前瞻性研究血浆高分子量激肽原和前激肽释放酶与冠心病、缺血性卒中和心力衰竭的发生情况。
Prospective study of plasma high molecular weight kininogen and prekallikrein and incidence of coronary heart disease, ischemic stroke and heart failure.
机构信息
Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, 1300 South 3nd Street, Suite 300, Minneapolis, MN 55454, United States.
Department of Epidemiology, University of North Carolina, 137 East Franklin Street, Suite 306, CB# 7435, Chapel Hill, NC 27514, United States.
出版信息
Thromb Res. 2019 Oct;182:89-94. doi: 10.1016/j.thromres.2019.08.009. Epub 2019 Aug 22.
INTRODUCTION
High molecular weight kininogen (HK) and prekallikrein (PK) are proteins in the kallikrein/kinin system of the coagulation cascade. They play an important role in the contact activation system of the intrinsic coagulation pathway, renin-angiotensin activation, and inflammation. Hence these proteins have been posited to affect the occurrence of cardiovascular events and thus to be potential therapeutic targets. Previous case-control studies have provided inconsistent evidence for an association of HK and PK with cardiovascular disease.
METHODS
In the prospective population-based Atherosclerosis Risk in Communities(ARIC) Study, we used Cox proportional hazards regression models to investigate the association in 4195 middle-aged adults of plasma HK and PK concentrations in 1993-95 (linearly and in quartiles) with incident coronary heart disease, ischemic stroke, and heart failure through 2016.
RESULTS
Over a mean of 18 years follow-up, we identified incident cardiovascular events (coronary heart disease and ischemic stroke) in 618 participants and heart failure in 667. We observed no significant relation between HK or PK and cardiovascular disease or heart failure, before and after adjusting for several potential confounding variables.
CONCLUSIONS
We found no compelling evidence to support an association of plasma HK or PK concentrations with incident CHD, ischemic stroke, or heart failure.
简介
高分子量激肽原（HK）和前激肽释放酶（PK）是凝血级联中激肽/激肽系统的蛋白质。它们在内在凝血途径的接触激活系统、肾素-血管紧张素激活和炎症中发挥重要作用。因此，这些蛋白质被认为会影响心血管事件的发生，从而成为潜在的治疗靶点。先前的病例对照研究提供了不一致的证据表明 HK 和 PK 与心血管疾病有关。
方法
在前瞻性的基于人群的动脉粥样硬化风险社区（ARIC）研究中，我们使用 Cox 比例风险回归模型，在 1993-95 年（线性和四分位数）调查了 4195 名中年成年人血浆 HK 和 PK 浓度与 2016 年之前的冠心病、缺血性中风和心力衰竭的发生率之间的关联。
结果
在平均 18 年的随访中，我们在 618 名参与者中发现了心血管事件（冠心病和缺血性中风），在 667 名参与者中发现了心力衰竭。我们观察到 HK 或 PK 与心血管疾病或心力衰竭之间没有显著的关系，在调整了几个潜在的混杂变量之前和之后都是如此。
结论
我们没有发现令人信服的证据支持血浆 HK 或 PK 浓度与冠心病、缺血性中风或心力衰竭的发生率之间存在关联。
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