Rationale and design of a multicenter, randomized, patients-blinded two-stage clinical trial on effects of endothelial function test in patients with non-obstructive coronary artery disease (ENDOFIND)

Abstract 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 cardio protective 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 eight weeks.DISCUSSION: Our study aim 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 Identifier: NCT04161339

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DIFFERENTIAL EFFECTS OF COLD PRESSOR AND ACETYLCHOLINE DURING ENDOTHELIAL FUNCTION ASSESSMENT IN WOMEN WITH NO OBSTRUCTIVE CORONARY ARTERY DISEASE: THE NHLBI-SPONSORED WOMEN'S ISCHEMIA SYNDROME EVALUATION (WISE) STUDY

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(12)61490-9 ◽

2012 ◽

Vol 59 (13) ◽

pp. E1489 ◽

Cited By ~ 1

Author(s):

R. David Anderson ◽

Puja Mehta ◽

Janet Wei ◽

B. Delia Johnson ◽

John Petersen ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Endothelial Function ◽

Obstructive Coronary Artery Disease ◽

Cold Pressor ◽

Differential Effects ◽

Artery Disease ◽

Function Assessment

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

Trials ◽

10.1186/s13063-021-05610-0 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Leticia Maria Tedesco Silva ◽

Antonio Cortes ◽

Beatriz Rossi ◽

Liliana Boll ◽

Gustavo Waclawovsky ◽

...

Keyword(s):

Coronary Artery Disease ◽

Clinical Trial ◽

Coronary Artery ◽

Sleep Apnea ◽

Endothelial Dysfunction ◽

Endothelial Function ◽

Randomized Clinical Trial ◽

Cardiovascular Events ◽

Gold Standard Method ◽

Artery Disease

Abstract 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.

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