21 results on '"Susie Yim Yeh"'
Search Results
2. Long-Term Noninvasive Ventilation in Chronic Stable Hypercapnic Chronic Obstructive Pulmonary Disease. An Official American Thoracic Society Clinical Practice Guideline
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Robert L. Owens, Shandra L Knight, Richard D. Branson, Simon Oczkowski, Shilpa Rahangdale, John M. Coleman, M. Bradley Drummond, Madalina Macrea, Amanda J. Piper, Dean R. Hess, Bram Rochwerg, Bartolome R. Celli, Naresh M. Punjabi, Jill A. Ohar, Susie Yim-Yeh, Peter J. Wijkstra, and Jeremy E. Orr
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Pulmonary and Respiratory Medicine ,American Thoracic Society Documents ,medicine.medical_specialty ,COPD ,business.industry ,Epworth Sleepiness Scale ,medicine.medical_treatment ,Polysomnogram ,noninvasive ventilation ,Guideline ,Critical Care and Intensive Care Medicine ,medicine.disease ,hypercapnic respiratory failure ,chronic obstructive pulmonary disease ,Obstructive sleep apnea ,Respiratory failure ,Oxygen therapy ,Medicine ,Noninvasive ventilation ,business ,Intensive care medicine - Abstract
Background: Noninvasive ventilation (NIV) is used for patients with chronic obstructive pulmonary disease (COPD) and chronic hypercapnia. However, evidence for clinical efficacy and optimal management of therapy is limited. Target Audience: Patients with COPD, clinicians who care for them, and policy makers. Methods: We summarized evidence addressing five PICO (patients, intervention, comparator, and outcome) questions. The GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach was used to evaluate the certainty in evidence and generate actionable recommendations. Recommendations were formulated by a panel of pulmonary and sleep physicians, respiratory therapists, and methodologists using the Evidence-to-Decision framework. Recommendations: 1) We suggest the use of nocturnal NIV in addition to usual care for patients with chronic stable hypercapnic COPD (conditional recommendation, moderate certainty); 2) we suggest that patients with chronic stable hypercapnic COPD undergo screening for obstructive sleep apnea before initiation of long-term NIV (conditional recommendation, very low certainty); 3) we suggest not initiating long-term NIV during an admission for acute-on-chronic hypercapnic respiratory failure, favoring instead reassessment for NIV at 2–4 weeks after resolution (conditional recommendation, low certainty); 4) we suggest not using an in-laboratory overnight polysomnogram to titrate NIV in patients with chronic stable hypercapnic COPD who are initiating NIV (conditional recommendation, very low certainty); and 5) we suggest NIV with targeted normalization of PaCO2 in patients with hypercapnic COPD on long-term NIV (conditional recommendation, low certainty). Conclusions: This expert panel provides evidence-based recommendations addressing the use of NIV in patients with COPD and chronic stable hypercapnic respiratory failure.
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- 2020
3. The Influence of Intermittent Hypoxemia on Platelet Activation in Obese Patients with Obstructive Sleep Apnea
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Mark I. Furman, Alan D. Michelson, Marc R. Barnard, Shilpa Rahangdale, Victor Novack, Atul Malhotra, Andrew L. Frelinger, KE Stevenson, and Susie Yim Yeh
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Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Sleep apnea ,Polysomnography ,Hypoxia (medical) ,medicine.disease ,Obesity ,respiratory tract diseases ,Surgery ,Hypoxemia ,Obstructive sleep apnea ,Neurology ,Internal medicine ,Cardiology ,medicine ,Platelet ,Neurology (clinical) ,Platelet activation ,medicine.symptom ,business - Abstract
Objectives:Literature regarding platelet function in obstructive sleep apnea (OSA) has considerable limitations. Given the central role of platelets in atherothrombosis and the known cardiovascular...
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- 2011
4. The effect of increased genioglossus activity and end-expiratory lung volume on pharyngeal collapse
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Atul Malhotra, Danny J. Eckert, Susie Yim-Yeh, Shilpa Rahangdale, Amy S. Jordan, David P. White, and Robert L. Owens
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Adult ,Male ,Time Factors ,Supine position ,Physiology ,medicine.medical_treatment ,Magnetometry ,Tongue ,Physiology (medical) ,Supine Position ,medicine ,Humans ,Lung volumes ,Continuous positive airway pressure ,Lung ,Sleep Apnea, Obstructive ,Genioglossus ,Continuous Positive Airway Pressure ,Electromyography ,business.industry ,Sleep apnea ,Articles ,Middle Aged ,medicine.disease ,Critical closing pressure ,Respiratory Muscles ,respiratory tract diseases ,Obstructive sleep apnea ,Treatment Outcome ,Exhalation ,Anesthesia ,Pharynx ,Female ,Sleep Stages ,Lung Volume Measurements ,Airway ,business - Abstract
Increasing either genioglossus muscle activity (GG) or end-expiratory lung volume (EELV) improves airway patency but not sufficiently for adequate treatment of obstructive sleep apnea (OSA) in most patients. The mechanisms by which these variables alter airway collapsibility likely differ, with increased GG causing airway dilation, whereas increased EELV may stiffen the airway walls through caudal traction. We sought to determine whether the airway stabilizing effect of GG activation is enhanced when EELV is increased. To investigate this aim, 15 continuous positive airway pressure (CPAP)-treated OSA patients were instrumented with an epiglottic catheter, intramuscular GG-EMG electrodes, magnetometers, and a nasal mask/pneumotachograph. Subjects slept supine in a sealed, head-out plastic chamber in which the extra-thoracic pressure could be lowered (to raise EELV) while on nasal CPAP with a variable deadspace to allow CO2 stimulation (and GG activation). The pharyngeal critical closing pressure (PCRIT) was measured by sudden reduction of CPAP for three to five breaths each minute during non-rapid eye movement (NREM) sleep in 4 conditions: a) baseline, b) 500 ml increased EELV, c) 50% increased GG, and d) conditions b and c combined. PCRIT was found to be reduced from 2.2 ± 0.7 cmH2O at baseline to −1.0 ± 0.5 with increased EELV, 0.6 ± 0.7 with increased GG and −1.6 ± 0.7 when both variables were raised ( P < 0.001). The slope of the PCRIT curves remained unchanged in all conditions ( P = 0.05). However, the CPAP level at which flow limitation developed was lower in both increased EELV conditions ( P = 0.001). These findings indicate that while both increased GG and EELV improve airway collapsibility, the combination of both variables has little additional effect over increasing EELV alone.
