Clinical reviewImpact of obstructive sleep apnea treatment by continuous positive airway pressure on cardiometabolic biomarkers: A systematic review from sham CPAP randomized controlled trials
Introduction
Obstructive sleep apnea (OSA) is a common clinical condition characterized by repeated episodes of apnea and hypopnea during sleep. Sleep fragmentation and chronic intermittent hypoxia (CIH) induce intermediate mechanisms such as activation of the sympathetic nervous system [1], oxidative stress and systemic inflammation, responsible for cardiometabolic consequences ∗[2], ∗[3] (Fig. 1). OSA is linked with hypertension, arrhythmia, stroke, coronary heart disease, and increased cardiovascular mortality [4]. In addition, OSA is also highly prevalent in patients with metabolic diseases including type 2 diabetes mellitus (T2DM), nonalcoholic fatty liver disease (NAFLD) [5] and is linked to several features of metabolic syndrome among them hypertension, insulin resistance (IR), abdominal obesity and dyslipidemia [6], ∗[7]. The effective treatment of OSA may thus represent an important target for reducing cardiometabolic risk. However, the impact of continuous positive airway pressure (CPAP), the first line therapy of OSA, on metabolic or inflammatory markers is still debated [8].
Although the effects of CPAP on various biomarkers have been investigated in hundreds of open clinical studies, the real effects of CPAP on cardiometabolic biomarkers are conflicting mainly owing to different study designs and the presence of major confounders. This review is a systematic analysis of randomized studies comparing therapeutic versus sham CPAP intervention and also includes studies using a CPAP withdrawal design ∗[9], [10].
To take account of the intermediary mechanisms involved in OSA pathophysiology (Fig. 1), we will address the impact of CPAP on the following cardiometabolic biomarkers: 1) plasma and urine catecholamines and their metabolites that reflect sympathetic activity; 2) insulin resistance and lipid metabolism biomarkers; 3) oxidative stress, systemic and vascular inflammation biomarkers; 4) liver enzymes highlighting the association between OSA and NAFLD; 5) coagulation biomarkers.
Section snippets
Literature search strategy
We selected only randomized sham-controlled trials i.e., with sham CPAP as the control, addressing the impact of CPAP on cardiometabolic biomarkers. An electronic literature search using the Medline medical research database was conducted. We looked for sham-controlled studies and investigating the effects of CPAP on blood and urinary cardiometabolic biomarkers. First, we used “sham CPAP” as the keyword, then the following keyword associations were used: “subtherapeutic CPAP” AND “randomized
Background: sympathetic activation and intermittent hypoxia
Oxidative stress and inflammation induced by OSA promote activation of the sympathetic nervous system and then endothelial dysfunction, arterial stiffness and atherosclerosis ∗[2], ∗[11], ∗[12]. As shown in Fig. 1, oxidative stress induces inflammation, while inflammation in turn promotes oxidative stress. This vicious circle results in sympathetic activation and endothelial dysfunction leading to atherosclerosis. Impaired arterial vasodilating capacity may contribute to hypertension and
Background: metabolic syndrome and OSA
OSA is associated with all the components of the metabolic syndrome including visceral obesity [27], hypertension, poor glycemic control and lipid metabolism abnormalities. It has been suggested that adipocytes exposed to hypoxia exhibit dysregulated adipocytokine production [28], which may contribute to insulin resistance and metabolic syndrome in OSA patients. We have demonstrated in patients with morbid obesity that chronic intermittent hypoxia is strongly associated with higher systemic
Acknowledgment
We thank Dr Alison Foote (Clinical Research Center, Grenoble University Hospital) for language editing.
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