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Impact of OSA primary therapy on antihypertensive drugs use

Revol, Bruno; Castelli, Christel; Joyeux-Faure, Marie; Pépin, Jean-Louis

2022 SLEEP

doi: 10.1093/sleep/zsac151pmid: 35802044

We appreciated the letter to the editor from Romigi et al. in response to our work dealing with the impact of obstructive sleep apnea (OSA) primary therapies on antihypertensive drug use [1]. This letter gives us the opportunity to clarify the methodology we used. Based on a random sample of the French population (representative for age and sex) affiliated to the main public health-insurance scheme (Echantillon généraliste des bénéficiaires), we analyzed data on adult patients with OSA starting treatment with continuous positive airway pressure (CPAP) or a mandibular advancement device (MAD) for the first time in 2017 and being concurrently treated with antihypertensive drugs. To limit selection bias, we excluded those who had received less than 3 months of antihypertensive treatment in the year preceding OSA treatment initiation. A total of 1153 patients were included, 61.9% of whom were men, the mean age was 65.1 years, and they had the following frequent comorbidities: diabetes (28%), arrhythmias (15.5%), and a history of stroke (6.7%). Their care consumption during the 12 months before and 12 months after the date of initiation of OSA treatment was extracted. In order to limit potential confounding factors, a cohort of controls was selected by matching each OSA subject with a beneficiary without OSA but with antihypertensive treatment and the same profile of age, sex, and associated comorbidities over the same period. The date of initiation of CPAP or MAD for each OSA patient was used as the index date applied to each matched non-OSA control subject, in order to compare the 1-year periods before and after between the two cohorts (OSA and non-OSA), thereby limiting temporality bias. Finally, 1151 beneficiaries without OSA were matched. We acknowledge the absence of the exact indication for each drug is a limitation of our data. However, this is an inherent limitation of any study using claims reimbursement databases. The main attribute of our data was the decrease in the use of two specific drug classes (calcium channels blockers and renin–angiotensin–system-acting agents). These are the most widely used medications for hypertension and associated complications, whereas diuretics and beta-blocking agents have much broader indications, as pointed out by Romigi et al. A concern of Romigi et al. was that comorbidities may have biased the deprescription rate. This was probably not the case as in our work non-OSA and OSA cohorts were matched for morbidities. Romigi et al. also discuss the respective effects of CPAP or MAD on blood pressure (BP) in a short-term randomized controlled trial [2]. The mean duration of the randomized controlled trials in the field is limited to less than four months of follow-up [3]. They do not inform on the long-term impact of CPAP on incident hypertension and mortality [4]. Studies in real-life conditions and in unselected OSA populations are providing important complementary results. In this context, our data on the representative sample of the French population provide new insights, as they reflect the real use of antihypertensive drugs in a large cohort of OSA patients over the long term. In addition, our results might be partly explained by other factors than an isolated effect of CPAP or MAD on BP. Weight loss and exercise, alcohol avoidance, or sodium restriction [5] are recommended for multimorbid OSA patients on primary therapy [6, 7]. In the general field of hypertension, higher success rates for cessation of antihypertensive therapy are observed in individuals who initiate and adhere to lifestyle modifications [8]. While in OSA, weight loss and CPAP have been demonstrated to have a synergistic effect for improving cardiometabolic health [9]. Finally, almost all national and international recommendations include dietary sodium reduction as part of the nonpharmacologic therapy for hypertension. In parallel, the potential role of sodium in the pathogenesis of OSA has been recently shown in hypertensive patients [10], suggesting that interventions to reduce bodily fluid content (e.g., low sodium