- Published
- 2010
5. Airway Dilator Muscle Activity and Lung Volume During Stable Breathing in Obstructive Sleep Apnea
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Matthias Eikermann, Susie Yim-Yeh, Atul Malhotra, KE Stevenson, Amy S. Jordan, David P. White, Yu-Lun Lo, Andrew Wellman, S. Smith, and Danny J. Eckert
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Adult ,Male ,Polysomnography ,medicine.medical_treatment ,Sleep, REM ,Non-rapid eye movement sleep ,stomatognathic system ,Sleep and breathing ,Physiology (medical) ,Humans ,Medicine ,Continuous positive airway pressure ,Slow-wave sleep ,Sleep Apnea, Obstructive ,Sleep Stages ,Genioglossus ,medicine.diagnostic_test ,Electromyography ,business.industry ,Airway Resistance ,musculoskeletal, neural, and ocular physiology ,Muscle, Smooth ,Middle Aged ,medicine.disease ,respiratory tract diseases ,Expiratory Reserve Volume ,Obstructive sleep apnea ,Muscle Tonus ,Anesthesia ,Female ,Airway Muscle Activity in OSA ,Neurology (clinical) ,Pulmonary Ventilation ,business - Abstract
Many patients with obstructive sleep apnea (OSA) have spontaneous periods of stable flow limited breathing during sleep without respiratory events or arousals. In addition, OSA is often more severe during REM than NREM and more severe during stage 2 than slow wave sleep (SWS). The physiological mechanisms for these observations are unknown. Thus we aimed to determine whether the activity of two upper airway dilator muscles (genioglossus and tensor palatini) or end-expiratory lung volume (EELV) differ between (1) spontaneously occurring stable and cyclical breathing and (2) different sleep stages in OSA.Physiologic observation.Sleep physiology laboratory.15 OSA patients with documented periods of spontaneous stable breathing.Subjects were instrumented with intramuscular electrodes for genioglossus and tensor palatini electromyograms (EMG(GG) and EMG(TP)), chest and abdominal magnetometers (EELV measurement), an epiglottic pressure catheter (respiratory effort), and a mask and pneumotachograph (airflow/ventilation). Patients slept supine overnight without CPAP.Peak and Tonic EMG(GG) were significantly lower during cyclical (85.4 +/- 2.7 and 94.6 +/- 4.7 % total activity) than stable breathing (109.4 +/- 0.4 and 103 +/- 0.8% total activity, respectively). During respiratory events in REM, tonic EMG(GG) activity was lower than during respiratory events in stage 2 (71.9 +/- 5.1 and 119.6 +/- 5.6% total activity). EMG(GG) did not differ between stable stage 2 and stable SWS (98.9 +/- 3.2 versus 109.7 +/- 4.4% total activity), nor did EMG(TP) or EELV differ in any breathing condition/sleep stage.Increased genioglossus muscle tone is associated with spontaneous periods of stable flow limited breathing in the OSA subjects studied. Reductions in genioglossus activity during REM may explain the higher severity of OSA in that stage. Increased lung volume and tensor palatini activity do not appear to be major mechanisms enabling spontaneous stable flow limited breathing periods.
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- 2009
6. Upper airway function in the pathogenesis of obstructive sleep apnea: a review of the current literature
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Susie Yim Yeh, Danny J. Eckert, Robert L. Owens, and Atul Malhotra
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Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,medicine.medical_treatment ,Respiratory System ,Disease ,Article ,Positive-Pressure Respiration ,Pathogenesis ,Humans ,Medicine ,Continuous positive airway pressure ,Intensive care medicine ,Collapse (medical) ,Sleep Apnea, Obstructive ,Lung ,Continuous Positive Airway Pressure ,business.industry ,Sleep apnea ,medicine.disease ,Respiratory Muscles ,respiratory tract diseases ,Obstructive sleep apnea ,medicine.anatomical_structure ,Anesthesia ,Pharynx ,medicine.symptom ,Airway ,business - Abstract
Obstructive sleep apnea is an increasingly prevalent disease, with a considerable societal burden. The disease is defined by recurrent intermittent collapse of the upper airway. Understanding of and treatment for the disease is largely confined to relief of the mechanical obstruction of the upper airway by application of continuous positive airway pressure, and less commonly weight loss or surgery. However, recent work has focused on the function, rather than structure alone, of the upper airway.The following contributors to upper airway structure and function have been studied: traditional fixed anatomical abnormalities, dynamic anatomical changes, upper airway dilator muscle dysfunction, lung volumes, and instability in control of breathing. In each patient with obstructive sleep apnea, the relative contribution of each of these components may be quite variable. The studies reviewed here describe methods to evaluate these factors, and some attempts at treatment.Ongoing studies are attempting to classify patients on the basis of the underlying pathophysiology. This work suggests that obstructive sleep apnea is a heterogeneous disease with multiple root causes. Ultimately, such a classification may allow more individualized treatment, not only relying on mechanical relief of the upper airway obstruction.
