Somers, Virend K.

BACKGROUND: People with narcolepsy are at increased risk for hypertension and cardiovascular disease; excessive sodium intake is linked to both. METHODS: We studied patients with narcolepsy and office systolic blood pressures (BPs) of 130 to 155 mm Hg taking twice-nightly high-sodium oxybate for ≥6 weeks who switched to low-sodium oxybate at the same dosage. The primary end point was the change from baseline in mean 24-hour ambulatory systolic BP at the end of treatment (≈6 weeks after switching). Secondary and exploratory end points included changes in diastolic BP, office BP, and 24-hour sodium excretion. RESULTS: Patients (n=43) had a mean age of 45 years, were 65% female, 33% on antihypertensives, with baseline mean (SD) office BP of 138.0/85.2 (5.7/6.6). Mean (SD) total high- and low-sodium oxybate dosages of 8.0 (1.1) and 8.1 (1.1) g/night, respectively, represented 1456.5 (206.2) and 117.8 (16.3) mg of sodium. The median 24-hour urinary sodium was 4278 mg/d at baseline and 2703 mg/d at the end of treatment (median change, 1288 mg/d). Mean (SE) 24-hour ambulatory systolic BPs at baseline and study end were 132.3 (1.8) and 128.2 (1.8) mm Hg (least-squares mean change, −4.1 [95% CI, −6.9 to −1.4] mm Hg; 1-sided P =0.0019). BP changes by narcolepsy subtype, sex, body mass index, baseline office BP, and baseline antihypertensive use were consistent with the overall effect size. CONCLUSIONS: People with narcolepsy switching from high- to low-sodium oxybate showed substantially reduced daily medication-related sodium intake and significant 24-hour BP reductions. These results demonstrate the importance of reducing pharmaceutical sodium content in this elevated cardiovascular risk patient population. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT05869773.

Abstract Background Obstructive sleep apnea (OSA) is a risk factor for hypertension and some evidence suggests this risk may not be mitigated with positive airway pressure. Low-intensity statin therapy can modestly reduce blood pressure (BP). In this exploratory analysis, we examined if six months of high-intensity statin therapy could lower resting or ambulatory BP in patients with OSA. Methods 39 patients with OSA (13F, age = 49 ± 9yrs, body mass index = 32.9 ± 4.2kg/m2, apnea-hypopnea index = 22.2 ± 12.4 events/hour) were randomized to high-intensity atorvastatin or placebo. BP was assessed using seated, “office” measurements and in 20-minute intervals over 24 consecutive hours at three timepoints (baseline, three- and six-months post-randomization). Participants maintained a diary denoting sleep and wake times for analysis. Changes (Δ) in BP from baseline were assessed and adjusted for adherence to participants’ intervention (atorvastatin or placebo) as well as to their treatment for OSA (yes or no). Results There were no between-group differences in baseline BP variables (P = .09-.96). At three months, the changes in resting (P = .74-.87), 24 hour mean (P = .54-.96), daytime (P = .70-.96), nor nighttime (P = .74-.96) BP did not differ between groups. Similarly, the changes in resting (P = .23-.92), 24 hour mean (P = .51-.82), daytime (P = .17-.78), and nighttime (P = .51-1.00) BP did not differ between groups following six months of their respective intervention. Conclusions Our data suggest that high-intensity atorvastatin does not lower resting or ambulatory BP in patients with OSA relative to a placebo. Thus, it does not appear that atorvastatin is a viable adjunct intervention for BP reduction in patients with OSA. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03308578.

Restless legs syndrome (RLS) is a frequent sleep-related sensorimotor disorder defined by an urge to move the legs in the evening while resting. Severe RLS symptoms can negatively impact sleep, mood, and quality of life. Periodic leg movements during sleep and wakefulness are found in 60% to 80% of patients with RLS. The pathophysiology of RLS and periodic leg movement is still poorly understood and involves brain iron deficiency, dopamine dysregulation, and genetic predisposition. Over the past decades, several cross-sectional and longitudinal studies have reported an association between RLS, cardiovascular disease, and hypertension although the magnitude, direction, and underlying mechanisms of these associations remain inconclusive. Periodic leg movements during sleep are concomitant with an increase in blood pressure and heart rate, which may affect the physiological nocturnal blood pressure dip and, therefore, lead to an increased incidence of cardiovascular disease. Insomnia and sleep deprivation linked to sensory discomfort could also increase the sympathetic tone and contribute to an increase in cardiovascular risk. Comorbidities and associated sleep disorders may also synergically increase cardiovascular risk. This narrative review details the current knowledge of RLS, a still underdiagnosed and poorly recognized disorder, and examines the epidemiological relationship between RLS, cardiovascular disease and hypertension, potential mechanisms underlying this association, and strategies to reduce the risk of cardiovascular disease in patients with moderate-to-severe RLS. Greater multidisciplinary collaborations between cardiologists and sleep specialists are needed to better identify, understand, and manage patients with sleep disorders, including those with RLS.

