From the Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands (J.T., A.v.d.P., I.T.K., R.A.d.B., W.H.v.G., A.A.V., D.J.v.V., P.v.d.M.); and Department of Social and Welfare Studies, Faculty of Health Sciences, Linköping University, Norrköping, Sweden (T.J.).
Circ Heart Fail. 2014 May;7(3):457-62. doi: 10.1161/CIRCHEARTFAILURE.113.000846. Epub 2014 Mar 19.
Syndecan-1 is a member of the proteoglycan family involved in cell-matrix interactions. Experimental studies showed that syndecan-1 is associated with inflammation in acute myocardial infarction and remodeling. The goal of this study was to explore the role of syndecan-1 in human heart failure (HF).
We analyzed plasma syndecan-1 levels in 567 patients with chronic HF. Primary end point was a composite of all-cause mortality and rehospitalization for HF at 18 months. Mean age was 71.0±11.0 years, 38% was women, and mean left ventricular ejection fraction was 32.5±14.0%. Median syndecan-1 levels were 20.1 ng/mL (interquartile range, 13.9-27.7 ng/mL). Patients with higher syndecan-1 levels were more often men, had higher N-terminal probrain-type natriuretic peptide levels, and worse renal function. Multivariable regression analyses showed a positive correlation between syndecan-1 levels and markers of fibrosis and remodeling but no correlation with inflammation markers. Interaction analysis revealed an interaction between left ventricular ejection fraction and syndecan-1 (P=0.047). A doubling of syndecan-1 was associated with an increased risk of the primary outcome in patients with HF with preserved ejection fraction (hazard ratio, 2.10; 95% confidence interval, 1.14-3.86; P=0.017) but not in patients with HF with reduced ejection fraction (hazard ratio, 0.95; 95% confidence interval, 0.71-1.27; P=0.729). Finally, syndecan-1 enhanced risk classification in patients with HF with preserved ejection fraction when added to a prediction model with established risk factors.
In patients with HF, syndecan-1 levels correlate with fibrosis biomarkers pointing toward a role in cardiac remodeling. Syndecan-1 was associated with clinical outcome in patients with HF with preserved ejection fraction but not in patients with HF with reduced ejection fraction.
硫酸乙酰肝素蛋白聚糖-1 是参与细胞-基质相互作用的蛋白聚糖家族的成员。实验研究表明，硫酸乙酰肝素蛋白聚糖-1 与急性心肌梗死和重塑中的炎症有关。本研究的目的是探讨硫酸乙酰肝素蛋白聚糖-1 在人类心力衰竭（HF）中的作用。
我们分析了 567 例慢性 HF 患者的血浆硫酸乙酰肝素蛋白聚糖-1 水平。主要终点是 18 个月时全因死亡率和因 HF 再住院的复合终点。平均年龄为 71.0±11.0 岁，38%为女性，平均左心室射血分数为 32.5±14.0%。中位数硫酸乙酰肝素蛋白聚糖-1 水平为 20.1ng/mL（四分位距，13.9-27.7ng/mL）。硫酸乙酰肝素蛋白聚糖-1 水平较高的患者更多为男性，N 末端脑利钠肽前体水平较高，肾功能较差。多变量回归分析显示，硫酸乙酰肝素蛋白聚糖-1 水平与纤维化和重塑标志物呈正相关，但与炎症标志物无相关性。交互分析显示左心室射血分数和硫酸乙酰肝素蛋白聚糖-1 之间存在交互作用（P=0.047）。硫酸乙酰肝素蛋白聚糖-1 水平加倍与射血分数保留的心力衰竭患者的主要结局风险增加相关（风险比，2.10；95%置信区间，1.14-3.86；P=0.017），但与射血分数降低的心力衰竭患者无关（风险比，0.95；95%置信区间，0.71-1.27；P=0.729）。最后，当将硫酸乙酰肝素蛋白聚糖-1 添加到具有既定危险因素的预测模型中时，它增强了射血分数保留的心力衰竭患者的风险分类。
在心力衰竭患者中，硫酸乙酰肝素蛋白聚糖-1 水平与纤维化生物标志物相关，表明其在心脏重塑中起作用。硫酸乙酰肝素蛋白聚糖-1 与射血分数保留的心力衰竭患者的临床结局相关，但与射血分数降低的心力衰竭患者无关。