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- 2008
7. A Pilot Investigation Of The Effects Of Continuous Positive Airway Pressure On Microcirculatory Reactivity Amongst Obese Obstructive Sleep Apnea Patients
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Shilpa Rahangdale, Susie Yim-Yeh, Atul Malhotra, Jayshankar Balachandran, Francesco Tecilazich, Pamela N. DeYoung, Aristidis Veves, and Jessie P. Bakker
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Obstructive sleep apnea ,business.industry ,medicine.medical_treatment ,Anesthesia ,medicine ,Continuous positive airway pressure ,medicine.disease ,Reactivity (psychology) ,business - Published
- 2012
8. Eszopiclone increases the respiratory arousal threshold and lowers the apnoea/hypopnoea index in obstructive sleep apnoea patients with a low arousal threshold
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Geoffrey B. Kehlmann, Shilpa Rahangdale, David P. White, Danny J. Eckert, Atul Malhotra, Andrew Wellman, Robert L. Owens, and Susie Yim-Yeh
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Adult ,medicine.drug_class ,Polysomnogram ,Article ,Piperazines ,Arousal ,Hypnotic ,Double-Blind Method ,Sleep and breathing ,Low arousal theory ,medicine ,Humans ,Hypnotics and Sedatives ,Eszopiclone ,Sleep Apnea, Obstructive ,business.industry ,Respiration ,Sleep apnea ,General Medicine ,medicine.disease ,respiratory tract diseases ,Anesthesia ,Sedative ,business ,Azabicyclo Compounds ,medicine.drug - Abstract
Recent insights into sleep apnoea pathogenesis reveal that a low respiratory arousal threshold (awaken easily) is important for many patients. As most patients experience stable breathing periods mediated by upper-airway dilator muscle activation via accumulation of respiratory stimuli, premature awakening may prevent respiratory stimuli build up as well as the resulting stabilization of sleep and breathing. The aim of the present physiological study was to determine the effects of a non-benzodiazepine sedative, eszopiclone, on the arousal threshold and the AHI (apnoea/hypopnoea index) in obstructive sleep apnoea patients. We hypothesized that eszopiclone would increase the arousal threshold and lower the AHI in patients with a low arousal threshold (0 to −15 cmH2O). Following a baseline overnight polysomnogram with an epiglottic pressure catheter to quantify the arousal threshold, 17 obstructive sleep apnoea patients, without major hypoxaemia [nadir SaO2 (arterial blood oxygen saturation) >70%], returned on two additional nights and received 3 mg of eszopiclone or placebo immediately prior to each study. Compared with placebo, eszopiclone significantly increased the arousal threshold [−14.0 (−19.9 to −10.9) compared with −18.0 (−22.2 to −15.1) cmH2O; P
- Published
- 2011
9. Effect of mild, asymptomatic obstructive sleep apnea on daytime heart rate variability and impedance cardiography measurements
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Jessie P. Bakker, Susie Yim-Yeh, Ary L. Goldberger, Shilpa Rahangdale, Jay S. Balachandran, Joseph E. Mietus, and Atul Malhotra
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Adult ,Male ,medicine.medical_specialty ,Supine position ,Time Factors ,Polysomnography ,Autonomic Nervous System ,Asymptomatic ,Cardiography, Impedance ,Article ,stomatognathic system ,Heart Rate ,Internal medicine ,medicine ,Heart rate variability ,Humans ,Prospective Studies ,Sleep Apnea, Obstructive ,medicine.diagnostic_test ,business.industry ,Sleep apnea ,medicine.disease ,Prognosis ,respiratory tract diseases ,Circadian Rhythm ,Impedance cardiography ,Obstructive sleep apnea ,Blood pressure ,Cardiology ,Female ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business ,Follow-Up Studies - Abstract
Dysregulation of autonomic nervous system dynamics is important in the pathophysiology of cardiovascular risk in obstructive sleep apnea (OSA). Heart rate variability (HRV) and impedance cardiography measures can estimate autonomic activity but have not gained traction clinically. The hypothesis of this study was that even in a cohort of patients with mild, asymptomatic OSA without overt cardiovascular disease, daytime HRV metrics and impedance cardiography measurements of preejection period would demonstrate increased sympathetic and decreased parasympathetic modulation compared to matched controls. Obese subjects (body mass index ≥30 kg/m 2 ) without any known cardiovascular or inflammatory co-morbidities were recruited from the community. Subjects underwent standard in-laboratory polysomnography followed by simultaneous electrocardiographic and impedance cardiographic recordings while supine, supine with paced breathing, and after standing. Seventy-four subjects were studied, and 59% had OSA (apnea-hypopnea index ≥10 events/hour), with a median apnea-hypopnea index of 25.8 events/hour. Subjects with OSA had significantly decreased daytime time- and frequency-domain HRV indexes, but not significantly different preejection periods, compared to controls. Apnea-hypopnea index was a significant independent predictor of time-domain HRV measures in all awake conditions, after controlling for age, gender, blood pressure, fasting cholesterol levels and glycosylated hemoglobin. In conclusion, these results demonstrate reductions in cardiac vagal modulation, as measured by multiple daytime time-domain markers of HRV, in patients with asymptomatic OSA compared to controls. Further prospective outcomes-based studies are needed to evaluate the applicability of these metrics for noninvasive screening of obese patients with asymptomatic OSA, before the onset of overt cardiovascular disease.
