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A new approach to improve the specificity of flow-mediated dilation for indicating endothelial function in cardiovascular research

机译:在心血管研究中改善血流介导的扩张以指示内皮功能的特异性的新方法

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Flow-mediated dilation (FMD) is a noninvasive indicator of endothelial function and is routinely expressed as the percentage change in arterial diameter (FMD%) from a resting baseline (Dbase) to a postischemic peak (Dpeak). This expression is equivalent to the ratio of Dpeak/Dbase and is, therefore, dependent on important statistical assumptions, which have never been analysed in the context of FMD%. We aimed to investigate these assumptions, via a comparison of FMD between samples of children and adults, as well as to explore other approaches to scaling diameter change for Dbase. We found that FMD% did not scale accurately for interindividual differences in Dbase but, as expected, overestimated endothelial function for low Dbase and vice versa. We argue that this imprecise scaling of FMD% is predictable, not explained by physiology and is probably common. This problem is resolved by applying scaling principles, whereby the difference in diameter is the outcome and Dbase is a covariate in a logarithmic-linked generalized linear model. A specific allometric expression of FMD can be derived and we found this to be Dpeak/Dbase rather than a simple ratio in our particular dataset. We found that sample differences in endothelial function were inaccurate with FMD% versus our new allometric approach, and that FMD% misclassified participants into 'high' and 'low'cohorts, which has implications for prognostic-type studies. We conclude that the general use of FMD% could have led to biased comparisons of different conditions and/or populations in past studies. Our new approach to scaling FMD is flexible for different datasets and is not based on the current assumption that a percentage change is appropriate in all circumstances.
机译:血流介导的扩张(FMD)是内皮功能的一种非侵入性指标,通常表示为从静止基线(Dbase)到缺血后峰值(Dpeak)的动脉直径变化百分比(FMD%)。该表达式等于Dpeak / Dbase的比率,因此取决于重要的统计假设,而这些假设从未在FMD%的背景下进行过分析。我们旨在通过比较儿童和成人样本中的口蹄疫来研究这些假设,并探索缩放Dbase直径变化的其他方法。我们发现,FMD%不能针对Dbase的个体差异准确缩放,但正如预期的那样,对于低Dbase而言,内皮功能被高估了,反之亦然。我们认为,FMD%的这种不精确缩放是可以预见的,不能由生理学解释,并且可能很常见。通过应用缩放原理可以解决此问题,在对数关联的广义线性模型中,直径的差异是结果,而Dbase是协变量。可以导出FMD的特定异形表达,我们发现这是Dpeak / Dbase,而不是特定数据集中的简单比率。我们发现,与我们的新异位测定方法相比,FMD%的内皮功能样本差异不准确,FMD%将参与者错误分类为“高”和“低”队列,这对预后型研究具有影响。我们得出的结论是,在过去的研究中,FMD%的一般使用可能导致不同条件和/或人群的偏倚比较。我们缩放FMD的新方法对于不同的数据集是灵活的,并且并非基于当前的假设,即在所有情况下均应采用百分比变化。

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