Aims Endothelial function is essential for cardiovascular health, and flow-mediated dilation (FMD) is an established technique to measure it. This paper is to assess FMD values in apparently healthy individuals and provide reference values to facilitate wider clinical use. Methods and Results In 1,579 apparently healthy individuals (aged 18-76), fasted FMD values (data from 44 studies, 6 institutions, 22 operators) were normally distributed and inversely univariately correlated with age, body-mass-index, glucose, cholesterol, blood pressure, and brachial artery diameter. Significant multivariate predictors of FMD were age (-0.4%/decade), BMI (0.04%/kg/m2), smoking (-0.7%), and brachial artery diameter (-0.44%/mm) that together explained 19% of the variability independent of operator, institution or ultrasound machine. Individuals in the high FMD tertile (>6.8%) were younger, had smaller brachial artery diameter, lower blood pressure and cholesterol. In individuals with low- and intermediate fatal cardiovascular risk (SCORE), 26% and 53% of individuals, respectively, had FMD values in the low tertile (<5.4%). After adding data from 385 patients with stable coronary artery disease (CAD), ROC analysis (c = 0.841, p < 0.001) showed that FMD of >6.5% excluded CAD (95% sensitivity; 60% specificity) and FMD <3.1% excluded 95% healthy individuals (95% specificity, 31% sensitivity). A meta-analysis and meta-regression of 82 clinical trials (11 countries, n = 3,509) using similar FMD methodology showed that despite considerable heterogeneity (I2 = 0.97) FMD in healthy individuals was on average 6.4% (95%CI: 6.2%, 6.7%) with no significant differences between countries but a significant age-dependent decline (-0.3%/decade, R2 = 0.13). Conclusions We provide an age-adapted frame of FMD reference intervals in apparently healthy individuals for use as a biomarker of CV health. As the degree of vascular endothelial function integrates environmental and genetic factors with classical CV risk factors, FMD may more comprehensively classify individuals with and without standard modifiable cardiovascular risk factors and serve as a target for cardiovascular prevention.

中文翻译：

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用于评价内皮功能和心血管健康的血流介导的扩张参考值

目的 内皮功能对心血管健康至关重要，血流介导的扩张 (FMD) 是一种成熟的测量内皮功能的技术。本文旨在评估表观健康个体的 FMD 值，并提供参考值以促进更广泛的临床使用。方法和结果 在 1,579 名表面健康的个体（18-76 岁）中，空腹 FMD 值（来自 44 项研究、6 家机构、22 名操作员的数据）呈正态分布，并且与年龄、体重指数、葡萄糖、胆固醇、血压和肱动脉直径。FMD 的重要多变量预测因子是年龄（-0.4%/十年）、BMI（0.04%/kg/m2）、吸烟（-0.7%）和肱动脉直径（-0.44%/mm），它们共同解释了 19% 的 FMD独立于操作员、机构或超声波机器的可变性。处于高 FMD 三分位数 (>6.8%) 的个体更年轻，肱动脉直径更小，血压和胆固醇更低。在具有低和中等致命心血管风险 (SCORE) 的个体中，分别有 26% 和 53% 的个体具有低三分位数 (<5.4%) 的 FMD 值。添加来自 385 名稳定型冠状动脉疾病 (CAD) 患者的数据后，ROC 分析 (c = 0.841，p < 0.001) 显示 FMD >6.5% 排除 CAD（95% 敏感性；60% 特异性）和 FMD <0.5% 3.1% 排除了 95% 的健康个体（特异性为 95%，敏感性为 31%）。使用类似的 FMD 方法对 82 项临床试验（11 个国家/地区，n = 3,509）进行的荟萃分析和荟萃回归表明，尽管存在相当大的异质性（I2 = 0.97），但健康个体的 FMD 平均为 6.4%（95%CI：6.2%） , 6. 7%），各国之间没有显着差异，但随着年龄的增长而显着下降（-0.3%/十年，R2 = 0.13）。结论 我们在表面健康的个体中提供了一个年龄适应的 FMD 参考区间框架，用作 CV 健康的生物标志物。由于血管内皮功能的程度将环境和遗传因素与经典的 CV 危险因素相结合，FMD 可以更全面地对具有和不具有标准可改变心血管危险因素的个体进行分类，并作为心血管预防的目标。