Effects of Hydroxychloroquine on endOthelial function in eLDerly with sleep apnea (HOLD): study protocol for a randomized clinical trial.

BACKGROUND: Sleep apnea and coronary artery disease are prevalent and relevant diseases. The mechanism by which sleep apnea leads to coronary artery disease remains unclear. Intermittent hypoxia, caused by sleep apnea, leads to inflammation and consequent endothelial dysfunction. Endothelial dysfunction precedes the development of atherosclerotic disease and the occurrence of cardiovascular events. Agents that potentially act to improve endothelial function can help prevent cardiovascular events. Patients using immunomodulators due to rheumatic diseases have a lower prevalence of cardiovascular diseases. However, the potential cardioprotective effect of these drugs in patients without autoimmune diseases is not clear. Hydroxychloroquine (HCQ) is an immunomodulator used to treat rheumatoid arthritis and systemic lupus erythematosus. In addition to its anti-inflammatory properties, HCQ reduces cholesterol and blood glucose levels and has antithrombotic effects. The drug is inexpensive and widely available. Adverse effects of HCQ are rare and occur more frequently with high doses. OBJECTIVE: In this randomized clinical trial, the effect of HCQ treatment on endothelial function will be tested in seniors with sleep apnea. METHODS: We will recruit participants over the age of 65 and with moderate-severe sleep apnea from an ongoing cohort. We chose to use this sample already evaluated for sleep apnea for reasons of convenience, but also because the elderly with sleep apnea are vulnerable to heart disease. Endothelial function will be assessed by examining flow-mediated dilation of the brachial artery, the gold standard method, considered an independent predictor of cardiovascular events in the general population and by peripheral arterial tonometry, the most recent and most easily obtained method. Hydroxychloroquine will be used at a dose of 400 mg/daily for 8 weeks. DISCUSSION: Our study aims to obtain evidence, albeit preliminary, of the efficacy of hydroxychloroquine in improving endothelial function and reducing cardiovascular risk markers. If the improvement occurs, we plan to design a randomized multicenter clinical trial to confirm the findings. TRIAL REGISTRATION: ClinicalTrials.gov NCT04161339 . Registered on November 2019.

Diagnosis of obstructive sleep apnea syndrome and its outcomes with home portable monitoring.

BACKGROUND: The use of portable respiratory monitoring (PM) has been proposed for the diagnosis of obstructive sleep apnea syndrome (OSAS), but most studies that validate PM accuracy have not followed the best standards for diagnostic test validation. The objective of the present study was to evaluate the accuracy of PM performed at home to diagnose OSAS and its outcomes after first validating PM in the laboratory setting by comparing it to polysomnography (PSG). METHODS: Patients with suspected OSAS were submitted, in random order, to PM at the sleep laboratory concurrently with PSG (lab-PM) or at home-PM. The diagnostic performance was assessed by sensitivity, specificity, positive and negative predictive values, positive likelihood ratio (+LR), negative likelihood ratio (-LR), intraclass correlation coefficients, kappa statistic, and Bland-Altman plot. RESULTS: One hundred fifty-seven subjects (73% men, mean age +/- SD, 45 +/- 12 yr) with an apnea-hypopnea index (AHI) of 31 (SD +/- 29) events/h were studied. Excluding inadequate recordings, 149 valid comparisons with lab-PM and 121 with unattended home-PM were obtained. Compared to PSG for detecting AHI > 5, the lab-PM demonstrated sensitivity of 95.3%, specificity of 75%, +LR of 3.8, and -LR of 0.11; the home-PM exhibited sensitivity of 96%, specificity of 64%, +LR of 2.7, and -LR of 0.05. Kappa statistics indicated substantial correlation between PSG and PM results. Bland-Altman plot showed smaller dispersion for lab-PM than for home-PM. Pearson product moment correlation coefficients among the three AHIs and clinical outcomes were similar, denoting comparable diagnostic ability. CONCLUSIONS: This study used all available comparison methods to demonstrate accuracy of PM in-home recordings similar to that of repeated PSGs. PM increases the possibility of correctly diagnosing and effectively treating OSAS in populations worldwide.