Ix Joachim H, Chertow Glenn M, Shlipak Michael G, Brandenburg Vincent M, Ketteler Markus, Whooley Mary A
Division of Nephrology, Department of Medicine, Box 0532, HSE 672, University of California, San Francisco, San Francisco, CA 94143-0532, USA.
Circulation. 2007 May 15;115(19):2533-9. doi: 10.1161/CIRCULATIONAHA.106.682450. Epub 2007 May 7.
Fetuin-A is a multifunctional hepatic secretory protein that inhibits dystrophic vascular and valvular calcification. Lower serum fetuin-A concentrations are associated with valvular calcification in persons with end-stage renal disease. Whether fetuin-A is associated with valvular calcification in other patient populations is unknown.
We evaluated the associations among serum fetuin-A concentrations, mitral annular calcification, and aortic stenosis in 970 ambulatory persons with coronary heart disease and without severe kidney disease. The presence or absence of mitral annular calcification and aortic stenosis was determined by transthoracic echocardiography. The subjects' mean age was 66 years; 81% were men; 189 (20%) had mitral annular calcification; and 79 (8%) had aortic stenosis. Participants were categorized by tertiles of fetuin-A concentrations. Those within the highest fetuin-A tertile had significantly lower odds of mitral annular calcification compared with the lowest tertile (adjusted odds ratio, 0.47; 95% confidence interval, 0.29 to 0.77; P=0.002); this association was similar regardless of diabetes status (P for interaction=0.34). In contrast, the association of fetuin-A with aortic stenosis was modified by the presence or absence of diabetes mellitus (P for interaction=0.03). Among participants without diabetes, the highest fetuin-A tertile had a significantly lower odds of aortic stenosis compared with the lowest tertile (adjusted odds ratio, 0.37; 95% confidence interval, 0.15 to 0.92; P=0.03), whereas among participants with diabetes, no statistically significant association was observed between fetuin-A and aortic stenosis (adjusted odds ratio, 1.49; 95% confidence interval, 0.48 to 4.63; P=0.49).
Among persons with coronary heart disease, we observed an inverse association of fetuin-A and mitral annular calcification. An inverse association also was observed between fetuin-A and aortic stenosis among participants without diabetes mellitus. Fetuin-A may represent an important inhibitor of dystrophic calcification in persons with coronary heart disease.
胎球蛋白-A是一种多功能肝分泌蛋白，可抑制营养不良性血管和瓣膜钙化。晚期肾病患者血清胎球蛋白-A浓度降低与瓣膜钙化有关。胎球蛋白-A是否与其他患者群体的瓣膜钙化相关尚不清楚。
我们评估了970例无严重肾病的冠心病门诊患者血清胎球蛋白-A浓度、二尖瓣环钙化和主动脉瓣狭窄之间的关联。通过经胸超声心动图确定二尖瓣环钙化和主动脉瓣狭窄的有无。受试者的平均年龄为66岁；81%为男性；189例（20%）有二尖瓣环钙化；79例（8%）有主动脉瓣狭窄。参与者按胎球蛋白-A浓度三分位数分类。与最低三分位数相比，胎球蛋白-A最高三分位数的参与者二尖瓣环钙化的几率显著降低（校正比值比，0.47；95%置信区间，0.29至0.77；P=0.002）；无论糖尿病状态如何，这种关联相似（交互作用P=0.34）。相比之下，胎球蛋白-A与主动脉瓣狭窄的关联因糖尿病的有无而改变（交互作用P=0.03）。在无糖尿病的参与者中，胎球蛋白-A最高三分位数与最低三分位数相比，主动脉瓣狭窄的几率显著降低（校正比值比，0.37；95%置信区间，0.15至0.92；P=0.03），而在有糖尿病的参与者中，未观察到胎球蛋白-A与主动脉瓣狭窄之间有统计学显著关联（校正比值比，1.49；95%置信区间，0.48至4.63；P=0.49）。
在冠心病患者中，我们观察到胎球蛋白-A与二尖瓣环钙化呈负相关。在无糖尿病的参与者中，胎球蛋白-A与主动脉瓣狭窄之间也观察到负相关。胎球蛋白-A可能是冠心病患者营养不良性钙化的重要抑制剂。
