Autonomic control in preterm infants - what we can learn from mathematical descriptions of vital signs

Background: Preterm birth is a major burden, affecting approximately 15 million infants each year. Recent advances in reproductive medicine increases that number even more. The population of preterm infants in particular suffers from autonomic dysregulation that manifests as temperature instability and poor control of heart rate and breathing. Thermal care, monitoring of vital signs in a neonatal intensive care unit, pharmacotherapy, and respiratory support over weeks to months is necessary. Improvements in neonatal care in the past years lead to a decrease in mortality, especially in very preterm infants. However, former preterm infants still are a high-risk population for acute and chronic sequelae as a result of the interruption of the physiological development. A better understanding of the pathophysiology of the autonomic dysregulation in that population would be very useful. Unfortunately, accurate diagnostic tools that objectively assess and quantify the immature autonomic control in neonates are lacking. Methods: In this PhD thesis we examined different effects of the immature autonomic control in very preterm infants under clinically relevant conditions. We conducted a prospective single center observational study, where we assessed fluctuations in body temperature, sleep behavior, and heart rate variability in very preterm infants. We described the different regulatory systems using distinct mathematical expressions, such as detrended fluctuation analysis and sample entropy. We assessed associations between these outcome parameters and relevant factors of the infant’s history, such as demographic parameters and co-morbidities. Besides that, we analyzed lung function measurements of preterm infants and healthy term controls at a comparable postconceptional age, to describe respiratory control. Results: This study is systematically assessing different physiological signals of autonomic dysregulation in preterm infants during their first days of life. We found associations between parameters describing the complexity of time series analysis and maturity or relevant co-morbidities of the infants. In the analysis of heart rate variability we even found that parameters derived from time series analysis, assessed during the infants first days of life, improve our ability to predict future evolution of the infants’ autonomic stability. Lastly, several weeks after the expected due date, tidal breathing pattern of preterm infants showed a different reaction in response to a sigh when compared to term born controls at equivalent postmenstrual age indicating that autonomic dysregulation in preterm infants is still present well beyond the expected due date. Conclusion: A better understanding about the resolution of autonomic dysregulation in this population is not only important for the infant and its family but has the potential to support resource allocation and identification of patients with elevated risk for future deterioration. We thus think that the insights about the immature autonomic control in preterm infants, gained through this PhD work, are of substantial scientific and clinical relevance

Dead in the Night: Sleep-Wake and Time-Of-Day Influences on Sudden Unexpected Death in Epilepsy

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of epilepsy-related death in patients with refractory epilepsy. Convergent lines of evidence suggest that SUDEP occurs due to seizure induced perturbation of respiratory, cardiac, and electrocerebral function as well as potential predisposing factors. It is consistently observed that SUDEP happens more during the night and the early hours of the morning. The aim of this review is to discuss evidence from patient cases, clinical studies, and animal research which is pertinent to the nocturnality of SUDEP. There are a number of factors which might contribute to the nighttime predilection of SUDEP. These factors fall into four categories: influences of (1) being unwitnessed, (2) lying prone in bed, (3) sleep-wake state, and (4) circadian rhythms. During the night, seizures are more likely to be unwitnessed; therefore, it is less likely that another person would be able to administer a lifesaving intervention. Patients are more likely to be prone on a bed following a nocturnal seizure. Being prone in the accouterments of a bed during the postictal period might impair breathing and increase SUDEP risk. Sleep typically happens at night and seizures which emerge from sleep might be more dangerous. Lastly, there are circadian changes to physiology during the night which might facilitate SUDEP. These possible explanations for the nocturnality of SUDEP are not mutually exclusive. The increased rate of SUDEP during the night is likely multifactorial involving both situational factors, such as being without a witness and prone, and physiological changes due to the influence of sleep and circadian rhythms. Understanding the causal elements in the nocturnality of SUDEP may be critical to the development of effective preventive countermeasures

