Does Obstructive Sleep Apnea Cause Cardiovascular Disease?

As our understanding of the prevalence and pathophysiology of obstructive sleep apnea (OSA) expands, so does the list of adverse consequences imposed by this disease on both health and quality of life. Of note, OSA has been identified as a significant cause of and/or contributor to cardiovascular disease.

OSA has been shown to increase the risk for hypertension, pulmonary vascular disease, ischemic heart disease, cerebral vascular accidents, congestive heart failure, and arrhythmias, independent of confounding or concomitant risk factors.[1-13] However, despite the growing body of evidence that links OSA to the development of cardiovascular disease, the true causal relationship remains controversial. Many risk factors for OSA are also known risk factors for cardiovascular disease, such as age, male gender, and obesity. In addition, OSA is associated with numerous conditions that are known to increase the risk for cardiac disease, such as diabetes mellitus and hypertension. Therefore, it is difficult to prove whether OSA independently causes cardiovascular disease.

Pathophysiology of Sleep-Disordered Breathing

Episodes of sleep-disordered breathing cause pathologic vascular changes and dysfunction, both of which can cause and contribute to cardiovascular disease, independent of confounding factors. The adverse effects that OSA imposes on cardiovascular function are thought to arise from several overlapping mechanisms. Apneic events, intermittent hypoxia, and the resulting arousals result in an increased sympathetic tone and endothelial dysfunction. This recurrent cycle of events ultimately leads to vasoconstriction and vascular remodeling, which in turn leads to the development of vascular and cardiac dysfunction.

Recurrent arousals resulting from episodic apneic episodes cause repetitive catecholamine surges and a marked increase in sympathetic tone. The increase in vascular sympathetic nerve activity and circulating catecholamines subsequently lead to increased peripheral vascular resistance, episodic elevations in nocturnal blood pressure, and propagation of atherosclerosis. Daytime hypertension develops secondary to the persistently elevated sympathetic state.[14] Intermittent hypoxia that follows these apneic events can further add to vascular dysfunction.[5,15] Hypoxic vasoconstriction and hypoxia-reperfusion oxidative stresses lead to vascular remodeling and the release of pro-inflammatory mediators such as cyclooxygenase-2, tissue necrosis factor-alpha, and interleukins, which ultimately cause vascular endothelium dysfunction and the development of arterial noncompliance.[16,17]

Hypertension
The causal link between OSA and systemic hypertension has been clearly established. Several studies have shown that sleep apnea increases the relative risk for hypertension, independent of other confounding factors.[1-4] In a cross-sectional analysis of more than 6000 patients, the Sleep Heart Health Study showed a linear relationship between mean systolic and diastolic blood pressures and OSA severity.[1] Likewise, the prevalence of hypertension linearly increased with the presence and severity of OSA.[1,2] A large Canadian population-based study found that each apneic event per hour increased the odds of hypertension by 1%, and each 10% reduction in nocturnal oxygen saturation increased the likelihood of hypertension developing by 13%.[2]

Approximately 50% of patients with OSA have hypertension, compared with only 30% of the general public. Because of the strength of evidence linking OSA with the development of hypertension, the seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-VII) now lists sleep apnea as a significant cause of secondary hypertension.[3]