异黄酮生物标志物与成年人动脉粥样硬化进展呈负相关：一项前瞻性研究。

Isoflavone biomarkers are inversely associated with atherosclerosis progression in adults: a prospective study.

机构信息

Department of Epidemiology, Guangdong Provincial Key Laboratory of Food, Nutrition, and Health, School of Public Health, Sun Yat-sen University, Guangzhou, China.

Department of Pediatrics,The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.

出版信息

Am J Clin Nutr. 2021 Jul 1;114(1):203-213. doi: 10.1093/ajcn/nqab008.

DOI:10.1093/ajcn/nqab008

PMID:33709111

Abstract

BACKGROUND

Many studies have examined associations between dietary isoflavones and atherosclerosis, but few used objective biomarkers.

OBJECTIVES

We examined the associations of isoflavone biomarkers (primary analyses) and equol production (secondary analyses) with the progression of carotid intima-media thickness (cIMT), and whether inflammation, systolic blood pressure (SBP), blood lipids, and sex hormone-binding globulin (SHBG) mediated these associations, in Chinese adults.

METHODS

This 8.8-y prospective study included 2572 subjects (40-75 y old) from the GNHS (Guangzhou Nutrition and Health Study; 2008-2019). The concentrations of daidzein, genistein, and equol were assayed by an HPLC-tandem MS in serum (n = 2572) at baseline and in urine (n = 2220) at 3-y intervals. The cIMT of the common carotid artery (CCA) and bifurcation segment were measured by B-mode ultrasound every 3 y, and the progressions of cIMT ( ∆cIMT) were estimated using the regression method.

RESULTS

Multivariable linear mixed-effects models (LMEMs) and ANCOVA revealed that subjects with higher serum isoflavones tended to have lower increases of CCA-cIMT. The mean ± SEM differences in 8.8-y ∆CCA-cIMT between extreme tertiles of serum isoflavones were -17.1 ± 8.4, -20.6 ± 8.3, and -23.3 ± 10.4 μm for daidzein, total isoflavone, and equol (P-trends < 0.05), respectively. LMEMs showed that the estimated yearly changes (95% CIs) (μm/y) in CCA-IMT were -2.0 (-3.8, -0.3), -1.9 (-3.6, -0.1), and -2.1 (-3.8, -0.3) in the highest (compared with the lowest) tertile of daidzein, genistein, and total isoflavones, respectively (P-interaction < 0.05). Path analyses indicated that the serum equol-atherosclerosis association was mediated by increased SHBG and decreased SBP. Similar beneficial associations were observed in the secondary analyses.

CONCLUSIONS

Serum isoflavones and equol exposure were associated with reduced cIMT progression, mediated by SHBG and SBP.

摘要

背景

许多研究都探讨了膳食异黄酮与动脉粥样硬化之间的关系，但很少有研究使用客观的生物标志物。

目的

我们检测了异黄酮生物标志物（主要分析）和马尿酸生成（次要分析）与颈动脉内膜中层厚度（cIMT）进展之间的关系，以及炎症、收缩压（SBP）、血脂和性激素结合球蛋白（SHBG）是否在中国人中介导了这些关联。

方法

本项为期 8.8 年的前瞻性研究纳入了来自 GNHS（广州营养与健康研究；2008-2019 年）的 2572 名 40-75 岁的受试者（n=2572）。基线时采用 HPLC-MS/MS 法检测血清中大豆苷元、染料木黄酮和马尿酸的浓度，间隔 3 年检测尿中大豆苷元、染料木黄酮和马尿酸的浓度。每隔 3 年使用 B 型超声检测颈总动脉（CCA）和分叉段的 cIMT，采用回归法估计 cIMT 的进展（∆cIMT）。

结果

多变量线性混合效应模型（LMEM）和方差分析显示，血清异黄酮水平较高的受试者，CCA-cIMT 的增加幅度往往较低。血清异黄酮水平处于极端三分位的受试者，8.8 年 CCA-cIMT 的平均差异分别为-17.1±8.4、-20.6±8.3 和-23.3±10.4μm，差异有统计学意义（P趋势<0.05）。LMEM 显示，CCA-IMT 的年估计变化（95%CI）（μm/y）在大豆苷元、总异黄酮和马尿酸最高（与最低）三分位组分别为-2.0（-3.8，-0.3）、-1.9（-3.6，-0.1）和-2.1（-3.8，-0.3）（P 交互<0.05）。路径分析表明，血清马尿酸与动脉粥样硬化的关系是通过增加 SHBG 和降低 SBP 来介导的。在次要分析中也观察到了类似的有益关联。