intake or diuretics) may have the potential to both reduce OSA severity and treat OSA-related hypertension [11]. Whatever the exact mechanisms, our results are consistent with those of an online survey commissioned by the American Academy of Sleep Medicine, revealing that 17% of patients had reduced their use of antihypertensive drugs and 3% had permanently stopped taking them after starting OSA primary therapy [12]. Further studies are therefore needed to characterize this specific population and highlight the underlying mechanisms leading to antihypertensive drug discontinuation, in order to move toward personalized and precision medicine for OSA. Acknowledgment We thank Alison Foote (Grenoble Alpes University Hospital, France) for critically reading and editing the manuscript. Disclosure Statement None declared. References 1. Revol B , et al. Deprescribing antihypertensive drugs after starting OSA primary therapy? Sleep . 2022 ; 45 ( 5 ). doi:10.1093/sleep/zsac060 Google Scholar OpenURL Placeholder Text WorldCat 2. Dissanayake HU , et al. Comparative effects of CPAP and mandibular advancement splint therapy on blood pressure variability in moderate to severe obstructive sleep apnoea . Sleep Med. 2021 ; 80 : 294 – 300 . doi:10.1016/j.sleep.2021.01.059 Google Scholar Crossref Search ADS PubMed WorldCat 3. Bratton DJ , et al. CPAP vs Mandibular advancement devices and blood pressure in patients with obstructive sleep apnea: a systematic review and meta-analysis . JAMA. 2015 ; 314 : 2280 – 2293 . doi:10.1001/jama.2015.16303 Google Scholar Crossref Search ADS PubMed WorldCat 4. Pépin J-L , et al. Relationship between cpap termination and all-cause mortality: a French nationwide database analysis . Chest. 2022 ; 161 : 1657 – 1665 . doi:10.1016/j.chest.2022.02.013 Google Scholar Crossref Search ADS PubMed WorldCat 5. Revol B , et al. Who may benefit from diuretics in OSA? A propensity score-match observational study . Chest. 2020 ; 158 : 359 – 364 . doi:10.1016/j.chest.2020.01.050 Google Scholar Crossref Search ADS PubMed WorldCat 6. Hudgel DW , et al. The role of weight management in the treatment of adult obstructive sleep apnea. An official American Thoracic Society clinical practice guideline . Am J Respir Crit Care Med. 2018 ; 198 : e70 – e87 . doi:10.1164/rccm.201807-1326ST Google Scholar Crossref Search ADS PubMed WorldCat 7. Mendelson M , et al. Obstructive sleep apnea syndrome, objectively measured physical activity and exercise training interventions: a systematic review and meta-analysis . Front Neurol. 2018 ; 9 : 73 . doi:10.3389/fneur.2018.00073 Google Scholar Crossref Search ADS PubMed WorldCat 8. Stamler R , et al. Nutritional therapy for high blood pressure. Final report of a four-year randomized controlled trial—the Hypertension Control Program . JAMA. 1987 ; 257 : 1484 – 1491 . doi:10.1001/jama.257.11.1484 Google Scholar Crossref Search ADS PubMed WorldCat 9. Chirinos JA , et al. CPAP, weight loss, or both for obstructive sleep apnea . N Engl J Med. 2014 ; 370 : 2265 – 2275 . doi:10.1056/NEJMoa1306187 Google Scholar Crossref Search ADS PubMed WorldCat 10. Giatti S , et al. Association of sodium with obstructive sleep apnea. The ELSA-Brasil Study . Ann Am Thorac Soc. 2021 ; 18 : 502 – 510 . doi:10.1513/AnnalsATS.202005-498OC Google Scholar Crossref Search ADS PubMed WorldCat 11. Revol B , et al. Diuretics in patients with obstructive sleep apnea and concomitant hypertension . Ann Am Thorac Soc. 2021 ; 18 : 2101 – 2102 . doi:10.1513/AnnalsATS.202104-496LE Google Scholar Crossref Search ADS PubMed WorldCat 12. Frost & Sullivan . In an Age of Constant Activity, the Solution to Improving the Nation’s Health May Lie in Helping It Sleep Better. What Benefits Do Patients Experience in Treating Their Obstructive Sleep Apnea? American Academy of Sleep Medicine ; 2016 . http://www.aasmnet.org/sleep-apnea-economic-impact.aspx. Google Scholar Google Preview OpenURL Placeholder Text WorldCat COPAC Author notes These authors contributed equally to this work © The Author(s) 2022. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For permissions, please e-mail: [email protected] This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model) © The Author(s) 2022. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For permissions, please e-mail: [email protected]

