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新型分子血浆标志物可对心血管疾病患者进行终生分层。

Novel molecular plasma signatures on cardiovascular disease can stratify patients throughout life.

机构信息

Department of Vascular Physiopathology, Hospital Nacional de Parapléjicos, SESCAM, Toledo, Spain.

Cardiovascular Proteomics Laboratory and CIBER-CV, CNIC, Madrid, Spain.

出版信息

J Proteomics. 2020 Jun 30;222:103816. doi: 10.1016/j.jprot.2020.103816. Epub 2020 May 8.

DOI:10.1016/j.jprot.2020.103816
PMID:32389841
Abstract

Several models are available to calculate the risk of developing cardiovascular complications in mid-life. The estimation of lifetime risk in the long-term remains an unmet clinical need. We previously identified new molecular plasma signatures for cardiovascular risk stratification in a young population (30-50-years old). The aim of the present study was to determine if the specific signature found in young population changes with age. Proteomic analysis was performed in plasma samples obtained from different age groups, middle-age (50-70-years old, n = 63) and elderly (>70-years old, n = 61), which, in turn were classified into 3 subgroups according to cardiovascular risk. Our previous results in a young population clearly showed two different proteomic signatures. Building on these findings, targeted-mass spectrometry and turbidimetry analyses were used to test these signatures in middle-age and elderly populations. This strategy identified three common proteomic signatures between young and adult patients related to cardiovascular stratification, organ damage and risk prediction. Furthermore, receiver operating characteristic analysis revealed the potential value of these novel markers for lifetime risk stratification. Our results provide new insight into altered molecular mechanisms in the pathogenesis of cardiovascular disease and, more importantly, identify novel protein panels that can stratify patients throughout life. SIGNIFICANCE: Our results revealed three common proteomic signatures between young and adult patients related to cardiovascular stratification, organ damage and risk prediction. The results obtained provide a deeper insight into the pathogenesis of CV diseases and allow the identification of novel protein panels to stratify patients according to CV risk throughout life. While current estimators calculate the risk of having a CV event considering age as the most important factor to CV disease, our results represent an alternative to traditional CV risk factors, allowing the stratification of CV risk regardless of the age. Using a combination of traditional markers and established algorithms with these findings as a future preventive strategy, could facilitate an adequate assessment of CV risk.

摘要

有几种模型可用于计算中年发生心血管并发症的风险。长期估计终生风险仍然是未满足的临床需求。我们之前在年轻人群(30-50 岁)中发现了新的分子血浆特征,用于心血管风险分层。本研究的目的是确定年轻人群中发现的特定特征是否会随年龄而变化。对来自不同年龄组(中年,50-70 岁,n=63;老年,>70 岁,n=61)的血浆样本进行了蛋白质组分析,这些样本又根据心血管风险分为 3 个亚组。我们之前在年轻人群中的研究结果清楚地显示了两种不同的蛋白质组特征。在此基础上,使用靶向质谱法和浊度分析法对中年和老年人群进行了这些特征的测试。这种策略确定了年轻和成年患者之间与心血管分层、器官损伤和风险预测相关的三种常见蛋白质组特征。此外,接受者操作特征分析显示了这些新型标记物用于终生风险分层的潜在价值。我们的结果为心血管疾病发病机制中改变的分子机制提供了新的见解,更重要的是,确定了可对终生分层的新型蛋白质组。

意义

我们的结果揭示了年轻和成年患者之间与心血管分层、器官损伤和风险预测相关的三种常见蛋白质组特征。获得的结果更深入地了解了 CV 疾病的发病机制,并允许识别新型蛋白质组,根据 CV 风险对患者进行分层。虽然目前的估计器在考虑年龄是 CV 疾病最重要的因素的情况下计算发生 CV 事件的风险,但我们的结果代表了传统 CV 危险因素的替代方法,允许不分年龄对 CV 风险进行分层。使用传统标志物的组合和这些发现的既定算法作为未来的预防策略,可以促进对 CV 风险的充分评估。

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