Circulating thrombospondin-2 reflects disease severity and predicts outcome of heart failure with reduced ejection fraction

循环血小板反应蛋白-2 反映疾病严重程度并预测射血分数降低的心力衰竭结果

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作者:Shinsuke Hanatani, Yasuhiro Izumiya, Seiji Takashio, Yuichi Kimura, Satoshi Araki, Taku Rokutanda, Kenichi Tsujita, Eiichiro Yamamoto, Tomoko Tanaka, Megumi Yamamuro, Sunao Kojima, Shinji Tayama, Koichi Kaikita, Seiji Hokimoto, Hisao Ogawa

Background

Thrombospondin-2 (TSP-2) is a matricellular protein found in human serum. Deletion of TSP-2 causes age-dependent dilated cardiomyopathy. We hypothesized that TSP-2 is a useful biomarker in patients with heart failure with reduced ejection fraction (HFrEF).

Conclusions

TSP-2 is a potentially useful biomarker for assessment of disease severity and prognosis in HFrEF.

Results

Serum TSP-2 was measured in 101 patients with HFrEF, and mortality and cardiovascular events were followed. Serum TSP-2 in the HFrEF group was significantly higher than in the non-HF group (n=17). Mean NYHA functional class was significantly higher in the high TSP-2 group (>median) than the low TSP-2 group (2.26 vs. 1.76, P=0.004). Circulating TSP-2 level was significantly associated with that of B-type natriuretic peptide (BNP; r=0.40, P<0.0001) on multivariate linear regression analysis. On Kaplan-Meier curve analysis the high TSP-2 group had a lower event-free rate than the low TSP-2 group (log-rank test, P=0.03). Multivariate Cox hazard analysis identified hemoglobin (hazard ratio [HR], 0.66; 95% confidence interval [CI]: 0.53-0.82, P<0.0001), and TSP-2 (ln[TSP-2]; HR, 3.34; 95% CI: 1.03-10.85, P=0.045) as independent predictors of adverse outcome. The area under the curve for 1-year events increased when TSP-2 was added to Framingham risk score (FRS; alone, 0.60) or BNP (alone, 0.69; FRS+TSP-2, 0.75; BNP+TSP-2, 0.76). Conclusions: TSP-2 is a potentially useful biomarker for assessment of disease severity and prognosis in HFrEF.

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