0890 Sleep Disordered Breathing is Associated With Endothelial Dysfunction and Atherosclerosis in Young Adults: Preliminary Longitudinal Findings in the Penn State Child Cohort

Abstract Introduction Sleep disordered breathing (SDB) in middle-age is an established risk factor for cardiovascular disease. However, population-based studies supporting its cardiovascular contribution at earlier stages of development are lacking, particularly with long-term follow-ups. Methods The Penn State Child Cohort is a population-based longitudinal sample of 700 children (8.7±1.7y), of whom 421 were followed-up 8.3 years later during adolescence (17.0±2.3y) with in-lab polysomnography (PSG). To date, 425 have been followed-up another 7.4 years later during young adulthood (24.4±2.6y) via a standardized survey and 136 of them (55.1% female, 21.3% racial/ethnic minority) have undergone a repeat of their PSG to ascertain apnea/hypopnea index. Subjects (n=121) also underwent Doppler ultrasounds to assess flow-mediated dilation (FMD) and carotid intima-media thickness (CIMT). Linear regression models stratified by body mass index in young adulthood. Results SDB was cross-sectionally associated with lower FMD (β=-0.239, p=0.008) and greater CIMT (β=0.330, p<0.001) in young adulthood. Longitudinally, childhood (n=121) and adolescence (n=90) SDB were significantly associated with CIMT (β=0.327, p<0.001 and β=0.286, p=0.006, respectively), but not with FMD (β=-0.158, p=0.08 and β=-0.101, p=0.35, respectively). These associations, particularly longitudinal ones between childhood and adolescence SDB with CIMT in young adulthood, were stronger in overweight than normal weight subjects (e.g., β=0.310, p=0.030 and β =0.089, p=0.582, respectively). Conclusion SDB and obesity appear to be synergistically associated with endothelial dysfunction and atherosclerosis in young adults from the general population. These data suggest that a childhood exposure to chronic SDB is associated with long-term atherosclerosis, while endothelial dysfunction may be a short-term outcome. This ongoing 16-year longitudinal study will test whether the natural history of SDB from childhood through adolescence into young adulthood shows differential trajectories for cardiovascular morbidity. Support National Institutes of Health (R01HL136587, R01HL97165, R01HL63772, UL1TR000127)

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Abstract 038: Cumulative Exposure To Sleep Disordered Breathing From Childhood Through Young Adulthood Is Associated With Impaired Endothelial Function

Circulation ◽

10.1161/circ.143.suppl_1.038 ◽

2021 ◽

Vol 143 (Suppl_1) ◽

Author(s):

Julio Fernandez-Mendoza ◽

Zhaohui Gao ◽

Myra Qureshi ◽

Baadal A Vachhani ◽

Jiangang Liao ◽

...

Keyword(s):

Young Adults ◽

Endothelial Dysfunction ◽

Endothelial Function ◽

Young Adulthood ◽

Sleep Disordered Breathing ◽

Population Based ◽

Cumulative Exposure ◽

Time Points ◽

The Mean ◽

Disordered Breathing

Introduction: Clinical and population-based studies in adults have shown that sleep disordered breathing (SDB) is associated with impaired endothelial function. However, there is a lack of population-based studies demonstrating an association between SDB and endothelial dysfunction in young adults using a developmental approach. Hypothesis: Exposure to SDB since childhood is associated with long-term impaired flow-mediated dilation (FMD) in young adulthood. Methods: We tested this hypothesis in a subsample of the Penn State Child Cohort, a population-based study of 700 children (median age 9y), of whom 421 were followed-up 6-13 years later during adolescence (median age 16y), and 178 have been followed-up 11-19 years later during young adulthood (median age 24y). Subjects (54.5% female, 20.8% racial/ethnic minority) underwent in-lab polysomnography to ascertain the apnea/hypopnea index (AHI) at all three time points, and ultrasounds to assess FMD in young adulthood. Based on the AHI truncated at ≥5 events/hour of sleep to include subjects already on positive airway pressure therapy, we averaged the exposure to AHI over the three time points (cAHI). The study outcomes were FMD, as a continuous measure, and endothelial dysfunction, defined as FMD<10.3% based on the median of the sample. Linear and logistic regression models simultaneously adjusted for sex, age, race/ethnicity, overweight and length of follow-up. Results: The mean cAHI was 1.31 (1.35) ranging from 0 to 5 and the mean FMD was 0.11 (0.04) ranging from 0.03 to 0.25. Linear models showed that cAHI was associated with significantly lower FMD in young adulthood (β = -0.006; 95% CI = -0.011, -0.0013; p = 0.014). To test the robustness of the analysis, we applied the same model with the square root of FMD as the outcome and similar results were obtained (β = -0.009; 95% CI = -0.016, -0.0017; p = 0.015). Logistic models showed that each point increase in cAHI was associated with 51% higher odds of endothelial dysfunction in young adulthood (OR = 1.51; 95% CI = 1.14, 2.06; p = 0.006). Conclusions: The preliminary data of this ongoing longitudinal study indicates that exposure to SDB during early stages of life is associated with increased risk for cardiovascular disease in young adults from the general population.

