It may be another link between OSA and cardiovascular disease. Dysfunctional endothelium is characterised by an imbalance in the production of vasoactive hormones, increase of inflammatory mediators to endothelial cells and hypercoagulability, this is also a known risk factor for cardiovascular events.
Frequently Asked Questions
OSA is associated with obesity, hypertension and metabolic deregulation, which may contribute to adverse effects on endothelium. Endothelial injury results in a change of endothelial hormones which are responsible for maintaining vascular tone and preventing abnormal cell proliferation. The treatment of obstructive sleep apnea with continuous positive airway pressure (CPAP) therapy has been shown to improve endothelial function in the systemic circulation. Book a consultation with our Health Renewal doctors for High Colesterol.
OSA is a condition of increased oxidative stress. Enhanced free radical production can also result from hypoxia-reoxygenation or from sympathetic activation. Oxidant stress can, lead to endothelial injury and consequently, atherosclerosis.
OSA is associated with increased levels of inflammatory mediators as well as up regulation of the expression of adhesion molecules in the vascular endothelium. The migration of leukocytes underneath the endothelium following adherence can lead to formation of early atherosclerotic lesions. CPAP therapy for OSA patients decrease monocyte adherence to human endothelial cells. C-reactive protein (CRP), a marker and a contributor to the vascular inflammatory process, is also increased in patients with OSA, and the levels decrease with CPAP therapy.
Obesity is an important risk factor for OSA; OSA as it may be associated with an increased propensity to gain weight. Leptin levels are higher in patients with OSA and decline with CPAP therapy. Leptin is associated with endothelial dysfunction and cardiovascular disorders. Leptin also induces ROS production in human endothelial cells that may be important in atherogenesis.
The factors secreted by the normal endothelium, which include nitric oxide and prostacyclin which decrease platelet aggregation, thrombomodulin that promote activated protein C generation and heparin sulfates which are cofactors of antithrombin III, and help maintain the normal fluidity of the blood. Endothelial dysfunction can lead to homeostasis alterations resulting in a pro-coagulant and atherogenic state. Patients with OSA have shown to have increased platelet aggregation.
CPAP treatment is associated with a decline in fibrinogen levels and PAI-1 activity. Elevated levels of soluble P-selectin are associated with an increased risk of future cardiovascular events.
P-selectin is increased in patients with OSA and the levels correlate with severity of OSA.
A genetic predisposition may have an increased risk for development of endothelial dysfunction, in some patients with OSA. The TNF-α gene responsible for overproduction of TNF-α, is more prevalent in subjects with OSA than normal controls, overproduction can result in endothelial dysfunction. ACE is a primary enzyme responsible for conversion of angiotensin I to angiotensin II, which is increased in OSA and can jeopardize endothelial function. Angiotensin II can lead to over expression of VEGF mRNA through AT-1 receptors, resulting in overproduction of vascular endothelial growth factor. Vascular endothelial growth factor is a potent angiogenic cytokine that can contribute to progression of atherosclerosis.