Intermittent Hypoxic-Hyperoxic Exposures Effects in Patients with Metabolic Syndrome: Correction of Cardiovascular and Metabolic Profile

Abstract

The aim of this study was to evaluate efficacy and applicability of the “intermittent hypoxic-hyperoxic exposures at rest” (IHHE) protocol as an adjuvant method for metabolic syndrome (MS) cardiometabolic components. A prospective, single-center, randomized controlled clinical study was conducted on 65 patients with MS subject to optimal pharmacotherapy, who were randomly allocated to IHHE or control (CON) groups. The IHHE group completed a 3-week, 5 days/week program of IHHE, each treatment session lasting for 45 min. The CON group followed the same protocol, but was breathing room air through a facial mask instead. The data were collected 2 days before, and at day 2 after the 3-week intervention. As the primary endpoints, systolic (SBP) and diastolic (DBP) blood pressure at rest, as well as arterial stiffness and hepatic tissue elasticity parameters, were selected. After the trial, the IHHE group had a significant decrease in SBP and DBP (Cohen’s d = 1.15 and 0.7, p < 0.001), which became significantly lower (p < 0.001) than in CON. We have failed to detect any pre-post IHHE changes in the arterial stiffness parameters (judging by the Cohen’s d), but after the intervention, cardio-ankle vascular indexes (RCAVI and LCAVI) were significantly lowered in the IHHE group as compared with the CON. The IHHE group demonstrated a medium effect (0.68; 0.69 and 0.71 Cohen’s d) in pre-post decrease of Total Cholesterol (p = 0.04), LDL (p = 0.03), and Liver Steatosis (p = 0.025). In addition, the IHHE group patients demonstrated a statistically significant decrease in pre-post differences (deltas) of RCAVI, LCAVI, all antropometric indices, NTproBNP, Liver Fibrosis, and Steatosis indices, TC, LDL, ALT, and AST in comparison with CON (p = 0.001). The pre-post shifts in SBP, DBP, and HR were significantly correlated with the reduction degree in arterial stiffness (ΔRCAVI, ΔLCAVI), liver fibrosis and steatosis severity (ΔLFibr, ΔLS), anthropometric parameters, liver enzymes, and lipid metabolism in the IHHE group only. Our results suggested that IHHE is a safe, well-tolerated intervention which could be an effective adjuvant therapy in treatment and secondary prevention of atherosclerosis, obesity, and other components of MS that improve the arterial stiffness lipid profile and liver functional state in MS patients.

Keywords: arterial stiffness; atherosclerosis; hypoxic-hyperoxic exposures; inflammation; intermittent hypoxic training; liver fibrosis; liver steatosis; low-density lipoprotein; metabolism.

Figure 1

MS—Metabolic Syndrome; IHHE: intermittent hypoxic-hyperoxic exposure.

Figure 2

Correlation analysis between pre-post deltas of key hemodynamic parameters (SBP, DBP, and HR) and other variables. Thick lines—strong correlations (r ≥ 0.60), thin lines—moderate correlations (r ≥ 0.40). SBP—systolic blood pressure, DBP—diastolic blood pressure, HR—heart rate, BMI—body mass index, BW—body weight, LS—Liver Steatosis, LFibr—Liver Fibrosis, HC—hip circumference, LDL-Ch—Low-Density Lipoproteins Cholesterol, TCh—Total Cholesterol, WC—waist circumference, RCAVI—right cardio-ankle vascular index, LCAVI—left cardio-ankle vascular index, RABI—right-ankle brachial index, LABI—left ankle-brachial index, ALT—alanineaminotransferase, AST—aspartateaminotransferase, NTproBNP—N-terminal prohormone of brain natriuretic peptide, CRP-hs—High-sensitivity C-reactive protein.