How does sleep apnea cause hypertension?

How Sleep Apnea Causes Hypertension

Sleep apnea causes hypertension primarily through sustained activation of the sympathetic nervous system triggered by intermittent hypoxemia and increased upper airway resistance during recurrent apneic episodes. 1

Primary Pathophysiologic Mechanisms

The causal pathway from obstructive sleep apnea to hypertension operates through several interconnected mechanisms:

Sympathetic Nervous System Activation

• The intermittent hypoxemia and increased upper airway resistance during apneic episodes induce a sustained increase in sympathetic nervous system (SNS) activity that persists even during wakefulness. 1, 2
• This heightened SNS output raises blood pressure through multiple pathways: increased cardiac output, elevated peripheral vascular resistance, and enhanced fluid retention through renal mechanisms. 1
• The sympathetic activation is not transient—it becomes a chronic state that maintains elevated blood pressure throughout the 24-hour cycle. 3

Oxidative Stress and Endothelial Dysfunction

• Sleep apnea increases reactive oxygen species production while simultaneously reducing nitric oxide bioavailability, impairing the vasculature's ability to regulate blood pressure through normal vasodilation. 1
• This oxidative stress contributes to vascular remodeling and arterial stiffness, which are hallmarks of resistant hypertension in OSA patients. 3

Renin-Angiotensin-Aldosterone System (RAAS) Activation

• The chronic sympathetic activation and intermittent hypoxia also stimulate the RAAS, providing an additional mechanism for blood pressure elevation and fluid retention. 4, 3
• This explains why medications targeting the RAAS (ACE inhibitors, ARBs, and aldosterone antagonists like spironolactone) show particular effectiveness in OSA-related hypertension. 4

Clinical Significance and Epidemiology

Prevalence and Association Strength

• Obstructive sleep apnea is extraordinarily common in resistant hypertension, affecting ≥80% of patients whose blood pressure remains uncontrolled despite multiple medications. 1
• In one study of consecutive patients with treatment-resistant hypertension, 83% had previously undiagnosed sleep apnea based on an apnea-hypopnea index ≥10 events/hour. 1, 5
• The severity of sleep apnea directly correlates with blood pressure control—more severe OSA predicts worse hypertension control despite increasing numbers of antihypertensive medications. 1, 6

Observational Evidence

• Prospective observational studies demonstrate that untreated OSA independently predicts the development of incident hypertension in previously normotensive individuals. 1, 6
• This relationship persists after adjusting for confounding factors like obesity, establishing OSA as an independent risk factor rather than merely an associated condition. 6

Important Clinical Caveats

Treatment Effects Are Modest

Despite the strong mechanistic and epidemiologic links, CPAP therapy produces only modest blood pressure reductions of 2-3 mm Hg on average, with effectiveness dependent on patient compliance, OSA severity, and presence of daytime sleepiness. 1, 6

This creates a clinical paradox: while OSA clearly causes hypertension through multiple mechanisms, treating the OSA with CPAP alone rarely normalizes blood pressure. The implication is that pharmacological antihypertensive therapy remains essential even when OSA is adequately treated with CPAP. 5, 4

Gender Differences

• Sleep apnea shows significant gender differences in patients with resistant hypertension—it is both more common and more severe in men compared to women. 1
• This should inform screening strategies, with particularly high suspicion warranted in men with treatment-resistant hypertension.

Cardiovascular Risk Beyond Blood Pressure

• Even when CPAP produces minimal blood pressure reduction, it significantly reduces cardiovascular events, with an adjusted hazard ratio of 0.34 (95% CI, 0.20-0.58) for vascular events. 6
• This suggests that OSA's cardiovascular toxicity extends beyond its hypertensive effects, likely through mechanisms involving arrhythmias, endothelial dysfunction, and metabolic derangements. 6