INTERMITTENT HYPOXEMIA IN PRETERM INFANTS

Intermittent hypoxemia (IH) is defined as episodic drops in oxygen saturation (SpO2). Virtually all preterm infants have IH events. Extremely preterm infants have hundreds of IH events per day. The extent of IH is not apparent clinically as accurately documenting cardiorespiratory events for day-to-day patient care management is challenging. High resolution pulse oximeters with 2 second averaging time are currently the ideal methods to measure IH. We have developed novel methods and processes to accurately and efficiently calculate an IH profile that reflects to spectrum of the problem. The natural progression of IH is dynamic. There is low incidence of IH in the few 2 weeks of life, followed by a progressive increase until peak IH at 4-5 week after which IH plateaus. Multiple factors place preterm infants at high risk for increased IH. These factors include respiratory immaturity, lung disease, and anemia. We also show that preterm infants prenatally exposed to opioids or inflammation (due to maternal chorioamnionitis) have increased IH measures compared to unexposed infants. Interestingly, the increased IH in the exposed groups persists beyond the immediate postnatal period. Brief episodes of oxygen desaturations may seem clinically insignificant; however, these events may have a cumulative effect on neonatal outcomes. There is mounting evidence from both animal models and clinical studies suggesting that IH is associated with injury and poor outcomes such as impaired growth, retinopathy of prematurity and neurodevelopmental impairment. In addition data from neonatal animal models and adults with obstructive sleep apnea suggest that IH is pro inflammatory itself. We demonstrate in this document for the first time in preterm infants that IH is associated with increased serum inflammatory marker, C-reactive protein. Finally, a valuable experience throughout this process is working with a talented and dedicated multidisciplinary team. We are a solid example of the value of team science during this new era of clinical and translational research. Our respiratory control research program is one of handful programs nationwide able to perform such high-fidelity studies related to cardiorespiratory events in preterm infants. We will continue to tackle complex questions involving health of infants

The Different Facets of Heart Rate Variability in Obstructive Sleep Apnea

Obstructive sleep apnea (OSA), a heterogeneous and multifactorial sleep related breathing disorder with high prevalence, is a recognized risk factor for cardiovascular morbidity and mortality. Autonomic dysfunction leads to adverse cardiovascular outcomes in diverse pathways. Heart rate is a complex physiological process involving neurovisceral networks and relative regulatory mechanisms such as thermoregulation, renin-angiotensin-aldosterone mechanisms, and metabolic mechanisms. Heart rate variability (HRV) is considered as a reliable and non-invasive measure of autonomic modulation response and adaptation to endogenous and exogenous stimuli. HRV measures may add a new dimension to help understand the interplay between cardiac and nervous system involvement in OSA. The aim of this review is to introduce the various applications of HRV in different aspects of OSA to examine the impaired neuro-cardiac modulation. More specifically, the topics covered include: HRV time windows, sleep staging, arousal, sleepiness, hypoxia, mental illness, and mortality and morbidity. All of these aspects show pathways in the clinical implementation of HRV to screen, diagnose, classify, and predict patients as a reasonable and more convenient alternative to current measures.Peer Reviewe

A review of automated sleep stage scoring based on physiological signals for the new millennia

Background and Objective: Sleep is an important part of our life. That importance is highlighted by the multitude of health problems which result from sleep disorders. Detecting these sleep disorders requires an accurate interpretation of physiological signals. Prerequisite for this interpretation is an understanding of the way in which sleep stage changes manifest themselves in the signal waveform. With that understanding it is possible to build automated sleep stage scoring systems. Apart from their practical relevance for automating sleep disorder diagnosis, these systems provide a good indication of the amount of sleep stage related information communicated by a specific physiological signal. Methods: This article provides a comprehensive review of automated sleep stage scoring systems, which were created since the year 2000. The systems were developed for Electrocardiogram (ECG), Electroencephalogram (EEG), Electrooculogram (EOG), and a combination of signals. Results: Our review shows that all of these signals contain information for sleep stage scoring. Conclusions: The result is important, because it allows us to shift our research focus away from information extraction methods to systemic improvements, such as patient comfort, redundancy, safety and cost

Rhythmic Masticatory Muscle Activity during Sleep: Etiology and Clinical Perspectives

