Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec Heart and Lung Institute, Laval University, Québec City, Québec, Canada.
University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
Can J Cardiol. 2014 Sep;30(9):1088-95. doi: 10.1016/j.cjca.2014.03.025. Epub 2014 Mar 24.
Matrix γ-carboxyglutamate protein is an inhibitor of cardiovascular calcification. The objective of this substudy of the Aortic Stenosis Progression Observation: Measuring Effects of Rosuvastatin (ASTRONOMER) trial was to examine the relationship between total (ie, carboxylated [active] form + uncarboxylated [inactive] form) circulating desphosphorylated matrix γ-carboxyglutamate protein (dpMGP) level and the progression rate of aortic stenosis (AS).
Among the patients included in the ASTRONOMER trial, 215 patients had measures of baseline circulating total dpMGP level and an echocardiographic follow-up (mean follow-up: 3.5 ± 1.3 years). Progression of AS was assessed according to the measurement of the annualized increase in peak aortic jet velocity.
In the whole cohort, baseline dpMGP level was associated with faster progression rate of peak aortic jet velocity (r = 0.16; P = 0.02) in individual analysis but not in multivariable analysis (P = 0.40). However, there was a significant interaction (P = 0.03) between dpMGP level and age, with respect to the effect on AS progression. After dichotomization according to median value of age (ie, 57 years old), total dpMGP level was associated with faster AS progression rate (r = 0.24; P = 0.008) in the younger patients, and this association remained significant in multivariable analysis (P = 0.04), but not in the older ones. The independent correlates of dpMGP level were fasting glucose (P = 0.009) and oxidized low-density lipoprotein (P = 0.01).
This is the first prospective study to demonstrate a relationship between increased circulating levels of total dpMGP and faster progression rate of AS in younger individuals. Future studies are needed to determine if dpMGP is simply a marker or a contributing factor to ectopic mineralization of aortic valve.
基质 γ-羧基谷氨酸蛋白是心血管钙化的抑制剂。本研究是 Aortic Stenosis Progression Observation: Measuring Effects of Rosuvastatin（ASTRONOMER）试验的子研究，旨在探讨总循环去磷酸化基质 γ-羧基谷氨酸蛋白（dpMGP）水平与主动脉瓣狭窄（AS）进展率之间的关系。
在 ASTRONOMER 试验中，纳入了 215 例基线时具有循环总 dpMGP 水平测量值且进行了超声心动图随访（平均随访时间：3.5±1.3 年）的患者。AS 的进展情况根据峰值主动脉射流速度的年增长率进行评估。
在整个队列中，基线 dpMGP 水平与峰值主动脉射流速度的进展率较快相关（r=0.16；P=0.02），但在多变量分析中无相关性（P=0.40）。然而，dpMGP 水平与年龄之间存在显著的交互作用（P=0.03），对 AS 进展有影响。根据年龄中位数（即 57 岁）进行二分法后，总 dpMGP 水平与年轻患者的 AS 进展率较快相关（r=0.24；P=0.008），且在多变量分析中仍具有相关性（P=0.04），但在年龄较大的患者中无相关性。dpMGP 水平的独立相关因素为空腹血糖（P=0.009）和氧化型低密度脂蛋白（P=0.01）。
这是第一项前瞻性研究，证明了循环总 dpMGP 水平升高与年轻个体 AS 进展率较快之间存在相关性。未来需要进一步研究以确定 dpMGP 是否仅是主动脉瓣异位矿化的标志物或促成因素。