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- 2011
10. PNN10 And PNN20, Markers Of Vagal Tone, Are Decreased In Obese Patients With Obstructive Sleep Apnea Compared To Controls
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Erik Smales, Susie Yim-Yeh, Andrea L. Carusona, KE Stevenson, Joe Mietus, Shilpa Rahangdale, Atul Malhotra, Ary L. Goldberger, Pamela N. DeYoung, and Jay S. Balachandran
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Obstructive sleep apnea ,medicine.medical_specialty ,business.industry ,Internal medicine ,medicine ,Cardiology ,Vagal tone ,medicine.disease ,business - Published
- 2011
11. Obstructive sleep apnea and aging effects on macrovascular and microcirculatory function
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Atul Malhotra, Susie Yim-Yeh, Anh Nguyen, Shilpa Rahangdale, Victor Novack, Amy S. Jordan, and Aristidis Veves
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Adult ,Male ,medicine.medical_specialty ,Aging ,Effects of OSA and Aging on Macro and Microvascular Functions ,Endothelium ,Population ,Ischemia ,Hypoxemia ,Cohort Studies ,Young Adult ,Sex Factors ,Physiology (medical) ,Internal medicine ,Laser-Doppler Flowmetry ,Medicine ,Humans ,Obesity ,Endothelial dysfunction ,education ,Pulse wave velocity ,education.field_of_study ,Sleep Apnea, Obstructive ,business.industry ,Microcirculation ,Age Factors ,Middle Aged ,medicine.disease ,respiratory tract diseases ,Obstructive sleep apnea ,Vasodilation ,Endocrinology ,medicine.anatomical_structure ,Case-Control Studies ,Arterial stiffness ,Cardiology ,Female ,Neurology (clinical) ,Endothelium, Vascular ,medicine.symptom ,business - Abstract
WITH THE OBESITY EPIDEMIC, THE PREVALENCE OF OBSTRUCTIVE SLEEP APNEA (OSA) IS ALMOST CERTAINLY ON THE RISE.1 MANY HAVE THEORIZED THAT repetitive hypoxemia and sympathetic surges, which characterize OSA, can lead to oxidative stress, systemic inflammation, endothelial dysfunction, and, ultimately, cardiovascular disease.2–4 OSA causes hypertension5,6 and has been associated with other cardiovascular sequelae, such as stroke,7 ischemic heart disease, heart failure,8 and arrhythmias.9 Physiologic studies of OSA and cardiovascular disease have been of predominantly male populations with comorbid conditions who present to sleep clinics. Often, data from patients with OSA from sleep clinics are matched with those obese control subjects from the general population or from primary care clinics. Studies that include patients referred to sleep clinics with suspected OSA, however, may have a referral bias. We sought, therefore, to study the effect of OSA on an obese but healthy population recruited primarily from the community to assess OSA effects. Because we wanted to assess subclinical effects of OSA in an obese population without comorbidities, we limited our study to correlates of cardiovascular endpoints, such as flow-mediated dilation (FMD), arterial stiffness, and skin microvascular reactivity. FMD is a measure of endothelial function derived by comparing arterial vessel dilation before and after hyperemic ischemia.10–14 Dysfunctional endothelium results in decreased arterial vessel dilation after hyperemic ischemia due to reduced endothelial nitric oxide production, likely a harbinger of atherosclerosis.15 Arterial stiffness is likely a composite measure of arterial elasticity, endothelial function, and sympathetic tone.16,17 Although important distinctions exist between various metrics of arterial stiffness (e.g., augmentation index [AIx] and pulse wave velocity),22,23 a number of studies have shown increases in OSA and improvements with treatment with continuous positive airway pressure.12,18,19,44 Finally, skin microvascular reactivity has been associated with poor wound healing and increased insulin resistance in diabetes, but the effect of OSA is unknown.24–26 We hypothesized that OSA would have an effect in this obese population on both macrovascular and microvascular reactivity and arterial stiffness (as estimated by the AIx). Furthermore, because age is a strong predictor of both endothelial function and arterial stiffness, we predefined a subgroup of younger subjects (< 50 years) for further analyses. We theorized that the effect of OSA on vascular function may be modulated by age and that such influences may be differentially expressed among our vascular measurements.27 As a result, we speculated that the effects of OSA on vascular function would be most pronounced in younger participants.
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- 2010
12. Vascular dysfunction in obstructive sleep apnea and type 2 diabetes mellitus
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Aristidis Veves, Susie Yim-Yeh, Victor Novack, Shilpa Rahangdale, Atul Malhotra, KE Stevenson, and Anh Nguyen
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Adult ,Male ,medicine.medical_specialty ,Adolescent ,Brachial Artery ,Endocrinology, Diabetes and Metabolism ,Polysomnography ,Medicine (miscellaneous) ,Type 2 diabetes ,Article ,Young Adult ,Endocrinology ,Diabetes mellitus ,Internal medicine ,medicine.artery ,Medicine ,Humans ,Sleep study ,Obesity ,Brachial artery ,Aged ,Ultrasonography ,Aged, 80 and over ,Sleep Apnea, Obstructive ,Nutrition and Dietetics ,medicine.diagnostic_test ,business.industry ,Sleep apnea ,Type 2 Diabetes Mellitus ,Middle Aged ,medicine.disease ,Obstructive sleep apnea ,Diabetes Mellitus, Type 2 ,Case-Control Studies ,Cardiology ,Blood Vessels ,Female ,business ,Diabetic Angiopathies - Abstract
Despite the high prevalence of obstructive sleep apnea (OSA) in type 2 diabetes mellitus (DM), the attributable vascular risk from each condition is unknown. We hypothesize that OSA may have a similar effect on vascular function as type 2 diabetes does. Healthy normal-weight subjects, healthy obese subjects, subjects with type 2 diabetes, and obese subjects with OSA were enrolled. Vascular function was assessed with brachial artery ultrasound for flow-mediated dilatation (FMD) and in skin microcirculation by laser Doppler flowmetry. One hundred fifty-three subjects were studied: healthy normal-weight controls (NCs) (n = 14), healthy obese controls (OCs) (n = 33), subjects with DM (n = 68), and obese subjects with OSA (n = 38). The DM group did not undergo sleep study and thus may have had subclinical OSA. The OSA and type 2 diabetes groups had impaired FMD as compared to both the normal-weight and OC groups (5.8 ± 3.8%, 5.4 ± 1.6% vs. 9.1 ± 2.5%, 8.3 ± 5.1%, respectively, P < 0.001, post hoc Fischer test). When referenced to the NC group, a multiple linear regression model adjusting for covariates found that baseline brachial artery diameter (β = -3.75, P < 0.001), OSA (β = -2.45, P = 0.02) and type 2 diabetes status (β = -2.31, P = 0.02), negatively predicted % FMD. OSA status did not seem to affect nitroglycerin-induced vasodilation (endothelium-independent) of the brachial artery or vascular function in the skin microcirculation. OSA impairs endothelial function in the brachial artery to a similar degree as type 2 diabetes does. OSA, however, does not appear to affect brachial endothelium-independent vasodilation or skin microcirculatory function. Treatment of OSA in patients with concomitant type 2 diabetes, therefore, may be a potential therapeutic option to improve macro-, but not microvascular outcomes.