L’activité rythmique des muscles masticateurs (ARMM) pendant le sommeil se retrouve chez environ 60% de la population générale adulte. L'étiologie de ce mouvement n'est pas encore complètement élucidée. Il est cependant démontré que l’augmentation de la fréquence des ARMM peut avoir des conséquences négatives sur le système masticatoire. Dans ce cas, l'ARMM est considérée en tant que manifestation d'un trouble moteur du sommeil connue sous le nom de bruxisme. Selon la Classification Internationale des Troubles du Sommeil, le bruxisme est décrit comme le serrement et grincement des dents pendant le sommeil. La survenue des épisodes d’ARMM est associée à une augmentation du tonus du système nerveux sympathique, du rythme cardiaque, de la pression artérielle et elle est souvent en association avec une amplitude respiratoire accrue. Tous ces événements peuvent être décrits dans le contexte d’un micro-éveil du sommeil. Cette thèse comprend quatre articles de recherche visant à étudier i) l'étiologie de l’ARMM pendant le sommeil en relation aux micro-éveils, et à évaluer ii) les aspects cliniques du bruxisme du sommeil, du point de vue diagnostique et thérapeutique. Pour approfondir l'étiologie de l’ARMM et son association avec la fluctuation des micro-éveils, nous avons analysé le patron cyclique alternant (ou cyclic alternating pattern (CAP) en anglais), qui est une méthode d’analyse qui permet d’évaluer l'instabilité du sommeil et de décrire la puissance des micro-éveils. Le CAP a été étudié chez des sujets bruxeurs et des sujets contrôles qui ont participé à deux protocoles expérimentaux, dans lesquels la structure et la stabilité du sommeil ont été modifiées par l'administration d'un médicament (la clonidine), ou avec l'application de stimulations sensorielles (de type vibratoire/auditif) pendant le sommeil. Dans ces deux conditions expérimentales caractérisées par une instabilité accrue du sommeil, nous étions en mesure de démontrer que les micro-éveils ne sont pas la cause ou le déclencheur de l’ARMM, mais ils représentent plutôt la «fenêtre permissive» qui facilite l'apparition de ces mouvements rythmiques au cours du sommeil. Pour évaluer la pertinence clinique du bruxisme, la prévalence et les facteurs de risque, nous avons effectué une étude épidémiologique dans une population pédiatrique (7-17 ans) qui était vue en consultation en orthodontie. Nous avons constaté que le bruxisme est un trouble du sommeil très fréquent chez les enfants (avec une prévalence de 15%), et il est un facteur de risque pour l'usure des dents (risque relatif rapproché, RRR 8,8), la fatigue des muscles masticateurs (RRR 10,5), les maux de tête fréquents (RRR 4,3), la respiration bruyante pendant le sommeil (RRR 3,1), et divers symptômes liés au sommeil, tels que la somnolence diurne (RRR 7,4). Ces résultats nous ont amenés à développer une étude expérimentale pour évaluer l'efficacité d'un appareil d'avancement mandibulaire (AAM) chez un groupe d'adolescents qui présentaient à la fois du bruxisme, du ronflement et des maux de tête fréquents. L'hypothèse est que dans la pathogenèse de ces comorbidités, il y a un mécanisme commun, probablement lié à la respiration pendant le sommeil, et que l'utilisation d'un AAM peut donc agir sur plusieurs aspects liés. À court terme, le traitement avec un AAM semble diminuer l'ARMM (jusqu'à 60% de diminution), et améliorer le ronflement et les maux de tête chez les adolescents. Cependant, le mécanisme d'action exact des AAM demeure incertain; leur efficacité peut être liée à l'amélioration de la respiration pendant le sommeil, mais aussi à l'influence que ces appareils pourraient avoir sur le système masticatoire. Les interactions entre le bruxisme du sommeil, la respiration et les maux de tête, ainsi que l'efficacité et la sécurité à long terme des AAM chez les adolescents, nécessitent des études plus approfondies.Approximately 60% of the general adult population experiences rhythmic masticatory muscle activity (RMMA) during sleep. The etiology of this movement is not yet understood. However, it has been demonstrated that an increased frequency of RMMA may have detrimental consequences on the stomatognathic system. In this case, RMMA is considered the manifestation of a sleep-related motor disorder known as sleep bruxism (SB). According to the definition of the International Classification of Sleep Disorders, SB is the activity of tooth grinding and clenching during sleep. The occurrence of SB-related activity, i.e., RMMA, is associated with rises of sympathetic tone, heart rate, blood pressure, and it is frequently concomitant with larger respiratory breaths. All these events can be described within a sleep arousal. The present thesis includes four research articles aimed to study i) the etiology of RMMA during sleep in relation to sleep arousal; and ii) the clinical perspectives of SB assessment and management. To further investigate the etiology of RMMA and its association with sleep arousal fluctuations we analyzed the cyclic alternating pattern (CAP), a scoring method to assess sleep instability and describe sleep arousal pressure. CAP was scored in SB subjects and controls that participated in two experimental protocols in which sleep architecture and stability