Advances and challenges in pursuing biomarkers for obstructive sleep apnea: Implications for the cardiovascular risk

Lebkuchen, Adriana; Freitas, Lunara S.; Cardozo, Karina Helena Morais; Drager, Luciano F.

doi:10.1016/j.tcm.2020.04.003

Cited by 24 publications

(26 citation statements)

References 84 publications

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“…Prior work has investigated phenotypic factors, biomarkers, and genetic variation to understand better and dissect the heterogenous effects of OSA on CAD, including multiple variables, such as age, gender and comorbid diagnoses that may moderate associations of OSA and CVD, as well as blood-based biomarkers of CVD [45, 46]. Nonetheless, prior research using genetic variation to explore the divergent individual responses to hypoxic conditions has been limited, despite suggestions advocating this approach to risk stratification of patients with OSA [47].…”

Section: Discussionmentioning

confidence: 99%

Pathway-specific Polygenic Risk Scores (PRS) identify OSA-related pathways differentially moderating genetic susceptibility to CAD

Shah

et al. 2021

Preprint

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Background: Obstructive sleep apnea (OSA) and its features, such as chronic intermittent hypoxia (IH), may differentially affect specific molecular pathways and processes in the pathogenesis of coronary artery disease (CAD) and influence the subsequent risk and severity of CAD events. In particular, competing adverse (e.g. inflammatory) and protective (e.g. increased coronary collateral blood flow) mechanisms may operate, but remain poorly understood. We hypothesize that common genetic variation in selected molecular pathways influences the likelihood of CAD events differently in individuals with and without OSA, in a pathway-dependent manner. Methods: We selected a cross-sectional sample of 471,877 participants from the UK Biobank, among whom we ascertained 4,974 to have OSA, 25,988 to have CAD, and 711 to have both. We calculated pathway-specific polygenic risk scores (PS-PRS) for CAD, based on 6.6 million common variants evaluated in the CARDIoGRAMplusC4D genome-wide association study (GWAS), annotated to specific genes and pathways using functional genomics databases. Based on evidence of involvement with IH and CAD, we tested PS-PRS for the HIF-1, VEGF, NFkB and TNF signaling pathways. Results: In a multivariable-adjusted logistic generalized additive model, elevated PS-PRSs for the KEGG VEGF pathway (39 genes) associated with protection for CAD in OSA (interaction odds ratio 0.86, p = 6E-04). By contrast, the genome-wide CAD PRS did not show evidence of statistical interaction with OSA. Conclusions: We find evidence that pathway-specific genetic risk of CAD differs between individuals with and without OSA in a qualitatively pathway-dependent manner, consistent with the previously studied phenomena whereby features of OSA may have both positive and negative effects on CAD. These results provide evidence that gene-by-environment interaction influences CAD risk in certain pathways among people with OSA, an effect that is not well-captured by the genome-wide PRS. These results can be followed up to study how OSA interacts with genetic risk at the molecular level, and potentially to personalize OSA treatment and reduce CAD risk according to individual pathway-specific genetic risk profiles.

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Section: Discussionmentioning

confidence: 99%

Pathway-specific Polygenic Risk Scores (PRS) identify OSA-related pathways differentially moderating genetic susceptibility to CAD

Shah

et al. 2021

Preprint

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“…12 OSA is also a major risk factor for other NCDs, notably cardiovascular disease (CVD), metabolic disorders, hypertension, depression, and stroke. 10, [12][13][14][15][16] The economic burden of OSA is high. 15,17 In 2015, the estimated annual cost of OSA for USA was US$12.4 billion.…”

Section: Sleep and Breathingmentioning

confidence: 99%

“…Obesity is a major risk factor for OSA 12 . OSA is also a major risk factor for other NCDs, notably cardiovascular disease (CVD), metabolic disorders, hypertension, depression, and stroke 10,12‐16 …”

Section: Obstructive Sleep Apnea (Osa)mentioning

confidence: 99%

A review of therapies for the overlap syndrome of obstructive sleep apnea and chronic obstructive pulmonary disease

