Diuretics in Patients with Obstructive Sleep Apnea and Concomitant Hypertension.

To the Editor:

We read with great interest the original article from Giatti and colleagues (1) exploring the relationship between dietary sodium intake and severity of obstructive sleep apnea (OSA) (1). These findings suggest that the role of dietary sodium in the pathogenesis of OSA cannot be generalized but rather is limited to hypertensive patients (2). We agree with the authors about the fact that fluid redistribution from the legs to the neck during sleep (i.e., fluid shift) contributes to the severity of OSA in the restricted population of patients with hypertension and may constitute a specific endotype and a potential therapeutic target.

We have recently published a propensity score-matched analysis addressing this issue in a huge national real-life prospective observational cohort of patients with OSA (3). The 69,564 included patients with OSA had a median age of 56.9 years (interquartile range: 47.4–65.6), 67% were men, and the median apnea–hypopnea index (AHI) was 28 (14–43) events/h. Among them, 9,783 (14.1%) were treated with diuretics. Severe OSA was defined as an AHI > 30 events/h, and the impact of diuretics on OSA severity was assessed by using a logistic regression model. We showed that diuretics reduce the severity of OSA only in patients with hypertension (P < 0.01) and particularly in patients with a body mass index (BMI) between 25 and 35 kg/m2 (P < 0.01). No association was found between diuretics and OSA severity when we considered the entire population or subgroups suffering from heart failure (whatever their BMI), suggesting that this physiopathological trait is of lesser impact in this situation.

Many drugs have been investigated in randomized trials as candidate therapeutic agents for the management of OSA related to specific endotypes (e.g., poor upper airway muscle activity, high loop gain, low arousal threshold) (4). These research data do not currently translate into routine practice, and there are no clear recommendations for medications as primary therapy for OSA. The prevalence of hypertension in patients with OSA consistently reaches 50% across studies with a high rate of uncontrolled and resistant hypertension (5). According to our results, which are consistent with those of Giatti and colleagues, diuretics may have the potential to both reduce OSA severity and treat OSA-related hypertension.

For primary hypertension, the main drug classes recommended for treatment initiation in monotherapy in all international guidelines are thiazide diuretics, β-blockers, long-acting calcium channel blockers, and renin–angiotensin blockers. In the general population, each of these therapeutic classes is considered equally effective. In view of our analysis and the existing literature, diuretics might be the first choice medication for patients with OSA with concomitant hypertension.

In addition, interventions to reduce bodily fluid content (e.g., low sodium intake or diuretics) in men with severe OSA have been shown to slightly decrease AHI, suggesting that rostral fluid displacement is one among other mechanisms determining pharyngeal collapsibility (6) and in turn OSA severity. A major goal for personalized and precision medicine is to combine therapies appropriate for specific well-defined OSA endotypes and phenotypes. Combinations of therapies can include continuous positive airway pressure (the gold standard therapy for OSA), lifestyle interventions (weight loss, low-salt diet, and/or exercise), and pharmacological interventions targeting OSA-related conditions. Further studies are needed to identify the role of diuretics in the distinct pathophysiological and clinical scenario of overweight or patients who are moderately obese with OSA and hypertension.