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可溶性黏附分子P-选择素与原发性高血压中的内皮功能障碍:对动脉粥样硬化形成有何影响?一份初步报告。

Soluble adhesion molecule P-selectin and endothelial dysfunction in essential hypertension: implications for atherogenesis? A preliminary report.

作者信息

Lip G Y, Blann A D, Zarifis J, Beevers M, Lip P L, Beevers D G

机构信息

University Department of Medicine, City Hospital, Birmingham, England.

出版信息

J Hypertens. 1995 Dec;13(12 Pt 2):1674-8.

PMID:8903631
Abstract

OBJECTIVE

Patients with essential hypertension are at high risk of atherosclerotic vascular disease. To investigate this further, we measured levels of the soluble adhesion molecule P-selectin, which is associated with platelet activity/function and atherosclerosis, von Willebrand factor, which is a marker of endothelial dysfunction, and plasma fibrinogen.

PATIENTS AND METHODS

We studied 104 consecutive patients (47 males, 57 females; mean +/- SD age 54.8 +/- 14.1 years) with essential hypertension compared with 47 normotensive healthy controls (55.0 +/- 19.2 years). Levels of soluble adhesion molecule P-selectin and von Willebrand factor were measured by enzyme-linked immunosorbent assay, and plasma fibrinogen by a clotting method (CLAUSS).

RESULTS

Compared with normotensives, the hypertensives showed significant increases in soluble P-selectin (300 versus 228 ng/ml; median difference 55 ng/ml, Mann-Whitney test P = 0.03), von Willebrand factor (114 versus 96 IU/I; unpaired t-test P < or = 0.001) and fibrinogen (3.3 versus 2.9 g/l; unpaired t-test P < or = 0.001). There were significant correlations between fibrinogen and P-selectin (r = 0.16; P = 0.02) and von Willebrand factor (r = 0.39; P<0.001), but not between P-selectin and von Willebrand factor. There were no differences in these factors between patients with (n = 53) and without (n = 51) antihypertensive therapy or between those with good blood pressure control (systolic/diastolic < or = 160/90 mmHg; n = 17) and those with poor control. A stepwise multiple regression analysis showed that diastolic blood pressure was a significant predictor for soluble P-selectin levels; diastolic blood pressure and von Willebrand factor levels were significant predictors for fibrinogen levels (P<0.05).

CONCLUSIONS

This study suggests that hypertensives have high plasma fibrinogen levels, platelet dysfunction (which could contribute to atherogenesis, as indicated by raised soluble P-selectin levels) and endothelial dysfunction (as indicated by high von Willebrand factor levels), which are related to diastolic blood pressure. These factors may act synergistically to increase atherogenesis and may explain the high risk of atherosclerotic vascular disease in hypertensives.

摘要

目的

原发性高血压患者患动脉粥样硬化性血管疾病的风险较高。为进一步研究这一问题,我们检测了可溶性黏附分子P-选择素、血管性血友病因子和血浆纤维蛋白原的水平。P-选择素与血小板活性/功能及动脉粥样硬化有关,血管性血友病因子是内皮功能障碍的标志物。

患者与方法

我们研究了104例连续的原发性高血压患者(47例男性,57例女性;平均±标准差年龄54.8±14.1岁),并与47例血压正常的健康对照者(55.0±19.2岁)进行比较。采用酶联免疫吸附测定法检测可溶性黏附分子P-选择素和血管性血友病因子的水平,采用凝血法(克劳斯法)检测血浆纤维蛋白原水平。

结果

与血压正常者相比,高血压患者的可溶性P-选择素(300对228 ng/ml;中位数差异55 ng/ml,曼-惠特尼检验P = 0.03)、血管性血友病因子(114对96 IU/I;非配对t检验P≤0.001)和纤维蛋白原(3.3对2.9 g/l;非配对t检验P≤0.001)水平显著升高。纤维蛋白原与P-选择素(r = 0.16;P = 0.02)和血管性血友病因子(r = 0.39;P<0.001)之间存在显著相关性,但P-选择素与血管性血友病因子之间无相关性。接受(n = 53)和未接受(n = 51)抗高血压治疗的患者之间,以及血压控制良好(收缩压/舒张压≤160/90 mmHg;n = 17)和控制不佳的患者之间,这些因素无差异。逐步多元回归分析显示,舒张压是可溶性P-选择素水平的显著预测因子;舒张压和血管性血友病因子水平是纤维蛋白原水平的显著预测因子(P<0.05)。

结论

本研究表明,高血压患者血浆纤维蛋白原水平较高、存在血小板功能障碍(可溶性P-选择素水平升高表明可能有助于动脉粥样硬化的发生)和内皮功能障碍(血管性血友病因子水平升高表明),这些均与舒张压有关。这些因素可能协同作用增加动脉粥样硬化的发生,这可能解释了高血压患者患动脉粥样硬化性血管疾病的高风险。

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