Circulating levels of cell adhesion molecules and risk of cardiovascular events in obstructive sleep apnea

Bernardo U Peres,Andrew J Sandford,Ismail Laher,Fernanda Almeida,Stephan F Van Eeden,Rachel Jen,A J Hirsch Allen,Patrick Daniele,Karin H Humphries,Najib T Ayas,Carolyn Taylor,James Andrew Rowley

doi:10.1371/journal.pone.0255306

Abstract

BackgroundObstructive sleep apnea (OSA) patients are at increased risk of cardiovascular disease (CVD). Cell adhesion molecules (CAM) are increased in OSA and CAM are also implicated in the development of CVD.Research questionDo CAM (ICAM-1, VCAM-1 and E-selectin) have prognostic value in identifying risk of cardiovascular events in OSA?Study design and methodsPatients with suspected OSA referred for a polysomnogram provided a fasting blood sample. Plasma levels of ICAM-1, VCAM-1 and E-selectin were determined by multiplex Luminex Assay (Milliporesigma ON, Canada). Cardiovascular events were determined by deterministic linkage to provincial health databases.Results418 patients were included in the analysis. Mostly male (68.2%), mean age of 50.7 yrs, median AHI 16.5 events/hour, and mean BMI of 31.7 kg/m2. 36 cardiovascular events occurred in 8-yrs of follow up. Higher levels of ICAM-1 were associated with developing CVD (HR = 3.65 95% CI 1.40–9.53, 2nd and 3rd tertiles vs. 1st tertile), including in patients with OSA (HR = 3.1 95% CI 1.16–8.25). E-selectin was significantly associated with cardiovascular events in patients with moderate to severe OSA (HR = 3.31 95% CI 0.94–11.72, 2nd and 3rd tertiles vs. 1st tertile) but not in patients without moderate to severe OSA (HR = 0.67 95% CI 0.19–2.38), p-value for interaction = 0.07.InterpretationIn a suspected OSA cohort, patients with higher levels of ICAM-1 (>816 ng/ml) were significantly more likely to experience a cardiovascular event within 8 years after PSG. In moderate to severe OSA patients, a higher E-selectin (>36.4 ng/ml) was significantly associated with cardiovascular events.

Highlights

Obstructive Sleep Apnea (OSA) is the most common respiratory sleep disorder with close to half a billion people having moderate to severe disease globally [1]
Higher levels of intercellular adhesion molecule-1 (ICAM-1) were associated with developing cardiovascular disease (CVD) (HR = 3.65 95% Confidence Intervals (CI) 1.40–9.53, 2nd and 3rd tertiles vs. 1st tertile), including in patients with OSA (HR = 3.1 95% CI 1.16–8.25)
Suspected OSA patients with elevated ICAM-1 levels are significantly more likely to experience a cardiovascular event in 8 years of follow up

Summary

Introduction

Obstructive Sleep Apnea (OSA) is the most common respiratory sleep disorder with close to half a billion people having moderate to severe disease globally [1]. OSA is characterized by intermittent hypoxia and oxidative stress, which in turn activates systemic inflammation [10]; both animals exposed to intermittent hypoxia and patients with OSA have increased levels of inflammatory markers including C-reactive protein (CRP), interleukins, and cellular adhesion molecules [11,12,13]. This inflammation is likely a contributing factor to premature CVD in OSA patients. Do CAM (ICAM-1, VCAM-1 and E-selectin) have prognostic value in identifying risk of cardiovascular events in OSA?

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Conclusion