The Clinical Role of Angiopoietin-Like Protein 3 in Evaluating Coronary Artery Disease in Patients with Obstructive Sleep Apnea

Juan Li,Ming Zhang,Yongxiang Wei,Yanwen Qin,Yunhui Du,Chaowei Hu,Huahui Yu,Xiaolu Jiao,Yunyun Yang

doi:10.1007/s10557-020-06991-1

Juan Li, Ming Zhang + Show 7 more

Open Access

https://doi.org/10.1007/s10557-020-06991-1

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Abstract

PurposeHyperlipidemia is the most important early atherosclerosis and coronary artery disease (CAD) indicator. Angiopoietin-like proteins (ANGPTLs) 3, 4, and 8 are lipid dysfunction markers that may be linked to CAD. We investigated whether these circulating ANGPTLs are associated with CAD in patients with obstructive sleep apnea (OSA).MethodsA total of 327 individuals participated in this study: 221 patients with OSA and CAD, 50 patients with OSA alone, and 56 controls. The Gensini Score was used to assess the severity of CAD. Serum ANGPTL3, ANGPTL4, and ANGPTL8 were measured in all subjects using Human Magnetic Luminex Screening Assay. The independent association between levels of ANGPTLs and CAD was evaluated by multivariate regression analysis.ResultsSerum ANGPTL3 levels were significantly higher in patients suffering from OSA and CAD compared with patients having OSA alone (46.97 ± 13.89 vs 38.25 ± 15.94 ng/ml, P < 0.001). Univariate analysis demonstrated that ANGPTL3 was a risk factor for CAD (OR = 1.72/10 ng ANGPTL3, 95% CI, 1.29–2.28, P < 0.001). In addition, multivariate analysis revealed that ANGPTL3 was independently associated with the presence of CAD (OR = 1.74/10 ng ANGPTL3, 95% CI, 1.29–2.35, P < 0.001) even after adjusting for cofounding factors. Furthermore, circulating ANGPTL3 levels were positively associated with triglyceride (r = 0.16, P = 0.01) and total cholesterol (r = 0.14, P = 0.02) levels, while ANGPTL3 levels had no significant correlation with the severity of CAD. No significant associations were found between the levels of ANGPTL4 and ANGPTL8 and CAD even after adjusting for established risk factors.ConclusionElevated levels of ANGPTL3 were independently associated with a higher likelihood of CAD in patients with OSA. It may be a novel biomarker for OSA patients at high risk of developing cardiovascular diseases.

Highlights

Obstructive sleep apnea (OSA) is a chronic somnipathy mainly manifesting as repeated apnea, hypopnea, arousal, intermittent hypoxemia (IH), and hypercapnia during sleep [1, 2]
Univariate analysis demonstrated that ANGPTL3 was a risk factor for coronary artery disease (CAD) (OR = 1.72/10 ng ANGPTL3, 95% CI, 1.29–2.28; P < 0.001)
After the adjustment for confounding factors, patients with a higher circulating ANGPTL3 level had a higher OR for CAD (OR = 1.74/10 ng ANGPTL3, 95% CI, 1.29–2.35; P < 0.001), indicating that ANGPTL3 level is an independent risk factor for CAD

Summary

Introduction

Obstructive sleep apnea (OSA) is a chronic somnipathy mainly manifesting as repeated apnea, hypopnea, arousal, intermittent hypoxemia (IH), and hypercapnia during sleep [1, 2]. OSA is identified as an independent risk factor for cardiovascular events, including coronary artery disease (CAD), hypertension, strokes, and atherosclerosis [3]. The incidence of CAD in OSA patients is about 20 to 30%, and the incidence of OSA in patients with acute coronary syndrome is as high as 69% [4]. Because cardiovascular disease is among the major causes of death worldwide [5], it is necessary to assess cardiovascular comorbidities in patients with OSA. Angiopoietin-like proteins (ANGPTLs) comprise a family of secreted proteins, eight members that have a variety of metabolic functions such as insulin resistance, dyslipidemia, Cardiovasc Drugs Ther (2020) 34:773–780 and oxidative stress [6]. ANGPTL3, ANGPTL4, and ANGPTL8 are associated with the regulation of lipid metabolism, which is essential for the development of CAD [7]

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