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Abstract P249: Incident Sleep-Disordered Breathing is Associated with Obesity: Penn State Child Cohort

Circulation ◽

10.1161/circ.127.suppl_12.ap249 ◽

2013 ◽

Vol 127 (suppl_12) ◽

Author(s):

Edward O Bixler ◽

Alexandros N Vgontzas ◽

Duanping Liao ◽

Susan Calhoun ◽

Julio Fernandez-Mendoza ◽

...

Keyword(s):

Risk Factors ◽

Logistic Regression ◽

Sleep Disordered Breathing ◽

Population Sample ◽

Population Based ◽

Penn State ◽

Potential Risk Factors ◽

State Child ◽

Disordered Breathing

Objectives: To study the epidemiology of sleep-disordered breathing (SDB) in adolescents, which has received little attention. Methods: The Penn State Child Cohort (PSCC) is a representative general population sample of 700 children aged 5-12 years. Our preliminary results are based on an average 8 year follow up of the initial 300 prospective subjects (~43%) from this ongoing cohort study. A logistic regression was used to assess the association between potential risk factors and incident SDB. Results: The mean age at the 8-year follow up examination was 17.2 ± 0.1 years, with an average BMI percentile of 66.6 ± 1.6 and 56.5% boys. At baseline 1.5% of this subsample had SDB, defined by Apnea Hypopnia Index (AHI > 5 /hour). Surprisingly, there was no persistence of SDB. Eight-year incident SDB was 10.5%. The average AHI in those with incident SDB was 12.7 with a maximum of 92.4. Incident SDB was similar for girls (7.8%) and boys (12.7%). Those with SDB were older than those without (18.7 vs 17.0 years, P<0.001) and girls with SDB were older than boys with SDB (20.0 vs 18.0 years, P=0.002). Those with incident SDB tended to have a greater change in BMI percentile (8.2 vs 1.8, P = 0.143) during the follow up and slightly higher minority representation (25.8% vs 21.9%, P=0.655). A logistic regression model identified three variables that were associated with incident SDB, controlling for baseline AHI: age (OR = 1.5 (1.3, 1.9) P<0.001), male (OR= 2.5 (1.11,10.00) P=0.021), and [[Unable to Display Character: ∆]]BMIPCT (OR=1.2(1.02, 1.5) P=0.032). Conclusion: In this population based sample of adolescents, the 8-year incidence of SDB was high (10.5%), whereas childhood SDB did not persist into adolescence. Further, the results indicate that risk factors for incident SDB in adolescents are age, male and the development of obesity.

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Abstract MP84: Incident Sleep-Disordered Breathing is Associated with Higher Blood Pressure and its Reactivity: Penn State Child Cohort

Circulation ◽

10.1161/circ.127.suppl_12.amp84 ◽

2013 ◽

Vol 127 (suppl_12) ◽

Author(s):

Edward O Bixler ◽

Duanping Liao ◽

Alexandros N Vgontzas ◽

Fan He ◽

Sol M Rodriguez-Colon ◽

...

