Abstract
Introduction: 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). Hypothesis: High TSP-2 serum levels reflect disease severity and can predict poor prognosis of patients with HFpEF. Methods: Serum TSP-2 levels were measured by ELISA in 150 patients with HFpEF. HFpEF was defined as clinical signs or symptom of HF, left ventricular ejection fraction >50%, B-type natriuretic peptide (BNP) >100 pg/ml or E/e’ >15. The endpoints of this study were mortality rate, HF-related hospitalization, stroke and non-fatal myocardial infarction. Results: The median serum TSP-2 level was 19.2 (14.4-26.0) ng/ml in all study participants. Serum TSP-2 levels correlated with the New York Heart Association (NYHA) functional class. Then the patients were divided into high and low TSP-2 groups based on the median value. Pulmonary capillary wedge pressure, and circulating levels of BNP and high-sensitivity cardiac troponin T were significantly higher in the high TSP-2 group than low TSP-2 group. Whereas, cardiac index was significantly lower in the high TSP-2 group. Kaplan-Meier survival curve showed high risk of adverse cardiovascular events in the high TSP-2 group, and that the combination of high TSP-2 and high BNP (>100 pg/ml) was associated with the worst event-free survival rate. Univariate Cox proportional hazard analysis showed that high levels of TSP-2, NYHA functional class, presence of atrial fibrillation, high levels of BNP, left atrium dilatation were associated with future adverse events. Stepwise multivariate Cox proportional hazard analysis identified BNP (ln(BNP)) (hazard ratio [HR]: 1.98; confidence interval [CI]: 1.26-3.10, p=0.003) and TSP-2 (HR: 2.59; CI: 1.09-6.14, p=0.031) as independent predictors of risk of death and cardiovascular events. Conclusions: 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.
Published Version
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