强直性脊柱炎患者血清Dickkopf相关蛋白水平与心血管钙化关系的研究

The study of association between serum DKK1 and coronary artery calcification score in patients with ankylosing spondylitis

目的探讨强直性脊柱炎（AS）患者血清Dickkopf相关蛋白（DKKl）与冠状动脉钙化和脊柱骨化之间的关系，分析影响AS患者心血管钙化的危险因素。方法75例AS患者和70例正常对照者作为研究对象。采用ELISA法测定2组受试者血清中DKKl的含量。采用64排螺旋CT扫描心脏计算冠状动脉钙化积分（CACS），用无创性全自动动脉测量仪器测量患者的脉搏传导速度（PwV），以x线记录的AS患者改良Stoke强直性脊柱炎脊柱评分（mSASSS）作为评价骨化进展的放射学指标。运用相关分析法分析DKKl水平与CACS、PwV、mSASSS评分及临床活动指标之间的关系。结果AS患者血中DKKI水平明显低于对照组（P〈0．01）；AS组患者CACS、PWV均明显高于对照组（P〈0．01）；与非钙化组相比，钙化组DKKl水平显著增高（P〈0．01），而钙化组mSASSS评分明显升高；其中DKK1水平与CACS、PWv、mSASSS评分呈明显负相关（P〈0．05），而CACS、冈w与mSASSS评分明显正相关（P〈O．05）。在受试者工作特征曲线下，冠状动脉钙化的最佳DKKI界值为54．3（曲线下面积为0．82，95％CI：0．71～0．87，敏感性为60％，特异性为81％），多元回归分析显示血清DKKl水平是CACS独立危险因素。结论AS患者血中DKKl水平的降低伴随动脉粥样硬化和脊柱骨化的发生，DKKl可能同时参与了AS患者心血管疾病及韧带骨赘的发生，可作为预测心血管钙化及骨化程度的生物学指标。

Objective To investigate the relations between serum DKK1 and coronary artery calcification score（CACS） or ossification process in ankylosing spondylitis （AS）, and to find the risk factors for coronary artery calcification in patients with AS. Methods Seventy-five AS patients （ AS group） and seventy healthy persons （control group） were enrolled in this study. The serum DKK1 was measured by enzyme-linked immunosorbent assay method （ELISA）. CACS was calculated by 64-slice spiral CT, PWV was measured by non-invasive vascular screening device. The modified Stoke AS Spine Score （mSASSS） was applied to evaluate ossification in the spine of patiente of AS. The clinical indices （ age, gender, course of disease,disease activity） and indices of inflammation,including erythrocyte sedimentation rate（ ESR）, C-reactive protein（CRP） were evaluated or measured. The relationship between DKK1 and clinical indexes, radiographic scoring,indices in inflammation were estimated by SPSS software, and the diagnostic value of DKK1 was analyzed by receiver operator characteristic（ROC） curve. Results The levels of serum DKK1 in AS patients were significantly lower than those in healthy controls（P 〈 0.01 ）. There was no significant correlation between DKK1 and ESR, CRP and BASFI score （ P 〉 0.05 ）. Spearman analysis showed that PWV,CACS or mSASSS were significant negatively correlated with serum DKK1 （P 〈 0.05 ） in AS Group. The mean CACS and PWV in AS group was significantly higher than that in control group. ROC curve revealed that the optimal DKK1 value of CAC was 54.3（ AUC =0.82,95% CI：O. 71-0.87） with a sensi- tivity of 60% and a specificity of 81%. Serum DKK1 remained as independent predictor of CACS and mSASSS in multivariate analysis（P 〈 0.05）. Conclusion Serum DKK1 is correlated with CAC and can thus be considered as an independent predictor for CAC. Serum DKK1 may serve as a diagnostic biomarker of AS.