, and Intellia. Dr Stitziel is an inventor on a patent application filed by Washington University focused on SVEP1 (Sushi, von Willebrand factor type A, epidermal growth factor, and pentraxin domain containing 1) and PEAR1 (platelet and endothelial aggregation receptor 1). The other authors report no conflicts.

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