Obstructive sleep apnea (OSA) is a highly prevalent sleep disorder, characterized by recurrent upper airway obstruction during sleep, resulting in intermittent hypoxia, increased sympathetic activation, and sleep deficiency. Over the past 2 decades, there has been a robust body of evidence to support a strong link between OSA and cardiometabolic diseases. Obesity is an important risk factor for OSA. Observational studies indicate that OSA is a strong risk factor for the development of hypertension and diabetes. Moreover, clinical and experimental studies support a causal role of OSA in hypertension and impairments in glucose metabolism, beyond excess weight. Notably, OSA is particularly underdiagnosed and undertreated in women, which may heighten the cardiometabolic risk. OSA is often overlooked during pregnancy and has been linked to adverse cardiometabolic outcomes in observational studies. In randomized clinical trials, treatment of OSA with continuous positive airway pressure reduces blood pressure in individuals with hypertension, but the beneficial effects of continuous positive airway pressure on glycemic outcomes are less convincing. Inconsistent cardiometabolic response to OSA treatment can be partly explained by failure to consider heterogeneity in OSA and variable continuous positive airway pressure adherence among diverse populations. In this review, we summarize the relationships between OSA and cardiometabolic conditions with a particular focus on obesity, hypertension, and diabetes. We review the current knowledge on the heterogeneity in OSA and discuss potential underlying mechanisms for impairments in blood pressure and glucose metabolism in OSA. We also provide a clinical perspective for OSA management considering current research gaps and emerging approaches for the prevention and treatment of cardiometabolic disease.

Atrial fibrillation (AF) is the most prevalent sustained cardiac arrhythmia, with its incidence rising due to aging populations, obesity, and advancements in diagnostic modalities. The interplay between sleep disorders and AF is increasingly recognized, with obstructive sleep apnea (OSA) serving as a well-established risk factor. However, emerging evidence implicates additional sleep disturbances—including central sleep apnea, insomnia, and restless legs syndrome—in AF pathogenesis and progression. Despite compelling observational data, interventional studies evaluating the impact of sleep disorder treatment on AF outcomes have yielded mixed results. Although continuous positive airway pressure therapy in patients with OSA mitigates AF recurrence, randomized controlled trials have yet to confirm a definitive causal benefit. This review synthesizes epidemiological, mechanistic, and interventional data linking sleep disorders to AF.

AbstractThe intricate role of the autonomic nervous system (ANS) in regulating cardiac physiology has long been recognized. Aberrant function of the ANS is central to the pathophysiology of cardiovascular diseases. It stands to reason, therefore, that neuroscience‐based cardiovascular therapeutics hold great promise in the treatment of cardiovascular diseases in humans. A decade after the inaugural edition, this White Paper reviews the current state of understanding of human cardiac neuroanatomy, neurophysiology and pathophysiology in specific disease conditions, autonomic testing, risk stratification, and neuromodulatory strategies to mitigate the progression of cardiovascular diseases. image

