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The Effect of Continuous Positive Airway Pressure on Vascular Function and Cardiac Structure in Diabetes and Sleep Apnea. A Randomized Controlled Trial.

ABSTRACT: Rationale: Although both type 2 diabetes mellitus (T2DM) and obstructive sleep apnea (OSA) are independently recognized as risk factors for cardiovascular disease, little is known about their interaction.Objectives: We hypothesized that T2DM and OSA act synergistically to increase vascular risk, and that treatment of OSA would improve vascular reactivity in patients with T2DM plus OSA.Methods: Cross-sectional study of 141 adults with T2DM, OSA, T2DM plus OSA, and control subjects, followed by a 3-month, parallel-arm, randomized, placebo-controlled trial comparing active and sham continuous positive airway pressure (CPAP) in 53 adults with T2DM plus OSA. Endothelium-dependent macro- and microvascular reactivity (flow-mediated dilation [FMD] of the brachial artery and acetylcholine-induced dilation of forearm microvasculature, respectively) and cardiovascular magnetic resonance to assess left- and right-ventricular mass/volume.Results: Mean (±SD) FMD was 6.1 (±4.0)%, 7.3 (±3.6)%, 6.8 (±4.5)%, and 4.8 (±2.9)% in control subjects, T2DM only, OSA only, and T2DM plus OSA, respectively. We observed a significant T2DM × OSA interaction on FMD, such that the mean effect of OSA in those with T2DM was 3.1% (95% confidence interval [CI], 0.6 to 5.6) greater than the effect of OSA in those without T2DM. A total of 3 months of CPAP resulted in a mean absolute increase in FMD of 0.3% (95% CI, -1.9 to 2.5; primary endpoint), with a net improvement of 1.1% (95% CI, -1.4 to 3.6) among those with adherence of 4 h/night or greater. A significant T2DM × OSA interaction was found for both left ventricular (LV) and right ventricular end-diastolic volume, such that OSA was associated with a 22.4 ml (95% CI, 3.2 to 41.6) greater LV end-diastolic volume and 23.2 ml (95% CI, 2.6 to 43.8) greater right ventricular end-diastolic volume in those with T2DM compared with the impact of OSA in those without T2DM. We observed a net improvement in LV end-diastolic volume of 8.7 ml (95% CI, -7.0 to 24.4).Conclusions: The combination of T2DM plus OSA is associated with macrovascular endothelial dysfunction beyond that observed with either disease alone. CPAP for 3 months did not significantly improve macrovascular endothelial function in the intent-to-treat analysis; however, cardiovascular magnetic resonance results suggest that there may be a beneficial effect of CPAP on LV diastolic volume.Clinical trial registered with www.clinicaltrials.gov (NCT01629862).

