不同种族和地域人群的循环代谢物谱与冠心病风险。

IF 6 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS
Kui Deng, Deepak K Gupta, Xiao-Ou Shu, Loren Lipworth, Wei Zheng, Hui Cai, Qiuyin Cai, Danxia Yu
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引用次数: 0

摘要

背景:代谢组学可能揭示冠心病(CHD)的新型生物标志物。我们的目的是在不同种族和地域的人群中识别循环代谢物,并构建与冠心病发病相关的代谢物风险评分(MRS):方法: 我们使用900个CHD病例和900个年龄/性别/种族匹配的对照组(分别为300对美国黑人、美国白人和中国成年人)的基线血浆样本进行了非靶向代谢组学研究,在≥80%的样本中检测到了927个已知代谢物。经过质量控制后,剩下的 896 对病例对照被随机分为发现集(70%)和验证集(30%)。在发现组中,应用条件逻辑回归和最小绝对缩减以及超过 100 个子样本的选择算子来确定与冠心病风险密切相关的代谢物,并构建 MRS。使用条件逻辑回归和 C 指数评估了 MRS 与心脏病的关联。还进行了中介分析,以检验 MRS 是否中介了常规风险因素与冠心病发病之间的关联。验证集的结果作为主要研究结果:在≥90%的子样本中选取的24种代谢物组成了MRS,MRS与冠心病的发生显著相关(调整社会人口统计学、生活方式、家族史和代谢健康状况后,每1 SD的几率比为2.21 [95% CI, 1.62-3.00])。MRS可将冠心病病例与匹配对照区分开来(C指数为0.69 [95% CI, 0.63-0.74]),并在加入常规风险因素后提高冠心病风险预测能力(C指数为0.71 [95% CI, 0.65-0.76] 对 0.67 [95% CI, 0.61-0.73];PC结论:在一个多样化的研究样本中,我们发现了 24 种循环代谢物,这些代谢物结合到 MRS 中时,与冠心病的发生密切相关,并在常规风险因素之外适度改善了冠心病风险预测。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Circulating Metabolite Profiles and Risk of Coronary Heart Disease Among Racially and Geographically Diverse Populations.

Background: Metabolomics may reveal novel biomarkers for coronary heart disease (CHD). We aimed to identify circulating metabolites and construct a metabolite risk score (MRS) associated with incident CHD among racially and geographically diverse populations.

Methods: Untargeted metabolomics was conducted using baseline plasma samples from 900 incident CHD cases and 900 age-/sex-/race-matched controls (300 pairs of Black Americans, White Americans, and Chinese adults, respectively), which detected 927 metabolites with known identities among ≥80% of samples. After quality control, 896 case-control pairs remained and were randomly divided into discovery (70%) and validation (30%) sets within each race. In the discovery set, conditional logistic regression and least absolute shrinkage and selection operator over 100 subsamples were applied to identify metabolites robustly associated with CHD risk and construct the MRS. The MRS-CHD association was evaluated using conditional logistic regression and the C-index. Mediation analysis was performed to examine if MRS mediated associations between conventional risk factors and incident CHD. The results from the validation set were presented as the main findings.

Results: Twenty-four metabolites selected in ≥90% of subsamples comprised the MRS, which was significantly associated with incident CHD (odds ratio per 1 SD, 2.21 [95% CI, 1.62-3.00] after adjusting for sociodemographics, lifestyles, family history, and metabolic health status). MRS could distinguish incident CHD cases from matched controls (C-index, 0.69 [95% CI, 0.63-0.74]) and improve CHD risk prediction when adding to conventional risk factors (C-index, 0.71 [95% CI, 0.65-0.76] versus 0.67 [95% CI, 0.61-0.73]; P<0.001). The odds ratios and C-index were similar across subgroups defined by race, sex, socioeconomic status, lifestyles, metabolic health, family history, and follow-up duration. The MRS mediated large portions (46.0%-74.2%) of the associations for body mass index, smoking, diabetes, hypertension, and dyslipidemia with incident CHD.

Conclusions: In a diverse study sample, we identified 24 circulating metabolites that, when combined into an MRS, were robustly associated with incident CHD and modestly improved CHD risk prediction beyond conventional risk factors.

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来源期刊
Circulation: Genomic and Precision Medicine
Circulation: Genomic and Precision Medicine Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
9.20
自引率
5.40%
发文量
144
期刊介绍: Circulation: Genomic and Precision Medicine is a distinguished journal dedicated to advancing the frontiers of cardiovascular genomics and precision medicine. It publishes a diverse array of original research articles that delve into the genetic and molecular underpinnings of cardiovascular diseases. The journal's scope is broad, encompassing studies from human subjects to laboratory models, and from in vitro experiments to computational simulations. Circulation: Genomic and Precision Medicine is committed to publishing studies that have direct relevance to human cardiovascular biology and disease, with the ultimate goal of improving patient care and outcomes. The journal serves as a platform for researchers to share their groundbreaking work, fostering collaboration and innovation in the field of cardiovascular genomics and precision medicine.
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