Keyword(s):

Blood Pressure ◽

Sleep Disordered Breathing ◽

Vascular Reactivity ◽

Population Based ◽

Increased Risk ◽

Penn State ◽

State Child ◽

The Difference ◽

Disordered Breathing

Objectives: To examine the association between incident sleep-disordered breathing (SDB) and blood pressure and blood pressure reactivity in a population based sample of adolescents. Methods: The Penn State Child Cohort is a general population based sample of 700 children aged 5-12 years at the baseline examination (2000-2005). Currently, 300 participants have completed their 8-year follow up examination. Blood pressure was assessed at follow up in the evening using an automated device prior to the sleep recording in three positions. Three assessments in the seated position were completed after 5 minutes of rest. This was followed by 3 assessments in the supine position after 5 minutes of rest. The averages of the 2 nd and 3 rd readings for both positions are reported. Finally the subject was asked to stand as fast as possible and 2 additional readings were completed immediately upon their foot hitting the floor. These two standing readings were averaged. The difference between standing and supine BP was used as measures of vascular reactivity. The age, gender and height adjusted mean level of BP measures comparing individuals with and without incident SDB (defined as Apnea Hypopnia Index, AHI>5/hr) after excluding individuals with baseline SDB were calculated. Results: We observed no significant differences in diastolic blood pressure across the three positions. However, systolic blood pressure across all three positions and vascular reactivity were significantly elevated in those with incident SDB, as summarized in Table 1. Conclusion: In an 8-year followup of this population based sample of children, there was no persistence of SDB from baseline. Incident SDB (about 11%) was significantly associated with elevated systolic BP across all three positions. Further, SDB was associated with increased systolic BP reactivity, which has been associated with increased risk of CVD and the development of hypertension in adults.

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Abstract P105: Sleep Disordered Breathing and Cardiac Autonomic Modulation in Adolescents - Penn State Child Cohort (PSCC) Study

Circulation ◽

10.1161/circ.129.suppl_1.p105 ◽

2014 ◽

Vol 129 (suppl_1) ◽

Author(s):

Edward O Bixler ◽

Fan He ◽

Sol Rodriguez-Colon ◽

Julio Fernandez-Mendoza ◽

Alexandros Vgontzas ◽

...

Keyword(s):

Heart Rate ◽

Sleep Disordered Breathing ◽

Population Based ◽

Apnea Hypopnea Index ◽

Autonomic Modulation ◽

Rr Intervals ◽

Cardiac Autonomic Modulation ◽

The Mean ◽

Frequency Power ◽

Disordered Breathing

Objectives: To investigate the relationship between sleep disordered breathing (SDB) and cardiac autonomic modulation (CAM) in a population-based sample of adolescents. Methods: We used available data from 400 adolescents who completed the follow up examinations in the population-based PSCC study. 1-night polysomnography was used to assess apnea hypopnea index (AHI). AHI was used to define no-SDB (AHI<1), mild SDB (1≤AHI<5), and moderate SDB (AHI≥5). CAM was assessed by heart rate variability (HRV) analysis of beat-to-beat normal R-R intervals from a 39-hour high resolution Holter ECG. The HRV indices in frequency domain [high frequency power (HF), low frequency power (LF), and LF/HF ratio] and time domain [standard deviation of normal RR intervals (SDNN), and the square root of the mean squared difference of successive normal RR intervals (RMSSD), and heart rate (HR)] were calculated on a 30-minute basis (78 repeated measures). Mixed-effects models were used to assess the SDB and HRV relationship. Results: The mean age was 16.9 yrs (SD=2.19), with 54% male and 77% white. The mean (SD) AHI were 0.52 (0.26), 2.38 (1.03), and 12.27 (14.54) for no-, mild-, and moderate-SDB participants. The age, race, sex, and BMI percentile adjusted mean (SE) HRV indices across three SDB groups are presented in Table 1. In summary, sleep disordered breathing was associated with lower HRV and higher HR in this population-based adolescent sample, with a significant dose-response relationship. Conclusion: moderate SDB in adolescents is already associated with lower HRV, indicative of sympathetic activation and lower parasympathetic modulation, which has been associated with cardiac events in adults.