SUBMITTER: Bakker JP

PROVIDER: S-EPMC7175977 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:RationaleImpaired endothelium-dependent vasodilation has been documented in patients with sleep apnea. This impairment may result in blood flow dysregulation during apnea-induced fluctuations in arterial blood gases.ObjectivesTo test the hypothesis that hypoxic and hypercapnic vasodilation in the forearm and cerebral circulation are impaired in patients with sleep apnea.MethodsWe exposed 20 patients with moderate to severe sleep apnea and 20 control subjects, to isocapnic hypoxia and hyperoxic hypercapnia. A subset of 14 patients was restudied after treatment with continuous positive airway pressure.Measurements and main resultsCerebral flow velocity (transcranial Doppler), forearm blood flow (venous occlusion plethysmography), arterial pressure (automated sphygmomanometry), oxygen saturation (pulse oximetry), ventilation (pneumotachograph), and end-tidal oxygen and carbon dioxide tensions (expired gas analysis) were measured during three levels of hypoxia and two levels of hypercapnia. Cerebral vasodilator responses to hypoxia (-0.65 +/- 0.44 vs. -1.02 +/- 0.72 [mean +/- SD] units/% saturation; P = 0.03) and hypercapnia (2.01 +/- 0.88 vs. 2.57 +/- 0.89 units/mm Hg; P = 0.03) were smaller in patients versus control subjects. Hypoxic vasodilation in the forearm was also attenuated (-0.05 +/- 0.09 vs. -0.10 +/- 0.09 unit/% saturation; P = 0.04). Hypercapnia did not elicit forearm vasodilation in either group. Twelve weeks of continuous positive airway pressure treatment enhanced hypoxic vasodilation in the cerebral circulation (-0.83 +/- 0.32 vs. -0.46 +/- 0.29 units/% saturation; P = 0.01) and forearm (-0.19 +/- 0.15 vs. -0.02 +/- 0.08 units/% saturation; P = 0.003), and hypercapnic vasodilation in the brain showed a trend toward improvement (2.24 +/- 0.78 vs. 1.76 +/- 0.64 units/mm Hg; P = 0.06).ConclusionsVasodilator responses to chemical stimuli in the cerebral circulation and the forearm are impaired in many patients with obstructive sleep apnea. Some of these impairments can be improved with continuous positive airway pressure.

Project description:Background: Obstructive sleep apnea syndrome (OSAS) is an independent risk factor for cardiovascular morbidity and mortality, and it has a detrimental effect on renal function. Obesity is the major risk factor for OSAS, and represents a risk factor for chronic kidney disease. Continuous positive airway pressure (CPAP) is the suggested therapy for moderate-to-severe OSAS. We designed this study to evaluate the effect of CPAP on estimated glomerular filtration rate (e-GFR) in a cohort of obese patients with moderate-to-severe OSAS and normal renal function. Methods: We enrolled 198 obese subjects, divided into two groups (OSAS+ and OSAS-), on the basis of cardiorespiratory monitoring; mild OSAS patients (n = 33) were excluded from the study, thus the analyses were conducted on 165 patients. Comparisons between groups were made by Student t-test or χ2 test as appropriate. Linear regression analyses were used to assess the relationship between baseline e-GFR and different covariates and, in the OSAS+ group, between Δe-GFR and different covariates. A multivariate regression analysis was performed to determinate the independent predictor of the Δe-GFR. Results: OSAS+ subjects showed significantly increased values of systolic blood pressure, HOMA, pulse wave velocity, high-sensitivity C reactive protein and uric acid compared with OSAS- group. OSAS+ group showed significantly lower values of e-GFR and increased values of microalbuminuria. At linear regression analysis e-GFR resulted significantly and inversely related to AHI in the whole study population and in the two groups. After 6 months of CPAP therapy, OSAS+ subjects showed an improvement in respiratory parameters, as well as a significant increase in e-GFR values (104.2 + 19.0 vs. 84.0 + 13.1 ml/min/1.73 m2, P < 0.0001). At multiple regression analysis, Δ apnea/hypopnea index (AHIa) resulted the main independent predictor of Δe-GFR explaining 22% of its variation. Conclusions: Obese OSAS patients show significantly lower values of e-GFR, even if in the normal range, compared with obese non-OSAS subjects. After 6 months of CPAP, e-GFR significantly improved (+20 ml/min/1.73 m2) and ΔAHIa resulted the most important independent predictor of Δe-GFR.

