P1252ASSOCIATIONS OF SERUM SCLEROSTIN AND DKK-1 PROTEIN WITH FUTURE CARDIOVASCULAR EVENTS AND MORTALITY IN HEMODIALYSIS PATIENTS; A PROSPECTIVE COHORT STUDY

Abstract

Abstract Background and Aims Sclerostin and Dickkopf-1 (Dkk-1) protein are inhibitors of the canonical Wnt/β-catenin bone pathway. Sclerostin but not Dkk-1 is associated with increased arterial stiffness. This study examined the prognostic significance of serum sclerostin and Dickkopf-related protein-1 (Dkk-1) levels for cardiovascular outcomes and mortality in hemodialysis patients. Method Serum sclerostin and Dkk-1 levels were measured with ELISA in 80 hemodialysis patients that were followed-up for a median of 45 months. Several factors that could interfere in the association of sclerostin and Dkk-1 with outcomes (including carotid-femoral pulse-wave-velocity (PWV), parathyroid hormone, calcium-phospate product and others) were assessed at baseline The primary end-point was a combination of all-cause death, non-fatal myocardial infarction, non-fatal stroke, coronary revascularization, hospitalization for decompensated heart failure and new-onset atrial fibrillation. Secondary end-points included cardiovascular and all-cause mortality. Results Cumulative freedom from the primary endpoint was significantly lower for higher tertiles of sclerostin (77.8%, 69.2%, and 40.7% for tertiles 1 to 3 respectively; log-rank-p=0.004). The corresponding risk for the primary outcome was gradually increasing for higher tertiles of sclerostin (Tertile 3: HR: 3.847, 95%CI: 1.502-9.851). No significant association was evident between sclerostin and all-cause mortality, whereas higher sclerostin levels presented a trend towards higher risk for cardiovascular mortality. Dkk-1 levels exhibited no association with the risk of the primary or the secondary endpoints. In stepwise Cox regression modeled analysis, sclerostin levels were associated with the primary outcome, independently of PTH, calcium-phosphate product, serum albumin, CRP and PWV levels (HR: 2.921, 95%CI: 1.401–6.090; p=0.004). Conclusion High serum sclerostin levels are associated with lower cumulative freedom and higher risk for a composite cardiovascular endpoint but not for all-cause mortality. Dkk-1 protein exhibited no association with the future risk of cardiovascular events.