Santos José L, Ruiz-Canela Miguel, Razquin Cristina, Clish Clary B, Guasch-Ferré Marta, Babio Nancy, Corella Dolores, Gómez-Gracia Enrique, Fiol Miquel, Estruch Ramón, Lapetra José, Fitó Montserrat, Aros Fernando, Serra-Majem Lluis, Liang Liming, Martínez María Ángeles, Toledo Estefanía, Salas-Salvadó Jordi, Hu Frank B, Martínez-González Miguel A
University of Navarra, Department of Preventive Medicine and Public Health, IdiSNA (Health Research Institute of Navarra), Pamplona, Spain; Department of Nutrition, Diabetes and Metabolism, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
University of Navarra, Department of Preventive Medicine and Public Health, IdiSNA (Health Research Institute of Navarra), Pamplona, Spain.
Nutr Metab Cardiovasc Dis. 2023 Apr;33(4):835-843. doi: 10.1016/j.numecd.2023.01.002. Epub 2023 Jan 12.
Plasma citric acid cycle (CAC) metabolites might be likely related to cardiovascular disease (CVD). However, studies assessing the longitudinal associations between circulating CAC-related metabolites and CVD risk are lacking. The aim of this study was to evaluate the association of baseline and 1-year levels of plasma CAC-related metabolites with CVD incidence (a composite of myocardial infarction, stroke or cardiovascular death), and their interaction with Mediterranean diet interventions.
Case-cohort study from the PREDIMED trial involving participants aged 55-80 years at high cardiovascular risk, allocated to MedDiets or control diet. A subcohort of 791 participants was selected at baseline, and a total of 231 cases were identified after a median follow-up of 4.8 years. Nine plasma CAC-related metabolites (pyruvate, lactate, citrate, aconitate, isocitrate, 2-hydroxyglutarate, fumarate, malate and succinate) were measured using liquid chromatography-tandem mass spectrometry. Weighted Cox multiple regression was used to calculate hazard ratios (HRs). Baseline fasting plasma levels of 3 metabolites were associated with higher CVD risk, with HRs (for each standard deviation, 1-SD) of 1.46 (95%CI:1.20-1.78) for 2-hydroxyglutarate, 1.33 (95%CI:1.12-1.58) for fumarate and 1.47 (95%CI:1.21-1.78) for malate (p of linear trend <0.001 for all). A higher risk of CVD was also found for a 1-SD increment of a combined score of these 3 metabolites (HR = 1.60; 95%CI: 1.32-1.94, p trend <0.001). This result was replicated using plasma measurements after one-year. No interactions were detected with the nutritional intervention.
Plasma 2-hydroxyglutarate, fumarate and malate levels were prospectively associated with increased cardiovascular risk.
ISRCTN35739639.
血浆柠檬酸循环（CAC）代谢物可能与心血管疾病（CVD）相关。然而，缺乏评估循环中与CAC相关的代谢物和CVD风险之间纵向关联的研究。本研究的目的是评估血浆中与CAC相关的代谢物的基线水平和1年水平与CVD发病率（心肌梗死、中风或心血管死亡的综合指标）之间的关联，以及它们与地中海饮食干预的相互作用。
PREDIMED试验中的病例队列研究，纳入心血管疾病高危的55 - 80岁参与者，分为地中海饮食组或对照饮食组。基线时选取791名参与者作为亚队列，中位随访4.8年后共识别出231例病例。使用液相色谱 - 串联质谱法测量9种血浆中与CAC相关的代谢物（丙酮酸、乳酸、柠檬酸、乌头酸、异柠檬酸、2 - 羟基戊二酸、富马酸、苹果酸和琥珀酸）。采用加权Cox多元回归计算风险比（HRs）。3种代谢物的基线空腹血浆水平与较高的CVD风险相关，2 - 羟基戊二酸的HR（每标准差，1 - SD）为1.46（95%CI：1.20 - 1.78），富马酸为1.33（95%CI：1.12 - 1.58），苹果酸为1.47（95%CI：1.21 - 1.78）（所有线性趋势的p值均<0.001）。这3种代谢物综合评分每增加1 - SD，CVD风险也更高（HR = 1.60；95%CI：1.32 - 1.94，p趋势<0.001）。使用1年后的血浆测量结果重复了这一结果。未检测到与营养干预的相互作用。
血浆2 - 羟基戊二酸、富马酸和苹果酸水平与心血管风险增加呈前瞻性关联。
ISRCTN35739639。