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Abstract WP357: Prevalence of Pre- and Post-intracerebral Hemorrhage Sleep-disordered Breathing

Stroke ◽

10.1161/str.48.suppl_1.wp357 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Richard V Scheer ◽

Lynda D Lisabeth ◽

Chengwei Li ◽

Erin Case ◽

Ronald D Chervin ◽

...

Keyword(s):

Ischemic Stroke ◽

Intracerebral Hemorrhage ◽

Mexican American ◽

Sleep Disordered Breathing ◽

Population Based ◽

Apnea Hypopnea Index ◽

Berlin Questionnaire ◽

Portable Monitor ◽

Before And After ◽

Disordered Breathing

Background: Sleep-disordered breathing (SDB) is an independent risk factor for stroke. The reported prevalence of SDB after stroke ranges from 60 to >70%, while the pre-stroke prevalence of SDB is less well described. Moreover, much of these data are derived from ischemic stroke or mixed ischemic stroke and intracerebral hemorrhage (ICH) cohorts. Studies that assess the prevalence of SDB before and after ICH are lacking, with only one prior study (n=32) that reported a post-ICH SDB prevalence of 78%. We report herein the results of a second, larger, prospective study that assessed the prevalence of pre- and post-ICH. Methods: Participants enrolled in the population-based stroke surveillance study, the Brain Attack Surveillance in Corpus Christi (BASIC) project, with ICH from 2010-2015 were screened for SDB with the well validated ApneaLink Plus portable monitor (SDB defined as apnea-hypopnea index (AHI) ≥10). The Berlin questionnaire was administered, with reference to the pre-ICH state, to assess for possible pre-stroke SDB. Results: Of the 60 ICH participants screened, the median age was 63 years (interquartile range (IQR): 55.5, 74.5). Twenty-one (35%) were female, 54 (90%) were Mexican American, and 53 (88%) had a history of hypertension. The median Glasgow Coma Scale score was 15.0 (IQR: 15.0, 15.0) and the median NIHSS was 5.5 (IQR: 1.5, 8.0). Post-ICH, the median AHI was 9.5 (IQR: 5.5, 19.0); almost half (46.7%) met criteria for SDB. Thirty-four participants (56.7%) screened as high risk for SDB pre-ICH. Conclusion: Sleep-disordered breathing was highly prevalent after ICH, and also likely common before ICH, in this mostly Mexican American, community-based sample. If SDB increases risk for ICH, the findings suggest a potential new treatment target to prevent ICH and recurrent ICH.

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Validation of the NoSAS Score for the Screening of Sleep-Disordered Breathing in a Sleep Clinic

Canadian Respiratory Journal ◽

10.1155/2020/4936423 ◽

2020 ◽

Vol 2020 ◽

pp. 1-6 ◽

Cited By ~ 1

Author(s):

Yi Rong ◽

Shihan Wang ◽

Hui Wang ◽

Feng Wang ◽

Jingjing Tang ◽

...

Keyword(s):

Predictive Value ◽

Sleep Disordered Breathing ◽

Screening Tool ◽

Characteristic Curve ◽

Population Based ◽

Screening Tools ◽

Apnea Hypopnea Index ◽

Portable Monitor ◽

Number Of Patients ◽

Disordered Breathing

Background. There is a growing number of patients with sleep-disordered breathing (SDB) referred to sleep clinics. Therefore, a simple but useful screening tool is urgent. The NoSAS score, containing only five items, has been developed and validated in population-based studies. Aim. To evaluate the performance of the NoSAS score for the screening of SDB patients from a sleep clinic in China, and to compare the predictive value of the NoSAS score with the STOP-Bang questionnaire. Methods. We enrolled consecutive patients from a sleep clinic who had undergone apnea-hypopnea index (AHI) testing by type III portable monitor device at the hospital and completed the STOP-Bang questionnaire. The NoSAS score was assessed by reviewing medical records. Sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve (AUC) of both screening tools were calculated at different AHI cutoffs to compare the performance of SDB screening. Results. Of the 596 eligible patients (397 males and 199 female), 514 were diagnosed with SDB. When predicting overall (AHI ≥ 5), moderate-to-severe (AHI ≥ 15), and severe (AHI ≥ 30) SDB, the sensitivity and specificity of the NoSAS score were 71.2, 80.4, and 83.1% and 62.4, 49.3, and 40.7%, respectively. At all AHI cutoffs, the AUC ranged from 0.688 to 0.715 for the NoSAS score and from 0.663 to 0.693 for the STOP-Bang questionnaire. The NoSAS score had the largest AUC (0.715, 95% CI: 0.655–0.775) of diagnosing SDB at AHI cutoff of ≥5 events/h. NoSAS performed better in discriminating moderate-to-severe SDB than STOP-Bang with a marginally significantly higher AUC (0.697 vs. 0.663, P=0.046). Conclusion. The NoSAS score had good performance on the discrimination of SDB patients in sleep clinic and can be utilized as an effective screening tool in clinical practice.

