Day/Night rhythm of hemostatic factors in obstructive sleep apnea

Abstract

Study objectives: To investigate the hypothesis that day/night patterns of prothrombotic activity differ between patients with obstructive sleep apnea (OSA) and individuals with no OSA.

Design: Prothrombotic markers' day/night rhythms recorded over one 24-h period.

Setting: General clinical research center.

Patients: 38 untreated OSA patients as verified by polysomnography (apnea-hypopnea index > or = 10/h sleep) and 22 non-OSA controls.

Measurements and results: Blood samples were collected every 2 h to measure plasma levels of fibrinolysis-inhibiting plasminogen activator inhibitor (PAI)-1 and the primary fibrin degradation product D-dimer. Day/night variation in hemostasis factors was examined using a cosinor analysis. Mesor (mean) PAI-1 over the 24-h period was higher (P = 0.015), and mesor of D-dimer was lower (P = 0.001) in patients with OSA than in the non-OSA controls. These group differences stayed significant when controlling for age and gender. After further adjustment for body mass index, mean arterial pressure, and smoking, the relationship between OSA and PAI-1 became non-significant, but the relationship between OSA and D-dimer continued to be significant (P = 0.006). In the fully adjusted analysis, the amplitude (peak) for D-dimer was lower in OSA patients than in non-OSA controls (P = 0.048). The acrophase (time of the peak) for PAI-1 and D-dimer did not significantly differ between groups.

Conclusions: The relatively higher average level of PAI-1 and lower average level of D-dimer across the 24-h in OSA patients might reflect decreased fibrinolytic capacity and fibrin degradation, respectively. The findings provide some evidence for a prothrombotic state in OSA, but were only partially independent of metabolic variables.

Figure 1a

Day/Night pattern of PAI-1 by obstructive sleep apnea status.

Figure 1b

Day/night pattern of D-dimer by obstructive sleep apnea status. The figures show the fitted day/night pattern with individual data points for plasminogen activator-inhibitor-1 (PAI-1; Figure 1a) and fibrin D-dimer (Figure 1b) in 38 patients with obstructive sleep apnea (blue) and 22 non-OSA controls (red).