journal article

Open Access Collection

Validation of blood-based transcriptomic circadian phenotyping in older adults

Smith, S Kendall; Tran, Peter; Madden, Katherine A; Boyd, Jill; Braun, Rosemary; Musiek, Erik S; Ju, Yo-El S

2022 SLEEP

doi: 10.1093/sleep/zsac148pmid: 35762800

Accepted manuscripts Accepted manuscripts are PDF versions of the author’s final manuscript, as accepted for publication by the journal but prior to copyediting or typesetting. They can be cited using the author(s), article title, journal title, year of online publication, and DOI. They will be replaced by the final typeset articles, which may therefore contain changes. The DOI will remain the same throughout. Article PDF first page preview Close This content is only available as a PDF. Author notes Co-first authors contributed equally to this manuscript © Sleep Research Society 2022. Published by Oxford University Press on behalf of the Sleep Research Society. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. © Sleep Research Society 2022. Published by Oxford University Press on behalf of the Sleep Research Society.

journal article

LitStream Collection

Reversing coronary vascular sequelae of intermittent hypoxia: what is the window of opportunity?

Pham, Luu V; Polotsky, Vsevolod Y

2022 SLEEP

doi: 10.1093/sleep/zsac172pmid: 35869780

Accepted manuscripts Accepted manuscripts are PDF versions of the author’s final manuscript, as accepted for publication by the journal but prior to copyediting or typesetting. They can be cited using the author(s), article title, journal title, year of online publication, and DOI. They will be replaced by the final typeset articles, which may therefore contain changes. The DOI will remain the same throughout. Article PDF first page preview Close This content is only available as a PDF. © The Author(s) 2022. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For permissions, please e-mail: [email protected] This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model) © The Author(s) 2022. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For permissions, please e-mail: [email protected]

journal article

Open Access Collection

Sleep spindle dynamics suggest over-consolidation in post-traumatic stress disorder

van der Heijden, Anna C; Hofman, Winni F; de Boer, Marieke; Nijdam, Mirjam J; van Marle, Hein J F; Jongedijk, Ruud A; Olff, Miranda; Talamini, Lucia M

2022 SLEEP

doi: 10.1093/sleep/zsac139pmid: 35731633

Devastating and persisting traumatic memories are a central symptom of post-traumatic stress disorder (PTSD). Sleep problems are highly co-occurrent with PTSD and intertwined with its etiology. Notably, sleep hosts memory consolidation processes, supported by sleep spindles (11–16 Hz). Here we assess the hypothesis that intrusive memory symptoms in PTSD may arise from excessive memory consolidation, reflected in exaggerated spindling. We use a newly developed spindle detection method, entailing minimal assumptions regarding spindle phenotype, to assess spindle activity in PTSD patients and traumatized controls. Our results show increased spindle activity in PTSD, which positively correlates with daytime intrusive memory symptoms. Together, these findings provide a putative mechanism through which the profound sleep disturbance in PTSD may contribute to memory problems. Due to its uniform and unbiased approach, the new, minimal assumption spindle analysis seems a promising tool to detect aberrant spindling in psychiatric disorders.

journal article

LitStream Collection

Homeostatic response to sleep deprivation and circadian rhythmicity are intact in older adults with insomnia

Tracy, Eunjin Lee; Zhang, Jun; Wilckens, Kristine; Krafty, Robert T; Hasler, Brant P; Hall, Martica H; Buysse, Daniel J

2022 SLEEP

doi: 10.1093/sleep/zsac162pmid: 35878753

Study ObjectivesWe examined whether homeostatic sleep drive and circadian rhythmicity differ in older adults with insomnia (OAI) compared to older good sleepers (GS).MethodsOAI (n = 37) and GS (n = 30) participated in a 60-h in-lab study with sleep deprivation and constant routine paradigms. Homeostatic sleep drive was assessed by examining the effect of sleep deprivation on delta EEG power and theta EEG power, and repeated sleep latency tests. Circadian rhythm was assessed with salivary melatonin (phase and amplitude), core body temperature (phase, amplitude, and mesor), and sleep latency during a constant routine paradigm. Mixed models were used to assess interactions of group (OAS vs GS) with homeostatic sleep and circadian effects.ResultsCompared to GS, OAI showed a greater linear increase in waking theta power during sleep deprivation, but the two groups did not show differential responses to sleep deprivation in delta EEG, or in repeated sleep latency tests. The two groups did not differ in circadian phase or amplitude of melatonin or core body temperature rhythms. OAI had a significantly elevated core body temperature mesor compared to GS.ConclusionsHomeostatic response to sleep deprivation was intact in OAI compared to GS; theta EEG power suggested a greater homeostatic response in OAI. Circadian rhythm amplitude and phase were similar in OAI compared to GS. Elevated body temperature mesor in OAI may indicate elevated physiological arousal. These findings suggest that effective treatments for insomnia in older adults may leverage intact sleep and circadian regulatory mechanisms, rather than repair defective sleep and circadian regulation.