Abstract Central sleep apnea, a rare polysomnographic finding in the general population, is prevalent in certain cardiovascular conditions including systolic and diastolic left ventricular dysfunction, atrial fibrillation, coronary artery disease, carotid artery stenosis, stroke, and use of certain cardiac-related medications. Polysomnographic findings of central sleep apnea with adverse cardiovascular impacts include nocturnal hypoxemia and arousals, which can lead to increased sympathetic activity both at night and in the daytime. Among cardiovascular diseases, central sleep apnea is most prevalent in patients with left ventricular systolic dysfunction; a large study of more than 900 treated patients has shown a dose-dependent relationship between nocturnal desaturation and mortality. Multiple small randomized controlled trials have shown mitigation of sympathetic activity when central sleep apnea is treated with nocturnal oxygen, continuous positive airway pressure, and adaptive servoventilation. However, two early randomized controlled trials with positive airway pressure devices have shown either a neutral effect on survival or excess premature mortality in the active treatment arm, compared to untreated central sleep apnea. In contrast, the results of the most recent trial using an advanced adaptive servoventilation device showed improved quality of life and no signal for mortality suggesting that treatment of central sleep apnea was at least safe. In addition to positive airway pressure devices, multiple medications have been shown to improve central sleep apnea, but no long-term trials of pharmacologic therapy have been published. Currently, phrenic nerve stimulation is approved for the treatment of central sleep apnea, and the results of a randomized controlled trial showed significant improvement in sleep metrics and quality of life.

Background Hyperlipidemia is a major cardiovascular disease (CVD) risk factor, but there are limited data on its mortality trends in CVD over time. We assessed annual hyperlipidemia‐related CVD mortality trends in the United States, including the COVID‐19 pandemic's impact. Methods and Results Mortality data were obtained from the Centers for Disease Control and Prevention repository between 1999 and 2020 among patients ≥15 years old, using International Classification of Diseases, Tenth Revision ( ICD‐10 ) codes for hyperlipidemia (E78.0–E78.5) and CVD (I00–I99). Age‐adjusted mortality rates (AAMRs) per 1 000 000 population were standardized to the 2000 US population. Log‐linear regression models were used to evaluate mortality shifts. Average annual percentage change from 1999 to 2019 was used to project 2020 AAMRs, estimating pandemic‐attributed excess deaths. From 1999 to 2020, 483 155 hyperlipidemia‐related CVD deaths occurred. Despite a general CVD mortality decline, hyperlipidemia‐related CVD AAMRs rose from 36.33 in 1999 to 99.77 in 2019. Ischemic heart diseases (AAMR 49.39) were the leading cause, whereas hypertension had the highest mortality increase (average annual percentage change +10.23%). Mortality rates were higher in men (AAMR 104.87) and non‐Hispanic (AAMR 82.49), and rural populations (AAMR 89.98). Highest mortality was observed in Black populations (AAMR 84.35), those ≥75 years old (AAMR 646.45), and Western US regions (AAMR 96.88). During the first pandemic year, deaths exceeded projections by 10.55%, with notable increases among ages 35 to 75 (14.23%), Hispanic (17.96%), Black (14.82%), and urban (11.68%) groups. Conclusions Hyperlipidemia‐related CVD mortality has risen over the past 2 decades, further heightened by the COVID‐19 pandemic, with higher impact on men, Black Americans, the older population, and rural residents. Further study is needed to understand contributing factors and mitigate disparities.

Abstract Study Objectives The majority of patients with insomnia exhibit abnormal sleep in objective testing (e.g. decreased sleep duration, decreased slow wave sleep [SWS]). Previous studies have suggested that some of these objective measures of poor sleep, such as decreased sleep duration, are associated with a higher risk of hypertension in insomnia. We examined the relationship between SWS and morning and evening blood pressure (BP) levels in patients with clinically diagnosed insomnia. Methods A total of 229 normal sleepers and 1378 insomnia patients were included in this study. Insomnia was defined based on standard diagnostic criteria with symptoms lasting ≥6 months. All participants underwent in-laboratory polysomnography. Patients were classified into quartiles of percent SWS. Evening and morning hypertension were defined using BP measurements taken in the evening before and in the morning after polysomnography, respectively. Multivariable logistic regression models were used to assess the relationship between insomnia, SWS, and hypertension. Results Insomniacs with <3.5% SWS (OR 3.27, 95% confidence intervals [CI]: 1.31 to 7.66) and those with 3.5%–10.2% SWS (OR 2.38, 95% CI: 1.28 to 5.91) had significantly greater odds of morning hypertension compared to normal sleepers. No associations were seen in insomnia with 10.2%–15.8% SWS and with >15.8% SWS. Significant effect modifications by sex (p = .043) were found, as decreased SWS was associated with morning hypertension only in men. Odds of evening hypertension were not significantly associated with SWS. Conclusions Decreased SWS is associated with morning hypertension in a dose-dependent manner in insomnia, especially in men.