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- 2010
13. Eszopiclone REDUCES Obstructive Sleep Apnea Severity In Patients With A Low Respiratory Arousal Threshold: A Randomized Controlled Study
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Danny J. Eckert, Andrew Wellman, Susie Yim-Yeh, David P. White, Shilpa Rahangdale, Robert L. Owens, Atul Malhotra, and Geoff Kehlmann
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Eszopiclone ,business.industry ,medicine.disease ,Arousal ,law.invention ,Obstructive sleep apnea ,Randomized controlled trial ,law ,Anesthesia ,medicine ,In patient ,Respiratory system ,business ,medicine.drug - Published
- 2010
14. A Non-Parametric Surrogate-based Test of Significance for T-Wave Alternans Detection
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Gari D. Clifford, Shamim Nemati, O Abdala, Violeta Monasterio, Susie Yim-Yeh, and Atul Malhotra
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Databases, Factual ,Noise reduction ,Biomedical Engineering ,Nonparametric statistics ,Models, Cardiovascular ,Beat (acoustics) ,Signal Processing, Computer-Assisted ,T wave alternans ,Article ,Statistics, Nonparametric ,Surrogate data ,Communication noise ,Electrocardiography ,Moving average ,Statistics ,Probability distribution ,Humans ,Computer Simulation ,Mathematics - Abstract
We present a nonparametric adaptive surrogate test that allows for the differentiation of statistically significant T-wave alternans (TWA) from alternating patterns that can be solely explained by the statistics of noise. The proposed test is based on estimating the distribution of noise-induced alternating patterns in a beat sequence from a set of surrogate data derived from repeated reshuffling of the original beat sequence. Thus, in assessing the significance of the observed alternating patterns in the data, no assumptions are made about the underlying noise distribution. In addition, since the distribution of noise-induced alternans magnitudes is calculated separately for each sequence of beats within the analysis window, the method is robust to data nonstationarities in both noise and TWA. The proposed surrogate method for rejecting noise was compared to the standard noise-rejection methods used with the spectral method (SM) and the modified moving average (MMA) techniques. Using a previously described realistic multilead model of TWA and real physiological noise, we demonstrate the proposed approach that reduces false TWA detections while maintaining a lower missed TWA detection, compared with all the other methods tested. A simple averaging-based TWA estimation algorithm was coupled with the surrogate significance testing and was evaluated on three public databases: the Normal Sinus Rhythm Database, the Chronic Heart Failure Database, and the Sudden Cardiac Death Database. Differences in TWA amplitudes between each database were evaluated at matched heart rate (HR) intervals from 40 to 120 beats per minute (BPM). Using the two-sample Kolmogorov-Smirnov test, we found that significant differences in TWA levels exist between each patient group at all decades of HRs. The most-marked difference was generally found at higher HRs, and the new technique resulted in a larger margin of separability between patient populations than when the SM or MMA were applied to the same data.
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- 2010
15. Asthma: Pathophysiology and Diagnosis
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Susie Yim Yeh and Richard Schwartzstein
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Pathophysiology of asthma ,medicine.medical_specialty ,education.field_of_study ,business.industry ,Population ,Disease ,medicine.disease ,Pathophysiology ,respiratory tract diseases ,Pathogenesis ,Hygiene hypothesis ,immune system diseases ,Medicine ,Disease process ,business ,Intensive care medicine ,education ,Asthma - Abstract
Although asthma is a common disorder affecting approximately 7.8% of the United States population (Schiller et al. 2006) or 23 million Americans, the pathogenesis of this disease remains to be fully elucidated. Extensive research over the last few decades has yielded a better understanding of asthma. We know that the basic features of asthma include episodic airways inflammation, airways hyperresponsiveness, and mucous hypersecretion. Although we understand the basic clinical features of asthma, the links between symptoms, physical signs, and underlying pathophysiological mechanisms are still being delineated. Asthma is a heterogeneous disease process with varying phenotypes and presentations. In this chapter, we will briefly explore some major theories of asthma pathogenesis, both new and old. We will also explore how understanding the pathophysiology of asthma can help us to understand the symptoms and presentation of asthma, as well as the best strategies for diagnosing this disease.
- Published
- 2009
16. Therapeutic interventions and oxidative stress in diabetes
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Susie Yim Yeh, Aristidis Veves, Atul Malhotra, and Shilpa Rahangdale
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chemistry.chemical_classification ,Reactive oxygen species ,Vascular disease ,business.industry ,Vitamin E ,medicine.medical_treatment ,Alpha-Lipoic Acid ,Nitrosation ,Psychological intervention ,Diabetic angiopathy ,medicine.disease ,medicine.disease_cause ,Bioinformatics ,Article ,Oxidative Stress ,chemistry ,Diabetes mellitus ,medicine ,Diabetes Mellitus ,Animals ,Humans ,Endothelium, Vascular ,business ,Oxidative stress ,Diabetic Angiopathies - Abstract
Many therapeutic agents that are used in patients with diabetes mitigate oxidative stress. These agents are of particular interest because oxidative stress is elevated in diabetes and is thought to contribute to vascular dysfunction. Agents that merely quench already formed reactive oxygen species have demonstrated limited success in improving cardiovascular outcomes. Thus, although vitamin E, C, and alpha lipoic acid appeared promising in animal models and initial human studies, subsequent larger trials have failed to demonstrate improvement in cardiovascular outcomes. Drugs that limit the production of oxidative stress are more successful in improving vascular outcomes in patients with diabetes. Thus, although statins, ACE inhibitors, ARBs and thiazolinediones are used for varied clinical purposes, their increased efficacy in improving cardiovascular outcomes is likely related to their success in reducing the production of reactive oxygen species at an earlier part of the cascade, thereby more effectively decreasing the oxidative stress burden. In particular, statins and ACE inhibitors/ ARBs appear the most successful at reducing oxidative stress and vascular disease and have potential for synergistic effects.
