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      Heart Rate Responses to Autonomic Challenges in Obstructive Sleep Apnea

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          Abstract

          Obstructive sleep apnea (OSA) is accompanied by structural alterations and dysfunction in central autonomic regulatory regions, which may impair dynamic and static cardiovascular regulation, and contribute to other syndrome pathologies. Characterizing cardiovascular responses to autonomic challenges may provide insights into central nervous system impairments, including contributions by sex, since structural alterations are enhanced in OSA females over males. The objective was to assess heart rate responses in OSA versus healthy control subjects to autonomic challenges, and, separately, characterize female and male patterns. We studied 94 subjects, including 37 newly-diagnosed, untreated OSA patients (6 female, age mean±std: 52.1±8.1 years; 31 male aged 54.3±8.4 years), and 57 healthy control subjects (20 female, 50.5±8.1 years; 37 male, 45.6±9.2 years). We measured instantaneous heart rate with pulse oximetry during cold pressor, hand grip, and Valsalva maneuver challenges. All challenges elicited significant heart rate differences between OSA and control groups during and after challenges (repeated measures ANOVA, p<0.05). In post-hoc analyses, OSA females showed greater impairments than OSA males, which included: for cold pressor, lower initial increase (OSA vs. control: 9.5 vs. 7.3 bpm in females, 7.6 vs. 3.7 bpm in males), OSA delay to initial peak (2.5 s females/0.9 s males), slower mid-challenge rate-of-increase (OSA vs. control: −0.11 vs. 0.09 bpm/s in females, 0.03 vs. 0.06 bpm/s in males); for hand grip, lower initial peak (OSA vs. control: 2.6 vs. 4.6 bpm in females, 5.3 vs. 6.0 bpm in males); for Valsalva maneuver, lower Valsalva ratio (OSA vs. control: 1.14 vs. 1.30 in females, 1.29 vs. 1.34 in males), and OSA delay during phase II (0.68 s females/1.31 s males). Heart rate responses showed lower amplitude, delayed onset, and slower rate changes in OSA patients over healthy controls, and impairments may be more pronounced in females. The dysfunctions may reflect central injury in the syndrome, and suggest autonomic deficiencies that may contribute to further tissue and functional pathologies.

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          Estimation of the clinically diagnosed proportion of sleep apnea syndrome in middle-aged men and women.

          The proportion of sleep apnea syndrome (SAS) in the general adult population that goes undiagnosed was estimated from a sample of 4,925 employed adults. Questionnaire data on doctor-diagnosed sleep apnea were followed up to ascertain the prevalence of diagnosed sleep apnea. In-laboratory polysomnography on a subset of 1,090 participants was used to estimate screen-detected sleep apnea. In this population, without obvious barriers to health care for sleep disorders, we estimate that 93% of women and 82% of men with moderate to severe SAS have not been clinically diagnosed. These findings provide a baseline for assessing health care resource needs for sleep apnea.
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            Effect of continuous positive airway pressure on the incidence of hypertension and cardiovascular events in nonsleepy patients with obstructive sleep apnea: a randomized controlled trial.

