From the Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Medical Ethics and History of Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Menopause. 2022 Sep 1;29(9):1062-1070. doi: 10.1097/GME.0000000000002016. Epub 2022 Aug 16.
Postmenopausal women are at increased risk of developing coronary artery disease (CAD). Metabolomic approaches aim at discovering more helpful biomarkers of CAD to reduce the disease burden in the future. Here, we intend to find potential blood biomarkers, amino acids, and acylcarnitines in postmenopausal women with different severity of CAD by using high-throughput methods.
This cross-sectional study was performed on postmenopausal women ( n = 183) who underwent coronary CT scans. Coronary artery calcium scoring (CACS) was assessed to detect plaque burden and degree of coronary artery obstruction. The participants were divided into three groups based on the score as follows (i) "low CACS" ( n = 96); a score of 0 to 10, (ii) "medium CACS" ( n = 35); a score between 11 and 100 and (iii) "high CACS" ( n = 52); a score greater than 100. Metabolites, including amino acids and acylcarnitines, were quantified using a targeted mass spectrometry method in serum samples. The association between metabolites and disease status was evaluated using univariate and multivariate regression analyses with adjustment for confounding factors. Factor analysis was used to deal with multiple comparisons.
Metabolites, including proline, glutamic acid, and phenylalanine, were significantly lower in the high CACS group than the low CACS one. Also, a lower level of lysine and phenylalanine in high CACS compared with medium one was observed. Concerning acylcarnitines, it was found that C4 and C8:1 significantly were higher in women with high CACS. The logistic regression analysis revealed that the circulating levels of these metabolites (except C4) were associated with the presence of coronary artery calcification independently of age, body mass index, and time of menopause. Also, the amino acids were associated independently of medication and diabetes.
The present study indicated that circulating levels of amino acids and acylcarnitines profile in postmenopausal women are partly associated with the severity of CAD in these participants.
绝经后女性患冠状动脉疾病(CAD)的风险增加。代谢组学方法旨在发现更多有助于 CAD 的生物标志物,以减轻未来的疾病负担。在这里,我们旨在通过高通量方法发现绝经后女性不同 CAD 严重程度的潜在血液生物标志物、氨基酸和酰基辅酶 A。
这项横断面研究纳入了 183 名接受冠状动脉 CT 扫描的绝经后女性。通过冠状动脉钙评分(CACS)评估斑块负担和冠状动脉阻塞程度。根据评分将参与者分为三组:(i)“低 CACS”(n = 96),评分 0-10;(ii)“中 CACS”(n = 35),评分 11-100;(iii)“高 CACS”(n = 52),评分大于 100。使用靶向质谱法在血清样本中定量测定代谢物,包括氨基酸和酰基辅酶 A。使用单变量和多变量回归分析,调整混杂因素后,评估代谢物与疾病状态之间的关系。采用因子分析处理多重比较。
与低 CACS 组相比,高 CACS 组的脯氨酸、谷氨酸和苯丙氨酸等代谢物明显降低。此外,与中 CACS 组相比,高 CACS 组的赖氨酸和苯丙氨酸水平也较低。关于酰基辅酶 A,发现 C4 和 C8:1 在 CACS 较高的女性中明显升高。逻辑回归分析显示,除 C4 外,这些代谢物(除外 C4)的循环水平与冠状动脉钙化的存在独立于年龄、体重指数和绝经时间相关。此外,这些氨基酸也与药物和糖尿病无关。
本研究表明,绝经后女性的循环氨基酸和酰基辅酶 A谱与这些参与者的 CAD 严重程度部分相关。