Department of Cardiology, University Medical Center Groningen, University of Groningen, The Netherlands.
Heart. 2012 Sep;98(18):1348-53. doi: 10.1136/heartjnl-2012-302390. Epub 2012 Jul 21.
Experimental studies have shown that adrenomedullin (ADM) has an important role in circulatory homeostasis. Mid-regional pro-ADM (MR-proADM) is a stable form of ADM. Observational studies found an important association with age, body mass index and kidney function. The aim of this study was to evaluate the prognostic performance of MR-proADM in the general population, controlling for these potential confounders.
7903 subjects (mean age 49 ± 13 years, 49% male) from the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) cohort with a median follow-up of 10.5 years were enrolled in a prospective cohort study.
Mean baseline MR-proADM was 0.39 ± 0.14 nmol/l. In cross-sectional analyses, age, blood pressure, C reactive protein, cystatin-C, N-terminal pro-brain type natriuretic peptide and urinary albumin excretion remained as independent determinants of MR-proADM. In prospective analyses, MR-proADM was associated with the primary endpoint (combined cardiovascular mortality and cardiovascular morbidity), with event rates ranging from 8% in the lowest quintile to 45% in the highest quintile (p for trend <0.001) independent of age, sex, components of the Framingham risk score and other cardiovascular markers. Overall Net Reclassification Improvement against the Framingham risk score was 2.2%, which was non-significant. However, significant modification of the effect of MR-proADM on outcome by age was observed. In subjects aged ≤70 years (N=7475), 8.8% were correctly reclassified in a higher risk category (p=0.017) and 3.4% in a lower risk category (p<0.001). In subjects aged >70 years (N=428) there was no improvement of reclassification (p=0.32).
This study gives a detailed overview of the distribution of ADM in a general population and provides evidence that it is a potent and interesting biomarker in predicting cardiovascular events. These results seem especially applicable to younger subjects.
实验研究表明，肾上腺髓质素（ADM）在循环稳态中具有重要作用。中区域前 ADM（MR-proADM）是 ADM 的一种稳定形式。观察性研究发现其与年龄、体重指数和肾功能有重要关联。本研究旨在评估 MR-proADM 在普通人群中的预后表现，同时控制这些潜在的混杂因素。
来自预防肾脏和血管终末期疾病（PREVEND）队列的 7903 名受试者（平均年龄 49 ± 13 岁，49%为男性）入组前瞻性队列研究，中位随访时间为 10.5 年。
基线时平均 MR-proADM 为 0.39 ± 0.14 nmol/l。在横断面分析中，年龄、血压、C 反应蛋白、胱抑素-C、N 端脑利钠肽前体和尿白蛋白排泄率仍然是 MR-proADM 的独立决定因素。在前瞻性分析中，MR-proADM 与主要终点（心血管死亡率和心血管发病率的复合终点）相关，事件发生率从最低五分位组的 8%到最高五分位组的 45%（p 趋势＜0.001），与年龄、性别、弗雷明汉风险评分的组成部分和其他心血管标志物无关。与弗雷明汉风险评分相比，总体净重新分类改善为 2.2%，但无统计学意义。然而，观察到 MR-proADM 对结果的影响因年龄而发生显著改变。在年龄≤70 岁的受试者（N=7475）中，8.8%被正确重新分类为更高风险类别（p=0.017），3.4%被重新分类为更低风险类别（p＜0.001）。在年龄＞70 岁的受试者（N=428）中，重新分类无改善（p=0.32）。
本研究详细概述了 ADM 在普通人群中的分布情况，并提供了证据表明，它是预测心血管事件的一种有效且有趣的生物标志物。这些结果似乎尤其适用于年轻的受试者。
