du Toit Wessel L, Kruger Ruan, Gafane-Matemane Lebo F, Schutte Aletta E, Louw Roan, Mels Catharina M C
Hypertension in Africa Research Team (HART), North-West University, Potchefstroom, South Africa.
MRC Research Unit for Hypertension and Cardiovascular Disease, North-West University, Potchefstroom, South Africa.
J Hypertens. 2022 Aug 1;40(8):1545-1555. doi: 10.1097/HJH.0000000000003182. Epub 2022 Jul 5.
Risk factors contributes to a dysregulated metabolism and may ultimately increase the predisposition for cardiovascular disease (CVD) development. To increase our understanding of mechanistic pathways associated with CVD risk, we profiled the urinary metabolome according to individual and clusters of CVD risk factors in comparison with a control group without any risk factors.
Healthy black and white women and men ( N = 1202), aged 20-30 years with a detailed CVD risk factor profile were included. CVD risk groups: obese, physical inactive, smoking, excessive alcohol intake, masked hypertensive, hyperglycaemic, dyslipidemic and low socioeconomic status. CVD risk clusters were based on the presence of 1, 2 and 3 or more risk factors. Liquid chromatography-tandem mass spectrometry was used to obtain urinary metabolomics data (amino acids and acylcarnities). Compared with the control group, higher levels of metabolites associated with aromatic and branched chain amino acid metabolism including phenylalanine, tyrosine and leucine/isoleucine were found in the obese, masked hypertensive, hyperglycaemic, low socioeconomic groups (all q ≤ 0.032) and 3+ CVD risk cluster (all P ≤ 0.034). Metabolites associated with the y-glutamyl cycle including glycine, histidine, serine, glutamine, methionine, cystine and pyroglutamic acid were found in the hyperglycaemic, low socioeconomic groups (all q ≤ 0.050), 2 and 3+ CVD risk clusters (all P ≤ 0.041). Metabolites associated with energetics including acetylcarnitine (lower levels), hexanoylcarnitine and decanoylcarnitine were found in the low socioeconomic group, 1 and 3+ CVD risk clusters ( q / P ≤ 0.050) ( β -oxidation). In addition to the above-mentioned amino acids, alanine and threonine were found in the hyperglycaemic, low socioeconomic groups, 2 and 3+ CVD risk clusters (all q / P ≤ 0.047) (glycolysis). Creatine in the obese, hyperglycaemic groups (all q ≤ 0.049) and 3+ CVD risk cluster (all P ≤ 0.041) (creatine pathway).
Exposure to CVD risk factors is associated with a dysregulated metabolism in the above-mentioned pathways that may precede the development of CVD.
风险因素会导致代谢失调，并最终可能增加心血管疾病（CVD）发生的易感性。为了加深我们对与CVD风险相关的机制途径的理解，我们根据个体和CVD风险因素集群对尿代谢组进行了分析，并与无任何风险因素的对照组进行比较。
纳入了年龄在20 - 30岁、具有详细CVD风险因素概况的健康黑人和白人女性及男性（N = 1202）。CVD风险组包括：肥胖、缺乏身体活动、吸烟、过量饮酒、隐匿性高血压、高血糖、血脂异常和低社会经济地位。CVD风险集群基于存在1个、2个以及3个或更多风险因素。采用液相色谱 - 串联质谱法获取尿代谢组学数据（氨基酸和酰基肉碱）。与对照组相比，在肥胖、隐匿性高血压、高血糖、低社会经济地位组（所有q≤0.032）以及3个及以上CVD风险因素集群组（所有P≤0.034）中，发现与芳香族和支链氨基酸代谢相关的代谢物水平较高，包括苯丙氨酸、酪氨酸和亮氨酸/异亮氨酸。在高血糖、低社会经济地位组（所有q≤0.050）、2个及3个及以上CVD风险因素集群组（所有P≤0.041）中发现了与γ-谷氨酰循环相关的代谢物，包括甘氨酸、组氨酸、丝氨酸、谷氨酰胺、蛋氨酸、胱氨酸和焦谷氨酸。在低社会经济地位组、1个及3个及以上CVD风险因素集群组（q/P≤0.050）（β-氧化）中发现了与能量代谢相关的代谢物，包括乙酰肉碱（较低水平）、己酰肉碱和癸酰肉碱。除上述氨基酸外，在高血糖、低社会经济地位组、2个及3个及以上CVD风险因素集群组（所有q/P≤0.047）（糖酵解）中发现了丙氨酸和苏氨酸。在肥胖、高血糖组（所有q≤0.049）以及3个及以上CVD风险因素集群组（所有P≤0.041）（肌酸途径）中发现了肌酸。
暴露于CVD风险因素与上述途径中的代谢失调相关，这可能在CVD发生之前出现。