were altered by either a medication (i.e., clonidine), or sensory stimulations (i.e., vibratory/auditory). Under these experimental conditions known to increase sleep instability, we were able to show that sleep arousal is not the trigger or cause of RMMA, rather the “permissive window” that facilitates the occurrence of RMMA during sleep. To evaluate the clinical relevance of SB, we conducted a survey on a 7-17 year old orthodontic population to investigate the prevalence and risk factors associated with SB. It appeared that SB is a highly prevalent sleep disorders in children (15% of prevalence), and is a risk factor for tooth wear (odds ratio, OR 8.8), jaw muscle fatigue (OR 10.5), frequent headache (OR 4.3), loud breathing during sleep (OR 3.1), and several sleep complaints, such as daytime sleepiness (OR 7.4). These findings led us to design an experimental trial using a mandibular advancement appliance (MAA) in adolescents in order to investigate the possible relationship between SB, snoring, and headache. We hypothesized that a common underlying mechanism related to breathing during sleep may be responsible for all concomitant conditions. The short-term use of an MAA appeared to reduce SB (up to 60%), and improve snoring and headache complaints in adolescents. However, the precise mechanism of action of MAA remains under debate; its effectiveness can be either related to the improvement of breathing during sleep, or its influence on the masticatory system. The interactions between SB, breathing, and headache as well as the long-term effectiveness and safety of the MAA in adolescents need further investigations.L’attività ritmica dei muscoli masticatori (ARMM) durante il sonno si osserva in circa il 60% della popolazione generale adulta. L'eziologia di questo movimento non è stata ancora del tutto compresa. Tuttavia, è dimostrato che un’aumentata frequenza di ARMM può avere conseguenze negative sul sistema stomatognatico. In questo caso, l’ARMM è considerato la manifestazione di un disturbo motorio del sonno noto come bruxismo. Secondo la Classificazione Internazionale dei Disturbi del Sonno, il bruxismo è l'attività di digrignamento e serramento dei denti durante il sonno. La comparsa di episodi di ARMM durante il sonno è associata a un aumento del tono del sistema nervoso simpatico, della frequenza cardiaca, della pressione arteriosa, ed è spesso in concomitanza con un aumentato volume inspiratorio. Le variazioni di questi parametri fisiologici sono compresi nel contesto di un arousal (micro risveglio) del sonno. Questa tesi comprende quattro articoli di ricerca volti a studiare i) l'eziologia dell’ARMM durante il sonno in relazione all’arousal, ed a valutare ii) l’inquadramento clinico del bruxismo nel sonno. Per approfondire l'eziologia dell’ARMM e l’associazione con l’arousal nel sonno, abbiamo analizzato il cyclic alternating pattern (CAP), che permette di valutare l'instabilità del sonno e descrivere la potenza degli arousals. Il CAP è stato esaminato in soggetti con bruxismo e soggetti controllo che hanno partecipato in due protocolli sperimentali, in cui la struttura e la stabilità del sonno sono stati modificati con la somministrazione di un farmaco (la clonidina), o con l’applicazione di stimolazioni sensoriali (di tipo vibratorio/uditivo) durante il sonno. In queste condizioni sperimentali caratterizzate da un’aumentata instabilità del sonno, siamo stati in grado di dimostrare che l’arousal non è la causa o il generatore dell’ARMM, ma piuttosto la "finestra permissiva" che facilita il verificarsi di questi movimenti ritmici durante il sonno. Per valutare la rilevanza clinica del bruxismo, abbiamo condotto uno studio epidemiologico in una popolazione pediatrica afferente alla clinica di ortodonzia per studiare la prevalenza e i fattori di rischio associati al bruxismo. Questa ricerca ha evidenziato che il bruxismo è un comune disturbo del sonno nei bambini (con una prevalenza del 15%), ed è un fattore di rischio per usura dentale (odds ratio, OR 8.8), fatica dei muscoli masticatori (OR 10.5), mal di testa frequenti (OR 4.3), respirazione rumorosa durante il sonno (OR 3.1), e diversi sintomi legati al sonno, quali la sonnolenza diurna (OR 7.4). Questi risultati ci hanno portato a progettare uno studio sperimentale per valutare l’efficacia di un apparecchio di avanzamento mandibolare (AAM) in un gruppo di adolescenti che presentavano al contempo bruxismo, russamento e frequenti cefalee. L’ipotesi è che nella patogenesi di tali comorbidità, vi sia un meccanismo comune, probabilmente legato alla respirazione durante il sonno, e che l’utilizzo di un AAM possa quindi avere un beneficio multiplo. Il trattamento a breve termine con un AAM sembra diminuire l’ARMM (fino al 60%) e migliorare il russamento e i mal di testa negli adolescenti. Tuttavia, l'esatto meccanismo di azione degli AAM rimane incerto; la loro efficacia può essere correlata sia al miglioramento della respirazione durante il sonno, ma anche all’influenza che questi apparecchi svolgono sul sistema masticatorio. Le interazioni tra il bruxismo nel sonno, la respirazione, e le cefalee, così come l'efficacia e la sicurezza a lungo termine degli AAM negli adolescenti, necessitano di ulteriori studi clinici