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0735 Longitudinal Association of the Natural Course of Childhood Overweight with Sleep Disordered Breathing in the Transition to Adolescence: The Penn State Child Cohort

SLEEP ◽

10.1093/sleep/zsz067.733 ◽

2019 ◽

Vol 42 (Supplement_1) ◽

pp. A295-A295

Author(s):

Jacqueline M Danisi ◽

Julio Fernandez-Mendoza ◽

Susan L Calhoun ◽

Fan He ◽

Kristina Puzino ◽

...

Keyword(s):

Sleep Disordered Breathing ◽

Childhood Overweight ◽

Natural Course ◽

Transition To Adolescence ◽

Penn State ◽

Longitudinal Association ◽

State Child ◽

Disordered Breathing

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Sleep characteristics and cognitive impairment in the general population

Neurology ◽

10.1212/wnl.0000000000003557 ◽

2016 ◽

Vol 88 (5) ◽

pp. 463-469 ◽

Cited By ~ 45

Author(s):

José Haba-Rubio ◽

Helena Marti-Soler ◽

Nadia Tobback ◽

Daniela Andries ◽

Pedro Marques-Vidal ◽

...

Keyword(s):

Cognitive Impairment ◽

General Population ◽

Sleep Disordered Breathing ◽

Neuropsychological Test ◽

Population Based ◽

Apnea Hypopnea Index ◽

Clinical Dementia Rating ◽

Sleep Complaints ◽

Confounding Variables ◽

Disordered Breathing

Objective:To assess the association between sleep structure and cognitive impairment in the general population.Methods:Data stemmed from 580 participants aged >65 years of the population-based CoLaus/PsyCoLaus study (Lausanne, Switzerland) who underwent complete sleep evaluation (HypnoLaus). Evaluations included demographic characteristics, personal and treatment history, sleep complaints and habits (using validated questionnaires), and a complete polysomnography at home. Cognitive function was evaluated using a comprehensive neuropsychological test battery and a questionnaire on the participant's everyday activities. Participants with cognitive impairment (global Clinical Dementia Rating [CDR] scale score > 0) were compared with participants with no cognitive impairment (global CDR score = 0).Results:The 291 participants with a CDR score > 0 (72.5 ± 4.6 years), compared to the 289 controls with CDR = 0 (72.1 ± 4.6 years), had significantly more light (stage N1) and less deep (stage N3) and REM sleep, as well as lower sleep efficiency, higher intrasleep wake, and higher sleepiness scores (all p < 0.05). Sleep-disordered breathing was more severe in participants with cognitive impairment with an apnea/hypopnea index (AHI) of 18.0 (7.8–35.5)/h (p50 [p25–p75]) (vs 12.9 [7.2–24.5]/h, p < 0.001), and higher oxygen desaturation index (ODI). In the multivariate analysis after adjustments for confounding variables, the AHI and the ODI ≥4% and ≥6% were independently associated with cognitive impairment.Conclusions:Participants aged >65 years with cognitive impairment have higher sleepiness scores and a more disrupted sleep. This seems to be related to the occurrence of sleep-disordered breathing and the associated intermittent hypoxia.

