Abstract

Introduction: Our group has shown the Wnt-pathway to be a key regulator of SMC function and to be expressed in human coronary atheroma. Dickkopf-related protein 1 (DKK-1) is a member of the Wingless (Wnt) signaling pathway molecules and has recently been shown to improve GRACIE-risk factor score prediction of coronary events in chest pain patients and to predict restenosis post coronary stenting. We tested its association with coronary plaque burden and cardiovascular risk factors in comparison with CRP-1; Hypothesis: DKK-1 may be associated with coronary artery plaque burden and cardiovascular risk factors and play a role in coronary artery disease through modulation of SMC. Methods: 218 patients with angiographic evidence of CAD (mildly obstructive CAD, n=35; obstructive stable CAD, n=154; unstable CAD, n=29) were enrolled in this study at the time of cardiac catherization. DKK-1 and CRP-1 were measured by ELISA. Data are shown as Mean p SEM. Values of DKK-1 and CRP1 were skewed, so non-parametric tests were used to determine the associations between DKK-1 and CRP-1 with Syntax Score, age, BMI, LDL, HDL, and HgbA1c. . Spearman’s Rank Order Correlation, Wilcoxon Rank Sum Test, and analysis of variance (ANOVA) were used to assess associations. Results: Data are shown as Mean p SEM.Variables were as follows: DKK-1 736 pg/ml p 129, CRP-1 0.108 mg/ml p 0.01, age 66 years p 1, BMI 32 p 0.5, LDL 97 p 3, HDL 46 p 2, HgbA1C 6.5 p 0.2, Syntax score 11 p 0.7. With DKK-1 the only statistically significant correlation observed was between DKK-1 and HgbA1c (r=0.18, P<0.05). There was no association between DKK-1 and CRP-1, Syntax Score, Age, BMI, LDL, and HDL. With CRP-1, however, we observed significant positive correlations with Syntax Score (r=0.2, P<0.05), BMI (r=0.18, P<0.05), LDL (r=0.18, P<0.05) and significant negative correlation with age (r= -0.19, P<0.05) and with HDL (r=-0.18, P<0.05). There was no association between CRP-1 and HDL as well as HgbA1c. Conclusions: In patients with angiographically established CAD DKK-1 in contrast to CRP-1 is not a predictor of coronary plaque burden and has as only significant association a positive correlation with HgbA1c. Our data suggest that the reported role of DKK-1 in coronary event risk and in restenosis might be related to Diabetes mediated effects.

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