            Continuous positive airway pressure (CPAP) is the first-line treatment for patients with symptomatic obstructive sleep apnea (OSA). However, its indication for all patients with sleep-disordered breathing, regardless of daytime symptoms, is unclear. To evaluate the effect of CPAP treatment on the incidence of hypertension or cardiovascular events in a cohort of nonsleepy patients with OSA. Multicenter, parallel-group, randomized controlled trial in 14 teaching hospitals in Spain. Between May 2004 and May 2006, 725 consecutive patients were enrolled who had an apnea-hypopnea index of 20 h(-1) or greater and an Epworth Sleepiness Scale score of 10 or less (scores range from 0-24, with values <10 suggesting no daytime sleepiness). Exclusion criteria were previous cardiovascular event, physical or psychological incapacity, chronic disease, or drug or alcohol addiction. Follow-up ended in May 2009. Patients were allocated to receive CPAP treatment or no active intervention. All participants received dietary counseling and sleep hygiene advice. Incidence of either systemic hypertension (taking antihypertensive medication or blood pressure greater than 140/90 mm Hg) or cardiovascular event (nonfatal myocardial infarction, nonfatal stroke, transient ischemic attack, hospitalization for unstable angina or arrhythmia, heart failure, or cardiovascular death). Seven hundred twenty-three patients underwent follow-up for a median of 4 (interquartile range, 2.7-4.4) years (1 patient from each group did not receive allocated treatment); 357 in the CPAP group and 366 in the control group were included in the analysis. In the CPAP group there were 68 patients with new hypertension and 28 cardiovascular events (17 unstable angina or arrhythmia, 3 nonfatal stroke, 3 heart failure, 2 nonfatal myocardial infarction, 2 transient ischemic attack, 1 cardiovascular death). In the control group there were 79 patients with new hypertension and 31 cardiovascular events (11 unstable angina or arrhythmia, 8 nonfatal myocardial infarction, 5 transient ischemic attack, 5 heart failure, 2 nonfatal stroke). The hypertension or cardiovascular event incidence density rate was 9.20 per 100 person-years (95% CI, 7.36-11.04) in the CPAP group and 11.02 per 100 person-years (95% CI, 8.96-13.08) in the control group. The incidence density ratio was 0.83 (95% CI, 0.63-1.1; P = .20). In patients with OSA without daytime sleepiness, the prescription of CPAP compared with usual care did not result in a statistically significant reduction in the incidence of hypertension or cardiovascular events. However, the study may have had limited power to detect a significant difference. clinicaltrials.gov Identifier: NCT00127348.
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              Thermoregulation: some concepts have changed. Functional architecture of the thermoregulatory system.

              While summarizing the current understanding of how body temperature (T(b)) is regulated, this review discusses the recent progress in the following areas: central and peripheral thermosensitivity and temperature-activated transient receptor potential (TRP) channels; afferent neuronal pathways from peripheral thermosensors; and efferent thermoeffector pathways. It is proposed that activation of temperature-sensitive TRP channels is a mechanism of peripheral thermosensitivity. Special attention is paid to the functional architecture of the thermoregulatory system. The notion that deep T(b) is regulated by a unified system with a single controller is rejected. It is proposed that T(b) is regulated by independent thermoeffector loops, each having its own afferent and efferent branches. The activity of each thermoeffector is triggered by a unique combination of shell and core T(b)s. Temperature-dependent phase transitions in thermosensory neurons cause sequential activation of all neurons of the corresponding thermoeffector loop and eventually a thermoeffector response. No computation of an integrated T(b) or its comparison with an obvious or hidden set point of a unified system is necessary. Coordination between thermoeffectors is achieved through their common controlled variable, T(b). The described model incorporates Kobayashi's views, but Kobayashi's proposal to eliminate the term sensor is rejected. A case against the term set point is also made. Because this term is historically associated with a unified control system, it is more misleading than informative. The term balance point is proposed to designate the regulated level of T(b) and to attract attention to the multiple feedback, feedforward, and open-loop components that contribute to thermal balance.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2013
                23 October 2013
                : 8
                : 10
                : e76631
                Affiliations
                [1 ]University of California at Los Angeles School of Nursing, University of California Los Angeles, Los Angeles, California, United States of America
                [2 ]Brain Research Institute, David Geffen School of Medicine at University of California Los Angeles, University of California Los Angeles, Los Angeles, California, United States of America
                [3 ]Department of Neurobiology, David Geffen School of Medicine at University of California Los Angeles, University of California Los Angeles, Los Angeles, California, United States of America
                [4 ]Department of Neurology, David Geffen School of Medicine at University of California Los Angeles, University of California Los Angeles, Los Angeles, California, United States of America
                Tokai University, Japan
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: PMM RK MAW RMH. Performed the experiments: PMM RK FLY MAW RMH. Analyzed the data: PMM RK RMH. Contributed reagents/materials/analysis tools: PMM RK FLY RMH. Wrote the paper: PMM RK FLY MAW RMH.

                Article
                PONE-D-13-20175
                10.1371/journal.pone.0076631
                3806804
                24194842
                9092bf30-2916-4c28-97de-181262f7be04
                Copyright @ 2013

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 16 May 2013
                : 23 August 2013
                Page count
                Pages: 15
                Funding
                Supported by the National Institutes of Health NR013693 ( http://www.ninr.nih.gov/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article

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