Prolonged fibrinolysis time is a risk factor for mortality in patients with chronic kidney disease - a propensity score matched analysis

Abstract

Abstract Purpose To investigate the role of fibrinolysis time and clot structure on cardiovascular mortality of patients with chronic kidney disease. Methods Clot characteristics were measured in 56 propensity score matched patients (i.e. based on gender, BMI, presence of CAD, presence of CVD and CKD stage) by a modified ROTEM assay with the addition of 175 ng/ml of tPA from the Care4HOMe study. Results In total 462 patients with CKD stage II-IV were included in the Care4HOMe study. Patients with cardiovascular death differed significantly from patients without cardiovascular mortality with respect to presence of cardiovascular disease (CVD), presence of coronary artery disease (CAD) and CKD stage (all p < 0.001). Therefore, to assess clot characteristics in a less confounded environment we propensity score matched patients with and without cardiovascular death in a 1:1 ratio. After matching a total of 56 patients with similar baseline characteristics remained. Interestingly, clot-formation time (CFT) and maximal lysis (ML) were significantly altered in patients that suffered cardiovascular death (CFT Event-free: 150±172sec; CFT CV-death: 80±61sec p = 0.035; ML Event-free: 30±61%; ML CV-death: 10±81% p = 0.021). To assess the prognostic importance of both parameters we stratified CFT and ML based on the median and calculated Kaplan-Meier curves and performed a Cox-proportional hazard regression analysis. Combined assessment revealed that a ML lower than the median significantly increased the cardiovascular mortality risk (HR 3.7 95%CI 1.3 – 10.3, p = 0.009; Log-rank 0.0059) while the stratified-CFT remained insignificant (HR 0.99 95%CI 0.99 – 1.00, p = 0.28, Log-rank p = 0.79). Additional C-statistic demonstrated that the predictive value of ML with respect to cardiovascular mortality in CKD patients was comparable to established CKD mortality predictors including Cystatin-C plasma levels and Urine Albumin/Creatine Ratio (UACR) (ML 0.69, 95%CI 0.53-0.86; CystatinC 0.70, 95%CI 0.51 – 0.80; UACR 0.70, 95%CI 0.56-0.84). Conclusions Prolonged fibrinolysis time may be an important prognostic parameter that links atherothrombotic risk to cardiovascular mortality in patients with chronic kidney disease.Maximum Lysis