Leukotriene B₄: early mediator of atherosclerosis in obstructive sleep apnoea?

¹ INSERM, ERI17, Grenoble, F-38042 France; Université Grenoble 1, Faculté de Médecine, IFR1, Grenoble, F-38042 France; and CHU, Hôpital A. Michallon, Laboratoire de pharmacologie, BP217, Grenoble, F-38043 France
² INSERM, ERI17, Grenoble, F-38042 France; Université Grenoble 1, Faculté de Médecine, IFR1, Grenoble, F-38042 France; and CHU, Hôpital A. Michallon, Laboratoire EFCR, BP217, Grenoble, F-38043 France
³ Université Grenoble 1, Faculté de Médecine, IFR1, Grenoble, F-38042 France; CHU, Hôpital A. Michallon, Clinique de cardiologie, BP217, Grenoble, F-38043 France; and INSERM, U8777, Grenoble, F-38042 France
⁴ CHU, Hôpital A. Michallon, Laboratoire de pharmacologie, BP217, Grenoble, F-38043 France

^* To whom correspondence should be addressed. E-mail: FStanke{at}chu-grenoble.fr.

	Abstract

Severity of oxygen desaturation is predictive of early atherosclerosis in obstructive sleep apnoea (OSA). Leukotrienes B₄ (LTB₄) are lipid mediators involved in atherogenesis.

In 40 non obese OSA patients free of cardiovascular history and in 20 healthy volunteers, we evaluated 1/ the LTB₄ production by polymorphonuclear leukocytes (PMNs) stimulated by A23187, 2/ the relationships between LTB₄ production and both OSA severity and infra-clinical atherosclerosis markers. Continuous positive airway pressure (CPAP) effect on LTB₄ production was also studied.

Overnight sleep study was followed by a first-morning blood sample. Isolated PMNs were stimulated by A23187 in order to induce LTB₄ production that was measured by liquid chromatography-tandem mass spectrometry. Carotid intima-media thickness (IMT) and luminal diameter (LD) were measured in subset groups of 28 OSA and 11 controls.

LTB₄ production was increased (p<0.05) in OSA compared to controls. LTB₄ values were correlated with the mean SaO₂ (r=-0.53, p<0.001) and minimal SaO₂ (r=-0.51, p<0.001). LTB₄ production was correlated to LD data in patients with mean SaO₂94% but not to IMT. Lastly, CPAP significantly reduced LTB₄ production by 50%.

LTB₄ production is increased in OSA in relation to oxygen desaturation. LTB₄ could promote early vascular remodelling in moderate to severe hypoxic OSA patients.