慢性肾脏病患者心血管疾病和动脉钙化的代谢特征。
The metabolic signature of cardiovascular disease and arterial calcification in patients with chronic kidney disease.
机构信息
Department of Nephrology, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen, Denmark.
Department of Clinical Biochemistry, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen, Denmark; Department of Biomedical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen, Denmark.
出版信息
Atherosclerosis. 2022 Jun;350:109-118. doi: 10.1016/j.atherosclerosis.2022.03.019. Epub 2022 Mar 21.
BACKGROUND AND AIMS
The relationship between chronic kidney disease (CKD) and cardiovascular events is well-established. Clinically recognised risk factors of cardiovascular disease cannot fully explain this association. The objective of the present cross-sectional study was to investigate associations between serum metabolites and prevalent cardiovascular disease, as well as subclinical cardiovascular disease measured as coronary artery calcium score (CACS) in patients with CKD.
METHODS
More than 200 preselected metabolites were quantified using nuclear magnetic resonance spectroscopy in 725 patients and 174 controls from the Copenhagen CKD Cohort. CACS was determined by computed tomography.
RESULTS
Mean age of patients was 57.8 years, and 444 (61.3%) were men. Most of patients had hypercholesterolemia, and 133 (18.3%) had type 2 diabetes. Overall, 85 metabolites were significantly associated with prevalent cardiovascular disease in a model adjusted for eGFR, age, and sex, as well as Bonferroni correction for multiple testing (p < 0.001). After further adjusting for diabetes, BMI, smoking, and cholesterol-lowering medication, the significance was lost for all but six metabolites (concentration of ApoA-1, cholesterol in total HDL and HDL2, total lipids and phospholipids in large HDL particles, and the ratio of phospholipids to total lipids in smaller VLDL particles). Of the 85 metabolites associated with prevalent cardiovascular disease, 71 were also associated with CACS in a similar pattern. Yet, in the model adjusted for all seven cardiovascular risk factors, only serum glucose levels and the ratio of triglycerides to total lipids in larger LDL particles remained significant.
CONCLUSIONS
In patients with CKD, associations with prevalent cardiovascular disease were mainly found for HDL-related metabolites, while CACS was associated with glucose levels and increased triglycerides to total lipids ratio in LDL particles.
背景与目的
慢性肾脏病（CKD）与心血管事件之间的关系已得到充分证实。临床公认的心血管疾病危险因素并不能完全解释这种关联。本横断面研究的目的是探讨血清代谢物与 CKD 患者中已确诊的心血管疾病以及亚临床心血管疾病（以冠状动脉钙评分（CACS）衡量）之间的关系。
方法
在哥本哈根 CKD 队列中，对 725 名患者和 174 名对照者进行了超过 200 种预先选择的代谢物的定量检测，采用核磁共振光谱法。通过计算机断层扫描确定 CACS。
结果
患者的平均年龄为 57.8 岁，其中 444 名（61.3%）为男性。大多数患者患有高胆固醇血症，133 名（18.3%）患有 2 型糖尿病。总体而言，在调整了 eGFR、年龄和性别以及多重测试的 Bonferroni 校正后，有 85 种代谢物与已确诊的心血管疾病显著相关（p<0.001）。进一步调整糖尿病、BMI、吸烟和降脂药物后，除 6 种代谢物（载脂蛋白 A-1 浓度、总 HDL 和 HDL2 中的胆固醇、大 HDL 颗粒中的总脂质和磷脂、较小 VLDL 颗粒中磷脂与总脂质的比值）外，其他代谢物的相关性均消失。与已确诊的心血管疾病相关的 85 种代谢物中，有 71 种也与 CACS 呈相似的相关性。然而，在调整了所有七种心血管危险因素的模型中，只有血清葡萄糖水平和较大 LDL 颗粒中甘油三酯与总脂质的比值仍然具有显著相关性。
结论
在 CKD 患者中，与已确诊的心血管疾病相关的主要是与 HDL 相关的代谢物，而 CACS 与葡萄糖水平和 LDL 颗粒中甘油三酯与总脂质的比值升高相关。
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