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- 2009
17. Endothelial function in obstructive sleep apnea
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Susie Yim Yeh, Atul Malhotra, Amy Atkeson, and Sanja Jelic
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medicine.medical_specialty ,Endothelium ,medicine.medical_treatment ,Inflammation ,medicine.disease_cause ,Nitric Oxide ,Antioxidants ,Article ,Internal medicine ,medicine ,Animals ,Humans ,Regeneration ,Continuous positive airway pressure ,Endothelial dysfunction ,Hypoxia ,Blood Coagulation ,Sleep Apnea, Obstructive ,Continuous Positive Airway Pressure ,business.industry ,Hemodynamics ,Sleep apnea ,Hypoxia (medical) ,medicine.disease ,nervous system diseases ,respiratory tract diseases ,Obstructive sleep apnea ,Oxidative Stress ,Endocrinology ,medicine.anatomical_structure ,Cardiovascular Diseases ,Sleep Deprivation ,Endothelium, Vascular ,medicine.symptom ,Inflammation Mediators ,Cardiology and Cardiovascular Medicine ,business ,Mandibular Advancement ,Oxidative stress - Abstract
Untreated obstructive sleep apnea (OSA) is an independent risk factor for hypertension, myocardial infarction, and stroke. The repetitive hypoxia/reoxygenation and sleep fragmentation associated with OSA impair endothelial function. Endothelial dysfunction, in turn, may mediate increased risk for cardiovascular diseases. Specifically, in OSA, endothelial nitric oxide availability and repair capacity are reduced, whereas oxidative stress and inflammation are enhanced. Treatment of OSA improves endothelial vasomotor tone and reduces inflammation. We review the evidence and possible mechanisms of endothelial dysfunction as well as the effect of treatment on endothelial function in OSA.
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- 2009
18. Carbon monoxide poisoning, or carbon monoxide protection?
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Atul Malhotra, Robert L. Owens, and Susie Yim-Yeh
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Pulmonary and Respiratory Medicine ,Lung Diseases ,medicine.medical_specialty ,ARDS ,Bilirubin ,Polysomnography ,Inflammation ,Critical Care and Intensive Care Medicine ,Hypoxemia ,chemistry.chemical_compound ,Carbon Monoxide Poisoning ,Internal medicine ,medicine ,Humans ,Cardiopulmonary disease ,Hyperoxia ,Carbon Monoxide ,Continuous Positive Airway Pressure ,business.industry ,medicine.disease ,Prognosis ,Pulmonary hypertension ,Heme oxygenase ,Oxidative Stress ,Endocrinology ,chemistry ,Anesthesia ,Heme Oxygenase (Decyclizing) ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business - Abstract
Carbon monoxide (CO) is a molecule generally presumed to be deleterious when inhaled at high concentrations, but is a marker of oxidative stress and inflammation when endogenously produced. Many reports1–3 have focused on increased endogenous CO production in pulmonary diseases, including asthma, COPD, acute pneumonia, and ARDS. In this issue of CHEST (see page 904), Kobayashi and colleagues4 add obstructive sleep apnea (OSA) to the list. In documented nonsmokers with OSA and control subjects, CO levels were measured before and after polysomnography. Although CO levels were similar in OSA patients and control subjects prior to sleep, those patients with OSA had elevations in venous CO level after sleep. Moreover, the nocturnal change in CO correlated modestly with the apnea-hypopnea index and duration of hypoxemia during sleep. Treatment with continuous positive airway pressure (CPAP) in some of these patients attenuated the rise in CO, so that treated OSA patients had no difference in CO when compared to control subjects. Linking OSA to cardiovascular morbidity, the authors conclude that “normalization of venous CO levels by CPAP therapy can potentially reduce the risk of disease associated cardiovascular events.” The authors also found concentrations of indirect bilirubin to be elevated after sleep in patients with OSA, suggesting that the sleep-related increase in CO is due to the induction of the heme oxygenase (HO) system. CO can be produced endogenously by the breakdown of heme into CO, biliverdin (subsequently degraded to bilirubin), and iron by HO.5 There are constitutively active isoforms of HO, but HO-1 is inducible and its byproduct CO has been suggested as a marker of the activity of the enzyme. HO was initially thought to have only a “housekeeping” role (ie, scavenging and breaking down free heme). However, several other observations suggested that it might have greater importance. For example, HO has a conserved structure across species (even those without circulating heme), it exists in organs not thought to play a role in heme degradation, and, most importantly, its function can be induced by cellular stressors such as inflammation and infection. The HO products CO and bilirubin are now understood to be mediators and effectors that promote cytoprotection via antiinflammatory, antiapoptotic, and antiproliferative effects, and also invoke antioxidant responses. Thus, the HO system is now thought to be protective from a variety of cellular insults. HO-1 is induced ubiquitously in most cell types with high levels of expression in lung endothelial cells, fibroblasts, airway epithelial cells, inflammatory cells, and type II pneumoctyes. Differences between the arterial and venous CO levels suggest that the lungs produce a significant proportion of all endogenous CO.6 HO-1 can be induced by various stimuli, including hyperoxia, inflammatory cytokines such as interleukin-6, and hypoxia. Continuous hypoxia has