Journal of Pulmonology and Respiratory Diseases
Open Access

Obstructive sleep apnea (OSA); Cardiovascular disease (CVD); Hypertension; Intermittent hypoxia; Continuous positive airway pressure (CPAP)

Introduction

Sleep apnea is a common and underdiagnosed disorder characterized by repeated episodes of upper airway obstruction during sleep, resulting in intermittent cessation of breathing. Obstructive sleep apnea (OSA) is the most prevalent form, affecting an estimated 15-30% of adults globally, with higher rates observed in certain populations such as those with obesity, hypertension, and diabetes. While the most immediate consequences of sleep apnea are disturbed sleep and daytime fatigue, the long-term cardiovascular risks associated with untreated OSA are significant [1,2]. The relationship between sleep apnea and cardiovascular disease (CVD) has become a major focus of research in recent decades. Increasing evidence suggests that OSA is not merely an isolated condition but rather a significant independent risk factor for a range of cardiovascular conditions, including hypertension, arrhythmias, coronary artery disease (CAD), heart failure, and stroke [3]. Understanding the mechanisms through which OSA contributes to CVD is crucial for both improving patient outcomes and developing effective management strategies.

Pathophysiology: mechanisms linking sleep apnea to cardiovascular disease

Intermittent hypoxia and reoxygenation

Each episode of apnea or hypopnea results in a temporary reduction in oxygen saturation, followed by a rapid reoxygenation phase upon resumption of breathing. This cycle of intermittent hypoxia (IH) causes a series of metabolic and cellular responses, including increased oxidative stress, inflammation, and endothelial dysfunction. Recurrent hypoxic episodes promote the release of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukins, which contribute to systemic inflammation and vascular damage [4].

Sympathetic nervous system activation

OSA is associated with chronic activation of the sympathetic nervous system, particularly during apneic events. The intermittent hypoxia and associated arousals from sleep trigger a "fight or flight" response, leading to increased sympathetic tone, elevated heart rate, and elevated blood pressure. Over time, this sympathetic overactivity can contribute to the development of hypertension, arrhythmias, and the promotion of atherosclerosis.

Endothelial dysfunction and atherosclerosis

Intermittent hypoxia and sympathetic activation result in the release of several vasoactive substances, including endothelin-1, which constrict blood vessels and contribute to endothelial dysfunction [5]. Chronic endothelial injury increases the risk of atherosclerosis, a key process in the pathogenesis of coronary artery disease and stroke. Furthermore, the resulting imbalance between vasodilation and vasoconstriction predisposes individuals with OSA to hypertension, another major risk factor for cardiovascular morbidity and mortality.

Increased blood pressure

OSA is strongly associated with the development of hypertension, with studies suggesting that untreated OSA may contribute to both the initiation and exacerbation of elevated blood pressure. The repetitive cycles of hypoxia and sympathetic activation during sleep lead to increased systemic vascular resistance, which can result in sustained elevation of blood pressure. The intermittent nature of the episodes makes blood pressure fluctuations more pronounced, contributing to the long-term damage to the cardiovascular system.

Inflammation and coagulation

Chronic systemic inflammation is a key feature of OSA, and the inflammatory response is thought to contribute to the development of cardiovascular disease through mechanisms such as increased platelet aggregation and the promotion of thrombosis. Elevated levels of C-reactive protein (CRP), fibrinogen, and other pro-inflammatory markers are commonly observed in individuals with untreated sleep apnea.

Alterations in lipid metabolism

Patients with OSA frequently exhibit dyslipidemia, characterized by increased levels of triglycerides and low-density lipoprotein (LDL) cholesterol. These lipid abnormalities, combined with increased inflammatory markers, create a favorable environment for the development of atherosclerotic plaques and increase the risk of coronary artery disease and stroke [6].

Clinical implications

The strong association between sleep apnea and cardiovascular disease underscores the importance of early identification and intervention. Recognizing sleep apnea as a modifiable risk factor for cardiovascular disease offers a unique opportunity for preventing or reducing cardiovascular events in high-risk individuals.

Hypertension and heart failure

OSA is particularly prevalent in patients with hypertension and heart failure, two conditions that are themselves highly associated with cardiovascular morbidity and mortality. The presence of OSA in these populations worsens disease progression and can lead to more difficult-to-manage blood pressure control and heart failure symptoms. Managing OSA effectively in these patients may improve blood pressure regulation, reduce hospitalizations for heart failure exacerbations, and improve overall survival.

Arrhythmias

OSA is an independent risk factor for arrhythmias, particularly atrial fibrillation (AF). The repeated episodes of hypoxia, hypercapnia, and sympathetic stimulation increase the likelihood of developing atrial and ventricular arrhythmias [7]. Treating sleep apnea in patients with AF has been shown to reduce the frequency of arrhythmia episodes and improve the success of other therapeutic interventions. OSA is also associated with an increased risk of both ischemic and hemorrhagic stroke. The intermittent hypoxia, blood pressure fluctuations, and systemic inflammation seen in OSA contribute to vascular damage and thrombogenesis, increasing the likelihood of stroke. Furthermore, the nocturnal nature of OSA means that it can exacerbate nocturnal hypertension, a significant risk factor for stroke.

Management of sleep apnea and cardiovascular Risk

Managing sleep apnea in patients with cardiovascular disease is a critical aspect of preventing disease progression and improving patient outcomes. Several management strategies have been shown to be effective in reducing the cardiovascular risks associated with OSA.

Continuous positive airway pressure (CPAP)

The most widely used treatment for OSA is continuous positive airway pressure (CPAP), which involves using a machine to provide a constant flow of air through a mask to keep the airway open during sleep. CPAP therapy has been shown to reduce the frequency of apneic events, lower blood pressure, and improve heart function in individuals with heart failure. In addition, it has been linked to a reduction in the incidence of arrhythmias and stroke in certain populations.

Positive airway pressure therapy (BiPAP and APAP)

For patients with more complex forms of sleep apnea or those who do not tolerate CPAP, bilevel positive airway pressure (BiPAP) or auto-adjusting positive airway pressure (APAP) may be more effective [8]. These devices offer greater comfort and can provide variable pressures during inhalation and exhalation, making them more suitable for certain patients with comorbidities such as heart failure.

Lifestyle modifications

Lifestyle changes such as weight loss, smoking cessation, and alcohol reduction can significantly improve both sleep apnea severity and cardiovascular risk. Weight loss, in particular, has been shown to reduce the severity of OSA in overweight and obese individuals, thus potentially lowering cardiovascular risk.

Pharmacological interventions

While there are no specific pharmacologic treatments for OSA itself, medications to manage comorbid conditions, such as antihypertensive drugs, lipid-lowering agents, and anticoagulants, may be prescribed in conjunction with OSA treatment. Medications aimed at controlling hypertension or preventing arrhythmias may help reduce cardiovascular events in patients with concurrent OSA.

Conclusion

Sleep apnea is a complex condition with significant cardiovascular implications. The pathophysiological mechanisms linking OSA to cardiovascular disease include intermittent hypoxia, sympathetic activation, inflammation, endothelial dysfunction, and increased blood pressure. Early diagnosis and treatment of OSA in patients at risk for cardiovascular disease are essential to reduce morbidity and mortality. Continuous positive airway pressure (CPAP) remains the cornerstone of treatment, but lifestyle modifications and pharmacological interventions may further improve outcomes. Ongoing research into novel treatments and a better understanding of the interactions between sleep apnea and cardiovascular disease will continue to shape the management of these interrelated conditions.

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