title: High serum levels of thrombospondin-2 correlate with poor prognosis of patients with heart failure with preserved ejection fraction.
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.
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, Kumamoto, 860-8556, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kimura
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, Kumamoto, 860-8556, Japan. izumiya@kumamoto-u.ac.jp.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Izumiya
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, Kumamoto, 860-8556, Japan.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Hanatani
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, Kumamoto, 860-8556, Japan.
authors.forename: Eiichiro
authors.initials: E
authors.lastname: Yamamoto
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, Kumamoto, 860-8556, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kusaka
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, Kumamoto, 860-8556, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Tokitsu
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, Kumamoto, 860-8556, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Takashio
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, Kumamoto, 860-8556, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Sakamoto
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, Kumamoto, 860-8556, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Tsujita
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, Kumamoto, 860-8556, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, Kumamoto, 860-8556, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Yamamuro
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, Kumamoto, 860-8556, Japan.
authors.forename: Sunao
authors.initials: S
authors.lastname: Kojima
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, Kumamoto, 860-8556, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Tayama
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, Kumamoto, 860-8556, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Kaikita
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, Kumamoto, 860-8556, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Hokimoto
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, Kumamoto, 860-8556, Japan.
authors.forename: Hisao
authors.initials: H
authors.lastname: Ogawa
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D018572:Disease-Free Survival; D005260:Female; D006333:Heart Failure / Q000503:physiopathology*; D006801:Humans; D007564:Japan; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D011379:Prognosis; D012720:Severity of Illness Index; D013318:Stroke Volume; D019699:Thrombospondins / Q000097:blood*; D016277:Ventricular Function, Left; D000099262:Thrombospondin 2
chemical_list: D015415:Biomarkers; D020097:Natriuretic Peptide, Brain; D019699:Thrombospondins; D000099262:Thrombospondin 2
keywords: Biomarker; HFpEF; Prognosis; Thrombospondin-2