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通过替代载脂蛋白 1 活性来评估冠心病风险:基于高密度脂蛋白功能的新型代谢相关心血管生物标志物。

Improved risk assessment of coronary artery disease by substituting paraoxonase 1 activity for HDL-C: Novel cardiometabolic biomarkers based on HDL functionality.

机构信息

Molecular and Cell Biology Research Center, Mazandaran University of Medical Sciences, Sari, Iran; Department of Clinical Biochemistry and Genetics, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

Department of Clinical Biochemistry and Genetics, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

出版信息

Nutr Metab Cardiovasc Dis. 2021 Apr 9;31(4):1166-1176. doi: 10.1016/j.numecd.2020.12.026. Epub 2021 Jan 1.

DOI:10.1016/j.numecd.2020.12.026
PMID:33579580
Abstract

BACKGROUND AND AIMS

Developing laboratory assays to evaluate HDL functions and improve cardiovascular disease (CVD) risk assessment has recently emerged as a challenge. The present study was conducted to help predict the risk of coronary artery disease (CAD) by investigating new cardiometabolic risk factors based on substituting paraoxonase 1 (PON1) as a critical enzyme in the functionality of HDL for that of HDL-C.

METHODS AND RESULTS

The present study recruited 274 subjects undergoing diagnostic coronary angiography, 92 without significant CAD (non-CAD), and 182 with a severe CAD. The diagnostic accuracy of the new biomarkers in non-CAD versus multi-vessel disease was obtained in descending order of AUC as 0.72 (P < 0.001) for log (TG/PON1), 0.70 (P < 0.001) for nonHDL-C/PON1, and 0.67 (P < 0.001) for LDL-C/PON1. After performing a multivariate adjustment for age, gender, BMI, statin therapy, and diabetes mellitus, the increased odds of CAD remained significant for the new cardiometabolic ratios as independent variables [adjusted OR = 1.47 (1.15-1.88), p = 0.002 for LDL-C/PON1; adjusted OR = 2.15 (1.41-3.5), p = 0.009 for nonHDL-C/PON1; adjusted OR = 5.03 (2.14-13.02), p = 0.004 for log (TG/PON1)]. CAD was diagnosed with an optimal discriminating cutoff of 1.84 for LDL-C/PON1, 2.8 for nonHDL-C/PON1, and 0.48 for log (TG/PON1).

CONCLUSIONS

To improve CAD's risk assessment, the PON1 activity was proposed as an alternative to HDL-C in the commonly used atherogenic lipid ratios. Substituting the PON1 activity for the HDL-C concentration can provide an index of the HDL activity. The present study sought to exploit the lipoprotein-related risk factors of CAD from a more effective perspective.

摘要

背景和目的

开发评估高密度脂蛋白 (HDL) 功能的实验室检测方法以改善心血管疾病 (CVD) 风险评估,这是当前面临的一项挑战。本研究旨在通过研究新的代谢心血管危险因素,用 PON1(一种关键酶)替代 HDL-C 来评估 HDL 的功能,从而帮助预测冠心病 (CAD) 的风险。

方法和结果

本研究纳入了 274 名接受诊断性冠状动脉造影的患者,其中 92 名无明显 CAD(非 CAD),182 名严重 CAD。新生物标志物在非 CAD 与多血管疾病中的诊断准确性,按 AUC 降序排列,log(TG/PON1)为 0.72(P<0.001),非 HDL-C/PON1 为 0.70(P<0.001),LDL-C/PON1 为 0.67(P<0.001)。对年龄、性别、BMI、他汀类药物治疗和糖尿病进行多变量调整后,新的代谢心血管比值作为独立变量,CAD 的发生几率仍然显著增加[调整后的 OR=1.47(1.15-1.88),p=0.002 对于 LDL-C/PON1;调整后的 OR=2.15(1.41-3.5),p=0.009 对于非 HDL-C/PON1;调整后的 OR=5.03(2.14-13.02),p=0.004 对于 log(TG/PON1)]。CAD 的诊断采用 LDL-C/PON1 的最佳截断值为 1.84,非 HDL-C/PON1 为 2.8,log(TG/PON1)为 0.48。

结论

为了改善 CAD 的风险评估,本研究提出用 PON1 活性替代常用的致动脉粥样硬化脂质比值中的 HDL-C。用 PON1 活性替代 HDL-C 浓度可以提供 HDL 活性的指标。本研究旨在从更有效的角度探讨与脂蛋白相关的 CAD 危险因素。

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