Physical properties of blood in patients with differing severities of obstructive sleep apnoea and the effect of continuous positive airway pressure treatment

Abstract

Background: Obstructive sleep apnoea (OSA) is a common sleep breathing disorder that results from the repetitive collapse of the upper airway. Clinical research has demonstrated complex multifaceted relationships between OSA and adverse cardiovascular events, such as coronary artery disease and stroke. Changes in blood rheology parameters represent a mechanistic link between aberrant coagulation and risk for cardiovascular events. Objectives: The main objective of the present thesis was to investigate the association between different OSA severity patterns and blood rheology-related parameters. The effects of acute OSA treatment with continuous positive airway pressure (CPAP) on blood rheology and rheology-related parameters were evaluated. Methods: The study involved a prospective evaluation of diagnosed OSA patients who were referred to perform a polysomnograph in a sleep laboratory of a tertiary teaching hospital. The design consisted of two research studies. First, the association between rheological and OSA severity was studied in three patient groups (mild, moderate, and severe) as well as polysomnographic variables (including apnoea-hypopnoea index (AHI), oxygen desaturation index (ODI), and arousal index (AI)). Second, the effect of acute CPAP therapy on rheological parameters was examined in the different OSA patient groups. Rheological parameters included whole blood viscosity (WBV), red blood cell (RBC) deformability, and RBC aggregation. Measurements of aggregation and WBV were performed at native and standardised (i.e., 0.4 L/L) haematocrit. Both the native and standardised viscosities were measured at the following shear rates: 75, 150, 300, 750, and 1500 s-1. RBC aggregation measured by the relevant magnitude parameters (after 10 s of stasis (M0), after 10 s at 3 sec⁻¹ (M1), and after 120 s at stasis (AI120)) as well as aggregation half time (T½). Rheology-related parameters were plasma fibrinogen concentration and routine haematology measurements. CPAP was performed for one night. Results: Patients (n=31) volunteered to participate in the study. Mean WBV was significantly higher in severe OSA patients (4.15 ± 0.58 mPa·s) than that in the moderate OSA patients at the highest shear rate (3.13 ± 0.42 mPa·s, p<0.05). There was no correlation between WBV at any shear rate and AHI, ODI, or AI. For both native and standardised haematocrit, a significant shear thinning effect was observed, whereby WBV decreased with increasing shear rates (p<0.05). There was no significant difference in RBC aggregation parameters between the different severity groups of OSA (p > 0.05). RBC aggregation at M0 was positively correlated with AHI (p = 0.036) and ODI (p = 0.026), whereas T½ was negatively correlated with AHI (p=0.032) and ODI (p=0.018). RBC deformability increased consistently in a linear pattern with increased shear stress among all OSA severity groups. Plasma fibrinogen concentrations were significantly elevated in severe OSA patients (3.35±0.62 g/L) when compared to mild (2.97±0.90 g/L, p < 0.05) and moderate patients (2.89±0.92 g/L, p < 0.05). Insulin and glycated haemoglobin levels differed significantly among OSA severity groups (p<0.05). Platelet count was positively correlated with ODI (p=0.023). When compared to baseline values, acute CPAP therapy caused a significant reduction of platelet count (259.9±46.9 vs 238.5±55.7 10⁹/L, respectively, p < 0.05), haematocrit (0.44±0.47 vs 0.41±0.56 %, respectively, P<0.05), and WBV at the moderate shear rate of 300 sec-1 in both native (5.0±0.9 vs 3.4±0.6 mPa·s, respectively, p < 0.05) and standardised (4.8 ± 0.41 vs 3.8 ± 0.78 mPa·s, respectively, p < 0.05) haematocrit samples. There was no significant effect of acute CPAP therapy on RBC aggregation, RBC deformability, and plasma fibrinogen concentrations. Conclusion: Patients with severe OSA had marked increases in high WBV and increased RBC aggregation. Therefore, blood rheology parameters may be related to the heightened cardiovascular risk associated with OSA. These blood rheology markers could therefore provide a meaningful insight into early disease processes. A single night of CPAP therapy improved blood viscosity and thus may be effective for reducing the risk of cardiovascular events in OSA patients. Future blood rheology-based studies should employ larger cohorts along with the recruitment of a control group. Long-term CPAP therapy should be prospectively evaluated for its impact on blood rheology in OSA patients.