Danziger John, Young Rebekah L, Shea M Kyla, Tracy Russell P, Ix Joachim H, Jenny Nancy S, Mukamal Kenneth J
From the Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA (J.D., K.J.M.); Department of Biostatistics, University of Washington, Seattle (R.L.Y.); Human Nutrition Research Center on Aging, Tufts University, Boston, MA (K.M.S.); College of Medicine (R.P.T.) and Department of Pathology (N.S.J.), University of Vermont, Burlington; and Nephrology Section, Veterans Affairs San Diego Healthcare System, CA (J.H.I.).
Arterioscler Thromb Vasc Biol. 2016 May;36(5):1037-42. doi: 10.1161/ATVBAHA.116.307273. Epub 2016 Mar 31.
Vitamin K-dependent proteins (VKDPs), which require post-translational modification to achieve biological activity, seem to contribute to thrombus formation, vascular calcification, and vessel stiffness. Whether VKDP activity is prospectively associated with incident cardiovascular disease has not been studied.
VKDP activity was determined by measuring circulating des-γ-carboxy prothrombin concentrations in a random sample of 709 multiethnic adults free of cardiovascular disease drawn from the Multi-Ethnic Study of Atherosclerosis (MESA). Lower des-γ-carboxy prothrombin concentrations reflect greater VKDP activity. Subjects were followed up for the risk of ischemic cardiovascular disease (coronary heart disease, stroke, and fatal cardiovascular disease) for 11.0 years of follow-up. A total of 75 first ischemic CVD events occurred during follow-up. The incidence of ischemic cardiovascular disease increased progressively across des-γ-carboxy prothrombin quartiles, with event rates of 5.9 and 11.7 per 1000 person-years in the lowest and highest quartiles. In analyses adjusted for traditional cardiovascular risk factors and measures of vitamin K intake, a doubling of des-γ-carboxy prothrombin concentration was associated with a 1.53 (95% confidence interval, 1.09-2.13; P=0.008) higher risk of incident ischemic cardiovascular disease. The association was consistent across strata of participants with diabetes mellitus, hypertension, renal impairment, and low vitamin K nutritional intake.
In this sample of middle-aged and older adults, VKDP activity was associated with incident ischemic cardiovascular events. Further studies to understand the role of this large class of proteins in cardiovascular disease are warranted.
维生素K依赖蛋白（VKDPs）需经翻译后修饰才能获得生物活性，似乎与血栓形成、血管钙化和血管僵硬度有关。VKDP活性与心血管疾病的发生是否存在前瞻性关联尚未得到研究。
在动脉粥样硬化多族裔研究（MESA）中随机抽取709名无心血管疾病的多族裔成年人样本，通过测量循环中去γ-羧基凝血酶原浓度来确定VKDP活性。较低的去γ-羧基凝血酶原浓度反映较高的VKDP活性。对受试者进行了11.0年的随访，以观察缺血性心血管疾病（冠心病、中风和致命性心血管疾病）的风险。随访期间共发生75例首次缺血性心血管疾病事件。缺血性心血管疾病的发病率在去γ-羧基凝血酶原四分位数中呈逐渐上升趋势，最低和最高四分位数的事件发生率分别为每1000人年5.9例和11.7例。在对传统心血管危险因素和维生素K摄入量进行校正的分析中，去γ-羧基凝血酶原浓度翻倍与缺血性心血管疾病发生风险升高1.53（95%置信区间，1.09 - 2.13；P = 0.008）相关。在患有糖尿病、高血压、肾功能损害和维生素K营养摄入低的参与者亚组中，这种关联是一致的。
在这个中老年人群样本中，VKDP活性与缺血性心血管事件的发生有关。有必要进一步开展研究以了解这类大量蛋白质在心血管疾病中的作用。
