Osawa Itsuki, Akita Keitaro, Hasegawa Kohei, Fifer Michael A, Tower-Rader Albree, Reilly Muredach P, Maurer Mathew S, Stitziel Nathan O, Javaheri Ali, Shimada Yuichi J
Division of Cardiology, Department of Medicine, New York, NY (I.O., K.A., M.P.R., M.S.M., Y.J.S.).
Columbia University Irving Medical Center, New York, NY (I.O., K.A., M.P.R., M.S.M., Y.J.S.).
Circ Heart Fail. 2025 Feb;18(2):e012343. doi: 10.1161/CIRCHEARTFAILURE.124.012343. Epub 2025 Jan 20.
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.
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.
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]; =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]; =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]; =0.04).
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.
肥厚型心肌病是最常见的遗传性心肌病，可导致主要不良心血管事件（MACE）。SVEP1（含寿司、血管性血友病因子A、表皮生长因子和五聚素结构域1）是一种可在血浆中检测到的大型细胞外基质蛋白。然而，将血浆SVEP1水平纳入包括NT-proBNP（N末端B型利钠肽原）在内的临床预测指标是否能改善肥厚型心肌病患者的预后尚不清楚。
我们对610例肥厚型心肌病患者进行了一项多中心前瞻性队列研究。结局为定义为心力衰竭住院或心源性死亡的MACE。在根据SVEP1和NT-proBNP的中位数水平分层的4组中，我们使用Cox比例风险模型比较了MACE风险，并对15个临床预测指标进行了校正。我们还开发了一种Lasso正则化Cox比例风险模型，通过在有或无NT-proBNP的情况下将SVEP1添加到15个临床预测指标中来预测首次发生MACE的时间，并使用10倍交叉验证基于C统计量比较预测性能。
即使在低NT-proBNP组中，高SVEP1组的MACE风险也高于低SVEP1组（校正风险比为4.52 [95% CI，1.05 - 19.4]；P = 0.042）。在预测首次发生MACE的时间时，添加SVEP1改善了临床加NT-proBNP模型的C统计量（0.87 [0.83 - 0.91] 对0.82 [0.78 - 0.86]；P = 0.01）。临床加SVEP1模型也优于临床加NT-proBNP模型（0.86 [0.82 - 0.91] 对0.82 [0.78 - 0.86]；P = 0.04）。
SVEP1改善了传统模型（包括有或无NT-proBNP的已知临床参数）对肥厚型心肌病患者未来MACE的预测性能。
