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High serum levels of thrombospondin-2 correlate with poor prognosis of patients with heart failure with preserved ejection fraction

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Abstract

Thrombospondin-2 (TSP-2) is highly expressed in hypertensive heart. Interstitial fibrosis is frequently observed in hypertensive heart, and it is a characteristic feature of heart failure with preserved ejection fraction (HFpEF). We tested here the hypothesis that high TSP-2 serum levels reflect disease severity and can predict poor prognosis of patients with HFpEF. Serum TSP-2 levels were measured by ELISA in 150 patients with HFpEF. HFpEF was defined as left ventricular ejection fraction ≥50 %, B-type natriuretic peptide (BNP) ≥100 pg/ml or E/e′ ≥15. The endpoints were mortality rate, HF-related hospitalization, stroke and non-fatal myocardial infarction. The median serum TSP-2 level was 19.2 (14.4–26.0) ng/ml. Serum TSP-2 levels were associated with the New York Heart Association (NYHA) functional class. Circulating levels of BNP and high-sensitivity troponin T were positively correlated with serum TSP-2 levels. Kaplan–Meier survival curve showed high risk of adverse cardiovascular events in the high TSP-2 group (>median value), and that the combination of high TSP-2 and high BNP (≥100 pg/ml) was associated with the worst event-free survival rate. Multivariate Cox proportional hazard analysis identified TSP-2 as independent predictor of risk of death and cardiovascular events. Circulating TSP-2 correlates with disease severity in patients with HFpEF. TSP-2 is a potentially useful predictor of future adverse cardiovascular events in patients with HFpEF.

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Acknowledgments

The authors thank Saeko Tokunaga, Megumi Nagahiro and Ayuko Tateishi for the excellent technical assistance. This work was supported in part by The Japan Health Foundation, and Mitsui Life Social Welfare Foundation to Y.I., and a Grant-in-Aid for Scientific Research (B-25293186) to H.O. from the Ministry of Education, Science, and Culture, Japan.

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Authors and Affiliations

  1. Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, Kumamoto, 860-8556, Japan

    Yuichi Kimura, Yasuhiro Izumiya, Shinsuke Hanatani, Eiichiro Yamamoto, Hiroaki Kusaka, Takanori Tokitsu, Seiji Takashio, Kenji Sakamoto, Kenichi Tsujita, Tomoko Tanaka, Megumi Yamamuro, Sunao Kojima, Shinji Tayama, Koichi Kaikita, Seiji Hokimoto & Hisao Ogawa

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  1. Yuichi Kimura
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  2. Yasuhiro Izumiya
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  13. Shinji Tayama
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  16. Hisao Ogawa
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Correspondence to Yasuhiro Izumiya.

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Kimura, Y., Izumiya, Y., Hanatani, S. et al. High serum levels of thrombospondin-2 correlate with poor prognosis of patients with heart failure with preserved ejection fraction. Heart Vessels 31, 52–59 (2016). https://doi.org/10.1007/s00380-014-0571-y

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