ANGPTL3 and Cardiovascular Outcomes in Patients With Acute Coronary Syndrome and Obstructive Sleep Apnea

Qianwen Lv, Xiaolu Jiao, Huahui Yu, Qiuju Sun, Fan Li, Yu Wang, Haili Sun, Zhiyong Du, Linyi Li, Chaowei Hu, Ming Zhang, Shaoping Nie, Yanwen Qin, Qianwen Lv, Xiaolu Jiao, Huahui Yu, Qiuju Sun, Fan Li, Yu Wang, Haili Sun, Zhiyong Du, Linyi Li, Chaowei Hu, Ming Zhang, Shaoping Nie, Yanwen Qin

Abstract

Background The aim of this prospective study was to determine the impact of elevated ANGPTL3 (angiopoietin-like protein 3) on cardiovascular events (CVEs) following acute coronary syndrome (ACS) in patients with or without obstructive sleep apnea (OSA). Methods and Results A total of 1174 patients with ACS underwent successful percutaneous coronary intervention were included in this prospective cohort study (NCT03362385). Patients were categorized according to the apnea-hypopnea index (≥15 events/h, OSA) and further classified by ANGPTL3 levels. We analyzed the incidence of CVEs in patients with ACS according to the status of OSA and ANGPTL3. During a median of 3.1 years of follow-up, 217 (18.48%) CVEs occurred. The patients with ACS with OSA had higher ANGPTL3 levels than those without OSA (30.4 [20.9-43.2] versus 27.80 [19.1-41.5] ng/mL; P<0.001). In all patients with ACS, 29≤ANGPTL3<42 mg/dL and ANGPTL3≥42 mg/dL were associated with an increased risk of CVEs with hazard ratios (HRs) of 1.555 (95% CI, 1.010-2.498) and 2.489 (95% CI 1.613-3.840), respectively. When the status of OSA or not was incorporated in stratifying factors, 29≤ANGPTL3<42 mg/dL and ANGPTL3≥42 mg/dL were associated with a significantly higher risk of CVEs in patients with ACS with OSA (HR, 1.916 [95% CI, 1.019-3.601] and HR, 2.692 [95% CI, 1.379-4.503]) but not without OSA. Moreover, adding ANGPTL3 to the Cox model increased C-statistic values by 0.035 and 0.029 in the OSA group and all patients with ACS, respectively, but was not statistically improved in patients with ACS without OSA. Conclusions In conclusion, our study demonstrates a predictive impact of plasma ANGPTL3 on cardiovascular risk in patients with ACS, especially in patients with ACS with OSA. It might be of clinical value in refining risk stratification and tailoring treatment of patients with ACS and OSA. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03362385.

Keywords: acute coronary syndrome; angiopoietin‐like protein 3; cardiovascular outcome; obstructive sleep apnea; prediction.

Figures

Figure 1. Flowchart of the study.
Figure 1. Flowchart of the study.
ACS indicates acute coronary syndrome; AHI, apnea–hypopnea index; CPAP, continuous positive airway pressure; OSA, obstructive sleep apnea; and PCI, percutaneous coronary intervention.
Figure 2. Kaplan–Meier analysis for cardiovascular events…
Figure 2. Kaplan–Meier analysis for cardiovascular events according to OSA status (A) and different ANGPTL3 levels (B) (with 95% confidence limits, shaded area).
ANGPTL3 indicates angiopoietin‐like protein 3; OSA, obstructive sleep apnea; Q1, quartile 1 (ANGPTL3

Figure 3. Kaplan–Meier analysis for cardiovascular events…

Figure 3. Kaplan–Meier analysis for cardiovascular events according to different ANGPTL3 levels in patients with…

Figure 3. Kaplan–Meier analysis for cardiovascular events according to different ANGPTL3 levels in patients with ACS with OSA and without OSA.
ANGPTL3 indicates angiopoietin‐like protein 3; OSA, obstructive sleep apnea; Q1, quartile 1 (ANGPTL3
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Figure 3. Kaplan–Meier analysis for cardiovascular events…
Figure 3. Kaplan–Meier analysis for cardiovascular events according to different ANGPTL3 levels in patients with ACS with OSA and without OSA.
ANGPTL3 indicates angiopoietin‐like protein 3; OSA, obstructive sleep apnea; Q1, quartile 1 (ANGPTL3

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