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


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.
Department of Cardiovascular Medicine, Graduate School of Medical Sciences.
Shinsuke
S
Hanatani
Yasuhiro
Y
Izumiya
Seiji
S
Takashio
Yuichi
Y
Kimura
Satoshi
S
Araki
Taku
T
Rokutanda
Kenichi
K
Tsujita
Eiichiro
E
Yamamoto
Tomoko
T
Tanaka
Megumi
M
Yamamuro
Sunao
S
Kojima
Shinji
S
Tayama
Koichi
K
Kaikita
Seiji
S
Hokimoto
Hisao
H
Ogawa
D000368:Aged; D015415:Biomarkers / Q000097:blood; D018572:Disease-Free Survival; D005500:Follow-Up Studies; D006333:Heart Failure / Q000097:blood / Q000401:mortality / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D011237:Predictive Value of Tests; D012720:Severity of Illness Index; D013318:Stroke Volume; D015996:Survival Rate; D019699:Thrombospondins / Q000097:blood*; D000099262:Thrombospondin 2
D015415:Biomarkers; D020097:Natriuretic Peptide, Brain; D019699:Thrombospondins; D000099262:Thrombospondin 2