journal article

Open Access Collection

The effect of time on task, sleep deprivation, and time of day on simulated driving performance

Marando, Isabella; Matthews, Raymond W; Grosser, Linda; Yates, Crystal; Banks, Siobhan

2022 SLEEP

doi: 10.1093/sleep/zsac167pmid: 35867054

Sleep deprivation and time of day have been shown to play a critical role in decreasing ability to sustain attention, such as when driving long distances. However, a gap in the literature exists regarding external factors, such as workload. One way to examine workload is via modulating time on task. This study investigated the combined effect of sleep deprivation, time of day, and time on task as a workload factor on driving performance. Twenty-one participants (18–34 years, 10 females) underwent 62 h of sleep deprivation within a controlled laboratory environment. Participants received an 8-h baseline and 9.5-h recovery sleep. Every 8 h, participants completed a Psychomotor Vigilance Task (PVT), Karolinska Sleepiness Scale (KSS), 30-min monotonous driving task and NASA-Task Load Index (TLX). Driving variables examined were lane deviation, number of crashes, speed deviation and time outside the safe zone. Workload was measured by comparing two 15-min loops of the driving track. A mixed model ANOVA revealed significant main effects of day and time of day on all driving performance measures (p < .001). There was a significant main effect of workload on lane deviation (p < .05), indicating that a longer time on task resulted in greater lane deviation. A significant main effect of day (p < .001) but not time of day for the NASA-TLX, PVT and KSS was found. Time on task has a significant further impact on driving performance and should be considered alongside sleep deprivation and time of day when implementing strategies for long-distance driving.

journal article

LitStream Collection

Leptin-mediated neural targets in obesity hypoventilation syndrome

Amorim, Mateus R; Aung, O; Mokhlesi, Babak; Polotsky, Vsevolod Y

2022 SLEEP

doi: 10.1093/sleep/zsac153pmid: 35778900

Obesity hypoventilation syndrome (OHS) is defined as daytime hypercapnia in obese individuals in the absence of other underlying causes. In the United States, OHS is present in 10%–20% of obese patients with obstructive sleep apnea and is linked to hypoventilation during sleep. OHS leads to high cardiorespiratory morbidity and mortality, and there is no effective pharmacotherapy. The depressed hypercapnic ventilatory response plays a key role in OHS. The pathogenesis of OHS has been linked to resistance to an adipocyte-produced hormone, leptin, a major regulator of metabolism and control of breathing. Mechanisms by which leptin modulates the control of breathing are potential targets for novel therapeutic strategies in OHS. Recent advances shed light on the molecular pathways related to the central chemoreceptor function in health and disease. Leptin signaling in the nucleus of the solitary tract, retrotrapezoid nucleus, hypoglossal nucleus, and dorsomedial hypothalamus, and anatomical projections from these nuclei to the respiratory control centers, may contribute to OHS. In this review, we describe current views on leptin-mediated mechanisms that regulate breathing and CO2 homeostasis with a focus on potential therapeutics for the treatment of OHS.

journal article

LitStream Collection

Comparison of rapid eye movement without atonia quantification methods to diagnose rapid eye movement sleep behavior disorder: a systematic review

Byun, Jung-Ick; Yang, Tae-Won; Sunwoo, Jun-Sang; Shin, Won Chul; Kwon, Oh-Young; Jung, Ki-Young

