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Medication-induced central sleep apnea (CSA) is one of the eight categories of causes of CSA but in the absence of awareness and careful history may be misclassified as primary CSA. While opioids are a well-known cause of respiratory depression and CSA, non-opioid medications including sodium oxybate, baclofen, valproic acid, gabapentin, and ticagrelor are less well-recognized. Opioids-induced respiratory depression and CSA are mediated primarily by µ-opioid receptors, which are abundant in the pontomedullary centers involved in breathing. The non-opioid medications, sodium oxybate, baclofen, valproic acid, and gabapentin, act upon brainstem gamma-aminobutyric acid (GABA) receptors, which co-colonize with µ-opioid receptors and mediate CSA. The pattern of ataxic breathing associated with these medications is like that induced by opioids on polysomnogram. Finally, ticagrelor also causes periodic breathing and CSA by increasing central chemosensitivity and ventilatory response to carbon dioxide. Given the potential consequences of CSA and the association between some of these medications with mortality, it is critical to recognize these adverse drug reactions, particularly because discontinuation of the offending agents has been shown to eliminate CSA.

OSA is a highly prevalent sleep disorder, and subjective excessive daytime sleepiness (EDS) is the cardinal symptom for which many individuals seek medical advice. Positive airway pressure (PAP) devices, first-line treatment for OSA, eliminates EDS in most patients. However, a subset of patients suffers from persistent EDS despite adherence to therapy. Multiple conditions, some reversible, could account for the residual sleepiness and need to be explored, requiring detailed history, review of PAP data from the smart card, and sometimes additional testing. When all known causes of EDS are excluded, in adequately treated subjects, the purported mechanisms could relate to long-termexposure to the OSA-related sleep fragmentation, sleep deprivation, and hypoxic injury to the arousal system, shifts in melatonin secretion, or altered microbiome. Independent of the mechanism, in well-treated OSA, pharmacological therapy with approved drugs can be considered. Modafinil is commonly prescribed to combat residual EDS, but more recently two drugs, solriamfetol, a dual dopamine-norepinephrine reuptake inhibitor, and pitolisant, a histamine H3 receptor inverse agonist, were approved for EDS. Solriamfetol has undergone randomized controlled trials for treatment of EDS associated with both OSA and narcolepsy, exhibiting robust efficacy. Solriamfetol is renally excreted, with no known drug interactions. Pitolisant, which is nonscheduled, has undergone multiple RCTs in narcolepsy, showing improvement in subjective and objective EDS and one OSA trial showing improvement in subjective EDS.

Supplemental digital content is available in the text.

Supplemental Digital Content is available in the text.

Insomnia is the most prevalent sleep disorder in the United States and has high comorbidity with a number of cardiovascular diseases (CVDs). In the past decade, a number of observational studies have demonstrated an association between insomnia and incident cardiovascular disease (CVD) morbidity and mortality, including hypertension (HTN), coronary heart disease (CHD), and heart failure (HF). Despite some inconsistencies in the literature, likely due to variations in how insomnia is defined and measured, the existing data suggest that insomnia, especially when accompanied by short sleep duration, is associated with increased risk for HTN, CHD and recurrent acute coronary syndrome, and HF. Purported mechanisms likely relate to dysregulation of the hypothalamic-pituitary axis, increased sympathetic nervous system activity, and increased inflammation. This paper reviews the most recent studies of insomnia and CVD and the potential pathophysiological mechanisms underlying this relationship and highlights the need for randomized trials to further elucidate the nature of the relationship between insomnia and CVD.

The presence and severity of obstructive sleep apnea (OSA) are associated with impaired left ventricular (LV) structure and function. Our goal was to quantify the associations between LV systolic function and mass with severity of OSA in an ethnically diverse cohort, assessing variations by age and sex.

There is limited research on racial/ethnic variation in sleep disturbances. This study aimed to quantify the distributions of objectively measured sleep disordered breathing (SDB), short sleep duration, poor sleep quality, and self-reported sleep disturbances (e.g., insomnia) across racial/ethnic groups.

We sought to quantify the association between slow-wave (stage N3) sleep and hypertension in a large cohort of middle-aged men and women. Data from 1850 participants free of baseline hypertension from the Sleep Heart Health Study were analyzed. The primary exposure was percentage of N3 sleep on baseline in-home polysomnography and the primary outcome was incident hypertension, defined as systolic blood pressure ≥ 140 mm Hg, diastolic blood pressure ≥ 90 mm Hg, and/or use of any blood pressure lowering medications at follow-up. Multivariable logistic regression models were adjusted for study site, age, sex, race, waist circumference, tobacco use, alcohol use, apnea–hypopnea index, nocturnal oxygen desaturation, sleep duration, sleep efficiency, and arousal index. Mean age was 59.4 ± 10.1 years and 55.5% were female. The mean baseline systolic and diastolic blood pressure was 118.8 and 70.6 mm Hg, respectively. Approximately 30% of the sample developed hypertension during a mean follow-up of 5.3 years. In the multi-adjusted model, participants in quartiles 1 (<9.8%) and 2 (9.8%–17.7%) of N3 sleep had significantly greater odds of incident hypertension compared with those in quartile 3 (17.7%–25.2%) (OR 1.69, 95% CI 1.21–2.36, p= .002 and OR 1.45, 95% CI 1.04–2.00, p= .03, respectively). No significant effect modification by sex on the N3-hypertension association was observed. In conclusion, compared with intermediate levels of N3 sleep (overlapping the “normal” adult range), lower levels of percent N3 sleep are associated with increased odds of incident hypertension in both men and women, independent of potential confounders, including indices of sleep apnea and sleep fragmentation.