The effect of continuous positive airway pressure on blood pressure in patients with obstructive sleep apnea and uncontrolled hypertension - Study design and challenges during the COVID-19 pandemic.

OBJECTIVES: To describe the MORPHEOS (Morbidity in patients with uncontrolled HTN and OSA) trial, and describe the challenges imposed by the COVID-19 pandemic. METHODS: MORPHEOS is a multicenter (n=6) randomized controlled trial designed to evaluate the blood pressure (BP) lowering effects of treatment with continuous positive airway pressure (CPAP) or placebo (nasal strips) for 6 months in adult patients with uncontrolled hypertension (HTN) and moderate-to-severe obstructive sleep apnea (OSA). Patients using at least one antihypertensive medication were included. Uncontrolled HTN was confirmed by at least one abnormal parameter in the 24-hour ABPM and ≥80% medication adherence evaluated by pill counting after the run-in period. OSA was defined by an apnea-hypopnea index ≥15 events/hours. The co-primary endpoints are brachial BP (office and ambulatory BP monitoring, ABPM) and central BP. Secondary outcomes include hypertension-mediated organ damage (HMOD) to heart, aorta, eye, and kidney. We pre-specified several sub-studies from this investigation. Visits occur once a week in the first month and once a month thereafter. The programmed sample size was 176 patients but the pandemic prevented this final target. A post-hoc power analysis will be calculated from the final sample. ClinicalTrials.gov: NCT02270658. RESULTS: The first 100 patients are predominantly males (n=69), age: 52±10 years, body mass index: 32.7±3.9 kg/m2 with frequent co-morbidities. CONCLUSIONS: The MORPHEOS trial has a unique study design including a run-in period; pill counting, and detailed analysis of hypertension-mediated organ damage in patients with uncontrolled HTN that will allow clarification of the impact of OSA treatment with CPAP.

Evaluation of central venous catheter and other risk factors for mortality in chronic hemodialysis patients with COVID-19 in Brazil.

PURPOSE: Hemodialysis patients with COVID-19 are at increased risk of death. We aimed to describe the characteristics of a cohort of Brazilian hemodialysis patients with COVID-19 and assess their mortality rate and risk factors for death. METHODS: Retrospective cohort study of 741 Brazilian hemodialysis patients with confirmed COVID-19 from Feb-Dec/2020, of 52 dialysis centers of the country. We analyzed comorbid conditions, sociodemographic factors, and dialysis-related parameters. To detect risk factors for mortality in hemodialysis patients, we performed multivariable Cox proportional hazard regression analysis. Survival was analyzed by Kaplan-Meier. RESULTS: From 9877 hemodialysis patients, 741 were diagnosed with COVID-19. Mean age was 57 ± 16 years, 61% were male, and 51% white. The most frequent symptoms were fever (54.1%), cough (50.9%), and dyspnea (37.2%); 14.2% were asymptomatic. There were 139 deaths (18.8%), with 66% within the disease's first 15 days. 333 patients (44.9%) required hospitalization, and 211 (28.5%) were admitted to an intensive care unit. The cumulative probability of survival at 90 days of diagnosis was 79% (95% CI 76-82%). In the fully adjusted multivariate model, the risk factors significantly associated with death were diabetes mellitus (HR 1.52, 95% CI 1.05-2.19, P = 0.026), use of a central venous catheter (CVC) (HR 1.79, 95% CI 1.22-2.64, P = 0.003), age (HR 1.03, 95% CI 1.01-1.04, P < 0.001), and origin from the North vs. Southeast region (HR 2.60, 95% CI 1.01-6.68, P = 0.047). CONCLUSIONS: Hemodialysis patients using a CVC as the vascular access, aside from diabetic and elderly ones, should be closely monitored due to their high risk of death in the course of the COVID-19.

Is Hypertension a Real Risk Factor for Poor Prognosis in the COVID-19 Pandemic?

PURPOSE OF REVIEW: There is increasing evidence indicating an association between several risk factors and worse prognosis in patients with coronavirus disease 2019 (COVID-19), including older age, hypertension, heart failure, diabetes, and pulmonary disease. Hypertension is of particular interest because it is common in adults and there are concerns related to the use of renin-angiotensin system (RAS) inhibitors in patients with hypertension infected with COVID-19. Levels of angiotensin-converting enzyme 2 (ACE2), a protein that facilitates entry of coronavirus into cells, may increase in patients using RAS inhibitors. Thus, chronic use of RAS inhibition could potentially lead to a more severe and fatal form of COVID-19. In this review, we provide a critical review to the following questions: (1) Does hypertension influence immunity or ACE2 expression favoring viral infections? (2) Are the risks of complications in hypertension mediated by its treatment? (3) Is aging a major factor associated with worse prognosis in patients with COVID-19 and hypertension? RECENT FINDINGS: Despite the potential involvement of immune responses in the pathogenesis of hypertension, there is no evidence supporting that hypothesis that hypertension or RAS inhibitors contributes to unfavorable outcomes in viral infections. Future investigations adopting a strict protocol for confirming hypertension status as well as assessing associated comorbidities that may influence outcomes are necessary. From the therapeutic perspective, recombinant ACE2 may serve as a potential therapy, but relevant studies in humans are lacking. Definitive evidence regarding the use of RAS inhibitors in patients with COVID-19 is needed; 5 randomized trials examining this issue are currently underway. There is no current scientific support for claiming that hypertension or its treatment with RAS inhibitors contribute to unfavorable outcomes in COVID-19.