Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy.
Centro Cardiologico Monzino, IRCCS, Milan, Italy; Department of Clinical Sciences and Community Health, Cardiovascular Section, University of Milan, Italy.
Int J Cardiol. 2021 Aug 1;336:14-21. doi: 10.1016/j.ijcard.2021.05.033. Epub 2021 May 20.
Traditional cardiovascular risk factors (RFs) and coronary artery disease (CAD) do not always run parallel. We investigated functional-metabolic correlations of CAD, RFs, or neither in the CAPIRE (Coronary Atherosclerosis in Outlier Subjects: Protective and Novel Individual Risk Factors Evaluation) 2 × 2 phenotypic observational study.
Two hundred and fortyone subjects were included based on RF burden, presence/absence of CAD (assessed by computed tomography angiography), age and sex. Participants displayed one of four phenotypes: CAD with ≥3 RFs, no-CAD with ≥3 RFs, CAD with ≤1 RF and no-CAD with ≤1 RF. Metabolites were identified by gas chromatography-mass spectrometry and pathways by metabolite set enrichment analysis.
Characteristic patterns and specific pathways emerged for each phenotypic group: amino sugars for CAD/high-RF; urea cycle for no-CAD/high-RF; glutathione for CAD/low-RF; glycine and serine for no-CAD/low-RF. Presence of CAD correlated with ammonia recycling; absence of CAD with the transfer of acetyl groups into mitochondria; high-risk profile with alanine metabolism (all p < 0.05). The comparative case-control analyses showed a statistically significant difference for the two pathways of phenylalanine, tyrosine and tryptophan biosynthesis and phenylalanine metabolism in the CAD/Low-RF vs NoCAD/Low-RF comparison.
The present 2 × 2 observational study identified specific metabolic pathways for each of the four phenotypes, providing novel functional insights, particularly on CAD with low RF profiles and on the absence of CAD despite high-risk factor profiles.
传统心血管危险因素（RFs）和冠状动脉疾病（CAD）并不总是平行的。我们研究了 CAD、RF 或两者均不存在的功能性代谢相关性，在 CAPIRE（外显子受试者的冠状动脉粥样硬化：保护和新型个体风险因素评估）2×2 表型观察性研究中。
根据 RF 负担、CAD（通过计算机断层扫描血管造影评估）的存在/不存在、年龄和性别，纳入了 241 名受试者。参与者表现出四种表型之一：CAD 伴≥3 个 RFs、无 CAD 伴≥3 个 RFs、CAD 伴≤1 个 RF 和无 CAD 伴≤1 个 RF。通过气相色谱-质谱法鉴定代谢物，通过代谢物集富集分析鉴定途径。
每种表型组都出现了特征性模式和特定途径：CAD/高-RF 组为氨基糖；无 CAD/高-RF 组为尿素循环；CAD/低-RF 组为谷胱甘肽；无 CAD/低-RF 组为甘氨酸和丝氨酸。CAD 的存在与氨回收有关；无 CAD 的存在与乙酰基转移到线粒体有关；高危特征与丙氨酸代谢有关（均 p<0.05）。对比病例对照分析显示，在 CAD/Low-RF 与 NoCAD/Low-RF 比较中，苯丙氨酸、酪氨酸和色氨酸生物合成及苯丙氨酸代谢的两条途径存在统计学显著差异。
本 2×2 观察性研究确定了四种表型中的每一种的特定代谢途径，提供了新的功能见解，特别是对于低 RF 谱的 CAD 和尽管存在高危因素谱但不存在 CAD 的情况。