been extensively studied as it provides a good model for the protective effects of HO. Mice exposed to hypoxia produce inflammatory cytokines and chemokines, then develop pulmonary hypertension. However, hypoxia also up-regulates transcription of the HO-1 gene, and increases CO and bilirubin production. The HO products counteract the acute effects of hypoxia. CO is a potent vasodilator, and bilirubin acts as an antioxidant against reactive oxygen species. In fact, transgenic mice overexpressing HO-1 are protected against both pulmonary inflammation and pulmonary hypertension, while HO-1 null mice have a maladaptive response to hypoxia and subsequent pulmonary hypertension.7,8 In this light, the induction of the HO system and the generation of CO is likely a protective response to the stress of OSA, rather than a causative mechanism of cardiovascular morbidity. This was the conclusion reached by Chin et al9 who found higher morning bilirubin levels in patients with OSA compared to control subjects. This difference was also ameliorated with CPAP therapy and correlated most strongly with the degree of hypoxemia. The new study by Kobayashi et al4 is important because it suggests the functional involvement of HO in OSA, and provides a basis for CO as a marker of OSA stress. In the current study, CO levels changed within hours of the stress, could be measured easily with a venous blood draw (and possibly could be measured in exhaled breath10), and were affected by treatment. Other biomarkers, such as tumor necrosis factor-α and C-reactive protein, which are thought to reflect the damaging effects of apnea, have been inconsistent in their utility in OSA, as these markers have multiple influences.11 These data suggest several future directions. For the scientist, some questions include: what stress influences CO in OSA patients, and is it repetitive arousal, hypoxemia, or some other factors? Does CO level predict long-term cardiovascular morbidity? Is a low CO level a marker of low cardiovascular risk, or instead is it a reflection of impaired protective responses in a patient who is at increased risk of cardiovascular morbidity? While the HO gene is thought to be relatively conserved, polymorphisms in the promoter region have been associated with variable HO-1 expression and associated with higher risks of cardiopulmonary disease. In the current study, there was wide unexplained variability in CO production among patients with OSA. Are these differences due to promoter polymorphisms or other factors? How should CO be measured (by exhaled breath, serum CO level, or hemoglobin-bound CO)? And when should it be measured (during sleep or on awakening, or do elevations persist for some time)? For clinicians, assuming that the CO level has prognostic value, is it a viable biomarker that should be measured to assess disease burden? Does it reliably reflect the response to treatment? And finally, will exogenous CO one day be a therapy (as has been suggested for other pulmonary diseases) to prevent cardiovascular disease in those with OSA, perhaps in patients nonadherent to CPAP therapy?12 We congratulate Kobayashi et al for fueling the fire on the CO discussion.
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- 2008
19. Metabolic Syndrome, Obstructive Sleep Apnea, and Continuous Positive Airway Pressure: A Weighty Issue
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Susie, Yim Yeh, Shilpa, Rahangdale, and Atul, Malhotra
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Adult ,Blood Glucose ,Male ,Metabolic Syndrome ,Sleep Apnea, Obstructive ,Time Factors ,Continuous Positive Airway Pressure ,Middle Aged ,Lipids ,Article ,Cohort Studies ,Oxidative Stress ,Cardiovascular Diseases ,Risk Factors ,Cytokines ,Humans ,Patient Compliance ,Female - Abstract
The increased risk of atherosclerotic morbidity and mortality in patients with obstructive sleep apnea (OSA) has been linked to arterial hypertension, insulin resistance, systemic inflammation, and oxidative stress. We aimed to determine the effects of 8 weeks of therapy with continuous positive airway pressure (CPAP) on glucose and lipid profile, systemic inflammation, oxidative stress, and global cardiovascular disease (CVD) risk in patients with severe OSA and metabolic syndrome.In 32 patients, serum cholesterol, triglycerides, high-density lipoprotein cholesterol, fibrinogen, apolipoprotein A-I, apolipoprotein B (ApoB), high-sensitivity C-reactive protein, interleukin-6, tumor necrosis factor (TNF)-alpha, leptin, malondialdehyde (MDA), and erythrocytic glutathione peroxidase (GPx) activity were measured at baseline and after 8 weeks of CPAP. The insulin resistance index (homeostasis model assessment [HOMA-IR]) was based on the homeostasis model assessment method, the CVD risk was calculated using the multivariable risk factor algorithm.In patients who used CPAP foror = 4 h/night (n = 16), CPAP therapy reduced systolic BP and diastolic BP (p = 0.001 and p = 0.006, respectively), total cholesterol (p = 0.002), ApoB (p = 0.009), HOMA-IR (p = 0.031), MDA (p = 0.004), and TNF-alpha (p = 0.037), and increased erythrocytic GPx activity (p = 0.015), in association with reductions in the global CVD risk (from 18.8 +/- 9.8 to 13.9 +/- 9.7%, p = 0.001). No significant changes were seen in patients who used CPAP for4 h/night. Mask leak was the strongest predictor of compliance with CPAP therapy.In patients with severe OSA and metabolic syndrome, good compliance to CPAP may improve insulin sensitivity, reduce systemic inflammation and oxidative stress, and reduce the global CVD risk.
