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一般人群中的多种内皮生物标志物和非侵入性血管功能:哥廷根健康研究。

Multiple endothelial biomarkers and noninvasive vascular function in the general population: the Gutenberg Health Study.

机构信息

University Heart Center, Department of General and Interventional Cardiology, Martinistr 52, 20246 Hamburg, Germany.

出版信息

Hypertension. 2012 Aug;60(2):288-95. doi: 10.1161/HYPERTENSIONAHA.112.191874. Epub 2012 Jun 11.

Abstract

Vascular reactivity is reflected by blood biomarkers and noninvasive vascular function measurement. The relation of biomarkers to flow-mediated dilation and peripheral arterial tonometry in the general population is little understood. In 5000 individuals (mean age, 56±11 years; age range, 35-74 years; 49% women) of the population-based Gutenberg Health Study we simultaneously assessed 6 biomarkers of cardiovascular function (midregional proadrenomedullin [MR-proADM], midregional pro atrial natriuretic peptide [MR-proANP], N-terminal pro B-type natriuretic peptide, copeptin, C-terminal proendothelin 1, and neopterin) in relation to flow-mediated dilation and peripheral arterial tonometry. Strongest partial correlations (adjusted for age and sex) were observed for baseline pulse amplitude with MR-proADM (r=0.13) and MR-proANP (r=-0.13); hyperemic response variables showed the highest correlation for MR-proADM and peripheral arterial tonometry ratio (r=-0.14). In multivariable linear regression models, strongest associations with baseline vascular function were observed for MR-proANP with baseline pulse amplitude (β per SD increase [99.17%], -0.080 [-0.115 to -0.044]; P<0.0001 after Bonferroni correction for multiple testing) and MR-proADM (-0.044 [-0.070 to -0.017]; P<0.0001), as well as MR-proANP (-0.033 [-0.057 to -0.009]; P=0.0017) and N-terminal pro B-type natriuretic peptide (-0.027 [-0.051 to -0.003]; P=0.015) with brachial artery diameter. For hyperemic response variables, highest associations were seen for peripheral arterial tonometry ratio with MR-proADM (-0.022 [-0.043 to -0.004]; P=0.043), MR-proANP (0.016 [-0.0034 to 0.035]; P=0.18), and C-terminal proendothelin 1 (-0.025 [-0.043 to -0.008]; P=0.00094]. In our large, population-based study, we identified MR-proADM and MR-proANP as circulating biomarkers of vascular function most strongly related to noninvasive measures of conduit artery and peripheral arterial performance. Whether determination of blood biomarkers helps to better understand vascular pathology and may provide prognostic information needs to be investigated in future studies.

摘要

血管反应性通过血液生物标志物和非侵入性血管功能测量来反映。在一般人群中,生物标志物与血流介导的扩张和外周动脉张力之间的关系知之甚少。在基于人群的古滕贝格健康研究(Gutenberg Health Study)的 5000 名个体(平均年龄 56±11 岁;年龄范围 35-74 岁;49%为女性)中,我们同时评估了 6 种心血管功能的生物标志物(中区域原肾上腺素[MR-proADM]、中区域原心房利钠肽[MR-proANP]、N-末端 B 型利钠肽前体、 copeptin、C-末端内皮素 1 和新蝶呤)与血流介导的扩张和外周动脉张力的关系。与基线脉搏振幅相关性最强的部分相关(经年龄和性别调整)是 MR-proADM(r=0.13)和 MR-proANP(r=-0.13);与高反应变量相关性最强的是 MR-proADM 和外周动脉张力比(r=-0.14)。在多变量线性回归模型中,与基线血管功能相关性最强的是 MR-proANP 与基线脉搏振幅(每增加一个标准差的 β [99.17%],-0.080 [-0.115 至-0.044];在多次检验的 Bonferroni 校正后 P<0.0001)和 MR-proADM(-0.044 [-0.070 至-0.017];P<0.0001),以及 MR-proANP(-0.033 [-0.057 至-0.009];P=0.0017)和 N-末端 B 型利钠肽前体(-0.027 [-0.051 至-0.003];P=0.015)与肱动脉直径。对于高反应变量,与外周动脉张力比相关性最强的是 MR-proADM(-0.022 [-0.043 至-0.004];P=0.043)、MR-proANP(0.016 [-0.0034 至 0.035];P=0.18)和 C-末端内皮素 1(-0.025 [-0.043 至-0.008];P=0.00094)。在我们这项大型的基于人群的研究中,我们确定了 MR-proADM 和 MR-proANP 是与大血管和外周动脉功能的非侵入性测量最密切相关的循环血管功能生物标志物。血液生物标志物的测定是否有助于更好地了解血管病理,并可能提供预后信息,这需要在未来的研究中进行调查。

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