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Robust, ECG-based detection of Sleep-disordered breathing in large population-based cohorts

SLEEP ◽

10.1093/sleep/zsz276 ◽

2019 ◽

Vol 43 (5) ◽

Cited By ~ 1

Author(s):

Mads Olsen ◽

Emmanuel Mignot ◽

Poul Jorgen Jennum ◽

Helge Bjarup Dissing Sorensen

Keyword(s):

Sleep Disordered Breathing ◽

Large Population ◽

Population Based ◽

Small Sample ◽

Health Study ◽

Apnea Hypopnea Index ◽

Automatic Data ◽

Highly Correlated ◽

Ecg Database ◽

Disordered Breathing

Abstract Study Objectives Up to 5% of adults in Western countries have undiagnosed sleep-disordered breathing (SDB). Studies have shown that electrocardiogram (ECG)-based algorithms can identify SDB and may provide alternative screening. Most studies, however, have limited generalizability as they have been conducted using the apnea-ECG database, a small sample database that lacks complex SDB cases. Methods Here, we developed a fully automatic, data-driven algorithm that classifies apnea and hypopnea events based on the ECG using almost 10 000 polysomnographic sleep recordings from two large population-based samples, the Sleep Heart Health Study (SHHS) and the Multi-Ethnic Study of Atherosclerosis (MESA), which contain subjects with a broad range of sleep and cardiovascular diseases (CVDs) to ensure heterogeneity. Results Performances on average were sensitivity(Se)=68.7%, precision (Pr)=69.1%, score (F1)=66.6% per subject, and accuracy of correctly classifying apnea–hypopnea index (AHI) severity score was Acc=84.9%. Target AHI and predicted AHI were highly correlated (R2 = 0.828) across subjects, indicating validity in predicting SDB severity. Our algorithm proved to be statistically robust between databases, between different periodic leg movement index (PLMI) severity groups, and for subjects with previous CVD incidents. Further, our algorithm achieved the state-of-the-art performance of Se=87.8%, Sp=91.1%, Acc=89.9% using independent comparisons and Se=90.7%, Sp=95.7%, Acc=93.8% using a transfer learning comparison on the apnea-ECG database. Conclusions Our robust and automatic algorithm constitutes a minimally intrusive and inexpensive screening system for the detection of SDB events using the ECG to alleviate the current problems and costs associated with diagnosing SDB cases and to provide a system capable of identifying undiagnosed SDB cases.

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Long-Term Changes in Sleep Disordered Breathing in Renal Transplant Patients: Relevance of the BMI

Journal of Clinical Medicine ◽

10.3390/jcm9061739 ◽

2020 ◽

Vol 9 (6) ◽

pp. 1739

Author(s):

Francesca Mallamaci ◽

Rocco Tripepi ◽

Graziella D’Arrigo ◽

Gaetana Porto ◽

Maria Carmela Versace ◽

...

Keyword(s):

Renal Transplant ◽

Sleep Disordered Breathing ◽

Repeated Measurements ◽

Apnea Hypopnea Index ◽

Longitudinal Changes ◽

Transplant Patients ◽

Long Term Changes ◽

Renal Transplant Patients ◽

Disordered Breathing

Sleep disordered breathing (SDB), as defined by the Apnea Hypopnea Index (AHI), is a highly prevalent disturbance in end stage kidney disease. SDB improves early on after renal transplantation but long-term changes in AHI in these patients have not been studied. We studied the long-term changes in AHI in a series of 221 renal transplant patients (mean age: 47 ± 12 years; 70% males) over a median follow up of 35 months. Data analysis was made by the generalized estimating equations method (GEE). On longitudinal observation, the median AHI rose from 1.8 (Interquartile range: 0.6–5.0) to 2.9 (IQR: 1.0–6.6) and to 3.6 (IQR: 1.7–10.4) at the second and third visit, respectively (p = 0.009 by the GEE model and the proportion of patients with moderate to severe SDB rose from 8% to 20%. Longitudinal changes in minimum oxygen saturation (minSaO2) mirrored those in the AHI. In adjusted analyses, repeated measurements of BMI (p < 0.009) emerged as the strongest independent longitudinal correlate of AHI and MinSaO2. The AHI worsens over time in renal transplant patients and longitudinal changes of this biomarker are directly related to simultaneous changes in BMI. Overweight/obesity, a potentially modifiable risk factor, is an important factor underlying the risk of SDB in this population.

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