Association Between Phase Coupling of Respiratory Sinus Arrhythmia and Slow Wave Brain Activity During Sleep

Phase coupling of respiratory sinus arrhythmia (RSA) has been proposed to be an alternative measure for evaluating autonomic nervous system (ANS) activity. The aim of this study was to analyze how phase coupling of RSA is altered during sleep, in order to explore whether this measure is a predictor of slow wave sleep (SWS). Overnight electroencephalograms (EEG), electrocardiograms (ECG), and breathing using inductance plethysmography were recorded from 30 healthy volunteers (six females, age range 21–64, 31.6 ± 14.7 years). Slow wave activity was evaluated by the envelope of the amplitude of the EEG δ-wave (0.5–4 Hz). The RSA was extracted from the change in the R-R interval (RRI) by band-pass filter, where pass band frequencies were determined from the profile of the power spectral density for respiration. The analytic signals of RSA and respiration were obtained by Hilbert transform, after which the amplitude of RSA (ARSA) and the degree of phase coupling (λ) were quantified. Additionally, the normalized high-frequency component (HFn) of the frequency-domain heart rate variability (HRV) was calculated. Using auto- and cross-correlation analyses, we found that overnight profiles of λ and δ-wave were correlated, with significant cross-correlation coefficients (0.461 ± 0.107). The δ-wave and HFn were also correlated (0.426 ± 0.115). These correlations were higher than that for the relationship between δ-wave and ARSA (0.212 ± 0.161). The variation of λ precedes the onset of the δ-wave by ~3 min, suggesting a vagal enhancement prior to the onset of SWS. Auto correlation analysis revealed that the periodicity of λ was quite similar to that of the δ-wave (88.3 ± 15.7 min vs. 88.6 ± 16.3 min, λ-cycle = 0.938 × δ-cycle + 5.77 min, r = 0.902). These results suggest that phase coupling analysis of RSA appears to be a marker for predicting SWS intervals, thereby complementing other noninvasive tools and diagnostic efforts

An integrated understanding of the effects of sleep disordered breathing on the physiology of the developing child

