Computational Medicine, Faculty of Medicine, University of Oulu and Biocenter Oulu, Oulu, Finland.
NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
Clin Chem. 2019 Aug;65(8):1042-1050. doi: 10.1373/clinchem.2018.299222. Epub 2019 Apr 17.
HDL-mediated cholesterol efflux capacity (HDL-CEC) is a functional attribute that may have a protective role in atherogenesis. However, the estimation of HDL-CEC is based on in vitro cell assays that are laborious and hamper large-scale phenotyping.
Here, we present a cost-effective high-throughput nuclear magnetic resonance (NMR) spectroscopy method to estimate HDL-CEC directly from serum. We applied the new method in a population-based study of 7603 individuals including 574 who developed incident coronary heart disease (CHD) during 15 years of follow-up, making this the largest quantitative study for HDL-CEC.
As estimated by NMR-spectroscopy, a 1-SD higher HDL-CEC was associated with a lower risk of incident CHD (hazards ratio, 0.86; 95%CI, 0.79-0.93, adjusted for traditional risk factors and HDL-C). These findings are consistent with published associations based on in vitro cell assays.
These corroborative large-scale findings provide further support for a potential protective role of HDL-CEC in CHD and substantiate this new method and its future applications.
高密度脂蛋白(HDL)介导的胆固醇外排能力(HDL-CEC)是一种功能属性,可能在动脉粥样硬化形成中具有保护作用。然而,HDL-CEC 的估计基于体外细胞检测,这些检测既繁琐又妨碍了大规模表型分析。
在这里,我们提出了一种经济高效的高通量核磁共振(NMR)光谱法,可直接从血清中估计 HDL-CEC。我们将新方法应用于一项基于人群的研究,该研究纳入了 7603 名个体,其中 574 名在 15 年的随访中发生了冠心病(CHD)。这是对 HDL-CEC 进行的最大规模的定量研究。
通过 NMR 光谱法估计,HDL-CEC 每增加 1 个标准差,冠心病的发病风险就会降低(风险比为 0.86;95%CI,0.79-0.93,经传统危险因素和 HDL-C 校正)。这些发现与基于体外细胞检测的已发表关联一致。
这些大规模的相互印证的发现为 HDL-CEC 在冠心病中的潜在保护作用提供了进一步的支持,并证实了这种新方法及其未来的应用。