Background: Thrombospondin-1 (TSP-1) is known to be involved in the regulation of angiogenesis, inflammation, and vascular function. Clinical studies have demonstrated its correlation with peripheral artery disease, coronary artery disease, and pulmonary hypertension. In this study, we explored its potential roles in the background of end-stage renal disease (ESRD).
Methods: A total of 140 ESRD outpatients (ages 61.0 ± 12.4 years) were prospectively followed for 34 ± 7 months. Their TSP-1 levels were analyzed from pre-hemodialysis blood sample. Cardiovascular survey included ankle- brachial index (ABI), echocardiography and Tl-201 dipyridamole single-photon emission computed tomography (SPECT).
Results: Plasma TSP-1 levels were higher in those patients with preexisting clinical evidence of cardiovascular disease (CVD) than those without (p = 0.002). TSP-1 concentrations were also correlated with ABI, left ventricular ejection fraction, and scar burden in SPECT. Stepwise logistic regression analysis revealed that TSP-1 level was independently associated with the presence of CVD, with an odds ratio of 1.38 [95% confidence interval (CI), 1.09-1.75, p = 0.008]. In survival analyses, 31 patients (22%) died during the follow-up, 16 (52%) arising from cardiovascular causes. Cox hazards analysis revealed that the patients with TSP-1 levels in the highest tertile had a 5.32- and 6.75-fold higher risk for all-cause and cardiovascular mortality than those in the lowest tertile. This predictive value for all-cause mortality still persisted after multivariate adjustment (hazard ratio, 8.71; 95% CI, 1.36-55.68; p = 0.02).
Conclusions: This study hallmarks the association of elevated TSP-1 level with CVD and adverse outcome among hemodialysis patients.
Key words: Thrombospondin-1; End-stage renal disease; Cardiovascular disease; Mortality.