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血浆组织激肽释放酶水平与新发和复发性卒中呈负相关:中国多中心病例对照研究。

Plasma tissue kallikrein level is negatively associated with incident and recurrent stroke: a multicenter case-control study in China.

机构信息

Institute of Hypertension and Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

出版信息

Ann Neurol. 2011 Aug;70(2):265-73. doi: 10.1002/ana.22404.

DOI:10.1002/ana.22404
PMID:21823154
Abstract

OBJECTIVE

Tissue kallikrein (TK) cleaves kininogen to produce the potent bioactive compounds kinin and bradykinin, which lower blood pressure and protect the heart, kidneys, and blood vessels. Reduction in TK levels is associated with cardiovascular disease and diabetes in animal models. In this study, we investigated the association of TK levels with event-free survival over 5 years in Chinese first-ever stroke patients.

METHODS

We conducted a case-control study with 1,268 stroke patients (941 cerebral infarction, 327 cerebral hemorrhage) and 1,210 controls. Plasma TK levels were measured with an enzyme-linked immunosorbent assay. We used logistic regression and Cox proportional hazards models to assess the relationship between TK levels and risk of first-time or recurrent stroke.

RESULTS

Plasma TK levels were significantly lower in stroke patients (0.163 ± 0.064mg/l vs 0.252 ± 0.093mg/l, p < 0.001), especially those with ischemic stroke. After adjustment for traditional risk factors, plasma TK levels were negatively associated with the risk of first-ever stroke (odds ratio [OR], 0.344; 95% confidence interval [CI], 0.30-0.389; p < 0.001) and stroke recurrence and positively associated with event-free survival during 5 years of follow-up (relative risk, 0.82; 95% CI, 0.74-0.90; p < 0.001). Compared with the first quartile of plasma TK levels, the ORs for first-ever stroke patients were as follows: second quartile, 0.77 (95% CI, 0.56-1.07); third quartile, 0.23 (95% CI, 0.17-0.32); fourth quartile, 0.04 (95% CI, 0.03-0.06).

INTERPRETATION

Lower plasma TK levels are independently associated with first-ever stroke and are an independent predictor of recurrence after an initial stroke.

摘要

目的

组织激肽释放酶(TK)能将激肽原裂解为具有生物活性的缓激肽和血管舒张素,从而降低血压并保护心脏、肾脏和血管。动物模型研究表明,TK 水平的降低与心血管疾病和糖尿病有关。在本研究中,我们调查了中国首次中风患者 5 年内无事件生存率与 TK 水平的相关性。

方法

我们进行了一项病例对照研究,纳入了 1268 名中风患者(941 例脑梗死,327 例脑出血)和 1210 名对照。采用酶联免疫吸附试验测定血浆 TK 水平。我们使用逻辑回归和 Cox 比例风险模型评估 TK 水平与首次或复发性中风风险之间的关系。

结果

中风患者的血浆 TK 水平明显降低(0.163 ± 0.064mg/L 比 0.252 ± 0.093mg/L,p<0.001),尤其是缺血性中风患者。在调整传统危险因素后,血浆 TK 水平与首次中风的风险呈负相关(比值比[OR],0.344;95%置信区间[CI],0.30-0.389;p<0.001),与中风复发和 5 年随访期间无事件生存率呈正相关(相对风险,0.82;95%CI,0.74-0.90;p<0.001)。与血浆 TK 水平最低的四分位区间相比,各四分位区间首次中风患者的 OR 分别为:第二四分位区间,0.77(95%CI,0.56-1.07);第三四分位区间,0.23(95%CI,0.17-0.32);第四四分位区间,0.04(95%CI,0.03-0.06)。

解释

较低的血浆 TK 水平与首次中风独立相关,是初次中风后复发的独立预测因子。

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