Project description:Study objectiveTo determine the neurocognitive effects of continuous positive airway pressure (CPAP) therapy on patients with obstructive sleep apnea (OSA).Design, setting, and participantsThe Apnea Positive Pressure Long-term Efficacy Study (APPLES) was a 6-month, randomized, double-blind, 2-arm, sham-controlled, multicenter trial conducted at 5 U.S. university, hospital, or private practices. Of 1,516 participants enrolled, 1,105 were randomized, and 1,098 participants diagnosed with OSA contributed to the analysis of the primary outcome measures.InterventionActive or sham CPAP MEASUREMENTS: THREE NEUROCOGNITIVE VARIABLES, EACH REPRESENTING A NEUROCOGNITIVE DOMAIN: Pathfinder Number Test-Total Time (attention and psychomotor function [A/P]), Buschke Selective Reminding Test-Sum Recall (learning and memory [L/M]), and Sustained Working Memory Test-Overall Mid-Day Score (executive and frontal-lobe function [E/F])ResultsThe primary neurocognitive analyses showed a difference between groups for only the E/F variable at the 2 month CPAP visit, but no difference at the 6 month CPAP visit or for the A/P or L/M variables at either the 2 or 6 month visits. When stratified by measures of OSA severity (AHI or oxygen saturation parameters), the primary E/F variable and one secondary E/F neurocognitive variable revealed transient differences between study arms for those with the most severe OSA. Participants in the active CPAP group had a significantly greater ability to remain awake whether measured subjectively by the Epworth Sleepiness Scale or objectively by the maintenance of wakefulness test.ConclusionsCPAP treatment improved both subjectively and objectively measured sleepiness, especially in individuals with severe OSA (AHI > 30). CPAP use resulted in mild, transient improvement in the most sensitive measures of executive and frontal-lobe function for those with severe disease, which suggests the existence of a complex OSA-neurocognitive relationship.Clinical trial informationRegistered at clinicaltrials.gov. Identifier: NCT00051363.CitationKushida CA; Nichols DA; Holmes TH; Quan SF; Walsh JK; Gottlieb DJ; Simon RD; Guilleminault C; White DP; Goodwin JL; Schweitzer PK; Leary EB; Hyde PR; Hirshkowitz M; Green S; McEvoy LK; Chan C; Gevins A; Kay GG; Bloch DA; Crabtree T; Demen WC. Effects of continuous positive airway pressure on neurocognitive function in obstructive sleep apnea patients: the Apnea Positive Pressure Long-term Efficacy Study (APPLES). SLEEP 2012;35(12):1593-1602.

Project description:Background Studies have shown that a significant percentage of patients with obstructive sleep apnea (OSA) do not tolerate continuous positive airway pressure (CPAP) therapy and long-term use may be as low as 30%. Given the lower levels of symptoms and health-related risks, patients with mild sleep apnea may be at even higher risk for non-adherence to long term CPAP. The purpose of our study was to investigate the prevalence and associations of long-term CPAP adherence in first time users with mild sleep apnea diagnosed by home sleep apnea testing (HSAT). Methods We identified all the patients who were diagnosed with mild sleep apnea (5 = < AHI < 15) by home sleep apnea testing from 01/2013 to 06/2019 at a large, combined community and hospital-based sleep practice. Only first time CPAP users were included. Compliance was defined as CPAP usage ≥ 4 h per night on ≥ 70% of nights over 30 consecutive days. We defined long term adherence as compliance on the 12th month following CPAP set up. Patient demographics, comorbidities, and CPAP compliance at 1st, 3rd, 6th, 9th and 12th month after therapy initiation were collected. We compared and identified the factors that had significant difference (P < 0.1) between compliant and non-compliant groups at the 12th month. Results 222 patients were included in the analysis. 57 (25.7%) patients were adherent with long term CPAP treatment. The following factors were associated with a greater likelihood for long-term CPAP adherence: older age, lower body mass index (BMI), presence of a bed partner, non-smoker, presence of Diabetes Mellitus (DM), presence of Heart Failure (CHF), lack of depression, and compliance at 1st, 3rd, 6th and 9th month. Conclusions Long term CPAP compliance in mild sleep apnea patients is low. Long term adherence to CPAP can be predicted based on CPAP adherence during the first three months. Supplementary Information The online version contains supplementary material available at 10.1186/s12890-023-02612-3.

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The Effect of Continuous Positive Airway Pressure on Vascular Function and Cardiac Structure in Diabetes and Sleep Apnea. A Randomized Controlled Trial.

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