不同种族和地理人群的循环代谢物谱与冠心病风险
Circulating Metabolite Profiles and Risk of Coronary Heart Disease Among Racially and Geographically Diverse Populations.
机构信息
Department of Medicine, Vanderbilt Epidemiology Center, Division of Epidemiology, Vanderbilt University Medical Center, Nashville, TN (K.D., X.-O.S., L.L., W.Z., H.C., Q.C., D.Y.).
Department of Medicine, Vanderbilt Translational and Clinical Cardiovascular Research Center and Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN (D.K.G.).
出版信息
Circ Genom Precis Med. 2024 Aug;17(4):e004437. doi: 10.1161/CIRCGEN.123.004437. Epub 2024 Jul 1.
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]; <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.
背景
代谢组学可能揭示出冠心病（CHD）的新生物标志物。我们旨在确定与不同种族和地理人群中发生 CHD 相关的循环代谢物，并构建代谢物风险评分（MRS）。
方法
使用 900 例新发 CHD 病例和 900 例年龄/性别/种族匹配的对照者（分别为 300 对美国黑人、美国白人、中国成年人）的基线血浆样本进行非靶向代谢组学分析，检测到 927 种在≥80%样本中具有已知身份的代谢物。经过质量控制后，896 对病例对照者被保留下来，并在每个种族内随机分为发现（70%）和验证（30%）集。在发现集中，应用条件逻辑回归和最小绝对收缩和选择算子（LASSO）在 100 个以上的子样本中进行分析，以确定与 CHD 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 MRS-CHD 关联。进行中介分析以检验 MRS 是否介导了传统危险因素与新发 CHD 之间的关联。验证集中的结果作为主要发现呈现。
结果
24 种在≥90%子样本中选择的代谢物组成了 MRS，与新发 CHD 显著相关（校正社会人口统计学、生活方式、家族史和代谢健康状况后，每 SD 增加的比值比为 2.21[95%CI，1.62-3.00]）。MRS 可以区分新发 CHD 病例和匹配对照者（C 指数为 0.69[95%CI，0.63-0.74]），并在添加到传统危险因素时改善 CHD 风险预测（C 指数为 0.71[95%CI，0.65-0.76]与 0.67[95%CI，0.61-0.73]；<0.001）。C 指数在按种族、性别、社会经济地位、生活方式、代谢健康、家族史和随访时间定义的亚组之间相似。MRS 介导了体质指数、吸烟、糖尿病、高血压和血脂异常与新发 CHD 之间大部分（46.0%-74.2%）的关联。
结论
在一个多样化的研究样本中，我们确定了 24 种循环代谢物，当它们组合成 MRS 时，与新发 CHD 密切相关，并在传统危险因素之外适度改善了 CHD 风险预测。
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