Obstructive sleep apnea and cardiovascular disease.

Obstructive sleep apnea (OSA) is a common disorder associated with an increased risk of cardiovascular disease and stroke. As it is strongly associated with known cardiovascular risk factors, including obesity, insulin resistance, and dyslipidemia, OSA is an independent risk factor for hypertension and has also been implicated in the pathogenesis of congestive cardiac failure, pulmonary hypertension, arrhythmias, and atherosclerosis. Obesity is strongly linked to an increased risk of OSA, and weight loss can reduce the severity of OSA. The current standard treatment for OSA-nasal continuous positive airway pressure (CPAP)-eliminates apnea and the ensuing acute hemodynamic changes during sleep. Long-term CPAP treatment studies have shown a reduction in nocturnal cardiac ischemic episodes and improvements in daytime blood pressure levels and left ventricular function. Despite the availability of effective therapy, OSA remains an underdiagnosed and undertreated condition. A lack of physician awareness is one of the primary reasons for this deficit in diagnosis and treatment.

Repetitive hypoxia increases lipid loading in human macrophages-a potentially atherogenic effect.

Obstructive sleep apnea (OSA) is characterized by repetitive episodes of hypoxia and is associated with an increase in cardiovascular disease. We, therefore, investigated the effect of repetitive hypoxia on two key early events in atherogenesis; lipid loading in foam cells and monocyte adhesion to endothelial cells. Human macrophages were loaded with acetylated low-density lipoproteins. During lipid loading, the cells were exposed to 30 min cycles of 2%/21% oxygen or control (room air, 5% CO(2) incubator). Human umbilical vein endothelial cells (HUVECs) were also exposed to 30 min cycles of repetitive hypoxia or control conditions and monocyte adhesion measured. Cell adhesion molecules E-selectin, ICAM-1 and VCAM-1 were measured by ELISA. Repetitive hypoxia increased cholesteryl ester uptake by macrophages (127+/-5% compared to controls; p=0.003). By contrast, monocyte adhesion to HUVECs and cell adhesion molecule expression were unchanged by exposure to repetitive hypoxia, compared to controls (p >0.1). Repetitive hypoxia, at levels relevant to tissues such as the arterial wall, enhances lipid uptake into human macrophages. This may contribute to accelerated atherosclerosis in OSA patients.

Treatment of obstructive sleep apnoea leads to enhanced pulmonary vascular nitric oxide release.

BACKGROUND: Obstructive sleep apnoea (OSA) is associated with pulmonary hypertension, however neither the pathogenesis of pulmonary vascular disease nor the effect of successful treatment of OSA on pulmonary vascular physiology has been characterised. METHODS: Seven subjects aged 52 (range 36-63) years with moderate to severe obstructive sleep apnoea (apnoea-hypopnoea index>15/h) had detailed pulmonary vascular reactivity studies, before and after 3 months of successful treatment with nasal continuous positive airways pressure (CPAP). On both occasions, we measured pulmonary pressure, flow velocity, flow and resistance, at baseline and in response to acetylcholine (an endothelium-dependent dilator), sodium nitroprusside (an endothelium-independent dilator), l-NMMA (an antagonist of nitric oxide synthesis) and l-Arginine (the substrate of nitric oxide). RESULTS: At baseline, pulmonary flow increased in response to acetylcholine and nitroprusside and fell in response to l-NMMA. Following CPAP treatment, the decrease in flow to l-NMMA was significantly greater (to 62+/-6% of control value vs 85+/-6% of pre-treatment; p=0.01), consistent with enhanced basal release of nitric oxide. The acetylcholine response tended to be greater after treatment (174+/-26% of control vs 147+/-12% of pre-CPAP, p=0.22), however the nitroprusside response was unchanged. CONCLUSION: Successful treatment of obstructive sleep apnoeic episodes in sleep results in enhanced nitric oxide release by the pulmonary microvascular circulation.