Suri

2021

FASEB BioAdvances

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Obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) are common chronic diseases. These two noncommunicable diseases (NCDs) are prevalent among approximately 10% of the general population. Approximately 1% of the population is affected by the co-existence of both conditions, known as the overlap syndrome (OS). OS patients suffer from greater degrees of nocturnal oxygen desaturation and cardiovascular consequences than those with either condition in isolation.Besides OS, patients with COPD may suffer from a spectrum of sleep-related breathing disorders, including hypoventilation and central sleep apnea. The article provides an overview of the pathogenesis, associated risk factors, prevalence, and management of sleep-related breathing disorders in COPD. It examines respiratory changes during sleep caused by COPD and OSA. It elaborates upon the factors that link the two conditions together to lead to OS. It also discusses the clinical evaluation and diagnosis of these patients. Subsequently, it reviews the pathophysiological basis and the current evidence for three potential therapies: positive airway pressure therapy [including continuous positive airway pressure (CPAP) and bilevel positive airway pressure], oxygen therapy, and pharmacological therapy. It also proposes a phenotypic approach towards the diagnosis and treatment of OS and the entire spectrum of sleep-related breathing disorders in COPD. It concludes with the current evidence gaps and future areas of research in the management of OS.

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“…Metabolomics, high‐sensitivity, high‐throughput profiling methods, can help elucidate the molecular signature of OSA and further our understanding of the pathophysiological mechanisms (Lebkuchen et al., 2020; Patti et al., 2012). A few studies have explored the association between metabolites in those with and without OSA, using gas chromatography or liquid chromatography coupled to mass spectrometry (GC‐MS or LC‐MS) (Ferrarini et al., 2013; Lebkuchen et al., 2018; Xu et al., 2016).…”

Section: Introductionmentioning

confidence: 99%

Metabolomic profile associated with obstructive sleep apnoea severity in obese pregnant women with gestational diabetes mellitus: A pilot study

Reutrakul

Chen

Chirakalwasan

et al. 2021

Journal of Sleep Research

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Obstructive sleep apnoea (OSA) is prevalent in obese women with gestational diabetes mellitus (GDM). The present pilot study explored associations between OSA severity and metabolites in women with GDM. A total of 81 obese women with dietcontrolled GDM had OSA assessment (median gestational age [GA] 29 weeks). The metabolic profile was assayed from fasting serum samples via liquid chromatographymass spectrometry (LC-MS) using an untargeted approach. Metabolites were extracted and subjected to an Agilent 1,290 UPLC coupled to an Agilent 6,545 quadrupole time-of-flight (Q-TOF) MS. Data were acquired using electrospray ionisation in positive and negative ion modes. The raw LC-MS data were processed using the OpenMS toolkit to detect and quantify features, and these features were annotated using the Human Metabolite Database. The feature data were compared with OSA status, apnea-hypopnea index (AHI), body mass index (BMI) and GA using "limma" in R. Correlation analyses of the continuous covariates were performed using Kendall's Tau test. The p values were adjusted for multiple testing using the Benjamini-Hochberg false discovery rate correction. A total of 42 women (51.8%) had OSA, with a median AHI of 9.1 events/hr. There were no significant differences in metabolomics profiles between those with and without OSA. However, differential analyses modelling in GA and BMI found 12 features that significantly associated with the AHI.These features could be annotated to oestradiols, lysophospholipids, and fatty acids, with higher levels related to higher AHI. Metabolites including oestradiols and phospholipids may be involved in pathogenesis of OSA in pregnant women with GDM. A targeted approach may help elucidate our understanding of their role in OSA in this population.

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Advances and challenges in pursuing biomarkers for obstructive sleep apnea: Implications for the cardiovascular risk

Cited by 24 publications

References 84 publications

Pathway-specific Polygenic Risk Scores (PRS) identify OSA-related pathways differentially moderating genetic susceptibility to CAD

Pathway-specific Polygenic Risk Scores (PRS) identify OSA-related pathways differentially moderating genetic susceptibility to CAD

A review of therapies for the overlap syndrome of obstructive sleep apnea and chronic obstructive pulmonary disease

Metabolomic profile associated with obstructive sleep apnoea severity in obese pregnant women with gestational diabetes mellitus: A pilot study

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