2022 SLEEP

doi: 10.1093/sleep/zsac150pmid: 35881545

Study ObjectivesRapid eye movement (REM) sleep without atonia (RWA) is essential for diagnosing REM sleep behavior disorder (RBD). Manual and automatic quantifications of RWA that use different criteria have been validated. This study compared the RWA quantification methods for diagnosing RBD.MethodsThe PubMed, EMBASE, Web of Science, and Cochrane Library databases were systemically searched for studies published from inception to December 2021. The inclusion criteria were cohort, cross-sectional, and case-control studies assessing the sensitivity and specificity of RWA quantification methods. Pooled estimates of the sensitivity, specificity, diagnostic odds ratio (DOR), and area under the curve (AUC) were determined. Risk of bias and certainty of evidence was assessed using the Quality Assessment of Diagnostic Accuracy Studies tool and the Grading of Recommendations, Assessment, Development, and Evaluations framework, respectively.ResultsFourteen articles including 402 patients with RBD met the inclusion criteria. Manual methods evaluating any chin and phasic flexor digitorum superficialis (FDS) activity had the highest DOR (138.8, 95% CI = 21.8% to 881.7%) and AUC (0.9686). The automatic REM atonia index (RAI) showed similar or higher sensitivity (89.1%, 95% CI = 84.6% to 92.7%) but a lower specificity (73.5%), DOR (43.1), and AUC (0.9369) than the manual techniques.ConclusionsIn this meta-analysis, manual RWA quantification that employed chin or phasic FDS activity had the best RBD diagnostic performance. The automatic RAI method may be useful for screening patients with RBD. The results should be interpreted carefully because of the high risk of bias in patient selection and significant heterogeneity among the studies.PROSPERO Registration numberCRD42021276445.

journal article

LitStream Collection

Temporal changes in coronary artery function and flow velocity reserve in mice exposed to chronic intermittent hypoxia

Badran, Mohammad; Bender, Shawn B; Khalyfa, Abdelnaby; Padilla, Jaume; Martinez-Lemus, Luis A; Gozal, David

2022 SLEEP

doi: 10.1093/sleep/zsac131pmid: 35661901

Study ObjectivesObstructive sleep apnea (OSA) is a chronic condition characterized by intermittent hypoxia (IH) that is implicated in an increased risk of cardiovascular disease (i.e., coronary heart disease, CHD) and associated with increased overall and cardiac-specific mortality. Accordingly, we tested the hypothesis that experimental IH progressively impairs coronary vascular function and in vivo coronary flow reserve.MethodsMale C57BL/6J mice (8-week-old) were exposed to IH (FiO2 21% 90 s–6% 90 s) or room air (RA; 21%) 12 h/day during the light cycle for 2, 6, 16, and 28 weeks. Coronary artery flow velocity reserve (CFVR) was measured at each time point using a Doppler system. After euthanasia, coronary arteries were micro-dissected and mounted on wire myograph to assess reactivity to acetylcholine (ACh) and sodium nitroprusside (SNP).ResultsEndothelium-dependent coronary relaxation to ACh was preserved after 2 weeks of IH (80.6 ± 7.8%) compared to RA (87.8 ± 7.8%, p = 0.23), but was significantly impaired after 6 weeks of IH (58.7 ± 16.2%, p = 0.02). Compared to ACh responses at 6 weeks, endothelial dysfunction was more pronounced in mice exposed to 16 weeks (48.2 ± 5.3%) but did not worsen following 28 weeks of IH (44.8 ± 11.6%). A 2-week normoxic recovery after a 6-week IH exposure reversed the ACh abnormalities. CFVR was significantly reduced after 6 (p = 0.0006) and 28 weeks (p < 0.0001) of IH when compared to controls.ConclusionChronic IH emulating the hypoxia-re-oxygenation cycles of moderate-to-severe OSA promotes coronary artery endothelial dysfunction and CFVR reductions in mice, which progressively worsen until reaching asymptote between 16 and 28 weeks. Normoxic recovery after 6 weeks exposure reverses the vascular abnormalities.

journal article

LitStream Collection

Assessing the performance of quantified rapid eye movement sleep without atonia methods for the diagnosis of rapid eye movement sleep behavior disorder: a dog biting its tail

Ferri, Raffaele; Schenck, Carlos H

2022 SLEEP

doi: 10.1093/sleep/zsac164pmid: 35811112

Accepted manuscripts Accepted manuscripts are PDF versions of the author’s final manuscript, as accepted for publication by the journal but prior to copyediting or typesetting. They can be cited using the author(s), article title, journal title, year of online publication, and DOI. They will be replaced by the final typeset articles, which may therefore contain changes. The DOI will remain the same throughout. Article PDF first page preview Close This content is only available as a PDF. © The Author(s) 2022. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For permissions, please e-mail: [email protected] This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model) © The Author(s) 2022. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For permissions, please e-mail: [email protected]

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