Abstract 2616: The Prognostic Value Of The Wnt Antagonist Dickkopf-1 (dkk-1) In Patients Presenting With An Acute Coronary Syndrome
Background The Wnt signalling pathway is an important regulator of adult tissue maintenance and homeostasis. Disorders in Wnt signaling cause human degenerative diseases as well as cancer. Dickkopf-1 (DKK-1) is negative regulator protein of the Wnt pathway and is associated with a variety of organic diseases. Under the hypothesis that DKK-1 as a regulator protein is involved in ventricular remodelling after myocardial infarction we aimed to investigate the prognostic value of serum measurement of DKK-1 in patients with acute coronary syndromes.
Methods and results From April 2003 until April 2005 1136 consecutive patients (age 64±12 years; 347 females) with an ACS within the last 48 hours, who were referred for early invasive diagnositc were included. Follow up data were available for 1128 (99.3%) patients. Serum samples on admission were available for 1092 (97%) patients and from 820 (72%) patients a second sample the day following admission. Values are expressed as median. Values of DKK-1 on admission and at the day following admission were elevated. There was no difference between patients with ST-elevation myocardial infarction (STEMI) and Non ST-elevation ACS (6.71 vs. 6.70 pg/ml; p=0.97 on admission and 5.35 vs. 5.57 pg/ml; p=0.32 and the day following admission). During follow up 77 (6.8%) patients deceased. Survivors had significant lower DKK-1 levels on admission (6.7 (4.4 –9.9) pg/ml vs. 7.8 (5.7–11.3) pg/ml; p= 0.02) and at the day following admission (5.5 (3.9 –7.7) pg/ml vs. 6.8 (4.9 –9.8) pg/ml; p=0,007) as compared to those patients who died. Elevated DKK-1 levels above an optimised cut-off value were related to an increased mortality rate (8.3% vs. 4.2%; p=0.015 for DKK-1 values on admission and 8.6% vs. 4.1%; p=0.018 for DKK-1 values at the day following admission). Similar findings were obtained by Kaplan-Meier analysis (Log Rank 6.07, p=0.014 for DKK-1 values on admission and Log Rank 6.65, p=0.01 for DKK-1 values at the day following admission).
Conlcusions Elevated serum levels of Dickkopf-1 (DKK-1), a major antagonist of the Wnt signalling pathway, are associated to an increased mortality rate in patients with an acute coronary syndrome and provide prognostic information. However, the underlying mechanisms are unknown