Effect of 5-year continuous positive airway pressure treatment on MMPs and TIMPs: implications for OSA comorbidities

Abstract

Continuous positive airway pressure (CPAP) treatment results in nearly complete remission of symptoms of obstructive sleep apnoea (OSA); however, its effect on OSA comorbidities including cardiovascular diseases remains contradictory. Here we investigated the short- and long-term effect of CPAP treatment on matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in patients with severe OSA. Serum levels of 7 MMPs and 3 TIMPs were followed in OSA patients (n = 28) with an apnoea-hypopnoea index of ≥30 events/h at the time of diagnosis and at control visits (2 months, 6 months and 5 years) after initiation of fixed-pressure CPAP treatment. The first few months of CPAP therapy resulted in significant decrease of MMP-8 and MMP-9 levels (MMP-8: 146 (79-237) vs. 287 (170-560) pg/mL; MMP-9: 10.1 (7.1-14.1) vs. 12.7 (10.4-15.6) ng/mL, p < 0.05 for each at 2 months), while the rest of the panel remained unchanged as compared to baseline values. In contrast, at 5 years, despite of uninterrupted CPAP treatment and excellent adherence the levels of MMP-8, MMP-9 and TIMPs significantly increased (p < 0.05). Our data suggest that initiation of CPAP therapy leads to a decrease in the level of key MMPs in the short-term; however, this effect is not sustained over the long-term.

Figure 1

Study flow chart. OSA: obstructive sleep apnoea, CPAP: continuous positive airway pressure, AHI: apnoea-hypopnoea index, PaCO₂: arterial carbon dioxide tension.

Figure 2

Serum MMP (Panel A–F) and TIMP (Panel G–I) levels of study subjects during the 5-year follow-up. Marker levels were assessed at the time of diagnosis (OSA), at 2 and 6 months (2M and 6M) and at 5 years of CPAP therapy (5Y). OSAS: obstructive sleep apnoea syndrome (baseline visit), CPAP: continuous positive airway pressure, MMP: matrix metalloproteinase, TIMP: tissue inhibitor of matrix metalloproteinase. Standard box plots with median (25^th and 75^th percentiles) and whiskers (at minimum and maximum values) are shown. *p < 0.05 vs. baseline visit; ^#p < 0.05 and ^###p < 0.001 vs. 2-month visit; ^°p < 0.05 and ^°°°p < 0.001 vs. 6-month visit.