Ceramides: a potential cardiovascular biomarker in young adult childhood cancer survivors?

European heart journal open Pub Date : 2024-04-04 eCollection Date: 2024-03-01 DOI:10.1093/ehjopen/oeae026
Olof Broberg, Constance G Weismann, Ingrid Øra, Thomas Wiebe, Reijo Laaksonen, Petru Liuba
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Abstract

Aims: The aim of this study was to investigate circulating ceramides involved in cardiovascular disease (CVD) in young adult childhood cancer survivors (CCS) and their correlations to previously reported adverse cardiovascular changes in this cohort.

Methods and results: Fifty-seven CCS and 53 healthy controls (age 20-30 years) were studied. Plasma long-chain ceramides, known to be cardiotoxic (C16:0, C18:0, C24:0, and C24:1), were analysed by mass spectrometry. The coronary event risk test 2 (CERT2) score was calculated from the ceramide data. Cardiac and carotid artery ultrasound data and lipid data available from previous studies of this cohort were used to study partial correlations with ceramide and CERT2 score data. All four analysed ceramides were elevated in CCS compared with controls (P ≤ 0.012). The greatest difference was noted for C18:0, which was 33% higher in CCS compared with controls adjusted for sex, age, and body mass index (BMI) (P < 0.001). The CERT2 score was higher in CCS compared with controls (P < 0.001). In the CCS group, 35% had a high to very high CERT2 score (7-12) when compared with 9% in the control group (P < 0.001). The CCS subgroup with a CERT2 score ≥ 7 had higher heart rate, systolic blood pressure, and higher levels of apolipoprotein B compared with CCS with a CERT2 score < 6 (P ≤ 0.011). When adjusted for age, sex, and BMI, CERT2 score was significantly correlated with arterial stiffness, growth hormone, and cranial radiotherapy (P < 0.044).

Conclusion: Ceramides could be important biomarkers in understanding the pathophysiology of CVD and in predicting CVD disease risk in young adult CCS.

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神经酰胺:年轻的成年儿童癌症幸存者的潜在心血管生物标志物?
目的:本研究旨在调查年轻的成年儿童癌症幸存者(CCS)中与心血管疾病(CVD)有关的循环神经酰胺及其与之前报道的该人群心血管不良变化的相关性:对 57 名儿童癌症幸存者和 53 名健康对照者(20-30 岁)进行了研究。通过质谱分析了血浆中已知具有心脏毒性的长链神经酰胺(C16:0、C18:0、C24:0 和 C24:1)。根据神经酰胺数据计算出冠状动脉事件风险测试 2 (CERT2) 分数。心脏和颈动脉超声波数据以及该队列先前研究中的血脂数据被用来研究神经酰胺和CERT2评分数据的部分相关性。与对照组相比,CCS 中所有四种被分析的神经酰胺都升高了(P ≤ 0.012)。C18:0的差异最大,与对照组相比,经性别、年龄和体重指数(BMI)调整后,CCS的C18:0高出33%(P < 0.001)。与对照组相比,CCS 的 CERT2 得分更高(P < 0.001)。与对照组的 9% 相比,CCS 组中有 35% 的人的 CERT2 得分为高到非常高(7-12)(P < 0.001)。与 CERT2 得分小于 6 的 CCS 相比,CERT2 得分≥ 7 的 CCS 亚组具有更高的心率、收缩压和脂蛋白 B 水平(P ≤ 0.011)。在对年龄、性别和体重指数进行调整后,CERT2评分与动脉僵化、生长激素和头颅放疗有显著相关性(P < 0.044):神经酰胺可能是了解心血管疾病的病理生理学和预测年轻成人心血管疾病风险的重要生物标志物。
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