BACKGROUND: In patients with obstructive sleep apnea (OSA), novel metrics such as hypoxic burden (HB) and sleep apnea-specific pulse-rate response (ΔHR) may better correlate with cardiovascular diseases (CVD) than the apnea-hypopnea index (AHI). This manuscript aims to assess the correlation between ΔHR and HB with subclinical atherosclerosis in patients with OSA, testing the hypothesis that elevated ΔHR and HB are associated with subclinical atherosclerosis development.
METHODS: In a prospective study, individuals aged 20-65 years with suspected OSA without known comorbidities were consecutively recruited and defined as OSA (AHI≥5events/h) or healthy controls. Using bilateral carotid ultrasonography, common carotid intima-media thickness (CIMT) was assessed and the identification of at least one atheromatous plaque defined the presence of subclinical atherosclerosis. ΔHR, and HB were derived from pulse-oximetry.
RESULTS: We studied 296 patients of age 45±10 years old, of whom 28% were women, and with a BMI of 30.3±5.3kg/m2. Overall, 245 had OSA and 51 were healthy controls. After controlling for confounding variables higher ΔHR but not HB, was associated with higher CIMT (p=0.006) and higher time spent with oxygen saturation below 90% (T90) was associated with an increase in carotid atheroma plaques (p=0.032). When stratifying OSA based on HB tertiles, we observed that within tertile 2 of HB, an increase in ΔHR was associated with larger CIMT (p=0.017).
CONCLUSIONS: A higher ΔHR is associated with an increase in CIMT among adult patients with OSA. This study suggests that ΔHR could be a biomarker of risk for CVD in patients with OSA.

UNASSIGNED: Obstructive sleep apnea (OSA) is a highly prevalent sleep-disordered breathing. It is associated with adverse co-morbidities, being the most scientific evidence of cardiovascular (CV) disease. Currently, OSA is measured through the apnea-hypopnea index (AHI), the total number of respiratory events per hour of sleep. However, different studies have questioned its utility in OSA management, highlighting the need to search for new parameters that better reflect the heterogeneity of the disease. Hypoxic burden (HB) has emerged as a novel biomarker that informs about the frequency, duration and depth of the desaturation related to the respiratory events. We conducted a systematic review in order to find publications about the heterogeneity of OSA measured by HB and its associations with future disease.
UNASSIGNED: Systematic review was conducted using PubMed and Web of Science. The terms \"sleep apne\" and \"hypoxic burden\" were used to look for publications from the date of inception to August 15, 2023. Inclusion criteria: articles in English published in peer-reviewed journals. Exclusion criteria: (1) not available publications; (2) duplicated articles; (3) letters, editorials, and congress communications; (4) articles not including information about HB as a specific biomarker of OSA.
UNASSIGNED: 33 studies were included. The results were classified in 2 main sections: (1) HB implication in the CV sphere: HB showed to be a better predictor of CV risk in OSA patients than traditional measures such as AHI with possible clinical management implication in OSA. (2) HB response to OSA treatment: pharmacological and nonpharmacological treatments have demonstrated to be effective in improving hypoxia measured through the HB.
UNASSIGNED: HB could be a better and more effective parameter than traditional measurements in terms of diagnosis, risk prediction and therapeutic decisions in patients with OSA. This measure could be incorporated in sleep units and could play a role in OSA management, driving the clinic to a more personalized medicine.

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OSA is diagnosed and managed by a metric called the apnea-hypopnea index (AHI). The AHI quantifies the number of respiratory events (apnea or hypopnea), disregarding important information on the characteristics and physiological consequences of respiratory events, including degrees of ventilatory deficit and associated hypoxemia, cardiac autonomic response, and cortical activity. The oversimplification of the disorder by the AHI is considered one of the reasons for divergent findings on the associations of OSA and cardiovascular disease (CVD) in observational and randomized controlled trial studies. Prospective observational cohort studies have demonstrated strong associations of OSA with several cardiovascular diseases, and randomized controlled trials of CPAP intervention have not been able to detect a benefit of CPAP to reduce the risk of CVD. Over the last several years, novel methodologies have been proposed to better quantify the magnitude of OSA-related breathing disturbance and its physiological consequences. As a result, stronger associations with cardiovascular and neurocognitive outcomes have been observed. In this review, we focus on the methods that capture polysomnographic heterogeneity of OSA.

OBJECTIVE: To determine the clinical impact of sleep apnea-related hypoxic burden in pregnant women and neonates.
METHODS: This is a secondary analysis of the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (nuMoM2b) study. Hypoxia burden was calculated from the home sleep apnea test (HSAT) and defined as the total area under respiratory events. Logistic regression analysis assessed the relationship between hypoxia burden and pregnancy/neonatal outcomes.
RESULTS: A total of 3006 subjects in the early term, and 2326 subjects in the middle term of pregnancy, had HSAT. A hypoxic burden greater than 6.8%min was present in 1740 at early term and associated with a higher risk of preeclampsia (odds ratio 1.297, 95 % confidence interval 1.032-1.630, p: 0.026) after adjusted by obstructive sleep apnea (OSA) severity. In the middle term, 1058 subjects had a hypoxia burden more than 11.8%min, which was a predictor for higher incidence of gestational diabetes (OR 1.795, 95 % CI 1.097-2.938, p: 0.020) and an Apgar <7 at 1 min (OR 1.446, 95 % CI 1.079-1.939, p: 0.012) after adjusted by obstructive sleep apnea (OSA) severity. After adjusted by oxygenation disturbance index, HB was not related with Apgar <7 at 1 min (p:0.565).
CONCLUSIONS: The hypoxic burden is an independent predictor for preeclampsia and gestational diabetes and an Apgar <7 at 1 min.

