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 (6SD) FMD was 6.1 (64.0)%, 7.3 (63.6)%, 6.8 (64.5)%, and 4.8 (62.9)% in control subjects, T2DM only, OSA only, and T2DM plus OSA, respectively. We observed a significant T2DM 3 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, 21.9 to 2.5; primary endpoint), with a net improvement of 1.1% (95% CI, 21.4 to 3.6) among those with adherence of 4 h/night or greater. A significant T2DM 3 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 enddiastolic volume of 8.7 ml (95% CI, 27.0 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).

Benefits of continuous positive airway pressure on glycaemic control and insulin resistance in patients with type 2 diabetes and obstructive sleep apnoea: A meta‐analysis

“…Of 3300 articles recognized by the initial search, 253 were retrieved for more detailed assessment, and seven articles 7,14,20–24 were included in the meta‐analysis (Figure 1). Baseline characteristics of trials included in the meta‐analysis are shown in Table 1.…”

Cardiovascular Disorders Triggered by Obstructive Sleep Apnea—A Focus on Endothelium and Blood Components

“…Among men 40 to 70 years old, those with AHI > or = 30 were 68% more prone to develop coronary artery disease than those with AHI < 5 [ 60 ]. Bakker et al study showed that the 3 months of CPAP therapy resulted in lowering the left ventricle (LV) end-diastolic volume, as assessed by the magnetic resonance imaging (MRI) [ 61 ]. Conversely, in another study no significant changes were noted in ventricular dimensions, systolic and diastolic function, valvular function and coronary vasodilation to nitroglycerin after 3 months of CPAP.…”

“…Lifestyle intervention and successful weight reduction significantly improved AHI, BMI, serum triglycerides and insulin resistance in mild OSA patients [ 64 ]. The CPAP effect on improving endothelial function measured by the FMD is even greater in OSA patients with coexisting diabetes [ 61 ]. The treatment efficiency in coexisting diabetes and OSA could be explained by common mechanisms leading to endothelial dysfunction, which comprises ROS overproduction.…”

Contemporary Concise Review 2019: Sleep and ventilation

“…These randomized clinical trials showing no beneficial effect of CPAP on overall cardiovascular events in moderate‐to‐severe OSA excluded severely sleepy patients. Thus, it remains unknown whether in the excessively sleepy OSA phenotype a beneficial effect on cardiovascular outcomes might have been observed . Ongoing efforts to understand OSA mechanisms may also help to develop personalized therapy for OSA and to improve clinical trial design.…”