The role of Sleep Disordered Breathing (SDB) in adult hypertension and cardiovascular morbidity is well established and increased blood pressure and cardiac remodeling has been demonstrated in children with severe SDB. There is less evidence suggesting that milder forms of SDB are associated with cardiovascular anomalies. Therefore this thesis contains a series of studies which compares the underlying physiology, particularly vascular function in children with mild SDB with aged matched healthy non-snoring children. Children with SDB were recruited at the Women’s and Children’s Hospital, through the Ear, Nose and Throat surgical waitlist, prior to treatment to resolve their SDB. All children underwent an overnight sleep study to assess their SDB severity for each study. Chapter 1 is a literature review which provides a brief summary of the autonomic nervous system and the physiology of sleep. A synopsis of the disorder is also presented including information on diagnosis and treatment of the disorder. An in depth assessment of the literature pertaining specifically to studies measuring cardiovascular, autonomic and inflammatory response in children with SDB is summarized and the physiological pathways that lead to hypertension are explained. Chapter 2 assesses Flow Mediated Dilatation, a validated measure of endothelial function in healthy children ranging from 6 – 16 years. At the time of publication there were no studies using FMD in children as young as 6 years. This study shows a positive relationship between the time to reach maximal dilation after ischemia in the brachial artery and both age and body habitus. Younger children reached maximal dilation by 35s while older children reached maximal dilation by 60s+. This paper is important as it helped to determine the age range and analysis for the following study. Chapter 3 outlines the results of a study in young children with primary snoring aged 5-9 years using FMD. We showed that both resting and hyperaemic velocity time integral (VTi; area under the curve of velocity over ejection time) was significantly higher in children referred for evaluation of SDB (n=23) compared with healthy matched controls (n=11). Other groups report similar results in blood flow velocity measured in middle cerebral arteries using transcranial Doppler in children with primary snoring. We also found that the brachial artery took approximately 20 seconds longer to fully dilate after induced hyperaemia in the children with SDB compared with controls. Of note is that both children with SDB and controls in our FMD study demonstrated similar rates of dilatation in the initial 30s, suggesting that endothelial function is preserved, but after 30s the groups diverged and children with SDB took longer to reach maximum dilatation. The time delay in maximum dilatation suggests augmented cell-to-cell connectivity as the dilatation process moves from the endothelial cells through smooth muscle, ending in the adventitial layer. Having defined vascular changes in medium sized vessels, in Chapter 3, Chapter 4 investigates the vascular effects of SDB on the heart and major vessels using cardiac MRI in children aged 5-14 years including primary snorers/mild SDB and non-snoring controls. This study found a significant increase in peak systolic blood flow velocity in the ascending aorta in children with SDB (n = 12) compared to controls (n = 7). The increase in blood flow velocity was similar to increases reported by other groups (20-30%) in cerebral blood flow and by our own group (Chapter 3). A blood sample was also analysed from the children in this study. We used Flow Cytometry to measure cytokine expression of markers of inflammation - Tumor Necrosis Factor alpha (TNFα) and interferon gamma (IFNγ) which are known indicators of cardiovascular disease. We found that there was a significantly higher level of CD8 + cells expressing both TNFα and IFNγ. Consistent with the paradigm that cardiovascular changes are coupled with an increased inflammatory state, we also found a strong positive association between these immune-markers and peak blood flow velocity in the ascending aorta and CD8 + cells expressing IFNγ and TNFα. Our findings support the interrelationship between mild SDB, abnormal vascular function and increased inflammation. While increased inflammatory pathways have been reported in children with severe OSA, this is the first time it has been shown in children diagnosed as primary snorers/mild SDB. Chapter 5 details the relationship between vascular changes observed in Chapter 3 (increased blood flow velocity and time to maximal dilatation in the brachial artery) in relation to autonomic function. We measured sympathetic overactivity using digital pupillometry, and found that it was closely associated with the haemodynamic changes we observed on FMD evaluation of the brachial artery of children with mild SDB. We further undertook the novel step of examining the effect of sympathetic overactivity on the arterial wall by studying the dorsal lingual artery of children undergoing adenotonsillectomy, the accepted treatment for SDB. We found that sympathetic nerve fibre density of the vessel (measured by immunohistochemistry) strongly correlated with the degree of sympathetic overactivity on pupillometric testing and the functional measure from the FMD. To our knowledge this is the first time that functional vascular changes have been correlated to vascular histology in humans. We also explored the association between the sympathetic nerve fibre density brachial artery blood flow velocity and FMD parameters, pupillometry and platelet aggregation (using whole blood samples). Platelet aggregation is a measure of endothelial integrity. Our results show that the children with increased brachial artery blood flow velocity also exhibited increased platelet aggregation in response to the collagen antigen, suggesting endothelial damage. Sympathetic nerve fibre density was also positively associated with increased platelet aggregation, in particular with the aggregation velocity. In addition, there was strong association between the pupillary light reflex variables and the platelet aggregation. Chapter 6 is an overall discussion that amalgamates the findings of each chapter and provides recommendation for future work and consideration.Thesis (Ph.D.) (Research by Publication) -- University of Adelaide, Adelaide Medical School, 201

The Severity of Obstructive Sleep Apnea and Hypertension Among Middle aged Asians

This study examined the prevalence rate of obstructive sleep apnea (OSA) as an independent variable in association with hypertension as an outcome. Studies conducted outside of the United States suggest that differences in craniofacial features among middle-aged Asians increase the prevalence of OSA in comparison to Caucasians with similar age and lower BMI. No similar study had been conducted in the United States. The sufficient component cause theory guided this study and was able to describe the association between OSA and hypertension among middle-aged Asians. The objective of this cross sectional retrospective study was to determine the prevalence rate of OSA and the association between OSA and hypertension among a sample of 462 middle-aged Asian patients. Also, the study evaluated the association of 8 clinical parameters: age, gender, smoking, body mass index, Mallampati score, Epworth Sleepiness Scale and Apnea-Hypopnea-Index, and hypertension. The logistic regression analysis showed that OSA is associated with hypertension. The model containing the 8 variables was statistically significant, x2 (8, N = 462) = 139.59, p \u3c .000). Age was the strongest predictor among the 8 variables. This study showed that OSA is common among middle-age Asians. This research may necessitate the need to evaluate to change current medical awareness, diagnosis, and treatment of OSA and hypertension among Asians, which could reduce the cardiovascular disease (CVD) morbidity and mortality