OBJECTIVE: The apnoea-hypopnoea index (AHI) and oxygen desaturation index (ODI) encounter challenges in capturing the intricate relationship between obstructive sleep apnoea (OSA) and cardiovascular disease (CVD) risks. Although novel hypoxic indices have been proposed to tackle these limitations, there remains a gap in comprehensive validation and comparisons across a unified dataset.
METHODS: Samples were derived from the Sleep Heart Health Study (SHHS), involving 4485 participants aged over 40 years after data quality screening. The study compared several key indices, including AHI, ODI, the reconstructed hypoxic burden (rHB), the percentage of sleep time with the duration of respiratory events causing desaturation (pRED_3p) and the sleep breathing impairment index (SBII), in relation to CVD mortality and morbidity risks. Adjusted Cox proportional models were employed to calculate hazard ratios (HRs) for each index, and comparisons were performed.
RESULTS: SBII and pRED_3p exhibited significant correlations with both CVD mortality and morbidity, with SBII showing the highest adjusted HR (95% confidence interval) for mortality (2.04 [1.25, 3.34]) and pRED_3p for morbidity (1.43 [1.09-1.88]). In contrast, rHB was only significant in predicting CVD mortality (1.63 [1.05-2.53]), while AHI and ODI did not show significant correlations with CVD outcomes. The adjusted models based on SBII and pRED_3p exhibited optimal performance in the CVD mortality and morbidity datasets, respectively.
CONCLUSIONS: This study identified the optimal indices for OSA-related CVD risks prediction, SBII for mortality and pRED_3p for morbidity. The open-source online platform provides the computation of the indices.

UNASSIGNED: Obstructive sleep apnea (OSA) is a widely prevalent condition with consequent multiple organ systems complications. There is consensus that OSA is associated with negative effects on pulmonary hemodynamics but whether it contributes to development of clinical pulmonary hypertension (PH) is unclear.
UNASSIGNED: In this review, we (1) highlight previous studies looking into the possible bidirectional association of OSA and PH, focusing on those that explore clinical prognostic implications, (2) explore potential pathophysiology, (3) discuss the new metrics in OSA, (4) describe endo-phenotyping of OSA, (5) recommend possible risk assessment and screening pathways.
UNASSIGNED: Relying only on symptoms to consider a sleep study in PH patients is a missed opportunity to detect OSA, which, if present and not treated, can worsen outcomes. The potential prognostic role of sleep study metrics such as oxygen desaturation index (ODI), hypoxic burden (HB) and ventilatory burden (VB) in OSA should be studied in prospective trials to identify patients at risk for PH. AHI alone has not provided clarity. In those with PH, we should consider replacing ambulatory overnight pulse oximetry (OPO) with home sleep studies (HST). In PH patients, mild OSA should be sufficient to consider PAP therapy.

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OBJECTIVE: We investigated the associations between multiple sleep dimensions in obstructive sleep apnea (OSA) and carotid intima-media thickness (CIMT), an early sign of atherosclerosis, in participants from the Shanghai Sleep Health Study.
METHODS: We performed secondary analysis of SSHS in a group of subjects who underwent ultrasound evaluation from 2018 to 2022. Multiple sleep dimensions were measured using standard polysomnography. CIMT was measured from ultrasound images as an early sign of atherosclerosis. Multivariable-adjusted linear regression and logistic regression analyses were performed to detect associations between sleep traits in OSA and CIMT.
RESULTS: CIMT was found to increase with increasing severity of OSA (P < .001). When adjusted for conventional risk factors, microarousal index and hypoxic burden were positively correlated with CIMT, while slow-wave sleep and mean apnea-hypopnea event duration showed a negative correlation with CIMT (all P < .01). In binary logistic regression analysis, participants with a high microarousal index, less slow-wave sleep, higher hypoxic burden, and shorter mean apnea-hypopnea event duration showed a higher prevalence of thick CIMT with no evidence of interaction by age, sex, or body mass index (P-interaction > .05).
CONCLUSIONS: Patients with more severe sleep fragmentation, more severe hypoxemia, and increased arousability were more likely to have increased CIMT after adjusting for potential confounders. It is important to evaluate novel indices of sleep fragmentation, hypoxemia, and arousability in OSA for early detection and prevention of cardiovascular disease, including stroke.
BACKGROUND: Registry: Chinese Clinical Trial Registry; Name: Establishing Bio-bank and Cohort of OSAHS in Hospital-based Population; URL: http://www.chictr.org.cn/showproj.aspx?proj=43057; Identifier: ChiCTR1900025714.
BACKGROUND: Huang W, Zhou E, Zhang J, et al. Association between multiple sleep dimensions in obstructive sleep apnea and an early sign of atherosclerosis. J Clin Sleep Med. 2024;20(7):1093-1104.