METHODS: The Multi-Ethnic Study of Atherosclerosis (MESA) followed participants with serial cardiac computed tomography (CT) measures of vascular calcification. Dp-ucMGP was measured at baseline in a subset of participants who completed baseline and follow-up CTs approximately 10 years later and had available plasma specimens (n = 2663). Linear mixed effects models (LMMs) were used to determine the association of dp-ucMGP with the simultaneous incidence and progression of coronary artery, ascending thoracic aortic, or descending thoracic aortic calcification (CAC, ATAC, DTAC)].
RESULTS: For every one standard deviation (SD, 178 pmol/L) increment in dp-ucMGP, CAC increased by 3.44 ([95% CI = 1.68, 5.21], p < 0.001) Agatston units/year (AU/year), ATAC increased by 0.63 ([95% CI = 0.27, 0.98], p = 0.001) AU/year, and DTAC increased by 8.61 ([95% CI = 4.55, 12.67], p < 0.001) AU/year. The association was stronger for DTAC in those ≥65 years and with diabetes.
CONCLUSIONS: We found a positive association of the inactive form of matrix Gla protein, dp-ucMGP, and long-term incidence/progression of CAC, ATAC, and DTAC. Future studies should investigate dp-ucMGP as a calcification regulator and MGP as a possible therapeutic target to slow progression of calcification in the vasculature.
方法:动脉粥样硬化(MESA)的多种族研究对参与者进行了连续的心脏计算机断层扫描(CT)测量血管钙化。在大约10年后完成基线和随访CT并且有可用血浆标本的一部分参与者中,在基线时测量Dp-ucMGP(n=2663)。线性混合效应模型(LMM)用于确定dp-ucMGP与冠状动脉同时发生和进展的相关性。升主动脉,或降胸主动脉钙化(CAC,ATAC,DTAC)]。
结果:对于每一个标准偏差(SD,178pmol/L)dp-ucMGP增量,CAC增加了3.44([95%CI=1.68,5.21],p<0.001)Agatston单位/年(AU/年),ATAC增加了0.63([95%CI=0.27,0.98],p=0.001)AU/年,DTAC增加了8.61([95%CI=4.55,12.67],p<0.001)AU/年。在≥65岁的人群中,DTAC与糖尿病的相关性更强。
结论:我们发现基质Gla蛋白的非活性形式呈正相关,dp-ucMGP,和CAC的长期发病率/进展,ATAC,和DTAC。未来的研究应该研究dp-ucMGP作为钙化调节因子和MGP作为减缓血管钙化进展的可能治疗靶点。