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- 2008
20. Metabolic Syndrome, Obstructive Sleep Apnea, and Continuous Positive Airway Pressure
- Author
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Shilpa Rahangdale, Atul Malhotra, and Susie Yim Yeh
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Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Framingham Risk Score ,business.industry ,medicine.medical_treatment ,Context (language use) ,Critical Care and Intensive Care Medicine ,medicine.disease ,nervous system diseases ,respiratory tract diseases ,law.invention ,Obstructive sleep apnea ,Randomized controlled trial ,law ,Internal medicine ,Cohort ,medicine ,Physical therapy ,Observational study ,Continuous positive airway pressure ,Risk factor ,Cardiology and Cardiovascular Medicine ,business - Abstract
The current obstructive sleep apnea (OSA) literature regarding cardiovascular (CV) risk has been missing the “holy grail” of studies: the definitive multicenter randomized trial assessing hard CV outcomes and mortality. Until this trial can be achieved, we will always be asking if OSA, independent of obesity, contributes to increased CV morbidity and mortality despite compelling evidence from in vitro, animal, epidemiologic, cross-sectional, and observational studies.1,2 Focusing on certain populations with known increased risk of CV disease and assessing treatment of concomitant OSA may be an acceptable strategy for now. In this issue of CHEST (see page 686), Dorkova et al3 study the effect of continuous positive airway pressure (CPAP) on CV risk in a well-defined cohort of patients with metabolic syndrome. Although the predictive value of the various components of the metabolic syndrome has been called into question,4 many features of syndrome X have been associated with OSA (so-called syndrome Z).5 The results of the study by Dorkova et al,3 that treatment of OSA in patients with metabolic syndrome improves insulin sensitivity, reduces systemic inflammation, and decreases CV risk, are promising. The authors acknowledge, however, that this study has the same limitations that have plagued other OSA/CV studies: relying on surrogate measures of CV outcomes, and comparing adherent CPAP users to nonadherent CPAP users. One of the surrogate measures used in this study was a calculation of CV risk using a sex-specific multivariable risk factor algorithm derived from the Framingham Heart study.6 Reduction of the calculated risk score was observed in the OSA group adherent to CPAP but not in the nonadherent group. What does this mean? Can we assume that a reduction of risk in a treated group translates to a “real” risk reduction? For instance, previous research has shown that for a given BP, patients undergoing antihypertensive treatment have a higher CV risk than nontreated patients.7,8 The recent Framingham risk algorithm takes into account treated BPs vs non-treated BPs. However, the algorithm is not necessarily able to predict CV risk for those undergoing changes in risk factors from other types of medical treatment, eg, CPAP. The decreases in BP and cholesterol in the CPAP group reduced the calculated CV risk, but does this necessarily translate to reduced CV events? Despite this concern, the lowering of BP in the CPAP group was impressive in this study. Previous studies9 have shown only modest differences in BP in CPAP vs control. Many of these studies, however, were looking at differences in BP among normotensive participants. Dorkova et al3 observed almost 10 mm Hg reductions in both systolic and diastolic BPs in subjects with baseline hypertension. Similarly, the CPAP-induced improvement in insulin sensitivity (measured with the Homeostasis Model Assessment–Insulin Resistance) and cholesterol is also notable. To see differences before and after treatment with OSA, there may have to be an underlying abnormality. Even in the nonadherent CPAP group, the total cholesterol was within normal limits, and so one may not have expected a change in total cholesterol even if CPAP treatment were successful. However, the exclusion of known cardiovascular comorbidities in order to assess the independent effect of OSA on CV outcomes has become more common place. A “clean” cohort, however, may not in the end be able to detect the beneficial effects of CPAP seen in sicker patients. Although the results of this study are encouraging, the study design comparing CPAP adherent to CPAP nonadherent groups may be problematic. Prior studies10,11 have revealed that adherent patients have better outcomes than nonadherent ones (regardless of the intervention), presumably because adherence is a marker of a more educated, more motivated patient who may be more likely to follow diet, exercise, medication instructions. For example, minor dietary changes may underlie some of the improvements in lipids observed in the present study. Further, we can see that the CPAP-nonadherent group has a higher body mass index, which may play a role in the differences noted between the two groups. One also wonders if there is a difference the pathogenesis of OSA. Whether these underlying differences affected the outcomes is unclear. It is also discouraging to see that despite intensive counseling and monitoring by Dorkova et al3 that 50% of the participants were nonadherent to CPAP, despite their being motivated to participate in a clinical trial. We are reminded that despite having an effective treatment for OSA, CPAP is difficult to use for many patients and new therapeutic targets are needed. Some researchers are moving away from comparing CPAP-adherent vs CPAP-nonadherent groups and using placebos in the form of pills or sham CPAP. The ethical dilemma of not treating OSA, however, is not trivial especially in sleepy patients. Untreated OSA patients have increased risk of car accidents and work-place accidents.12,13 It does not seem right to withhold treatment in symptomatic OSA patients in order to study whether they may or may get heart disease, a process that takes years. Other researchers are working around this problem by randomizing nonsleepy OSA patients to CPAP (who may have poor adherence to therapy), or by doing research in countries that would otherwise not have any access to CPAP therapy. Whether these approaches are ethical or not is still debated, but there are not many other options. Even the use of sham CPAP controls have been criticized since “sham” can still provide partial treatment of OSA or cause sleep disruptions.14 Although these results are promising, the link between OSA and CV outcomes requires further study. What is a researcher to do? As long as we recognize potential limitations and understand the context of the outcomes reported, there is still valuable information to be gleaned. Targeting patients with OSA and metabolic syndrome and observing the benefits of CPAP therapy may alert physicians in other fields, such as endocrine, renal, or cardiology, to send their patients for sleep evaluations. At the end of the day, we all just want OSA to be recognized and treated whenever appropriate.
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- 2008
21. Total serum bilirubin does not affect vascular reactivity in patients with diabetes.
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Susie Yim Yeh, Doupis, John, Rahangdale, Shilpa, Horr, Samuel, Malhotra, Atul, and Veves, Aristidis
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BILIRUBIN , *PEOPLE with diabetes , *DIABETES , *IONTOPHORESIS , *VASODILATION , *CARDIOVASCULAR diseases risk factors - Abstract
Bilirubin may have a major role in the prevention of cardiovascular disease based on recent data regarding its anti-oxidant properties. We determined the relationship between total serum bilirubin and vascular reactivity in a large cohort of individuals with diabetes, a disease associated with known oxidant stress. We studied 302 individuals: 52 controls, 37 with type 1 diabetes, 213 with type 2 diabetes. Highresolution ultrasound was used to measure flow-mediated dilation (FMD; endotheliumdependent) and nitroglycerin-induced dilation (NID, endothelium-independent) of the brachial artery. Laser Doppler perfusion imaging was used to measure microvascular reactivity in the forearm skin before and after iontophoresis of acetylcholine (endothelium-dependent) and sodium nitroprusside (endothelium-independent). Bilirubin levels were higher in the type 2 diabetes group (0.71 ± 0.34 mg/dl) compared to controls (0.56 ± 0.26 mg/dl, p < 0.0001). A weak inverse correlation was observed between bilirubin and FMD (r = -0.125, p = 0.032) and skin endothelium-dependent vasodilation (r = -0.157, p = 0.019). In multivariate analyses, however, these correlations were not statistically significant. There is no association between bilirubin levels and vascular reactivity in the macro- and microcirculation of individuals with diabetes. Bilirubin, therefore, does not correlate with predictors of cardiovascular risk in the diabetic population. [ABSTRACT FROM AUTHOR]
- Published
- 2009
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