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Plasma tissue kallikrein level is negatively associated with incident and recurrent stroke: A multicenter case–control study in China

Authors

  • Qin Zhang PhD,

    1. Institute of Hypertension and Department of Internal Medicine,Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
    2. Department of Anesthesiology,Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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  • Hu Ding PhD,

    1. Institute of Hypertension and Department of Internal Medicine,Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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  • Jiangtao Yan PhD,

    1. Institute of Hypertension and Department of Internal Medicine,Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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  • Wei Wang PhD,

    1. Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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  • Aiqun Ma PhD,

    1. Department of Internal Medicine, First Affiliated Hospital, Xi'an Communication University, Xi'an, China
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  • Zhiming Zhu PhD,

    1. Internal Medicine Department, Third Military Medical University, Chongqing, China
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  • Katherine Cianflone PhD,

    1. Quebec Center of the University Research Institute of Cardiology and Pneumology, Laval University, Quebec City, Quebec, Canada
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  • Frank B. Hu MD, PhD,

    1. Departments of Nutrition and Epidemiology, Harvard School of Public Health, Boston, MA
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  • Rutai Hui PhD,

    Corresponding author
    1. Fuwai Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
    • Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095# Jiefang Ave, Wuhan 430030, People's Republic of China
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  • Dao Wen Wang MD, PhD

    Corresponding author
    1. Institute of Hypertension and Department of Internal Medicine,Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
    • Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095# Jiefang Ave, Wuhan 430030, People's Republic of China
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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. ANN NEUROL 2011;

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