For decades, sleep was treated as a biological off switch a passive state where the body simply idled until morning. A new mechanistic review from researchers at Mayo Clinic makes clear that nothing could be further from the truth. Sleep is a period of intense, dynamic autonomic nervous system activity, and when that activity goes awry, the consequences for the cardiovascular system can be profound.
The review, published June 25 in Arteriosclerosis, Thrombosis, and Vascular Biology by Shahid Karim, Saifullah Khan, and Virend K. Somers, synthesizes a body of evidence built over decades of work from Somers’ laboratory, which has been at the forefront of research linking sleep disordered breathing to cardiovascular disease. The paper weaves together findings from human physiology studies, animal models, and clinical observations to map the mechanistic chain connecting sleep disruption to hypertension, atrial fibrillation, myocardial ischemia, and sudden cardiac death.
Sleep is not physiologically uniform. During non-rapid eye movement (NREM) sleep, the autonomic nervous system shifts toward parasympathetic dominance. Heart rate slows, blood pressure drops, and the cardiovascular system gets what is often called a “nightly reset.” This nocturnal dip in blood pressure is a normal, protective phenomenon. But during rapid eye movement (REM) sleep, the picture flips entirely. The autonomic nervous system becomes volatile, with bursts of sympathetic activity interspersed with parasympathetic surges. These oscillations are normally contained and benign in healthy sleepers. In people with obstructive sleep apnea (OSA), they become a cardiovascular threat.
OSA amplifies autonomic instability through three synergistic mechanisms. The first is intermittent hypoxia repeated cycles of oxygen desaturation and reoxygenation that trigger chemoreflex activation and a cascade of cellular stress responses. The second is recurrent arousals, which fragment sleep and produce repeated sympathetic surges. The third is intrathoracic pressure swings the dramatic negative pressure generated by each attempted breath against an obstructed airway, which mechanically stresses the heart and great vessels. Together, these three drivers create a perfect storm of autonomic volatility that persists even during wakefulness.
At the cellular level, the consequences are sweeping. Intermittent hypoxia drives oxidative stress and systemic inflammation. Endothelial function deteriorates. Neuroendocrine systems, including the renin-angiotensin-aldosterone axis and the hypothalamic-pituitary-adrenal axis, become dysregulated. The chemoreflex system becomes sensitized, meaning the body overreacts to normal fluctuations in oxygen and carbon dioxide. Maladaptive neuroplasticity changes in the brainstem circuits that control autonomic outflow locks these abnormalities into place, producing a state of chronic 24-hour sympathetic overactivity.
The clinical consequences are specific and mechanistically grounded. In hypertension, OSA blunts or eliminates the normal nocturnal dip in blood pressure, leaving the cardiovascular system under continuous pressure load. For atrial fibrillation, the combination of mechanical stress from intrathoracic pressure swings and the autonomic conflict of simultaneous sympathetic and parasympathetic activation creates a perfect substrate for arrhythmia initiation and maintenance. In ischemic heart disease, the increased myocardial oxygen demand driven by sympathetic activation combines with a prothrombotic state and endothelial dysfunction to heighten risk.
The review also highlights an especially vulnerable population: patients with inherited channelopathies such as long QT syndrome or Brugada syndrome. In these individuals, the autonomic volatility of REM sleep and the additional insult of comorbid sleep disordered breathing can trigger malignant arrhythmias. The authors note that sleep disordered breathing is often unrecognized in these patients, representing a potentially modifiable risk factor.
The therapeutic implication is that treating sleep disordered breathing is also treating cardiovascular risk. Continuous positive airway pressure (CPAP) therapy, when effective and adherent, can reduce sympathetic activity, restore nocturnal blood pressure dipping, lower atrial fibrillation recurrence after cardioversion, and improve outcomes in heart failure. But the review also underscores a sobering reality: CPAP adherence is poor, and many patients with OSA remain untreated or undertreated. The authors call for greater integration of sleep evaluation into cardiovascular care, from hypertension clinics to electrophysiology services.
Source: Karim S, Khan S, Somers VK. Sleep, Neural Circulatory Control, and Cardiovascular Disease: A Mechanistic Review. Arteriosclerosis, Thrombosis, and Vascular Biology. 2026 Jun 25. doi: 10.1161/ATVBAHA.125.324076. PMID: 42345098.