Abstract
ObjectiveDickkopf-1 (DKK-1), a major regulator of the Wnt pathway, plays an important role in cardiovascular disease. However, no study has evaluated the association of DKK-1 and acute coronary syndrome (ACS). We investigated this association and whether the Global Registry of Acute Coronary Events (GRACE) hospital-discharge risk score predicting major adverse cardiac events (MACE) can be improved by adding the DKK-1 value.MethodsWe enrolled 291 patients (46 with ST-segment elevation myocardial infarction [STEMI] and 245 with non-ST elevated ACS [NSTE-ACS]) who were divided into groups by tertiles of baseline plasma DKK-1 level measured by ELISA. The GRACE risk score was calculated and predictive value alone and together with DKK-1 and/or high-sensitivity C-reactive protein (hs-CRP) level were assessed, respectively.ResultsCompared with patients with NSTE-ACS, those with STEMI had higher plasma DKK-1 level at baseline (P = 0.006). Plasma DKK-1 level was correlated with hs-CRP level (r = 0.295, P<0.001) and was greater with high than intermediate or low GRACE scores (P = 0.002 and P<0.001, respectively). We found 44 (15.1%) MACEs during a median 2-year follow-up. DKK-1 levels were higher for patients with than without events (P<0.001). The rate of MACE increased with increasing DKK-1 level (P<0.001). The area under the receiver operating characteristic curve for GRACE score with MACE was 0.524 and improved to 0.791 with the addition of hs-CRP level, 0.775 with the addition of DKK-1 level and 0.847 with both values added.ConclusionsDKK-1 is an independent predictor of long-term MACE of patients with ACS. The long-term predictive ability of post-discharge GRACE score may be enhanced by adding DKK-1 level.
Highlights
Accumulating evidence indicates that atherosclerosis is a chronic disease characterized by inflammation and lipid accumulation [1,2]
The Wnt pathway is regulated by multiple families of secreted antagonists, including soluble frizzled related receptors and dickkopfs (DKK); the best-studied of DKKs is DKK-1
We investigated the association of DKK-1 in acute coronary syndrome (ACS) and whether the Global Registry of Acute Coronary Events (GRACE) hospital-discharge risk score for major adverse cardiac events (MACE) could be improved by adding the DKK-1 value
Summary
Accumulating evidence indicates that atherosclerosis is a chronic disease characterized by inflammation and lipid accumulation [1,2]. Levels of plasma markers of inflammation such as CRP are elevated in acute coronary syndrome (ACS) [3]. Recent data point to a key role of the Wnt signaling pathway in the regulation of inflammation [4]. Recent reports [5] showed increased expression of DKK-1 in advanced atherosclerotic plaque, and serum levels of DKK-1 gave prognostic information for patients with multiple myeloma and other malignancies, as well as osteoarthritis [6,7,8]. The inammatory process that underlines atherosclerosis is mediated by a multitude of cytokines and is unlikely to be totally reected by CRP level alone [9,10,11,12]
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