Safety and Efficacy of Intermittent Hypoxia Conditioning as a New Rehabilitation/ Secondary Prevention Strategy for Patients with Cardiovascular Diseases: A Systematic Review and Meta-analysis

Background: Once used by mountaineers to facilitate rapid adaptations to altitude and by athletes to improve their aerobic capacity, exposure to hypoxia has been proven to affect various physiological, clinically relevant parameters. A form of conditioning known as Intermittent Hypoxia Conditioning (IHC) consists of repeated exposures to intermittent hypoxia, combined with normoxia and hyperoxia, which has been shown to have potential as a treatment to improve cardio- metabolic risks profile in cardiac patients but results across studies are inconsistent. This systematic review and meta-analysis aimed to evaluate the clinical effectiveness of IHC. Methods: Four electronic databases (PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials) were searched (from inception to December 2019) to retrieve all studies focused on IHC in elderly patients with cardiovascular disease. A meta-analysis of functional, efficacy and safety outcomes in cardiac patients was completed to compare IHC to sham treatments. Results: Fourteen studies with 320 patients in the Interval Hypoxia-normoxia Group (IHNG) or Interval Hypoxia-hyperoxia training Group (IHHG) and 111 patients in the control group were included in our meta-analysis. IHNT and IHHT were associated with significant reduction in heart rate, SBP, and DBP at rest after treatment [MD= -5.35 beat/min, 95% CI (-9.19 to -1.50), p=0.006], [MD= -13.72 mmHg, 95% CI (-18.31 to -9.132), p<0.001], and [MD= -7.882 mmHg, 95% CI (-13.163 to -2.601), p=0.003], respectively. There were no significant complications or serious adverse events related to IHNT/IHHT. Conclusion: The current evidence suggested that the use of the IHNT/IHHT program in elderly patients with CVDs can be safe and effective in terms of heart rate and elevated blood pressure. However, currently, there is no supporting evidence that IHNT/IHHT can significantly improve hematological parameters or lipid profile. Exercise tolerance increased at the end of the course of hypoxic conditioning within IHC group, but did not differ from controls. Further research is needed.