The Non-Targeted Lipidomic-Based Classifier Reveals Two Candidate Biomarkers for Ischemic Stroke in Hypertensive Individuals

IF 2.7 4区医学 Q2 HEALTH CARE SCIENCES & SERVICES Risk Management and Healthcare Policy Pub Date : 2024-07-30 DOI:10.2147/rmhp.s465135

Wenbin Wang, Lin Liu, Weida Qiu, Chaolei Chen, Yuqing Huang, Anping Cai, Zhiqiang Nie, Yanqiu Ou, Yicheng Zhu, Yingqing Feng

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Abstract

Introduction: Traditional clinical risk factors are insufficient to estimate the residual risk of large-vessel ischemic stroke. Non-targeted lipidomic techniques provide an opportunity to evaluate these risks.
Methods: Plasma samples were collected from 113 hypertensive individuals, including 55 individuals at high risk of ischemic stroke and 58 matched individuals, in a prospective nested case-control cohort. To identify dysregulated lipid metabolites, we conducted multivariate and univariate analyses. A classifier based on a cross-validated procedure was employed to select the optimal combination of lipid species and their ratios.
Results: We identified 23 dysregulated lipid species in patients with and without ischemic stroke, including 16 (69.6%) up-regulated and 7 (30.4%) down-regulated lipid species. Through internal cross-validation, the optimal combination of two lipid features (phosphatidylcholine 34:2 and triglyceride 18:1/18:1/22:1 / phosphatidylcholine 34:2, referred to as ischemic stroke-related 2 lipid features - IS2LP) was selected, leading to a more precise prediction probability for ischemic stroke within 3.9 years. In the comparison of different risk factors, the traditional risk score, the IS2LP risk score, and the combination of the traditional risk score with IS2LP yield AUC values of 0.613(95% CI:0.509– 0.717), 0.833(95% CI:0.755– 0.911), and 0.843(95% CI:0.777– 0.916), respectively. The combination of the traditional risk score and IS2LP exhibited significantly improved discriminative performance, with an integrated discrimination improvement (IDI) of 0.31 (p< 0.001) and a continuous net reclassification improvement (NRI) of 1.06 (p < 0.001) compared to the traditional risk score.
Conclusion: We identified new lipidomic biomarkers associated with the futural event of large-vessel ischemic stroke. These lipid species could serve as potential blood biomarkers for assessing the residual risk of ischemic stroke in hypertensive individuals.

Keywords: hypertension, lipidomics, ischemic stroke, risk factors

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基于非靶向脂质体的分类器揭示了高血压患者缺血性中风的两个候选生物标志物

导言：传统的临床风险因素不足以估计大血管缺血性卒中的残余风险。非靶向脂质体技术为评估这些风险提供了机会：在前瞻性巢式病例对照队列中收集了 113 名高血压患者的血浆样本，其中包括 55 名缺血性脑卒中高危人群和 58 名匹配人群。为了确定失调的脂质代谢物，我们进行了多变量和单变量分析。我们采用了基于交叉验证程序的分类器来选择脂质种类及其比率的最佳组合：结果：我们在缺血性脑卒中患者和非缺血性脑卒中患者中发现了 23 种调控失调的脂质，包括 16 种（69.6%）上调脂质和 7 种（30.4%）下调脂质。通过内部交叉验证，选出了两种脂质特征（磷脂酰胆碱 34:2 和甘油三酯 18:1/18:1/22:1 / 磷脂酰胆碱 34:2，简称为缺血性中风相关 2 种脂质特征 - IS2LP）的最佳组合，从而更精确地预测了 3.9 年内缺血性中风的概率。在不同风险因素的比较中，传统风险评分、IS2LP 风险评分以及传统风险评分与 IS2LP 的组合的 AUC 值分别为 0.613（95% CI：0.509- 0.717）、0.833（95% CI：0.755- 0.911）和 0.843（95% CI：0.777- 0.916）。与传统风险评分相比，传统风险评分和IS2LP的组合具有显著的鉴别性能，综合鉴别改进（IDI）为0.31（p< 0.001），连续净再分类改进（NRI）为1.06（p< 0.001）：我们发现了与大血管缺血性卒中未来事件相关的新脂质体生物标志物。这些脂质种类可作为潜在的血液生物标志物，用于评估高血压患者缺血性脑卒中的残余风险。

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来源期刊

Risk Management and Healthcare Policy Medicine-Public Health, Environmental and Occupational Health

CiteScore

6.20

自引率

2.90%

发文量

242

审稿时长

16 weeks

期刊介绍： Risk Management and Healthcare Policy is an international, peer-reviewed, open access journal focusing on all aspects of public health, policy and preventative measures to promote good health and improve morbidity and mortality in the population. Specific topics covered in the journal include: Public and community health Policy and law Preventative and predictive healthcare Risk and hazard management Epidemiology, detection and screening Lifestyle and diet modification Vaccination and disease transmission/modification programs Health and safety and occupational health Healthcare services provision Health literacy and education Advertising and promotion of health issues Health economic evaluations and resource management Risk Management and Healthcare Policy focuses on human interventional and observational research. The journal welcomes submitted papers covering original research, clinical and epidemiological studies, reviews and evaluations, guidelines, expert opinion and commentary, and extended reports. Case reports will only be considered if they make a valuable and original contribution to the literature. The journal does not accept study protocols, animal-based or cell line-based studies.