Sleep Disordered Breathing-induced Endothelial Dysfunction and Its Association with Fetomaternal Outcomes in Preeclampsia

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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Cumulative Hypoxemia During Sleep Predicts Vascular Endothelial Dysfunction in Patients With Sleep-Disordered Breathing

American Journal of Hypertension ◽

10.1093/ajh/hpv135 ◽

2015 ◽

Vol 29 (4) ◽

pp. 458-463 ◽

Cited By ~ 12

Author(s):

Hiroyuki Sawatari ◽

Akiko Chishaki ◽

Mari Nishizaka ◽

Tomotake Tokunou ◽

Sonomi Adachi ◽

...

Keyword(s):

Endothelial Dysfunction ◽

Sleep Disordered Breathing ◽

Vascular Endothelial ◽

Vascular Endothelial Dysfunction ◽

Disordered Breathing

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Sleep Disordered Breathing in Children is Associated with Increased Platelet Aggregation, Systemic Inflammation and Endothelial Dysfunction

Heart Lung and Circulation ◽

10.1016/j.hlc.2011.05.051 ◽

2011 ◽

Vol 20 ◽

pp. S21

Author(s):

S. Willoughby ◽

C. van den Heuvel ◽

A. Chin ◽

G. Hodge ◽

J. Martin ◽

...

Keyword(s):

Platelet Aggregation ◽

Endothelial Dysfunction ◽

Systemic Inflammation ◽

Sleep Disordered Breathing ◽

Disordered Breathing

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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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